Biomedical subjects
Publications and source records attributed to G Morgan.
Smoking is a complex process influenced by social, environmental, psychologic, and biologic factors. This article explores the multiple determinants of smoking and how these variables interact to promote the persistence of smoking. Further examination of how smoking persistence varies in relation to several specific diseases is discussed.
Two hundred and forty-one prostitutes working in The Gambia were tested for retroviral infections and their immune system evaluated. Sixty-three were seropositive for HIV-2 only, five for HIV-1 only and six for both HIV-1 and HIV-2 (26.1, 2.1 and 2.5%, respectively). When compared to seronegative individuals, the 63 women infected with HIV-2 clearly had an abnormal immune system, with significantly lower CD4+ and higher CD8+ lymphocyte counts and percentages, lower CD4+:CD8+ ratios, lower CD25+ (activated) lymphocyte counts, and lower lymphocyte proliferation responses after stimulation with phytohaemagglutinin, purified protein derivative (PPD), Candida or pokeweed mitogen, and higher levels of neopterin and beta 2-microglobulin. However, when the HIV-2-seropositive prostitutes were compared with the five women infected with HIV-1, the former were less abnormal, with significantly higher CD4+ percentages and CD4+:CD8+ ratios and lower CD8+ percentages and counts. Immunological anomalies were seen in five women known to have been infected with HIV-2 for less than 17 months. Coinfection with HTLV-1 resulted in more severe immunological alterations than infection with HIV-2 alone.
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A new form of bilateral renal dysplasia in lambs appeared in a commercial sheep flock in 1982. The nature of the problem, the field investigations and the laboratory examinations carried out over three lambing seasons are described. It was concluded that the condition was vertically transmitted and genetic in origin. During the two years that accurate records were kept approximately 30 per cent of the suspected ram's progeny died with lesions of renal dysplasia. The condition recurred during a breeding trial in progeny from one of the two commercial rams originally used on the farm. An autosomal dominant mode of inheritance is suggested. The incidence illustrates the importance of keeping breeding records, especially when several rams are maintained in a flock, and the value of examining a large number of lambs post mortem.
The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.
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Sheep and goat binucleate cells (BNC) play a central role in placental growth and development. This study reports a simple method for isolating 60-70% pure populations of BNC of high viability. After incubation of the isolated BNC with a brief pulse of 14C-leucine or 3H-fucose or 3H-galactose, electron microscope autoradiography showed that label was eventually incorporated into the characteristic BNC granules via the Golgi body. Fucose and galactose initially showed a much higher Golgi body label than leucine, which was at first predominantly localised in the endoplasmic reticulum. 35S-methionine incorporation by BNC suspensions was extensive enough to allow an immunoprecipitation investigation which demonstrated that the protein hormone ovine placental lactogen and the SBU-3 antigen were synthesised de novo. Previous studies with isolated BNC have shown a remarkable range of substances to be released into the incubation medium but not necessarily synthesised during the incubation. The results demonstrate unequivocally that isolated BNC's are capable of total synthesis in vitro of two of the proteins that these same cells are known to secrete in vivo.
A protein of Mr 14,000 (14K protein) has been identified in the medium after culturing sheep conceptuses in vitro. However, it was also a component of uterine flushes of nonpregnant ewes during the luteal phase of the estrous cycle. The 14K protein, which consists of several isoforms, was purified from conceptus culture medium by a simple three-step procedure, involving ammonium sulfate precipitation, high-performance anion-exchange chromatography, and gel filtration on Sephacryl S-200. Western blotting procedures with an anti-14K antiserum showed that endometrium from ovariectomized ewes began to release the 14K protein after 6 to 14 days of progesterone treatment. Immunostaining of tissue from Day 16 pregnant ewes and from ewes treated with progesterone for 14 or 30 days showed the protein to be confined to the surface and upper glandular epithelium of the endometrium and to be absent from the deep glands. It was also present in trophectoderm of Day 16 conceptuses. Immunogold labeling in conjunction with electron microscopy revealed that within trophectoderm the 14K protein was localized to large, membrane-bound rhomboidal or needle-shaped crystal structures, and it seems likely that the protein was accumulated by the conceptus as a result of uptake of uterine histotroph. In the uterine epithelium, immunogold label was again most strongly concentrated over crystal-like structures but was also uniformly present over the cytoplasm and nucleoplasm. It was absent over mitochondria, over lipid droplets, and over non-epithelial types of endometrial cell. Such a cellular distribution for a secretory protein is novel, and it remains unclear whether the protein is synthesized by these cells.
Mother-to-child infection with HIV-2 is thought to be rare, and there have been few previous reports of transmission by this route. Reports of morbidity associated with HIV-2 infection in children are also rare. We describe eight children born to mothers who were infected with HIV-2; five developed AIDS, and three were still seropositive at 17-49 months of age. The only apparent route of HIV-2 transmission was from mother to child, except for one child who had been transfused. Three of the children with AIDS died, all having decreased CD4+ lymphocytes and mitogen responses. Further studies are needed to determine the prevalence and natural history of mother-to-child transmission of HIV-2.
The records of 28 patients with chronic granulomatous disease born over a 32 year period were reviewed. The characteristics of the group, and the frequency with which various clinical and laboratory features had been recorded, was assessed. Nine patients were known to have died, in most cases of progressive suppurative infection. Actuarial analysis showed 50% survival through the third decade of life. The long term survival of patients developing symptoms after the end of the first year of life was significantly better than that of patients whose illness started in infancy. Our data confirm that the severity of chronic granulomatous disease is not uniform, and that the prognosis for long term survival is better than that suggested in earlier reports. Early onset may be a poor prognostic sign and invasive aspergillosis is a life threatening complication. In the absence of curative treatment, trials to assess the effectiveness of interferon gamma are necessary and early antenatal diagnosis should be offered to as many affected families as possible.
Reactive oxygen metabolites are potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. To evaluate their role in inflammatory bowel disease, we investigated the effects of lowering the activities of reactive oxygen metabolites in experimental colitis induced by intracolonic administration of acetic acid in rats. Intracolonic administration of 5% acetic acid caused severe inflammation (mean (SEM) inflammatory score was 24.3 (0.7) of a maximum score of 32). Acetic acid at 2.5% produced moderate inflammation (score = 17 (1.4) v 4.0 (0.5) in control rats). This lower dose was used for subsequent experiments. Specific superoxide anion scavenger methoxypolyethylene glycol:superoxide dismutase, and reactive oxygen metabolites scavenger, sulfasalazine, significantly decreased the severity of inflammation (scores: 8 (4.4) and 9.8 (2.2) respectively). The xanthine oxidase inhibitors, tungsten and pterin aldehyde, failed to improve inflammation but another xanthine oxidase inhibitor, allopurinol, a compound with known superoxide anion scavenging effect, did limit the inflammation (10(2)). Inhibition of hydroxyl radical production by deferoxamine or lowering hydroxyl radical values by a scavenger, dimethyl sulfoxide, did not affect the severity of inflammation. These data suggest: (1) that reactive oxygen metabolites play an important role in experimental colitis, (2) that the xanthine oxidase pathway is not a major source of reactive oxygen metabolites in colitis, and (3) that tissue injury in experimental colitis is not caused by generation of hydroxyl radicals.
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The coordinated dietetic internship/master's degree program (CDI/MDP) was formed in 1965 as a consortium of three hospitals and a university combining a hospital internship and graduate degree program. As of 1984, there were 317 graduates. The purpose of this study was to determine the employment, professional activity, and further education profiles of graduates in a 20-year period. The critical path method (CPM) was used as the blueprint for the 6-month project in which 267 questionnaires were sent and 152 were returned. Findings on areas of practice of graduates of the CDI/MDP indicated that their employment generally follows the same rankings as those found in previous studies of internship, CUP, and Plan IV programs, except for greater frequency of employment in education. Activities in professional associations were notable, with many graduates serving as officers or committee members. Twenty-one percent of respondents have earned or are in the process of pursuing study beyond the master of science earned with the internship. This may indicate that students interested in completing an internship/master's program have a strong achievement orientation or that they have an unusually high regard for education. Our findings provide valuable data for understanding the career impact of advanced education combined with the internship.
The graft status of 14 patients, 13 of whom had received an allogeneic bone marrow transplant (BMT) for severe combined immunodeficiency disease (SCID) and one patient with SCID in whom intrauterine maternal engraftment was suspected, was examined using bone marrow or peripheral blood DNA and a combination of locus-specific minisatellite probes for the sex-matched and locus-specific and a Y specific probe for the sex-mismatched patients. The sensitivity of the assay systems was such that less than 0.1% recipient DNA was detectable in a background of donor DNA. Graft status could be satisfactorily documented by 2.5 weeks post-transplant and in one case was of particular value as immunological parameters were misleading. In the six long-term survivors of allogeneic BMT for SCID, the use of the locus-specific probes showed total donor lymphoid and myeloid haemopoietic engraftment in five cases and mixed host/donor populations in one case. The diagnosis in approximately 10% of cases of SCID may prove difficult due to engraftment of the fetus by maternal cells. Diagnosis may be facilitated by the use of the locus specific minisatellite probes and indeed we found specific evidence for such maternal engraftment in one patient at presentation. The combination of these probes together with a Y specific probe thus provides a rapid and accurate method of assessing graft take following allogeneic BMT for SCID. The simple pattern of inheritance obtained and the high level of sensitivity of detection of low numbers of allogeneic cells make the techniques amenable for use in any routine DNA diagnostic laboratory.
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Fatal graft versus host disease (GVHD) developed in a child with purine nucleoside phosphorylase (PNP) deficiency following an unirradiated platelet transfusion. IV treatment with an anti-T-cell monoclonal antibody (CD7) led to a transient improvement of his GVHD (Grade IV) but did not prevent the fatal outcome. This report emphasizes the need for blood products to be irradiated when cell mediated immunodeficiency is suspected, even in patients with residual immunocompetence.
Three children presenting with neurological symptoms were subsequently diagnosed as being infected with the human immunodeficiency virus I (HIV). All children showed normal development for about 12-18 months of age but later developed psychomotor and developmental regression. One child presented with generalised hypotonia, another with focal seizures, and the third with spastic quadriplegia. Two of the children showed areas of abnormal brain density on computed tomography and in one case there was calcification of the basal ganglia. In two of the children cerebrospinal fluid contained reduced amounts of total folate and elevated concentrations of neopterin. The possibility of a link between the deranged folate metabolism and the neurological symptoms in HIV infection is discussed.