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Biomedical subjects

C Morrow

Publications and source records attributed to C Morrow.

At least 37 records · Page 2Linked to original sources

Inositol phospholipids are probably not the source of arachidonic acid for eicosanoid synthesis in astrocytes.

In astrocyte-enriched cultures of the rat cerebral cortex the Ca2+ ionophore A23187 provoked the breakdown of inositol phospholipids, the liberation of arachidonic acid and the release of prostaglandins E2, F2 alpha, I2 and thromboxane A2. However, agonists for receptors also coupled to inositol phospholipid metabolism in these cells failed to produce an increase in the release of both arachidonic acid and eicosanoids. Results suggest that the A23187-stimulated release of arachidonic acid and eicosanoids is caused by a phospholipase A2-mediated attack on lipids other than the inositol phospholipids. Moreover, receptors linked to inositol lipid turnover are not involved in the control of eicosanoid release from astrocytes.

Animals↗

Phorbol ester stimulates proliferation of astrocytes in primary culture.

Near-confluent primary cultures of astrocytes from the neonatal rat cerebral cortex were transferred to low serum (0.1%) growth medium for 24 h before a single addition of phorbol-12-myristate-13-acetate (0.01-100 ng X ml-1), a phorbol ester which mimics diacylglycerol activation of protein kinase C. After 48 h the cultures were pulsed with [methyl-3H]thymidine. Cultures exposed to phorbol ester exhibited dose-dependent increases in thymidine incorporation which were reversed by amiloride.

Amiloride↗

Primary aortoduodenal fistula caused by Salmonella aortitis.

We report the management and follow-up of two cases of primary aortoduodenal fistulas caused by Salmonella aortitis. The origin, presentation, diagnosis, and results of operative therapy for patients with primary aortoduodenal fistulas, especially patients with positive aortic wall cultures, are reviewed. Successful therapeutic principles included early intervention, primary duodenal repair, aneurysm resection, aortic reconstruction with an in situ Dacron graft, and prolonged courses of bactericidal antibiotics.

Adult↗

Spontaneous iliac arteriovenous fistula.

The formation of an iliac arteriovenous fistula caused by rupture of an atherosclerotic iliac artery aneurysm is unusual. We describe a case and review the previously reported 18 cases of spontaneous iliac arteriovenous fistula. The presence of a palpable abdominal mass associated with a thrill or bruit and unilateral leg symptoms of venous engorgement or arterial insufficiency, with or without acute onset of congestive heart failure, should result in a high index of suspicion of this entity. Prompt recognition and surgical closure of the iliac fistula are most important in successful management.

Aged↗

Duodenal varices as a cause of massive upper gastrointestinal bleeding.

Duodenal varices are an uncommon but serious manifestation of portal hypertension. Our management of three patients with massive bleeding due to duodenal varices stimulated a review of this subject. Thirteen cases of this condition were previously reported. Endoscopic examination of the entire duodenal mucosa is essential to document bleeding from duodenal varices. Medical therapies, including vasopressin and endoscopic sclerotherapy, have had limited success in controlling active duodenal variceal bleeding. Duodenal varix suture ligation or resection also resulted in a high rate of rebleeding. End-to-side portocaval shunt was the most effective procedure in stopping acute and subsequent bleeding in patients with duodenal varices. Despite therapy with or without portosystemic shunt, mortality risk is high in Child's class C patients and in patients with emergency duodenal variceal bleeding.

Adult↗

Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux.

Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [3H]myoinositol or 45Ca2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca2+ flux with the following rank order of efficacy: quisqualate greater than or equal to glutamate (Glu) greater than kainate much greater than N-methyl-D-aspartate. Experiments performed with the Ca2+ ionophore A23187 and in the absence of medium Ca2+ suggested that Glu-evoked 45Ca2+ efflux was primarily the result of an increased influx of extracellular Ca2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca2+. The quisqualate-preferring receptor antagonist gamma-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca2+ channel opening in astrocytes.

Amino Acids↗

Receptor-mediated inositol phospholipid hydrolysis in astrocytes.

Astrocyte-enriched cultures of the neonatal rat cortex were incubated for 24 h with [3H]inositol to prelabel the membrane inositol phospholipids. Exposure of the cultures to either noradrenaline or carbachol in the presence of Li+ produced a time- and dose-dependent accumulation of intracellular [3H]inositol phosphates. The separation of the individual inositol phosphates formed in response to receptor stimulation revealed that the major 3H-metabolite accumulated under these conditions was inositol monophosphate but that at least some of this was due to the initial formation of inositol trisphosphate. The use of selective receptor antagonists showed that noradrenaline- and carbachol-induced [3H]inositol phosphate accumulation was the result of the activation of alpha 1-adrenoceptors and muscarinic acetylcholine (probably of the M1 subtype) receptors respectively. Agonist-evoked [3H]inositol phosphate accumulation were found to be additive but the simultaneous addition of agonists and the Ca2+ ionophore A23187, which also promoted inositol phospholipid hydrolysis, was not. Agonist-induced [3H]inositol phosphate accumulation was only partially dependent on extracellular Ca2+, whilst that elicited by A23187 was entirely Ca2+-dependent. The results suggest that alpha 1-adrenoceptors and muscarinic acetylcholine receptors in these cultures are present either on the same cells and linked to separate inositol lipid pools or associated with different subpopulations of astrocytes in these cultures. Moreover, inositol lipids other than phosphatidylinositol 4,5-bisphosphate may be hydrolysed in response to agonist stimulation.

Animals↗

Astrocytes have both M1 and M2 muscarinic receptor subtypes.

In astrocytes, carbachol evoked the turnover of membrane inositol phospholipids prelabelled with [3H]inositol, as revealed by [3H]inositol phosphate accumulation in the presence of 5 mM lithium. This effect was blocked by atropine and by pirenzepine (IC50 2.2 nM and 56 nM, respectively). Carbachol partially attenuated the isoproterenol-stimulated cyclic adenosine 3',5'-monophosphate production in astrocytes by a direct effect on adenylate cyclase, an effect blocked by atropine and pirenzepine. These results suggest that astrocytes express muscarinic receptor subtypes.

Animals↗

Activation of muscarinic and of alpha 1-adrenergic receptors on astrocytes results in the accumulation of inositol phosphates.

Astrocyte-enriched cultures prepared from the newborn rat cortex incorporated [3H]myo-inositol into intracellular free inositol and inositol lipid pools. Noradrenaline and carbachol stimulated the turnover of these pools resulting in an increased accumulation of intracellular [3H]inositol phosphates. The effects of noradrenaline and carbachol were dose-dependent and blocked by specific alpha 1-adrenergic and muscarinic cholinergic receptor antagonists, respectively. The increase in [3H]inositol phosphate accumulation caused by these receptor antagonists was virtually unchanged when cultures were incubated in Ca2+-free medium, but was abolished when EGTA was also present in the Ca2+-free medium. Cultures of meningeal fibroblasts, the major cell type contaminating the astrocyte cultures, also accumulated [3H]myo-inositol, but no increased accumulation of [3H]inositol phosphates was found in response to either noradrenaline or carbachol.

Animals↗

Methylmethacrylate induces pulmonary hypertension and increases lung vascular permeability in sheep.

Methylmethacrylate (MMA) is a bone cement used to attach prosthetic joints to raw bone surfaces. Occasional reports of pulmonary complications following total hip replacement suggest that MMA may induce pulmonary microvascular abnormalities. We studied the hemodynamic and pulmonary edemagenic effects of 2 mg/kg and 12 mg/kg MMA in 23 sheep. After the 12 mg/kg dose there was a marked fall in mean systemic blood pressure (SBP) within 30 s from 92 +/- 7 to 59 +/- 3 mmHg (p less than 0.05). The SBP returned to normal and then decreased, again becoming significantly lower than baseline at 120 min. Mean pulmonary artery pressure (PAP) increased from 16.8 +/- 1.2 to 27.0 +/- 1.5 mmHg at 0.5 min (p less than 0.01 then slowly returned to normal over 1 h. Despite the transient changes in pulmonary hemodynamics, baseline lymph flow (QL) doubled at 30 min and tripled at 120 min to 3.0 +/- 0.4 and 4.4 +/- 0.6, respectively (p less than 0.01). Lymph/plasma ratio for albumin was 0.83 +/- 0.03 at baseline and was unchanged throughout the study. Lung tissue water/blood free dry weight ratio was 5.4 +/- 0.4 compared to 3.6 +/- 0.3 for normal sheep (p less than 0.05). After the low dose there was no change in SBP or PAP, and QL only doubled (1.0 +/- 0.3 to 2.3 +/- 0.7). The L/P albumin was unchanged. We found no evidence of polymorphonuclear leukocyte (PMN) trapping in the pulmonary parenchyma by lung biopsy or by counts of PMNs in pulmonary artery and aortic blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Foreign body granulomatosis. Clinical and immunologic findings.

We studied the clinical and immunologic features of 10 patients with foreign body granulomatosis associated with injection of pentazocine. Five had typical micronodules on chest radiographs, 9 had abnormal 67Ga lung images, and 9 had elevated serum angiotensin-converting enzyme levels. Pulmonary function tests showed significant decreases in diffusing capacity in 8 subjects, but were otherwise normal. Bronchoalveolar lavage fluid had significantly (p less than 0.02) increased total cell numbers (13.8 +/- 7.5 x 10(7) and significantly lower percentages of lymphocytes (2 +/- 1) and neutrophils (2 +/- 1) (p less than 0.02) when compared with that from control subjects. Peripheral blood lymphocytes were normal when expressed as percentages of total leukocytes or as percent T-lymphocytes. Monoclonal antibody determinations of T-lymphocyte subsets (helper and suppressor) were similar to those in control subjects (p = NS). Lymphocyte transformation responses to a variety of antigens and skin test reactivity were normal. Foreign body granulomatosis contrasts with other interstitial lung diseases in its bronchoalveolar lavage cellular profile and in the absence of altered peripheral immunologic indexes.

Adult↗

Cis-diamminedichloroplatinum(II) nephrotoxicity and its relationship to renal gamma-glutamyl transpeptidase and glutathione.

To investigate the mechanism of cis-diamminedichloroplatinum(II) (cisplatin) nephrotoxicity, male Sprague-Dawley rats were given one injection of cisplatin (6 mg/kg i.v.). Urinary levels of amino acids and gamma-glutamyl transpeptidase were monitored for 8 days; kidney homogenate content of gamma-glutamyl transpeptidase was followed for 50 hr, and that of selenium-dependent glutathione peroxidase and total glutathione was followed for 4 hr. Peak urinary levels of amino acids and gamma-glutamyl transpeptidase occurred 4.5 hr after the i.v. dose. Glutamine, glycine, and ethanolamine were all elevated greater than 20 times that of the control at 4.5 hr and were still significantly elevated at 50 hr. Total renal glutathione content increased 51 +/- 17% (S.D.) of control values 20 min after cisplatin was given, before returning to base-line levels. No depletion of either renal glutathione or glutathione peroxidase was detected over the time interval studied. These results demonstrate an earlier physiological impairment than has hitherto been shown. Furthermore, depletion of glutathione and glutathione peroxidase does not occur in the rat kidney following therapeutic doses of cisplatin, in contrast to the changes observed in cardiac tissue following doxorubicin treatment.

Acyltransferases↗

Surgical treatment of duodenal ulcer: a prospective randomized study.

From 1960 to 1980, 344 patients were included in a prospective randomized study for elective surgical treatment of duodenal ulcer disease. Results of vagotomy and pyloroplasty were compared with vagotomy and hemigastrectomy. There were no postoperative deaths, the postoperative complication rates were similar for both groups. Ulcerations recurred in 12% of the vagotomy-pyloroplasty group and in 3% of the vagotomy-hemigastrectomy group (P less than .05). Independent analyses of recurrence were performed for young patients, for alcoholics, and for patients who had obstructions or were bleeding preoperatively. Recurrence rates in these special populations were not found to be significantly different. Eight percent of the vagotomy-pyloroplasty group required reoperations for recurrent ulceration; only 2% of the vagotomy-hemigastrectomy group required reoperation. Postoperative dumping symptoms were significantly more frequent in the vagotomy hemigastrectomy group. Postoperative diarrhea was also more frequent and more severe in the vagotomy-hemigastrectomy group.

Adult↗

Subpopulations of circulating B cells and regulatory T cells involved in in vitro immunoglobulin E production in atopic patients with elevted serum immunoglobulin E.

The B lymphocyte subpopulations producing immunoglobulin (Ig)E and the regulatory T cells modulating this IgE production in normals, and in atopic patients with respiratory allergy, atopic dermatitis, and markedly elevated serum IgE levels (>5,000 ng/ml), were investigated. Peripheral blood lymphocytes (PBL) were separated into T and B cell fractions and the ability of B cells to produce IgE in the presence or absence of pokeweed mitogen (PWM) and/or T cells ws determined. The patients had a circulating population of cells which spontaneously produced up to 6 ng of IgE in vitro (per 4 X 10(5) non-E-rosetting cells) in the absence of T lymphocytes and PWM. PBL from normals did not possess such cells. This IgE synthesis occurred primarily (>75%) over the first 72 h of culture. There was a wide range in their activity between patients and from the same patient studied on repeated occasions (from <300 to 6,000 pg per culture). This spontaneous IgE production was inhibited by PWM (mean inhibition, 37%) or normal T lymphocytes (mean inhibition, 42%). The patients lacked T lymphocytes capable of inhibiting this spontaneous IgE synthesis in 7 of 13 experiments. Functionally distinct B cells were identified in the patients and normals that responded to PWM with IgE production in vitro and required T-helper cell activity. Patients had normal PWM-responsive B cell IgE biosynthetic activity and T-helper function for these B cells. Suppressor T cell activity for PWM-driven IgE synthesis was also evaluated. Both the normals' and the patients' T lymphocytes provided similar levels of T cell suppressor function for PWM-driven IgE production. Patients with elevated serum IgE possessed these inhibitory T cells at times when the T lymphocytes which suppressed spontaneous igE production were absent from their PBL.

Adult↗