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M Hosomi

Publications and source records attributed to M Hosomi.

47 records · Page 3Linked to original sources

Role of polyamines in intestinal adaptation in the rat.

The cellular mechanisms controlling adaptive intestinal mucosal hypo- and hyperplasia are poorly understood but changes in tissue polyamine levels and in the activity of the key enzymes controlling their synthesis (ornithine decarboxylase: ODC) and degradation (diamine oxidase: DAO) have been implicated. Therefore, in two models of adaptive mucosal hyperplasia (pancreatico-biliary diversion, PBD, achieved by surgically transposing the jejunum to lie between pylorus and ampulla of Vater, and 90% small bowel resection, SBR-both studied 8 weeks after surgery) and in one model of hypoplasia (8 days total parenteral nutrition) we measured indices of mucosal mass (wet weight, protein and DNA per 10-cm intestine), the growth-associated polyamines (putrescine, spermidine and spermine per 10-cm intestine and per mg DNA) and DAO activity in the duodenum, five 10-cm segments of jejunum, five 10-cm segments of ileum and in the colon, and compared the results with those found in transected or unoperated controls. The results for the indices of mucosal mass confirmed that TPN led to a modest degree of small bowel mucosal hypoplasia whilst PBD, and particularly 90% SBR, stimulated marked adaptive hyperplasia. There were corresponding changes in the amounts of putrescine and spermidine (but not of spermine)-not only when the results were expressed per unit length but also when calculated per mg mucosal DNA and in the ratio of spermidine:spermine. There was an increasing proximal-to-distal gradient in mucosal DAO per unit length intestine in all experimental groups but when the results were expressed per mg DNA, the ileal DAO levels were significantly reduced in the PBD and resection groups, when compared with the controls. These data support the hypothesis that polyamines play a major, and perhaps a controlling, role in regulating adaptive intestinal mucosal growth.

Amine Oxidase (Copper-Containing)↗

Mucosal polyamine profile in normal and adapting (hypo and hyperplastic) intestine: effects of DFMO treatment.

The polyamines, putrescine, spermidine, and spermine, are believed to play an important role in modulating normal and adaptive intestinal mucosal growth. Polyamine synthesis is rate limited by ornithine decarboxylase (ODC) and ODC activity is specifically inhibited by -difluoromethyl ornithine (DFMO). To assess the importance of polyamines in adaptive growth we first measured mucosal polyamine profiles at different sites in the normal rat intestine and compared the results with those obtained in adaptive hypoplasia (seven days parental nutrition, TPN), in the adaptive hyperplasia of two weeks after 90% small bowel resection (SBR) or pancreatico biliary diversion (PBD). We then examined the effects of DFMO (2% in drinking water, daily from two days before surgery) on the polyamine concentrations and the adaptive response to PBD. The hyperplasia of SBR and PBD was associated with increases in all the polyamine concentrations particularly putrescine. TPN induced a modest degree of hypoplasia and little change in polyamine synthesis resulting in subnormal polyamine concentrations and significantly inhibited the mucosal adaptive response. Changes in polyamine metabolism are important in intestinal mucosal adaptation and by controlling these changes adaptive growth can be controlled.

Adaptation, Physiological↗

Polyamine distribution in the rat intestinal mucosa.

As the first step in a study of mucosal polyamine metabolism during intestinal adaptation, we have measured mucosal polyamine concentrations at different sites along the normal rat intestine. Putrescine, spermidine, spermine and cadaverine were measured by spectrofluorometric analysis after thin-layer chromatography of their dansylated derivatives. Spermidine was present in the largest amounts at each of the sampling sites. The ratio of the concentration of spermidine to that of spermine paralleled the established pattern of cellular proliferation in the normal intestine as did the putrescine concentration (nmol per 10 cm) which decreased from duodenum to colon. These results provide the essential background to an assessment of the role of polyamines in the intestinal adaptive response.

Animals↗

Hormones and polyamines in intestinal and pancreatic adaptation.

The evidence for and against an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, and exocrine pancreatic, structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of 'enterotrophin' while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO). When polyamine synthesis is blocked with the ODC inhibitor, difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreatico-biliary diversion is either inhibited or completely prevented. A proposed sequence of events might be as follows: luminal nutrients, particularly long-chain fats, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines, which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division, and adaptive tissue growth.

Adaptation, Physiological↗

An ultrastructural study of Pick bodies.

We report the results of an ultrastructural study of Pick bodies (PB). A histogram constructed with the maximal width of each filamentous component in PB revealed a wide range of sizes among the filaments, in contrast to the unique composition of the paired helical filaments (PHF) seen in the neurofibrillary tangle of Alzheimer type (NFT-AT). Morphologically, three groups of filaments could be distinguished. The first group consisted of straight smooth-surfaced filaments of 10-14 nm diameter, which were presumably altered neurofilaments. The second one was of straight smooth-surfaced "tubules" of 15-22 nm diameter, smaller than normal microtubules. The third one was of PHF thought to be formed by a pair of filaments of the first group. The PHF found in PB differed from PHF of NFT-AT in the distance between crossovers, and rather resembled the loosely interwinding PHF reported in NFT of progressive supranuclear palsy.

Cerebral Cortex↗

The role of intestinal bacteria in gallstone formation in animal model. A study on biliary lipid composition and bile acid profiles in bile, small intestinal contents and feces of clostridium butyricum Miyairi No. 588 monocontaminated mice.

Contradictory results in the studies on experimental gallstone formation using conventional and germfree mice have been reported. To study the role of bacteria in gallstone formation in the animal model JCL:ICR male germfree mice were monocontaminated with Clostridium butyricum MIYAIRI No. 588. Gallstone formation, biliary lipid composition and bile acid profiles in the bile, small intestinal contents and feces were analyzed after feeding the diet containing cholesterol and cholic acid. The rate of gallstone formation in the monocontaminated mice (38%) was less than that in the germfree mice (100%). The relative concentrations of biliary lipids of the two groups were located out of the micellar zone on the triangular co-ordinates by Admirand and Small. The bile acid concentrations in the small intestine and fecal excretions in the monocontaminated mice were higher than in the germfree mice. The composition as well as the mode of conjugation of the bile acids did not differ significantly between the two groups. The infestation of bacteria in the intestine enhanced the excretion of bile acids and inhibited the gallstone formation in mice, in which direct metabolic activity by bacterial enzymes on bile acid did not seem necessary to exert such effect.

Animals↗

Fecal bile acid analysis in healthy Japanese subjects using a lipophilic anion exchanger, capillary column gas chromatography and mass spectrometry.

Detailed fecal bile acid profiles of healthy Japanese subjects were studied using a lipophilic anion exchanger, capillary gas chromatography and mass spectrometry. Total dairy excretion of bile acid into feces corrected for by fecal markers were between 127.99 to 366.33 mumole per day. Unconjugated bile acids constituted a major part, between 80 and 96%, of fecal bile acids. Glycine conjugated, taurine conjugated and sulfated bile acids were between 1 to 6, 0 to 3 and 1 to 10%, respectively. Esterified bile acids at C-24 position existed between 1 to 5%. Primary bile acids ranged from 0 to 55%. There were a number of epimers of hydroxy- and keto-bile acids, and lithocholic and deoxycholic acid were major secondary bile acids among them. A cholenoic acid was detected in the unconjugated fraction of one subject. It seems necessary to analyze the details not only on the type of bile acids but also on the mode of conjugation in biological samples. Thus, the methodology described in this study has made it easier to investigate on the role of bile acid in the physiology or pathophysiology of the gastrointestinal tract.

Adult↗

Treatment of PCB-contaminated soil in a pilot-scale continuous decomposition system.

The BCDP (Base Catalyzed Decomposition Process) is a process by which difficult-to-decompose organic chlorine compounds, such as PCBs, are chemically decomposed and dechlorinated. Pilot-plant tests for PCB contaminated soil were carried out. PCB contaminated soil (32 mg/kg-530 mg/kg) was decontaminated to a level (0.038 mg/kg-4.8 mg/kg) which satisfied the corresponding Japanese environmental standard which stipulates, "there must be no discharge of PCB containing leachate".

Environmental Pollution↗