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Biomedical subjects

K Shibasaki

Publications and source records attributed to K Shibasaki.

71 records · Page 4Linked to original sources
PubMed1978

Changes of LH, TSH, GH, FSH and PRL in pituitaries and sera of rats after thyroidectomy and thyroxine treatment as studied by radioimmunoassay and disc electrophoresis.

Rat pituitary hormones (LH, TSH, GH, FSH and PRL) were located in polyacrylamide gels after the separation of rat pituitary homogenate with the aid of electrophoresis. Furthermore, the incorporation of 3H-glucosamine and 14C-leucine into various protein fractions of incubation media and pituitaries incubated for 6 h in vitro, homogenized and then subjected to disc electrophoresis was measured in six groups of rats: 1. control; 2. two weeks after thyroidectomy (Tx); 3.--6. two weeks after thyroidectomy and injected 20 micrograms L-thyroxine (T4) i.p. per animal at 6, 12, 24 and 48 h before sacrifice, respectively. A decrease of 14C-leucine incorporation into GH and PRL after thyroidectomy was found which was improved by T4 treatment. Moreover, an increase of 3H-glucosamine and 14C-leucine incorporation into TSH zone and origin zone was observed, the former presumably representing the extracted TSH and the latter consisting of unextracted portion of TSH, other hormones and unidentified proteins. Such increase was significantly less after T4 treatment. Finally, changes of radioimmunoassayable LH, TSH, GH, FSH and PRL in pituitaries and sera of analogous groups of rats, but consisting of another animals were measured. The content of TSH in the pituitary slightly increased after Tx, but increased further after T4 treatment. In contrast, the content of all other hormones in the pituitary decreased after Tx, while T4 treatment resulted in a stepwise increase. In plasma, a significant decrease of GH and PRL after Tx was found with no remarkable changes after T4 treatment. The level of LH and FSH was unchanged, while that of TSH increased significantly after Tx and sharply decreased to the original level as early as at 6 h after the injection of T4.

Animals↗
PubMed1978

Vertebral metastases and spinal cord compression.

Clinical interest in spinal compression and resultant paraplegia due to metastases has mounted in recent years. This has stimulated attention to the neuropathology of the condition. 14 cases of spinal cord compression due to vertebral metastases are compared with over 100 traumatic cases. In the traumatic lesions there is central haemorrhagic necrosis leading to cavitation and gliosis with nerve root regeneration in the late stages. In the metastatic cases, lesions are often peripheral, pie-shaped and are related to vascular factors. The neuropathology of cord necrosis due to metastatic spinal disease is therefore different from that caused by trauma. These observations have clinical importance in planning treatment.

Adult↗
PubMed1977

Beta-conglycinin from soybean proteins. Isolation and immunological and physicochemical properties of the monomeric forms.

Beta-conglycinin consisting of six major isomers (designated B1- to B6-conglycinin) was dissociated and fractionated on columns of DEAE- and CM-Sephadex in buffers containing 6 M urea. Three major (alpha, alpha' and beta) and one minor (gamma) subunits were isolated and further characterized by gel electrophoresis and gel electrofocusing. Gel electrophoresis in urea and in sodium dodecyl sulfate, and gel filtration in 6 M guanidine hydrochloride gave a molecular weight of 57 000 for alpha, alpha' subunits; and 42 000 for beta and gamma subunits. The isoelectric points of the isolated subunits, measured by disc gel electrofocusing, were as follows: alpha, 4.90; alpha', 5.18; beta, 5.66-6.00. On gel electrofocusing, beta subunit showed four microheterogeneous components; three of them comprised 95% of the total beta subunit. Leucine and valine were the N-terminal amino acids of beta and alpha alpha' subunits, respectively. The isolated subunits contained mannose and glucosamine in varying quantities. Two carbohydrate moieties were calculated for one mole of alpha, alpha' subunits; and one carbohydrate moiety for the beta subunit. Considerable similarity in the amino acid composition of alpha and alpha' subunits was observed. The beta subunit was devoid of cysteine and methionine; and in comparison with alpha, alpha' subunits, had a higher content of hydrophobic amino acids. The isolated subunits exhibited antigen-antibody reaction with antisera to the native beta-conglycinin. Each of them was partglycinins. The alpha and alpha' subunits were in addition identical with each other and with B5-, B6-conglycinins. They were immunologically unrelated with beta subunit. The recovery of immuno-properties from the individual subunits may be attributed to the reconstruction of the three-dimensional structure upon removal of denaturing reagents.

Amino Acids↗
PubMed1976

Heterogeneity of beta-conglycinin.

Beta-conglycinin, a major 7 S soybean globulin, purified by ion-exchange and gel chromatography was fractionated into six distinct components on columns of DEAE-Sephadex. The six components (designated B1 to B6-conglycinins) were characterized by disc electrophoresis. Gel electrophoresis and gel electrofocusing in dissociating buffers indicate that the six conglycinins are isomers containing varying proportions of three kinds of subunits (alpha, alpha' and beta). The subunit structures of these isomers are alpha' beta (B1-), alpha beta (B2-), alpha alpha' beta (B3-), alpha beta (B4-), alpha alpha' (B5-), and alpha (B6-conglycinin). Beta subunit is a major constitutent of B1- and B2-conglycinins, whereas B3- to B6-conglycinins are composed predominantly of alpha subunit. The six beta-conglycinins are all glycoproteins containing mannose and glucosamine. They differ in the N-terminal amino acid composition. The isolated B1- to B4-conglycinins are immunologically identical with one another and with the total beta-conglycinin. B5- and Bl-conglycinins which comprise no beta subunit are partially identical with the total protein. Some antigenic determinants that are lacking in the B5- and B6-conglycinins are expected to be located on the beta subunit.

Amino Acid Sequence↗
PubMed1975

Isolation and Characterization of the Multiple 7S Globulins of Soybean Proteins.

Two major proteins (the 7S and 11S globulins) of soybean (Glycine max) were simultaneously isolated by a simple method based on their different solubilities in dilute tris (hydroxymethyl) aminomethane buffers. The purified 7S globulins, which represented essentially the entire 7S soybean protein fraction capable of dimerization at 0.1 ionic strength, were fractionated into five components by diethylaminoethyl Sephadex A-50 column chromatography. The five 7S components were characterized by disc-electrophoresis.

Journal Article↗
PubMedDate not supplied

A pathology database system for autopsy diagnoses using free-text method.

Using natural language a computerized indexing and retrieval system was developed on a commercial database program, DATATRIEVE (Digital Equipment Corporation, Japan). Summarized anatomical diagnoses of nearly 4000 autopsy cases have been registered over a 13-year period at Tokyo Metropolitan Geriatric Hospital. There were 187,367 words in the pathological diagnoses with 4689 distinct words excluding articles, prepositions and conjunctions. 'Atrophy', 'congestion' and 'metastasis' were the most frequent words with frequencies of 4335, 3377, and 3373, respectively. Distinct clinical diagnoses were 2497, among which 'pneumonia', 'hypertension' and 'DIC' predominated. Each step of retrieval by character strings from the sequential data file requires less than a minute.

Aged↗
PubMedDate not supplied

Effect of interferon on incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND/AIMS: The aim of this study was to evaluate whether IFN prevents the development of HCC in patients with chronic hepatitis C. METHODOLOGY: 103 patients with chronic hepatitis C received IFN and 30 control patients were enrolled in this study. RESULTS: In 33 patients (32.0%) who received IFN, alanine aminotransferase (ALT) decreased to normal range and HCV RNA became negative (complete response: CR). In 7 patients (6.7%), ALT decreased to less than 50 IU/L or stayed within the normal range, but HCV RNA remained positive (biochemical response: BR). In 63 patients (61.1%) and 30 control patients, ALT did not change and HCV RNA remained positive (no response: NR). HCC developed in 5 (4.9%) of the 103 patients who received IFN and 7 (23.3%) of the control patients (p<0.01). In 5 patients who developed HCC, the response to IFN was NR and no HCC developed in patients with CR or BR. In addition, 5-year cumulative rate of development of HCC in 63 IFN NR patients and in control was 7.9% and 23.3% (p<0.05). CONCLUSIONS: IFN decreased the development of HCC in not only patients with CR or BR but also patients with NR.

Adolescent↗
PubMedDate not supplied

Calcium entry blocking, beta 1-adrenoceptor blocking and hypotensive effects of YM-16151-4.

The calcium entry blocking, beta 1-adrenoceptor blocking and hypotensive effects of YM-16151-4 were studied in pithed rats and in conscious normotensive rats. In pithed rats, intravenous injection of YM-16151-4 inhibited a YC-170-induced pressor response and an isoproterenol-induced positive chronotropic response with DR10 values of 4.20 and 0.31 mg/kg, respectively. Similarly, a single oral dose of YM-16151-4 inhibited YC-170 and isoproterenol-induced responses with DR10 values of 109.94 and 9.14 mg/kg, respectively. On the other hand, both intravenous and single oral doses of YM-16151-4 produced a dose-dependent hypotensive effect with no increase in heart rate in conscious normotensive rats. The onset of this effect was slow but long-lasting. During repeated oral administration of YM-16151-4 (30 mg/kg) for 5 days, the hypotensive effect of the compound did not change, indicating that this effect did not increase and tolerance did not develop. The time course of the calcium entry blocking activity of YM-16151-4 was very similar to that of its beta 1-adrenoceptor blocking activity, suggesting that the activities of calcium antagonism and beta 1-adrenoceptor blockade of the compound were almost constant at any time after oral dosing. We conclude that YM-16151-4 combines calcium entry and beta 1-adrenoceptor blocking activities in vivo, and produces a hypotensive effect without an increase in heart rate.

Administration, Oral↗
PubMedDate not supplied

Pharmacological properties of YM-15430-1, a 1,4-dihydropyridine derivative with beta 1-adrenoceptor-blocking activity.

The pharmacological properties of YM-15430-1 and its stereoisomers (YM-15430-2, YM-15430-3 and YM-15430-4) were evaluated in in vitro experiments. In the rabbit isolated aorta, all compounds antagonized the CaCl2-induced contraction with a negative logarithm of the dissociation constant in calcium antagonism of 8.51, 7.13, 8.68 and 7.16, respectively. In the rat isolated right atrium, YM-15430-1 produced a competitive antagonism of the isoprenaline-induced tachycardia with a pA2 value of 7.59. YM-15430-2, YM-15430-3 and YM-15430-4 also antagonized the isoprenaline-induced tachycardia, with pA2 values of 7.91, 7.09 and 6.24, respectively. Because it was the most active of the 4 stereoisomers, YM-15430-1 was particularly studied. YM-15430-1 showed an about 100-fold greater selectivity for beta 1- than for beta 2-adrenoceptors, and had no intrinsic sympathomimetic activity. These results suggest that YM-15430-1 is a hybrid compound which combines calcium entry-blocking and selective beta 1-adrenoceptor-blocking activities in one molecule.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Potassium channel-opening and vasorelaxant profiles of a novel compound YM099 in rat isolated portal vein and rabbit isolated aorta.

The potassium channel-opening and vasorelaxant profiles of YM099, a newly synthesized benzoxadiazol derivative K channel opener, were evaluated in vitro. In the rat isolated portal vein, YM099 and a benzopyran derivative K channel opener levcromakalim concentration-dependently inhibited the frequency of spontaneous rhythmic contractions, with IC50 values of 104 and 38 nM, respectively. In the rabbit isolated aorta, YM099 (10(-7)-3 x 10(-5) M) and levcromakalim (10(-7)-3 x 10(-5) M) also concentration-dependently relaxed the contractions induced by 20 mM KCl, but they were ineffective against the contractions induced by 50 mM KCl. These effects of YM099 and levcromakalim were competitively antagonized by a K channel blocker glibenclamide (10(-7)-3 x 10(-6) M). In the rabbit isolated aorta, YM099 (3 x 10(-8)-3 x 10(-6) M), but not the calcium antagonist nifedipine (10(-8)-3 x 10(-6) M), relaxed the contractions induced by norepinephrine (10(-6) M) or prostaglandin F2 alpha (3 x 10(-6) M). These vasorelaxant effects of YM099 were also antagonized by glibenclamide. In conclusion, YM099 is a potent vascular smooth muscle-relaxant agent and possesses a vasorelaxant effect different from that of nifedipine. These effects of YM099 may be mediated, like those of levcromakalim, by the opening of glibenclamide-sensitive K channels.

Animals↗
PubMedDate not supplied

Cardiovascular effects of YM-16151-1 and its optical isomers: a novel calcium entry blocking and beta 1-adrenoceptor blocking agent.

The pharmacological activities of YM-16151-1, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, and its optical isomers were investigated on the cardiovascular system of dogs anesthetized with pentobarbital. YM-16151-1 (0.1-1 mg/kg, i.v.) dose-dependently increased coronary arterial blood flow and decreased mean blood pressure, total peripheral resistance, heart rate and dp/dtmax with almost no effect on cardiac output. S-(-)- and R-(+)-isomers (0.1-1 mg/kg, i.v.) resembled YM-16151-1 in increasing coronary arterial blood flow and decreasing mean blood pressure and total peripheral resistance and were almost equipotent with YM-16151-1 in these effects. However, these optical isomers differed from YM-16151-1 in the changes in heart rate, dp/dtmax and cardiac output. The rank order of potency for these cardiac effects was S-(-)-YM-16151-1 > YM-16151-1 > R-(+)-YM-16151-1. In vagotomized dogs, YM-16151-1 inhibited the isoproterenol (0.2 microgram/kg, i.v.)-induced tachycardia with an ED50 value of 0.11 mg/kg, i.v. S-(-)- and R-(+)-isomers also inhibited the isoproterenol-induced tachycardia with ED50 values of 0.039 and 0.39 mg/kg, i.v., respectively. Thus, the difference in cardiac effects obtained from the anesthetized dog study among these compounds may be caused by the potency difference of their beta 1-adrenoceptor blocking activities. In addition, R-(+)-isomer, possessing a less potent beta 1-adrenoceptor blocking activity than S-(-)-isomer, only produced a dose-dependent tachycardia at the hypotensive doses in conscious dogs. The present results demonstrate that YM-16151-1 behaves as a hybrid compound combining calcium entry blocking and beta 1-adrenoceptor blocking activities, and also demonstrate that YM-16151-1 is a racemic mixture with equal proportions of the two optical isomers, and, as such, the overall activity may be due to the sum of the activities of the individual optical isomers.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Serum des-gamma-carboxyprothrombin level by a modified enzyme immunoassay method in hepatocellular carcinoma: clinical significance in small hepatocellular carcinoma.

BACKGROUND/AIMS: In the diagnosis of hepatocellular carcinoma (HCC), serum des-gamma-carboxyprothrombin (DCP) is a useful tumor marker. The conventional immunoassays for measurement of DCP levels, however, are not sensitive enough to detect small HCC. Therefore, we intended to elevate the minimal detection level of DCP by a modified enzyme linked immunosorbent assay method. METHODOLOGY: This modified assay method is similar to the conventional enzyme linked immunosorbent assay (ELISA) method, but the first reaction occurs overnight. As a result, the minimal detection levels of DCP varied from 0.06 AU/ml, by the conventional method, to 0.008 AU/ml, by the modified method. Two hundred and twenty five serum samples from 100 patients with HCC, 75 with liver cirrhosis and 50 with chronic hepatitis were subjected to the present study. Simultaneous determinations of serum DCP by the modified assay and a-fetoprotein (AFP) levels were performed. RESULTS: Eighty five of 100 patients with HCC had increased DCP levels of more than 0.008 AU/ml. This method yielded a sensitivity of 85%, a specificity of 90% and a total accuracy value of 88%. In 27 patients with small HCC (less than 30 mm in diameter), 12 had elevated DCP levels, resulting in a sensitivity of 44%. When the modified DCP assay together with AFP measurement (more than 20 ng/ml) were introduced, the sensitivity was 67% in the 27 patients with small HCC. CONCLUSIONS: This modified ELISA method increased the sensitivity in patients with small HCC, and the combination assay of serum DCP and AFP levels was more useful for the early diagnosis of HCC.

Adult↗