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Copyright of Revista de Psiquiatría Infanto-Juvenil is the property of Asociacion Espanola de Psiquiatria del Nino y el Adolescente (AEPNyA) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood.Methods: In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets.Results: Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression.Conclusions: FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling. [ABSTRACT FROM AUTHOR]

This article, published in the journal Endoscopy, examines the impact of cholangioscope diameter variation on cholangioscopy outcomes. The study compares the success rates of diagnostic and therapeutic procedures using cholangioscopes of different diameters. The results show that the 9.3F cholangioscope is more suitable for diagnostic procedures and has a higher technical success rate, while the 11.1F cholangioscope is preferable for therapeutic interventions, especially for larger biliary stones. The study also suggests that the 7F cholangioscope can be an effective alternative for evaluating intrahepatic ducts. [Extracted from the article]

This article compares the quality and adverse events of three different techniques for liver biopsy: percutaneous liver biopsy (PC-LB), transjugular liver biopsy (TJ-LB), and endoscopic ultrasound-guided liver biopsy (EUS-LB). The study analyzed 21 original studies from 1993 to 2023 and found that EUS-LB had comparable quality to PC-LB and superior quality to TJ-LB in terms of total sample length (TSL). The mean number of complete portal triads (CPT), rate of appropriate sample for diagnosis, and major adverse events were similar among the three techniques. However, further studies are needed to determine the rate of sample fragmentation for each technique. [Extracted from the article]

This article discusses a study comparing the effectiveness of plastic pancreatic stents (PPS) and biodegradable stents (BDS) in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The study was conducted on 97 patients with biliary tract disease who underwent ERCP. The results showed that there was a lower, but not statistically significant, rate of PEP prevention with BDS compared to PPS. The study provides valuable information on the efficacy of different types of pancreatic stents for preventing PEP. [Extracted from the article]

Background: The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of combination-induced molecular mechanisms bears significant value for the further development of interventional approaches. Methods: Combined application of conventional cytostatic agents (cytarabine and dexamethasone) with the PI3K-inhibitor Idelalisib was analysed on cell-biologic parameters in two acute pro-B lymphoblastic leukaemia (B-ALL) cell lines. In particular, for comparative characterisation of the molecular signatures induced by the combined and mono application, whole transcriptome sequencing was performed. Emphasis was placed on pathways and genes exclusively regulated by drug combinations. Results: Idelalisib + cytostatics combinations changed pathway activation for, e.g., "Retinoblastoma in cancer", "TGF-b signalling", "Cell cycle" and "DNA-damage response" to a greater extent than the two cytostatics alone. Analyses of the top-20 regulated genes revealed that both combinations induce characteristic gene expression changes. Conclusion: A specific set of genes was exclusively deregulated by the drug combinations, matching the combination-specific anti-proliferative cell-biologic effects. The addition of Idelalisib suggests minor synergistic effects which are rather to be classified as additive. [ABSTRACT FROM AUTHOR]

Copyright of Acta Pediátrica Española is the property of Ediciones Mayo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Deoxyribonucleic acid (DNA) vaccines are used for experimental immunotherapy of equine melanoma. The injection of complexed linear DNA encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a clinical study including 27 grey horses. To date, the detailed mechanism of the anti-tumour effect of this treatment is unknown. Results: In the present study, the clinical and cellular responses of 24 healthy horses were monitored over 72 h after simultaneous intradermal and intramuscular application of equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of CG). Although the strongest effect was observed in horses treated with expressing DNA, horses in all groups treated with DNA showed systemic responses. In these horses treated with DNA, rectal temperatures were elevated after treatment and serum amyloid A increased. Total leukocyte and neutrophil counts increased, while lymphocyte numbers decreased. The secretion of tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral mononuclear blood cells ex vivo increased after treatments with DNA, while IL-10 secretion decreased. Horses treated with DNA had significantly higher myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression in skin samples at the intradermal injection sites compared to horses treated with transfection reagent only, suggesting an inflammatory response to DNA treatment. In horses treated with expressing DNA, however, local CXCL-10 expression was highest and immunohistochemistry revealed more intradermal IL-12-positive cells when compared to the other treatment groups. In contrast to non-grey horses, grey horses showed fewer effects of DNA treatments on blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the dermis. Conclusion: Treatment with complexed linear DNA constructs induced an inflammatory response independent of the coding sequence and of CG motif content. Expressing IL-12/IL-18 DNA locally induces expression of the downstream mediator CXCL-10. The grey horses included appeared to display an attenuated immune response to DNA treatment, although grey horses bearing melanoma responded to this treatment with moderate tumour remission in a preceding study. Whether the different immunological reactivity compared to other horses may contributes to the melanoma susceptibility of grey horses remains to be elucidated. [ABSTRACT FROM AUTHOR]

Copyright of Acta Pediátrica Española is the property of Ediciones Mayo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective:Assess the impact of intercurrent respiratory infections in infants <29 weeks gestational age (GA).Study design:A retrospective cohort study of 111 infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD) severity and assessing pulmonary health over the first year of life through oxygen, diuretic and inhaled steroid use.Result:Regression analysis showed viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4), P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not.Conclusion:Viral infections caused more long-term pulmonary morbidity/mortality than bacterial infections on premature lung health, even when controlling for BPD. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Psiquiatría Infanto-Juvenil is the property of Asociacion Espanola de Psiquiatria del Nino y el Adolescente (AEPNyA) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective:To assess pulmonary outcomes of infants <29 weeks gestational age (GA), delivered at level I, II and III facilities, to identify potentially modifiable factors affecting bronchopulmonary dysplasia (BPD) severity and to assess the external generalizability of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) BPD Outcome Estimator.Study Design:Outcomes for infants <29 weeks GA born during (2008-2010) and delivered either at an inborn level III center or in a level II or III metropolitan area hospital with transfer to a level IV center, or delivered in a distant level I or II center and then transported to a level IV center were assessed. BPD severity was compared with the NICHD Neonatal BPD Outcome Estimator.Result:Of 158 infants who comprised the cohort, 28 (17.8%) had no BPD, 39 (24.2%) had mild BPD, 45 (28.7%) had moderate BPD, 31 (19.7%) had severe BPD and 15 (9.6%) died at 36 weeks post menstrual age. Site of birth did not predict severe BPD or death. Receiver operator characteristic curves showed fair predictability for none/mild and severe BPD.Conclusion:BPD severity was not dependent on site of birth. The NICHD BPD outcome estimator provides fair prediction for extreme outcomes. [ABSTRACT FROM AUTHOR]

Reasons for performing study: CD14 positive (CD14+) cells are the precursor cells of monocyte-derived dendritic cells (DCs). In horses their potent antigen-presenting capacity and ability to induce an effective immune response classify these cells suitable for several therapeutic approaches such as for equine sarcoid. However, in horses, the generation efficiency of DCs from adherent peripheral blood mononuclear cells (PBMCs) is currently still poor. Objectives: Establishment of a simple short protocol to enhance DC generation in horses by using a human CD14 monoclonal antibody (mAb) and an automated magnetic activated cell sorting (MACS) system. Methods: Peripheral blood mononuclear cells were isolated from fresh heparinised blood samples of 3 horses and primarily stained for flow cytometric analysis (FACS) with a mAb against human CD14 as well as a secondary phycoerythrin (PE) conjugated antibody to determine the initial percentage of CD14 cells in the sample. Peripheral blood mononuclear cells were used for automated MACS using the same primary and secondary antibodies and analysed by FACS. CD14+ selected cells were cultured for 4 days adding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to the culture media. Dendritic cell generation was assessed analysing cell morphology and surface marker expression (hCD83, hCD86, eqMHCII). Results: Prior to selection, the mean percentage of CD14+ cells in the total cell population was 5.5%, further gaiting of this cell population resulted in 78.46% CD14+ monocytes. After our positive selection the mean percentage of CD14+ cells in the population was 98% without affecting viability. After culture, DC yield was 2-fold higher than in previous published outcomes. Conclusions: The additional CD14 cell separation step after PBMC isolation significantly amplified the number of CD14+ cells, increasing the number of generated DCs. Potential relevance: The number of DCs available is critical for further use of these cells and the herein described protocol will therefore help to improved DC generation for therapeutic approaches in horses. [ABSTRACT FROM AUTHOR]

Multipotency and self-renewal are considered as most important features of stem cells to persist throughout life in tissues. In this context, the role of HMGA proteins to influence proliferation of adipose-derivedmesenchymal stem cell (ASCs) whilemaintaining their multipotent and self-renewal capacities has not yet been investigated. Therefore, extracellular HMGA1 and HMGA2 application alone (10-200 ng/mL) and in combination with each other (100, 200 ng/mL each) was investigated with regard to proliferative effects on canine ASCs (cASCs) after 48 hours of cultivation. Furthermore, mRNA expression of multipotency marker genes in unstimulated and HMGA2-stimulated cASCs (50, 100 ng/mL) was analyzed by RT-qPCR. HMGA1 significantly reduced cASCs proliferation in concentrations of 10-200 ng/mL culture medium. A combination of HMGA1 and HMGA2 protein (100 and 200 ng/mL each) caused the same effects, whereas no significant effect on cASCs proliferation was shown afterHMGA2 protein application alone. RT-qPCR results showed that expression levels of marker genes including KLF4, SOX2, OCT4, HMGA2, and cMYC mRNAs were on the same level in bothHMGA2-protein-stimulated and -unstimulated cASCs. Extracellular HMGA protein application might be valuable to control proliferation of cASCs in context with their employment in regenerative approaches without affecting their self-renewal and multipotency abilities. [ABSTRACT FROM AUTHOR]

One of the main goals in cancer immunotherapy is the efficient activation of the host immune system against tumour cells. Dendritic cells (DCs) can induce specific anti-tumour immune responses in both experimental animal models and humans. However, most preclinical studies using small animal models show only limited correlation with studies carried out in clinical settings, whereas laboratory dogs naturally develop tumours that are biologically and histopathologically similar to their human counterparts. Here, we describe the generation and characterization of recombinant antibodies against canine DCs, isolated using the Tomlinson phage display system. We successfully isolated highly specific single-chain variable fragment (scFv) antibodies in a sequential three-step panning strategy involving depletion on canine peripheral blood mononuclear cells followed by positive selection on native canine DCs. This provides the basis for an antibody-based method for the immunological detection and manipulation of DCs and for monitoring antigen-specific immune responses. [ABSTRACT FROM AUTHOR]

Human and canine lymphoid neoplasms are characterized by non-random cytogenetic abnormalities. However, due to the low mitotic activity of the B cells, cytogenetic analyses of B-cell lymphoid proliferations are difficult to perform. In the present study we stimulated canine B-cell lymphoma cells with the immunostimulatory CpG-oligonucleotide DSP30 in combination with interleukin-2 (IL-2) and obtained an adequate number of metaphases. Cytogenetic analyses revealed the loss of one X chromosome as the sole cytogenetic aberration. Chromosome analysis of the corresponding blood showed a normal female karyotype. Monosomy X as the sole clonal chromosomal abnormality is found in human hematopoietic malignancies as well, thus the dog may serve as a promising animal model. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Besides man, the dog is the only known mammalian species that spontaneously develops carcinomas of the prostate with considerable frequency. For this reason, the dog is considered to be the only useful animal model for spontaneously occurring prostate malignancies in man. Cytogenetic investigations of human prostate cancers have revealed the frequent occurrence of trisomies 7, 8, and 17. Chromosome analyses of canine prostate carcinomas are rare. In this report we present 2 cases of canine prostate cancer showing a clonal polysomy 13 along with complex karyotype changes. Along with a previous report demonstrating polysomy 13 as the only karyotype deviation in a canine prostate cancer the present report supports the hypothesis that in canine prostate cancer, polysomy 13 is a recurrent cytogenetic aberration linked to the development of the disease. As human chromosomes (HSA) 8q and 4q and the canine chromosome (CFA) 13 share high homology, these results suggest that a conserved area on these chromosomes is involved in tumorigenesis in both species. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Overexpression of high mobility group A ( HMGA) genes was described as a prognostic marker in different human malignancies, but its role in canine haematopoietic malignancies was unknown so far. The objective of this study was to analyse HMGA1 and HMGA2 gene expression in lymph nodes of canine lymphoma patients. The expression of HMGA1 and HMGA2 was analysed in lymph node samples of 23 dogs with lymphoma and three control dogs using relative quantitative real-time RT-PCR. Relative quantity of HMGA1 was significantly higher in dogs with lymphoma compared with reference samples. HMGA2 expression did not differ between lymphoma and control dogs. With the exception of immunophenotype, comparison of disease parameters did not display any differences in HMGA1 and HMGA2 expression. The present findings indicate a role of HMGA genes in canine lymphoma. This study represents the basis for future veterinary and comparative studies dealing with their diagnostic, prognostic and therapeutic values. [ABSTRACT FROM AUTHOR]

The architectural transcription factor HMGA2 is highly expressed during embryogenesis but scarcely detectable in non-dividing adult cells. Previously, HMGA2 re-expression was detected in blood from CML patients by conventional RT-PCR, while blood samples from healthy volunteers were HMGA2 negative. Using the sensitive method of real-time quantitative RT-PCR, herein HMGA2 expression was detectable not only in peripheral blood from leukaemia patients but also in blood from healthy donors. Statistical analysis revealed a highly significant correlation between white blood cell count and HMGA2 transcript levels. The results indicate that up-regulation of HMGA2 expression is correlated to the undifferentiated phenotype of leukaemic cells accumulating during progression of chronic phase to blast crisis. [ABSTRACT FROM AUTHOR]

A total number of 111 dogs were included in the present prospective study investigating the prevalence of Anaplasma phagocytophilum in dogs in Germany. Dogs were divided into two groups. Dogs of group 1 ( n = 49) showed clinical and/or haematological signs seen in infections with A. phagocytophilum, whereas those of group 2 ( n = 62) did not have any evidence of anaplasmosis. For each dog, an A. phagocytophilum 16S rRNA-nested polymerase chain reaction (PCR) of ethylenediaminetetraacetic acid (EDTA)-anticoagulated whole blood analysis, a microscopic evaluation of a buffy coat and a serum indirect fluorescent antibody test (IFAT) were performed. Forty-eight seroreactive dogs were identified altogether, which amounts to an overall point prevalence of 43.2%. There was no significant difference between the seroreactivity to A. phagocytophilum antigens among group 1 (44.9%) and 2 (41.9%) ( P > 0.5). Seven dogs (6.3%) had positive PCR results. All of them were seroreactive. Six belonged to group 1. Morulae in neutrophilic granulocytes were found in two dogs of group 1 but in none of group 2. Both dogs were seroreactive. Very high antibody titres (≥1:1024) were detected significantly more frequently in dogs with clinical signs attributable to infection with A. phagocytophilum (group 1) than in those without (group 2) ( P < 0.001). There was no significant correlation of overall positives or antibody titres to age, breed, sex, or whether the dogs were family or working dogs. Dogs with high tick infestation were significantly more often seroreactive to A. phagocytophilum than those with no or low tick infestation ( P = 0.007). In conclusion, there seems to be a high risk of infection with A. phagocytophilum in Germany. Results of this study suggest that severe illness solely caused by A. phagocytophilum may be possible although definitive evidence does not exist. Very high antibody titres (>1:1024) may be associated with clinical anaplasmosis. [ABSTRACT FROM AUTHOR]

HMGA1 nonhistone proteins are reported to participate in various cellular processes including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the induction of neoplastic transformation and promotion of metastatic progression of cancer cells. Overexpression of HMGA1 was shown to he characteristic for various malignant tumors, suggesting a relation between the neoplastic phenotype and a high titer of the protein. Also chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in several tumors, e.g., uterine leiomyomas, pulmonary, chondroid hamartomas, and follicular thyroid adenomas. We characterize the molecular structure of the canine HMGA1 cDNA, its splice variants, and predicted proteins HMGA1a and HMGA1b. Furthermore, we compared the CDS of both splice variants for 12 different breeds, screened them for SNPs, characterised a basic expression pattern, and mapped the gene via FISH. Additionally, we compared the known human, canine, murine, rat, hamster, bovine, pig, Xenopus, and chicken HMGA1 transcripts. [ABSTRACT FROM AUTHOR]

Akin to the situation in humans, dogs are frequently affected by tumors of the prostate. The malignancies share man), similarities between both species, for example, median age at the onset of the disease and metastatic behavior. In human prostatic tumor samples, investigations of prepared metaphase spreads showed a variety., of chromosomal aberrations, with trisomies of chromosomes 7, 8, and 17 as the leading cytogenetic abnormalities. In this article we present one case of a canine adenocarcinoma of the prostate, including clinical examination and establishment of a cell line from a tumor sample obtained from the affected 10-year-old male Briard. Searching for similarities between both species in respect to chromosomal changes within the tumor samples, we investigated prepared metaphases of the canine cell line cytogenetically. These investigations presented a highly rearranged karyotype showing a large biarmed marker consisting of material from chromosomes 1 and 2 in addition to centromeric fusions between dog chromosomes 1 and 5 that both could be identified in every metaphase investigated, while centric fusions of chromosomes 4 and 5 occurred in up to 50% of the metaphases. The cell line grew very well and showed evidence of being spontaneously immortalized when it crossed the 20th passage. [ABSTRACT FROM AUTHOR]

Akin to the situation in humans, dogs are frequently affected by tumors of the prostate. The malignancies share many similarities between both species, for example, median age at the onset of the disease and metastatic behavior. In human prostatic tumor samples, investigations of prepared metaphase spreads showed a variety of chromosomal aberrations, with trisomies of chromosomes 7, 8, and 17 as the leading cytogenetic abnormalities. In this article we present one case of a canine adenocarcinoma of the prostate, including clinical examination and establishment of a cell line from a tumor sample obtained from the affected 10-year-old male Briard. Searching for similarities between both species in respect to chromosomal changes within the tumor samples, we investigated prepared metaphases of the canine cell line cytogenetically. These investigations presented a highly rearranged karyotype showing a large biarmed marker consisting of material from chromosomes 1 and 2 in addition to centromeric fusions between dog chromosomes 1 and 5 that both could be identified in every metaphase investigated, while centric fusions of chromosomes 4 and 5 occurred in up to 50% of the metaphases. The cell line grew very well and showed evidence of being spontaneously immortalized when it crossed the 20th passage. [ABSTRACT FROM PUBLISHER]

HMGA1 nonhistone proteins are reported to participate in various cellular processes including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the induction of neoplastic transformation and promotion of metastatic progression of cancer cells. Overexpression of HMGA1 was shown to be characteristic for various malignant tumors, suggesting a relation between the neoplastic phenotype and a high titer of the protein. Also chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in several tumors, e.g., uterine leiomyomas, pulmonary chondroid hamartomas, and follicular thyroid adenomas. We characterize the molecular structure of the canine HMGA1 cDNA, its splice variants, and predicted proteins HMGA1a and HMGA1b. Furthermore, we compared the CDS of both splice variants for 12 different breeds, screened them for SNPs, characterised a basic expression pattern, and mapped the gene via FISH. Additionally, we compared the known human, canine, murine, rat, hamster, bovine, pig, Xenopus, and chicken HMGA1 transcripts. [ABSTRACT FROM PUBLISHER]

Translocations involving chromosomal region 19q13 are a frequent finding in follicular adenomas of the thyroid and might represent the most frequent type of structural aberration in human epithelial tumors. By positional cloning, a putative candidate gene, ZNF331 (formerly RITA) located close to the breakpoint was identified. Recently, aberrant expression of ZNF331 has been described in two cell lines of follicular thyroid adenomas with aberrations in 19q13 indicating an involvement of ZNF331 in tumorigenesis. Nevertheless, knowledge about structure and expression of ZNF331 is limited. We performed RACE-PCR and genomic sequence analyses to gain a deeper insight into its molecular structure. To elucidate ZNF331 expression patterns we performed Northern blot analyses on various normal tissues as well as on thyroid carcinoma and adenoma cell lines. Herein, unique expression of a 3.4-kbp transcript is described in thyroid adenoma cell lines with 19q13 aberrations, which was not detected either in normal tissues or in thyroid carcinoma cell lines. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

During 1991 to 1998 at least one Stenotrophomonas maltophilia pulmonary infection was observed in 25 (24%) of 104 cystic fibrosis patients at the same unit of our hospital in Spain. Ribotyping and pulse-field gel electrophoresis (PFGE) characterization of 76 S. maltophilia isolates from these patients indicated an overall clonal incidence of 47.1%, reflecting new strains in 44% of patients with repeated positive cultures for S. maltophilia. Six patients with repeated episodes were persistently colonized (> or = 6 months) with the same strain. S. maltophilia bacterial counts were higher (geometric mean, 2.9 x 10(8) cfu/mL) in patients with repeated episodes than in those with a single episode (8.4 x 10(4) cfu/mL, p < 0.01). Single episodes of S. maltophilia occurred in patients < 10 years of age (43% [6/14]), whereas chronic colonization occurred more frequently in older patients (> 16 years of age). [ABSTRACT FROM AUTHOR]

The evolution of imipenem resistance was evaluated in Pseudomonas aeruginosa sequentially isolated from 42 patients with cystic fibrosis. Susceptibility was determined using a commercial microdilution system and imipenem resistance was confirmed by the agar dilution technique. Resistance to imipenem increased during the years from 1988 to 1992. A total of 12 patients (28.5%) carried resistant strains (11.6% of the total P. aeruginosa isolates) but only two of them were treated with the carbapenem. The other patient under imipenem treatment did not harbour resistant isolates. Sixty-four percent of the imipenem resistant isolates were also meropenem resistant and showed low susceptibility to the other β-lactams and tobramycin and amikacin. Twenty-one strains were selected for biochemical study. Imipenem susceptible strains showed normal OprD in two strains and diminished OprD in two more. Five strains with MIC of imipenem of 4–8 mg‐L lacked OprD while another two had a band with decreased density. All strains with MIC higher than 8 completely lacked this band in western-blot analysis. Imipenem MICs of 0.5–2 mg/L only slightly increased to 1–4 mg/L when a pattern of β-lactamase derepression was observed. While those with imipenem MICs between 8–16 mg/L increased the imipenem MIC to 16–64 mg/L in the population with a β-lactamase derepression phenotype. [ABSTRACT FROM PUBLISHER]

Unlabelled: In children, anal abnormalities due to various causes may be confused with sexual abuse. We present the case of a child in whom the suspicion of abuse due to anal dilatation led to the previously unknown diagnosis of myotonic dystrophy. Myopathic involvement of the perianal musculature is a known feature of congenital myotonic dystrophy that usually appears in late childhood or adolescence.Conclusion: We stress the importance of considering an underlying myopathic condition in the differential diagnosis of anal laxity. Further studies, such as anal ultrasonography, may help when the diagnosis of abuse is not clear. [ABSTRACT FROM AUTHOR]

Ultrasound-guided fine-needle aspiration (US-FNA) biopsy is a widely used minimally invasive sampling procedure for cytological diagnosis. This study investigates the feasibility of using US-FNA samples for both cytological diagnosis and whole transcriptome RNA-sequencing analysis (RNA-Seq), with the ultimate aim of improving canine prostate cancer management. The feasibility of the US-FNA procedure was evaluated intra vitam on 43 dogs. Additionally, aspirates from 31 euthanised dogs were collected for standardising the procedure. Each aspirate was separated into two subsamples: for cytology and RNA extraction. Additional prostate tissue samples served as control for RNA quantity and quality evaluation, and differential expression analysis. The US-FNA sampling procedure was feasible in 95% of dogs. RNA isolation of US-FNA samples was successfully performed using phenol-chloroform extraction. The extracted RNA of 56% of a subset of US-FNA samples met the quality requirements for RNA-Seq. Expression analysis revealed that only 153 genes were exclusively differentially expressed between non-malignant US-FNAs and tissues. Moreover, only 36 differentially expressed genes were associated with the US-FNA sampling technique and unrelated to the diagnosis. Furthermore, the gene expression profiles clearly distinguished between non-malignant and malignant samples. This proves US-FNA to be useful for molecular profiling. [ABSTRACT FROM AUTHOR]

Background: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. Methods: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL. Further, efficacy of HMA and concomitant application of cytostatic drugs (cytarabine and doxorubicin) were evaluated on established SEM and RS4;11 cell lines. In addition, promising approaches were studied on BCP-ALL cell line- and patient-derived xenograft models. Results: In general, DEC effects were stronger compared to AZA on MLL-positive BCP-ALL cells. DEC significantly reduced proliferation by induction of cell cycle arrest in G0/G1 phase and apoptosis. Most sensitive to HMA were SEM cells which are characterized by a fast cell doubling time. The combination of low-dose HMA and conventional cytostatic agents revealed a heterogeneous response pattern. The strongest antiproliferative effects were observed when ALL cells were simultaneously exposed to HMA and cytostatic drugs. Most potent synergistic effects of HMA were induced with cytarabine. Finally, the therapeutic potential of DEC was evaluated on BCP-ALL xenograft models. DEC significantly delayed leukemic proliferation in xenograft models as demonstrated longitudinally by non-invasive bioluminescence as well as 18F-FDG-PET/CT imaging. Unexpectedly, in vivo concomitant application of DEC and cytarabine did not enhance the antiproliferative effect compared to DEC monotherapy. Conclusions: Our data reveal that DEC is active in MLL-positive BCP-ALL and warrant clinical evaluation. [ABSTRACT FROM AUTHOR]

Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these rumors in dogs. [ABSTRACT FROM AUTHOR]

Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs. [ABSTRACT FROM PUBLISHER]

Presents the abstract of the article "The Canine KRAS2 Gene Maps to Chromosome 22," by S. Winkler, H. Murua Escobar, K. G¨nther, A. Richter, G. Dolf, C. Schellig, J. Bullerdiek and Ingo Nolte.

Presents the abstract of the article "The Protein Kinase B, Gamma (AKT3) Gene Maps to Canine Chromosome 7," by H. Murua Escobar, J. Meyer, S. Winkler, C. Schellig, I. Nolte and J. Bullerdiek.

Presents the abstract of the article "The Canine MRAS Gene Maps to CFA 17," by A. Ritcher, H. Murua Escobar, K. G¨nther, B. Meyer, S. Winkler, G. Dolf, C. Schellig, I. Nolte and J. Bullerdiek.

Focuses on the molecular characterization and mapping of the canine KRAB zinc finger gene ZNF331. Use of dogs as model organism for human diseases and tumors; Utilization of the propidium iodide/antifade solution to counterstain the chromosomes; Description of the aberrations in tumors of the dog.

This article cites a study on DNA sequence, polymorphism and mapping of luteinizing hormone receptor fragment (LHCGR) gene in Great Dane dogs. Exon 11 of the canine LHCGR gene was polymerase chain reaction amplified and sequenced. Primers were designed based upon previous bovine LHCGR gene sequence. Activating and inactivating mutations have been described in the same receptor in humans. Genomic DNA was isolated from Great Dane dog's peripheral blood leucocytes using phenol/chloroform purification based protocols.

Describes human chromosomal rearrangements on 6p21 involving the HMGA1 gene in various benign mesenchymal tumors. Uncertainty in the occurrence of translocations in the corresponding canine tumor; Mapping of the canine HMGA1 gene; Finding that chromosomal rearrangements of HSA 6p21 involving HMGA1 represent the second most frequent specific translocations in human tumors.

The dog offers an increasingly important model for several human diseases, including cancer. Accordingly, the results of canine gene mapping studies will be of considerable significance. Herein, we have addressed the mapping of the canine gene ERBB2 (alias HER2, NEU). ERBB2 is a protooncogene encoding a tyrosine kinase receptor protein, the overexpression of which correlates with a more rapid progression and a worse prognosis in breast cancer. In addition, it apparently plays a role in the development of other tumors as well. By fluorescence in situ hybridization (FISH), we have mapped the canine ERBB2 to 1q13.1. Cytogenetic studies of canine tumors revealed that this region is very often affected by clonal chromosome aberrations in tumors of the dog. Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]