Search PubMed⌕ Search

Biomedical subjects

J G Wilson

Publications and source records attributed to J G Wilson.

At least 73 records · Page 4Linked to original sources

Characterization of human T lymphocytes that express the C3b receptor.

The presence of the C3b receptor (C3bR) on human peripheral blood T lymphocytes was recognized by the capacity of rabbit F(ab')2 anti-C3bR and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat F(ab')2 anti-rabbit F(ab')2 to stain 14.5 +/- 3.7% (mean +/- SEM; n = 5) of lymphocytes forming rosettes with sheep erythrocytes (E). The F(ab')2 anti-C3bR also blocked the capacity of peripheral blood lymphocytes stained with OKT11 to form rosettes with bovine E bearing C3b and immunoprecipitated a single membrane protein having a m.w. of approximately 250,000 from detergent lysates of 125I-labeled, purified T cells. Measurement by fluorescent flow cytometry of the quantitative expression of the C3bR indicated that T cells had slightly more antigenic sites/cell than did E and approximately 10-fold fewer sites than were present on B cells. The surface constituents of the peripheral blood T cells expressing the C3bR were assessed in an assay that employed simultaneously three markers: rosette formation with sheep E, TRITC staining with anti-C3bR and fluorescein isothiocyanate (FITC)-staining with a panel of monoclonal antibodies or with aggregated IgG. Among lymphocytes forming rosettes with sheep E and expressing the C3bR, 99.6 +/- 0.4%, 65.0 +/- 5.8%, 17.2 +/- 6.2%, and 15.3 +/- 5.0% of the cells expressed antigens detected by OKT3, OKT4, OKT8, and OKM1 monoclonal antibodies, respectively. Ninety-seven per cent of the C3bR-bearing T cells were also capable of specifically binding aggregated IgG, indicating the presence of Fc receptors for IgG (Fc gamma R) on these cells. The T cells expressing the C3bR had large nuclei, thin rims of basophilic cytoplasm and no azurophilic granules. Thus, the C3bR is present on some T cells, all of which have a typical lymphocyte morphology, the T3 antigen and the Fc gamma R.

Animals↗

Mode of inheritance of decreased C3b receptors on erythrocytes of patients with systemic lupus erythematosus.

The erythrocytes of patients with systemic lupus erythematosus have been shown to have a decreased number of receptors for the major cleavage fragment of the third component of complement (C3b). We studied the basis for this decreased number of C3b receptors by measuring the uptake of anti-C3b-receptor antibody on cells from 113 normal subjects, 38 patients with systemic lupus erythematosus, 14 of their spouses, and 47 of their relatives. The normal subjects had 5014 +/- (mean +/- S.E.M.) receptor sites per cell, but the patients and their relatives had significantly fewer sites--2809 +/- 241 and 3167 +/- 196, respectively (P less than 0.0005). The number of sites in the patients' spouses did not differ from normal (P greater than 0.3). Three phenotypes, indicated by the numbers of receptors, occurred in the normal population; a high phenotype (HH, with 5500 to 8500 sites per cell), an intermediate phenotype (HL, with 3000 to 5499), and a low phenotype (LL, less than 3000). These three phenotypes were present in 34, 54, and 12 percent, respectively, of the normal subjects; in contrast, 5, 42, and 53 per cent of patients had these respective phenotypes. Pedigree analyses indicated that these phenotypes were inherited in an autosomal codominant manner. We conclude that the decreased number of C3b receptors in lupus is inherited, not acquired.

Adult↗

Potentiative interactions between caffeine and various teratogenic agents.

Acetazolamide and inhibitors of DNA synthesis (hydroxyurea, 5-fluoro-2'-deoxyuridine), RNA synthesis (actinomycin D), and protein synthesis (cycloheximide, emetine) were each administered to pregnant rats together with caffeine at doses where each agent alone caused minimal embryotoxicity. Caffeine co-administered with any of the other agents induced a powerful potentiative response. It is not clear from the present experiments whether much lower caffeine dosage, as normally encountered in humans, would potentiate embryotoxicity due to other agents.

Abnormalities, Drug-Induced↗

Are female sex hormones teratogenic?

An analysis of available epidemiologic data leads the present reviewers to conclude that the use of exogenous hormones during human pregnancy has not been proved to cause developmental abnormality in nongenital organs and tissues. This conclusion is further supported by the animal laboratory data. The preponderance of evidence at this writing indicates a lack of causal association between hormonal use during pregnancy and nongenital malformation of the offspring. The quality of the epidemiologic data does not, at this time, permit a definitive conclusion that sex hormones during pregnancy may not, under as yet to be defined conditions, have some adverse effect on human prenatal development. If there are increased risks of nongenital malformations associated with the administration of certain sex steroids, the risks are very small, may not be causal, and are substantially below the spontaneous risk of malformations. In spite of the present degree of uncertainty, the clinical, epidemiologic, and laboratory data do permit the formulation of a rational approach to handling problems related to sex steroid usage and exposure in pregnant women.

Abnormalities, Drug-Induced↗

Indomethacin--placental transfer, cytotoxicity, and teratology in the rat.

Aspirin is a well-known teratogen in laboratory animals and is an inhibitor of prostaglandin synthesis. To further investigate the inhibition of prostaglandin synthesis as a mechanism of teratogenesis, we examined the teratologic potential, cytotoxic potential, and placental transfer of indomethacin in the rat. Indomethacin was not teratologic, not cytotoxic to cells in the embryonic hindlimb bud, and did not cross the placenta in physiologically significant amounts on days 11 to 12 of gestation. Near parturition, however, indomethacin crossed the placenta in pharmacologically significant amounts. The pharmacokinetics of placental drug transfer are discussed.

Abnormalities, Drug-Induced↗

Aspirin-induced teratogenesis: a unique pattern of cell death and subsequent polydactyly in the rat.

Offspring of pregnant rats treated with a high dose of aspirin on day 11 of gestation frequently had predominantly right-sided polydactyly of the hindlimbs at term. Aspirin-treated embryos removed on day 12 exhibited a unique pattern of preaxial mesodermal cell death in the hindlimb buds. In addition, these embryos had a delay of the normal episode of cells death in the preaxial apical ectodermal ridge and an absence of cell death in a zone of physiological necrosis in the preaxial mesoderm thought to be instrumental in controlling preaxial digit formation. The role of cell death in the pathogenesis of polydactyly is discussed.

Abnormalities, Drug-Induced↗

Comparative studies on acetazolamide teratogenesis in pregnant rats, rabbits, and rhesus monkeys.

Acetazolamide produces a characteristic forelimb reduction deformity when administered to pregnant rodents. Past studies indicated that non-rodent species (rabbit and monkey) are resistant to this effect. The present studies confirmed this fact and demonstrated that transport of acetazolamide into the rabbit embryo was similar to that in sensitive rat embryos. In monkeys, however, the concentrations of acetazolamide within maternal plasma and embryo were much lower than in rats. Carbonic anhydrase activity was also measured since inhibition of this enzyme is the primary pharmacologic effect of acetazolamide. Again the rabbit embryo had carbonic anhydrase specific activity levels similar to that of the rat. Monkey embryos, on the other hand, contained negligible levels of enzyme activity during the presumed sensitive period of development. Thus the resistance of monkey embryos to acetazolamide teratogenesis may be due to low carbonic anhydrase activity and/or the small amount of drug reaching the embryo. No basis for the resistance of rabbit embryos to acetazolamide teratogenesis was uncovered.

Acetazolamide↗

Problems encountered in the early diagnosis and management of congenital dislocation of the hip.

This paper reports the results of screening 53033 infants for congenital dislocation of the hip between 1970 and 1979, and compares them with the results of a similar screening programme between 1960 to 1969. The number of dislocations missed at neonatal examination is unaltered at 0.11 per cent of live births. Operative treatment was needed in a further 0.07 per cent of the recent series even though the dislocations had been diagnosed within 24 hours of birth. The reasons for the failure of neonatal screening are discussed, and suggestions are made which will improve the situation.

Child, Preschool↗

A metabolite of a structural analog of thalidomide lacks teratogenic effect in pregnant rhesus monkeys.

A metabolite of CG 3033, a structural analog of thalidomide, was examined for teratogenic potential in rhesus monkeys. The metabolite EM 240 is produced in man by hydrolysis of the parent compound but the pathway is absent in nonhuman primates. Fifteen mg/kg administered orally throughout organogenesis to pregnant rhesus monkeys produced no evidence of embryotoxicity, including malformation.

Abnormalities, Drug-Induced↗

Effect of 5-fluoro-2'-deoxyuridine on deoxyribonucleotide pools in vivo.

5-Fluoro-2'-deoxyuridine (FdUrd) lowered the dTTP levels in rapidly frozen 12-day W rat embryos and in a human neuroblastoma grown in nude N:NIH(S) mice to about 20% of control values. This effect was associated with greatly increased dCTP levels and reduction of dGTP levels essentially to zero. Elimination of the dGTP pool correlated temporally with the cytotoxicity of FdUrd. Extremely rapid fixation of tissue was required to avoid artifactually high deoxyribonucleoside triphosphate values.

Animals↗

The evolution of teratological testing.

The beginnings of mammalian experimental teratology in this century are briefly reviewed and it is noted that prior to 1960 a degree of sophistication in concept and technology had already been achieved. Thus, contrary to claims that teratology had its beginning with the thalidomide catastrophe, a modest but expanding activity and body of knowledge already existed before this unfortunate event. This activity and this knowledge, however, were largely confined to academic and research institute laboratories and made little impact on the agencies in medicine, government and industry which oversaw public health and safety and set policies intended to preserve them. No individual, group, or agency can rightly be blamed for not having sooner brought together the concepts and methodology needed for meaningful animal testing and the regulatory insignt and experience needed intelligently to apply test data to human safety evaluation and experience needed intelligently to apply test data to human safety evaluation. To accomplish this liaison seems to have required the largest toxicological catastrophe yet recorded in human history. The major events leading to formulation of the first standardized guidelines are reviewed, but it is emphasized that even today the best animal testing can only provide a limited statement of probability regarding human risk vis-à-vis safety.

Abnormalities, Drug-Induced↗

Chronic mucocutaneous candidiasis. Immunologic studies of three generations of a single family.

A family consisting of eight members in three generations (age 10 months to 53 years) affected with chronic mucocutaneous candidiasis was studied along with three unaffected relatives. Dermatophytosis, loss of teeth and recurrent viral infections were present in some members. Results of tests for endocrinologic, muscle or liver disease, thymoma, iron deficiency, antitissue antibodies and malabsorption were normal in all patients. Antibody function and levels, B cell counts, serum complement, leukocyte enzymes, chemotaxis, phagocytosis and adherence were normal in all members. Plasma inhibitors to lymphocyte transformation and leukocyte inhibitory factor were not found. No unique HLA haplotype or antigen segregated in this family. Evaluation of cell-mediated immunity revealed total cutaneous anergy in three of eight whereas four of the other five had negative lymphocyte transformation and skin tests to Candida but responded normally to other antigens. Leukocyte inhibitory factor was not produced to Candida antigen in all four patients tested. T cell counts were within normal limits in all. Extensive evaluation of all limbs of the immune system in this family revealed a defect in cell-mediated immunity to Candida that appeared to be inherited as a dominant characteristic.

Adolescent↗

Ethanol and heat-treated plasma fractionation methods in South Africa.

Modifications of the Cohn techniques are the methods of choice for the preparation fo dilute albumin (PPS) and gamma-globulin solutions on an industrial scale. For the manufacture of refined albumin solutions, however, considerable labour and material is saved if crude, ethanol-precipitated fractions are heated in the presence of stabilisers in order to purify the albumin. The technique is simple and cheap, and yields a safe product of high quality. Bacterially contaminated and highly haemoglobinized plasma can be successfully heat-treated.

Animals↗

Embryotoxicity of the folate antagonist methotrexate in rats and rabbits.

The prenatal effects of methotrexate (MTX) in rats and rabbits were assessed. It was found highly embryotoxic in postimplantation rat embryos; 0.3 mg/kg ip or less caused nearly total embryolethality with slight teratogenicity. Rabbit embryos were far more resistant to small doses of MTX than rats, but 19.2 mg/kg iv, when given during days 10 to 15 of gestation, produced little death and a constant spectrum of malformation in a high percentage of offspring. Cleft palate, skull defects, and severe fore- and hindlimb dysplasias, occurred with a high degree of regularity and were strongly dose and developmental-stage specific.

Abnormalities, Drug-Induced↗