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Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 145 records · Page 8Linked to original sources
PubMed1996

Functional specialization in the ruminant placenta: evidence for two populations of fetal binucleate cells of different selective synthetic capacity.

Trophoblast binucleate cells (BNC) in the ruminant placenta demonstrate a characteristic development, mature structure and migratory capacity whether situated in cotyledonary or intercotyledonary regions of the placenta. However, previous immunocytochemical studies demonstrated clear differences in gene expression in granule contents of BNC according to their anatomical location with some proteins being expressed in all BNC (e.g. ovine placental lactogen) whereas others were unique to a particular origin (e.g. SBU3 antigen in cotyledonary BNC only). We have used enriched preparations of binucleate cells and showed differences in steroid metabolic capacity in vitro which is more related to their species origin (sheep or goat) than to their anatomical location. The predominant product from [3H]pregnenolone is progesterone (sheep) and 5 beta-pregnane-3 alpha, 20 alpha-diol (goat) and the amount formed (corrected for the number of BNC) is similar irrespective of whether BNC were derived from the cotyledonary or intercotyledonary regions. These studies indicate specific forms of regional functional specialization of BNC and emphasize their multifunctional role in the ruminant placenta.

Animals↗
PubMed1996

Deleterious effects of prostaglandin E2 in reflux oesophagitis.

There is good evidence in the medical literature that nonsteroidal anti-inflammatory drugs exert salutory effects in animal models of reflux oesophagitis. This hypothesis accounts for these observations by describing the biochemical mechanism of nonsteroidal anti-inflammatory drugs. Since nonsteroidal anti-inflammatory drugs inhibit the synthesis of prostaglandins, it is proposed that prostaglandins exert deleterious effects during oesophagitis. This hypothesis is supported by clinical observations and can explain several features of oesophagitis, especially the relationship between inflammation and dysmotility. The controversial implication of this hypothesis is that nonsteroidal anti-inflammatory drugs may be useful in the therapy of severe oesophagitis.

Animals↗
PubMed1996

X linked agammaglobulinaemia with a 'leaky' phenotype.

Typical X linked agammaglobulinaemia (XLA) is characterised by absence of immunoglobulin production and lack of mature B cells. The gene responsible for XLA has recently been identified, and codes for a B cell tyrosine kinase, BTK. A family affected by a B cell immunodeficiency, which is less severe than classical XLA, is described but they had a pedigree suggestive of X linked inheritance. Demonstration of a mutation in the BTK gene confirms that this is a mild form of XLA.

Agammaglobulinemia↗
PubMed1996

Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome.

AIM: To assess the results of supportive treatment with intravenous immunoglobulin (IVIG) and antibiotic prophylaxis in combination with splenectomy in patients with Wiskott-Aldrich syndrome. STUDY DESIGN: Retrospective review of case records of 21 patients from March 1984 to February 1996. RESULTS: Thrombocytopenia was cured in 14 of 15 patients who had splenectomy, but it recurred intermittently in three. Mean platelet volume (MPV) was normal transiently in some patients, but all MPV values were subnormal 8-23 months after splenectomy. Antibiotic and IVIG prophylaxis may have contributed to the lack of a detectable increase in the number of severe acute bacterial infections in the 451 months after splenectomy. Four patients died in 2205 months of observation before and after splenectomy (median 82, range 16-248): two of cerebral B cell lymphoma, one of progressive multifocal leucoencephalopathy, and one with severe chronic chest disease of pneumonia. CONCLUSION: Adequate supportive treatment with IVIG and antibiotic prophylaxis together with splenectomy enables good survival and quality of life in the short and medium term in patients with Wiskott-Aldrich syndrome. Persistence of infection, bleeding, and vasculitic and allergic symptoms in a significant minority and the risk of development of lymphoma, however, suggest that bone marrow transplantation may be indicated if an HLA identical donor is available.

Anti-Bacterial Agents↗
PubMed1996

Immunological studies of herpes simplex virus infection in children with atopic eczema.

This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (> 3) to HSV antigen, and high HSV IgG antibody titres measured by ELISA, Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.

Acute Disease↗
PubMed1996

Clinical heart transplantation. Total lymphoid irradiation for resistant rejection after heart transplantation: only moderate success medium-term.

Total lymphoid irradiation (640 cGy) was given to 19 heart and 1 heart-lung recipients on maintenance triple therapy at a mean of 4.9 +/- 4 months after transplantation (range 46 to 519 days). Mean number of treated rejection episodes before, during, and after total lymphoid irradiation was 6.4 +/- 1.7, 0.8 +/- 1.2, and 1.2 +/- 1.3 episodes per patient, respectively. During total lymphoid irradiation, 37% had at least one episode of rejection requiring treatment; after total lymphoid irradiation, 42% had no further rejection episodes, 21% had one further episode, and 37% had 2 or more episodes. Metastatic squamous cell carcinoma in one patient and coronary artery disease in three of five patients studied to date is of concern and requires longer follow-up.

Adult↗
PubMed1996

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

OBJECTIVE: For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. METHODS: Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and continued through the first 10 and 11 days, respectively, after bone marrow transplantation (a total of 14 injections). RESULTS: The overall sustained engraftment rate was 69.8%, with full chimerism in 80.6% of patients and no late graft rejection with the use of two MoAbs versus 65.7% and 58.1%, respectively, in the control group, in which only one MoAb was infused. The overall actuarial survival rate with a functional graft was 40.9%, with a mean follow-up of 39.3 months with two MoAbs versus 37.8% with one. The engraftment rate was significantly influenced by the T-cell depletion method, with better results for recipients of E rosette- depleted marrow (78.6% vs 20% for Campath 1-M plus complement-depleted marrows). Graft-versus-host disease and the kinetics of immune reconstitution were similar in both groups. CONCLUSIONS: The overall engraftment rate and overall survival rate with engraftment in patients treated with anti-LFA-1 and anti-CD2 were similar to those in patients treated with anti-LFA-1 antibody alone. However, although the number of patients is too small to draw definitive conclusions, results from the combined use of the two MoAbs indicates a trend toward better engraftment and survival after infusion of E rosette-depleted marrow. Further improvement in survival would demand additional strategies to hasten immunologic recovery.

Antibodies, Monoclonal↗
PubMed1996

Bone marrow gene transfer in three patients with adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency results in severe combined immune deficiency disease (SCID), which is fatal without treatment. Allogeneic bone marrow transplantation (BMT) is the treatment of choice if an HLA-identical sibling bone marrow donor is available, resulting in almost 100% cure rate. BMT-related mortality is high in patients lacking such a donor. For these patients, efficient transfer of a recombinant ADA gene into hematopoietic stem cells is a therapeutic option if it results in the outgrowth of a 'genetically repaired' lymphoid system. Based on successful gene transfer studies in monkeys, we performed retrovirus-mediated gene transfer into CD34+ bone marrow cells of three patients with ADA deficiency. Two patients received bovine ADA conjugated to polyethylene glycol (PEG-ADA); in the third patient, PEG-ADA was started 4 months after gene transfer. Gene transfer resulted in a 5-12% transduction frequency of in vitro colony forming cells (CFU-Cs). No toxicity was observed during and after infusion of the graft. Following infusion of the transduced CD34+ cells, transduced granulocytes and mononuclear cells persisted in the circulation for 3 months. In addition, the gene was present in the marrow of one of the patients at 6 months after gene transfer. Expression of the gene was not detected. After this period, the gene could not be detected. In monkey studies we showed that myeloablation, which was not performed in the patients, may enhance engraftment of genetically modified cells. We hypothesize that lack of myeloablation, administration of bovine ADA and low numbers of transduced progenitor cells all may have contributed to the relative low numbers of transduced cells in the patients. Under these conditions, no selective advantage of the genetically corrected progenitor cells was observed.

Adenosine Deaminase↗
PubMed1996

Aspirin chemoprevention of colorectal and oesophageal cancers. An overview of the literature and homeopathic explanation.

Recent reports in the medical literature indicate that the regular consumption of aspirin reduces the risk of both colorectal and oesophageal cancers. This paper reviews the scientific evidence for and against this suggestion. In extension of the science, a homeopathic basis for protection is proposed. The homeopathic mechanism relates to the ability of aspirin to induce the symptoms suggestive of cancer in these organs. Since homeopathy employs small doses of the mother compound, perhaps low doses of aspirin could be used to reduce the risk of cancer in the general population or in patients with precancerous colorectal and oesophageal lesions. This approach would also help to minimize the risk of adverse aspirin side-effects on the digestive system. Furthermore, in patients with colorectal and oesophageal cancers, high doses of aspirin could be given to concentrate the pharmacological/homeopathic effects.

Aspirin↗
PubMed1995

Demonstration of induction of erythrocyte inosine monophosphate dehydrogenase activity in Ribavirin-treated patients using a high performance liquid chromatography linked method.

The activity of inosine monophosphate dehydrogenase (IMPDH: EC 1.2.1.14) was measured in erythrocyte lysates using a non-radiolabelled method linked to reversed-phase liquid chromatography (RPLC). The mean activity in erythrocytes from healthy controls using this sensitive method was extremely low (mean 85 pmol/h per mg protein, range 4-183). The elevated erythrocyte IMPDH activity reported previously in hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency was confirmed (mean 234 pmol/h per mg protein). Erythrocyte IMPDH activity of patients with other disorders of purine metabolism, or with leukaemias and lymphomas, showed no marked difference from controls, except in one instance--an immunodeficient child with purine nucleoside phosphorylase (PNP) deficiency, treated with Ribavirin, where a 30-fold increase in activity was found (2670 pmol/h per mg protein). Investigation of erythrocyte IMPDH in other immunodeficient children with normal PNP activity demonstrated that this grossly elevated erythrocyte activity was attributable to induction of IMPDH by Ribavirin therapy.

Antimetabolites↗
PubMed1995

Gene transfer to primary chronic granulomatous disease monocytes.

For somatic gene therapy to become a realistic therapeutic strategy for chronic granulomatous disease (CGD), we have to be able to assign the molecular lesion to a specific component of the NADPH oxidase and to confirm that transfer of a functional copy of the corresponding defective gene will result in correction of the cellular defect. We used an adenovirus vector expressing p47phox to transduce monocytes from patients with CGD. We showed by nitroblue-tetrazolium staining that NADPH-oxidase activity was restored to these cells. This technique offers a rapid means for molecular diagnosis. In the short term, this approach may have therapeutic potential.

Adenoviridae↗