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Biomedical subjects

W T London

Publications and source records attributed to W T London.

At least 19 recordsLinked to original sources
PubMed1979

Betamethasone and the rhesus fetus: multisystemic effects.

In this controlled study of betamethasone administration to pregnant rhesus monkeys, using dosages per gram of fetal body weight similar to those reported in several human clinical studies, the most significant fetal pulmonary changes observed were increases in maximum lung volumes. The fact that comparable increases in peak volumes were demonstrated on saline filling supports our contention that these changes are related primarily to lung structural alterations rather than surfactant effects. Additional findings in the treated animals included reduced fetal head circumference, thymus weight, adrenal weight, placental weight, and maternal postoperative weight and increased fetal hepatic weight. Any of these glucocorticoid-induced changes could portend serious side effects. Further studies are needed to delineate the risk:benefit ratio of such treatment.

Adrenal Glands↗
PubMed1979

Sex differences in response to hepatitis B virus. III. Responses to HBV and sex of donor and recipient in kidney and bone marrow transplantation.

We proposed the hypothesis that there is an antigen on the hepatitis B virus (HBV) that cross-reacts with a male associated antigen to explain four observations: 1) sex differences in the responses to HBV infection, 2) sex differences in the prevalence of chronic liver diseases associated with hepatitis B, 3) the association of parental responses to HBV with the sex ratio (at birth) of their offspring, and 4) the relation of kidney graft survival with the combination of anti-HBs in the recipients and the sex of the organ donor. Patients with aplastic anemia treated with bone marrow transplantation from HLA identical sibling donors were studied to further test this hypothesis and the results provide additional support. Cross reactivity of HBsAg with H-Y antigen, however, has not been demonstrated.

Anemia, Aplastic↗
PubMed1979

Induction of congenital hydrocephalus with mumps virus in rhesus monkeys.

Rhesus monkey fetuses were inoculated intracerebrally with wild-type mumps virus near the beginning of the last third of the gestation period. Within three days after inoculation, mumps virus was isolated from many fetal tissues. Thirteen animals receiving virus were delivered at term. Five of these showed slight to severe hydrocephalus. Hydrocephalus was most prominent in the posterior horns of the lateral ventricles, but other lesions occurred at various levels of the ventricular system. Virus was isolated from three animals at one day of age (two months after inoculation). However, mumps virus was not recovered from one-month-old monkeys. The recovery of mumps virus from newborn rhesus monkeys two months after inoculation suggests that attempts should be made to document similar persistence of the virus in humans. Furthermore, this model indicates that mumps virus infection in humans may result in hydrocephalus.

Amniotic Fluid↗
PubMed1979

Respiratory syncytial virus infection in owl monkeys: viral shedding, immunological response, and associated illness caused by wild-type virus and two temperature-sensitive mutants.

Intranasal inoculation of owl monkeys with wild-type respiratory syncytial virus induced upper respiratory tract disease in each of seven animals. The response of owl monkeys to two highly defective, temperature-sensitive, multiple-lesion mutants was then compared to the pattern seen with wild-type respiratory syncytial virus. These mutants, ts-1 NG-1 and ts-1 NG-16, were derived from the ts-1 mutant that had been remutagenized with nitrosoguanidine (NG). Previously the ts-1 NG-1 and ts-1 NG-16 mutants had been shown to be more temperature sensitive and more stable genetically than their ts-1 parent. Both ts-1 NG-1 and ts-1 NG-16 produced infection that was delayed in onsent compared to wild-type virus infection. However, the mutants were shed from the upper respiratory tract for the same period of time and at the same titer as wild-type virus. The serum neutralizing antibody response to infection with the mutants was nearly equivalent to that elicited by wild-type virus. However, the extent of disease induced by the mutants was significantly less than that seen with wild-type virus. These observations suggest that the mutants are potential vaccine condidates and should be subjected to additional in vivo testing in primates and, ultimately, humans.

Animals↗
PubMed1979

Effect of betamethasone on pressure-volume relationship of fetal rhesus monkey lung.

We have investigated the acceleration of fetal lung maturity following glucocorticoid administration. Air-filling of saline-filling pressure-volume curves were obtained on fetal rhesus monkey lungs after treatment with betamethasone. With air filling there was a marked increase in the total lung capacity (ml air/g at 40 cmH2O) in the treated animals. By normalizing the curves and plotting volume as a percent maximal volume, we examined the shape of deflation curves, a common functional measure of surfactant activity. We found little difference in the shapes between control and steroid-treated animals. With saline filling there was also a similar increase in the lung capacity. As surface tension has a negligible effect on saline pressure-volume curves, we conclude that the primary functional effect of glucocorticoids on the fetal lung may not be an alteration of surface forces. Rather the glucocorticoids seem to accelerate maturity more by increasing lung compliance through structural changes that allow the lung to contain more air for equivalent transpulmonary pressures or pressure changes. This may occur either by increasing the distensibility of already inflatable alveoli or by recruiting new units.

Animals↗
PubMed1979

Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas).

A disease characterized by edema, proteinuria, hypoproteinemia and hypertension was seen in late gestation in patas monkeys. The initial sign was edema of the perineum, ankles and lower trunk. The onset was abrupt, occurring 7 days or less prepartum. The affected animals were not depressed, and convulsions were not seen. In 6 of the 98 pregnancies during a 1-year period, symptoms of the disease were present. The highest incidence was manifested by primiparous animals with 3 of 36 pregnancies affected. Two of 38 second pregnancies and 1 of 24 third pregnancies were also affected. Five of the animals recovered spontaneously and were normal 14 days postpartum. Edema persisted for 30 days in one female. This animal continued to be hypertensive and had persistent mild proteinuria and hypoproteinemia. She was killed approximately 1 year postpartum due to severe renal disease. The spontaneous disease seen in patas monkeys resembled toxemia of pregnancy in humans more closely than the experimentally induced disease in other animals.

Animals↗
PubMed1979

Transplacental effects of ethylnitrosourea in a nonhuman primate, Erythrocebus patas.

A breeding colony of the Old World monkey Erythrocebus patas, an African species, has been established to study transplacental carcinogensis in a representative primate species. ENU was administered by repeated iv injections to pregnant females and to juveniles of both sexes. Repeated doses of 0.1 mmole/kg body weight per injection, given at 14-day intervals, are tolerated without apparent signs of toxicity by fetal and by pregnant and nonpregnant adult or juvenile monkeys. The internal can be reduced to 7 days, at least during the latter two-thirds of pregnancy. Large single doses (1.0 mmole/kg) are tolerated by pregnant females but are frequently abortifacient. These doses produce acute cytolytic damage to the cells of the periventricular germinal matrix in the fetal brain. Studies with [14C]ethyl-ENU indicate that there is no placental barrier to this carcinogen. As of December 1975, no tumors had been observed.

Animals↗
PubMed1979

Lymphocyte surface markers and serum immunoglobulins in persons with Down's syndrome.

Distributions of the serum immunoglobulins, of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. Noninstitutionalized Down's syndrome children, who were 2 to 6 years of age, had lower serum IgM levels, lower total white blood cell counts, lower total lymphocytes, lower B lymphocytes, and lower IgM- and IgA-producing lymphocytes than did retarded controls. Institutionalized Down's syndrome adults, 17 to 51 years of age, had significantly higher serum IgG and IgA levels than did retarded controls. Their total lymphocytes, B lymphocytes, and IgM-producing lymphocytes were in the same direction as in the Down's syndrome children but were of borderline statistical significance (between p = .09 and .11). T lymphocytes were not significantly lower for any of the Down's syndrome-retarded groups than those for controls, but the trend was in that direction.

Adolescent↗
PubMed1978

Experimental group B streptococcal infection in the rhesus monkey. I. Disease production in the neonate.

Group B streptococci (GBS) are responsible for serious infections of newborn infants. An experimental model for GBS infection was developed in the newborn rhesus monkey in order to obtain more information concerning the pathogenesis of such infections. A series of 29 newborn monkeys were inoculated with either type Ic or type III GBS or sterile broth. Fatal neonatal meningitis without associated pneumonia was produced consistently following intracerebral inoculation with either type Ic or type III; intracerebral inoculation with sterile broth produced no apparent disease. Variable disease production followed intravenous or intra-amniotic GBS inoculation, and clinical manifestations ranged from no apparent disease to fatal meningitis and pneumonia. This monkey model may be useful for further investigation of treatment and prevention of neonatal GBS infection.

Animals↗
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

Glucocorticoids and the rhesus fetal lung.

The effects of glucocorticoids on primate fetal lung function have not been clearly delineated. In this prospective study of preterm rhesus fetuses exposed in utero to betamethasone for 72 hours, the most significant alteration was a striking increase in maximum lung volumes. Functionally less significant increases in residual lung volumes were also noted. The lungs of the treated fetuses did not exhibit lower extract surface tensions or increased phospholipid concentrations. These findings suggest that the major effect of betamethasone is on lung connective tissue elements, with minimal effects on alveolar surfactant. Additional evidence of the multisystemic effects of glucocorticoids was obtained in that significant differences in fetal, adrenal, hepatic, and placental weights also were observed.

Amniotic Fluid↗
PubMed1978

Experimental respiratory syncytial virus pneumonia in cebus monkeys.

Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.

Animals↗
PubMed1978

Solid-phase microtiter radioimmunoassay for detection of the Norwalk strain of acute nonbacterial, epidemic gastroenteritis virus and its antibodies.

The development of microtiter solid-phase radioimmunoassays for the detection of Norwalk antigen and its antibody is described. The tests are simple to perform and are sensitive and specific. The test for antigen can be used on crude stool filtrates and suspensions. Both tests are at least as sensitive as immune electron microscopy and more sensitive than immune adherence assay.

Animals↗
PubMed1978

Evaluation of five temperature-sensitive mutants of respiratory syncytial virus in primates: II. Genetic analysis of virus recovered during infection.

Five temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus (ts-1, ts-1 NG-1, ts-1 NG-16, ts-2, and ts-7), previously evaluated forinfectivity and virulence in chimpanzees and owl monkeys, were also assayed for in vivo genetic stability. None of the five mutants tested was completely stable genetically. Thus, virus which had lost some or all of the ts property was recovered from each infected chimpanzee. Significantly, each ts-1 NG-1 isolate retained some degree of temperature sensitivity and hence was not true wild-type virus. Clonal analysis of viruses shed by ts-1, ts-1 NG-1, ts-1 NG-16, or ts-7 infected chimpanzees indicated that in most instances only a minority of the virus shed was altered genetically. Of five chimpanzees infected with the ts-2 mutant, three shed only ts virus, and the remaining two chimpanzees shed only ts+ virus. Such ts+ virus proved to be avirulent when evaluated in chimpanzees or owl monkeys, indicating that loss of the ts property did not restore virulence. Based upon these findings, the ts-2 mutant appears to be a suitable candidate for clinical trials in man.

Animals↗