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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 901 records · Page 50Linked to original sources

Pancreatic endocrine function after total gastrectomy and truncal vagotomy.

Oral and intravenous glucose tolerance tests were performed in four groups: (1) preoperative patients, (2) patients with interposition reconstruction after total gastrectomy, (3) patients with Roux-Y reconstruction after total gastrectomy, and (4) patients with intrathoracic replacement after esophagectomy. We obtained the following results: (1) Hyperglucagonemia in response to orally administered glucose occurred after truncal vagotomy and occurred in the presence and absence of gastric tissue. (2) compared wtih the preoperative study, all postoperative groups demonstrated glucose intolerance. (3) The glucose intolerance was due to increased glucagon, insulinopenia, and possibly nutritional factors. (4) The insulin response to intravenous glucose suggests an impairment in the first phase of insulin secretion in the surgically treated group, demonstrating a role for the vagus in insulin secretion. (5) The glucose tolerance curve shows that the interposition operation is superior the the Roux-Y operation.

Adult↗

Duality of alpha-subunit of canine kidney sodium- and potassium-activated adenosinetriphophatase in electrophoresis.

Sodium- and potassium-activated adenosinetriphosphatase (Na+, K+-ATPase) purified from dog kidney outer medulla was examined by polyacrylamide gel electrophoresis and by photoaffinity labeling with N-(ouabain)-N'-(2-nitro-4-azidophenyl)-ethylenediamine (NAP-ouabain). The large subunit band (alpha-band) split into two bands on the gel after the enzyme was heat-treated in the presence of 1% sodium dodecylsulfate (SDS). Of the two bands (alpha I and alpha II), alpha I had the same electrophoretic mobility as the original band, while alpha II moved slightly faster. Total conversion into alpha II was not observed, about half of the original remaining as alpha I. Below 60 degree C, heat treatment did not produce alpha II. Phenylmethylsulfonyl fluoride did not prevent the appearance of alpha II. Both alpha I and alpha II were labeled with [3H]NAP-ouabain. Nonspecific incorporation of [3H]NAP-ouabain also occurred irrespective of illumination, but it was removed either by diffusion during staining and destaining of the gel or by treatment of the enzyme with trichloroacetic acid. It is tentatively concluded that the splitting of the band reflects some intrinsic differences in situ of the alpha-subunit of dog kidney membrane Na+,K+-ATPase.

Affinity Labels↗

Simultaneous quantitative estimation of galactose-1-phosphate and galactose in blood for the diagnosis of galactosemia.

A new microfluorometrical simultaneous assay method of galactose-1-phosphate and galactose in blood discs was devised by use of alkaline phosphatase and beta-galactose dehydrogenase. Our method statistically corresponded well with the Kirkman's method. It can detect 1 X 10(-10) mole of minimal concentration of galactose-1-phosphate and galactose in one blood disc paper (3 mm in diameter), and this means the sensitivity of assay of galactose-1-phosphate was 0.1 mg%. Assay range in our method was very broad (0-2 mM or 0-10 mM). The accuracy and reproducibility of galactose-1-phosphate assay were 3.4 +/- 0.1 mg%, 8.0 +/- 0.4 mg% or 15.1 +/- 0.6 mg%. Mean values of galactose-1-phosphate and galactose in blood on normal infants were 0.8 mg% and 0.3 mg%, respectively. We applied this method to mass screening of galactosemia and could accurately distinguish many positive and false positive cases detected by Paigen's and Beutler's methods. This method gave us an easy and accurate assay system for the diagnosis of uridyl transferase and galactokinase deficiencies.

Alkaline Phosphatase↗

[Early adenine arabinoside therapy in herpes simplex encephalitis (HSE)].

Five patients with HSE were treated with adenine arabinoside and one additional patient with cytosine arabinoside. The diagnosis of HSE was confirmed in retrospect by the rising CF titers and the Enzyme-Linked Immunosorbent Assay (ELISA) levels in CSF (Table 2). Brain biopsy was not performed. The treatment was started promptly when HSE was strongly suspected by symptoms and signs, EEG, CT and CSF findings before the specific laboratory data were available. The clinical and laboratory data on the 6 patients were shown in Table 1. All the 5 patients of HSE treated with adenine arabinoside survived: 3 returned to normal daily life, including one having no neurological deficits, and the other 2 had mild to moderate memory disturbances. Improvement of CT abnormalities indicated a good prognosis. Age or sex did not have influence on the prognosis. The patient treated with cytosine arabinoside died of complications after being in a state of apallic syndrome for 1 year and 8 months. On the basis of the analysis of our patients, one of the crucial factors in the treatment of HSE seems to be the earliest possible use of adenine arabinoside: in our patients on the 2nd up to 9th day of onset, although there was no correlation between the day the medication was started and the morbidity. The other important factor includes the management of acute stage of HSE: the treatment of cerebral edema and generalized convulsions. The major side effects of adenine arabinoside included diarrhea (one case), elevation of GOT, GPT or LDH (one case) which all improved after the treatment. Adenine arabinoside could be an effective drug for HSE reducing the mortality and morbidity with few side effects.

Adult↗

Morphological and electrophysiological evidence for axonal regeneration of axotomized cerebellothalamic neurons in kittens.

Against the current concept of abortive regeneration of axotomized neurons in the mammalian central nervous system, the occurrence of remarkable axonal regeneration of cerebellothalamic projection neurons following transection of the decussation of the superior cerebellar peduncle was proved in kittens morphologically by utilizing anterograde axonal transport of horseradish peroxidase and electrophysiologically by recording the cerebellar-induced cerebral cortical potential. Following axotomy, not only axonal regeneration occurred but also retrograde degeneration of somata which was apparently noticeable as cell loss. The extent of cerebellar nuclear cell loss was inversely related to the extent of regeneration of cerebellofugal axons.

Animals↗

Effect of polyamines on purified poly(ADP-ribose) synthetase from rat liver nuclei.

Using the purified enzyme system, we investigated the spermine-induced stimulation of poly(ADP-ribose) formation. In the presence of 2 microgram DNA and 10 mM Mg2+ in a reaction mixture of 0.2 ml, the optimal concentrations of spermine, spermidine and putrescine were 10, 12.5 and 35 mM, respectively. With the omission of Mg2+, there was an increase in optimal concentrations of polyamines without changes in the rate of poly(ADP-ribose) formation. The concentrations of spermine required for maximum synthesis of poly(ADP-ribose) were increased in proportion to the increase in the amount of DNA. Kinetic analysis of poly(ADP-ribose) formation showed a decrease in Km values for NAD with the addition of spermine. The possible relationship of polyions with regard to DNA, spermine and histone in the purified enzyme system was discussed.

Animals↗

Effect of sodium n-butyrate on induction of prostaglandin synthase activity in cloned mastocytoma P-815 2-E-6 cells.

Treatment of a cloned mastocytoma P-815 cell line (2-E-6) with 1 mM-sodium n-butyrate for 40h induced prostaglandin synthase activity and arrested cell growth. The induction of enzyme activity by n-butyrate was not associated with suppression of DNA synthesis, since hydroxyurea had no effect on prostaglandin synthase induction. The effect of sodium n-butyrate was reversible. Experiments with cycloheximide and actinomycin D showed that the induction of prostaglandin synthase activity involved synthesis de novo of protein and RNA. The time of half-maximal induction of the newly synthesized RNA for prostaglandin synthase activity was estimated as about 15h, which is similar to the generation time of the cells. Selective induction of fatty acid cyclo-oxygenase activity by sodium n-butyrate was suggested by the following two pieces of experimental evidence. (1) There was no significant difference between treated and untreated cells in the activities of radioactive prostaglandin H2 conversion into individual prostaglandins. (2) The incorporation of [3H]acetylsalicylic acid into the fraction equivalent to protein of mol.wt. approx. 75000 of sodium n-butyrate-treated cells was higher than that of untreated cells, on analysis of cell particulate fraction by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. A high concentration (5 mM) of sodium propionate also induced prostaglandin synthesis, but other short-chain fatty acids, such as isobutyrate and sodium acetate, had no effect.

Animals↗

Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives.

The structure--activity relationships of imidazole derivatives as inhibitors of thromboxane (TX) synthetase were investigated. Introduction of various substituents (e.g., one or two methyl groups, a halogen atom, a methylidene group, unsaturated bonds, or a phenylene group) into the alpha position or other positions in the carboxy-bearing side chain of 1-(7-carboxyheptyl)imidazole (15) was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum for the inhibitory potency on TX synthetase in the region of 8.5-9.0 A. Among the tested imidazole derivatives, 1-(7-carboxy-7-methyl-2-octynyl)imidazole (47), 4-[3-(1-imidazolyl)-propyl]benzoic acid (50), and (E)-4-(1-imidazolylmethyl)cinnamic acid (54) and its alpha-methyl analogue (57) showed the highest potency with an IC50 in the range of 10(-8) to 10(-9) M. Inhibition by these derivatives was highly selective for the TX synthetase, since other enzymes such as fatty acid cyclo-oxygenase and prostacyclin synthetase were not affected.

Animals↗

Highly selective inhibitors of thromboxane synthetase. 2. Pyridine derivatives.

The enzyme thromboxane (TX) synthetase is inhibited by pyridine. The beta-substituted pyridine derivatives showed higher inhibitory potency than the gamma-substituted ones having the same side chain. Among the beta-substituted derivatives containing the omega-carboxyalkyl group, the compounds with 6-8 carbon atoms in the side chain were especially effective. The derivatives holding the phenylene group in the side chain exhibited much higher inhibitory activity than those of the alkylene type. Among them, (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid hydrochloride (5a) had the highest potency (IC50 = 3 x 10(-9) M). The beta-substituted pyridine derivatives and 1-substituted imidazole derivatives which had the same side chain showed almost the same potency. The beta-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidonic cascade.

Animals↗