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Biomedical subjects

C Dive

Publications and source records attributed to C Dive.

At least 73 records · Page 4Linked to original sources
PubMed1991

Multiparametric flow cytometry of the modulation of tumor cell membrane permeability by developmental antitumor ether lipid SRI 62-834 in EMT6 mouse mammary tumor and HL-60 human promyelocytic leukemia cells.

(+-)-2-[Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2- yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide, inner salt (SRI 62-834) is a tetrahydrofuran analogue of platelet activating factor (PAF) that is currently entering clinical trial. Like other ether lipids it is of interest as a membrane-active antitumor agent. Here, we have used two-color multiparameter flow cytometry to study simultaneously its effects on cell membrane permeability, intracellular pH, and cell size/structure of EMT6 mouse mammary tumor cells and HL-60 human promyelocytic leukemia cells in vitro. Concentrations as low as 1 microM up to 100 microM SRI 62-834 caused a rapid, dose-dependent increase in membrane permeability, initially towards outward efflux of the preloaded fluorescein probe bis(carboxyethyl)carboxyfluorescein (green fluorescence) and then towards influx of extracellular propidium (red fluorescence). At the same time, median cell size from light scatter was reduced with an increased coefficient of variation, and the proportion of cell debris was elevated. In vitro antitumor activity was seen over the same concentration range, as measured by tetrazolium dye reduction and cell growth curves. Neither low concentrations of PAF (50 nM) nor the potent PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]tria- zolo[4,3a][1,4]diazepin-2-yl]-1-(4-morpholinyl)-1-propanone (0.5-100 microM) had any influence on the membrane effects of SRI 62-834, and at higher concentrations (1-200 microM) PAF mimicked the behavior of SRI 62-834. In addition, the PAF antagonist did not modulate the cytotoxicity of SRI 62-834 or PAF. HL-60 cells were more sensitive to SRI 62-834 than were EMT6 cells in terms of both cytotoxicity and membrane permeability. However, PAF was more potent than SRI 62-834 in causing membrane permeabilization with both cell lines, whereas PAF was less active than SRI 62-834 in cytotoxicity assays. The results support a membrane-damaging role in the cytotoxicity of SRI 62-834 but suggest that additional factors are also involved. Membrane permeabilization may be related to its reported effects on protein kinase C-dependent intracellular calcium signaling but apparently does not involve a conventional PAF receptor in HL-60 or EMT6 cells.

Animals↗
PubMed1991

Noninvasive measurement of liver regeneration with positron emission tomography and [2-11C]thymidine.

The feasibility of liver regeneration determination with [2-11C]thymidine and positron emission tomography was investigated in partially hepatectomized rats. Serial tomographic scans were performed over a 120-minute period after injection of [2-11C]thymidine together with tritium-labeled thymidine. Within 10 minutes after injection, positron emission tomography scans showed a twofold higher hepatic uptake in regenerating than in nonregenerating livers. Time-activity curves over the liver area indicated that the maximal uptake was followed by a faster decrease of 11C radioactivity in controls than in regenerating animals, so that total 11C activity remaining in the liver at 120 minutes accounted for 68% of maximum in regenerating and only 38% in controls. Tissue distribution studies performed at 120 minutes showed that total 11C radioactivity, expressed in percent injected dose per gram, was six times higher in regenerating livers than in controls (0.62% +/- 0.07% in regenerating livers and 0.10% +/- 0.03% in nonregenerating livers; P less than 0.001) and correlated with 3H radioactivity measured in the nuclear fraction (r = 0.92; P less than 0.001). When the hepatic uptake was expressed in percent of dose per organ, the difference between both groups increased (2.31% +/- 0.23% in regenerating livers and 0.29% +/- 0.02% in nonregenerating livers; P less than 0.001) because of higher weight of regenerating livers than of nonregenerating livers (3.83 +/- 0.11 g in regenerating livers and 2.96 +/- 0.16 g in nonregenerating livers; P less than 0.001). In other organs examined, no difference in 11C radioactivity was found between the two groups of rats. These results indicated the potential usefulness of [2-11C]thymidine and positron emission tomography for noninvasive measurement of liver regeneration.

Animals↗
PubMed1991

Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases.

Clinical presentation, changes in liver function test results, and liver morphology were examined in 41 consecutive patients with vitamin A hepatoxicity. The cause of liver disease was suspected at initial interview in only 13 instances, whereas histological evidence of fat-storing cell hyperplasia with fluorescent vacuoles led to the diagnosis in the remaining cases. Cirrhosis was found in 17, mild chronic hepatitis in 10, noncirrhotic portal hypertension in 5, and "increased storage" alone in 9 cases. During a mean follow-up period of 4.6 years, 6 patients died of causes related to the liver disease. A precise appraisal of drug consumption was obtained in 29 cases. Among them the total cumulative intake was the highest in patients with cirrhosis (423 +/- 103 x 10(6) IU) and significantly lower in those with noncirrhotic liver disease (88.5 +/- 41; P less than 0.02). The smallest continuous daily consumption leading to cirrhosis was 25,000 IU during 6 years, whereas higher daily doses (greater than or equal to 100,000 IU) taken during 21/2 years resulted in similar histological lesions. It was concluded that at least in some western countries chronic vitamin A consumption might represent an appreciable cause of chronic liver disease, the recognition of which mainly relies on expert liver biopsy interpretation. The data also indicate that prolonged and continuous consumption of doses in the low "therapeutic" range can result in life-threatening liver damage.

Chemical and Drug Induced Liver Injury↗
PubMed1991

Jejunal immunoglobulin secretion in alcoholic patients with and without cirrhosis.

Alcoholic liver diseases are associated with an elevation of serum immunoglobulin A (IgA). This could be the result of increased IgA production by the intestinal mucosa. Serum and jejunal immunoglobulin, albumin and orosomucoid were measured in 13 alcoholic patients with (n = 6) and without (n = 7) cirrhosis and compared to 11 controls. Jejunal secretions were obtained by segmental perfusion under an occluding balloon. High levels of serum monomeric and polymeric IgA were only found in patients with cirrhosis. Alcoholics with and without cirrhosis had normal monomeric and polymeric IgA jejunal secretion rates. jejunal clearances of albumin, orosomucoid and immunoglobulin G were significantly higher in both non-cirrhotic and cirrhotic patients than in controls. These findings indicate normal jejunal IgA secretion and increased permeability to plasma proteins, such as albumin and immunoglobulin G in alcoholics.

Adult↗
PubMed1991

Drug-target interactions: only the first step in the commitment to a programmed cell death?

The search for novel antitumour drugs has reached a plateau phase. The carcinomas remain almost as intractable as they did 40 years ago and the need for effective therapy is pressing. There is an argument that the current pharmacopoeia is sufficient but, to be effective, the biochemical mechanisms of drug resistance must be circumvented. In tackling the question of why certain cancer cells are resistant, the converse question of why others are sensitive still remains to be answered fully. Asking the fundamental question of why and how a cell dies may provide clues as to what avenues lie open for improved chemotherapy. In this review we survey the recent literature on cell death and we argue that it is possible that the outcome of chemotherapy may be determined by the response of the cell to the formation of the drug-target complex, and/or its sequellae, rather than to the biochemical changes brought about by the drug alone. One of these responses, determined by the phenotype of the cell, may be activation of a genetic programme for cell death.

Animals↗
PubMed1990

Multiparametric analysis of cell membrane permeability by two colour flow cytometry with complementary fluorescent probes.

We describe an improved twin-probe multiparameter flow cytometric technique to examine cell membrane permeability. Ability to retain preloaded intracellular bis-carboxyethyl carboxy fluorescein (BCECF, green fluorescence) and to exclude extracellular propidium (red fluorescence) is measured, simultaneously with forward and right-angle scatter. This has significant advantages over an earlier method using fluorescein together with ethidium. In addition to the two expected cell populations which were stained green positive, red negative (by convention membrane "intact" and "viable," Region 1) and green negative, red positive ("membrane-damaged" and "non-viable," Region 3), a third population was seen which fluoresced neither green nor red and displayed intermediate light scatter characteristics (Region 2). This was true for each of 9 cell types in vitro. For EMT6 mouse mammary tumour cells held under sub-optimal conditions or treated with membrane-active drugs, progression from Region 1 to Region 2 was observed, followed by further progression from Region 2 to Region 3. Cells eventually accumulated in Region 3. These results suggest that sequential changes in membrane structure lead to increased permeability, first with respect to intracellular BCECF and in turn to extracellular propidium.

Animals↗
PubMed1990

Stimulation of secretory IgA and secretory component of immunoglobulins in small intestine of rats treated with Saccharomyces boulardii.

Saccharomyces boulardii (S.b.) is largely used in Western European countries for the treatment of acute infectious enteritis and antibiotic-induced gastrointestinal disorders. To study the mechanisms of the protective effect of S.b. against enteral pathogen infection, we assessed the response of the intestinal secretion of secretory IgA (s-IgA) and of the secretory component of immunoglobulins (SC) to oral administration of high doses (0.5 mg/g body weight, three times per day) of S.b. cells in growing rats. S.b. cells (biological activity: 2.8 x 10(9) viable cells/100 mg) were administered daily by gastric intubation to weanling rats from day 14 until day 22 postpartum. Control groups received either 0.9% saline or ovalbumin following the same schedule. Expressed per milligram of cell protein, SC content was significantly increased in crypt cells isolated from the jejunum (48.5% vs saline controls, P less than 0.05) as it was in the duodenal fluid (62.8% vs saline controls, P less than 0.01) of rats treated with S.b. Oral treatment with S.b. had no effect on the secretion of SC by the liver. In the duodenal fluid of rats treated with S.b. cells, the mean concentration of s-IgA was increased by 56.9% (P less than 0.01) over the concentration of s-IgA measured in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Refeeding after starvation in the rat: comparative effects of lipids, proteins and carbohydrates on jejunal and ileal mucosal adaptation.

To compare the tropic effect of different dietary nutrients on mucosal adaptation in the jejunum and ileum, adult rats were submitted to a 96-h period of starvation and refed isocaloric liquid diets (1.5 kcal ml-1) containing either protein (casein), carbohydrate (starch) or lipids. In the jejunum, 4 days of starvation caused mucosal hypoplasia, villus and crypt shortening and a decrease in the total activity of disaccharidases with the exception of lactase which was markedly enhanced. In contrast, mucosal hypoplasia was incomplete in the ileum which exhibited an increase in crypt depth and in the specific and total activities of disaccharidases and of aminopeptidase. Compared with protein and carbohydrates, lipids exerted the strongest stimulatory effect for mucosal regeneration. In the jejunum as well as in the ileum, mucosal mass parameters, villus length, crypt depth and lactase activity did reverse towards their initial value within 1-3 days of refeeding lipids, even though the animals received only one-third of their normal daily caloric intake. Our results indicate that the pattern of response to fasting differs between the proximal and distal small intestine, and that the intestinal changes induced by starvation are rapidly reversed by refeeding small amounts of a diet rich in fat.

Animals↗
PubMed1990

Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.

We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component. The results were compared to the number of Ig-containing plasma cells in the test segment. There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects. The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria. In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate. The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid. Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease. Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum. This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease.

Adolescent↗
PubMed1990

Chronic idiopathic constipation with outlet obstruction.

Defecatory difficulties may be a source of great distress to patients. Normal defecation requires the coordination of abdominal and pelvic muscles. Throughout the last decade, many studies have demonstrated various and often mixed abnormalities of these mechanisms. Pathophysiological studies are able to determine, in a specific patient, the most probable causes of the obstructive symptom. Progress in the management of such disorders can only be achieved by understanding their pathophysiology.

Aged↗
PubMed1989

Inhibition of cellular esterases by the antitumour imidazotetrazines mitozolomide and temozolomide: demonstration by flow cytometry and conventional spectrofluorimetry.

Using flow cytometry and conventional spectrofluorimetry we have previously shown that chloroethylnitrosoureas (CNUs) can exhibit marked inhibition of cellular enzymes catalysing hydrolysis of fluorescein diacetate (FDA). More potent inhibition was seen for the carbamoylating CNUs, whereas alkylating agents were largely inactive. We now report results obtained with the developmental imidazotetrazines mitozolomide and temozolomide in comparison with BCNU, the novel alkylating agents clomesome and cyclodisone, and the active mitozolomide metabonate MCTIC. Inhibition of EMT6 mouse mammary-tumour esterases was seen for mitozolomide and temozolomide, and activity against purified porcine carboxylesterase was demonstrated. Flow cytometric analysis showed that inhibition occurred across the entire EMT6 cell population, with no evidence of a subpopulation resistant to enzyme inhibition. Inhibitory potency for the imidazotetrazines was much weaker than for BCNU. With EMT6 cells, I50 values from flow cytometry were 9.7 x 10(-3) M and 1.5 x 10(-3) M for mitozolomide and temozolomide compared with 3.7 x 10(-4) M for BCNU. These were higher than the ID50 values for in vitro antitumour activity (MTT assay), 8.5 x 10(-6) M in the case of mitozolomide and 1.2 x 10(-5) M for BCNU, but similar to that of 5.6 x 10(-4) M for the less toxic temozolomide. MCTIC and cyclodisone showed very low activity, but significant inhibition was seen for clomesome. The results are consistent with the view that the imidazotetrazines do not exhibit major carbamoylating ability, although significant effects are seen at cytotoxic concentrations of temozolomide. In addition, the potential for the generation of carbamoylating species at the enzyme active site cannot be ruled out.

Animals↗
PubMed1989

Changes in serum and intestinal diamine oxidase (DAO) activity after proximal enterectomy in rats. Correlation of DAO activity with mucosal mass parameters.

To determine whether serum and mucosal DAO activity reflects quantitative changes in the small bowel mucosal mass, we have chosen an experimental model of mucosal hyperplasia which is known to occur in the rat after enterectomy. A 50% proximal enterectomy or a single transection was performed in 20 growing rats weighing 145-160 g. Ten days following surgery, we determined mucosal mass parameters (weight, protein, and DNA content), sucrase activity, and DAO activity in the duodenum (segment A), proximal ileum (segment B), and distal ileum (segment C) of the remaining small intestine. Mucosal hyperplasia was demonstrated by the finding that in each segment, mucosal weight, protein, and DNA content per centimeter of gut length were significantly (P less than 0.01) higher (+38 to + 78%) in the resected group than in transected controls. In segments B and C of resected rats, the changes in DAO activity expressed per gram of mucosa paralleled the changes in mucosal mass, the activity being increased by +69% and +49% (P less than 0.05) compared to the values recorded in transected controls. Expressed per centimeter of gut length, total DAO activity was also enhanced by +141% in segment B (P less than 0.05 vs controls) and by +87% in segment C (P less than 0.01 vs controls) of resected rats. In the duodenum, the changes in DAO activity were small (+36%) and not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗
PubMed1989

Colonic angiodysplasia. Follow-up of patients after endoscopic treatment for bleeding lesions.

Endoscopic electrocoagulation or photocoagulation is now the method of choice for treating colonic angiodysplasia. Follow-up of such patients has not been extensive. The authors report 26 patients with typical and symptomatic lesions who have been treated endoscopically. Follow-up (mean duration, 29.3 months) revealed that 21 patients remained symptom-free after a single procedure. Two patients needed a second procedure before being considered cured. In two others, the need for transfusions was lessened considerably after treatment. The last patient died of terminal cardiac failure. No complications occurred during treatment. Endoscopic treatment is a safe and efficient method for treating bleeding colonic angiodysplasia.

Adolescent↗
PubMed1989

Primary sclerosing cholangitis and idiopathic pulmonary fibrosis: a case report.

Primary sclerosing cholangitis (PSC) and idiopathic pulmonary fibrosis (IPF) were each separately described in association with a variety of chronic idiopathic inflammatory diseases such as retroperitoneal fibrosis, Sicca complex or Riedel's thyroiditis. We report a case which may be the first description of the association between PSC and IPF. The physiopathogenic implications of such an association are discussed.

Biopsy↗
PubMed1989

Hyperamylasemia with papillary serous cystadenocarcinoma of the ovary.

High levels of serum amylase and CA19.9 were noted in a patient with papillary serous cystadenocarcinoma of the ovary. Electrophoresis identified isoamylases of salivary type. Both markers decreased rapidly after removal of the ovarian tumour. These considerations argue in favor of the early detection of amylase isoenzymes in patients in whom history, objective signs, and routine diagnostic studies fail to disclose a pancreatic disease.

Aged↗
PubMed1988

Inhibition of intracellular esterases by antitumour chloroethylnitrosoureas. Measurement by flow cytometry and correlation with molecular carbamoylation activity.

Antitumour chloroethylnitrosoureas (Cnus) decompose in physiological conditions yielding alkylating species and organic isocyanates. While antitumour activity is mainly attributed to the alkylation of DNA, carbamoylation of intracellular proteins by isocyanates may also have pharmacological and toxicological relevance. We previously reported a novel dynamic flow cytoenzymological assay for esterase inhibition in intact murine cells by BCNU and related isocyanates, and proposed that this might form the basis of an assay for intracellular carbamoylation. We have now examined a wide range of Cnus, isocyanates, and alkylating agents for their ability to inhibit cellular esterases. BCNU, CCNU, their derived isocyanates, and the 4-OH metabolites of CCNU exhibited potent inhibitory activity (I50 values 5.5 x 10(-5)-7.3 x 10(-4) M). Chlorozotocin and GANU were relatively inactive (I50 much greater than 10(-2) M). ACNU, TCNU and the 2-OH metabolites of CCNU exhibited intermediate activity (I50 values 1.1 x 10(-3)-2.3 x 10(-2) M). Compounds not able to form isocyanates were essentially inactive. Poor membrane permeability was also implicated in the weak activity of chlorozotocin and GANU. There was overall a good correlation between esterase inhibition and chemical carbamoylating activity, but some particular differences were identified. We concluded that flow cytoenzymological assay appears to have the potential to provide useful measurement of intracellular protein carbamoylation by existing Cnus and novel derivatives, and also offers the advantage of cell subpopulation identification for in vivo evaluation of these agents.

Animals↗
PubMed1988

Massive plasma cell infiltration of the digestive tract. Secretory component as the rate-limiting factor of immunoglobulin secretion in external fluids.

A 29-yr-old Tunisian man had a clinical immunoproliferative small intestinal disease, different from alpha-chain disease. Serum contained 52.5 mg/ml of polymeric immunoglobulin A (IgA). Immunohistochemistry revealed a massive diffuse polyclonal IgA (99%)-plasma cell infiltration in the small bowel mucosa, with a smaller increase of IgA-producing cells in gastric and colonic mucosae. Secretory IgA levels were normal in jejunal and bronchoalveolar secretions. However, both fluids contained polymeric IgA devoid of secretory component, and free secretory component was absent. This suggests that secretory component was the limiting factor in transport of IgA in the secretions. A relative deficiency in secretory component, as compared with the huge supply of polymeric IgA, may have limited the secretory component-mediated active transport of IgA into secretions. This resulted in the appearance of high levels of polymeric IgA, unlinked to secretory component, both in serum and in the jejunal and bronchoalveolar fluids.

Adult↗