Different composition of the human and the mouse gammadelta T cell receptor explains different phenotypes of CD3gamma and CD3delta immunodeficiencies

The γδ T cell receptor for antigen (TCR) comprises the clonotypic TCRγδ, the CD3 (CD3γε and/or CD3δε), and the ζζ dimers. γδ T cells do not develop in CD3γ-deficient mice, whereas human patients lacking CD3γ have abundant peripheral blood γδ T cells expressing high γδ TCR levels. In an attempt to identify the molecular basis for these discordant phenotypes, we determined the stoichiometries of mouse and human γδ TCRs using blue native polyacrylamide gel electrophoresis and anti-TCR–specific antibodies. The γδ TCR isolated in digitonin from primary and cultured human γδ T cells includes CD3δ, with a TCRγδCD3ε₂δγζ₂ stoichiometry. In CD3γ-deficient patients, this may allow substitution of CD3γ by the CD3δ chain and thereby support γδ T cell development. In contrast, the mouse γδ TCR does not incorporate CD3δ and has a TCRγδCD3ε₂γ₂ζ₂ stoichiometry. CD3γ-deficient mice exhibit a block in γδ T cell development. A human, but not a mouse, CD3δ transgene rescues γδ T cell development in mice lacking both mouse CD3δ and CD3γ chains. This suggests important structural and/or functional differences between human and mouse CD3δ chains during γδ T cell development. Collectively, our results indicate that the different γδ T cell phenotypes between CD3γ-deficient humans and mice can be explained by differences in their γδ TCR composition.     

Antimicrobial susceptibility of clinical isolates of Serratia marcescens.

The in vitro susceptibilities of 242 isolates of Serratia marcescens to 17 antibacterial drugs have been determined. Oxolinic acid, nalidixic acid, cefoxitin, and amikacin were the most active drugs. Ampicillin, kanamycin, and cephalothin were among the least active. A 4-year study showed that resistance of S. marcescens to dibekacin, tobramycin, sisomycin, and gentamicin has increased at least one order of magnitude in that period, whereas resistance to amikacin showed but a twofold increase.     

Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC)

BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.     

Selective disbalances of peripheral blood T lymphocyte subsets in human CD3γ deficiency

The selection of T lymphocytes in the thymus and their activation upon the encounter with foreign antigens in the periphery require the aggregation and signals of the Tcell receptor (TcR)/CD3 complex and several surface molecules termed coreceptors (notably CD4 or CD8 and CD45). The spatial arrangement and interactions of the different molecules in the resulting multimolecular recognition structure are mostly unknown. Here we report, from studies on a healthy human CD3γ deficiency, that the lack of the CD3γ component of the TcR/CD3 complex is associated with a long-term severe defect of peripheral blood CD4⁺CD45RA⁺ and CD8+ lymphocytes, whereas CD4⁺CD45RO⁺, B and natural killer lymphocytes are unaffected. These results suggest that the CD3y site of the TcR/CD3 complex is required for the peripheral representation of certain Tcell types.     

Modificated plication technique of the tunica albuginea in penis curvature correction

We present our penile curvature treatment experience in Peyronie's disease and cogenital curvature, using a modificated plication technique of the tunica albuginea with Prolene inverted sutures covered with Vicryl ones. The first suture gives security to the plication and the second one hides the first dots avoiding the nonabsorbable sutures bother.