HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes

Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HIV-1-infected cells.     

Synthesis and dopamine receptor selectivity of the benzyltetrahydroisoquinoline, (R)-(+)-nor-roefractine

Colonic variceal bleeding is a rarity and is most commonly due to portal hypertension. The present report describes a patient with portal hypertension due to portal vein thrombosis who, following esophageal transection and successful sclerotherapy, developed a massive lower gastrointestinal bleeding from colonic varices. The literature is reviewed, and the pathophysiology of this complication is discussed. Possible etiologies of this condition may be esophageal transection and devascularization, successful sclerotherapy, and extensive thrombosis of the portal vein resulting in obliteration of the coronary-azygous anastomotic system. In such a situation other potential sites of portosystemic anastomoses, such as the colon, may be opened up, resulting in the development of colonic varices. Indeed, the incidence of colonic varices in two series after sclerotherapy for esophageal varices was 60-100%. Of 33 candidates evaluated for liver transplantation, colonic varices were found in 1.     

On-the-fly fluorescence lifetime detection of dye-labeled DNA primers for multiplex analysis

Mixtures of dye-labeled, M13-forward DNA primers were separated by capillary gel electrophoresis and detected on-the-fly, using fluorescence lifetime measurements, to evaluate four-decay detection for multiplex DNA sequencing. Three different four-dye systems were used, two that were excited at 488 nm and one that was excited at 514 nm. Each dye-labeled primer was identified on the basis of the lifetime of the conjugated dye using nonlinear least squares or the maximum entropy method to analyze the lifetime data. Overlapping electrophoretic peaks were generated by making multiple injections of mixtures of the dye-labeled primers. The overlapping peaks were resolved by fitting the data to two-, three- or four-component lifetime models used in nonlinear least-squares analysis in which each lifetime component was fixed to the predetermined lifetime of the corresponding dye-labeled primer. In two of the dye systems, the lifetimes of the four dye-labeled primers were sufficiently different to allow peak resolution. In the other dye system, addition of 10% DMSO to the run buffer changed the lifetime of one dye-labeled primer, allowing it to be resolved from another dye-labeled primer with similar lifetime.     

The sedimentation equilibrium of heterogeneously associating systems and mixtures of non-interacting solutes: analysis without determination of molecular weight averages

In 8 healthy subjects (group A) and 4 subjects with respiratory symptoms (group B), the lung pressure-volume curve (P-V curve), maximum expiratory flow-volume curve (MEFVC) and respiratory resistance (Rrs) at all vital capacities were measured. To avoid laryngeal artifact on a mouth pressure, an intratracheal catheter was used for measurement of Rrs which was obtained with 3 cycles/sec oscillatory forced pressure. Group B did not show a different elastic recoil from group A. In comparison of the maximum expiratory flow (Vmax) at 80, 70, 60 and 50% of the total lung capacity (TLC). Vmax of group B showed lower values than that of group A. Rrs was almost the same in both groups from 70% TLC upwards, but Rrs of group B was higher than that of group A from 65%TLC downwards. Since the lung elastic recoil pressures (Pst (1)) in the two groups were not different and Rrs's were different significantly only at low lung volumes, the decrease in Vmax of group B was supposed to be due to the increased Rrs which might reflect small airway obstruction.     

Lymphomagenesis in AKR.Fv-1b congenic mice

In the AKR.Fv-1b congenic strain the Fv-1n allele of the AKR/J mice was substituted with the Fv-1b allele, thereby limiting viral replication and spread of the endogenous N-tropic murine leukemia virus. As a result of this genetic change AKR.Fv-1b mice develop a low spontaneous incidence (7%) of T-cell lymphomas and about 28% of Ly-1+ B-cell lymphomas are observed in old mice. Characteristic changes in thymus subpopulations of AKR/J mice (related to the formation of the dual tropic mink cell focus inducing (MCF) type virus in the thymus) were not observed in the thymus of AKR.Fv-1b mice. In contrast to the low susceptibility to spontaneous T-cell lymphoma development, these mice were highly sensitive to fractionated irradiation or to radiation leukemia virus (a mixture of N- and B-tropic viruses) induced T-cell lymphoma. Potential lymphoma cells (that would ultimately develop into Ly-1+ B-cell lymphomas) were demonstrated in bone marrow and spleens of 16-24-month-old mice. Analysis of the Ly-1+ IgM+ B-cell population in spleens of 18-month-old mice revealed a significant increase in this population (35% versus 2% in young spleens). The spontaneous Ly-1+ B-cell lymphoma incidence could be enhanced (up to 77%) by in vivo administration of anti-CD8 monoclonal antibody or IL-4 to 18-month-old mice. Virological analysis of T/B-cell lymphomas for class I MCF viruses indicated that Class I MCF development was tightly correlated with T-lymphoma development (except radiation induced tumors that showed no MCF provirus involvement). In contrast, Ly-1+ B-cell lymphoma development was independent of Class I MCF pathogenic virus involvement.