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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

At least 73 records · Page 4Linked to original sources
PubMed1986

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↗
PubMed1985

TORCH tests and what they mean.

TORCH tests can be used to document immunity or recent infections. Many laboratories now offer TORCH tests and there are a large variety of methods, kits, and reporting systems. Some of the TORCH tests are not accurate and should be avoided. In general, we prefer enzyme immunoassays for documentation of past infections or immunity. To demonstrate recent infections with toxoplasmosis and rubella we use IgM enzyme-linked immunosorbent assay tests but for cytomegalovirus and herpes infections we prefer virus isolation. Physicians should send specimens only to laboratories that participate in proficiency surveys or similar tests that document the accuracy of the laboratory. All TORCH test sera should be held by the laboratory for 1 year to permit repeat testing and analysis with subsequent specimens if necessary.

Complement Fixation Tests↗
PubMed1985

Progressive multifocal leukoencephalopathy: investigation of three cases using in situ hybridization with JC virus biotinylated DNA probe.

Using the technique of in situ DNA-to-DNA hybridization, a JC virus biotinylated DNA probe was developed and applied to formalin-fixed, paraffin-embedded, or fixed, frozen sections of brain tissue from three subjects with progressive multifocal leukoencephalopathy (PML). Light microscopy was carried out to correlate the presence of JC virus DNA with the selective infection of oligodendrocytes and astrocytes in PML. Oligodendrocytes (lytically infected) showed the greatest evidence of viral DNA. More astrocytes showing bizarre morphological changes had evidence of viral DNA than did astrocytes that were simply reactive. Viral DNA was not evident in vascular endothelial cells using this technique. Viral DNA replication may be an important initial step which produces the bizarre "transformed" astrocytes of PML. Findings in this study do not support the hypothesis that vascular endothelial replication is important in the pathogenesis of JC virus-induced PML. In situ hybridization with biotinylated JC virus probe may be useful in the diagnosis of PML on brain biopsy specimens.

Adult↗
PubMed1985

Comparison of enzyme-linked immunosorbent assay with enzyme-linked fluorescence assay with automated readers for detection of rubella virus antibody and herpes simplex virus.

The enzyme-linked immunosorbent assay (ELISA) was compared with the enzyme-linked fluorescence assay (ELFA) for the detection of rubella antibody and herpes simplex virus antigen. Test parameters, specimens, antigen or antibody, and conjugates for the two types of assays were identical except that p-nitrophenyl phosphate was used as the substrate for the ELISA and 4-methylumbelliferyl phosphate was used as the substrate for ELFA. Automated readers were used for both assays. Antibody titers and sensitivity of antigen detection were quite similar for ELISA and ELFA. ELFA for rubella antibody, however, could be conducted with less antigen or shorter substrate incubation time (5 min for ELFA versus 30 min for ELISA). For herpes simplex virus antigen detection, ELFA could also be read after a shorter substrate incubation time (15 min for ELFA versus 30 min for ELISA). Clear polystyrene microtiter plates routinely used for ELISA could be used for ELFA, but clear polyvinyl chloride plates had high background fluorescence. Black polystyrene and polyvinyl chloride plates gave lower background fluorescence than did clear plates. ELFA is of particular value as a substitute for ELISAs in which long substrate incubations are required or antigens of only low titer are available.

Antibodies, Viral↗
PubMed1985

Immunologic alterations in monkeys with simian acquired immunodeficiency syndrome (SAIDS).

Levels of lymphocyte responsiveness to T- and B-cell-specific mitogens and expressions of Ia, T4, T8, and T11 surface markers were monitored during the course of Simian acquired immunodeficiency syndrome (SAIDS) in four Rhesus macaques that either died or became ill and survived. The monkey that died showed progressively suppressed responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM), and Staphylococcus aureus Cowan I strain (SAC) through the time of death (5 1/2 weeks). For the three animals that survived, the responses of peripheral blood mononuclear cell (PBMC) to the same mitogens were decreased significantly during the period 4-6 weeks after inoculation. Levels of Ia-bearing cells in the PBMC population were markedly reduced in the moribund monkey but were not significantly decreased in the three survivors. There was no significant change in the percentage of T11-bearing cells in any of the study animals. The ratio of T4- and T8-positive cells did not vary significantly during the 18 weeks of observation in any of the animals. The infected animals showed other evidence of immunosuppression including neutropenia, lymphopenia, and depletion of lymphocytes in lymph nodes. The animal that had progressive disease and death also had Kaposi-like lesions and staphylococcal septicemia. These results indicated that in vitro evidence of immunosuppression due to SAIDS appears within a few weeks after infection and this may progress in animals that die.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Five drug regimens for treatment of acute toxoplasmosis in squirrel monkeys.

Five drug regimens for the treatment of acute toxoplasmosis were compared in a monkey model. Systemic disease that is almost always fatal in squirrel monkeys within 7-9 days was produced by oral inoculation of a brain suspension made from mice chronically infected with the Beverly strain of Toxoplasma gondii. All untreated controls died of toxoplasmosis (6/6) while treatment gave the following results: sulfamethoxazole, 0/3; spiramycin, 5/5; clindamycin/sulfadiazine (CLD/SLD), 0/4; pyrimethamine/sulfadiazine (PYR/SLD), 0/5; trimethoprim/sulfamethoxazole (TMP/SMZ), 0/4. Three of the five monkeys treated with CLD/SLD died during or shortly after the experiment from probable CLD toxicity. Sulfonamides alone or in combination with PYR or TMP were significantly more effective than spiramycin in treating toxoplasmosis in this model. The dose regimen used in this study did not allow us to determine if the addition of PYR or TMP changed the protection of sulfa alone.

Animals↗
PubMed1985

NIH Conference. Herpes simplex virus infection: biology, treatment, and prevention.

Herpes simplex viruses cause common mucocutaneous infections, but many aspects of their epidemiology and transmission are incompletely defined. Although the incidence of oral herpes remains relatively unchanged, the incidence of genital herpes is increasing significantly. Definitive diagnosis of herpes remains dependent on virus isolation, but techniques involving direct examination of clinical specimens are increasingly sensitive and may simplify and speed diagnosis. With the advent of acyclovir, effective therapy and suppression of infection are feasible for immunodeficient and selected normal patients. Unanswered questions remain regarding the long-term safety of acyclovir and the potential for emergence of clinically significant drug resistance. No effective vaccines are yet available for herpes virus infections. Promising strategies for vaccine development include preparation of immunogenic proteins, engineering of specially attenuated live virus strains, and incorporation of selected herpes genes into live vaccinia virus vectors.

Acyclovir↗
PubMed1985

Comparison of detection of oligoclonal immunoglobulin G bands in cerebrospinal fluid specimens by Coomassie blue and silver stains.

Cerebrospinal fluid (CSF) specimens from 45 clinically definite MS patients were studied for the presence of oligoclonal IgG bands by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The protein bands were identified by Coomassie blue (CB) dye and silver staining. Thirteen patients showed no bands in their CSF by the CB method. Nine of these 13 patients showed presence of bands by silver staining alone. Thirty-two patients showed more than two bands in their CSF by either technique, and 28 of the 32 patients showed from one to five additional bands by silver staining compared to Coomassie blue staining. The silver staining method was thus more sensitive in identification of oligoclonal bands in CSF.

Clone Cells↗
PubMed1985

Changing perspectives of the effects of infectious diseases.

There are a large number of infectious agents which damage or kill the developing fetus or child. In this report I have summarized the changing status of information available for just six of these diseases. For rubella there has been excellent success with the development of a vaccine for prevention of this disease. Unfortunately the vaccine is only used extensively in a few countries. Herpes simplex has become a particular problem because of the rapid increase in the frequency of genital herpes infections, the spontaneous recurrences of the lesions, and the difficulty in prevention or treating congenital infections. Cytomegalovirus infections are now known to occur in 1% of newborns, and some damage is produced in about 10% of these children. We have no methods for preventing or treating this infection. Varicella at term is also an important risk to the child but this can now be controlled by the use of VZIG. Varicella earlier in pregnancy may be teratogenic. Venezuelan equine encephalitis virus can cause severe brain damage to the fetus, and one of the vaccines for this infection was shown to be teratogenic in monkeys. Lastly, congenital toxoplasmosis has been known for many years to cause fetal damage and death. Further studies of serological detection of infection and treatment are needed. A number of other viral, bacterial, and parasitic diseases must also be considered as part of the total group of these preventable causes of physical and mental damage to the fetus and newborn.

Chickenpox↗
PubMed1985

Approaches used for the detection of infectious agents as human teratogens.

A review of the events which lead up to the recognition of six infectious agents as teratogens showed that in most cases the associations were made through studies of the pathology of the disease or in association with epidemics which affected large numbers of pregnant women. Epidemiological studies of various populations were then conducted to obtain more complete information about the frequency of infection; the syndrome produced in the child; the effect of time of maternal infection; the method of transmission of infection; and approaches to diagnosis, treatment, and prevention of the disease. Investigation of other possible teratogens should emphasize examination of the pathology of the disease and the analysis of pregnancy outcomes of large numbers of women who experience a given infection.

Chickenpox↗
PubMed1985

Improved separation of rhesus monkey lymphocytes with Percoll.

The total yield and the proportions of Rhesus monkey peripheral blood mononuclear cells (PBMC) with detectable T4, T8, T11 and Ia markers that were purified by density gradient centrifugation through solutions of polyvinyl pyrrolidone (Percoll) were significantly greater than those found in PBMC suspensions obtained by using Ficoll-Hypaque. The percentages of recovery of PBMC and of cells expressing the above markers were lowest among PBMC isolated with a Ficoll-Hypaque mixture of density 1.077 and highest among PBMC obtained by using a solution of Percoll of density 1.077. Percoll of density 1.077 was also better than Ficoll-Hypaque in that it yielded PBMC with the lowest levels of erythrocyte (less than 1%) and granulocyte (less than 1%) contamination. The reduced levels of PBMC with detectable markers appeared to result from an effect of either Ficoll or Hypaque on the lymphocytes rather than from loss of lymphocyte subpopulations since higher proportions of cells bearing T4, T8, T11 and Ia were found when PBMC were isolated with a solution of Percoll which yielded a percentage of PBMC as low as that recovered with Ficoll-Hypaque. Altered marker expression by cells obtained with Ficoll-Hypaque was not seen with similarly prepared human PBMC.

Animals↗
PubMed1985

Incidence of clinical infections in a defined population of pregnant women.

The incidence of clinical maternal infections was determined in a prospective study of 44,016 pregnant women at 12 university hospitals. Viral and bacterial infections were the most frequently reported. Overall, the highest incidence of infections was for vaginitis, influenza/"flu"-like disease, and infections of the kidney, ureter, bladder; parasitic and fungal infections occurred at low rates. Most women experienced only one infection during pregnancy (89.7%); however, some had two different infections (8.5%), and a few had three or more (1.7%). The analysis of the effects of some of the maternal infections on the pregnant women and their children have been published, and further studies are in progress.

Black or African American↗
PubMed1984

Successful immunization of infants with and without maternal antibody by aerosolized measles vaccine. II. Vaccine comparisons and evidence for multiple antibody response.

In 4- and 5-month-old infants in whom the undiluted chick embryo fibroblast (CEF) Schwarz strain measles vaccine had a poor immunogenic effect, there was an increase in immunogenicity when the high sugar concentration was diminished without reference to added albumin. The human diploid cell (HDC) measles vaccine was still superior in this age group even in a lower concentration of the Ikić, Edmonston-Zagreb strain of virus. More aerosolized, HDC Ikić strain virus was required for high seroconversion rates in 4- and 5-month-old infants who had higher titers of prevaccination plaque-neutralizing (PN) antibodies. Some of these infants had a delayed immune response that was absent at six weeks but present at three months after vaccination. The data provided evidence that the PN and enzyme-linked immunosorbent assay techniques measured different antibodies that develop and persist in different ways in 4- to 5-month-old infants. The HDC lyophilized measles vaccine yielded unexpectedly high seroconversion rates after subcutaneous injection of 5,000 plaque-forming units (PFUs) in 4-, 5-, and 6-month-old infants: 69%, 89%, and 100% respectively, at 14 weeks. In 12- to 23-month-old infants there was seroconversion of 92% and 100% at six weeks after inhalation of an estimated 175 PFUs of the CEF vaccine and 375 PFUs of the HDC vaccine, respectively. Within six weeks after vaccination, the PN antibody titers were significantly higher with the CEF vaccine (geometric mean titer of 2,275) than with the HDC vaccine (geometric mean titer of 343).

Aerosols↗