The organization of human leucocyte antigen class I epitopes in HIV genome products: implications for HIV evolution and vaccine design

Knowledge of human leucocyte antigen (HLA) peptide binding motifs permits rapid selection of candidate viral protein fragments for induction of T cell-mediated immunity. A search for HLA class I peptide binding motifs in structural proteins of human immunodeficiency virus (HIV) of different genetic lineages provides a map of the genetic organization of potential T cell antigenic sites, and at the same time identifies all motifs in highly conserved regions of HIV-1 env, gag and pol. The density of motifs is anomalous at both the high and low end of the spectrum: local organization is characterized by clustering in relatively short regions, while large scale organization is characterized by anomalously long runs between motifs. The former is expected simply due to the fact that motifs often have overlapping anchor residue sets. A detailed statistical analysis of the latter, however, shows that the length of the runs cannot be accounted for by chance alone. Although motif clusters show no preference to be in either conserved or variable regions, low motif density stretches occur preferentially in variable portions of the protein sequence, which suggests that the virus may be mutating to evade the cellular arm of the immune system.     

Leptin

Three strains of yellow fever virus (YFV) were isolated in 1982 in The Ivory Coast, one from a human case and two from Aedes luteocephalus, during and subsequent to an epidemic. The complete genomic sequence of the human strain was determined and compared to that of the 1927 Asibi strain of YFV. The divergence observed was on average of 8.3%, ranging from 5.5 to 11.7% in the coding region. The transitions to transversions ratio was 5.9. Most mutations (84.3%) occurred on the third position of the codons, with synonymous mutations representing 92.5%. However, when partial sequences representing 60% of each genome were compared, homology between the three Ivory Coast strains was greater than 99%. These results demonstrate the homogeneity of the virus strains circulating in different hosts and vectors in a limited geographical region and validate the concept of topotype in viral quasi-species.     

Potentiation of 5-fluorouracil-leucovorin activity by alpha2a-interferon in colon adenocarcinoma xenografts

The present study examined the effect of received support on adjustment by foreign students, with data from 33 Chinese students who completed questionnaires at three occasions: three months (the first period), nine months (the second period), and one year and nine months (the third period) after they arrived in Japan. The Social Support Scale for Chinese Students in Japan (Jou, 1993a) and items for measurement of adjustment were used in the questionnaires. Analysis of Variance results revealed no differences among the amounts of support received during the three periods, but compared with the first or second, adjustment was better during the third period. Results from path analysis indicated that support in the first period was positively related to adjustment in the first period, the first period adjustment and second period support positively to the second period adjustment, and only the second period adjustment positively to the third period adjustment. Thus, the present study suggests that it is especially necessary to provide more support to foreign students during the critical early period in order to facilitate their adjustment.     

Expression of deletion-containing dystrophins in mdx muscle: implications for gene therapy and dystrophin function

The expression of full-length dystrophin and various dystrophin deletion mutants was monitored in mdx mouse muscle after intramuscular injection of dystrophin-encoding plasmid DNAs. Recombinant dystrophin proteins, including those lacking either the amino terminus, carboxyl terminus, or most of the central rod domain, showed localization to the plasma membrane. This suggests that there are multiple attachment sites for dystrophin to the plasma membrane. Only those constructs containing the carboxyl terminus were able to stabilize dystrophin-associated proteins (DAP) at the membrane, consistent with other studies that suggest that this domain is critical to DAP binding. Colocalization with DAP was not necessary for membrane localization of the various dystrophin molecules. However, stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of mutant dystrophins beyond 1 wk and these same criteria seemed important for mitigating the histopathological consequences of dystrophin deficiency.     

Preserved viability of the isolated bowel segment, created by omentoenteropexy: a histological observation

Creation of the isolated bowel segment (IBS) by omentoenteropexy in rats and dogs consists of a two-step procedure: initial omentoenteropexy to the antimesenteric border of a jejunal segment, and division of its mesentery 6 weeks later. Viability of this IBS is maintained by the angiogenic process, which occurs at the level of the myoenteropexy. Histological studies were performed by light microscopy on the bowel wall structures of the IBS before and after the mesenteric division, as well as after a lengthening procedure performed on the IBS in one dog. The authors conclude that (1) in rats and dogs the intestinal wall structures of all IBS variants created by omentoenteropexy appear close to normal, and (2) neovascularization can be clearly detected at the level of the omentoenteropexy.     

Resolution of a left ureteral stone using electrohydraulic lithotripsy in a thoroughbred colt

A 3-year-old Thoroughbred colt was presented for evaluation of azotemia and anorexia. Physical examination revealed a ureterolith in the left ureter, approximately 10 cm from the bladder, which was thought to obstruct urine flow by approximately 90% when viewed cystoscopically. Ultrasonographic examination of both kidneys revealed indistinct corticomedullary junctions, and the right kidney was more hyperechoic. A percutaneous biopsy of the right kidney revealed chronic interstitial nephritis with marked interstitial medullary fibrosis. Medical therapy consisting of IV fluids, sodium chloride PO, and ammonium chloride PO was initiated. Ureteroscopic electrohydraulic lithotripsy via a perineal urethrostomy was used to successfully remove the stone. Klebsiella oxytoca, which responded to oral enrofloxacin therapy, was cultured from the urine after surgery. Azotemia resolved and the horse resumed training.     

Radiolabeled monoclonal antibodies

Monoclonal antibodies (MoAbs) are biologically engineered proteins designed to bind to antigens emanating from tumor cells. Selected radioactive isotopes are fused with MoAbs to allow radioimmunodetection of external imaging of metastatic deposits in patients with colon cancer. For the past 10 years, radiolabeled MoAbs have improved tumor localization techniques and influenced the clinical management of surgical patients. Intraoperatively, surgeons use appropriately shielded, handheld, gamma detection probes to locate radiolabeled MoAbs and corresponding colon cancers (ie, residual, recurrent tumors). Using gamma detection probes intraoperatively, surgeons can localize nonpalpable occult tumors and disease not suspected from external antibody scans or other traditional diagnostic methods. This success confirms the need for complete tumor resections, thorough scanning of entire tumor beds, and ex vivo scanning of surgical specimens to assess for potential nodal metastases.