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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

At least 55 records · Page 3Linked to original sources

Frequency of asymptomatic genital herpes in pregnant women at term.

A group of 579 asymptomatic women from Jackson Memorial Hospital, Miami, Florida, and 207 from Kaiser Foundation Hospital in Honolulu, Hawaii, admitted in labor at 37 to 40 weeks of gestation had vaginal cultures for herpes simplex virus (HSV). No cultures were positive and no neonates developed HSV infection. Seven patients gave a history of previous HSV infection in the group from Florida and three from the group in Hawaii. Herpes appears to be a low incidence risk factor in both the populations studied.

Cross-Sectional Studies↗

Maternal rubella and the congenital rubella syndrome.

The major goal of rubella immunization is the prevention of the congenital rubella syndrome. As many as 20 per cent of women in the reproductive age group in the United States continue to be susceptible to rubella despite the immunization programs currently in place. Intensified efforts are therefore needed to identify persons at risk for infection and to vaccinate them. Women who develop a rubella-like illness during pregnancy should have the diagnosis confirmed serologically because a diagnosis based on clinical criteria alone is unreliable and because of the serious implications of gestational rubella infection. The rubella virus can infect the fetus at any stage of pregnancy, but defects are rarely noted when this occurs after the 16th week of gestation. The most common abnormalities in the congenital rubella syndrome are hearing loss, mental retardation, cardiac malformations, and eye defects. Diabetes mellitus, thyroid disease, glaucoma, and other delayed manifestations of congenital rubella syndrome are common, thereby necessitating long-term followup of these patients. The detection of rubella-specific IgM antibodies in fetal blood is helpful in establishing the diagnosis prenatally and can aid in the management of pregnancies complicated by this infection. Susceptible women identified through screening during pregnancy should be immunized in the immediate postpartum or postabortion period. Although the live, attenuated rubella vaccine is contraindicated during pregnancy, pregnant women who are inadvertently immunized are not candidates for pregnancy termination because no defects consistent with congenital rubella have been reported to date in the offspring of other similarly vaccinated women.

Female↗

Human T-lymphotropic virus type I antibodies in the serum of patients with tropical spastic paraparesis in the Seychelles.

Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV-I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV-I could also be an etiologic agent of TSP.

Adult↗

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↗

Typing of herpes simplex virus by capture biotin-streptavidin enzyme-linked immunosorbent assay and comparison with restriction endonuclease analysis and immunofluorescence method using monoclonal antibodies.

A sensitive enzyme-linked immunosorbent capture assay using biotin and streptavidin (capture B/SA ELISA) was developed using type-specific monoclonal antibodies for typing of herpes simplex virus. Rabbit anti-herpes simplex virus immunoglobulin G was used as the capturing antibody, and biotin-linked type-1-specific mouse monoclonal antibody or rabbit type-1- or type-2-specific polyclonal antibody served as the detecting antibody. The captured antigen was detected by an ELISA with alkaline phosphatase-conjugated streptavidin, which reacted with biotin molecules on the detector antibody. The capture B/SA ELISA was compared with other methods for efficiency and reliability in typing. Results obtained by restriction endonuclease digestion of the radiolabeled viral genome were used to determine the type (1 or 2) of clinical isolates. These results were then used as a reference for determining the accuracy of the capture B/SA ELISA, as well as that of the immunofluorescence method, both of which are easily adaptable for use in the clinical laboratory. The three methods were in perfect agreement. It was determined that both the capture B/SA ELISA and the immunofluorescence method using monoclonal antibodies provided typing results with 100% specificity and 100% sensitivity and thus were accurate and reliable. However, the ELISA was the method of choice because of its simplicity, rapidity, and use of nonradioisotopic reagents.

Antibodies, Monoclonal↗

Capillary enzyme immunoassay for rapid detection of herpes simplex virus in clinical specimens.

Capillary enzyme immunosorbent assay (CapELISA) is a modification of the standard enzyme immunosorbent assay which permits rapid detection of viral antigens in clinical specimens. The capillary tube format provides a very large reactive surface relative to the sample size. The close proximity of antigen to antibody in the tube optimizes the reaction, resulting in increased sensitivity and shorter incubation requirements. Sensitivity is further enhanced by use of a biotin-avidin enzyme detector system and a fluorogenic rather than a colorigenic substrate. The assay is performed at ambient temperature and requires less than 2 h. It is read with an inexpensive hand-held black light. Data for the use of CapELISA for the detection of herpes simplex virus in clinical specimens are presented. The results show greater than or equal to 85% sensitivity and 100% specificity when compared with tissue culture tests on the same samples. This new system should be advantageous for the diagnosis, treatment, and management of patients with herpesvirus infections and for the prevention of neonatal herpes acquired by passage of the fetus through an infected birth canal.

Antigens, Viral↗

Owl monkey astrocytoma cells in culture spontaneously produce infectious JC virus which demonstrates altered biological properties.

A tumor cell suspension of an explanted JC virus (JCV)-induced owl monkey glioblastoma was inoculated intracranially into four recipient juvenile owl monkeys. Twenty-eight months following inoculation one owl monkey developed a glioblastoma, which was explanted into tissue culture. DNA from both the tumor tissue and tumor cells in culture hybridized to a JCV DNA probe by Southern analysis, indicating that free, as well as integrated, viral DNA may be present. At the time of the second culture passage, viral JCV DNA was extracted from these cells and cloned into a plasmid vector. Nucleotide sequencing of the regulatory region of the cloned DNA demonstrated homology with the prototype Mad-1 strain of JCV and revealed a 19-base-pair deletion in the second 98-base-pair tandem repeat that eliminated a second TATA box. This deletion is characteristic of the Mad-4 strain of JCV, which is highly neurooncogenic. By the third culture passage, 100% of the cells were T-antigen positive. Approximately one-third of the cells in culture hybridized to a biotinylated JCV DNA probe when in situ hybridization was used, a technique that only detects high-copy-number of replicating viral sequences. By the culture passage 5 and continuing through culture passage 14, viable JC virions could be recovered. The T protein synthesized by this virus, now termed JCV-586, differed from both the Mad-1 and Mad-4 strains in that it formed a stable complex with the cellular p53 protein in the tumor cells. Also, the JCV-586 T protein reacted to several monoclonal antibodies made to the simian virus 40 T protein that were not recognized by either the Mad-1 or Mad-4 strains.

Animals↗

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↗

Difficulties associated with serological diagnosis of Toxoplasma gondii infections.

Physicians often rely on serology to help determine whether a patient has had a recent infection with Toxoplasma gondii and as an aid in estimating the possible teratogenic effect on the fetus. For this reason the diagnostic laboratory should take every precaution to avoid misleading results. The best serological analysis is based on a rise in IgG titer with two appropriately spaced serum samples. Also, the presence of a high IgM titer in one serum sample is generally considered to be good evidence that infection has occurred recently. The indirect fluorescent antibody (IFA) test has been the most widely used test for detection of IgG or IgM. Recently enzyme-linked immunosorbent assays (ELISA) have also been developed for this purpose. In this study we reaffirm that false IgM positive results can occur with these tests because of the presence of rheumatoid factor in serum, and false negative results can also occur because of competitive inhibition by specific IgG. We show that a preabsorption of serum with a Staphylococcus/Streptococcus preparation (Staffinoc, MA Bioproducts, Walkersville, MD) removes IgG and IgA and eliminates many of the false reactions. We have also found that elevated levels of specific IgM can persist for at least several years in some women. This suggests that the presence of IgM alone is not always an indication of recent infection.

Enzyme-Linked Immunosorbent Assay↗

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↗

Administration of recombinant human leukocyte alpha 2-interferon in patients with amyotrophic lateral sclerosis.

Recombinant leukocyte alpha 2-interferon (with greater than 98% purity) was evaluated in a pilot treatment in six patients with amyotrophic lateral sclerosis and one patient with slowly progressive postpoliomyelitis motor neuron disease. Interferon, administered subcutaneously in doses of 2 million units three times per week for four months, was ineffective in improving, arresting, or slowing the pace of progression in all the patients who were followed up for ten to 14 months after the end of therapy.

Adult↗

Reye's syndrome. Salicylate metabolism, viral antibody levels, and other factors in surviving patients and unaffected family members.

To investigate possible etiologic factors for Reye's syndrome (RS), five survivors and their unaffected family members were studied. This study showed low salicylate levels among the patients with RS compared with siblings and parents when challenged with three doses of aspirin. Thus, the patients with RS, three to ten years after having had RS, exhibited normal or increased ability to metabolize aspirin. We found significantly higher antibody levels to influenza A and varicella among the patients with RS, further supporting the importance of these viral infections in the etiology of the syndrome.

Adolescent↗

Experimental congenital disease with simian cytomegalovirus in rhesus monkeys.

Cytomegalovirus (CMV) infections occur worldwide and are responsible for severe damage to the child in from one to five newborns per 20,000 births. Animal models of congenital CMV infection resulting in disease have been developed in mice and guinea pigs. We report here the development of ventricular dilatation and leptomeningitis in rhesus monkeys, Macaca mulatta, following intrauterine infection with rhesus cytomegalovirus (RCMV). Central nervous system (CNS) lesions were associated with low cytomegalovirus fluorescent antibody titers in affected fetuses. In several infected animals, RCMV was isolated at necropsy from neural and nonneural tissues taken shortly after birth. This model allows investigators to study the pathogenesis and prevention of CNS changes following RCMV infection.

Animals↗

Progressive multifocal leukoencephalopathy: JC virus detection by in situ hybridization compared with immunohistochemistry.

In four cases of progressive multifocal leukoencephalopathy (PML), we compared biotin-labeled DNA:DNA in situ hybridization with peroxidase immunohistochemistry for the detection of JC virus (JCV). The localization of JCV DNA and JCV capsid protein was compared in formalin-fixed, paraffin-embedded brain tissues. Infected oligodendrocytes showed both JCV DNA and JCV protein. However, bizarre astrocytes demonstrated JCV capsid protein less often than JCV DNA. In situ hybridization with a biotinylated probe was as sensitive and specific as immunohistochemistry for diagnosis on formalin-fixed tissue. The presence of both JCV DNA and viral capsid protein in bizarre astrocytes suggests that these cells are neither truly transformed nor permissively infected, but are distinctively altered by JCV.

Adolescent↗