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Biomedical subjects

K Tohyama

Publications and source records attributed to K Tohyama.

125 records · Page 7Linked to original sources
PubMed1983

Alteration in sensitivity of transmural electrical response to propionate in rat colon after chronic luminal infusion of short-chain fatty acids.

The colon is always exposed to abundant short-chain fatty acids (SCFA) produced by gut fermentation. In order to know an effect of chronic load of SCFA on colonic functions, we studied that the acute and chronic effects of SCFA on transmural potential difference (p.d.) across the proximal colon of germ-free (GF), gnotobiotic (GB) and conventionalized (CV) rats in vivo. Intravenous administration of SCFA (acute effect), such as propionate, butyrate, valerate or caproate, caused a transient increase in the p.d. The acute effects of propionate were studied in detail. The dose-response curve of CV rats shifted markedly to the right compared to that of GF rats, suggesting that CV rats were less sensitive to the acute effects of propionate than GF rats. Decreased sensitivity also appeared in GB rats (monocontamination with Fusobacterium varium). By chronic luminal infusion of isotonic sodium propionate or butyrate (25.5 ml/day) into the proximal colon of GF rats for 7 days (chronic effect), the acute effects of propionate were reduced. Atropine reduced the p.d. increment produced by propionate and shifted the dose-response curve of propionate to the right. These results suggest that chronic luminal load of SCFA resulted in a type of chronic refractoriness.

Animals↗
PubMed1983

Nearest-neighbor distance of intermediate filaments in axons and Schwann cells. Distinction between axons and schwann cell processes in the denervated and reinnervated peripheral nerves.

To distinguish axons from Schwann cell processes in the denervated (Büngner's bands) and reinnervated peripheral nerves, the nearest-neighbor distance of intermediate filaments (NND) was measured in axons and Schwann cells from denervated and subsequent regenerating peripheral nerves. It was revealed that the NND was much larger in regenerating axons (41.9 +/- 14.1 nm) than in Schwann cell processes (23.1 +/- 7.1 nm in regeneration and 19.7 +/- 5.8 nm in denervation). In addition, the NND was also measured in the normal adult and developing peripheral nerves, and it became clear that in all cases the NND in axons (29.0-41.9 nm) was larger than in Schwann cells (19.7-23.1 nm). Thus, it can be generally considered that the NND is larger in axons than in Schwann cells. This fact can be used for the distinction between axons and Schwann cell processes, when the latter have a profile similar to that of the former as in Büngner's bands and in the regenerating nerves.

Animals↗
PubMed1983

Inhibition of gastric emptying by chinoform and its relation to strain differences in acute toxicity of chinoform in mice.

Significant difference in oral LD50 of chinoform in mice was observed between strains C57BL/6 and C3H/He. C57BL mice were more sensitive to oral toxicity of chinoform than C3H mice. Doses of 200 mg/kg of chinoform gave a more rapid and prolonged inhibition of gastric emptying in C57BL mice than in C3H mice. Small intestinal transit in C57BL mice was slower than that in C3H mice. The delayed gastric emptying and slow small intestinal transit in C57BL mice affected the blood levels of chinoform, and these factors may be, at least partly, responsible for the difference in the lethal toxicity of chinoform between the two strains.

Animals↗
PubMed1983

[Clinical observation on the transport of cefotiam into the bile and gall bladder tissue].

A clinical study was performed on concentration of cefotiam (CTM) in the gallbladder bile and the gallbladder tissue in benign diseases of the biliary tract. By an hour intravenous infusion the CTM concentration obtained 2 hours after the start of the infusion revealed that the level of the CTM in A bile was atmost same as that in B bile (3.1--46.0 micrograms/ml). The concentration in gallbladder tissue was 5.7--116 micrograms/ml. In addition, the CTM level was higher enough than the MIC of CTM covering more than 80% of the strains of E. coli and Klebsiella obtained from the focus. From these results, it is concluded that CTM is clinically effective and useful in the case of biliary disease.

Aged↗
PubMed1982

Effect of indole on adenylate energy charge and mitochondrial phosphorylative activity of rat liver.

1. Luminal perfusion of 5.0 mM indole (0.5 ml/min) in small intestine lowered hepatic adenylate energy charge [(ATP + ADP/2)/(ATP + ADP + AMP)] from 0.85 to 0.80. 2. Liver perfusion of indole (0.5, 5.0 mM) also lowered adenylate energy charge. 3. In liver perfusion experiments, both ketone body ratio (beta-hydroxybutyrate/acetoacetate) and oxygen concentration of the effluent fluid were decreased by infusion of 0.5 mM indole, but they were increased by 5.0 mM indole. 4. In the isolated liver mitochondria system, indole uncoupled oxidative phosphorylation at lower concentrations than 2.0 mM. However, higher concentrations of indole inhibited the electron transport system.

Adenine Nucleotides↗
PubMed1982

Biosynthesis of microvillus membrane-associated glycoproteins of small intestinal epithelial cells in germ-free and conventionalized mice.

We studied the effect of intestinal microorganisms on the synthesis of membrane-associated glycoproteins in the upper small intestine by intraperitoneally administering L-[3H]fucose, D-[14C]glucosamine, or L-[3H]leucine to germ-free mice and mice exposed to microorganisms for 4 weeks (conventionalized). The incorporation of the labeled compounds into sucrase-isomaltase complex and maltase was determined by immunoprecipitating Triton X-100-solubilized microvillus membranes with their antibodies. Purified microvillus membranes from germ-free and conventionalized mice differed in the activities of some marker enzymes but not in the number and mobility of the components on SDS-polyacrylamide gel electrophoresis. Maximal incorporation of [3H]fucose and [14C]glucosamine into the microvillus membrane and two enzymes was reached 2-3 h post-injection in both groups, however, the amounts incorporated were larger in conventionalized mice. There was little difference in [3H]leucine incorporation into the total glycoproteins of microvillus membranes between the two groups. Our results suggest that the introduction of microorganisms stimulates the synthesis of sugar chains of microvillus membrane-associated glycoproteins. The enhanced in vitro fucosyltransferase activity in conventionalized mice partly supports this suggestion.

Animals↗
PubMed1981

Network structure in gels of rod-like polypeptides.

The formation of a mechanically self-supporting, macromolecular gel or network is understood on a molecular scale in terms of cross-links or branch points, either of a permanent nature by covalent bond formation, or of a reversible nature, such as in the gelation of gelatin. In thermally reversible gels each branch point may contain numerous monomeric units, indicative of local crystallite or aggregate formation, as in cellulose acetate or gelatin, or only two monomeric units as in polyacrylylglycinamide. The formation of reversible networks in nonionic, rod-like polypeptide homopolymers, particularly at low concentrations (<0.1 wt%), is surprising in that the molecular origin of the branch points is not obvious. We have suggested previously that this network constitutes a thermodynamic phase resulting from a particular kinetic mechanism of phase formation made favourable by the unusual polymerdiluent phase equilibria occurring with stiff-chain polymers. Here, the network is visualized by electron microscopy, and shown to be compatible with the proposed mechanism.

Biopolymers↗
PubMed1981

Appearance of fucolipid after conventionalization of germ-free mice.

Incorporation of [6-3H]fucose and [1-14C]glucosamine into the lipid fraction of microvillus membrane (MVM) was studied in germ-free and conventionalized mice after intraperitoneal injection of the radioactive precursors. Incorporation of [6-3H]fucose was clearly detected in conventionalized mice but not detectable in germ-free mice. There was no difference in the incorporation of [1-14C]glucosamine between the two groups. The lipid fraction of MVM labeled with [6-3H]fucose showed a spot of slower mobility than asialo GM1 on TLC with autoradiography and it was confirmed to be a fucolipid on abolishing the radiolabeled original spot by alpha-L-fucosidase treatment. These results suggest that the synthesis of the fucolipid is induced by conventionalization of germ-free mice.

Animals↗
PubMed1981

Presence of asialo GM1 and glucosylceramide in the intestinal mucosa of mice and induction of fucosyl asialo GM1 by conventionalization of germ-free mice.

Two major neutral glycolipids of the intestinal mucosa were purified by a series of column chromatographies and the structures were determined to be glucosylceramide and asialo GM1 by gas liquid chromatography. The carbohydrate structure of asialo GM1 was also confirmed from the reactivity of the glycolipid to rabbit anti-asialo GM1 antibody by an enzyme linked-immunosorbent antibody. The ceramide portion of both glycolipids had an extremely hydrophilic nature and more than 90% of the ceramide was composed of phytosphingosine and alpha-hydroxy fatty acids. In the previous paper we reported that the induction of a fucolipid in the microvillus membrane of mouse intestinal mucosa by conventionalization was observed on monitoring the incorporation of radiolabeled fucose in vivo. A fucoglycolipid having the same mobility on an autoradiogram as the fucolipid labeled in vivo was produced by in vitro incubation of intestinal asialo GM1 and GDP-[14C]fucose with the mucosal homogenates. Moreover, asialo GM1 prepared from brain gangliosides exhibited a similar ability to accept fucose and it was converted to fucosyl asialo GM1 which moved faster than the product from intestinal asialo GM1. The difference is considered to be due to the ceramide composition. These results suggest that conventionalization can induce the fucosyl asialo GM1 in the microvillus membrane probably through the induction of fucosyltransferase. Understanding the molecular mechanism of interaction between the physiological flora and host is the matter of further study.

Animals↗
PubMed1981

Effect of lactobacilli on urinary indican excretion in gnotobiotic rats and in man.

The effect of Lactobacillus species on urinary indican excretion in two types of gnotobiotic rats (GBH-9 and GB-5) and in man was studied. L. salivarius, L. plantarum and L. casei colonized in the cecum and colon of both types of rats at levels of 10(7) to 10(8) per gram of contents following one-dose oral administration and caused a significant reduction in urinary indican excretion, whereas two strains of L. acidophilus which colonized at low levels (10(4) to 10(5)/g) did not reduce indican excretion. Daily feeding of Lactobacillus concentrates caused a further significant reduction in indican excretion which was corrected by tryptophan intake, even in the case of L. acidophilus. There was a clear relationship between fecal lactobacillus counts and urinary indican. A significant reduction of indican secretion was obtained only when the fecal counts of lactobacilli exceeded 10(7).4/g in rats. L. casei also had an effect in man, reducing urinary excretion of indican and p-cresol. Reduction in indican excretion seems to be accompanied by decreasing fecal tryptophanase activity in rats and man. A negative correlation was also obtained between fecal resident lactobacilli and urinary indican in man (r = -0.532, n = 28, p less than 0.01). Subjects with lactobacilli at a level of 10(6)/g or more excreted less indican than those harboring the bacteria at levels below 10(5)/g.

Adult↗
PubMed1980

Characterization of acetate uptake by the colonic epithelial cells of the rat.

The characteristics of acetate uptake by colonic epithelial cells of the rat were studied. Clear saturation kinetics of acetate uptake were not observed in these experiments at either 0 degrees C or 30 degrees C. A decrease in the pH of the medium markedly increased the acetate uptake. The activation energy for acetate uptake derived from an Arrhenius plot was about 6.1 kcal/mole. Among the inhibitors tested, no effective inhibition of acetate uptake at 0 degrees C was observed. Metabolic inhibitors severely inhibited transport at 30 degrees C. Inhibition of acetate uptake by other short chain fatty acids, which was non-competitive, was observed. The finding that efflux from the cells was stimulated in the presence of compounds such as pyruvate and bicarbonate supported the notion of a close interrelationship between weak electrolyte transports in vivo. Although the H+ gradient across the cell membrane is suggested to be one of the factors determining the uptake rate, it seems difficult to explain all the results in this way.

Absorption↗
PubMedDate not supplied

A novel Philadelphia chromosome-positive cell line with multipotential properties.

A novel Philadelphia chromosome-positive cell line was established from the peripheral blood of a patient with chronic myelogenous leukemia in megakaryoblastic crisis. This cell line, designated TN922 showed the positive phenotypes for myeloid, monocyte-macrophage, erythroid and megakaryocytic markers. The stimulation with phorbol 12-myristate 13-acetate (PMA) increased the expression of megakaryocytic markers including the platelet peroxidase activity, dimethylsulfoxide or transforming growth factor-beta promoted up-regulation of the erythroid markers. Stimulation with PMA, tumor necrosis factor-alpha or interleukin-6 also brought about the expression of monocytoid markers. These findings indicated that TN922 cell line has the property of acting as multipotential progenitor cells. TN922 cells showed gradual growth in the absence of growth factors but the addition of granulocyte/macrophage colony-stimulating factor (GM-CSF) promoted cell growth. The message of GM-CSF was detected in TN922 cells and the neutralizing antibody against GM-CSF receptor alpha-subunit suppressed cell growth. These results indicated that TN922 cell line proliferates in an autocrine secretion of GM-CSF.

Aged↗
PubMedDate not supplied

Pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex treatment in patients with myelodysplastic syndrome.

Ubenimex is an orally active aminopeptidase inhibitor with an immunomodulating action. A pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex was performed in patients with myelodysplastic syndrome. Ubenimex (150 mg/body) was administered orally, twice per day (at a 3 hr interval), twice a week, for at least 8 weeks. The concentrations of ubenimex and p-OH ubenimex, another active metabolite, increased gradually up to 7.1 +/- 4.7 micrograms/ml (mean +/- SD) at 5 hr and 0.25 +/- 0.15 mu/ml at 6 hr. The low percentage (4.2%) of the AUC ratio (p-OH ubenimex/ubenimex) suggested minimal metabolism. The plasma half-life of ubenimex was 2.1 +/- 0.7 hr and the total urinary recovery of both was 71.4% in 48 hr. Among 8 patients clinically studied, one achieved good response and another achieved minor response. These findings suggested good bioavailability, and a certain effectiveness of ubenimex in this administration method, which was worth trying, at least in restricted cases, such as cases with refractory disease or with a poor performance status.

Adult↗