1H MR Spectroscopy of the Brain in HIV-1-Seropositive Subjects: Evidence for Diffuse Metabolic Abnormalities

PURPOSE: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process.MATERIALS and METHODS: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T. Nine patients were classified as being neuropsychiatrically unimpaired and six as having HIV-1-associated dementia on the basis of a full neuropsychological examination. Spectra were analysed from multiple voxels located in the fronto-parietal cortex and white matter at the level of centrum semiovale.RESULTS: A significant reduction in mean peak area ratios of NAA/Cr (p<0.005 in the grey matter, p<0.01 in the white matter) and an elevation in mean Cho/Cr (p<0.005 in both grey matter and white matter) were observed in patients with HIV-1-associated dementia when compared to healthy volunteers. No significant metabolite abnormalities were detected in the neuropsychiatrically unimpaired group, although there was a similar trend in the metabolite ratios. The changes in metabolite ratios were of the same order of magnitude in the cortical grey matter and subcortical white matter as in the deeper white matter in all patients. There were also no significant regional variations in mean metabolite ratios between right and left hemispheres or anterior and posterior voxels at the level of the brain studied. There were no abnormalities in Glx/Cr in any spectra analysed from either patient group.CONCLUSION: The absence of significant regional variation in metabolite ratios at the level of the centrum semiovale provides some evidence that abnormalities of cerebral metabolites in HIV-infected patients may be part of a diffuse process.     

The relationship of psychological variables and disease progression among long-term HIV-infected men

This study investigated the contribution of psychological factors to disease progression among long-term HIV-1 infected gay men. Participants completed self-report measures including coping strategies, life events, social support, personality and psychological morbidity and were followed clinically for up to 30 months. Cox proportional hazards survival analyses were carried out to CD4<200 x 106/1 and AIDS-related complex (ARC) or AIDS diagnosis controlling for viral load, antiretroviral drug use and CD4 count. Only acceptance coping was a significant predictor of time to ARC or AIDS diagnosis: the risk of ARC or AIDS was almost 5 times greater for those scoring within the lowest tertile compared with those scoring in the highest tertile (HR=4.7, 95% CI 1.8-12.3).     

Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection

Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, during and after seroconversion. These positively selected HIV-1 variants carried epitope sequence changes that either diminished or escaped CTL recognition. Other proviruses had mutations that abolished the Nef epitope altogether. These results provide clear evidence that CTLs exert selection pressure on the viral population in acute HIV-1 infection.     

A new cytoplasmic organelle,related to both lipid and glycogen storage materials in the yolk sac of the bat,Tadarida brasiliensis cynocephala

The gestation period of Tadarida is approximately four months long extending from late February to June. During the first half of gestation the yolk sac undergoes a complete collapse bringing two layers of endodermal cells into contact with one another and obliterating the cavity of the yolk sac. Both the endodermal and the mesodermal cells hypertrophy and develop into a glandular-looking organ during the latter half of gestation. Approximately a month before parturition the endodermal cells become progressively laden with lipid and glycogen. Immediately before birth, however, both of these storage materials are depleted. This depletion is preceded by the formation of an extensive array of hexagonal membranous channels within the cytoplasm. Some of the membranes of this organelle are closely applied to lipid droplets and glycogen granules can be observed in linear patterns within the hexagonal channels. Tissues taken at term showed the membranes of the hexagonal channels continuous with a paracrystalline membranous structure. The close morphological association of the membranous organelle to both the lipid and glycogen storage materials indicates that it is involved in their metabolism in the yolk sac of the bat.     

Two bacteriophages of Clostridium difficile.

Two temperate bacteriophages of differing morphology and host range were isolated by screening 94 isolates of Clostridium difficile. Phage 41 had a 300-nm flexible tail, whereas phage 56 had a shorter tail with a contractile sheath. Electron microscopy of phage 56 lysates exposed to elevated magnesium concentrations showed small virus-like particles which were 21 nm in diameter. The addition of MgCl2 to semisolid agar overlays enhanced both the titer and plaque size of phage 56. Phage 56 was more temperature labile than phage 41 and demonstrated unusual lability in buffer at pH 7.0. One-step growth and adsorption experiments revealed that both phages had latent periods of about 60 min, but phage 56 adsorbed to its indicator strain more efficiently. Phage 56, which was obtained from a toxigenic strain of C. difficile, was used to lysogenize its nontoxigenic indicator strain, but no conversion to toxigenicity was observed in this strain.     

Is corneal deposition of antimalarial any indication of retinal toxicity?

Ninety-five percent of patients on chloroquine demonstrate corneal deposition of the drug with the pupil dilated; less than 10% of patients on hydroxychloroquine show any corneal changes when so examined. I describe one patient on chloroquine and two on hydroxychloroquine who demonstrated large amounts of corneal antimalarial drug, leading to the early diagnosis of definite retinopathy. Examination of the cornea with the pupil dilated may reveal the presence of retinal toxicity in some patients.