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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 289 records · Page 16Linked to original sources
PubMed1984

Rapid kinetic analysis of the bile-salt-dependent secretion of phospholipid, cholesterol and a plasma-membrane enzyme into bile.

Isolated rat livers were perfused under 'one-pass' conditions and bile was collected at 1 min intervals. After 1 min pulse, taurocholate appeared in the collected bile within 2 min, peak output occurring 2 min later. In contrast, the increased output of phospholipids and cholesterol was slower, peak output occurring 6-11 min after the original pulse of taurocholate. These results suggest that mixed micelles cannot be formed inside the cell or during passage of bile salts through the membrane, since bile salt and lipids should then parallel each other. The bile salts must therefore be pumped into the lumen and the lipids added subsequently, due to the actions of the bile salts in the canalicular lumen. It is suggested that the biliary lipid is obtained from microdomains of biliary-type lipid in the canaliculus membrane, which are vesiculated and solubilized by the action of bile salts. It is also suggested that this biliary-type lipid is brought continuously to the membrane via vesicle traffic; this traffic is increased during increased bile-salt output, and is a process that can be inhibited by colchicine.

Animals↗
PubMed1984

The effects of colchicine on secretion into bile of bile salts, phospholipids, cholesterol and plasma membrane enzymes: bile salts are secreted unaccompanied by phospholipids and cholesterol.

Colchicine, a drug which interferes with microtubular function, has no effect on the secretion of taurodehydrocholate into bile; it is therefore suggested that bile salts are unlikely to be packaged in vesicles during cellular transit from sinusoidal to canalicular membranes. Colchicine greatly reduces the secretion of phospholipid and cholesterol into bile; it is suggested that this is due to an interruption in the supply of vesicles bringing lipids to repair the canalicular membrane during bile salt output. In the absence of the protective effect of a continuous supply of repair vesicles, micelleforming bile salts damage the canalicular membrane; the increased concentration of plasma membrane enzymes in bile and the increased aspartate aminotransferase activity in plasma and bile are evidence of this damage. Damage to the canalicular membrane may also be an explanation for the reduction in taurocholate transport and the taurocholate-induced cholestasis which are seen with colchicine-treated livers. Such membrane damage is not observed in colchicine-treated livers during the secretion of the non-micelle forming bile salt, taurodehydrocholate.

Animals↗
PubMed1983

Abnormal secretion of proteins into bile from colchicine-treated isolated perfused rat livers.

The microtubule poison, colchicine, caused an abnormal output of a variety of proteins into rat bile. After 3 h of exposure to the drug, livers were isolated and perfused with media of defined protein composition. There was no essential change in permeability of the hepatobiliary system to proteins (e.g. bovine serum albumin) entering bile from the perfusion fluid. The rat (serum) albumin and fibrinogen that were secreted into bile from colchicine-treated livers were probably derived from the hepatocytes. Disruption of the microtubular system reduces the secretion of proteins at the sinusoidal face of the hepatocyte and results in an accumulation of secretory vesicles in the cytoplasm. It is suggested that under these conditions some of the vesicles discharge their contents into the bile canaliculus.

Animals↗
PubMed1983

Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers.

Isolated perfused rat livers were used to study the effects of taurochenodeoxycholate (TCDC) and tauroursodeoxycholate (TUDC) upon some aspects of biliary composition. After depletion of the endogenous bile salt pool of the liver, introduction of either bile salt brought about increases in bile flow, bile salt output and biliary phospholipid output. Taurochenodeoxycholate needed a lower biliary concentration to produce phospholipid output than did tauroursodeoxycholate. TCDC perfusion caused a substantial output of plasma-membrane enzymes (5'-nucleotidase and alkaline phosphodiesterase) into the bile, whereas TUDC caused little output of either enzyme; this may represent a characteristic difference between the effects of the two bile salts on the hepatobiliary system. The results from TUDC perfusion indicate also that much of the output of biliary phospholipid promoted by bile salts, may be independent of the output of plasma-membrane enzymes promoted by bile salts.

5'-Nucleotidase↗
PubMed1983

Biliary protein output by isolated perfused rat livers. Effects of bile salts.

The output of proteins into bile was studied by using isolated perfused rat livers. Replacement of rat blood with defined perfusion media deprived the liver of rat serum proteins (albumin, immunoglobulin A) and resulted in a rapid decline in the amounts of these proteins in bile. When bovine serum albumin was incorporated into the perfusion medium it appeared in bile within 20 min and the amount in the bile was determined by the concentration of the protein in the perfusion medium. The use of a defined perfusion medium also deprived the livers of bile salts and the amounts of these, and of plasma-membrane enzymes [5'-nucleotidase (EC 3.1.3.5) and phosphodiesterase I], in bile declined rapidly. Introduction of micelle-forming bile salts (taurocholate or glycodeoxycholate) to the perfusion medium 80 min after liver isolation markedly increased the output of plasma-membrane enzymes but had no effect on the other proteins. The magnitude of this response was dependent on the bile salt used and its concentration in bile; there was little effect on plasma-membrane enzyme output until the critical micellar concentration of the bile salt had been exceeded in the bile. A bile salt analogue, taurodehydrocholate, which does not form micelles, did not produce the enhanced output of plasma-membrane enzymes. This work supports the view that the output of plasma-membrane enzymes in bile is a consequence of bile salt output and also provides evidence for mechanisms by which serum proteins enter the bile.

5'-Nucleotidase↗
PubMed1983

Ventilatory status early after head injury.

The ventilatory status of patients within the first few hours following head injury has not been well established. We prospectively studied 63 patients who presented to an urban trauma center with varying severity of head injury to determine whether any trend toward hypo- or hyperventilation existed within the first two hours following injury. Arterial blood gas analysis done on emergency presentation showed that 14 patients with severe head injury (Glasgow coma scale less than or equal to 4) had mean pH values of 7.29 and mean PaCO2 of 41.86 torr. Twenty patients categorized as moderate head injury (GCS = 5-11) had mean pH values of 7.38 with a mean PaCO2 of 34.1 torr. Twenty-nine patients with GCS greater than or equal to 12 had mean pH and PaCO2 values of 7.4 and 31.8 torr, respectively. These differences in pH and PaCO2 were statistically significant between the GCS groups with mild and severe head injury (P less than or equal to .01 pH), (P = .05 PCO2), and could not be explained on the basis of hypoxemia, blood alcohol level, hypotension, or associated chest injury. It is concluded that patients with severe craniocerebral trauma show an early trend toward hypercapnea and acidosis. Immediate control of airway and assisted ventilation is necessary in order to reduce PaCO2 to optimal levels in patients with severe head injury.

Adult↗
PubMed1983

Increased tight junction permeability: a possible mechanism of oestrogen cholestasis.

Ethinyl oestradiol increased rat biliary permeability for 3H-inulin and 14C-sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment (P less than 0.0005) and bilirubin after 7 days (P less than 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol-treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein (P less than 0.0005 after 3 and 7 days), bromsulphthalein-glutathione conjugate (P less than 0.005 after 3 days; P less than 0.0005 after 7 days) and phenolphthalein glucuronide (P less than 0.005 after 3 days; P less than 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen-treated rats. 'Leakiness' of canalicular tight junctions may explain the pathophysiology of oestrogen-induced cholestasis.

Animals↗
PubMed1983

Stimulation of renal prostaglandins by pressor hormones in man: comparison of prostaglandin E2 and prostacyclin (6 keto prostaglandin F1 alpha).

The effect of vasoconstrictive agonists and their nonpressor analogs on renal prostaglandin production was investigated in normal subjects maintained on constant diets. Arginine vasopressin (AVP), 10 U, desamino-d arginine vasopressin (dDAVP), 4 micrograms, angiotensin II (AII), 5 ng/kg . min, des-Asp angiotensin II (AIII), 5 ng/kg . min, norepinephrine (NE), 0.1 microgram/kg . min, and NE plus phenoxybenzamine (PHB), 0.8 mg/kg, were administered on separate days. Prostaglandin E2 (PGE2) and the stable prostacyclin metabolite, 6 keto prostaglandin F1 alpha were measured in 4-h urine collections by procedures with high resolution chromatography and RIA using highly specific antisera. AVP and dDAVP similarly reduced urine volume and increased urine osmolality. AII, AIII, NE, and NE + PHB did not alter basal urine volume, osmolality, creatinine, or electrolyte excretion. Blood pressure was similarly increased by AII and NE infusions (23 +/- 3 vs. 19 +/- 2 (SE) mm Hg). AVP and AII increased only PGE2 excretion (61 +/- 8 to 151 +/- 34 ng/4 h for AVP, and 38.7 +/- 7 to 75 +/- 19 ng/4 h for AII, P less than 0.05). The nonpressor analogs, dDAVP and AIII, had no effect on urinary prostaglandin excretion. In contrast, NE increased both PGE2 (from 38.7 +/- 7 to 74.5 +/- 12 ng/4 h, P less than 0.02) and 6 keto prostaglandin F1 alpha (from 34.6 +/- 8 to 56.1 +/- 9 ng/4 h, P less than 0.02). alpha-Blockade with PHB totally abolished the NE-induced systemic pressor and prostaglandin stimulatory effect. These data suggest that renal PGE2 and prostacyclin are not altered in parallel by vasoactive stimuli. PGE2 appears to be released in response to agents that induce renal vasoconstriction and reduced renal blood flow whereas renal prostacyclin excretion is stimulated by an adrenergic agonist via alpha-receptor activation and not vasoconstriction per se.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Effects of colchicine and vinblastine on output of proteins into bile.

The microtubule poisons colchicine and vinblastine caused a reduction in the biliary output of total protein, compared with controls, in bile-fistula rats. The various protein components of bile showed patterns of change in output differing from one another. Alkaline phosphodiesterase I, a 'plasma-membrane' enzyme, showed a decline in output during the first hour after drug administration. Immunoglobulin A output did not decline until after the first hour. In contrast with these reductions, the biliary output of (rat) plasma albumin into bile was increased. At no time was there any evidence (as measured by lactate dehydrogenase release into bile) for any cytolytic damage. These results are discussed in relation to current theories on the output of proteins into bile and the repair of the plasma membrane in the bile canaliculus.

Animals↗
PubMed1982

Fluorescence anisotropy from diphenylhexatriene in rat liver plasma membranes.

Rat livers were fractionated to obtain intracellular membrane preparations and a highly purified preparation of bile canaliculi. The fraction containing bile canaliculi was homogenized and subfractionated to give fractions representing fragments of contiguous membrane and of canalicular microvilli. The relative purity and extent of contamination of each preparation was determined. When the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene was incorporated into aliquots of each fraction at the same probe: lipid ratio and the steady-state anisotropy of its fluorescence measured, it was found that the plasma membrane preparations were much more ordered than the intracellular membrane preparations. Of the plasma membrane preparations, that containing the canalicular microvilli was the most ordered, even allowing for any contribution of contaminants. Thus the microvillus membrane of the bile canaliculus appears to be the most ordered domain of the plasma membrane of the hepatocyte. The high order in this domain may be a factor in reducing the susceptibility to bile salt damage during bile secretion, since it is this region which is exposed to high concentrations of bile salts in vivo.

Animals↗
PubMed1982

Percutaneous lung biopsy: experiences during the first 54 biopsies.

The first 54 consecutive percutaneous aspiration biopsies of pulmonary lesions of an ongoing prospective trial performed in this hospital between July 1977 and March 1980 have been evaluated. The technique was found to be safe and provided a reliable and rapid diagnosis. An overall diagnostic accuracy of 83% was achieved. In malignant lesions a correct diagnosis was made in 85% of biopsies. These results are compared with other workers using the same technique and with fiberoptic bronchoscopy and sputum cytology. Aspiration is recommended as an excellent alternative to other more established techniques, particularly in the diagnosis of the peripheral lesion.

Adult↗
PubMed1982

Circadian rhythm disturbances and sleep disorders in shift workers.

Employment which requires frequent shift rotation may lead to the development of specific sleep disorders. Delayed sleep phase (DSP) insomnia, a syndrome identified recently, can greatly impair an individual's circadian rhythm-dependent functions; it can occur when shift work disrupts normal sleep-waking schedules. Disorders of excessive daytime sleepiness, such as narcolepsy, occur in some subjects after they have been subjected to frequently rotating shifts. Understanding the problems associated with circadian rhythm disturbances and their interaction with sleep disorders is particularly important in industrial medicine; any clinician whose patients are subjected to frequent shift rotations should consider the effects of disrupted sleep-waking schedules.

Circadian Rhythm↗
PubMed1981

Enzymes and proteins in bile. Variations in output in rat cannula bile during and after depletion of the bile-salt pool.

The protein concentration in bile from several species is reported. The changes in output of protein, bile salts and several enzymes have been followed in rat bile over a 48 h cannulation period. Bile-salt concentration dropped rapidly owing to interruption of the enterohepatic circulation but the output of protein, lysosomal enzymes [acid phosphatase (EC 3.1.3.2) and beta-D-glucuronidase (EC 3.2.1.31)] and plasma-membrane enzymes [5'-nucleotidase (EC 3.1.3.5) and phosphodiesterase I (EC 3.1.4.1)] was maintained. Liver cell damage, monitored by output of lactate dehydrogenase, was very low throughout. Protein, lysosomal enzymes and plasma-membrane enzymes showed different patterns of output with time, but all showed a net increase between 12 and 24 h. The output of lysosomal and plasma-membrane enzymes was between 1 and 5% of the total liver complement over the first 24 h; if inhibition by biliary components is taken into account the output of some of these enzymes, particularly acid phosphatase, may be greater. Ultracentrifugation of bile showed that as the concentration of bile salts decreases the proportion of plasma-membrane enzymes in a sedimentable form increases. The results are discussed in relation to other studies of biliary proteins and to studies of the perturbation of membranes and cells with bile salts.

Animals↗
PubMed1981

Membrane fluidity and bile salt damage.

The lysis, by bile salts, of membranes of different fluidities was studied; it was shown that membranes of low fluidity were less readily lysed than membranes of higher fluidity. Membrane fluidity levels were controlled (i) by the use of erythrocytes, from different species, systematically differing in their lipid composition; (ii) by using each membrane at a range of temperatures; and (iii) by incorporating into the membranes the fluidizing agent, benzyl alcohol, at a range of concentrations. Membrane fluidity (and order) in each case was monitored by measuring the degree of polarization of fluorescence from the hydrophobic probe molecule, 1,6-diphenyl-1,3,5-hexatriene. The response of lytic behaviour to modulations of membrane fluidity also indicated a difference between the bile salts, glycodeoxycholate and glycocholate; the former initiates lysis close to (at or below) its critical micellar concentrations whereas the latter only causes lysis above, and often substantially above, its critical micellar concentration. In their respective ranges of lytic concentrations, both bile salts are far less effective with membranes of low fluidity. The results are discussed with regard to the features of a membrane which would be expected to be resistant to high concentrations of bile salts in vivo, i.e., the plasma membranes of the bile canaliculus and lumenal surface of biliary tract cells.

Animals↗
PubMed1981

Factors influencing vascular hyporesponsiveness to angiotensin II.

Bartter's syndrome is characterized, in part, by hyporesponsiveness to the pressor effect of exogenous angiotensin II (AII). This has been attributed to volume contraction, hypokalemia, and/or increased prostaglandin (PG) levels. In order to investigate factors responsible for a diminished response to the pressor effect of AII, rats were made hypokalemic or volume contracted and hypokalemic (VCHK) by dietary restriction. AII sensitivity was examined by determining the dose of AII required to raise the mean arterial pressure 20 mm Hg. When compared with control rats. VCHK and hypokalemic rats were significantly less sensitive to AII. VCHK rats were significantly less sensitive to AII than hypokalemic rats. Both experimental groups were similarly hypokalemic, but plasma renin activity (PRA) of VCHK only was greater than control values. In VCHK rats, acute K+ restoration partially corrected AII hyporesponsiveness, although plasma K+ increased to normal. In VCHK rats, acute volume expansion with normal saline similarly achieved only partial correction of AII hyporesponsiveness although PRA values fell to the control range. Simultaneous K+ restoration and volume expansion to VCHK rats successfully restored AII sensitivity to the control range. Dietary sodium, chloride, and potassium restriction did not increase urinary excretion to PGE2. Indomethacin (5 mg/kg, iv) given acutely to VCHK rats did not significantly after baseline hyporesponsiveness to AII. Norepinephrine vascular sensitivity was not affected by either volume contraction or hypokalemia. These data demonstrate that volume contraction and hypokalemia individually depress exogenous AII sensitivity in the rat and do so by separate and additive mechanisms. Furthermore, these mechanisms appear to be independent of PG.

Angiotensin II↗
PubMed1980

Membrane lipid composition and susceptibility to bile salt damage.

Erythrocyte membranes with low sphingomyelin : choline-containing phospholipid ratios haemolyse at low concentrations of the bile salt, glycocholate. Erythrocytes with higher sphingomyelin : choline-containing phospholipid ratios require progressively greater concentrations of the bile salt for lysis. Sublytic concentrations of glycocholate remove phospholipid and acetylcholinesterase from the membranes. Membranes with low sphingomyelin : choline-containing phospholipid ratios lose both particulate (microvesicles of distinct composition) and 'solubilized' material, the particulate form predominating. The proportion of particulate material falls with increase of the membrane sphingomyelin : choline-containing phospholipid ratio and those membranes of highest sphingomyelin : choline-containing phospholipid ratio lose material predominantly in 'solubilized' form. Sheep erythrocytes treated to increase their content of phosphatidylcholine (and thereby reduce their membrane sphingomyelin : choline-containing phospholipid ratio) become more susceptible to lysis by glycocholate. These observations indicate a correlation between membrane lipid composition and the perturbation of membranes with bile salt; they also point to possible features of membranes capable of surviving exposure to the high bile salt concentrations of the biliary tract.

Animals↗
PubMed1980

Effects of bile salts on the plasma membranes of isolated rat hepatocytes.

The conjugated trihydroxy bile salts glycocholate and taurocholate removed approx. 20--30% of the plasma-membrane enzymes 5'-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I from isolated hepatocytes before the onset of lysis, as judged by release of the cytosolic enzyme lactate dehydrogenase. The conjugated dihydroxy bile salt glycodeoxycholate similarly removed 10--20% of the 5'-nucleotidase and alkaline phosphatase activities, but not alkaline phosphodiesterase activity; this bile salt caused lysis of hepatocytes at approx. 10-fold lower concentrations (1.5--2.0mM) than either glycocholate or taurocholate (12--16mM). At low concentrations (7 mM), glycocholate released these enzymes in a predominantly particulate form, whereas at higher concentrations (15 mM) glycocholate further released these components in a predominantly 'soluble' form. Inclusion of 1% (w/v) bovine serum albumin in the incubations had a small protective effect on the release of enzymes from hepatocytes by glycodeoxycholate, but not by glycocholate. These observations are discussed in relation to the possible role of bile salts in the origin of some biliary proteins.

Animals↗