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Biomedical subjects

M Gravell

Publications and source records attributed to M Gravell.

At least 37 records · Page 2Linked to original sources

Predictors of clinical AIDS in young homosexual men in a high-risk area.

One hundred and sixty-seven homosexual men in Los Angeles characterized by HIV antibody, T-cell numbers, titres to cytomegalovirus (CMV), and specific sexual practices were followed for two years for immune changes and for more than three years for development of clinical AIDS. Thirty-five per cent had antibody to HIV at baseline. The mean level of T-helper (Th) cells was significantly lower and of T-suppressor (Ts) cells significantly higher in HIV seropositives than in seronegatives. The annualized incidence of HIV seroconversion was 7%. Eight men developed AIDS, an attack rate of 14% in those with HIV antibody at baseline. A number of observations were made: T-cell alterations, except a transient elevation in Ts cells, were unusual in the absence of HIV antibody; a seropositive man with a T-cell alteration was significantly less likely to revert to 'within normal limits' than was a seronegative man; a steady decline in the number of Th cells preceded onset of clinical AIDS; the number of Ts cells remained higher in men subsequently developing AIDS than in other seropositive men; clinical AIDS occurred only in men with HIV antibody whose CMV antibody levels were above the median for the group (1:1600); and the attack rate for clinical AIDS was 50% in men with HIV antibody and elevated CMV who at baseline had either: fewer than 325 Th cells/cc, or whose Th/Ts ratio was below 0.8 (but whose levels of Th and Ts cells were within normal limits).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Morphological changes of an inflammatory myopathy in rhesus monkeys with simian acquired immunodeficiency syndrome.

Eleven of 25 rhesus monkeys which died of simian acquired immunodeficiency syndrome (SAIDS) caused by infection with a type D retrovirus related to Mason-Pfizer monkey virus showed evidence of muscle weakness and atrophy and had elevated levels of muscle enzymes. Biopsies of affected muscle studied with enzyme histochemistry showed the characteristic features of polymyositis. Inflammatory cells consisting of lymphocytes, macrophages, and large vacuolated bizarre-shaped cells of undetermined type were surrounding or invading muscle fibers and were present in the perivascular spaces and endomysia septa. Within the perivascular infiltrates, lymphocytes were abundant but very few macrophages were present. Other myopathic features including profound proliferation of fibrous tissue, necrosis, and phagocytosis of muscle fibers were noted to a variable degree. The retrovirus was isolated from affected muscles. The clinical and historical features of polymyositis in rhesus monkeys with SAIDS are very similar to those of human polymyositis. The polymyositis in SAIDS induced by a type D retrovirus related to Mason-Pfizer monkey virus is an excellent primate model to study the mechanism and morphological changes of viral-induced muscle damage.

Acquired Immunodeficiency Syndrome↗

Polymyositis associated with AIDS retrovirus.

Two homosexual men were initially seen with polymyositis as the only manifestation of the acquired immunodeficiency syndrome (AIDS) retrovirus infection. They developed AIDS-related complex a few weeks later and typical AIDS two to six months after onset of muscle weakness. By use of anti-human T-cell lymphotropic virus type III antiserum and monoclonal antibodies to lymphocyte subsets in an immunofluorescence technique, viral antigens were found in the OKT4-positive lymphoid cells surrounding muscle fibers and invading the endomysia septa. We concluded that an initial infection with the AIDS retrovirus can be associated with polymyositis, which may be the first clinical manifestation of an impending AIDS-related complex or AIDS.

Acquired Immunodeficiency Syndrome↗

Polymyositis in an immunodeficiency disease in monkeys induced by a type D retrovirus.

Fifty percent of primates with acquired immunodeficiency caused by a well-characterized type D retrovirus (SAIDS D) developed clinical, laboratory, and histologic features of polymyositis. By use of specific antisera and immunochemical techniques, we found the virus in the lymphoid cells surrounding muscle fibers and invading the endomysia septa. SAIDS D virus was isolated from the involved muscles and infected myotubes of normal muscle in tissue culture. These results suggest that retroviruses, a group of viruses increasingly associated with human diseases, can cause polymyositis with immunodeficiency in nonhuman primates and could play a role in human polymyositis.

Acquired Immunodeficiency Syndrome↗

Differences among isolates of simian hemorrhagic fever (SHF) virus.

Simian hemorrhagic fever (SHF) virus is a member of the Togaviridae family which currently is unclassified to genus. We have studied the relatedness of four different SHF virus isolates obtained from infected macaque or patas monkeys. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, viral antigens, and levels of specific antibody induced in patas monkeys. Based on these criteria, the four isolates have been grouped in two categories: those producing acute infections in patas monkeys (LVR, P-180) and those producing persistent infections (P-248, P-741). The P-180 isolate induced the most severe disease in experimentally infected patas monkeys, but only occasionally were their infections fatal. Persistently infected patas monkeys were viremic over a period of years, but showed no signs or symptoms of infection. All four isolates were found to be antigenically related by use of enzyme-linked immunosorbent assay (ELISA); the P-248 isolate showing the weakest antigenic relationship. However, none of the four isolates induced cross-neutralizing antibodies in infected patas monkeys. High titers of specific IgG antibody (up to 31,250 as determined by ELISA) were induced in acutely infected patas monkeys (LVR, P-180), but antibody was barely detectable (less than or equal to 50) in persistently infected patas monkeys (P-248, P-741). LVR lytically infected USU-104 cells, patas monkey peritoneal macrophages (PMAC), and rhesus monkey PMAC. The P-180 isolate lytically infected both patas monkey PMAC and rhesus monkey PMAC, but not USU-104 cells. The isolates producing persistent infections (P-248, P-741) lytically infected only rhesus monkey PMAC. These results show that marked differences exist among isolates of SHF virus from naturally infected animals. These differences should be useful in categorizing new isolates.

Animals↗

Elimination of persistent simian hemorrhagic fever (SHF) virus infection in patas monkeys.

Devastating epizootics of simian hemorrhagic fever (SHF) have been iatrogenically initiated in captive colonies of macaque monkeys by strains of SHF virus emanating from asymptomatic persistently infected patas monkeys. We have found that persistently infected patas monkeys can be cleared of their infection by superinfection with strains of SHF virus which cause acute infections in this species. All 20 persistently infected animals subjected to this procedure have been cleared of their infection within 3 months. These animals were shown to be virus free by the most sensitive in vitro and in vivo tests currently available and periodic tests of serum from these animals over several years have shown them to remain virus free. Superinfection has in some cases caused some adverse clinical symptoms (anorexia, lethargy, facial edema, dehydration, and mild subcutaneous hemorrhages), but with supportive care, no fatal infections have occurred. Thus, superinfection with acute strains of SHF virus is a highly effective method of eliminating persistent infection in patas monkeys.

Animals↗

Simian AIDS: isolation of a type D retrovirus and transmission of the disease.

A type D retrovirus related to but distinct from Mason-Pfizer monkey virus was isolated in vitro from the blood of two rhesus monkeys (Macaca mulatta) with simian acquired immunodeficiency syndrome (SAIDS). Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks.

Acquired Immunodeficiency Syndrome↗

Transmission of simian acquired immunodeficiency syndrome (SAIDS) with blood or filtered plasma.

Simian acquired immunodeficiency syndrome (SAIDS), a disease clinically and pathologically similar to acquired immunodeficiency syndrome in humans, was transmitted from diseased rhesus monkeys (Macaca mulatta) to normal monkeys by inoculation with heparinized whole blood or plasma that had been passed through filters of 0.45 micrometer pore size. This suggests that the causative agent is small and most probably a virus. No viruses, however, were isolated by standard cell culture techniques from the blood or filtered plasma which caused SAIDS. Both cellular and humoral immunity were markedly depressed in animals with advanced SAIDS.

Acquired Immunodeficiency Syndrome↗

Transmission of simian acquired immunodeficiency syndrome (SAIDS) with type D retrovirus isolated from saliva or urine.

Saliva and urine specimens from rhesus monkeys with SAIDS were found to contain a type D retrovirus related to Mason-Pfizer monkey virus (MPMV) which has been linked etiologically to SAIDS. Virus isolates from saliva and urine were shown to have the characteristics of the SAIDS agent by their reverse transcriptase divalent cation preference for synthetic template-primers, production of characteristic cytopathology in Raji cells and antigenic relatedness to MPMV as determined by enzyme-linked immunosorbent assay (ELISA) and competition radioimmunoassay (RIA). Electron micrographs of parotid tissue from an animal with SAIDS also showed budding particles with type D retrovirus morphology. A tissue culture grown virus isolate from urine of an animal with SAIDS, produced SAIDS when inoculated into two normal juvenile rhesus monkeys. Since saliva and urine of monkeys with SAIDS contain infectious SAIDS virus, they are likely sources of virus by which the disease is naturally transmitted. Thus, care should be taken to avoid contact of normal and infected animals.

Acquired Immunodeficiency Syndrome↗

Morphology of the retroviruses associated with AIDS and SAIDS.

Thin section electron microscopy of tissue culture preparations of viruses associated with AIDS and SAIDS have shown that the mature particles have a similar morphology following budding from the cell membrane. The model provided explains the various core morphologies seen in section and provides a basis for identifying these agents in clinical tissues.

Acquired Immunodeficiency Syndrome↗

Experimental transmission of simian acquired immunodeficiency syndrome (SAIDS) and Kaposi-like skin lesions.

A disease that is similar to human AIDS may occur in monkeys. Simian AIDS (SAIDS) was experimentally transmitted from 2 rhesus monkeys dying of the disease to 4 cytomegalovirus (CMV) antibody-negative rhesus monkeys. The inocula consisted of the supernatant fluid from 10% homogenates of various tissues with or without buffy-coat cells from blood. Lymphadenopathy, splenomegaly, neutropenia, polymyositis, and other signs of the disease appeared in recipients within a few weeks after inoculation. Two animals developed Kaposi-like "patch" and "plaque" skin lesions and one died of sepsis and profound lymphoid depletion. A second animal also died with lymphoid depletion. All animals became infected with CMV but antibody levels were low in two animals, appeared and then disappeared in one, and never developed in the second monkey which died.

Acquired Immunodeficiency Syndrome↗

Simian haemorrhagic fever (SHF): new virus isolate from a chronically infected patas monkey.

A new strain of simian haemorrhagic fever (SHF) virus was isolated from chronically infected patas monkey no. 248 (P-248) in USU-104 cells. The P-248 isolate had the same size, morphology and cytoplasmic site of replication as the prototype LVR strain. However, the P-248 isolate caused a persistent infection without noticeable cytopathology in USU-104 cells rather than the strongly lytic infection produced by prototype LVR virus. The capacity of P-248 virus to produce a persistent, non-lytic infection of USU-104 cells was a very stable characteristic of the isolate. Extensive serial passage of this isolate through USU-104 cells (over 50 passages) and rhesus monkeys (six passages) failed to unmask virus with lytic properties for USU-104 cells. Culture medium from persistently infected cultures assayed in rhesus monkey peritoneal mononuclear phagocytes, where measurable cytopathology occurs, was found to contain about 10(5) to 10(6) TCID50/ml of cell-free P-248 virus. Immunolabelling techniques showed only a low percentage of infected cells in persistently infected cultures. The mechanism of persistence of the P-248 isolate in USU-104 cells has not been determined but evidence suggests it does not involve interferon or defective interfering particles.

Animals↗

Method to detect asymptomatic carriers of simian hemorrhagic fever virus.

Evidence was obtained that mononuclear phagocytic cells are the target cells for simian hemorrhagic fever virus replication. Using peritoneal macrophages from rhesus monkeys in an in vitro, 18 of 20 asymptomatic chronically infected patas monkeys were detected from coded samples. The two chronically infected patas monkeys not detected by the test, nevertheless, contained virus. This was determined by inoculating macrophage cultures with plasma from macaques dying as a result of inoculation with plasma from these chronically infected animals. in addition to virus found in chronically infected animals, all isolates of simian hemorrhagic fever virus tested previously described epizootics lytically infected rhesus monkey macrophages. These data suggested that the highly fatal nature of simian hemorrhagic fever in macaques was related to the extreme sensitivity of their mononuclear phagocytic cells to infection and lysis.

Animals↗

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Antibodies, Viral↗

Multiple sclerosis associated agent (MSAA): failure to confirm an association with multiple sclerosis.

Recent reports indicate that a multiple sclerosis agent (MSAA) has been isolated. This agent was detected in mice by a depression in the percentage of mouse polymorphonuclear neutrophils (PMNs). We attempted to repeat these studies using coded specimens. The test, itself, was extremely variable and difficult to reproduce. In the first study, three of three multiple sclerosis (MS) patients and one of two control patients' specimens showed some PMN depression. In a repeat study of these same samples, one of three MS patients and one of two controls were associated with PMN depression. With a second set of coded specimens, one of four MS patients, one of three patients with neurologic diseases, and none of three controls showed PMN depression. We were unable to confirm the presence of MSAA and conclude that the results were random.

Adult↗