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Verbal memory deficits have been related to reduced volume of medial temporal structures in several neurological and psychiatric populations, including schizophrenic patients. Impairments in verbal memory have been proposed to be a marker of risk for schizophrenia. Recently, relatives of schizophrenic patients have been reported to have reduced volume of the amygdala-hippocampal complex. In this study, we evaluate the possibility that amygdala-hippocampal volume reductions may constitute one neural substrate of verbal memory deficits in first-degree relatives. Subjects were 20 healthy first-degree relatives of schizophrenic patients and 14 demographically similar controls. Verbal memory was assessed with the Logical Memory Test. Subjects were scanned with high-resolution MRI and the images were transformed into Talairach space. Volumes of interest were amygdala-anterior hippocampus and posterior hippocampus. Relatives of schizophrenic patients had intact immediate verbal memory but significantly poorer delayed verbal memory than controls. Relatives also had significantly reduced amygdala-anterior hippocampus volumes. Across all subjects, delayed verbal memory was significantly correlated with amygdala-anterior hippocampus volume. The magnitude of the correlation did not differ between the groups. These data provide an empirical link between memory performance and volumetric abnormalities in the amygdala-hippocampal complex in the relatives of schizophrenic patients.

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BACKGROUND AND PURPOSE: A measles outbreak in a facility housing Old World nonhuman primates developed over a 2-month period in 1996, providing an opportunity to study the epidemiology of this highly infectious disease in an animal-handling setting. METHODS: Serum and urine specimens were collected from monkeys housed in the room where the initial measles cases were identified, other monkeys with suspicious measles-like signs, and employees working in the affected areas. Serum specimens were tested for measles virus-specific IgG and IgM antibodies, and urine specimens were tested for measles virus by virus isolation or reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: A total of 94 monkeys in two separate facilities had evidence of an acute measles infection. The outbreak was caused by a wild-type virus that had been associated with recent human cases of acute measles in the United States; however, an investigation was unable to identify the original source of the outbreak. Quarantine and massive vaccination helped to control further spread of infection. CONCLUSIONS: Results emphasize the value of having a measles control plan in place that includes a preventive measles vaccination program involving human and nonhuman primates to decrease the likelihood of a facility outbreak.

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N-Butyl benzenesulfonamide (NBBS), a plasticizer used commercially in the polymerization of polyamide compounds, is neurotoxic. Young adult New Zealand white rabbits, inoculated repeatedly with NBBS by the intracisternal or intraperitoneal routes, developed a dose-dependent motor dysfunction characterized by limb splaying, hyperreflexia, hypertonia, gait impairment, and abnormal righting reflexes. Histopathological changes consisted of intramedullary thickening of the ventral horn axons, random neuroaxonal spheroids confined to brain stem nuclei and spinal motor neurons, and swollen dendritic processes of spinal motor neurons. Immunoreactivity to a monoclonal antibody against microtubule-associated protein-2 (MAP-2) was markedly increased in the dendrites of spinal motor neurons following thrice weekly intraperitoneal inoculations of NBBS for 4 months, whereas after 12 monthly intracisternal inoculations, MAP-2 immunoreactivity was absent or strikingly reduced in the same neuronal populations. Ultrastructurally, postsynaptic zones contained vacuoles and multilamellar bodies. These findings raise questions about the safety of NBBS to humans.

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Young adult New Zealand white rabbits, inoculated intracisternally once monthly with 100 micrograms AlCl3, developed progressive hyperreflexia, hypertonia, gait impairment, weight loss, muscle wasting and abnormal righting reflexes over the course of 8 months. No overt encephalopathic features were present. In spinal motor neuron perikarya, dendrites and axonal processes, argentophilic globular inclusions were extensive. Additionally, neurofibrillary tangle-like argentophilic inclusions were consistently present in the gigantocellularis, reticularis, raphe and trapezoid nuclei, but rarely present in the dorsal and ventral subiculum, parasubiculum and anterior thalamus, and never found in the cerebral cortex, substantia nigra, locus ceruleus, or cerebellum. All neuronal inclusions were immunoreactive with monoclonal antibodies recognizing phosphorylated and nonphosphorylated high and intermediate weight neurofilament proteins (SMI 31, SMI 32). Also, some spinal motor neuron inclusions were immunoreactive with a monoclonal antibody recognizing an 'age-related' phosphorylation state of neurofilament (SMI 34). Ultrastructurally, the inclusions consisted of straight or interwoven skeins of 10 nm filaments. This study demonstrates unique variability in the phosphorylation state of aluminum-induced neurofilamentous inclusions in a predominantly motor system degeneration induced by chronic low dose AlCl3.

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Scrapie-infected hamsters had slightly elevated non-fasting plasma glucose levels, markedly abnormal glucose tolerance tests, and impaired release of insulin in response to a glucose load. Plasma cortisol levels were essentially the same in infected and uninfected animals. Histological examination of the pancreas revealed no morphological changes in infected animals with no alteration in distribution of cells secreting insulin, glucagon and somatostatin. In contrast, brains of scrapie-infected animals had the diffuse vacuolation typical of spongiform encephalopathy. These experiments suggest that scrapie-induced diabetes mellitus in hamsters may result from damage to the central nervous system.

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Chimpanzees are susceptible to infection by divergent strains of human immunodeficiency virus type 1 (HIV-1), none of which cause clinical or immunological abnormalities. Chimpanzees were inoculated with one of four strains of HIV-1: human T-lymphotropic virus (HTLV) type IIIB, lymphadenopathy virus (LAV) type 1, HTLV type IIIRF, or an isolate from the brain of a patient with acquired immunodeficiency syndrome. Within 6 months after inoculation with the closely related strains HTLV-IIIB or LAV-1, six chimpanzees developed serum antibodies to the C-terminal half (amino acids 288-467) of the HTLV-IIIB external envelope glycoprotein gp120. Sera from five of those chimpanzees had HTLV-IIIB cell-fusion-inhibiting antibody titers greater than or equal to 20 at that time, indicating that they neutralized the infecting strain of HIV-1 in vitro. No antibodies to the carboxyl terminus of HTLV-IIIB gp120 were observed in sera of chimpanzees inoculated with HTLV-IIIRF or with the brain-tissue strain, and those sera did not neutralize HTLV-IIIB. A rabbit immunized with the C-terminal portion of gp120 acquired neutralizing antibodies that bound to four domains of the HTLV-IIIB external envelope as analyzed by reactivity to 536 overlapping nonapeptides of gp120. One of these domains in the variable region V3, with the amino acid sequence IRIQRGPGRAFVTIG (amino acids 307-321), bound to all chimpanzee sera that neutralized HTLV-IIIB but not to the serum of the HTLV-IIIRF-inoculated chimpanzee that did not neutralize HTLV-IIIB. The HTLV-IIIRF sequence at the same location, ITKGPGRVIYA, was recognized by the serum of the HTLV-IIIRF-inoculated chimpanzee but not by any sera of the HTLV-IIIB-inoculated or LAV-1-inoculated chimpanzees. The HTLV-IIIB residues RIQR and AFV and the HTLV-IIIRF residues lysine and VIYA, flanking a highly conserved beta-turn (GPGR), appear to be critical for antibody binding and subsequent type-specific virus neutralization. This neutralization epitope, putatively consisting of a loop between two cysteine residues (amino acids 296 and 331) connected by a disulfide bond, is immunodominant in HIV-1-infected chimpanzees and induces antibodies restricted to the homologous viral strain.

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Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which was common to LAV-1 as well as to HTLV-IIIB reisolated from infected chimpanzees. It thus appears that a group-specific neutralizing antibody response as well as a group-specific cytotoxic response can develop in chimpanzees after an inoculation of a single HIV variant. This finding suggests that a common, less immunodominant determinant(s) is present on a single HIV strain which could induce group-specific antibodies during viral infection and replication. The identification of this group-specific epitope and the induction of analogous immunity may be relevant to vaccine development against human acquired immunodeficiency syndrome.

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The presence of human immunodeficiency virus (HIV) antigens in cerebrospinal fluid (CSF) was associated with progressive encephalopathy in adult and pediatric patients with acquired immunodeficiency syndrome (AIDS). HIV antigen was detected in CSF from 6 of 7 AIDS patients with progressive encephalopathy. By contrast, HIV antigen, whether free or complexed, was detected in CSF from only 1 of 18 HIV antibody seropositive patients without progressive encephalopathy and from 0 of 8 experimentally infected chimpanzees without clinical signs. Intra-blood-brain barrier synthesis of HIV-specific antibody was demonstrated in the majority of patients with AIDS (9/12) or at risk for AIDS (8/13) as well as in the experimentally infected chimpanzees, indicating HIV-specific B-cell reactivity in the brain without apparent neurological signs. In 6 of 11 patients with HIV infection, antibodies synthesized in the central nervous system were directed against HIV envelope proteins. Active viral expression appears to be necessary for both the immunodeficiency and progressive encephalopathy associated with HIV infection.

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