51 results on '"Lutz Gürtler"'
Search Results
2. [SARS-CoV-2 vaccines and reaction of the immune system. Can the epidemic spread of the virus be prevented by vaccination?]
- Author
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Jonas, Schmidt, Frithjof, Blessing, and Lutz, Gürtler
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Immunity, Cellular ,COVID-19 Vaccines ,Time Factors ,SARS-CoV-2 ,Immune System ,Vaccination ,COVID-19 ,Humans ,Immunity, Humoral - Abstract
Since the end of 2019 a new coronavirus, SARS-CoV-2, first identified in Wuhan, China, is spreading around the world partially associated with a high death toll. Besides hygienic measurements to reduce the spread of the virus vaccines have been confected, partially based on the experiences with Ebola virus vaccine, based on recombinant human or chimpanzee adenovirus carrying the spike protein and its ACE2 receptor binding domain (RBD). Further vaccines are constructed by spike protein coding mRNA incorporated in lipid nano vesicles that after entry in human cells produce spike protein. Both vaccine types induce a strong immune response that lasts for months possibly for T-cell immunity a few years. Due to mutations in the coronavirus genome in several parts of the world variants selected, that were partially more pathogenic and partially easier transmissible - variants of concern (VOC). Until now vaccinees are protected against the VOC, even when protection might be reduced compared to the Wuhan wild virus.An open field is still how long the vaccine induced immunity will be sufficient to prevent infection and/or disease; and how long the time period will last until revaccination will be required for life saving protection, whether a third vaccination is needed, and whether revaccination with an adenovirus-based vaccine will be tolerated.
- Published
- 2021
3. Convalescent plasma for administration of passive antibodies against viral agents
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Louis M. Aledort, Giovanni Di Minno, Pier Mannuccio Mannucci, James W. Ironside, Lutz Gürtler, and Carlo Federico Perno
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2019-20 coronavirus outbreak ,Convalescent plasma ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunization, Passive ,COVID-19 ,Hematology ,Virology ,Plasma ,biology.protein ,Medicine ,Humans ,Antibody ,business ,Coronavirus Infections ,COVID-19 Serotherapy - Published
- 2020
4. Thromboinflammation in COVID-19: Can α
- Author
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Rainer, Seitz, Lutz, Gürtler, and Wolfgang, Schramm
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Inflammation ,SARS-CoV-2 ,Forum ,COVID-19 ,Endothelial Cells ,neutrophil ,Thrombosis ,Extracellular Traps ,COVID‐19 ,Host-Pathogen Interactions ,thromboinflammation ,Animals ,Humans ,alpha-Macroglobulins ,α2‐macroglobulin ,Inflammation Mediators ,Blood Coagulation - Abstract
The complex COVID‐19‐associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2‐macroglobulin (α2‐M) levels from severe COVID‐19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone‐ and protease‐coated web‐like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and “versatile” inhibitor α2‐M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2‐M in COVID‐19.
- Published
- 2020
5. HIV transmission by human bite: a case report and review of the literature-implications for post-exposure prophylaxis
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Christoph Ruwwe-Glösenkamp, Christian Hoffmann, Dirk Schürmann, Miriam Stegemann, and Lutz Gürtler
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,HIV Infections ,Case Report ,medicine.disease_cause ,Post-exposure prophylaxis ,Route of transmission ,Plasma viral load ,03 medical and health sciences ,0302 clinical medicine ,Bites, Human ,Risk Factors ,Internal medicine ,Germany ,parasitic diseases ,medicine ,Humans ,Human bite ,030212 general & internal medicine ,Risk factor ,Hiv transmission ,business.industry ,Transmission (medicine) ,Human immunodeficiency virus ,virus diseases ,General Medicine ,Berlin ,HIV transmission ,030104 developmental biology ,Infectious Diseases ,business ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case.
- Published
- 2020
6. Severe underquantification of HIV-1 group O isolates by major commercial PCR-based assays
- Author
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Ina Ambiel, Mark Wasner, Robert Ehret, Lutz Gürtler, Jean-Christophe Plantier, Lena Stegmann, Albert Heim, Volker Daniel, Annemarie Berger, Josef Eberle, Christoph Sarrazin, Marhild Kortenbusch, Kai Hourfar, Annette Haberl, Martin Stürmer, Maximilian Muenchhoff, and Oliver T. Keppler
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0301 basic medicine ,Microbiology (medical) ,Serial dilution ,030106 microbiology ,Pcr assay ,Human immunodeficiency virus (HIV) ,HIV Infections ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Genetic diversity ,virus diseases ,Reproducibility of Results ,General Medicine ,Viral Load ,Virology ,Therapeutic monitoring ,Infectious Diseases ,Nucleic acid ,HIV-1 ,RNA, Viral ,Viral load ,Nucleic Acid Amplification Techniques ,Nucleic acid detection - Abstract
HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.
- Published
- 2019
7. Human immunodeficiency virus 1 dual-target nucleic acid technology improves blood safety: 5 years of experience of the German Red Cross blood donor service Baden-Württemberg-Hessen
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Kai, Hourfar, Josef, Eberle, Markus, Müller, C, Micha Nübling, Michael, Chudy, Julia, Kress, Lutz, Gürtler, Uschi, Mayr-Wohlfart, Hubert, Schrezenmeier, Inke, Hellmann, Jürgen, Luhm, Sabine, Kraas, Jürgen, Ringwald, Knut, Gubbe, Kerstin, Frank, Andreas, Karl, Torsten, Tonn, Maike, Jaeger, Walid, Sireis, Erhard, Seifried, and Michael, Schmidt
- Subjects
Male ,Reverse Transcriptase Polymerase Chain Reaction ,Blood Safety ,Blood Donors ,Red Cross ,gag Gene Products, Human Immunodeficiency Virus ,Donor Selection ,Germany ,HIV-1 ,Humans ,RNA, Viral ,Female ,Reagent Kits, Diagnostic ,HIV Long Terminal Repeat ,Retrospective Studies - Abstract
RNA viruses are associated with a high frequency of mutations because of the missing proofreading function of polymerases, such as reverse transcriptase. Between 2007 and 2010, six blood donations with false-negative nucleic acid technology (NAT) results were reported in Germany. Therefore, NAT screening in two viral genome regions was introduced by our blood donation service in 2010 on a voluntary basis and became mandatory in Germany since the beginning of 2015.Blood donor screening was done using, in parallel, the German Red Cross (GRC) HIV-1 CE long terminate repeats (LTR) PCR kit and the GRC HIV-1 gag CE PCR kit. In total, 7 million blood donations were screened during the study period from 2010 to 2014 with the GRC dual-target human immunodeficiency virus 1 (HIV-1) NAT system. Additionally, three suspicious specimens were analyzed by four monotargeted NAT assays and by five dual-target NAT assays.Three of 7 million donations tested negative using the 5'LTR-polymerase chain reaction, but they were positive if amplification was performed in the gag region. HIV antibodies were detected in all three donations. Nucleic acid sequence analysis identified a deletion of 22 bases within the 5'LTR probe binding region. Three different ltr-based monotargeted assays missed two donations, except for a low-reactive result obtained by one of the assays. In total, the detection rates for HIV-1-positive donations were 37.5% (3/8) for monotargeted assays and 100% (10/10) for dual-target assays.The current data demonstrate that dual-target NAT systems reduce the risk of false-negative HIV-1 NAT screening results.
- Published
- 2017
8. Establishment and evaluation of a loop-mediated isothermal amplification (LAMP) assay for the semi-quantitative detection of HIV-1 group M virus
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Raphael Lwembe, Eddy Okoth Odari, Josef Eberle, Hans Nitschko, Lutz Gürtler, and Alex Maiyo
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Detection limit ,Genotype ,biology ,Human immunodeficiency virus (HIV) ,Loop-mediated isothermal amplification ,HIV Infections ,Viral Load ,medicine.disease ,medicine.disease_cause ,Kenya ,Sensitivity and Specificity ,Virology ,Virus ,Integrase ,Acquired immunodeficiency syndrome (AIDS) ,Germany ,HIV-1 ,medicine ,biology.protein ,Humans ,Drug Monitoring ,Viral load ,HIV drug resistance - Abstract
The past decade has witnessed a dramatic increase of anti-retroviral treatment of human immunodeficiency virus (HIV) infected patients in many African countries. Due to costs and lack of currently available commercial viral load assays, insufficient attention has been paid to therapy monitoring through measurement of plasma viral load. This challenge of patient monitoring by tests as viral load, CD4 cell count, and finally HIV drug resistance could reverse achievements already made against HIV/AIDS infection. Loop-mediated isothermal amplification (LAMP) has been shown to be simple, rapid and cost-effective, characteristics which make this assay suitable for viral load monitoring in resource limited settings. This paper describes a revised LAMP assay using primers in the HIV-1 integrase region. The assay can be used for semi-quantitative measurement of HIV-1 group M viral load. The lower limit of detection (LLOD) was determined as 1200copies/mL and lower limit of quantitation (LLOQ) at 9800copies/mL. Sensitivities of 82 and 86% (in 135 and 99 plasma samples respectively from Kenya) and 93% (in 112 plasma samples from Germany) and specificities of 99 and 100% were realized. HIV-1 group O and HIV-2 virus samples were not detected. This LAMP assay has the potential for semi-quantitation of HIV-1 group M viral load in resource limited countries. There is still a need for further improvement by refinement of primers in respect to detection of HIV-1 group M non-B virus.
- Published
- 2015
9. Pathogen reduction/inactivation of products for the treatment of bleeding disorders: what are the processes and what should we say to patients?
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Hermann Eichler, Andreas Tiede, James W. Ironside, Giovanni Di Minno, Mariana Canaro, David Navarro, Carlo Federico Perno, Lutz Gürtler, Di Minno, Giovanni, Navarro, David, Perno, Carlo Federico, Canaro, Mariana, Gürtler, Lutz, Ironside, James W., Eichler, Hermann, and Tiede, Andreas
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Infection risk ,Blood transfusion ,medicine.medical_treatment ,Review Article ,030204 cardiovascular system & hematology ,Hemorrhagic disorder ,Inactivation ,0302 clinical medicine ,Risk Factors ,Blood product ,Medicine ,Pathogen ,Bleeding disorder ,Hematology ,Viru ,General Medicine ,Blood Coagulation Disorders ,Virus ,Hemorrhagic Disorder ,Blood ,Blood-Borne Pathogens ,Human ,medicine.medical_specialty ,Sepsi ,Blood Safety ,Hemorrhagic Disorders ,Risk Assessment ,Sepsis ,03 medical and health sciences ,Internal medicine ,Journal Article ,Humans ,Blood Transfusion ,Blood Coagulation Disorder ,business.industry ,Risk Factor ,Clotting ,medicine.disease ,Blood-Borne Pathogen ,Residual risk ,Disinfection ,Patient information ,Immunology ,business ,Removal ,030215 immunology - Abstract
Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered.
- Published
- 2017
10. Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins
- Author
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Ruth Brack-Werner, Stephanie Rebensburg, Martha Schneider, Josef Eberle, Markus Helfer, Michael Schindler, Herwig Koppensteiner, and Lutz Gürtler
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0301 basic medicine ,viruses ,030106 microbiology ,Microbial Sensitivity Tests ,Drug resistance ,Biology ,Virus Replication ,Antiviral Agents ,Article ,Virus ,Cell Line ,Marburg virus ,03 medical and health sciences ,Viral Envelope Proteins ,Viral envelope ,Drug Resistance, Viral ,Humans ,Antibody-dependent enhancement ,Cells, Cultured ,Multidisciplinary ,Dose-Response Relationship, Drug ,Plant Extracts ,Cistus ,Polyphenols ,Cistus × incanus ,Filoviridae ,Virology ,In vitro ,030104 developmental biology ,Cell culture ,HIV-1 - Abstract
Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles.
- Published
- 2016
11. The Evolution of Drug Resistance Interpretation Algorithms: ANRS, REGA and Extension of Resistance Analysis to HIV-1 Group O and HIV-2
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Josef Eberle and Lutz Gürtler
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Genotype ,Hepacivirus ,Human immunodeficiency virus (HIV) ,Microbial Sensitivity Tests ,Drug resistance ,medicine.disease_cause ,Interpretation (model theory) ,Virology ,Drug Resistance, Viral ,medicine ,Humans ,Single amino acid ,Genetics ,Mutation ,biology ,Computational Biology ,biology.organism_classification ,Molecular Typing ,Infectious Diseases ,Virus Diseases ,Data Interpretation, Statistical ,HIV-2 ,HIV-1 ,Algorithm ,Algorithms ,HIV drug resistance - Abstract
Antiretroviral drug resistance is mostly linked to a complex interaction of several amino acids with variable importance or a single amino acid. To facilitate the interpretation of observed mutation patterns, hospital university centers have developed several interpretation systems. All the currently available interpretation algorithms evolved, are being continuously updated and have been improved during the last decade. Some discrepancies are still evident that are partially smoothened by link of the individual programs with other systems. After the interpretation of HIV-1 group M subtype B mutations, a refined algorithm for the other group M subtypes was developed followed by the interpretation of HIV-1 group O and HIV-2 mutations. The process of improvement is ongoing, due to the better understanding and interpretation of single and cluster mutations and the availability of new antiretroviral substances. The knowledge gained from the experience of HIV drug resistance testing has been used to establish the interpretation of HBV polymerase mutations and will be extended for the treatment of HCV infected with protease inhibitors.
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- 2012
12. Confirmation of Putative HIV-1 Group P in Cameroon
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Lutz Gürtler, Sushil G. Devare, Lazare Kaptue, Julie Yamaguchi, Dora Mbanya, Charlotte Ngansop, Catherine A. Brennan, Ana Vallari, Florence Makamche, Barbara J. Harris, Nicaise Ndembi, and Vera Holzmayer
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Male ,Lineage (genetic) ,Genotype ,Molecular Sequence Data ,Immunology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,Virology ,Prevalence ,medicine ,Humans ,Cameroon ,Hospital patients ,virus diseases ,Sequence Analysis, DNA ,Middle Aged ,Simian immunodeficiency virus ,biology.organism_classification ,Clinical research ,Genetic Diversity and Evolution ,Insect Science ,Lentivirus ,HIV-1 ,Simian Immunodeficiency Virus - Abstract
We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of adaptation to humans.
- Published
- 2011
13. Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus
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Martin Stürmer, Hans Wilhelm Doerr, and Lutz Gürtler
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Microbiology (medical) ,Sexually transmitted disease ,Anti-HIV Agents ,Immunology ,HIV Infections ,Review ,medicine.disease_cause ,Virus ,Orthohepadnavirus ,Acquired immunodeficiency syndrome (AIDS) ,HBV ,medicine ,Virus maturation ,Humans ,Immunology and Allergy ,Diagnostics ,Hepatitis B virus ,biology ,HIV ,General Medicine ,Hepatitis B ,biology.organism_classification ,medicine.disease ,Hepatitis C ,Virology ,Drug Design ,HCV ,Therapy ,Viral load - Abstract
The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered.
- Published
- 2009
14. Near Full-Length Genome Characterization of an HIV Type 1 CRF25_cpx Strain from Cameroon
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John Hackett, Charlotte Ngansop, Vera Holzmayer, Priscilla Swanson, Lazare Kaptue, Dora Mbanya, Lutz Gürtler, Nicaise Ndembi, Sushil G. Devare, Catherine A. Brennan, and Ka-Cheung Luk
- Subjects
Genotype ,Molecular Sequence Data ,Immunology ,Human immunodeficiency virus (HIV) ,Sequence Homology ,HIV Infections ,Genome, Viral ,Biology ,medicine.disease_cause ,Genome ,Virus ,law.invention ,law ,Virology ,medicine ,Cluster Analysis ,Humans ,Cameroon ,Phylogeny ,Full length genome ,Recombination, Genetic ,Genetics ,Genetic diversity ,Phylogenetic tree ,Strain (biology) ,Sequence Analysis, DNA ,Infectious Diseases ,HIV-1 ,Recombinant DNA ,RNA, Viral - Abstract
Recombinant forms of HIV-1 contribute significantly to the ongoing epidemic. In the present study, we characterized the near full-length genome of one candidate HIV-1 CRF25_cpx strain originating in Cameroon, 06CM-BA-040. Viral RNA was extracted from plasma, and the genome was obtained using RT-PCR amplification to generate 10 overlapping fragments. Bootscanning, recombination breakpoint analysis, and phylogenetic trees confirmed that 06CM-BA-040 had a genomic structure consistent with two available CRF25_cpx reference sequences. The CRF25_cpx mosaic composition consisted of nine segments derived from subtypes A and G as well as unclassified (U) regions. Subtype G and CRF25_cpx clusters diverged from each other with long branch lengths but were distinct from other known subtypes with high bootstrap support (94%). The epidemiological significance of CRF25_cpx strains is unknown; however, the availability of additional genomic sequences will improve our understanding of the overall genetic diversity within this recombinant form of HIV-1.
- Published
- 2008
15. HIV-2EU-Supporting Standardized HIV-2 Drug-Resistance Interpretation in Europe: An Update
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Charlotte, Charpentier, Ricardo, Camacho, Jean, Ruelle, Josef, Eberle, Lutz, Gürtler, Alejandro, Pironti, Martin, Stürmer, Françoise, Brun-Vézinet, Rolf, Kaiser, Diane, Descamps, and Martin, Obermeier
- Subjects
HIV-2 ,Mutation ,Humans ,HIV Infections - Published
- 2015
16. Near-Full-Length Genomic Sequence of a Human Immunodeficiency Type 1 Subtype G Strain from Cameroon
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Vera Holzmayer, Lutz Gürtler, Leopold Zekeng, Sushil G. Devare, Lazare Kaptue, and John Hackett
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Genetics ,Strain (biology) ,Molecular Sequence Data ,Immunology ,Human immunodeficiency virus (HIV) ,Blood Donors ,Genomics ,Genome, Viral ,Sequence Analysis, DNA ,Biology ,medicine.disease_cause ,Virology ,Infectious Diseases ,HIV Seropositivity ,HIV-1 ,medicine ,Humans ,Cameroon ,Phylogeny ,Sequence (medicine) - Published
- 2005
17. Rates of Postoperative Complications among Human Immunodeficiency Virus–Infected Women Who Have Undergone Obstetric and Gynecologic Surgical Procedures
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Manfred Stauber, Bernd H. Belohradsky, Olaf Dathe, Daniela Reindell, Thomas Grubert, Lutz Gürtler, and Ralph Kästner
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Adult ,Microbiology (medical) ,medicine.medical_specialty ,medicine.medical_treatment ,Obstetric Surgical Procedures ,HIV Infections ,Gynecologic Surgical Procedures ,Postoperative Complications ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Humans ,Medicine ,Antibiotic prophylaxis ,Risk factor ,Sida ,biology ,business.industry ,Immunity ,Odds ratio ,biology.organism_classification ,medicine.disease ,Curettage ,Surgery ,Women's Health Services ,Infectious Diseases ,Female ,Morbidity ,business ,Complication ,Abdominal surgery - Abstract
Clinical observations indicate that human immunodeficiency virus (HIV)‐positive women experience more postoperative problems than do HIV-negative women. To obtain a better estimate of the individual risk of postoperative morbidity among HIV-infected women, and to determine which procedures pose the greatest risk, we performed a retrospective case-control study in which we assessed the outcomes after 235 obstetric and gynecologic surgical procedures. For purposes of comparison, an HIV-negative control patient was matched for each of the 235 surgical procedures performed, on the basis of the type of procedure and patient age. We found a significantly greater number of postoperative complications among the HIV-positive women. Higher complication rates occurred after abdominal surgery (odds ratio [OR], 3.6; ) and curettage (OR, 7.7; P p .001 ). Among HIV-infected women, the risk of complications was associated with immune status. AntiP p .06 retroviral therapy and standard perioperative antibiotic prophylaxis did not decrease the risk of complications. Indications for performing abdominal surgery and curettage on HIV-infected women should be carefully weighed against the potential risk of postoperative complications.
- Published
- 2002
18. A new antioxidative vitamin B 6 analogue modulates pathophysiological cell proliferation and damage
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Kurt Polborn, Andreas K. Nussler, Manuel Modolell, Walter Oberthür, Kesel Andreas Johannes, Isolde Sonnenbichler, Lutz Gürtler, and Wolfgang E. F. Klinkert
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CD4-Positive T-Lymphocytes ,Models, Molecular ,Programmed cell death ,Time Factors ,Clinical Biochemistry ,Pharmaceutical Science ,Bone Marrow Cells ,Crystallography, X-Ray ,Models, Biological ,Biochemistry ,Nitric oxide ,Mice ,chemistry.chemical_compound ,Drug Discovery ,Tumor Cells, Cultured ,Animals ,Humans ,Molecular Biology ,Nitrites ,chemistry.chemical_classification ,Syncytium ,Reactive oxygen species ,Dose-Response Relationship, Drug ,biology ,Cell growth ,Organic Chemistry ,Pyridoxine ,Metabolism ,In vitro ,Rats ,Nitric oxide synthase ,Models, Chemical ,chemistry ,HIV-1 ,biology.protein ,Molecular Medicine ,Cell Division - Abstract
The new large scale synthesis of the yellow colored vitamin B6 analogue 5′-O-phosphono-pyridoxylidenerhodanine (2) (B6PR) leads to oligohydrates of its monosodium salt (4). The light-red hemiheptadecahydrate (8 1 2 hydrate) (4a) was crystallized and its three-dimensional structure determined by X-ray crystallography. Special nucleotide and protein interaction properties together with scavenging antioxidative function are combined in this simple water-soluble vitamin B6 analogues B6PR. High (mM) concentrations were untoxic to ‘healthy’ not affected cells and primary tissues. Complexation of ions (e.g. Ca2+, Fe2+, and Zn2+), modulation of nitric oxide synthases (NOS I-III), nitric oxide (NO) metabolism, and reactive oxygen species (ROS) was found. Special cytoprotecting, immunomodulating, stimulating and inhibiting activities were observed in vitro, not in comparison with some natural and synthetic pyridoxines. Low B6PR suppressed proliferation, high induced selective cell death of some cancer cell lines. Low B6PR protected HIV-1-infected CD4+ HUT 78 cells against HIV-1-mediated destruction (complete inhibition of HIV-1-induced syncytia formation and cell death) and reduced p24 level. Autoreactive S100β-specific T cells of Lewis rat, a model of multiple sclerosis, could be influenced. Oxidative damage and age, acquired and inherited disease related pathophysiological disorders can be treated by this new cytopathology-selective versatile acting B6PR. ©
- Published
- 1999
19. Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus
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Bernd H. Belohradsky, Josef Eberle, Theoni Petropoulou, Florian Hoffmann, Uwe Wintergerst, Gundula Notheis, Lutz Gürtler, and B. Sölder
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Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Anti-HIV Agents ,HIV Infections ,Indinavir ,Gastroenterology ,Statistics, Nonparametric ,Cohort Studies ,Zidovudine ,Internal medicine ,medicine ,Humans ,Child ,Reverse-transcriptase inhibitor ,Nucleoside analogue ,business.industry ,Stavudine ,Infant ,Lamivudine ,HIV Protease Inhibitors ,Viral Load ,Virology ,CD4 Lymphocyte Count ,Infectious Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,Female ,Viral disease ,business ,Viral load ,medicine.drug - Abstract
Objective. The effects of two antiretroviral triple combinations including the protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells were evaluated. Methods. Fifteen patients with high viral load or disease progression under their prior antiretroviral therapy were switched to zidovudine/ lamivudine/indinavir (Group A, n = 10) or stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral load and CD4 cells were performed. Results. The median reduction of the viral load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and 2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of 10 patients in Group A and 3 of 5 patients in Group B had viral load reductions below the detection limit of the assay. Patients with an additional switch of nucleoside analogues at start of indinavir therapy (regardless of the specific reverse transcriptase inhibitor used) had significantly better reductions of the viral load than patients without such a switch (median 2.3 log vs. 0.2 log after 6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians of the relative increase of CD4 cells were 145 and 163% (not significant), respectively. Two patients from Group A and 1 from Group B developed renal calculi, which resolved after adequate hydration. One patient was withdrawn because of intractable vomiting attributed to indinavir. Conclusion. In a small cohort of HIV-infected pediatric patients with extensive prior antiretroviral treatment, triple therapy including indinavir had a sustained effect on the decrease of the viral load and the increase of CD4 cells similar to results obtained in antiretrovirally experienced adults. This effect was significantly better in patients with an additional switch of a nucleoside analogue at start of triple therapy with indinavir than in patients without such a change.
- Published
- 1998
20. HIV Type 1 V3 Serotyping of Tanzanian Samples: Probable Reasons for Mismatching with Genetic Subtyping
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Fred Minja, Davis Mwakagile, Jonathan Weber, Michael Hoelscher, Sabine Hanker, Ursula Dietrich, Elisabeth Nägele, Rachanee Cheingsong-Popov, Francis Barin, Frank von Sonnenburg, Andreas Markuzzi, David O. Olaleye, Lutz Gürtler, and Brigitte Jordan-Harder
- Subjects
Serotype ,Genotype ,Molecular Sequence Data ,Immunology ,Enzyme-Linked Immunosorbent Assay ,HIV Envelope Protein gp120 ,World Health Organization ,Tanzania ,Protein Structure, Secondary ,Virus ,Viral envelope ,Virology ,Humans ,Medicine ,Amino Acid Sequence ,Typing ,Serotyping ,Immunodeficiency ,Acquired Immunodeficiency Syndrome ,biology ,business.industry ,medicine.disease ,biology.organism_classification ,Peptide Fragments ,Subtyping ,Infectious Diseases ,Data Interpretation, Statistical ,Lentivirus ,HIV-1 ,Neural Networks, Computer ,business - Abstract
HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Findings are reported from a study conducted to determine whether HIV-1 serotyping could be effectively used to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. The HIV-1 genetic subtypes of 86 people with AIDS in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were then compared with V3 serotyping results obtained by analysis with tests manufactured by Behring and the Pettenkofer Institute, tests conducted by St. Mary's Hospital Medical School, tests conducted by Georg-Speyer-Haus, and tests conducted by Universite Francois Rabelais. The following HIV-1 genetic subtypes were identified: 25 cases of A (29%), 47 of C (55%), 13 of D (15%), and 1 of G (1%). The sensitivity and specificity of the serotyping assays varied considerably. These data indicate that HIV-1 serotyping is not accurate enough to predict genetic subtypes in Tanzania. This conclusion was reached based upon the highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. The serotyping results instead reflect the frequency distribution of V3 serotypes.
- Published
- 1998
21. Complement Activation by HIV-1–Infected Cells
- Author
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Anton Hittmair, Christina Ochsenbauer, Valerie Bosch, Josef R. Patsch, Lutz Gürtler, Manfred P. Dierich, Peter Marschang, and Ute Krüger
- Subjects
Blotting, Western ,Immunology ,Transfection ,Epitope ,Cell Line ,Classical complement pathway ,Virology ,Chlorocebus aethiops ,Animals ,Humans ,Immunology and Allergy ,Fluorescent Antibody Technique, Indirect ,Complement Activation ,Decay-accelerating factor ,biology ,Complement component 2 ,Complement C1q ,virus diseases ,Complement C3 ,Flow Cytometry ,Molecular biology ,HIV Envelope Protein gp41 ,Complement system ,Factor H ,CD4 Antigens ,HIV-1 ,biology.protein ,Alternative complement pathway ,HeLa Cells ,Complement control protein - Abstract
To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.
- Published
- 1997
22. Effect of antiretroviral combination therapy (zidovudine/didanosine or zidovudine/lamivudine) on quantitative plasma human immunodeficiency virus–ribonucleic acid in children and adolescents infected with human immunodeficiency virus
- Author
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Lutz Gürtler, Brigitte Sölder, Uwe Wintergerst, Bernd H. Belohradsky, Gundula Notheis, and Josef Eberle
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Combination therapy ,Anti-HIV Agents ,HIV Infections ,Gastroenterology ,Virus ,Group B ,Zidovudine ,Internal medicine ,Humans ,Medicine ,Viremia ,Child ,Didanosine ,AIDS-Related Opportunistic Infections ,business.industry ,Infant ,Lamivudine ,Viral Load ,Virology ,CD4 Lymphocyte Count ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,Viral disease ,business ,Viral load ,medicine.drug - Abstract
Objective: To assess human immunodeficiency virus (HIV) ribonucleic acid load in children and adolescents with HIV infection who are being treated with antiretroviral combination therapy. Study design: Five patients whose disease progressed with their prior antiretroviral therapy had treatment regimens changed to zidovudine (ZDV)/didanosine (DDI) (group A), and the regimens of six patients were changed to ZDV/lamivudine (3TC) (group B). Patients were followed every 4 to 8 weeks for an average period of 8.6 months. Serial determinations of viral copy numbers and CD4 cells were performed. Results: In group A patients' mean relative changes in CD4 cells showed a 20% increase after 4 months (difference not significant [NS]) and a return to baseline after 8 months; in group B patients' mean relative increases of CD4 cells were 72% ( p = 0.046) and 50% (NS), respectively. In group A mean relative viral load increased 21% (0.08 log 10 , NS) and 71% (0.23 10 log, NS), whereas in group B viral load decreased 22% (0.1 log 10 , NS) and 74% (0.58 log 10 , p = 0.03) after 4 and 8 months, respectively. After starting antiretroviral combination therapy in group A, there was a slight trend of a decreasing ratio of viral load per number of CD4 cells, whereas in group B this ratio significantly decreased, indicating a marked suppression of viral turnover with ZDV/3TC treatment. Conclusion: In a small cohort of pediatric patients, combination therapy with ZDV/3TC was well tolerated and had a strong and sustained effect on the decrease of viral load similar to results obtained in adults. In patients with ZDV/DDI therapy the reduction of viral load was less pronounced, but treatment groups A and B were not comparable for statistic evaluation. (J Pediatr 1997;130:293-9)
- Published
- 1997
23. Pathogen safety of long-term treatments for bleeding disorders: still relevant to current practice
- Author
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Andreas Tiede, James W. Ironside, Mariana Canaro, Giovanni Di Minno, Carlo Federico Perno, Lutz Gürtler, David Navarro, DI MINNO, Giovanni, Canaro, M, Ironside, Jw, Navarro, D, Perno, Cf, Tiede, A, and Gürtler, L.
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Time Factors ,Long term treatment ,Blood transfusion ,medicine.medical_treatment ,Treatment outcome ,Editorials and Perspectives ,Hemophilia A ,Hemorrhagic Disorders ,Hemorrhagic disorder ,hemic and lymphatic diseases ,Blood-Borne Pathogens ,medicine ,Humans ,Blood Transfusion ,Pathogen ,Clotting factor ,business.industry ,Hematology ,Recombinant Proteins ,Treatment Outcome ,Current practice ,Immunology ,business - Abstract
Hemophilia defines a group of hereditary bleeding disorders: hemophilia A (deficiency of Factor VIII, FVIII), hemophilia B (deficiency of FIX), and para-hemophilia (deficiency of FV). These result from mutations in clotting factor genes. As in the large majority of bleeding disorders ([Table 1][1
- Published
- 2013
24. Reduced CD21 (CR2) and CD54 (ICAM-1) expression in MT2 cells with HIV-1 or HIV-2 strains
- Author
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M. Tötsch, Clara Larcher, N. Julen, M. P. Dierich, Lutz Gürtler, and W.M. Prodinger
- Subjects
ICAM-1 ,biology ,T-Lymphocytes ,Receptor expression ,CD3 ,Immunology ,Down-Regulation ,hemic and immune systems ,chemical and pharmacologic phenomena ,Intercellular Adhesion Molecule-1 ,Molecular biology ,Cell culture ,hemic and lymphatic diseases ,HIV-2 ,HIV-1 ,biology.protein ,Humans ,Immunology and Allergy ,Receptors, Complement 3d ,RNA, Messenger ,IL-2 receptor ,Functional ability ,Receptor ,CD8 ,Cell Line, Transformed - Abstract
Alterations in the expression of cell-surface receptors have been reported in HIV-infected cells for CD4, CD25 (IL-2 receptor), CD2, CD3 and CD8 and CD26. In the present study we provide evidence that CD21 is down-regulated in the human T-lymphoblastoid cell line MT2 after infection with HIV-1 and -2 isolates. The same effect was observed with ICAM-1 (CD54). CD21 expression was monitored by means of fluorescence intensity, its functional ability to bind to C3d and by quantitative measurement of CD21-antigen in supernatants and cell lysates using an immunoassay. In addition, the decrease of CD21 and ICAM-1-specific mRNA suggests a mechanism at a transcriptional level. Our data suggest that HIV might have a direct influence on the receptor expression.
- Published
- 1995
25. Comparison of Drug Resistance Scores for Tipranavir in Protease Inhibitor-Naïve Patients Infected with HIV-1 B and Non-B Subtypes ▿
- Author
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Martin Stürmer, Pierre Lecocq, G Knecht, Hans Wilhelm Doerr, Lutz Gürtler, Peter Gute, Markus Bickel, Christoph Stephan, H. R. Brodt, and Margriet Van Houtte
- Subjects
Genotype ,Anti-HIV Agents ,Pyridines ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,Biology ,medicine.disease_cause ,Antiviral Agents ,Drug Resistance, Viral ,medicine ,HIV Protease Inhibitor ,Humans ,Pharmacology (medical) ,Protease inhibitor (pharmacology) ,Pharmacology ,Sulfonamides ,Protease ,HIV Protease Inhibitors ,Infectious Diseases ,Pyrones ,Immunology ,Cohort ,Mutation ,Tipranavir ,medicine.drug - Abstract
Genotypes of samples from protease inhibitor-naïve patients in Frankfurt's HIV Cohort were analyzed with five tipranavir resistance prediction algorithms. Mean scores were higher in non-B than in B subtypes. The proportion of non-B subtypes increased with increasing scores, except in weighted algorithms. Virtual and in vitro phenotype analyses of samples with increased scores showed no reduced tipranavir susceptibility. Current algorithms appear suboptimal for interpretation of resistance to tipranavir in non-B subtypes; increased scores might reflect algorithm bias rather than “natural resistance.”
- Published
- 2011
26. Human Immunodeficiency Virus Cannot Productively Infect Freshly Cultured Human Cartilage Cells
- Author
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Eberhard Wilmes, Hans Meyer, Lutz Gürtler, Claus Hammer, and Jesús Bujía
- Subjects
Acquired Immunodeficiency Syndrome ,Virulence ,Cartilage ,HIV Core Protein p24 ,virus diseases ,In Vitro Techniques ,Biology ,Virology ,Endocytosis ,Reverse transcriptase ,In vitro ,Virus ,medicine.anatomical_structure ,Phagocytosis ,Otorhinolaryngology ,Antigen ,Cartilage transplantation ,In vivo ,Cell culture ,HIV-1 ,medicine ,Humans ,Cells, Cultured ,Nasal Septum - Abstract
The use of cartilage allografts is being discussed because of the possible transmission of the human immunodeficiency virus (HIV). To further delineate the possibility for an HIV infection of cartilage cells the susceptibility and permissivity of normal human chondrocytes to HIV-1 was assessed in culture. Isolated cartilage cells were incubated during 30 days with the HIV, testing the production of viral p24 antigens and the formation of particle-bound reverse transcriptase (RT) in the supernatant. The H9 cell line was used as positive control. The production of p24 antigen did not occur on chondrocytes during the whole culture time. Furthermore, no RT activity was detected throughout the entire experimental period. Our results indicate clearly that HIV was not able to infect cartilage cells under these in vitro conditions, and, conclusively, HIV infection of cartilage in vivo is improbable.
- Published
- 1993
27. Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment
- Author
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Martin Stürmer, Lutz Gürtler, I Michels, A Müller, L Locher, Gaby Nisius, Schlomo Staszewski, and H-W Doerr
- Subjects
genotypic resistance ,RNase H ,RNase P ,Anti-HIV Agents ,antiretroviral therapy ,Drug Resistance ,lcsh:Medicine ,HIV Infections ,Biology ,medicine.disease_cause ,Virus Replication ,Polymerase Chain Reaction ,Virus ,Zidovudine ,Genotype ,reverse transcriptase ,medicine ,Humans ,Taq Polymerase ,connection domain ,Genetics ,Mutation ,Research ,lcsh:R ,General Medicine ,Virology ,Reverse transcriptase ,HIV Reverse Transcriptase ,polymerase ,Amino Acid Substitution ,Anti-Retroviral Agents ,biology.protein ,HIV-1 ,RNA, Viral ,Primer (molecular biology) ,medicine.drug - Abstract
Objective Replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome. For RT inhibitors, almost all identified mutations are located within the polymerase; therefore, general genotyping confines to investigate this subunit. Recently several studies have shown that substitutions within the RNase H and the connection domain increase antiviral drug-resistance in vitro, and some of them are present in patient isolates. Aim The aim of the present study was to investigate the prevalence of these substitutions and their association with mutations in the polymerase domain arising during antiretroviral treatment. Materials and methods We performed genotypic analyzes on seventy-four virus isolates derived from treated and untreated patients, followed at the HIV Centre of the Johann Wolfgang Goethe University Hospital (Frankfurt/Main, Germany). We subsequently analysed the different substitutions in the c-terminal region to evaluate whether there were associations with each other, n-terminal substitutions or with antiretroviral treatment. Results We identified several primer grip substitutions, but almost all of them were located in the connection domain. This is consistent with other in-vivo studies, in which especially the primer grip residues located in the RNase H were unvaried. Furthermore, we identified other substitutions in the connection domain and in the RNase H. Especially E399D seemed to be associated with an antiretroviral treatment and N-terminal resistance-delivering mutations. Conclusion Some of the identified substitutions were associated with antiviral treatment and drug resistance-associated mutations. Due to the low prevalence of C-terminal mutations and as only a few of them could be associated with antiviral treatment and N-terminal resistance-delivering mutations, we would not recommend routinely testing of the C-terminal RT region.
- Published
- 2010
28. Human immunodeficiency virus type-1 group M quasispecies evolution: diversity and divergence in patients co-infected with active tuberculosis
- Author
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Jaroslav Cinatl, T. Biru, Lutz Gürtler, Gabriele Nisius, Schlomo Staszewski, Christoph Stephan, Tessa Lennemann, and Martin Stürmer
- Subjects
Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Genotype ,Immunology ,Molecular Sequence Data ,Antitubercular Agents ,Virus Attachment ,HIV Infections ,Viral quasispecies ,Biology ,Polymerase Chain Reaction ,Virus ,law.invention ,Evolution, Molecular ,Plasma ,Medical microbiology ,Receptors, HIV ,law ,Polymorphism (computer science) ,medicine ,Immunology and Allergy ,Humans ,Cloning, Molecular ,Polymerase chain reaction ,Polymorphism, Genetic ,env Gene Products, Human Immunodeficiency Virus ,virus diseases ,General Medicine ,Sequence Analysis, DNA ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,Lentivirus ,HIV-1 ,RNA, Viral ,Female - Abstract
The evolution of intra-host human immunodeficiency virus type 1 (HIV-1) quasispecies prior and after treating active tuberculosis (TB) with chemotherapy in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV-1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated. C2V5 env was amplified by PCR and molecular cloning was performed. Eight to twenty-five clones were sequenced from each patient. Various phylogenetic analyses were performed. We found a significant increase in diversity and divergence in HIV-1/TB compared to the HIV-1/non-TB. For HIV-1/TB, the average rate of evolution of C2V5 env was higher than previous reports (2.4 × 10−4 substitution/site/day). Two groups of HIV-1/TB were observed based on the rate of HIV-1 evolution and coreceptor usage: A fast evolving R5-tropic dominating group and a relatively slowly evolving X4 group. The results demonstrated that active TB has an impact on HIV-1 viral diversity and divergence over time. The influence of active TB on longitudinal evolution of HIV-1 may be predominant for R5 viruses.
- Published
- 2010
29. The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex
- Author
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Pauline Dowd, Helga Rübsamen-Waigmann, Richard R Doherty, Lutz Gürtler, Oliviero E. Varnier, David A. Cooper, Françoise Brun-Vézinet, Yvonne Pérol, Court Pedersen, David C. Shanson, Jacques Leibowitch, Karl Otto Habermehl, Peter Skinhøj, and Ruedi Lüthy
- Subjects
Sexually transmitted disease ,medicine.medical_specialty ,Immunology ,HIV Core Protein p24 ,AIDS-related complex ,Acyclovir ,Placebo ,law.invention ,Zidovudine ,Double-Blind Method ,Acquired immunodeficiency syndrome (AIDS) ,Randomized controlled trial ,AIDS-Related Complex ,law ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Outpatient clinic ,Aciclovir ,Acquired Immunodeficiency Syndrome ,business.industry ,virus diseases ,medicine.disease ,Surgery ,Infectious Diseases ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
OBJECTIVE To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS). DESIGN Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.
- Published
- 1992
30. Near full-length genome characterization of three additional HIV type 1 CRF13_cpx strains from Cameroon
- Author
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Lutz Gürtler, John Hackett, Hermine Gayum, Charlotte Ngansop, Dora Mbanya, Vera Holzmayer, Marcelline Ngounoue Djuidje, Catherine A. Brennan, Sushil G. Devare, Donatien Kamdem, Julie Yamaguchi, Ka-Cheung Luk, Nicaise Ndembi, Priscilla Swanson, and Lazare Kaptue
- Subjects
Adult ,Male ,Immunology ,Molecular Sequence Data ,HIV Infections ,Biology ,Genome ,law.invention ,Phylogenetics ,law ,Virology ,Humans ,Cameroon ,Phylogeny ,Genetics ,Genetic diversity ,Phylogenetic tree ,Sequence Analysis, RNA ,Strain (biology) ,Breakpoint ,Infectious Diseases ,Recombinant DNA ,HIV-1 ,Female ,Recombination ,Reassortant Viruses - Abstract
Recombinant forms of HIV-1 contribute significantly to the ongoing epidemic. In the present study, we characterized the near full-length genomes of three candidate HIV-1 CRF13_cpx strains originating in Cameroon, 04CM-173-9, 04CM-632-28, and 02CM-A1394. Bootscanning, recombination breakpoint analysis, and phylogenetic trees confirmed similar genomic structures with identical breakpoint positions compared to the three available CRF13_cpx sequences. The candidate and reference sequences formed a distinct cluster well separated from other group M subtypes and had a mosaic structure derived from subtypes A1, G, J, and CRF01_AE. The similarity in genomic composition and position of recombination breakpoints suggest that these isolates share a common ancestor. The epidemiological significance of CRF13_cpx strains in Cameroon is unknown; however, the availability of three additional genomic sequences will improve our understanding of the overall genetic diversity within this recombinant form of HIV-1.
- Published
- 2007
31. Influence of Chemical Allograft Preservation Procedures on the Human Immunodeficiency Virus
- Author
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Eberhard Wilmes, Jesús Bujía, Ernst Kastenbauer, and Lutz Gürtler
- Subjects
Cialit ,Molecular Sequence Data ,Human immunodeficiency virus (HIV) ,HIV Infections ,Spleen ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Virus ,law.invention ,Serology ,law ,Formaldehyde ,medicine ,Humans ,Transplantation, Homologous ,Polymerase chain reaction ,Base Sequence ,Transmission (medicine) ,Thimerosal ,Brain ,HIV ,virus diseases ,Virology ,Preservation Procedure ,Trachea ,Transplantation ,Blood ,Cartilage ,medicine.anatomical_structure ,Otorhinolaryngology ,Connective Tissue ,Immunology ,Tissue Preservation - Abstract
Since chemically preserved allogenic transplants have an established place in reconstructive procedures, the possibility of transferring the human immunodeficiency virus (HIV) with these transplants has been intensively discussed. In this study the authors obtained brain and spleen samples from six HIV-infected cadavers and preserved them with Merthiolate, Cialit, and formaldehyde. After preservation, the tissues were examined for proviral HIV-1 DNA (gag, pol, env) using the polymerase chain reaction. Proviral sequences were clearly demonstrated after the preservation procedure. The results of this study indicate that HIV remains in tissues that have been treated with Merthiolate, formaldehyde, or Cialit. Further investigations are necessary to determine if the virus is in an inactivated or activated form. It can be concluded that, because of the possible transmission of HIV by chemically preserved homografts, serologic screening of donors should be mandatory.
- Published
- 1996
32. Construction and characterization of an HIV-1 group O infectious molecular clone and analysis of vpr- and nef-negative derivatives
- Author
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Hans-Georg Kräusslich, Oliver T. Fackler, Lutz Gürtler, Ottmar Herchenröder, Denis M. Tebit, Lazare Kaptue, Leopold Zekeng, and Oliver T. Keppler
- Subjects
viruses ,Genes, vpr ,Molecular Sequence Data ,Reading frame ,Clone (cell biology) ,Gene Products, gag ,Gene Products, pol ,HIV Infections ,Biology ,medicine.disease_cause ,Virus Replication ,Virus ,Molecular clone ,Virology ,medicine ,Coding region ,Humans ,Primary isolate ,Cloning, Molecular ,Gene ,Cells, Cultured ,Phylogeny ,Mutation ,Virulence ,virus diseases ,Genes, nef ,Viral replication ,HIV-1 ,Gene Deletion - Abstract
In this report, we describe the construction and characterization of the first full-length infectious molecular clone from the Cameroonian HIV-1 group O primary isolate MVP8913. Virus obtained after transfection of the proviral clone pCMO2.3 replicated to levels comparable to its parental isolate in the human T-cell line PM-1, although replication was reduced by fivefold in peripheral blood mononuclear cells (PBMC) and was barely detectable in primary monocyte-derived macrophages (MDM). Phylogenetic analysis of the complete proviral sequence revealed a closer relationship to ANT70 than to MVP5180, the two prototypic group O primary isolates. All reading frames for structural and accessory genes were open except for vpr that contained an in-frame stop codon. In the nef gene, a mutation disrupting the functionally important myristoylation signal was observed. Repairing the defect in nef enhanced replication in PBMC and MDM, although repairing the vpr defect only affected replication in MDM, consistent with the known phenotypes of vpr and nef mutants in HIV-1 group M viruses. Repairing both vpr and nef showed an additive effect, but the resulting virus was still impaired compared to the parental isolate. This defect was overcome when the gag-pol coding region was exchanged for that from another O-type isolate giving rise to the proviral clone pCMO2.5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses.
- Published
- 2004
33. Blood-borne viruses: hepatitis A to G
- Author
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Lutz Gürtler
- Subjects
Hepatitis, Viral, Human ,business.industry ,Hepatitis A ,Hematology ,medicine.disease ,Virology ,Vaccination ,Blood donor ,Immunology ,Blood-Borne Pathogens ,Medicine ,Humans ,Viral disease ,Cardiology and Cardiovascular Medicine ,business ,Viral hepatitis ,Selection (genetic algorithm) ,Oncovirus - Published
- 2002
34. Shortening of the diagnostic window with a new combined HIV p24 antigen and anti-HIV-1/2/O screening test
- Author
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Hedwig Duttmann, Rigmor Thorstensson, Jürgen Feldner, S. Brust, Lutz Gürtler, and François Simon
- Subjects
Time Factors ,HIV Antigens ,HIV Core Protein p24 ,Blood Donors ,Enzyme-Linked Immunosorbent Assay ,HIV Infections ,Biology ,HIV Antibodies ,Acquired immunodeficiency syndrome (AIDS) ,Antigen ,Virology ,medicine ,Humans ,Mass Screening ,Multicenter Studies as Topic ,Seroconversion ,virus diseases ,AIDS Serodiagnosis ,Reproducibility of Results ,Viral Load ,medicine.disease ,Residual risk ,Cell culture ,Evaluation Studies as Topic ,Immunology ,HIV p24 Antigen ,HIV-2 ,biology.protein ,HIV-1 ,Reagent Kits, Diagnostic ,Antibody ,Viral load - Abstract
Because antibodies to the human immunodeficiency virus (HIV) are absent in the very early phase of HIV infection, there remains a slight residual risk for HIV transmission by blood donations by viremic but antibody negative donations. To shorten the diagnostic window between infection and the detection of antibodies, Enzygnost HIV Integral (Dade Behring, Germany) was developed. With this new test, HIV p24 antigen and HIV antibodies can be detected simultaneously in a single test. In a multicenter study the new screening assay has been compared with various tests that detect only HIV antibodies or HIV p24 antigen and with assays which permit a simultaneous detection of HIV antigen and HIV antibodies. The new assay showed 100% sensitivity for the detection of antibodies to HIV-1, groups M (n=1102) and O (n=55), and HIV-2 (n=289). In 23 out of 52 seroconversion panels, seroconversion was detected 2-18 days earlier with the new combined antigen/antibody test compared to single antibody tests. All samples from a viral load panel (n=451), all samples containing p24 antigen (n=302), and all but one of the cell culture supernatants (n=38) infected with various HIV-1 subtypes or HIV-2 were identified reliably by the new test. The specificity of the assay for 4002 unselected blood donors was 99.78% initially and 99.80% after retesting. Potentially interfering factors had no systematic influence on specificity. By testing for p24 antigen, which is present prior to the onset of antibody production in some cases of recent HIV infection, the new assay reduces the diagnostic window as compared to third generation screening assays, thus permitting an earlier diagnosis of HIV infection.
- Published
- 2000
35. Comparison of ritonavir plus saquinavir- and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection
- Author
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Bernd H. Belohradsky, Josef Eberle, Uwe Wintergerst, Gundula Notheis, Florian Hoffmann, and Lutz Gürtler
- Subjects
Microbiology (medical) ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Salvage therapy ,HIV Infections ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Protease inhibitor (pharmacology) ,Child ,Saquinavir ,Retrospective Studies ,Salvage Therapy ,Chemotherapy ,Nelfinavir ,Ritonavir ,business.industry ,HIV Protease Inhibitors ,Prognosis ,Virology ,Infectious Diseases ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,HIV-1 ,Drug Therapy, Combination ,Female ,Viral disease ,business ,Viral load ,medicine.drug - Abstract
Background. In this retrospective study we compared the antiretroviral effect of regimens consisting of simultaneous administration of two protease inhibitors (PI) with at least one nucleoside reverse transcriptase inhibitor on plasma viral load (VL) and CD4 cell count in HIV-infected children intensively pretreated with nucleoside reverse transcriptase inhibitors and PIs. Methods. Eleven HIV-infected children were changed to antiretroviral combination regimens including two PIs and followed for a median time of 24 weeks. Group A comprised six patients who were given ritonavir + saquinavir (SQV) and Group B consists of five patients who were changed to nelfinavir + SQV. Patients were treated with these combinations with 2 PIs because of treatment failure (increasing viral load) of prior PI therapy or clinical signs of disease progression. Outcome measures. Serial determinations of plasma viral load (Amplicor, Roche) and CD4 cells were performed every 4 to 8 weeks. The detection limit of the Amplicor-reverse transcriptase-PCR assay was 50 copies/ml (1.7 log 10 ). Results. In Group A the median VL reduction was 1.1 log 10 after 3 months and 1.4 log 10 after 6 months. In Group B median VL decreased 0.1 and 0.2 log 10 after 3 and 6 months. In both groups during the study period none of the patients reached undetectable VL. The relative changes of CD4 cells above baseline in Group A showed a median increase of 7% after 3 months and 23% after 6 months. In Group B after 3 months CD4 cells did not increase, and after 6 months the median relative increase was only 7%. Both combination therapies were well tolerated, not necessitating any drug interruption during study period. Conclusions. In children with intensive prior antiretroviral treatment, a salvage therapy including two PIs demonstrated antiretroviral efficacy in some patients. In this study the reduction of the VL as well as the increase of CD4 cells was more pronounced with ritonavir + SQV than with nelfinavir + SQV. With both combinations complete suppression of HIV replication was not achieved. Therefore the long term effect of these combinations may be limited by the emergence of resistant HIV strains.
- Published
- 2000
36. Detection of HIV-1 infection in dried blood spots from a 12-year-old ABO bedside test card
- Author
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Erwin Strobel, Ch. Emminger, J. Eberle, Lutz Gürtler, and G. Mayer
- Subjects
medicine.medical_specialty ,Human immunodeficiency virus (HIV) ,Blood Donors ,medicine.disease_cause ,Pathology and Forensic Medicine ,ABO Blood-Group System ,Risk Factors ,ABO blood group system ,Internal medicine ,Bedside test ,Genetics ,medicine ,Humans ,Mass Screening ,Dried blood ,Acquired Immunodeficiency Syndrome ,Hematologic Tests ,Spots ,business.industry ,Public Health, Environmental and Occupational Health ,virus diseases ,Transfusion Reaction ,Hematology ,General Medicine ,Middle Aged ,Psychiatry and Mental health ,Blood Stains ,HIV-1 ,Female ,business - Abstract
We tested dried blood from an ABO bedside test card which had been stored at room temperature for 12 years, to prove that a patient with HIV-1 infection had been infected by blood transfusion.Immunoblots for HIV-1 antibodies and threefold PCRs with half-nested primers for the HIV-1 integrase gene were done with eluates from the dried blood spots.HIV-1 antibodies and HIV-1 DNA could be detected in the sample from one unit of blood, but not from the two other units or from the recipient before transfusion.Further studies should be done on the validity of stored dried blood as an alternative to the storage of frozen donor serum for several years for 'look-back' studies.
- Published
- 1999
37. Reduction of the diagnostic window with a new combined p24 antigen and human immunodeficiency virus antibody screening assay
- Author
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Hanns Hofmann, Giancarlo Paggi, Walter Melchior, Bernard Weber, Lutz Gürtler, Ulrike Michl, Roberto G. Villaescusa, Vincenzo Bossi, Rigmor Thorstensson, Annelies Mühlbacher, Frederic Donie, JoseManuel Hernandez, and Adolfo Eiras
- Subjects
Time Factors ,HIV Core Protein p24 ,HIV Infections ,HIV Antibodies ,Virus ,Immunoenzyme Techniques ,Acquired immunodeficiency syndrome (AIDS) ,Antigen ,Virology ,medicine ,Humans ,Seroconversion ,biology ,business.industry ,virus diseases ,medicine.disease ,biology.organism_classification ,Immunology ,Lentivirus ,Monoclonal ,HIV-2 ,biology.protein ,HIV-1 ,Viral disease ,Reagent Kits, Diagnostic ,Antibody ,business - Abstract
In order to reduce the window phase between time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new fourth generation screening assays which permit a simultaneous detection of HIV antigen and antibody have been developed. In a multicenter study, a new automated fourth generation assay, Enzymun-Test HIV Combi (Boehringer Mannheim GmbH) was compared to third generation assay, p24 antigen tests and Western blot. A total of 37 seroconversion panels, samples of the early infection (n = 42), HIV-1 antibody positive sera, including subtypes A E, and O (n = 1118), HIV-2 positive samples (n = 252) and cell culture supernatants infected with different HIV-1 subtypes and HIV-2 (n = 50), blood donors (n = 6649), hospitalized patients (n = 475), HIV neg. sera with indeterminate Western blot (n = 32), potentially cross reactive serum samples (n = 435) and HIV negative specimens from Cameroon (n = 68) were tested. A total of 16 of 29 seroconversions were detected on average 8.5 days earlier with Enzymun-Test HIV Combi than HIV-1/HIV-2 3rd generation EIA (Abbott Laboratories). Overall, in the 29 panels investigated comparatively with the two assays, the mean time delay between Enzymun-Test HIV Combi and HIV-1/HIV-2 3rd generation EIA was 4.7 days. HIV antigen was detected in three out of 35 seroconversions one bleed earlier with HIV-1 Ag Monoclonal than with Enzymun-Test HIV Combi. Enzymun-Test HIV Combi showed a sensitivity of 100% for HIV antibody detection for HIV-1 group M and O and HIV-2 positive specimens. While p24 antigen of different HIV-1 subtypes was detected with Enzymun-Test HIV Combi in all the 49 cell culture supernatants, HIV Ag was not detected in an HIV-2 virus lysate. A total of 66 false positive results out of 7659 HIV negative samples were obtained with the Enzymun-Test HIV Combi. The specificity for unselected blood donors was 99.6%. The Enzymun-Test HIV Combi permits an earlier diagnosis of HIV infection than third generation assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion and it shows an excellent sensitivity for antibodies to all known HIV-1 subtypes and HIV-2. The specificity in blood donors and hospitalized patients is comparable to that of other assays.
- Published
- 1998
38. Inhibition of tryptase TL2 from human T4+ lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues
- Author
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Thomas Brinkmann, Nobuhiko Katunuma, Lutz Gürtler, Jochen Schäfers, Hiroshi Kido, Yasuharu Niwa, and Harald Tschesche
- Subjects
CD4-Positive T-Lymphocytes ,Serine Proteinase Inhibitors ,medicine.medical_treatment ,tryptase TL2 ,Molecular Sequence Data ,Biology ,V3 loop ,HIV Envelope Protein gp120 ,Virus Replication ,Biochemistry ,Kunitz-type inhibitor ,law.invention ,Cell Line ,Serine ,Aprotinin ,law ,medicine ,Humans ,Amino Acid Sequence ,Glycoproteins ,chemistry.chemical_classification ,Protease ,Membrane Glycoproteins ,bikunin ,Serine Endopeptidases ,HIV infection ,Molecular biology ,Recombinant Proteins ,Enzyme ,chemistry ,Viral replication ,Cell culture ,Recombinant DNA ,HIV-1 ,Tryptases ,Trypsin Inhibitor, Kunitz Soybean ,medicine.drug - Abstract
The serine esterase TL2 from human T4(+) lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism. Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin were investigated for their ability to inhibit tryptase TL2 and the binding of gp120 to this enzyme, Furthermore, the viral replication of HIV-1 was investigated in H9 cell cultures under the influence of recombinant aprotinin and bikunin variants. In contrast to native aprotinin, the recombinant variant [Arg(15), Phe(17), Glu(52)]aprotinin with a reactive-site sequence homologous to the V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (>80%). However, the [Leu(15), Phe(17), Glu(52)]aprotinin variant with hydrophobic subsites was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our results show that the enzyme activity of purified tryptase TL2 is inhibited not only by variants with basic amino acids, but also those with hydrophobic residues in the reactive-site region. Therefore, tryptase TH2 is not a typical trypsin-like or chymotrypsin-like protease, Investigations on inhibition of HIV-1 replication in H9 cell cultures showed that tryptase TL2 is involved in the mechanism of virus internalization into human lymphocytes. The [Leu(15), Phe(17), Glu(52)]aprotinin showed a significant retardation of syncytium formation over a period of 5 days in a 1 mu M concentration. Similar investigations were performed with recombinant variants of bikunin, the light chain of human inter-alpha-trypsin inhibitor, Only the single-headed variant [Arg(94)](delta 2) bikunin inhibited slightly the syncytium formation over a period of 2 days in a 2.2 mu M concentration, Wild-type bikunin and all full-length variants showed no effect, possibly due to steric hindrance by the second domain of the double-headed inhibitor.
- Published
- 1997
39. Difficulties and strategies of HIV diagnosis
- Author
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Lutz Gürtler
- Subjects
Adult ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,HIV Infections ,Window period ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Serology ,Acquired immunodeficiency syndrome (AIDS) ,Predictive Value of Tests ,Medicine ,Humans ,Child ,biology ,business.industry ,Infant, Newborn ,AIDS Serodiagnosis ,General Medicine ,medicine.disease ,Virology ,Subtyping ,Blot ,Agglutination (biology) ,Child, Preschool ,Immunology ,biology.protein ,Female ,Viral disease ,Antibody ,business - Abstract
HIV infection is commonly diagnosed by detection of antibodies (anti-HIV) by ELISA or agglutination. Reactive results are confirmed by western blot (immunoblot) or further specific tests such as competitive ELISA, which, when evaluated quantitatively, allow the differentiation of HIV types and partially subtypes. Detection of infection of newborn babies, characterisation of individual strains for subtyping and forensic identification, and therapeutic monitoring are the domain of nucleic-acid-based assays. Nucleic-acid-based assays narrow the serological diagnostic window period in early HIV infection and, when quantified, give some indication of clinical status.
- Published
- 1996
40. Analysis of the V3 loop sequences from 10 HIV type 1-infected AIDS patients from Paraguay
- Author
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Lutz Gürtler, Renate Kiefer, Marìa Elisa Vera, Ricardo Moreno Azorero, Josef Eberle, Margarita Cabral, Albrecht von Brunn, and Agueda Cabello
- Subjects
Male ,Immunology ,Molecular Sequence Data ,Human immunodeficiency virus (HIV) ,V3 loop ,Biology ,HIV Envelope Protein gp120 ,medicine.disease_cause ,Virus ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,medicine ,Cluster Analysis ,Humans ,Amino Acid Sequence ,Sida ,DNA Primers ,Acquired Immunodeficiency Syndrome ,Base Sequence ,Sequence Homology, Amino Acid ,Nucleic acid sequence ,medicine.disease ,biology.organism_classification ,Peptide Fragments ,Infectious Diseases ,Paraguay ,GenBank ,DNA, Viral ,HIV-1 ,Viral disease - Abstract
HIV-1 consists of eight subtypes, A through H, and group O. The HIV epidemic has only recently come to Paraguay. According to available data from the National AIDS Control Program of Paraguay, there were only 95 individuals known to have had AIDS in the country by the end of 1994. The authors report their findings from the study of HIV-1 from ten people with AIDS living in Asuncion. The subjects were male, with AIDS-related symptoms, and largely contracted HIV through homosexual contact. Some, however, contracted HIV through IV drug use or heterosexually. The nucleic acid sequences obtained from the collected viruses grown in tissue culture have been deposited in GenBank under accession numbers U28949 through U28959. All of the isolated viruses are of subtype B. Virus PY.3616, however, had a V3 loop with the rare motif APGR. The individual from whom this virus was obtained acquired his HIV infection through IV drug use, most probably in Argentina. Two viruses were obtained with V3 loop crown motifs of GPRR and GWRR (PY.12838 and PY.12839), motifs which have not been previously described, but which come close to the V3 loops of HIV-1 isolates found in Brazil with a crown motif GWGR, and also GMGR and GFGR. A motif with an arginine at another position, GRGQ, has been found in HIV-1 subtype H in Cameroon. The different motifs found in the sequences of the Paraguayan patients show greater homogeneity than those of African patients in the Central African Republic and in Paris. The observed diversity reflects the connection of Paraguayans with Brazil and other countries where HIV-1 subtype B prevails. The authors note that their findings are most likely representative of the ongoing, young HIV epidemic in Paraguay.
- Published
- 1995
41. Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959
- Author
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Josef Eberle, Klaus Von Der Helm, Hans Nitschko, Lutz Gürtler, Brigitte Bechowsky, D. Rose, and Ulrike Hauser
- Subjects
Immunology ,DNA Mutational Analysis ,Molecular Sequence Data ,Virus Replication ,Polymerase Chain Reaction ,chemistry.chemical_compound ,Cytopathogenic Effect, Viral ,HIV Protease ,Proteinase 3 ,Valine ,Virology ,HIV Protease Inhibitor ,Humans ,Amino Acid Sequence ,Amino Acids ,Saquinavir ,chemistry.chemical_classification ,Methionine ,biology ,Base Sequence ,Drug Resistance, Microbial ,HIV Protease Inhibitors ,Isoquinolines ,Molecular biology ,Amino acid ,Infectious Diseases ,chemistry ,Biochemistry ,Enzyme inhibitor ,biology.protein ,HIV-1 ,Quinolines ,Isoleucine ,Leucine ,Sequence Alignment - Abstract
During replication of human immunodeficiency virus type 1 (HIV-1), proteolytic cleavage of Gag and Gag-Pol precursor proteins into different functional protein subunits is catalyzed by the viral proteinase, and this enzyme is the target of the antiviral proteinase inhibitor, Ro 31-8959. We investigated in vitro which HIV mutants with reduced sensitivity to Ro 31-8959 emerged during proteinase inhibition treatment; from three different HIV-1 strains, comparable progeny virus resistant to proteinase inhibitor were found, whereas the same experimental protocol detected no resistant HIV-2 mutants. Molecular analysis of the mutations underlying resistance revealed a multistep mechanism in which an amino acid exchange was common to all resistant isolates, and in all experiments preceded further exchanges at position 90 (leucine to methionine) and/or at position 54 (isoleucine to valine). For wild-type strains the 90% inhibitory concentrations of Ro 31-8959 were close to 20 nM, whereas HIV-1 mutants with all 3 amino acid exchanges had more than 50-fold increased 90% inhibitory concentrations (above 1000 nM). The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance. Detailed knowledge of this stereotypic process could open inhibitor design, thus preventing conceivable escape of resistant virus on proteinase inhibitor action.
- Published
- 1995
42. Absence of HIV-1 DNA in cartilage from HIV positive patients
- Author
-
Eberhard Wilmes, Jesús Bujía, Zietz C, P Randolph, and Lutz Gürtler
- Subjects
Adult ,Male ,Molecular Sequence Data ,Polymerase Chain Reaction ,Virus ,law.invention ,Acquired immunodeficiency syndrome (AIDS) ,law ,Immunopathology ,HIV Seropositivity ,Cadaver ,medicine ,Humans ,Perichondrium ,Polymerase chain reaction ,Base Sequence ,business.industry ,Cartilage ,Gene Amplification ,Brain ,virus diseases ,General Medicine ,Middle Aged ,medicine.disease ,Virology ,Transplantation ,medicine.anatomical_structure ,Otorhinolaryngology ,Connective Tissue ,DNA, Viral ,Immunology ,HIV-1 ,Female ,Viral disease ,business ,Spleen - Abstract
Human immunodeficiency virus (HIV) infections are mainly transferred by blood, semen or organ transplantations. Since allogenic transplants have an established place in reconstructive surgery, the possibility of transferring HIV with such transplants has been a subject of much concern. Postmortem cartilage samples were obtained from eight HIV-infected patients and examined using the polymerase chain reaction in order to detect proviral HIV-1 DNA (gag, pol, env). Blood, brain and spleen samples were also obtained and used as positive controls. Results showed that no cartilage sample contained any HIV-DNA, whereas proviral sequences were clearly demonstrated in perichondrium from six patients. These findings indicate that HIV is not present in cartilage of HIV-infected patients, making HIV transmission through cartilage grafting improbable when transplants from HIV-negative donors are used.
- Published
- 1994
43. A critical analysis of human immunodeficiency virus transmission using human cartilage allografts
- Author
-
Claus Hammer, P. Pitzke, Eberhard Wilmes, Jesús Bujía, and Lutz Gürtler
- Subjects
Pathology ,medicine.medical_specialty ,Cell type ,medicine.drug_class ,Fluorescent Antibody Technique ,HIV Infections ,Ribs ,Cell Separation ,Immunofluorescence ,Monoclonal antibody ,Flow cytometry ,Immunoenzyme Techniques ,Receptors, HIV ,Cartilage transplantation ,medicine ,Humans ,Transplantation, Homologous ,Ear, External ,Receptor ,Nasal Septum ,medicine.diagnostic_test ,business.industry ,Cartilage ,HIV ,General Medicine ,Transplantation ,medicine.anatomical_structure ,Otorhinolaryngology ,CD4 Antigens ,business - Abstract
Allogeneic cartilage represents an important source of tissue for reconstructive surgery in the head and neck. The use of allografts is now being discussed because of the possible transmission of the human immunodeficiency virus (HIV). The receptor for HIV in most cell types is the CD-4 molecule. Since cartilage is a popular homograft source, the purpose of this study was to investigate the presence of CD-4 molecules on cartilage tissue as detected with an immunoperoxidase staining and immunofluorescence flow cytometric analysis using a monoclonal antibody. Our results indicate clearly the absence of the HIV receptor on human cartilage tissue. We have concluded therefore that normal cartilage tissue cannot be infected by HIV, at least not through a CD-4-dependent mechanism.
- Published
- 1993
44. Prevalence of antibodies against hepatitis A virus, hepatitis B virus, and Treponema pallidum in Mauritius
- Author
-
Wolfgang Jilg, Clement Chan Kam, Lutz Gürtler, Bettina Wilske, George Law Min, Tino F. Schwarz, and Friedrich Deinhardt
- Subjects
Microbiology (medical) ,Adult ,Male ,Adolescent ,viruses ,Population ,medicine.disease_cause ,Virus ,Serology ,medicine ,Humans ,Hepatitis Antibodies ,Hepatovirus ,Treponema pallidum ,Hepatitis B Antibodies ,education ,Child ,Aged ,Hepatitis B virus ,Aged, 80 and over ,education.field_of_study ,Treponema ,General Immunology and Microbiology ,biology ,business.industry ,virus diseases ,Infant ,General Medicine ,Hepatitis A ,Middle Aged ,biology.organism_classification ,Hepatitis B ,Virology ,Antibodies, Bacterial ,digestive system diseases ,Vaccination ,Infectious Diseases ,Hepadnaviridae ,Child, Preschool ,Immunology ,Mauritius ,Female ,Viral disease ,business - Abstract
A seroepidemiological study on the prevalence of antibodies against heptitis A virus (HAV), hepatitis B virus (HBV) and Treponema pallidum was conducted in various groups of the population of the state of Mauritius (Islands of Mauritius and Rodrigues). 618 sera were tested. The overall prevalence of anti-HAV was 86.1% and yielded an age-dependent increase. Serological evidence for acute or chronic HBV infection was found in 3.8%; 4.5% were positive for anti-HBc alone, and in 12.6% past HBV infection was detected. No age- or sex-dependent increase in the prevalence of anti-HBc was found. There were differences in the anti-HBc prevalence among the various groups of population ranging from 5.9 (flight personnel) to 58.3% (prison inmates). Treponemal antibodies were detected in 6.0% and showed a fairly marked age-dependent increase. Our study suggests that vaccination programmes against HAV and HBV would be beneficial for the Mauritian population.
- Published
- 1991
45. Multicenter evaluation of a new recombinant enzyme immunoassay for the combined detection of antibody to HIV-1 and HIV-2
- Author
-
Laura Ayres, Francisca Avillez, Ana Garcia-Benito, Friedrich Deinhardt, Lutz Gürtler, François Denis, Guy Léonard, Sylvie Ranger, Peter Grob, Helen Joller-Jemelka, Georg Hess, Siegfried Seidl, Heidi Flacke, François Simon, Françoise Brun-Vézinet, Danièle Sondag, Albert André, Hartmut Hampl, Robert Schoen, Susan Stramer, and Hugo Troonen
- Subjects
Recombinant antigen ,medicine.medical_treatment ,Immunology ,Blotting, Western ,Human immunodeficiency virus (HIV) ,Blood Donors ,HIV Antibodies ,medicine.disease_cause ,Asymptomatic ,Recombinant enzyme ,law.invention ,Immunoenzyme Techniques ,law ,HIV Seroprevalence ,HIV Seropositivity ,medicine ,Immunology and Allergy ,Humans ,biology ,medicine.diagnostic_test ,business.industry ,virus diseases ,AIDS Serodiagnosis ,Virology ,Europe ,Infectious Diseases ,Evaluation Studies as Topic ,Immunoassay ,HIV-2 ,biology.protein ,Recombinant DNA ,HIV-1 ,Plasmapheresis ,Antibody ,medicine.symptom ,business - Abstract
A newly developed recombinant antigen-based anti-HIV-1/HIV-2 enzyme immunoassay (Abbott Recombinant HIV-1/HIV-2 EIA) was evaluated against a second generation anti-HIV-1 EIA (Abbott Recombinant HIV-1 EIA). Five thousand and twenty-nine sera from European blood donors and 403 sera from central African blood donors were used in the evaluation, along with four panels and one cohort. The panels included 99 'problem' sera, 733 sera with antibodies to HIV-1 from asymptomatic people and from patients at different disease stages, 25 serial bleeds from five plasmapheresis donors seroconverting for antibodies to HIV-1, and 202 sera with antibodies to HIV-2 collected from healthy and diseased people of European or west African origin. In addition, 734 sera collected from a west African cohort were tested. Using Western blot as the reference standard, the specificity obtained by the recombinant anti-HIV-1 EIA (HIV-i EIA) was 99.90% [99.81-99.99%; 95% confidence limits (95% CL)] with European blood donor sera; 99.50% (98.78-100%) with Central Africa blood donor sera; 92.93% (87.78-98.08%) with 'problem' sera and 99.43% (98.87-100%) with sera from a west African cohort. Using the same samples, the recombinant anti-HIV-1/HIV-2 EIA (HIV-1/HIV-2 EIA) yielded a specificity of 99.84% (99.73-99.95%), 99.50% (98.78-100%), 95.96% (92.00-99.92%) and 98.58% (97.69-99.47%), respectively. All 776 Western blot-confirmed anti-HIV-1 sera were reactive in both EIAs, and the EIA-reactive samples from seroconverting plasma donors were always observed for both assays in the same serial bleed. For HIV-2, the HIV-1 EIA yielded an overall sensitivity of 75.83% (69.93-81.72%) compared with 99.53% (98.58-100%) for HIV-1/HIV-2 EIA. The addition of a recombinant env-protein of HIV-2 to the recombinant env and core proteins of HIV-1 on the solid phase of HIV-1 EIA improved the detection of anti-HIV-2 while preserving the assay's overall specificity and sensitivity for the detection of anti-HIV-1.
- Published
- 1990
46. Inter-α-trypsin inhibitor polymorphism in African blacks
- Author
-
Lutz Gürtler, Ulrike Vogt, and Hartwig Cleve
- Subjects
Genetics ,education.field_of_study ,Polymorphism, Genetic ,Isoelectric focusing ,Allele distribution ,Inter α trypsin inhibitor ,Clinical Biochemistry ,Population ,Black People ,Biology ,Biochemistry ,Molecular biology ,Analytical Chemistry ,Cote d'Ivoire ,α1 antitrypsin ,Polymorphism (computer science) ,Alpha-Globulins ,Humans ,Allele ,Trypsin Inhibitors ,education ,Allele frequency - Abstract
The inter-alpha-trypsin inhibitor (ITI) polymorphism was analyzed in an African Negroid population using polyacrylamide gel isoelectric focusing and subsequent immunoblotting. Gene frequencies of ITI*1, ITI*2, ITI*3 and ITI*4 were calculated to be 0.564, 0.083, 0.337 and 0.004, respectively. One unknown rare allele, ITI*6, determines further phenotypes in combination with the alleles ITI*1 and ITI*3. Gene frequency of ITI*6 was calculated to be 0.012. The common alleles are represented by ITI*1 and ITI*3. The allele distribution is therefore different from European and Asian populations.
- Published
- 1992
47. A new second-generation anti-HIV-1 enzyme immunoassay using recombinant envelope and core proteins
- Author
-
Uwe Bäcker, Adolf Gathof, Jörg Howe, Erwin Strobel, Friedrich Deinhardt, Lutz Gürtler, Peter Grob, Helen Joller-Jemelka, Peter Kühnl, Siegfried Seidl, Rosario Fico, Jessie Shih, and Hugo Troonen
- Subjects
HIV Antigens ,Immunology ,HIV Core Protein p24 ,Retroviridae Proteins ,Blood Donors ,Human leukocyte antigen ,HIV Antibodies ,Immunofluorescence ,Asymptomatic ,law.invention ,Immunoenzyme Techniques ,Viral Envelope Proteins ,Antigen ,Western blot ,law ,HIV Seropositivity ,medicine ,Humans ,Mass Screening ,Multicenter Studies as Topic ,Immunology and Allergy ,Diagnostic Errors ,biology ,medicine.diagnostic_test ,business.industry ,Molecular biology ,HIV Envelope Protein gp41 ,Recombinant Proteins ,Infectious Diseases ,Immunoassay ,HIV-1 ,Recombinant DNA ,biology.protein ,medicine.symptom ,Antibody ,business - Abstract
In a multicenter collaborative study a new second-generation HIV-1 antibody enzyme immunoassay (Abbott recombinant HIV-1 EIA) using Escherichia coli-expressed recombinant p24 and p41 proteins as solid-phase antigens was compared with the first-generation H9 cell-line-based Abbott HIV-1 EIA. The results of the confirmatory assays (Western blot, immunofluorescence), combined with clinical information, were used as the reference standard for the detection of HIV-1 antibodies in 10,676 random blood donor serum specimens, in a panel of 840 specimens from symptomatic and asymptomatic patients and a total of 63 serial blood specimens from 23 people at risk. With fresh blood donor sera, the specificity of the first-generation assay ranged between 99.54 and 99.76% (95% confidence limits, CL) compared with 99.81-99.95% (95% CL) for the second-generation EIA. With panel specimens the recombinant HIV-1 EIA achieved an overall sensitivity of 100% and a specificity range of 98.3-99.7% (95% CL); the corresponding sensitivity and specificity ranges observed for the first-generation EIA were 98.0-99.5% (95% CL) and 94.3-96.8% (95% CL), respectively. The improved sensitivity for the second-generation assay was confirmed by testing serial samples from seroconverting patients. The use of recombinant proteins eliminated non-specific reactions due to class II human leukocyte antigen (HLA)-directed antibodies.
- Published
- 1988
48. Flow cytometric analysis of the binding of eleven lectins to human T- and B-cells and to human T- and B-cell lines
- Author
-
G. Valet, John Anthony Forrester, Lutz Gürtler, Jeannette Malin‐Berdel, and Eckhart Thiel
- Subjects
T-Lymphocytes ,Biophysics ,Cell Line ,Pathology and Forensic Medicine ,Flow cytometry ,Blood cell ,Endocrinology ,Lectins ,Abrus precatorius ,medicine ,Humans ,B cell ,B-Lymphocytes ,biology ,medicine.diagnostic_test ,Lectin ,Cell Biology ,Hematology ,Flow Cytometry ,biology.organism_classification ,Ulex europaeus ,medicine.anatomical_structure ,Biochemistry ,Cell culture ,Receptors, Mitogen ,biology.protein ,Neuraminidase - Abstract
The relative surface binding of 11 lectins to human peripheral blood T- and B-lymphocytes, to Molt-4 and JM T-cell lines, and to 6410 and NC37 B-cell lines was determined by flow cytometry. The lectins from Lens culinaris (LCA), Ricinus communis (RCA), Arachis hypogaea (PNA), Abrus precatorius (APA), Ulex europaeus (UEA-F), Sarothamnus scoparius (SAS-F), Helix pomatia (HPA), Phaseolus coccineus (L-PHA), Glycine max (SBA), and Triticum vulgare (WGA) were fluoresceinated and incubated with living, formaldehyde-fixed, or neuraminidase-treated cells. Except LCA, which preferentially bound to the two B-cell lines tested in this study, none of the other lectins exhibited selective binding to the undifferentiated cells of the cell lines. The T-cell lines and, in part, the peripheral blood T-cells bound less WGA, APA, LCA, and L-PHA than the B-cell lines and the peripheral blood B-cells. Binding of PNA was found only after neuraminidase treatment of the cells; the binding of PNA, HPA, and UEA-F after neuraminidase treatment was higher for the T-cells than the B-cells from peripheral blood. No significant differences were detected between both cell types for RCA, ConA, SBA, and SAS-F.
- Published
- 1984
49. Immunoblot test with recombinant HIV antigens
- Author
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Manfred Motz, Gert Frösner, Lutz Gürtler, E. Soutschek-Bauer, M. Schall, and Hans Wolf
- Subjects
HIV Antigens ,610 Medizin ,HIV Antibodies ,Antibodies, Viral ,law.invention ,Antigen ,law ,Antigens, Viral/immunology ,Medicine ,Antibodies, Viral/analysis ,Humans ,Acquired Immunodeficiency Syndrome/diagnosis ,Viral immunology ,Antigens, Viral ,Recombinant Proteins/immunology ,Immunoassay ,Acquired Immunodeficiency Syndrome ,ddc:610 ,biology ,medicine.diagnostic_test ,business.industry ,HIV ,General Medicine ,Virology ,Recombinant Proteins ,Immunology ,biology.protein ,Recombinant DNA ,Antibody ,business ,HIV/immunology - Published
- 1987
- Full Text
- View/download PDF
50. Effect of antiretroviral triple combinations including the protease inhibitor nelfinavir in heavily pretreated children with HIV-1 infection
- Author
-
Hoffmann, F., Funk, M., Linde, R., Notheis, G., Petropoulou, T., Eberle, J., Lutz Gürtler, Belohradsky, B. H., and Wintergerst, U.
- Subjects
Male ,Nelfinavir ,Time Factors ,Adolescent ,Anti-HIV Agents ,Infant ,HIV Infections ,HIV Protease Inhibitors ,Viral Load ,CD4 Lymphocyte Count ,Treatment Refusal ,Child, Preschool ,Drug Resistance, Viral ,Disease Progression ,HIV-1 ,Humans ,RNA, Viral ,Drug Therapy, Combination ,Female ,Viremia ,Child ,Retrospective Studies - Abstract
In this retrospective study the effect of antiretroviral triple therapy including the protease-inhibitor nelfinavir (NFV) on CD4-cells and viral load (VL) in heavily pretreated HIV-infected children was evaluated.20 children (18 years) were included. Median duration of antiretroviral pretreatment was 27 months (range, 7 65), median initial VL was 4.7 log subset 10 (3.2 6.1) and median relative CD4-cells was 17.5% (3 33). Patients were put on combinations with NFV because of treatment failure (increasing VL), intolerance to prior therapy with PIs or adherence problems with prior indinavir. Viral load (RT-PCR, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks.Median viral load decreased 1.2 log(10) (-1.3 2.5), 0.9 log(10) (-0.8 - 2.5) and 0.4 log(10) (-0.5 - 3.0) after 12, 24 and 36 weeks. The VL of 2 patients was below the detection limit (50 copies/ml) after 24 weeks. The relative CD4-cell count increased from a median of 17.5% to 22%, 23% and 25% after 12, 24 and 36 weeks, respectively. Side effects of NFV were usually mild. WHO grade 1 or 2 diarrhea occurred in 70% and moderate elevations of triglycerides in 40% of the patients. At 48 weeks 18/20 patients had to be switched to other combinations due to virological failure.In children with intensive prior antiretroviral therapy combination therapy including NFV lead to a modest short-term reduction of the VL and increase in CD4-cells. However, the long-term antiretroviral effect was poor.
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