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Biomedical subjects

G Burke

Publications and source records attributed to G Burke.

At least 145 records · Page 8Linked to original sources
PubMed1988

Decreases in mortality on a large urban medical service by facilitating access to critical care. An alternative to rationing.

The admission and case fatality rate (CFR) on a large urban medical service for 12 months before and after the creation of an intermediate care unit were examined. In the year after the intermediate care unit was opened, total admissions to the ICU/CCU decreased by 7.1% as a result of a 14.6% decrease in admission of low-risk patients who did not require critical care services. The CFR of patients on the medical service decreased by 13.3% in the year after implementation of the intermediate care unit. The decrease in mortality was accounted for by a 25.0% decrease in general ward deaths and a 38.8% decrease in ward cardiac arrests. There was no significant difference in the ICU/CCU CFR. The admission of low-risk patients to an intermediate care unit provided greater access to intensive care and was associated with an overall lower medical service CFR.

Chicago↗
PubMed1987

The effects of polyamine antimetabolites on polyamine-responsive casein kinase activity.

The effects of two inhibitors of ornithine decarboxylase activity, alpha-difluoromethylornithine (DMFO) and (2R,5R) 6-heptyne-2,5 diamine (HDA), and an inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis-guanylhydrazone (MGBG), were tested on casein kinase activity and endogenous phosphorylation in the cytosol fractions of mouse thyroid and a rat prostate tumor model, Dunning R 3327 MAT LyLu subline. When tested at 5 mM, spermine, DMFO, HDA, and MGBG stimulated mouse thyroid casein kinase activity by 230%, 14%, 65% and 106%, respectively. Similar responses were observed in prostate tumor cytosol. In mouse thyroid cytosol, spermine stimulates 32P incorporation primarily into 3 proteins (MW: 107, 88, and 56 kDa). At 5 mM, MGBG partially reproduces the effects of spermine; HDA is less effective and DMFO is without effect. Similar effects were observed on 3 proteins in prostate tumor cytosol with molecular weights of 91, 41, and 32 kDa. These data provide additional support for the hypothesis that the observed synergistic inhibitory effect of DMFO and MGBG on cell growth may not be due solely to the inhibition of polyamine biosynthesis. Our findings suggest that MGBG-mediated reduction in the phosphorylation of casein kinase substrate should be considered as one locus of action.

Adenocarcinoma↗
PubMed1987

Treatment of recurrent colonic pseudo-obstruction by endoscopic placement of a fenestrated overtube. Report of a case.

The case of a 73-year-old man who developed acute colonic pseudo-obstruction (Ogilvie's syndrome) following chemotherapy for lymphoma is reported. Cecal dilatation resolved after a single colonoscopic decompression. Following his next course of chemotherapy, colonic dilatation again developed. The recurrence was treated successfully by introducing a fenestrated colonoscopic overtube transanally for continuous decompression. The literature concerning acute, colonic pseudo-obstruction is reviewed. The colonoscopic overtube is a convenient and effective treatment for recurrent colonic distention.

Acute Disease↗
PubMed1987

Perforation of the terminal ileum with cytomegalovirus vasculitis and Kaposi's sarcoma in a patient with acquired immunodeficiency syndrome.

This case report documents a perforation of the terminal ileum in a 40-year-old white male homosexual with the acquired immunodeficiency syndrome. The perforation occurred at a site that had severe cytomegalovirus infection and was in close proximity to multiple nodules of Kaposi's sarcoma. The ileum showed multiple deep ulcers with large numbers of cytomegalovirus inclusions and vasculitis with infected endothelial cells, small-vessel thrombosis, focal disruption, and hemorrhage. We review the evidence that cytomegalovirus infection--and not Kaposi's sarcoma--was responsible for this perforation and, in light of the new medical therapy for such infections, should be regarded as an important cause of gastrointestinal perforation in patients with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Calcium-activated, calmodulin-dependent protein kinase activity in bovine thyroid cytosol.

Bovine thyroid 100,000 X g supernatant contained calcium-activated, calmodulin-dependent protein kinase (PK-CaM) activity. The PK-CaM was partially purified using ion-exchange chromatography and characterized. PK-CaM, using casein as exogenous substrate, was not stimulated by Ca2+(0-500 microM) or calmodulin (1-10 micrograms) by themselves, but was stimulated by the combination of the two by 100%. The activation of the enzyme by Ca2+ and calmodulin was dose-dependent with maximal stimulation evident at 1 microM free-Ca2+ and 3 micrograms calmodulin. Both chlorpromazine and trifluoperazine inhibited the thyroid enzyme in a dose-related manner. The molecular weight (MW) of the PK-CaM, based on gel filtration, was approximately 500,000. PK-CaM could also be demonstrated using endogenous thyroid cytosol proteins as substrate. Separation of these 32P-labelled proteins by SDS-PAGE and subsequent autoradiography revealed that one major protein of approximately 56,000 MW was phosphorylated by PK-CaM. In some experiments, a second, less-intense protein band of approximately 64,000 MW was also phosphorylated. Evidence is presented, suggesting that these two protein bands may result from the autophosphorylation of the PK-CaM holoenzyme. These results offer a molecular mechanism, in addition to protein kinase C, by which Ca2+ effects may be mediated in thyroid.

Animals↗
PubMed1986

The structure of the wall of the rat intraacinar pulmonary artery: an electron microscopic study of microdissected preparations.

Rat intraacinar arterial segments that by light microscopy lack a medial muscle layer are capable of constriction and, during pulmonary hypertension, acquire morphologically differentiated smooth muscle. These facts suggest that effector cells of smooth muscle type are present in the normal vessel wall. Studies in the literature, however, fail to agree on their location or even existence. By combining microdissection, step sectioning, and electron microscopy, we have now performed a serial study of six arterial pathways. At its proximal end, the artery has a circumferentially continuous single layer of smooth muscle cells, separated from the endothelium by a fenestrated internal elastic lamina. Myoendothelial junctions are frequent and incorporate basal laminae of both cell types. More distally, the internal elastic lamina is discontinuous and the smooth muscle cells lose myofilaments and dense bodies so as to resemble intermediate cells. They still form a continuous layer, however. At mid-alveolar-duct level, this layer is discontinuous, and in the most distal arteries investigated, the cells are often solitary. They lie close to the endothelial cell, but, except for localized regions of contact, are separated from it by a single basal lamina that is continuous with one covering their abluminal surface.

Animals↗
PubMed1986

Costs in the ICU.

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Costs and Cost Analysis↗
PubMed1985

Polyamines stimulate endogenous protein phosphorylation in thyroid cytosol.

The polyamine, spermine (1-5 mM), when added to rat thyroid cytosol, increases the phosphorylation of a 107 kDa protein 4-fold as analyzed by sodium dodecyl sulfate polyacrylamide gradient gel electrophoresis (SDS-PAGE) and autoradiography; spermidine was less effective and putrescine was without effect. Sodium chloride, when tested at equivalent ionic strengths (4-40 mM), did not reproduce the effects of spermine. In addition to stimulating the phosphorylation of a 107 kDa protein, spermine had an apparent biphasic effect on the phosphorylation of 88 and 65 kDa proteins; maximum stimulation of approximately 60-70% was observed at 0.5-2 mM. Both basal and spermine-stimulated protein phosphorylation patterns were identical whether [gamma-32P] ATP or [gamma-32P] GTP was used as phosphate donors. Heparin (1 microgram/ml) reduced spermine-stimulated phosphorylation of the 107 kDa protein by 64%. Phosphorylation of a 107 kDa protein was not restricted to rat thyroid as spermine was found to augment the phosphorylation of 107 kDa protein(s) in mouse and beef thyroid cytosol preparations.

Animals↗
PubMed1985

Diacylglycerol-activated, calcium/phospholipid-dependent protein kinase (protein kinase C) activity in bovine thyroid.

Bovine thyroid 100,000 X g supernatant contained diacylglycerol-activated, calcium/phospholipid-dependent protein kinase (protein kinase C). The protein kinase C was partially purified using ion-exchange chromatography and characterized. Substrate specificity studies revealed that the enzyme was most active when histone F1 was used as substrate. The thyroid protein kinase C was not stimulated by Ca2+ or phosphatidylserine (PS), but was stimulated by the combination of the two by 570%. Diolein stimulated the kinase by increasing its sensitivity to Ca2+. Other phospholipids could not substitute for PS and were ineffective in stimulating the protein kinase C in the absence of diolein. However, in the presence of diolein some of the other phospholipids were stimulatory albeit not to the extent of PS. Quercitin, a protein kinase C inhibitor in other systems, inhibited the thyroid enzyme in a dose-related manner. Protein kinase C could also be demonstrated using endogenous thyroid proteins as substrate. Separation of these 32P-labelled proteins by electrophoresis and subsequent autoradiography revealed that three proteins were phosphorylated by the protein kinase C of approximate molecular weights 60,000, 45,000, and less than 29,000. These results offer a possible mechanism by which Ca2+ and/or diacylglycerol effects may be mediated in thyroid.

Animals↗
PubMed1985

Forskolin and 12-0-tetradecanoylphorbol-13-acetate mimic thyrotropin-stimulated protein iodination in mouse thyroid.

In the present study, the capacity of the diterpene, forskolin, and the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA), to stimulate protein iodination in freshly dispersed mouse thyroid open follicles was assessed. Although both agents stimulated 125I incorporation into TCA precipitable material, dose response curves (0.1 - 25 microM) showed that maximal concentrations of either agonist alone failed to reproduce the stimulatory effect of a maximal concentration of thyrotropin (TSH; 50 mU/ml). When a maximal concentration of forskolin (20 microM) and TPA (10 microM) were added in combination, the stimulatory effect was additive and mimicked the effect of TSH. TPA had no significant effect on either basal or forskolin-stimulated cyclic-AMP production. We conclude that the regulation of protein iodination by TSH may involve both the adenylate cyclase-cyclic-AMP-dependent protein kinase system and the diacylglycerol-activated calcium/phospholipid-dependent protein kinase C pathway.

Adenylyl Cyclases↗
PubMed1985

Differential effects of polyamines on rat thyroid protein kinase activities.

Ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis, has been shown to be regulated in thyroid by thyrotropin both in vivo and in vitro. Little, however, is known of the role of polyamines in thyroid cell function. Since studies in other tissues suggest that polyamines may influence protein phosphorylation, we studied the effect of the polyamines on various protein kinase activities in rat thyroid. Putrescine, spermidine, and spermine inhibit cyclic-AMP-dependent histone H1 kinase activity when measured in the cytosol fraction of rat thyroid; this effect is largely reproduced by NaCl concentrations of equivalent ionic strength. Both spermidine and spermine effect a 1.6-2.4-fold increase in cytosolic cyclic-AMP-independent (messenger-independent) casein kinase activity; stimulation by both polyamines is maximal at 5mM. A similar profile of stimulation is observed for messenger-independent casein kinase activity in crude nuclear preparations. Sodium chloride fails to stimulate both cytosolic and nuclear messenger-independent casein kinase activities at ionic strength equivalent to the spermine concentrations used. Spermine, but not putrescine, spermidine, or sodium chloride, inhibits calcium/phospholipid-dependent protein kinase C activity in cytosol extracts partially purified by DEAE chromatography. These findings suggest that regulation of protein kinase(s) by polyamines may represent a proximal locus (i) of action of thyrotropin-regulated ornithine decarboxylase activity in thyroid.

Animals↗
PubMed1984

RHC 80267 inhibits thyrotropin-stimulated prostaglandin release from rat thyroid lobes.

In the present report, we studied the effect of the diglyceride (DG) lipase inhibitor, RHC 80267 on basal and thyrotropin (TSH)-stimulated prostaglandin (PG) release from rat thyroid lobes Further, we tested the effect of RHC 80267 on phosphatidylinositol phospholipase C (PIPLC), DG lipase, and arachidonate cyclo-oxygenase activities in rat thyroid cytosol, plasma membrane, and whole homogenate preparations, respectively. Whereas RHC 80267 inhibited DG lipase activity in a dose-related manner from 0.5-10 microns (17-80% inhibition), it failed to inhibit either PIPLC or arachidonate cyclo-oxygenase activities by more than 9% when tested at 5 and 10 microns (n = 3). RHC 80267 reduced TSH-stimulated 6-keto-PGF1alpha and PGF2alpha release by 100 +/- 14% and 57 +/- 12%, respectively (means + S.E.; p less than 0.01 for both; n = 10-12); the diglyceride lipase inhibitor did not reduce basal release of either PG. These data provide additional evidence which implicate a PIPLC-DG lipase pathway in TSH-stimulated PG synthesis in thyroid.

Animals↗
PubMed1983

Effects of proteolytic enzymes and protease inhibitors on bovine thyroid adenylate cyclase activity.

Trypsin, chymotrypsin, and papain stimulate basal adenylate cyclase activity in bovine thyroid plasma membranes in a dose-related, albeit biphasic, fashion. Each of the proteases enhanced TSH-stimulated adenylate cyclase activity over basal activity. The proteases also enhanced GTP-, guanosine 5'-(beta, gamma-imidotriphosphate)-, prostaglandin E1-, and cholera toxin-stimulated adenylate cyclase to varying degrees. Fluoride-stimulated activity was enhanced by chymotrypsin and papain, but not by trypsin. When Mn++ was substituted for Mg++ in the adenylate cyclase assay, no stimulation by the proteases were observed. To see if endogenous membrane proteases are required for optimal thyroid adenylate cyclase response to TSH and other stimulators, studies were performed using the protease inhibitors tosylamide 2-phenylethyl-chloromethyl ketone (TPCK) and p-tosyl-L-arginine methyl ester (TAME), inhibitors of chymotrypsin and trypsin, respectively. TPCK (0.15 mM) had no effect on basal adenylate cyclase activity, but did inhibit TSH-, trypsin-, and chymotrypsin-stimulated activities by approximately 90%. Guanosine 5'-(beta, gamma-imido) triphosphate- as well as cholera toxin-stimulated activities were inhibited by approximately 50%, whereas prostaglandin E1- and fluoride-stimulated activities were inhibited by approximately 25%. TAME (6 mM) produced similar results, except that no effect on fluoride activity was seen, while basal activity was inhibited by approximately 20%. Thus, various serine proteases augment both basal and hormone-stimulated adenylate cyclase in bovine thyroid. Since both trypsin- and chymotrypsin-stimulated as well as TSH-induced enzyme activities were inhibited by TPCK and TAME, it would appear that augmentation of thyroid adenylate cyclase activity may, in part, result from stimulation of endogenous proteases.

Adenylyl Cyclases↗