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R Coleman

Publications and source records attributed to R Coleman.

At least 235 records · Page 13Linked to original sources
PubMed1990

Inhibitory action of cyclobutyrol on the secretion of biliary cholesterol and phospholipids.

A number of organic anions are known to decrease biliary secretion of cholesterol and phospholipid without affecting bile acid secretion. Cyclobutyrol (CB) is a choleretic agent which also inhibits biliary lipid secretion. Using isolated perfused rat liver we have studied this inhibition in relation to possible mechanisms suggested for other anions. Shortly after its administration to the isolated perfused liver, CB decreases biliary outputs of cholesterol and phospholipid, without changes in bile acid secretion, at low (450 nmol/min), high (1350 nmol/min) and nil taurocholate infusion rates. The absolute inhibition does not appear to be decreased by elevated bile acid secretion. There is a differential effect on secretion of cholesterol and phospholipid, more marked at low bile acid secretion rates. Biliary outputs of the canalicular membrane enzymes 5'-nucleotidase and alkaline phosphodiesterase I are also depressed by CB administration, but the anion does not affect the biliary output of bovine serum albumin or the output of rat serum albumin into the perfusion fluid. Since CB does not inhibit intracellular vesicular transport or apparently inhibit intracanalicular events, its effect is different from the effect of several other anions. From these studies it appears that the most likely effect of CB is exerted at the level of the canalicular membrane.

5'-Nucleotidase↗
PubMed1990

Modulation of biliary lipid secretion by forskolin and cyclic AMP analogues.

Exposure of isolated perfused rat livers to either 100 microM-forskolin, a potent activator of adenylate cyclase, or to 0.5 mM-concentrations of the cAMP analogues chlorophenylthio cAMP (CPTcAMP), dibutyryl cAMP (dbcAMP) and 8-bromo cAMP (8BrcAMP), to provoke increases in intracellular concentrations of cAMP, resulted in marked changes in bile volume and composition. Bile flow reached a peak after 10 min, before declining towards control levels, and an increase in several secretory parameters was also observed at this time. At 20 min, a substantial decrease in the output of both phospholipid and cholesterol was evident, and this suppression of secretion was maintained throughout the remainder of the experiment. The order of effectiveness of the cAMP-elevating agents at decreasing biliary lipid output was CPTcAMP greater than forskolin greater than dbcAMP greater than 8BrcAMP. Biliary output of bile acids was essentially unaltered compared with controls; similarly, no decrease in the secretion of protein and triacylglycerols into the perfusion medium was observed. This suggests that the elevation of intracellular levels of cAMP may cause a selective inhibition of biliary lipid output rather than a more general inhibition of hepatic secretion.

Animals↗
PubMed1990

Oral motor dysfunction in individuals at risk of Huntington disease.

We studied the performance of 34 as yet undiagnosed individuals known to be at risk of Huntington disease (HD), on a maximum-effort oral-motor task. Results were compared with those from a normal control group matched for age and sex. The at-risk-of-HD population was significantly slower overall than the normal group on all 5 of the oral-motor tasks. This is interpreted as indicating that the presence of HD in the one half of the population expected to have it, affected the group's overall performance even though the clinical signs associated with HD had not yet appeared. In addition, rankings of repetition rates in both groups indicate that approximately one half of the at-risk population was consistently associated with the slowest 25% of the combined groups forming, in essence, a subgroup of the at-risk population. The performance of the other one half of the at-risk group did not differ systematically from that of the normal control persons. Minimal repetition rates were identified on each oral-motor task that may serve as early clinical "indicators" for the presence of HD in the population known to be at risk.

Humans↗
PubMed1990

Secretion of mucoid material by lymphokine-activated killer cells: study by light and electron microscopy.

When lymph node cells from nude mice were grown on embryonic fibroblast monolayers together with rat interleukin-2, only one type of colonies developed. These colonies were composed of cytotoxic cells termed "granular/lymphokine-activated killer/mucus-secreting cells" (LAK-GM). An extensive differentiation course, in which all the cellular components were involved, ended with a population of short-lived, mature, nondividing large cells that apparently synthesized and deposited a flowing mucoid material (FMM) that stained distinctly blue with periodic acid-Schiff/alcian blue (PAS-Ab) at pH 1 and distinctly red by the naphthol AS-D-chloracetate method for specific esterase. So far, the best monolayers to trigger the FMM synthesis were those prepared from 16- to 18-day-old whole embryos. These cells were compared with LAK cells that developed on monolayers (such as embryonic skin or adult kidney) that did not trigger FMM synthesis. They were also compared with other cell types that differentiated in colonies on the fibroblast monolayers: histiocytes (fixed macrophages), mixed granulocytes/monocytes, mucosal mast cells; and with populations of mature rat T-killer cells developed on same mouse monolayers. Features distinctive to the secreting LAK-GM cells were presence of masses of membrane-limited vesicles that were strictly confined to the surface of the cells in FMM-containing colonies. All transitional forms of budding activity could be seen on the cell surface facing the masses. Within the same cells, many granules displayed varying degrees of degradation, the granular material being transformed into flocculent material that formed small pools facing each degraded surface. Other characteristics of the LAK-GM lineage were the accumulation of glycogen prior to the appearance of the FMM, the presence of several structures of a ribosome-lamella complex in the LAK-GM in colonies that did not accumulate FMM, and filopodia commonly emerging from the pole proximal to the nucleus. Of various fixation methods tried, only after treatment with absolute alcohol and subsequent drying was the FMM stained with PAS-Ab. By subsequent wetting, the capacity to be stained was irreversibly lost. After incubation of the living cultures with the enzymes hyaluronidase or chondroitinases AC or ABC, the FMM disappeared. These observations suggest a triggering mechanism by the embryonic mesenchymal fibroblastoid cells for synthesis and secretion of mucous material that is a proteoglycan of the chondroitin sulfate group.

Animals↗
PubMed1990

Long-term physical exercise retards trabecular bone loss in lumbar vertebrae of aging female mice.

The present study examined the effect of long-term, moderate physical exercise on trabecular bone volume (TBV), calcium content, 3H-proline uptake, and the activities of alkaline and acid phosphatases in lumbar vertebrae of aging and senescent mice. It became apparent that if physical activity starts at an early stage of life, i.e., prior to middle age and is extended until old age, it exerts beneficial effects on trabecular bone mass and mineralization. Such a positive effect is not obtained if the training program is initiated after middle age. The training-induced reduction in bone loss was accompanied by a significant decrease in acid phosphatase activity whereas no changes took place with regard to the activity of alkaline phosphatase. Long-term physical exercise also enhanced the uptake of 3H-proline by lining cells along the bone trabecules. In spite of its moderate nature, the endured training program served as a stress factor for the involved animals, a fact that was manifested by an increase in the serum levels of corticosterone. Thus, it seems that whereas young animals respond favorably to such a stimulatory stress, older animals lose this ability of adaptation.

Acid Phosphatase↗
PubMed1989

The effects of long-term lead intoxication on the nervous system of the chicken.

In order to study the possible etiologic role of lead in human motor neuron disease we produced chronic lead intoxication in the chicken by daily administration of lead acetate. Control animals received sodium acetate. During life, periodic measurements were made of motor function, motor nerve conduction velocity and response amplitude. After sacrifice, histologic analysis was performed on spinal cord, peripheral nerve and muscle. A syndrome was produced characterized by a fall in motor response amplitude, spinal motor neuron degeneration, motor axonal loss and atrophy of muscle, similar to that seen in human motor neuron diseases.

Animals↗
PubMed1989

Oestradiol 17 beta-glucuronide increases tight-junctional permeability in rat liver.

By using rat liver perfusion under one-pass conditions with a single pulse of horseradish peroxidase (HRP), the biliary output of HRP was used as an indicator of paracellular permeability change caused by the cholestatic compound oestradiol 17 beta-glucuronide (E17G). Since E17G reduced bile flow, we have also used, during the assessment of junctional permeability after E17G treatment, the choleretic compound taurodehydrocholate to enhance bile flow back to control levels. At both low and restored bile flow rates, the acute administration of E17G (3.4 mumol) increased the HRP peak height, thereby indicating that one of the hepatotoxic actions of E17G is to increase the permeability of hepatic tight junctions. The action of E17G in affecting bile acid secretion and biliary volume are also explored.

Animals↗
PubMed1989

Retrograde intrabiliary injection of amphipathic materials causes phospholipid secretion into bile. Taurocholate causes phosphatidylcholine secretion, 3-[(3-cholamidopropyl)dimethylammonio]-propane-1-sulphonate (CHAPS) causes mixed phospholipid secretion.

The control of biliary phospholipid and cholesterol secretions by bile acid was studied by using the technique of retrograde intrabiliary injection. Taurocholate (TC), a moderately hydrophobic bile acid, taurodehydrocholate (TDHC), a hydrophilic non-micelle-forming bile acid, and 3-[(3-cholamidopropyl)-dimethylammonio]propane-1-sulphonate (CHAPS), a detergent, were individually administered by retrograde intrabiliary injection (RII) into the biliary tree, and bile acids, phospholipids and cholesterol subsequently appearing in the bile were measured. TC (1.3 mumol; 45 microliters) injected retrogradely provoked a 3.5-fold increase in biliary phospholipid output for 40 min, as compared with the saline control. Injection of 2.7 mumol of TC (90 microliters) caused a 7.5-fold increase in phospholipid output, which reached a peak at 12 min after RII, and phospholipid output continued for 40 min. Cholesterol output was also elicited under these conditions, showing both dose-dependency and extended secretion. Injection of 1.8 mumol of TDHC caused very little increase in either biliary phospholipid or cholesterol. Injection of 0.9 mumol of CHAPS (45 microliters) provoked a single substantial peak of phospholipid output in the 3 min bile sample. T.l.c. analysis of the phospholipid extracts of the bile collected after each compound showed, for TC, a single compound which co-migrated with the phosphatidylcholine standard, whereas for CHAPS substantial amounts of other phospholipids were present.

Animals↗
PubMed1989

A phase II study of mitozantrone in advanced carcinoma of the ovary.

A total of 37 patients with advanced epithelial ovarian cancer were treated with single-agent mitozantrone at a dose of 12-16 mg/m2. All patients had received previous chemotherapy, including a platinum compound in 36. In all, 35 patients were evaluable for response. One patient (3%) achieved a partial response lasting 4 months. Treatment was well tolerated, and at the doses used in this study significant bone marrow suppression was uncommon. Our results suggest that mitozantrone has only minimal activity in previously treated ovarian cancer. However, the possibility of its useful activity in first-line treatment or at higher doses has not been excluded.

Adult↗
PubMed1989

Age-related bone loss in lumbar vertebrae of CW-1 female mice: a histomorphometric study.

Age-related changes in vertebral cortical and trabecular bone were quantitated in female CW-1 mice. Histomorphometric measurements involved the use of two different systems of image analysis: Olympus Cue 2 and Zeiss Morphomat 10. The peak of bone mass, both cortical and trabecular, was found in mice aged 13.5 months. Thereafter, there was a progressive decline in the area occupied by bone tissue and this became highly significant in elderly female and male mice. A loss of about 60% of bone tissue was encountered in both the trabecular and cortical bone, as determined by automated image analysis system. Hence, aging CW-1 mice reveal structural features consistent with vertebral osteopenia. Despite the fact that to date we lack the precise etiology for the above-mentioned phenomenon, it is suggested that the laboratory mouse might serve as an appropriate experimental model for investigations related to age-related bone loss.

Aging↗
PubMed1989

Correlation between alkaline and acid phosphatase activities and age-related osteopenia in murine vertebrae.

Lumbar vertebrae (L4) from CW-1 female mice were examined for age-related changes in alkaline and acid phosphatase activities from young to old age. Histochemically, both enzymes were encountered along the bony surfaces of both trabecular and cortical bones with no significant age-related changes in their distribution. Biochemical determinations of bone alkaline phosphatase (Alk'ase) activity revealed that for a given unit level of bone or the bone as a whole no significant changes took place, whereas acid phosphatase (Acid'ase) activity was found to have increased significantly with age. A high positive correlative relationship was noted between the calcium content and the trabecular bone volume of the same vertebrae. It may, therefore, be proposed that age-related bone loss in mice could be attributed to an enhanced resorption rather than to a substantial reduction in the formative potential of bone cells.

Acid Phosphatase↗