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Most otolaryngologists treat patients with chondrodermatitis nodularis (CDN) by wedge excision. Although the results of this technique are generally good, it can leave the patient with an asymmetric, deformed ear.In the dermatological literature, a relatively straightforward technique has been described for the treatment of CDN by smoothing only the underlying cartilage. This is based on the assumption that CDN is caused by pressure necrosis of protuberant cartilage, and thus is primarily not a skin disease. Reports on this technique claim excellent cosmetic results with only a small chance of recurrence.In the present study we analyse the application of this technique to 34 patients with 37 CDN lesions. All patients were symptom-free with a minimum follow-up of three months according to their medical reports.Seventeen patients with 19 lesions were interviewed later by telephone. In a mean follow-up of 30.7 months, 34 of these patients remained symptom-free and only one required revision surgery. The authors recommend this safe and simple technique to other physicians who treat patients with CDN.

An on-line high-performance liquid chromatography/mass spectrometry (HPLC/MS) method is described for the rapid characterization of any type of oligosaccharide released from glycoproteins. The procedure can be applied without further manipulation to fractions collected from a high-performance anion-exchange chromatography-pulse amperometric detection (HPAEC-PAD) system commonly used for glycosylation mapping of glycoproteins, or to a pool of oligosaccharides directly released from glycoproteins. The system consists of a porous graphitized high-performance chromatography column (Hypercarb) coupled to a quadrupole time-of-flight (TOF) mass spectrometer. Oligosaccharides are eluted from the column with a gradient of ammonium acetate/acetonitrile and directly identified following in-source fragmentation. Some applications of the method are presented, as well as information about the spectra and fragmentation behavior observed for N- and O-linked oligosaccharides released from some recombinant glycoproteins. Low femtomole limits of detection are achieved using proper miniaturization. Copyright (C) 2002 John Wiley Sons, Ltd.

Rehabilitation for vestibular disease is a safe method to partially alleviate symptoms of vertigo. It was hypothesized that principles of military aviation vestibular desensitization procedures that have a success rate of more than 80% can be extrapolated to chronic vestibular disease as well.The virtual reality motion base computer-assisted rehabilitation environment was used as treatment modality in 17 patients. They were exposed to sinusoidal vertical passive whole body motion in increasing intensity for a maximum of 12 sessions. The Dizziness Handicap Inventory (DHI) was used for assessment of the subjective complaints of vertigo.The median DHI scores of 50 points at baseline dropped to 22 points (P

Research on CD8 T cell-mediated inflammatory diseases requires a better understanding of target epitopes and the constraints placed upon these by major histocompatibility complex (MHC) class I binding restrictions, especially those that relate to predisposing alleles. We used linear trap quadrupole fourier transform (LTQ-FT) tandem mass spectrometry to identify naturally processed and presented peptides eluted from the MHC-negative myeloid leukaemia cell line K562 transfected with specific MHC class I genes. We provide information on the peptidome of HLA-B*39:06, which is associated with the autoimmune disease type 1 diabetes, and extend the analysis to include a further five human leukocyte antigen (HLA) alleles (HLA-A*02:01/-A*11:01/-A*24:02/-B*18:01/-B*38:01) studied under identical experimental conditions. We identified a total of 3095 individual peptides with a mascot score ≥40 (HLA-A*02:01 = 569 peptides, -A*11:01 = 904, A*24:02 = 257, -B*18:01 = 615, -B*38:01 = 453, -B*39:06 = 297). Peptides had a preferential length of nine amino acids and originated mainly from cytoplasmic or nuclear proteins. Eluted peptides revealed a strong binding motif with binding anchor positions at position 2 (P2) and the C-terminus (PΩ). Peptides eluted from HLA-A*02:01 showed a P2 preference for leucine (62% of total peptides have Leu at P2) and PΩ preference for valine (49%). Similar data are provided for HLA-A*11:01 (P2:Thr, 29%; PΩ:Lys, 49%), -A*24:02 (P2:Tyr, 78%; PΩ:Phe, 41%), -B*18:01 (P2:Glu, 77%; PΩ:Tyr, 32%), -B*38:01 (P2:His, 51%; PΩ:Leu, 45%) and -B*39:06 (P2:Arg/His, 24%; PΩ:Ala, 64%). This work thus gives an overview of the naturally processed and presented repertoire of several common and autoimmune disease-related HLA alleles, which may be useful in studying autoreactive CD8 T cell responses and the role of HLA in disease susceptibility.

Background:Ototoxicity caused by medication can lead to debilitating symptoms such as dizziness, vertigo and postural instability. There is no current ‘gold standard’ treatment available.Case report:A 79-year-old male, with bilateral loss of vestibular function caused by gentamicin toxicity after surgery for prosthetic valve endocarditis, complained of dizziness, difficulty in walking and an increased risk of falling. Physical examination showed a positive head thrust test suggesting bilateral loss of vestibular function.Results:The patient underwent a specific motion-based virtual reality enhanced protocol for peripheral vestibular disease. He showed a great improvement, with a 50 per cent reduction in his Dizziness Handicap Inventory score.Conclusion:Computer-aided rehabilitation programmes might represent an important advance in gait and posture training.

Human peptidylarginine deiminases (hPADs) have been implicated in several diseases, particularly in rheumatoid arthritis. Since hPAD2 and hPAD4 are the isotypes expressed in the inflamed joints of RA patients and protein citrullination by PADs has been proposed to play a pathophysiological role, they represent unique therapeutic targets. To facilitate the development of substrate-based PAD inhibitors the substrate specificity of hPAD2 and hPAD4 was determined. Recombinant hPADs were expressed in bacteria or mammalian cell lines and allowed to citrullinate proteins in cell lysates, as well as a series of synthetic peptides. The citrullinated residues in proteins and the efficiency of peptide citrullination were determined by mass spectrometry. In total 320 hPAD2 and 178 hPAD4 citrullination sites were characterized. Amino acid residues most commonly found in citrullination sites for both isotypes are Gly at +1 and Tyr at +3 relative to the target arginine. For hPAD4 several additional amino acids were observed to be preferred at various positions from -4 to +4. The substrate motifs determined by amino acid substitution analysis partially confirmed these preferences, although peptide context dependent differences were also observed. Taken together, our data show that the enzyme specificity for cellular substrates and synthetic peptides differs for hPAD2 and hPAD4. hPAD4 shows more restrictive substrate specificity compared to hPAD2. Consensus sequences, which can be used as the basis for the development of PAD inhibitors, were derived for the citrullination sites of both hPAD2 and hPAD4.

Aim: To describe the prevalence of somatic and psychiatric co-morbidity in children diagnosed with ADHD and other behavioural problems compared to this prevalence in children seen at the outpatient department without either of these conditions. Methods: A retrospective controlled case study was conducted in 369 children. All children with ADHD were diagnosed by a clinical psychologist in a hospital setting according to the DSM IV classification. Co-morbidity was determined by pediatricians. Results: Somatic co-morbidity was seen in 94 % of the children. However, there was no significant difference in the prevalence of somatic co-morbidity in patients with ADHD nor in patients with behavioural problems other than ADHD when compared with the control group. Only two differences slight were observed. In the ADHD group and the group with behavioural problems motor impairment was seen more often and in the control group constipation was diagnosed more frequently. Conclusion: Except for motor impairment, somatic co-morbidity of any kind does not seem to occur more frequently in children with ADHD.

Posttranslational modification (PTM) of islet autoantigens can cause lack of central tolerance in type 1 diabetes (T1D). Tissue transglutaminase (tTG), involved in PTM of gluten antigens in celiac disease, creates negatively charged peptides favored by T1D-predisposing HLA-DQ molecules, offering an attractive candidate modifying islet autoantigens in T1D. The highly predisposing HLA-DQ8cis/trans molecules share preferences for negatively charged peptides, as well as distinct peptide-binding characteristics that distinguish their peptide-binding repertoire. We screened islet autoantigens with the tTG substrate motif for candidate-modified epitopes binding to HLA-DQ8cis/trans and identified 31 candidate islet epitopes. Deamidation was confirmed for 28 peptides (90%). Two of these epitopes preferentially bound to HLA-DQ8cis and six to HLA-DQ8trans upon deamidation, whereas all other peptides bound equally to HLA-DQ8cis/trans. HLA-DQ8cis–restricted T cells from a new-onset T1D patient could only be generated against a deamidated proinsulin peptide, but cross-reacted with native proinsulin peptide upon restimulation. The rate of T-cell autoreactivity in recent-onset T1D patients extended from 42% to native insulin to 68% adding responses to modified proinsulin, versus 20% and 37% respectively, in healthy donors. Most patients responded by interferon-γ, whereas most healthy donors produced interleukin-10 only. Thus, T-cell autoreactivity exists to modified islet epitopes that differs in quality and quantity between patients and healthy donors.

Contains fulltext : 139085.pdf (Publisher’s version ) (Open Access) The Mycobacterium tuberculosis Beijing genotype, consisting of the more ancient (atypical) and modern (typical) emerging sublineage, is one of the most prevalent and genetically conserved genotype families and has often been associated with multidrug resistance. In this study, we employed a 2D-LC-FTICR MS approach, combined with dimethylation of tryptic peptides, to systematically compare protein abundance levels of ancient and modern Beijing strains and identify differences that could be associated with successful spread of the modern sublineage. The data is available via ProteomeXchange using the identifier PXD000931. Despite the highly uniform protein abundance ratios in both sublineages, we identified four proteins as differentially regulated between both sublineages, which could explain the apparent increased adaptation of the modern Beijing strains. These proteins are; Rv0450c/MmpL4, Rv1269c, Rv3137, and Rv3283/sseA. Transcriptional and functional analysis of these proteins in a large cohort of 29 Beijing strains showed that the mRNA levels of Rv0450c/MmpL4 are significantly higher in modern Beijing strains, whereas we also provide evidence that Rv3283/sseA is less abundant in the modern Beijing sublineage. Our findings provide a possible explanation for the increased virulence and success of the modern Beijing sublineage. In addition, in the established dataset of 1817 proteins, we demonstrate the pre-existence of several, possibly unique, antibiotic efflux pumps in the proteome of the Beijing strains. This may reflect an increased ability of Beijing strains to escape exposure to antituberculosis drugs.

Indian and Chinese rhesus macaques are often used in biomedical research. Genetic analyses of the major histocompatibility class I region have revealed that these macaques display a substantial level of polymorphism at Mamu-A and Mamu-B loci, which have been subject to duplication. Only a few Mamu class I allotypes are characterised for their peptide-binding motifs, although more information of this nature would contribute to a better interpretation of T cell-mediated immune responses. Here, we present the results of the characterisation of the functional properties of Mamu-B*037:01, an allotype commonly encountered in rhesus macaques of Indian and Chinese origin. Mamu-B*037:01 is seen to have a strong preference for acidic amino acids at the third residue, and for arginine, lysine, and tyrosine at the carboxyl terminus. This peptide-binding motif is not described in the human population.

To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery.A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed chronic pain at the implantation site. The pain led to minimal neck movement, which resulted in complaints of the shoulder and arm on the left side. She was treated by an orthopaedic surgeon for a frozen shoulder. Pain medication and occipital nerve blocking had no sustained effect on the pain.Occipital neuropathy is a syndrome with continuous aching involving the occipital and parietal scalp caused by trauma or peripheral compression of the occipital nerves. The most common causes of occipital neuropathy are probably direct trauma to the nerve and hypertrophic fibrosis of subcutaneous tissue surrounding the nerve. Scar formation after surgery may therefore cause entrapment of the nerve.We describe a case of occipital neuropathy as a complication of BAHA surgery.

Commentary on: Lee HY, Byun JY, Park MS, et al. Steroid-antiviral treatment improves the recovery rate in patients with severe Bell's palsy. Am J Med 2013;126:336–41.[OpenUrl][1][CrossRef][2][PubMed][3] Bell's palsy is an acute, peripheral facial paresis of unknown cause. Fortunately, many patients with Bell's palsy recover completely. However, about 15% end up with sequelae. The more severe the initial paresis, the poorer the patient's prognosis. Age is also an influencing factor, with less than 50% of patients aged over 60 achieving complete recovery.1 The existing literature suggests that Bell's palsy is caused by a reactivation of herpes simplex virus type 1 and in some cases of varicella zoster virus (sine herpete). The inflammatory reaction against the virus causes swelling of the nerve, which consequently … [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BMed%26rft.volume%253D126%26rft.spage%253D336%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.amjmed.2012.08.020%26rft_id%253Dinfo%253Apmid%252F23394867%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/j.amjmed.2012.08.020&link_type=DOI [3]: /lookup/external-ref?access_num=23394867&link_type=MED&atom=%2Febmed%2F19%2F1%2F15.atom

T cell recognition of minor histocompatibility Ags (MiHA) plays an important role in the graft-versus-tumor effect of allogeneic stem cell transplantation. Selective infusion of T cells reactive for hematopoiesis-restricted MiHA presented in the context of HLA class I or II molecules may help to separate the graft-versus-tumor effects from graft-versus-host disease effects after allogeneic stem cell transplantation. Over the years, increasing numbers of MiHA have been identified by forward immunology approaches, and the relevance of these MiHA has been illustrated by correlation with clinical outcome. As the tissue distribution of MiHA affects the clinical outcome of T cell responses against these Ags, it would be beneficial to identify additional predefined MiHA that are exclusively expressed on hematopoietic cells. Therefore, several reverse immunology approaches have been explored for the prediction of MiHA. Thus far, these approaches frequently resulted in the identification of T cells directed against epitopes that are not naturally processed and presented. In this study we established a method for the identification of biologically relevant MiHA, implementing mass spectrometry–based HLA-peptidomics into a reverse immunology approach. For this purpose, HLA class I binding peptides were eluted from transformed B cells, analyzed by mass spectrometry, and matched with a database dedicated to identifying polymorphic peptides. This process resulted in a set of 40 MiHA candidates that were evaluated in multiple selection steps. The identification of LB-NISCH-1A demonstrated the technical feasibility of our approach. On the basis of these results, we present an approach that can be of value for the efficient identification of MiHA or other T cell epitopes.

Peptides presented by human leukocyte antigen (HLA) molecules on the cell surface play a crucial role in adaptive immunology, mediating the communication between T cells and antigen presenting cells. Knowledge of these peptides is of pivotal importance in fundamental studies on T cell action, and in cellular immunotherapy and transplantation. In this study we present the in-depth identification and relative quantification of 14,500 peptide ligands constituting the HLA-ligandome of B-cells. This large number of identified ligands provides a general insight in the presented peptide repertoire and antigen presentation. Our uniquely large set of HLA-ligands allowed us to characterize in detail the peptides constituting the ligandome in terms of relative abundance, peptide length distribution, physicochemical properties, binding affinity to the HLA molecule and presence of post-translational modifications. The presented B-lymphocyte ligandome is shown to be a rich source of information by the presence of minor histocompatibility antigens, virus-derived epitopes and post-translationally modified HLA ligands and can be a good starting point to solve a wealth of specific immunological questions. These HLA ligands can form the basis for reversed immunology approaches to identify T cell epitopes, not based on in silico predictions, but based on the bona fide eluted HLA-ligandome.

Large volume injections —involving on-column focusing— were evaluated for packed micro and capillary liquid chromatography columns of 300 μm and 1.0 mm inner diameter (I.D.) respectively. It was found that the I.D. of the injection loop plays a critical role in sample dispersion, effecting peak asymmetry and injection reproductibility. The use of injection loops with too large or too small an I.D. resulted in a reduced injection performance. Ideally the I.D. should be in between 100–150 μm. Further it was investigated what influence the loop volume and the use of a low dispersion injection technique had on the column stability. The combination of large volume injections—up to 1 μl and 5 μl for 300 μm and 1.0 mm I.D. columns, respectively—and additional switching of the injection valve did not affect column lifetime. Typical decreases of only 10% in efficiency over 1500 injections were found.

In pre-1994 South Africa the discourse on sexuality was rigidly controlled by apartheid and a distinct bias in favour of a certain brand of Christianity. Based on the concept of marriage as defined in Christendom, any kind of recognition of same-sex unions was prohibited in South Africa, and sexual relations between persons of the same-sex were characterised as deviant and criminal behaviour. With the abolition of apartheid and the establishment of a new constitutional dispensation based on the values of equality, human dignity and freedom, discrimination against homosexuals was officially relegated to the past. The relegation is attributed to the political alliances formed between minority and marginalised members of our society. Political alliances inevitably led to the acceptance in the South African Constitution, 1996, that discrimination on the ground of sexual orientation would automatically be unfair until proven otherwise. This constitutional commitment led to various piecemeal legislative and judicial developments after 1994, when the recognition and protection of same-sex life partnerships have been at issue. The Constitutional Court declared the common-law definition of marriage to be inconsistent with the Constitution and as a result the Civil Union Act 17 of 2006 was enacted to govern same-sex marriage. This article demonstrates how same-sex couples are made to feel like outsiders due to certain legal provisions, and that the guarantee of democratic tolerance for all South Africans still remains somewhat illusory.

Bepaalde stoffen in bloed en urine, zogeheten biomarkers, kunnen gebruikt worden voor het stellen van de diagnose van de stofwisselingsziekte Mucopolysaccharidose type I (MPS I) op basis van bloed afgenomen bij de hielprikscreening. Dit blijkt uit het onderzoek van Minke de Ru dat zich richtte op het bereiken van overeenstemming tussen behandelaars over de twee behandelingsvormen van MPS I, het beter onderscheiden van de verschillende varianten van de ziekte en het vroegtijdig diagnosticeren ervan. Opname van MPS I in nationale hielprikscreeningsprogramma’s kent meerdere voordelen, maar ook ethische dilemma’s. De Ru toont tevens aan dat de biomarkers ook een rol kunnen spelen in het beoordelen van het effect van behandeling en het beter onderscheiden van de verschillende varianten van de ziekte. MPS I is een zeldzame stofwisselingsziekte, waarbij het lichaam niet in staat is bepaalde suikerketens af te breken. Door toenemende stapeling hiervan in het lichaam ontstaat een grote verscheidenheid aan ziekteverschijnselen. De ziekte is soms ernstig (ziekte van Hurler), soms relatief mild (ziekte van Scheie). Het vroeg stellen van een diagnose is vaak lastig, maar essentieel voor het behalen van een zo optimaal mogelijk behandelingsresultaat.