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R Coleman

Publications and source records attributed to R Coleman.

At least 181 records · Page 10Linked to original sources
PubMed1994

Effect of oxidative stress and disruption of Ca2+ homeostasis on hepatocyte canalicular function in vitro.

Isolated rat hepatocyte couplets were used to study the effects of menadione and a rise in the intracellular concentration of calcium on biliary canalicular function. Canalicular function was assessed by counting the percentage of couplets which were able to accumulate the fluorescent cholephile, cholyl lysyl fluorescein (CLF) into the canalicular vacuole between the two cells. Menadione induced a concentration-dependent inhibition of the canalicular vacuole accumulation (CVA) of CLF reaching 7.6 +/- 1.8% of control at 100 microM menadione. This disruption was not prevented by blocking receptor-operated calcium channels with Ni2+ (300 microM). The concentration range of menadione used did not deplete cellular ATP content. In contrast glutathione content was reduced to 52% of its control value by 100 microM menadione. A rise in cytosolic calcium induced by the calcium ionophore, A23187 (up to 30 microM) also disrupted CVA in a concentration-dependent manner. Release of endoplasmic reticulum calcium stores by thapsigargin (50 nM) affected the retention of canalicular contents to a much lesser extent, although it was able to stimulate a reduction in canalicular area to 40% of its original value, assumed to be due to canalicular contraction. Menadione (30 and 100 microM) reduced the fluorescence of phalloidin-FITC-labelled F-actin in both the total and pericanalicular cytoskeleton. Canalicular function was therefore disrupted by non-lethal concentrations of menadione via a mechanism which does not appear to involve ATP depletion or the entry of extracellular calcium, but is associated with a depletion of both cellular glutathione and F-actin. An increase in the concentration of intracellular calcium can stimulate canalicular contraction, and at relatively high concentrations calcium can also disrupt canalicular function.

Actins↗
PubMed1994

Atopic children with cystic fibrosis have increased urinary leukotriene E4 concentrations and more severe pulmonary disease.

BACKGROUND: We investigated the hypothesis that cysteinyl leukotriene (LT) production is altered in atopic patients with cystic fibrosis (CF). METHODS: Urinary LTE4 was measured in two groups of children with CF: atopic (ACF group, n = 22) and nonatopic (NACF group, n = 13); and in two groups of unaffected children, those with atopic asthma (AA group, n = 11) and nonatopic normal control subjects (NN group, n = 12). RESULTS: Atopic groups excreted significantly more urinary LTE4 (geometric means [95% confidence intervals] in picomoles per millimole creatinine), ACF group: 104 (73-147) and AA group: 195 (136-282) compared with NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF group had significantly more airflow obstruction than the NACF group, with forced expiratory volume in 1 second (percent predicted, mean +/- SD) in ACF: 58 +/- 21 versus NACF: 81 +/- 23, and forced vital capacity (percent predicted, mean +/- SD) 72 +/- 17 versus 87 +/- 23, respectively. There were significant correlations between the degree of airflow obstruction, bronchodilator responsiveness, and urinary LTE4 concentration within the entire CF group. We used multiple regression analysis to assess the respective influence of age, atopy, sensitization to Aspergillus fumigatus, and colonization with Pseudomonas aeruginosa on urinary LTE4 concentration. The atopic state was the only significant variable associated with urinary LTE4 production in subjects with CF. CONCLUSIONS: The similarities in urinary LTE4 between ACF and AA groups suggest that the atopic state is the prime determinant of urinary LTE4 excretion. Enhanced cysteinyl LT production associated with atopy in CF may increase the severity of pulmonary disease.

Adolescent↗
PubMed1994

Phase II study of liposomal muramyl tripeptide phosphatidylethanolamine (MTP/PE) in advanced soft tissue sarcomas of the adult. An EORTC Soft Tissue and Bone Sarcoma Group study.

The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with intravenous muramyl tripeptide phosphatidylethanolamine (MTP/PE) at a dose of 4 mg once weekly in 20 patients with metastatic soft tissue sarcomas. Responses were not seen in 19 evaluable patients. Toxicity consisted mainly of a mild flu-like syndrome after 62% of drug administrations. It is concluded that MTP/PE at this dose and schedule has no activity in metastatic soft tissue sarcoma.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Fluorescent choleretic and cholestatic bile salts take different paths across the hepatocyte: transcytosis of glycolithocholate leads to an extensive redistribution of annexin II.

We have used fluorescent derivatives of the choleretic bile salts cholate and chenodeoxycholate, the cholestatic salt lithocholate, and the therapeutic agent ursodeoxycholate to visualize distinct routes of transport across the hepatocyte and delivery to the canalicular vacuole of isolated hepatocyte couplets. The cholate and chenodeoxycholate derivatives produced homogeneous intracellular fluorescence and were rapidly transported to the vacuole, while the lithocholate analogue accumulated more slowly in the canalicular vacuole and gave rise to punctate fluorescence within the cell. Fluorescent ursodeoxycholate showed punctate intracellular fluorescence against a high uniform background indicating use of both pathways. Inhibition of vesicular transport by treatment with colchicine and Brefeldin A had no effect on the uptake of any of the compounds used, but it dramatically impaired delivery of both the lithocholate and the ursodeoxycholate derivatives to the canalicular vacuole. We conclude that while the chenodeoxycholate and cholate analogues traverse the hepatocyte by a cytoplasmic route, lithocholate and ursodeoxycholate analogues are transported by vesicle-mediated transcytosis. Treatment of couplets with glycine derivatives of lithocholate and ursodeoxycholate, but not cholate or chenodeoxycholate, led to a marked relocalization of annexin II, which initially became concentrated at the basolateral membrane, then moved to a perinuclear distribution and finally to the apical membrane as the incubation progressed. This suggests that lithocholate and ursodeoxycholate treatment leads to a rapid induction of transcytosis and that annexin II exchange occurs upon membrane fusion at all stages of the hepatocyte transcytotic pathway. These results indicate that isolated hepatocyte couplets may provide an inducible model system for the study of vesicle-mediated transcytosis.

Actins↗
PubMed1994

Modulation of phenobarbitone-induced loss of gap junctional intercellular communication in hepatocyte couplets.

Phenobarbitone (PB) produced a dose- and time-dependent decrease in gap junctional intercellular communication (GJIC) (up to 25.0 +/- 5.3% inhibition) in rat hepatocyte couplets (4 h cultures). The effect was reversible and independent of protein synthesis. This inhibition was exacerbated (to 53.3 +/- 5.4% inhibition) by depletion of intracellular glutathione following pretreatment with diethylmaleate (0.5 microM, 15 min). Inhibition was also significantly enhanced by addition of the cytochrome P450 inhibitors SKF 525A (25 microM) and metyrapone (20 nM). In contrast, hepatocyte couplets derived from rats pretreated with PB (0.1% w/v in drinking water) for up to 28 days were fully functional regarding GJIC and were found to be refractory to the effects of PB added in vitro. This, coupled with the lack of effect of p-hydroxy-PB, suggests that an active metabolite of PB is not involved in the inhibition of GJIC which may, instead, be through an oxidative stress, which is prevented by glutathione.

Animals↗
PubMed1994

Effects of purified perforin and granzyme A from cytotoxic T lymphocytes on guinea pig ventricular myocytes.

OBJECTIVE: Involvement of cytotoxic T lymphocytes (CTL) in heart transplant rejection as well as in viral myocarditis is well established, but the precise mechanisms whereby infiltrating CTL damage the myocardium are unknown. The aim of the study was to investigate how CTL derived perforin, the serine protease granzyme A, and the combination of both, damage guinea pig ventricular myocytes. METHODS: Action potentials and membrane currents were recorded by means of the whole cell configuration from guinea pig ventricular myocytes. RESULTS: Resembling the effects of CTL derived lytic granules, perforin caused gradual myocyte shortening and contracture, leading to complete loss of the rod shaped morphology and to cell destruction. These changes were preceded by shortening of action potential duration and reduction of resting potential and action potential amplitude, followed by complete inexcitability. Granzyme A alone was ineffective, but accelerated the deleterious effects of perforin on the morphological and electrophysiological properties of myocytes. The effects of perforin were further evaluated by measuring membrane currents by means of the whole cell voltage clamp. Perforin induced discrete changes in membrane current, reminiscent of single ion channels, with large conductance and open time of up to several seconds. Linear regression analysis of the channel I-V relations resulted in a conductance of 890 pS and a reversal potential of -7.6 mV. These results suggest that perforin induces large non-selective channels, which can account for most of the observed adverse effects. CONCLUSIONS: As CTL participate in the immunological rejection of the transplanted heart, it is conceivable, but remains to be shown, that part of this damage is inflicted by perforin containing lytic granules.

Action Potentials↗
PubMed1994

Treatment of posterior circulation aneurysms using platinum coils.

In this case example it was determined that midbrain ischemia and hyponatremia caused a decreased level of consciousness and inappropriate behavior in this patient. As serum sodium levels corrected and the collateral circulation improved, her level of consciousness increased accordingly. Despite her rocky clinical course, GDCs proved to be a viable alternative to surgery. The GDCs successfully obliterated her aneurysm and she fully recovered. Basilar tip aneurysms have a significant risk associated with location and the possibility of aneurysmal rupture. Surgical intervention is difficult, furthering coil embolization as a reasonable alternative treatment in some cases. Quality care of these patients focuses on diligent neurological assessment, comfort strategies and patient and family education. Management of this population requires close assessment and early intervention to achieve expected outcomes.

Basilar Artery↗
PubMed1994

Hairy elbows syndrome (familial hypertrichosis cubiti).

Hairy elbows syndrome was first described by Beighton in 1970. An association with short stature has been suggested. A 5-year-old girl with the hairy elbows syndrome who is otherwise healthy is described. Her height is on the 25th centile and appropriate for her family, in which no other members are affected. The mode of inheritance of this disorder remains to be determined.

Body Height↗
PubMed1994

Waxy keratoses of childhood.

Three cases of waxy keratoses of childhood occurring in two families are described. The disorder seen in these three cases appears to be clinically and histopathologically distinct from previously described familial disorders of keratinization, which also feature multiple discrete papules.

Child↗
PubMed1993

Periportal- and perivenous-enriched hepatocyte couplets: differences in canalicular activity and in response to oxidative stress.

Unlike isolated single hepatocytes, hepatocyte couplets retain their apical polarity, and, during short-term culture form an enclosed canalicular space or vacuole between the two adjacent cells into which biliary secretion is initiated. Hepatocyte couplets were prepared after partial collagenase perfusion of rat liver. Centrifugal elutriation was used to fractionate the preparation into six couplet-containing suspensions. Image analysis was used to determine the size of cultured couplets. The size of the couplets ranged from 34.1 +/- 0.76 microns and 684 +/- 24.1 microns 2 (mean length and area respectively +/- S.E.M.) in Fraction 2, to 43.7 +/- 0.57 microns and 1033 +/- 33.8 microns 2 length and area respectively in Fraction 7. Glutamine synthetase activity was assessed in each freshly eluted fraction and was shown to be predominant in Fractions 6 and 7. Pretreatment of rats with CCl4, which selectively destroys perivenous hepatocytes, decreased the proportion of couplets in these fractions by over 67%, and their glutamine synthetase activity by over 97%. It was concluded that Fractions 2 and 3 contained predominantly couplets of Zone 1 (periportal) origin, Fractions 4 and 5 those from Zone 2, and Fractions 6 and 7 predominantly couplets of Zone 3 (perivenous) origin. The development of canalicular secretory activity was assessed in the couplets after a 15 min incubation with a fluorescent bile acid, cholyl-lysyl-fluorescein (CLF). This was sigmoidal in all fractions, but slower in the periportal couplets, taking 5.1 h for 50% to show secretory activity in Fraction 2, compared with 2.7 h for Fraction 7. Incubation of hepatocyte couplets with 1 or 10 microM taurodehydrocholate, a non-toxic bile acid analogue, did not influence the rate of development of accumulation of CLF by the couplets or the area of the canalicular vacuole in any fraction. However, it did decrease the CLF content of couplets incubated with CLF for 15 min to a greater extent in those of perivenous origin. After subjecting the couplets to oxidative stress by incubation with 20 microM menadione (2-methyl-1,4-naphthoquinone), it was evident that periportal couplets were less able to maintain canalicular secretory activity than perivenous couplets.

Animals↗
PubMed1993

Chromosome 11q13 and atopy underlying atopic eczema.

Genetic linkage has been reported between atopic respiratory disease and chromosome site 11q13. We recruited 95 multiplex families through probands with active atopic eczema. Linkage analyses between atopy and markers on 11q13 excluded a major susceptibility locus for atopy in this region. Nor was there significant deviation from the expected proportions of alleles shared by affected sib-pairs. When we analysed families according to parental atopic phenotype, we observed a positive lod score (0.8) in 19 families with unaffected fathers, in contrast to markedly negative scores for other combinations of affected parental phenotype. The possibility of a maternal influence on the inheritance of atopy cannot, therefore, be excluded.

Adult↗
PubMed1993

Effect of diosgenin on biliary cholesterol transport in the rat.

Biliary cholesterol output in rats was stimulated over 3-fold by feeding diosgenin for 5 days, whereas biliary outputs of phospholipid and bile salts were not changed by diosgenin feeding. Isolating and perfusing the liver without bile salts resulted in a rapid and substantial decrease in biliary bile salt output; bile salt depletion abolished the diosgenin-induced increment in biliary cholesterol output, showing that the diosgenin-elevated biliary cholesterol output was bile-salt-dependent. Diosgenin treatment also produced a significant decrease in biliary alkaline phosphodiesterase I. Fresh bile obtained from control and diosgenin-fed rats was subjected to gel-permeation chromatography in order to separate different-sized biliary cholesterol carriers. Two major peaks of cholesterol were eluted, with cholesterol also being eluted between the peaks. The cholesterol peak eluted at the lower molecular mass (20-30 kDa) was observed in all bile samples. The higher-molecular-mass peak, which was eluted at the void volume, was not observed in all biles; control biles contained very little high-molecular-mass form of cholesterol, whereas biles from the diosgenin group contained up to 47% of cholesterol in the high-molecular-mass fraction. Diosgenin treatment produced a range of elevated biliary cholesterol values which positively correlated with the proportion of cholesterol contained in the high-molecular-mass fraction (r = 0.98). The results show that diosgenin induced a marked bile-salt-dependent increase in biliary cholesterol output and a shift in biliary cholesterol transport to higher-molecular-mass structures.

Animals↗