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Biomedical subjects

J E Morgan

Publications and source records attributed to J E Morgan.

At least 163 records · Page 9Linked to original sources
PubMed1986

Association constants for the interaction of double-stranded and single-stranded DNA with spermine, spermidine, putrescine, diaminopropane, N1- and N8-acetylspermidine, and magnesium: determination from analysis of the broadening of thermal denaturation curves.

The effect of Mg2+, putrescine, diaminopropane, N1-acetylspermidine, N8-acetylspermidine, spermidine, and spermine on the thermal denaturation of calf thymus DNA was investigated. As in a previous study with magnesium [W.F. Dove and N. Davidson, (1962) J. Mol. Biol. 5, 467-478], these ligands were found to raise the thermal denaturation temperature of the DNA and to broaden the thermal denaturation curve dramatically at the point where 10 to 20% of the DNA charge had been neutralized. At higher levels of charge neutralization the curves became sharper again. This behavior was due to differential binding of the ligands to single- and double-stranded DNA. The broadening was used to determine the ratio of the association constants of each ligand to the two forms of DNA using either an independent sites model of binding or an excluded sites model. The results show that the primary mode of binding of the ligands to DNA is electrostatic but that important secondary, nonelectrostatic, effects are also present.

Animals↗
PubMed1986

Antagonistic analogs of luteinizing hormone-releasing hormone are mast cell secretagogues.

The histamine-releasing activity of luteinizing hormone-releasing hormone (LHRH) antagonistic analogs has been documented. Antagonists of LHRH elicited in vitro histamine release from mast cells obtained from previously unexposed rats. Intradermal injection of the antagonists caused increased local skin permeability. Anaphylactoid reactions followed subcutaneous injection of the antagonists and in some cases these edematous reactions were accompanied by increased serum histamine levels. These studies show that these small peptides can cause mast cell degranulation and suggest that the neuropeptide, LHRH, may have modulating effects on the immune system.

Anaphylaxis↗
PubMed1985

The Marlex sling operation for the treatment of recurrent stress urinary incontinence: a 16-year review.

Between 1968 and 1983, 281 patients with recurrent stress urinary incontinence and nine patients with primary stress urinary incontinence were treated with a two-team (suprapubic vaginal) Marlex urethral sling operation. Selection was based on the patient's history and the clinical demonstration of an anatomic defect in the closure mechanism of the urethra. The operative technique as described in 1970 remains unchanged. The bladder neck is released from the scar and replaced in a midretropubic position on a hammock of Marlex mesh attached to Cooper's ligaments. Patients with a sloughed urethra had a sling operation in conjunction with the reconstruction of a neourethra. The overall success rate based on a minimum 5-year follow-up of 208 patients was 77.4%. There was a high failure rate in the sloughed urethra group. Significant overall complications include bladder neck obstruction and chronic cystitis.

Female↗
PubMed1984

Long term survival of allografted muscle precursor cells following a limited period of treatment with cyclosporin A.

Previous work (Watt et al., 1982) has shown that, in the mouse, skeletal muscle can be transplanted successfully in the form of a suspension of it's mononucleate precursors. Eventual therapeutic application of this technique by the implantation of precursor cells derived from normal muscle into myopathic individuals would require a means of preventing allograft rejection applicable to man. We have therefore investigated the use of the drug cyclosporin A (CyA) as a means of prolonging the survival in mice of allografts of mononucleate muscle cells made into a region of regenerating host muscle. We have administered CyA to the hosts at doses of either 75 or 150 mg/kg body weight/day for 42 days from the day of grafting. By using isoenzyme allotypes as markers of host and donor tissues, we have shown that allografted mononucleate cells become incorporated in host muscle fibres and that the mosaic host/donor muscle fibres so formed survive for as long as we continued the experiment, a maximum of 107 days after grafting, or 65 days after the end of CyA treatment.

Animals↗
PubMed1983

Gastric carcinoid (gastrinoma) associated with achlorhydria (pernicious anemia).

This report presents a case of multicentric gastric carcinoid (gastrin containing) tumors of the fundus associated with achlorhydria and pernicious anemia. It is suggested that stimulation of the antral G cells and possibly fundic argyrophilic cells by achlorhydria associated with atrophic gastritis may lead to hyperplasia, and eventually to neoplasia in the latter, in the form of gastric carcinoid with gastrin production.

Achlorhydria↗
PubMed1982

Incorporation of donor muscle precursor cells into an area of muscle regeneration in the host mouse.

Normal muscle precursor cells, prepared by the enzymatic disaggregation of neonatal mouse muscle, were implanted into an area of regenerating muscle in a genetically different inbred strain. This was done in an attempt to determine, first, whether donor muscle precursor cells prepared in this way would fuse with the developing muscle fibres of the host; and second, whether in the "mosaic" muscle fibres thus formed donor as well as host genes were expressed. As markers of the host and donor genes we used the allelic isoenzyme variants of glucose-6-phosphate isomerase (GPI). In 43 out of 60 grafts we detected the presence of a "hybrid" isoenzyme intermediate between host and donor types. This "hybrid" indicated that donor muscle precursor cells had fused with regenerating host muscle cells, and had expressed their GPI genes within the resulting mosaic muscle fibres. We have developed this technique with a view to inserting normal genes into genetically abnormal myopathic muscle.

Animals↗
PubMed1982

Immunology of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) represents a spectrum of granulomatous, interstitial, and alveolar-filling lung disorders of which farmer's lung is a classic example. A major source of offending antigens in these diseases are thermophilic actinomycetes growing in moldy vegetable matter especially Micropolyspora faeni, and members of the Thermoactinomyces genus. Acutely, hypersensitivity pneumonitis presents as cough, dyspnea and fever, with crepitant rales, leucocytosis, diffuse interstitial and alveolar pulmonary infiltrates and a restrictive-type pulmonary functional deficit. Symptoms usually begin 4 to 6 hr after exposure to large quantities of causative organic dust. Chronically, these diseases may present with the gradual onset of cough, dyspnea on exertion, fatigue, anorexia, and weight loss which may progress to pulmonary fibrosis or severe pulmonary insufficiency. While early ideas on the pathogenesis of hypersensitivity pneumonitis support the role of Type III immune complex hypersensitivity, more recent evidence attests to the important and integral role of Type IV or delayed-type hypersensitivity. It is the purpose of this review, therefore, to describe those immune mechanisms relevant to the pathogenesis of hypersensitivity pneumonitis and stress the importance of "local" pulmonary immune responsiveness.

Alveolitis, Extrinsic Allergic↗
PubMed1981

Interactions between misonidazole and hyperthermia in EMT6 spheroids.

The effect of hypoxic misonidazole (MISO) pretreatment on the subsequent heat sensitivity of EMT6 multicellular tumour spheroids has been investigated. Spheroids were grown in static culture and treated when either 200-300 micrometers or 650-800 micrometers in diameter. Pretreatment was carried out in glass spinner vessels containing 100 ml medium with or without 5mM MISO under conditions of hypoxia. Three-hour hypoxic pretreatment with 5mM MISO significantly enhanced the subsequent response of 200 micrometers spheroids to heat at 43 degrees C. Oxic incubation at 37 degrees C between pretreatment and heating caused progressively loss of heat sensitization with time, recovery being almost complete after 6 h. Recovery was inhibited by incubation at 0 degree C during the interval. Preheating 200 micrometers spheroids at 43 degrees C for 2 h increased their subsequent sensitivity to hypoxic MISO at 37 degrees C. These results are discussed in relation to known mechanisms of MISO metabolism.

Cell Survival↗
PubMed1981

Response of EMT6 multicellular tumour spheroids to hyperthermia and cytotoxic drugs.

The response of multicellular tumour spheroids of the EMT6 cell line to combinations of hyperthermia and Bleomycin (BLM) or Adriamycin (ADM) has been investigated. Using this model system, we have demonstrated enhanced BLM cytotoxicity at 43 degrees C and also heat-induced drug tolerance to BLM at 43 degrees C. ADM cytotoxicity was not significantly increased after 43 degrees C x 1 h but after 6 h at 42 degrees C greatly enhanced cell-killing was evident. These results are discussed in relation to our previous data for EMT6 cells growing either as monolayer cultures in vitro or as solid tumours in mice.

Animals↗
PubMed1981

Surgical tape.

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Acrylates↗
PubMed1981

The road to GMENAC.

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Education, Medical↗
PubMed1980

Effects of local hyperthermia on the pharmacokinetics of misonidazole in the anaesthetized mouse.

The effects of sodium pentobarbitone anaesthesia, the presence of a tumour, and local hyperthermia to a tumour-bearing leg, on the pharmacokinetics of MISO in the mouse are reported. Analysis of MISO and its metabolite Ro 05-9963 was by high-performance liquid chromatography. The plasma kinetics of MISO were largely unaffected by any of these treatments, but hyperthermia substantially reduced tumour concentrations of the drug. The effects of tumour site and size on unheated-tumour drug concentrations were also studied, and an increase in tumour size was shown to decrease tumour MISO levels, but to different degrees according to whether implanted in the leg or flank. Uniformity of MISO distribution throughout heated and unheated tumours was examined, and levels were found to be constant within tumours. The presence of a temperature detector in heated tumours did not affect their drug concentration.

Abdomen↗
PubMed1980

The nonspecific inhibitory effect of synovial tissue extracts on leucocyte migration in vitro.

The leucocyte migration inhibition test (LMT) has been used to search for specific antigens in rheumatoid synovial tissue. Synovial samples were collected from 20 patients with rheumatoid arthritis, from 1 patient with ankylosing spondylitis, and from 1 patient with pigmented villonodular synovitis. Inhibitory material was obtained from all 21 synovia with inflammatory disease but not from the noninflammatory synovium. The tissue extracts generally caused nonspecific migration inhibition when tested against a total of 157 pairs of rheumatoid and control leucocytes. However, occasional samples did induce migration inhibition restricted to either rheumatoid or control cells. The inhibitory factor was shown to be membrane associated and of high molecular weight (greater than 10(6) daltons). The results of this extensive study do not support the conclusions drawn from earlier reports based on smaller numbers of experiments. No evidence was obtained for the existence of specific antigenic material associated with the synovial membrane in rheumatoid arthritis.

Adult↗
PubMed1979

The interaction of thermal tolerance with drug cytotoxicity in vitro.

The effect of preheating EMT6 cells in vitro on their response to cytotoxic agents of either 43 degrees C or 37 degrees C has been investigated. Preheating for 3 h at 40 degrees C produced measurable protection (thermal tolerance) to subsequent treatment for 1 h at 43 degrees C. This preheat treatment was further found to reduce cell killing by BLM and BCNU (drug tolerance) present during 1 h at 43 degrees C. In contrast, no such heat-induced drug tolerance was seen with ADR. An additional effect with ADR was the apparent elimination of heat-induced thermal tolerance at toxic drug doses. However, preheating under these conditions had no effect on the subsequent cytotoxicity of any of these drugs at 37 degrees C. Also, preheating for 1 h at 43 degrees C was found to sensitize cells to BLM and BCNU toxicity at 37 degrees C but to protect against ADR toxicity. The results are discussed in relation to known mechanisms of cell killing by heat and of thermal tolerance.

Animals↗
PubMed1979

The early history of tuberous sclerosis.

The early history of tuberous sclerosis can be traced from European wax models of the skin lesions in the 1830s to its recognition as a systemic disease by the early 1900s. There are various origins for the terms used for tuberous sclerosis, including Pringle's disease, Bourneville's disease, adenoma sebaceum, and epiloia. Since these terms are confusing and inaccurate, we urge that they no longer be used.

Adenoma↗
PubMed1978

The sloughed urethra syndrome.

Sloughing of the urethra following obstetric trauma or pelvic surgery usually results in total urinary incontinence. Nine patients in a series of 2,000 investigated for incontinence presented with this syndrome. A technique of urethral reconstruction from the vaginal wall using a supporting bulbocavernosus graft and a Marlex sling is presented and results are discussed.

Adult↗