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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

At least 109 records · Page 6Linked to original sources

Epidemic of acquired immunodeficiency in rhesus monkeys.

A syndrome closely resembling acquired immunodeficiency syndrome (AIDS) in man has been identified in a group of 64 rhesus monkeys (Macaca mulatta) maintained outdoors at the California Primate Research Center. The syndrome is characterised by generalised lymphadenopathy, severe opportunistic infections including cytomegalovirus, chronic wasting, and high mortality. In 1 animal a multifocal cutaneous fibrosarcoma developed. This syndrome in monkeys may provide an animal model for human AIDS.

Acquired Immunodeficiency Syndrome↗

Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases.

We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 microliters of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.

Central Nervous System Diseases↗

Detection of genital herpes simplex infections by a tissue culture-fluorescent-antibody technique with biotin-avidin.

Several cell lines were evaluated for their suitability for rapid detection of herpes simplex virus (HSV) from clinical genital specimens. Human foreskin fibroblast (Flow 7000) cells were found to be most suitable in terms of sensitivity and adherence characteristics. HSV in clinical specimens was isolated by a standard tissue culture method by monitoring the cytopathic effect, and the titers of the HSV-positive specimens were determined. More than 65% of the HSV-positive genital specimens showed titers of less than or equal to 10(4) 50% tissue culture infective doses per ml. The standard tissue culture-cytopathic effect method required 3 to 10 days for detection of HSV in clinical specimens of low infectivity. A more rapid technique was developed which involved a short-term tissue culture (24 h) on Lab-Tek chambers followed by staining with biotin-linked HSV antibody and avidin-fluorescein conjugate. Because of the high binding affinity of this system due to multiple binding of biotin to avidin and multiple attachment of biotin to the antibody molecule, the biotin-avidin fluorescent-antibody technique produced a quality of fluorescence far superior to that of the conventional fluorescent-antibody techniques. The tissue culture-biotin-avidin fluorescent-antibody method was as sensitive as the tissue culture-cytopathic effect test. This method provides an improved, more rapid test (26 h) for detecting HSV in clinical specimens.

Antigens, Viral↗

Rapid latex agglutination test for rubella antibody.

The latex agglutination card test (Rubascan) for the detection of rubella antibody was compared with the standard hemagglutination inhibition and enzyme-linked immunosorbent assay tests. There was complete agreement with sera which had hemagglutination inhibition titers of >/=16. Sera with low levels of antibody which were positive in the enzyme-linked immunosorbent assay, however, gave negative latex agglutination results approximately 25% of the time (false negatives), whereas sera which were negative in the enzyme-linked immunosorbent assay gave false-positive results in about 3% of the cases. The use of capillary "finger stick" plasma instead of venous sera resulted in additional false-negative latex agglutination tests among patients with very low antibody titers. Because of the simplicity of the method, it should be possible to use this test in physicians' offices and in large immunization campaigns. Care should be taken to become completely familiar with the procedures and reading of the agglutination patterns. Control sera should always be used. Interpretation of results should take into consideration the rates of false-negative and false-positive results noted above. These rates apply to sera with little or no antibody. In particular, negative tests should be confirmed with more specific methods in critical cases, such as pregnant women exposed to rubella or women of childbearing age who are being considered for immunization. There was no problem with the latex agglutination findings for sera with higher titers. Since results are available in 8 min, physicians should be able to counsel their patients rapidly and immunize, if necessary, while the patient is still present.

Antibodies, Viral↗

Detection of group B streptococcal antigens in amniotic fluid of rhesus monkeys.

To simulate group B streptococci (GBS) amniotic fluid infections common in humans and to examine bacterial growth and the appearance of GBS antigens in vivo, GBS were injected into the amniotic cavity of 19 near-term rhesus monkeys. Transabdominal aspirates of amniotic fluid were obtained before bacterial challenge, after 2 and 6 h, and during cesarean section delivery (24 h). Each fluid was quantitatively cultured for GBS. Specimens of amniotic fluid and gastric aspirate from each infant were tested for the presence of GBS antigens with a commercial latex particle agglutination test (Wellcogen Strep B; Wellcome Diagnostics, Dartford, England). To eliminate nonspecific latex particle agglutination reactivity, presumably caused by proteins, a processing procedure was required. Despite active proliferation of bacteria, only 12% of the 2-h amniotic specimens were latex particle agglutination positive. In contrast, 94% of th3 6-h and 100% of the 24-h specimens had detectable antigens, as did 89% of the gastric fluid specimens aspirated from the 19 newborns. Latex particle agglutination tests, after proper processing, will readily detect GBS antigens in amniotic or gastric aspirate fluid from experimentally infected rhesus monkeys.

Amniotic Fluid↗

Frequency of antibody to BK antigen in women whose children developed malignancies and women who developed detectable carcinoma in situ of the cervix during this pregnancy.

Paired sera from 21 women whose children had malignancy and 15 women who were diagnosed as having abnormal pathology in the cervix and matched normal controls were studied for presence of BK antibodies by the ELISA technique. BK antibody was detected in 74% of the women in the first serum sample obtained. Evidence of BK antibody rises were observed in eight of 72 women (11%) and was distributed equally among women with abnormal children and women with abnormal pathology in the cervix and controls and that the level of antibody was not influenced by vaccination with killed polio vaccine during this pregnancy. Our serological data fails to show an association between infection with BK virus and malignancy in the children or carcinoma in situ of the cervix.

Adolescent↗

Detection of antibody to BK virus by enzyme-linked immunosorbent assay compared to hemagglutination inhibition and immunofluorescent antibody staining.

The enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition test (HAI), and immunofluorescent antibody staining (IFAS) test were compared for their ability to detect IgG antibody to BK virus (BKV). Antibody titers to BKV antigen were determined for 35 sera by each of the three assays. The ELISA tests agreed with either HAI or IFAS with regard to BKV antibody status in all but one serum. On this basis the HAI accounted for four discordant determinations while IFAS was not in agreement in three cases. Geometric mean titers of ELISA and HAI were similar but greater than that of IFAS. The ELISA is particularly well suited for use in large-scale seroepidemiological studies since automated spectrophometric equipment can provide rapid, objective, numerical data.

BK Virus↗

New world primates as a model of viral-induced astrocytomas.

Owl and squirrel monkeys are susceptible to the oncogenic effects of JCV. These species of New World monkeys can be safely inoculated intracerebrally. Care must be taken with owl monkeys since they have an inherited clotting abnormality. Incubation times for the development of tumors range from 14 to 30 months. Anorexia was the first clinical sign of tumor development. The clinical course is rapid with death within two to three days. This model provides a means for studying diagnostic, virological, immunological and therapeutic techniques which are applicable to human patients with astrocytomas.

Animals↗

Viral-induced astrocytomas in squirrel monkeys.

Saimiri sciureus, the squirrel monkey, is susceptible to the oncogenic effects of JCV following intracerebral inoculation. As in owl monkeys, tumor development follows an incubation time of 14 to 30 months. Four of six virus-inoculated monkeys developed cerebral tumors, three of which were astrocytomas grade 4 and the remaining tumor was a poorly differentiated astrocytoma. All tumors showed high cellularity, mitotic figures, and cellular pleomorphism. In the astrocytoma grade 4, neovascularization was a prominent feature. The blood vessels in the poorly differentiated astrocytoma appeared normal. Multinucleated giant cells were present in all four astrocytomas. Antemortem hemorrhage was seen in one astrocytoma grade 4. Other tumor types were not seen. The occurrence of astrocytomas in a second species of New World monkeys confirms the oncogenicity of JCV for nonhuman primates.

Animals↗

Glial and divergent cells in primate central nervous system tumors induced by JC virus isolated from human progressive multifocal leukoencephalopathy (PML).

Immunofluorescent stains for fibronectin (FN) and glial fibrillary acidic protein (GFAP) were used in conjunction with routine histologic stains to study tumors induced in squirrel and owl monkeys by JC virus from progressive multifocal leukoencephalopathy (PML). Three varieties of glioma were identified. The first and most common variety was a neoplasm similar to grade 4 astrocytoma in humans. The second had thin, normal-appearing FN-positive vessel walls and a vastly expanded neuroectodermal parenchyma which could not be characterized by routine histologic stains. Anti-GFAP revealed the glial nature of the parenchyma. Isolating glial parenchymal cells from divergent FN-positive cells has become important to neurooncology. This type of tumor may be of particular interest for such isolations due to its high ratio of glial cells to divergent cells. The third variety was not a homogeneous neoplasm. It occurred as focal regions within tumors of the first type, and consisted of giant cells with huge nuclei. These cells resemble the cells of a human giant cell glioblastoma and bear a slight similarity to the bizarre glial cells seen in PML. The rare human giant cell glioblastoma might have an association with JC virus or with PML.

Animals↗

Neuroradiological studies of JCV-induced astrocytomas in nonhuman primates.

Astrocytomas in nonhuman primates following JC virus inoculation provides a model which can be used to evaluate diagnostic and therapeutic techniques used in humans. The CT scan appearance of astrocytomas in nonhuman primates closely resembles that seen in humans. Our studies have shown that tumors may be detected in asymptomatic monkeys. Serial scans have shown astrocytomas to grow rapidly with breakdown of the blood-brain barrier. CT scanning has demonstrated the presence of tumor which was undetectable by gross examination at necropsy but confirmed by light microscopy. Studies are in progress to further define the radiological appearance of gliomas, to evaluate contrast-tagged anti-tumor antibodies as a diagnostic tool in evaluating gliomas by computerized tomography, and to evaluate metabolic parameters of actrocytomas by positron emission tomography.

Animals↗

Paralysis in nude mice caused by polyomavirus-induced vertebral tumors.

Eighty-one of 95 BaLB/c nude mice infected intracranially with the LID strain of polyomavirus developed tumors of the vertebrae which compressed the spinal cord or peripheral nerves and produced paralysis. Wallerian degeneration was the only pathological alteration found in the nervous system of polyoma-infected mice. While polyomavirus was demonstrated in the brain and spinal cord by viral isolation and immunoperoxidase staining, no evidence of a primary demyelinating process was found. The disease produced in the present study is not a satisfactory animal model of progressive multifocal leukoencephalopathy.

Animals↗

Teratological effects of western equine encephalitis virus on the fetal nervous system of Macaca mulatta.

Fetal rhesus monkeys were inoculated intracerebrally with an attenuated strain of western equine encephalitis virus. All animals developed microcephaly. Twelve of sixteen monkeys developed ex vacuo hydrocephalus. All virus inoculated fetuses developed WEE virus antibody. Virus could not be recovered at the time of delivery. Monkeys with the highest WEE antibody titers showed the greatest degree of hydrocephalus.

Animals↗