[Glucose absorption in the everted small intestine of rats--a new method for serial observation].
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Biomedical subjects
Publications and source records attributed to M Tsuchiya.
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The synthesis of a fully protected dodecamer, GUAUCAAUAAUG, has been achieved by avoiding the side reactions on the base residues of Guo and Urd by use of the diphenylcarbamoyl and anisoyl as the protecting groups of the amide and imide functions, respectively.
To see if UDP accelerates the metabolism of ethanol, Wistar female rats were given UDP(100 mg/kg b.w.) intra-gastrically prior to a single dose of ethanol (3 g/kg b.w.) ingestion. UDP pretreatment accelerated blood ethanol disappearance rate by 50% (mg/kg animal/hr) by Widmark formula. Increases of the hepatic triglyceride concentration 6 hours and 20 hours after ethanol administration were significantly low in UDP pretreated animals suggesting the lipotropic effect of UDP. Neither the activity of alcohol dehydrogenase nor microsomal ethanol oxidizing system was affected by UDP pretreatment. The ratio of lactate to pyruvate in liver 6 hours after ethanol was not changed as compared with that of the control whether the rats were pretreated with UDP or not. There were significant increases in hepatic ATP content and the size of the adenylate pool in UDP pretreated group, whereas the energy charge was unchanged as compared with ethanol-alone group. These data suggest that UDP enhances ethanol metabolism possibly by causing a change in ATP metabolism.
A total of 191 gastric adenomas in 178 patients was studied macroscopically by endoscopy and histopathologically by endoscopic biopsy. Among the lesions, 85 in 74 patients were followed-up for six months to 12 years. Gastric adenomas were found to be more frequent in the aged, with a rate of 0.1% in the third decade but 3.7% in the ninth decade, on gastroscopic examination. Gastric cancers coexistent with the gastric adenomas were seen in 14 cases (8%), and were more frequent in male than in female patients (sex ratio, 12:2). Only eight of the 85 lesions (9%) revealed macroscopic changes. Four of these showed a reduction in size, while the other four lesions showed enlargement. In 21 of the 85 lesions (25%), histologic changes were observed. Four (5%) changed from moderate dysplasia (Group III) to nondysplastic or intestinal metaplasia (Group I), eight lesions (9%) revealed histologic changes (Group III to IV, or vice versa) without malignant transformation, and nine lesions (11%) showed malignant changes. Neither submucosal invasion nor lymph node metastasis was found. These lesions consisted of carcinoma in situ with small foci in the lesions exhibiting moderate dysplasia, and a gradual transition from severe dysplasia to cancer was seen in resected lesions obtained by endoscopic polypectomy or surgical resection. In addition, a gradual increase in dysplasia of tissue from moderate to severe was revealed by repeated gastroscopic biopsy. These findings suggest that the gastric adenomas underwent malignant changes with gradual transformation from moderate through severe dysplasia.
Intestinal fat absorption was examined in rats with CCl4-induced liver cirrhosis. Marked lymphangiectasia of the small intestine was observed in rats after CCl4 was given subcutaneously biweekly for 10--12 weeks. Intestinal epithelial uptake of linoleic acid administered in the loop was not impaired, but accumulation of lipid droplets in the intestinal epithelial cells and disturbed lymphatic transport of absorbed fat were observed in these rats. These data suggest that lymphostasis of the intestine may play an important role in fat malabsorption in liver cirrhosis.
Ultrastructural and immunohistochemical studies of the small intestine are described in a Japanese patient with alpha heavy chain disease who had a history of colonic ulcers. Endoscopic examinations revealed multiple gastric erosion, duodenal ulcer, and a thickened, cobblestone-like pattern composed of small nodules in the duodenum and jejunum, which was similar in appearance to Crohn's disease. An electron microscopic study showed that the numerous, infiltrated cells in the jejunal lamina propria were matured plasma cells with atypical structure of the organelles. These plasma cells had alpha heavy chain protein devoid of light chain. Although secretory component was demonstrated normally in the epithelial cells by immunofluorescent methods, no association of this component with alpha heavy chain protein could be observed in any of the plasma and epithelial cells of this case. These facts suggest the absence of secretory alpha chain or secretory IgA, and a deficiency of the mucosal secretory immune system in this patient.
It is conceivable that brush border enzyme activities of the intestinal mucosa will change when bacterial toxins are exposed to the intestinal microvillous membranes. The effect of cholera toxin on the activity of intestinal alkaline phosphatase in rats was therefore determined in the intestinal mucosa by the histochemical method as well as in intestinal lymph by using lymph fistulated-rats. Activity of intestinal alkaline phosphatase in the intestinal mucosa and lymphatics changed biphasically after the oral administration of cholera toxin to rats. For the first three hours after the administration of cholera toxin it was depressed; it then increased and at eight hours reached a maximum. These changes in the activity of intestinal alkaline phosphatase were prevented by the administration of chlorpromazine, a known inhibitor of adenylate cyclase activity.
The purpose of this study is to examine whether intestinal alkaline phosphatase (IAP) plays a role in transporting lipoproteins to lymphatics during fat absorption. In control rats, the increased activity of IAP in intestinal lymph was observed parallel with the amount of absorbed linoleic acid. In colchicine-treated rats, lymphatic absorption of intraduodenally administered linoleic acid was decreased and administered lipid was transported slowly to lymphatics, mostly in the form of free fatty acid. However, the equal or slightly larger amount of output of IAP to lymphatics was observed in spite of the decrease in lipid absorption in colchicine-treated rats. Histochemically, prolonged activity of IAP in stroma and submucosal lymphatics was found in colchicine-treated rats fed with fat. These results suggest that microtubules are not involved in IAP transport into lymphatics, and these data do not necessarily rule out that IAP plays a role in lipoprotein transport.
This study was performed to clarify how disturbance of lipid metabolism occurred in patients with protein-losing enteropathy (PLE) as compared with that of control individuals and patients with malabsorption syndrome. Analysis of plasma lipids at fasting state showed a decreased proportion of essential fatty acid, especially linoleic and arachidonic acid fractions in patients with malabsorption syndrome as well as in patients with PLE group A, which was due to proven disorders of intestinal lymphatics. An increase in percentage of oleic acid fraction and a percentage increase in plasma triglyceride levels after an oral administration of olive oil was depressed in patients with malabsorption syndrome and PLE group A when compared with that of normal subjects. Patients with PLE group B, which was not due to major lymphatic disorders, were similar to normal in these parameters. These abnormalities were found to be marked when remarkable abnormalities of lymphatics were accompanied.
The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.
Alterations in the concentration of plasma dehydroepiandrosterone sulfate (DHEA-S) and cortisol in patients with essential hypertension (EH) were investigated. The subjects were 25 patients with EH: 7 of low plasma renin activity (PRA) group, 10 of normal PRA group and 8 of high PRA group; 7 normal subjects were used as the controls. Plasma DHEA-S and cortisol were measured before and after the following tests: (1) circadian rhythm (6:00, 16:00 and 24:00), (2) furosemide (0.7 mg/kg) test, (3) ACTH (12.5 IU/4 hr) infusion test, (4) dexamethasone (1.0 mg) test, (5) furosemide (0.7 mg/kg) test under dexamethasone (1.0 mg) treatment, (6) metopirone (1.5 g) test, (7) angiotensin II (8 ng/kg/min, 30 min) infusion test and (8) saline (1000 ml/hr) test. The alterations of the endogenous ACTH-adrenal hormone system as well as the renin-angiotensin-aldosterone system induced by these tests did not cause significant changes of plasma levels of DHEA-S in the 3 groups with EH. However, significant enhancement of plasma DHEA-S was observed after both the administration of exogenous ACTH and angiotensin II. It is considered that the responsiveness of DHEA-S to ACTH may increase in the low and normal PRA groups and that the responsiveness of DHEA-S to angiotensin II may increase in the high PRA group. Based on these results, it is suggested that plasma DHEA-S hardly or only partially participates as a causal factor of EH.
In order to systematically analyze the regulation and metabolism of steroid hormones in a case of primary aldosteronism with multiple lesions, including adenoma and nodular hyperplasia of the left adrenal gland, the amounts of 9 steroids (progesterone (P), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH-B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone (17-OH-P), 11-deoxycortisol (S), cortisol (F) and dehydroepiandrosterone sulfate (DHEAS)) contained in the plasma and in the adrenal tissues were measured. The patient (a 39-year-old female) was admitted to our hospital because of hypokalemia and hypertension. A diagnosis of primary aldosteronism was made on the basis of a complete evaluation, and an adenoma (1.8 x 1.2 cm), a nodular hyperplasia (0.5 x 0.5 cm), a microadenoma and a cortical nodule were found on the left adrenal gland. In vivo studies revealed that the plasma level of Aldo was high, but those of the other steroid hormones were within the normal range. After ACTH infusion, the plasma levels of the 9 steroid hormones increased by 2 to 17 times the base levels. In particular, the responses of DOC and B were markedly high. In vitro studies on P, DOC, B, Aldo and F content in the adenoma (A), the nodular hyperplasia (A'), the adjacent adrenal tissue (C) and the right normal adrenal tissue (D) revealed that, except for F, they were highest in A, followed by A', D and C in that order. In incubation studies with ACTH using A and C, it was found that the levels of 8 steroid hormones with the exception of DHEAS were high in A than in C. In particular, the response of B in A was markedly increased. These findings suggest that aldosteronoma produces 8 steroid hormones under conditions of excess ACTH, while at physiological levels of ACTH, it produces only Aldo in excess.
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A culture product of Streptomyces pseudovenezuelae MF722-02, with a molecular formula of C29H32N2O7, was isolated as yellow needles from culture broths and mycelia of the organism by means of a series of solvent extraction, column chromatography and crystallization. The antibiotic is active against some Gram-positive bacteria, inhibits growth in vitro of cells of mouse leukemia L-1210, prolongs the life span of mice inoculated with the leukemia cells, enhances deoxycholate-induced hemolysis in vitro and inhibits (Na+, K+)-ATPase in vitro.
The 4"-O-substituted tylosin derivatives were prepared by selective esterification of the 4"-OH, and relationships between the substituent groups and antimicrobial activity against macrolide-resistant strains were examined. Introduction of branched-chain aliphatic acyl groups such as 2-methoxyisovaleryl or 4-methylvaleryl group afforded derivatives with good antibacterial activity; MIC values were 12.5 microgram/ml against Staphylococcus aureus MS-8710. MIC values of tylosin, erythromycin and josamycin against this strain were 800 microgram/ml or more. Further improved activity was obtained by introduction of aromatic groups such as phenylthioacetyl, phenylsulfonylacetyl, 4-nitrophenylacetyl, 4-nitrophenylsulfonyl and phenylethanesulfonyl groups; MIC values were 6.25 microgram/ml. These derivatives had also an improved antimycoplasmal activity; MIC values were 0.08 microgram/ml against macrolide-resistant strains of Mycoplasma gallisepticum. MIC values of tylosin against these strains were from 2.5 to 10 microgram/ml. Introduction of the groups described above into the 4"-OH was confirmed to increase the uptake by a resistant strain.
The resistance of Staphylococcus aureus MS-9610 to tylosin and 3-O-acetyltylosin was due to the decreased affinity of its ribosome system to these macrolides. However, 3-O-acetyl-4"-O-isovaleryltylosin was found to bind to ribosomes of the strain about three times more than 3-O-acetyltylosin. This binding was not interfered by tylosin and 3-O-acetyltylosin. The 4"-O-acyl group and the mycinose moiety were suggested to have an important role in the binding of tylosin derivatives to ribosomes of resistant strains.