An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells

Patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related conditions are known to have abnormalities of T cell subpopulations, including a decreased helper/inducer (bearing the CD4 antigen) to suppressor/cytotoxic (bearing the CD8 antigen) T cell ratio and decreased absolute numbers of T cells with the CD4+ phenotype. Infection of T cells with a retrovirus, termed human immunodeficiency virus (HIV), is thought to be important in these abnormalities. HIV infection alone does not adequately explain the CD4+ T-cell abnormalities seen in AIDS, however, and the nature of T-cell destruction in this disease remains poorly characterized. Here we describe an AIDS-related serum autoantibody that reacts with an antigen of relative molecular mass 18,000 (Mr 18K) restricted to lectin-stimulated or HIV-infected CD4+ T cells. The antibody also suppresses proliferation of CD4+ T cells in vitro and induces cytotoxicity of these cells in the presence of complement. Its role in the development of AIDS merits attention.     

NO is necessary and sufficient for egg activation at fertilization

The early steps that lead to the rise in calcium and egg activation at fertilization are unknown but of great interest--particularly with the advent of in vitro fertilization techniques for treating male infertility and whole-animal cloning by nuclear transfer. This calcium rise is required for egg activation and the subsequent events of development in eggs of all species. Injection of intact sperm or sperm extracts can activate eggs, suggesting that sperm-derived factors may be involved. Here we show that nitric oxide synthase is present at high concentration and active in sperm after activation by the acrosome reaction. An increase in nitrosation within eggs is evident seconds after insemination and precedes the calcium pulse of fertilization. Microinjection of nitric oxide donors or recombinant nitric oxide synthase recapitulates events of egg activation, whereas prior injection of oxyhaemoglobin, a physiological nitric oxide scavenger, prevents egg activation after fertilization. We conclude that nitric oxide synthase and nitric-oxide-related bioactivity satisfy the primary criteria of an egg activator: they are present in an appropriate place, active at an appropriate time, and are necessary and sufficient for successful fertilization.     

Amorphous calcium phosphate in the stylets produced by a marine worm (Nemertea)

Summary Electron microprobe analyses of the calcified stylets produced by the nemertean wormAmphiporus formidabilis reveal large calcium and phosphorus peaks. IR spectroscopy and X-ray diffraction indicate that the calcium and phosphorus in stylets constitute an amorphous calcium phosphate rather than a crystalline mineral phase.     

Altered brain response to verbal learning following sleep deprivation

The effects of sleep deprivation on the neural substrates of cognition are poorly understood. Here we used functional magnetic resonance imaging to measure the effects of 35 hours of sleep deprivation on cerebral activation during verbal learning in normal young volunteers. On the basis of a previous hypothesis, we predicted that the prefrontal cortex (PFC) would be less responsive to cognitive demands following sleep deprivation. Contrary to our expectations, however, the PFC was more responsive after one night of sleep deprivation than after normal sleep. Increased subjective sleepiness in sleep-deprived subjects correlated significantly with activation of the PFC. The temporal lobe was activated after normal sleep but not after sleep deprivation; in contrast, the parietal lobes were not activated after normal sleep but were activated after sleep deprivation. Although sleep deprivation significantly impaired free recall compared with the rested state, better free recall in sleep-deprived subjects was associated with greater parietal lobe activation. These findings show that there are dynamic, compensatory changes in cerebral activation during verbal learning after sleep deprivation and implicate the PFC and parietal lobes in this compensation.     

Supersensitivity after intraventricular 6-hydroxydopamine: Relation to dopamine depletion

Summary 6-Hydroxydopamine increased behavioral response to L-DOPA in proportion to the decrease of dopamine (DA) and DA uptake in rat striatum. The increased response to apomorphine, however, only occurred after >80% DA loss. Thus, 6-hydroxydopamine may induce postsynaptic changes only following large lesions.Supported in part by USPHS grants No. MH-00058 and MH-20620. We thank Kathleen Hays, Suzanne Wuerthele and Dennis McKeag for technical assistance.     

Caffeine restores feeding response to 2-deoxy-D-glucose in 6-hydroxydopamine-treated rats

A large portion of the central catecholaminergic nerve terminals of the rat are destroyed by administering 6-hydroxydopamine (6-HDA) via the cerebrospinal fluid. Animals lesioned in this way often appear normal, yet show many subtle behavioural abnormalities. We have been examining one example of this phenomenon, the failure of 6-HDA-lesioned rats to increase food intake when given a systemic injection of 2-deoxy-D-glucose (2-DG) (refs 5, 6). This glucose analogue seems to elicit feeding in intact rats due to its inhibition of glycolysis in cerebral chemoreceptor cells. We have proposed that lesioned animals do not eat because of an insufficient central catecholaminergic response to the severe decrease in glucose utilisation induced by 2-DG (ref. 10). If so, then pretreatments which serve to augment this neurochemical response might be expected to reinstate behavioural function. Consistent with this hypothesis, very large increases in telencephalic tyrosine hydroxylase activity in 6-HDA-lesioned animals, which occur following chronic insulin treatment, are associated with the restoration of 2-DG-induced feeding. Many of the physiological effects of catecholamines in the sympathetic nervous system seem to be mediated by an increase in the cyclic AMP concentration of the target cells. Methylxanthenes, such as caffeine and theophylline, inhibit phosphodiesterase, prevent cyclic AMP degradation, and thereby potentiate the catecholamine-stimulated rise in cyclic nucleotide. They also enhance many of the behavioural and physiological effects of catecholamines, presumably by the same mechanism. We therefore sought to determine whether the acute administration of those sympathomimetic agents, in intact and 6-HDA-lesioned rats, also would potentiate 2-DG-induced feeding, a behaviour that seems to be mediated, in part, by central catecholaminergic neurons. We report that caffeine restores the 2-DG-induced feeding response.