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M Gravell

Publications and source records attributed to M Gravell.

15 recordsLinked to original sources
PubMed1992

Relationship of neurologic status in macaques infected with the simian immunodeficiency virus to cerebrospinal fluid quinolinic acid and kynurenic acid.

Increased concentrations of the excitotoxin quinolinic acid (QUIN) have been implicated in the neurologic deficits and brain atrophy that may accompany infection with the human immunodeficiency virus type-1. Key neuropathologic features of the AIDS encephalitis are replicated in some macaques following infection with the simian immunodeficiency virus (SIV). In the present studies, cerebrospinal fluid (CSF) QUIN concentrations increased within 2 weeks following infection of 11 rhesus macaques (Macaca mulatta) with a neurotropic sooty mangabey isolate of the simian immunodeficiency virus (SIVsm) and were sustained to greater than 2 standard deviations above uninfected control macaques. Highest CSF QUIN concentrations (up to 400-fold above pre-inoculation levels) were observed in 6 SIVsm-infected macaques with motor and behavioral abnormalities during life, brain atrophy on MRI scan and inflammatory lesions within the brain and meninges. Four of the 6 neurologic macaques deteriorated rapidly within 12 weeks after inoculation and had substantially larger increases in CSF QUIN levels than 2 other neurologic macaques and 5 macaques without neurologic signs which survived for longer than 37 weeks. Increases in serum QUIN and CSF kynurenic acid also occurred but generally to a lesser degree than the increases in CSF QUIN. In some animals, increases in serum L-kynurenine concentrations and reductions in CSF and serum L-tryptophan occurred and were consistent with activation of indoleamine-2, 3-dioxygenase, the first enzyme of the kynurenine pathway in extrahepatic tissues. CSF QUIN exceeded serum QUIN in 8.8% of samples from macaques with neurologic signs, supporting increased QUIN synthesis within the central nervous system. Production of [13C6]QUIN was demonstrated in one SIVsm-infected macaque and one uninfected control macaque following an intracisternal injection of [13C6]L-tryptophan and suggests that L-tryptophan is a substrate for QUIN synthesis within the nervous system or meninges, although the cellular localization of QUIN synthesis remain to be determined. We conclude that increases in kynurenine pathway metabolism occur in SIV-infected macaques and are most prominent in macaques with neurologic signs. Macaques infected with SIV offer a model to investigate the relationship between the metabolism of neuroactive kynurenines and neurologic disturbances associated with retroviral infection.

Animals↗
PubMed1991

Observations after human immunodeficiency virus immunization and challenge of human immunodeficiency virus seropositive and seronegative chimpanzees.

Two human immunodeficiency virus (HIV)-seropositive chimpanzees (A-3 and A-86c) infected 4 yr earlier with HIV, along with one uninfected animal (A-36), were inoculated intramuscularly three times in a year with a gamma-irradiated gp120-depleted HIV immunogen in incomplete Freund's adjuvant. Both previously infected animals promptly developed an anamnestic humoral antibody response after the first dose, and the uninfected animal developed a primary humoral response to the first dose and then an anamnestic response to the second dose. Although HIV had been recovered repeatedly from the seropositive animals, they became persistently virus-culture negative at the time of or just before the first inoculation of the immunogen. Intravenous challenge with 40 chimpanzee-infectious-doses of a heterologous HIV strain (HIVIIIB) was done 4 mo after the third inoculation in the three treated chimpanzees and in an untreated control animal (A-189a). The immunized naive animal (A-36) and the unimmunized control (A-189a) became infected, and virus has been isolated from their peripheral blood mononuclear cells for greater than 2 yr after challenge. However, the two previously infected chimpanzees (A-3 and A-86c) resisted challenge and have remained virus negative by peripheral blood mononuclear cell cocultivation for greater than 2 yr of observation after challenge; moreover, no evidence of reinfection was detectable by PCR. Despite the in vivo resistance, however, peripheral blood mononuclear cells from the resistant animals (A-3, A-86c) remained susceptible to infection by HIV in vitro. These findings reveal that a state of immunity can develop and/or be induced to control and/or prevent HIV infection in the chimpanzees. In the absence of any detectable level of neutralizing antibody in A-3 and a low level in A-86c, the patterns of the responses to challenge seen in the four animals suggest that the cell-mediated immune mechanism must have played a significant role in the resistant chimpanzees both in control of their HIV infection and in their resistance to challenge.

Animals↗
PubMed1991

In situ hybridization detection of HTLV-I RNA in peripheral blood mononuclear cells of TSP/HAM patients and their spouses.

This is the first report of the direct detection of HTLV-I RNA in uncultured peripheral blood mononuclear cells (PBMNC's) of patients with tropical spastic paraparesis and HTLV-I-associated myelopathy (TSP/HAM) and their spouses, using the technique of in situ hybridization. Twenty-one Colombian patients were tested, all of whom had antibodies to HTLV-I; the presence of HTLV-I proviral DNA in their PBMNC's was confirmed by the polymerase chain reaction technique. Of the 21 patients 15 had a clinical diagnosis of tropical spastic paraparesis (TSP/HAM), 5 were asymptomatic relatives, and 1 patient had leukemia. In situ hybridization was positive in samples from 5 patients; 2 of these were TSP/HAM patients and the other 3 were healthy wives of TSP/HAM patients. This study demonstrates for the first time that viral RNA is expressed in uncultured PBMNC's of some patients with TSP/HAM in whom proviral DNA is also present; furthermore, the detection of HTLV-I RNA in the blood of female partners of TSP/HAM patients clearly illustrates the high likelihood of HTLV-I transmission through sexual contact.

Cell Line↗
PubMed1991

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis.

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.

Animals↗
PubMed1990

Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta) naturally infected with simian retrovirus type-D.

Sustained increases in CSF concentrations of the excitotoxin quinolinic acid (QUIN) occur in patients with AIDS and have been implicated in the pathogenesis of the AIDS dementia complex. Macaques in captivity may also develop immunodeficiency syndromes caused by retrovirus infection, including simian retrovirus type-D. In the present study, CSF QUIN concentrations were moderately increased in retrovirus type-D-positive/antibody-negative macaques (163.8 +/- 35.1 nmol/l; P less than 0.0001, n = 21) but not virus-negative/antibody-positive macaques (27.4 +/- 9.4 nmol/l, n = 8) compared to uninfected control macaques (23.0 +/- 1.6 nmol/l; n = 22). CSF QUIN concentrations in virus-positive/antibody-negative macaques tended to remain elevated over a 4-20 month period. Post-mortem studies of 9 virus-positive/antibody-negative macaques and 6 virus-negative/antibody-positive macaques revealed inflammatory responses in the brains of 6 of 9 virus-positive/antibody negative macaques, including lymphocytic infiltrates of the choroid plexus in 3 macaques, glial nodules in 3 macaques and perivascular infiltrates in 1 macaque. These lesions were not extensive and no evidence of brain atrophy was observed. No lesions were observed in the 6 antibody-positive/virus-negative macaques. Small increases in plasma L-kynurenine in virus-positive/antibody-negative macaques are consistent with activation of indoleamine-2,3-dioxygenase, the first enzyme in the kynurenine pathway. We conclude that sustained moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques. The increases in CSF QUIN may reflect inflammatory responses within the brain or synthesis of QUIN precursors in systemic tissues, their entry into brain and subsequent conversion to QUIN. The neuropathologic significance of these increases in CSF QUIN remains to be determined.

Animals↗
PubMed1990

Simian immunodeficiency viruses from African green monkeys display unusual genetic diversity.

African green monkeys are asymptomatic carriers of simian immunodeficiency viruses (SIV), commonly called SIVagm. As many as 50% of African green monkeys in the wild may be SIV seropositive. This high seroprevalence rate and the potential for genetic variation of lentiviruses suggested to us that African green monkeys may harbor widely differing genotypes of SIVagm. To investigate this hypothesis, we determined the entire nucleotide sequence of an infectious proviral molecular clone of SIVagm (155-4) and partial sequences (long terminal repeat and Gag) of three other distinct SIVagm isolates (90, gri-1, and ver-1). Comparisons among the SIVagm isolates revealed extreme diversity at the nucleotide and amino acid levels. Long terminal repeat nucleotide sequences varied up to 35% and Gag protein sequences varied up to 30%. The variability among SIVagm isolates exceeded the variability among any other group of primate lentiviruses. Our data suggest that SIVagm has been in the African green monkey population for a long time and may be the oldest primate lentivirus group in existence.

Amino Acids↗
PubMed1990

Molecular characterization of simian lentiviruses from east African green monkeys.

Asymptomatic infection with simian lentiviruses (also called simian immunodeficiency viruses, or SIV) is common among feral African green monkeys. To characterize the range of SIV genetic diversity among infected African green monkeys, we have determined nucleotide sequences from complete or partial molecular clones of four distinct SIVagm isolates from Kenya and Ethiopia. The nucleotide and amino acid variability we observed among the SIVagm isolates was greater than the variability within any other group of primate lentiviruses. These data suggest that: a) African green monkeys have been infected with simian lentiviruses for many years; and b) novel and uncharacterized primate lentiviruses may exist in the feral African green monkey population in other parts of Africa.

Amino Acid Sequence↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

Detection of antibody to rubella virus by enzyme-linked immunosorbent assay.

Titers of antibody to rubella virus in 68 human sera were compared by hemagglutination inhibition and enzyme-linked immunosorbent assay (ELISA). In general, the titers measured by ELISA were higher than those found by hemagglutination inhibition. Although the titers differed, the two methods showed parallel trends. Use of purified rubella virus and addition of 1% bovine serum albumin to the test wash solution aided in reducing false-positive titers in ELISA.

Animals↗
PubMed1976

Epstein-Barr virus in an American patient with Burkitt's lymphoma: detection of viral genome in tumor tissue and establishment of a tumor-derived cell line (NAB).

Epstein-Barr virus (EBV) DNA (17.7 genome equivalents/cell) was found in tumor tissue from an American patient with Burkitt's lymphoma who had never traveled outside the United States. A lymphoid cell line (NAB) containing the EBV genome was established from tumor tissue from this patient; characteristics of this cell line were described. Previous Burkitt's tumors found in Americans and examined by molecular hybridization were negative for EBV DNA. Our results suggested that EBV is associated with at least some American Burkitt's tumors.

Adolescent↗
PubMed1976

A search for herpes simplex virus type 2 markers in cervical carcinoma.

Carcinoma of the uterine cervix is now clearly recognized as the second most common malignant disease of women in the United States. Epidemiological studies provided the first suggestive evidence that an infectious, venereally transmitted agent was involved in this disease in either a causal or a casual fashion. Later cytohistopathological, virological, and seroepidemiological studies confirmed this observation and identified the suspect agent as herpes simplex virus type 2. Recently, several laboratories have directed their energies towards establishing lines of direct evidence linking herpes simplex virus type 2 etiologically with human cervical carcinoma. Some of these approaches have involved attempts to detect infectious virus, viral components, or virus-specific modifications in neoplastic cervical tissues. Results obtained utilizing human tissues will be reviewed and discussed.

Antibodies, Viral↗