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Biomedical subjects

H Shibata

Publications and source records attributed to H Shibata.

At least 505 records · Page 28Linked to original sources
PubMed1990

Reversal of resistance to doxorubicin with cepharanthine in murine P388 leukemia cells.

Cytotoxic effect in vitro and antitumor effect in vivo of doxorubicin (DOX) combined with cepharanthine were investigated on DOX-resistant murine P388 leukemia (P388/R) cells. Cepharanthine was minimally cytotoxic in the cell line, but reversed DOX-resistance in a dose-related manner in P388/R cells. The administration of cepharanthine to mice bearing the P388 leukemia enhanced the antitumor activity of DOX. These results indicate that cepharanthine is an effective agent to reverse DOX-resistant cells.

Alkaloids↗
PubMed1990

In vitro responsiveness of aldosterone-producing adenoma to angiotensin II, K and ACTH.

In vitro responsiveness to various stimulators of aldosterone secretion was studied in a perifusion system using slices obtained from three aldosterone-producing adenomas (APAs), three adjacent nontumorous glands and three normal adrenal glands. All three APA tissues responded to angiotensin II, K and ACTH in vitro. Angiotensin II (10 nM), K (12 mM) and ACTH (10 nM) caused more than a 2-fold increase in aldosterone secretion. The sensitivity of APA tissues to angiotensin II was identical to that in normal adrenal cortex. In slices obtained from APA, angiotensin II induced rapid increases in [3H]inositol and [45Ca] efflux, both of which preceded the aldosterone response. These results suggest that APA cells have an almost normal transducing system to stimulators of aldosterone secretion.

Adenoma↗
PubMed1990

The changes in the levels of dihydrofolate reductase mRNA and its gene dosage in 5-fluorouracil-resistant L1210 cells.

5-Fluorouracil (5-FU)-resistant L1210 cell line (L1210/5-FU-1) was established in this laboratory, and maintained by serial passage in the peritoneal cavities of BDF1 mice. This and another 5-FU-resistant cell line (L1210/5-FU-2) showed approximately 50-fold increase in resistance to 5-FU, i.e., IC50 of 5-FU determined for wild type L1210 cells was 3 x 10(-7) M, whereas those for 5-FU-resistant lines, L1210/5-FU-1 and L1210/5-FU-2 were 1.65 x 10(-5) M and 1.35 x 10(-5) M, respectively. The incorporation of 3H-5-FU into L1210/5-FU-1 cells was about 57% of that observed in wild type L1210 cells. Northern blot analysis of DHFR mRNA obtained from 5-FU-sensitive and -resistant cell lines revealed four distinct bands of 1.6 kb, 1.2 kb, 1.0 kb and 0.75 kb in length. Although all these bands showed higher density in autoradiography in 5-FU-resistant lines than in wild type, no extra band was observed. Southern blot analysis of DHFR DNA, digested with the restriction enzymes, EcoRI, BamHI or HindIII, revealed no rearrangement. However, all the fragments were expanded, showing that DHFR gene increased in 5-FU-resistant cells. The karyotype analysis carried out for L1210/5-FU-1 showed abnormal banding region in a part of chromosome X, and this chromosomal aberration was considered to be the reflection of the amplification of DHFR gene. Many investigators have reported that thymidylate synthetase (TS), a target enzyme for 5-FU, increased in 5-FU-resistant cells and that the increase of TS was responsible for the drug resistance to 5-FU. The increase both in DHFR mRNA and DHFR DNA suggested the increase in DHFR and also in N5, N10 methylenetetrahydrofolate (methylene THF), a coenzyme of TS. The increase of methylene THF, together with the increase of TS, might result in the resistance of the cells to 5-FU.

Animals↗
PubMed1990

Effect of DL-ethionine on blood clearance of 99mTc-phytate in dogs.

The effect of DL-ethionine (EthN) on the blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and the blood clearance test of 99mTc-P was compared with the cases of the serum transaminase and bilirubin test. Serum transaminase and bilirubin levels in dogs increased dose-dependently after the administration of EthN. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of EthN and with the passage of time after EthN administration. Changes of the blood clearance of 99mTc-P after EthN treatment in dogs may be influenced by the disorder in the hepatocytes. The blood clearance test of 99mTc-P in dogs showed a reaction for the acute hepatic dysfunction induced by EthN equally to the serum transaminase and bilirubin test.

Alanine Transaminase↗
PubMed1990

[Chewing ability in relation to physical health status].

The purpose of the present study is to explore relationship of chewing ability to physical health status in the elderly. Subjects were 722 community elderly adults aged 65 years and over (participation rate 88.6%). They were divided into 2 groups according to chewing ability as rated by a questionnaire: good and bad. Results obtained were as follows; 1. Those who had good ability of chewing accounted for 86% of the subjects. The chewing ability was determined by dental status. Those with more natural teeth were better able to chew. 2. Multiple regression analyses controlled by age and sex showed that good chewing ability had significantly positive effect on weight, body mass and length of time for standing on one leg with eyes open.

Aged↗
PubMed1990

Intestinal calcium transport in spontaneously hypertensive rats (SHR) and their genetically matched WKY rats.

Calcium transport across the basolateral membranes of the enterocyte represents the active step in calcium translocation. This step occurs by two mechanisms, an ATP-dependent pump and a Ca2+/Na+ exchange process. These studies were designed to investigate these two processes in jejunal basolateral membrane vesicles (BLMV) of the spontaneously hypertensive rats (SHR) and their genetically matched controls, Wistar-Kyoto (WKY) rats. The ATP-dependent calcium uptake was stimulated several-fold compared with no ATP condition in both SHR and WKY, but no differences were noted between rate of calcium uptake in SHR and WKY. Kinetics of ATP-dependent calcium uptake at concentrations between 0.01 and 1.0 microM revealed a Vmax of 0.67 +/- 0.03 nmol/mg protein/20 sec and a Km of 0.2 +/- 0.03 microM in SHR and Vmax of 0.69 +/- 0.12 and a Km of 0.32 +/- 0.14 microM in WKY rats. Ca2+/Na+ exchange in jejunal BLMV of SHR and WKY was investigated in two ways. First, sodium was added to the incubation medium (cis-Na+). Second, Ca2+ efflux from BLMV was studied in the presence of extravesicular Na+ (trans-Na+). Both studies suggest a decreased exchange of calcium and Na+. Kinetic parameters of Na(+)-dependent Ca2+ uptake at concentrations between 0.01 and 1.0 microM exhibited Vmax of 0.05 +/- 0.01 nanmol/mg protein/5 sec and a Km of 0.21 +/- 0.13 microM in SHR and Vmax of 0.11 +/- 0.02 nanmol/mg protein/5 sec and a Km of 0.09 +/- 0.05 in WKY, respectively. These results confirm that the intestinal BLMV of SHR and WKY rats have two mechanisms for calcium extrusion, an ATP-dependent Ca2+ transport process and a Na+/Ca2+ exchange process. The ATP-dependent process appears to be functional in SHR; however, the Ca2+/Na+ exchange mechanism appears to have a marked decrease in its maximal capacity. These findings suggest that calcium extrusion via Ca2+/Na+ is impaired in the SHR, which may lead to an increase in intracellular calcium concentration. These findings may have relevance to the development of hypertension.

Adenosine Triphosphate↗
PubMed1990

[Concentration and behavior of radiocesium in higher basidiomycetes in some Kanto and the Koshin districts, Japan].

Concentration of 137Cs, 134Cs and potassium were measured in several higher fungi and in substrates, soils, woods and litters in some Kanto and the Koshin districts, Japan, following the Chernobyl accident during October to November 1989. 137Cs concentrations in fungi were in the range of 0.7-101 Bq kg-1.fresh. Maximum 137Cs level in them was observed in Boletopsis leucomelas (Pers.: Fr.) Fayod. Significnatly higher levels of concentration ratios of 137Cs in fungi to substrates (e.g.; 137Cs concentration.fresh in fungus/137Cs concentration.dry in soil), 10(-1) to 10 x 10(-1), were found nearly 10 to 1000 times as much as leaf vegetables, root crops and potatoes to substrates. It was confirmed that levels of concentration ratios of potassium were similar to those of 137Cs. In all fungi, 134Cs which released from the Chernobyl accident and is not present in nuclear weapons fallout was not detected.

Accidents↗
PubMed1990

[Bedridden period before death (BPbd) and factors relating to it in a rural community in Yamagata Prefecture].

The purpose of this study is to analyze the 'Bedridden period before death (BPbd)' and factors relating to it in a community. In the period from January 1986 through December 1988, 352 persons aged 40 years and over were recorded as having died in a rural town with a population of 13,000 in Yamagata Prefecture. The care-givers of 312 subjects (88.6%) were interviewed regarding the BPbd, and demographic, medical, social and familial factors were also investigated. Results obtained are as follows; 1) Subjects who had more than six months BPbd were more frequent in females than in males. 2) Neither age of death nor age of the bedridden had any significant relationship to BPbd in either sex. 3) Positive significant factors relating to BPbd were, occupation (male), history of cerebrovascular diseases (both sexes), care-giver knowledge of health or social services in the town (both sexes) and the presence of pressure sores (both sexes). 4) About half of the subjects had less than two weeks BPbd, though less than 20% of the subjects had more than six months BPbd. This result agreed with that of the national report, "TSUI-NO MITORI CHOSA", where subjects ranged in age from 70 to 85. These results indicate that in the study community most of the adults, including the elderly, have a fairly short BPbd.

Activities of Daily Living↗
PubMed1990

Difference in onset between cytomegalovirus and idiopathic interstitial pneumonitis following allogeneic bone marrow transplantation for leukemia.

Interstitial pneumonitis is one of the major causes of morbidity and mortality following bone marrow transplantation (BMT). Based on the Japanese BMT Registry, however, since 1983 the incidence of interstitial pneumonitis at one year has decreased to 32% by means of several efforts, such as fractionated low-dose rate total body irradiation, selection of platelet donor from cytomegalovirus (CMV) seronegative donor, and prophylactic administration of anti-CMV high titer globulin. Cytomegalovirus (58%) was the most frequently causative organism within 100 days after bone marrow transplantation. On the other hand, idiopathic interstitial pneumonitis (44%) was the leading cause more than 100 days after bone marrow transplantation. There was a significant difference in onset after bone marrow transplantation against leukemia between cytomegalovirus (mean: 90 +/- 15 days) and idiopathic interstitial pneumonitis (mean: 186 +/- 32 days) (p less than 0.01).

Bone Marrow Transplantation↗
PubMed1990

[DNA damage and anticancer effect].

In a sense, cancer chemotherapy is similar to antibacterial chemotherapy. The main target for both chemotherapies is on DNA and its precursors. Whenever anticancer drugs exhibit its activity on cancer cells, damage or metabolic abnormality of DNA is usually accompanied. Among various anticancer drugs, the main cellular target of alkylating agents or anticancer antibiotics is DNA strand, and many of newly introduced anticancer drugs exert effect on DNA strand or DNA synthesis. The mechanism of action of quinocarmycin, KT 6149, which is a derivative of mitomycin C, YM534, which shows thrombocyte agglutination activity, and MCNU, a nitrosourea, were studied for their antitumor action and damage to DNA strand. It was found that there was a close relationship between anticancer effect and single strand scission of DNA in all the agents tested.

Animals↗
PubMed1990

[Antitumor activity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea, LY 186641 against various human cancers using subrenal capsule assay].

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively. The antitumor effect obtained by LY 186641 was comparable to that of the standard anticancer drugs including adriamycin, 5-fluorouracil and cisplatin evaluated in this assay simultaneously. Based upon these results, LY 186641 is considered to have antitumor activity against some human cancers.

Antineoplastic Agents↗
PubMed1990

[Studies on the deviation of short-term FRC measurements with He closed-circuit method and on diurnal variation of FRC].

It was revealed by chance that the second FRC value measured by Chest Chestac 65V was significantly smaller than the first FRC value measured by Fukuda FRC Computer COMF-100 if the second repeated measurement in the same subjects was done shortly after the first FRC measurement with He closed-circuit method was performed. In order to clarify this phenomenon, the volumes of two different machines were accurately checked by a cylinder. No significant differences were found in the FRC values of two machines. In adult healthy subjects a small but significant difference between the first and the second ten minutes behind measurement was found even if the same machine was used. If FRC measurement was reexamined within a few minutes after the first one was done, much differences were found. Furthermore, diurnal variation of FRC values in the same subjects was also observed. FRC value in the morning was the highest.

Adult↗
PubMed1990

Disposition and effect of the new thromboxane synthetase inhibitor 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid in man.

The disposition of a new thromboxane synthetase inhibitor, 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904) upon administration of a single 200-mg oral dose to normal Japanese volunteers was studied. DP-1904 proved to be rapidly absorbed from the gastrointestinal tract and converted to its ester glucuronide, which appeared in plasma within 30 min after dosing. The AUCs of DP-1904 and its ester glucuronide were 7.23 +/- 0.54 and 7.93 +/- 0.86 micrograms.h/ml (mean +/- S.E., n = 5), respectively. Both compounds were also eliminated very rapidly from the body (half-lives greater than 60 min). The primary route of elimination was renal, with 52.1 +/- 2.2 and 37.6 +/- 1.6% of the dose being excreted in the urine as the unchanged form and the glucuronide conjugate within 48 h, respectively. The cumulative fecal excretion rates of DP-1904 up to 48 h after dosing were approximately 0.5%. The main metabolite of DP-1904 in humans was DP-1904 glucuronide. Serum thromboxane (TX) B2 levels were reduced more than 98% within 1 h after dosing. There was still more than 75% suppression of serum TXB2 levels at 12 h after dosing. At 72 h TXB2 concentrations returned to control levels. These data indicate that DP-1904 is a potent and long-acting thromboxane synthetase inhibitor.

Adult↗
PubMed1989

Cyclic GMP-dependent stimulation of the membrane-bound insulin-sensitive cAMP phosphodiesterase from rat adipocytes.

The insulin-sensitive cAMP phosphodiesterase (phosphodiesterase) in rat adipocytes is a membrane-bound low Km enzyme that can be recovered in a crude microsomal fraction (Fraction P-2). The action of this enzyme to hydrolyze cAMP is known to be inhibited by cGMP; nevertheless, it was found in our present study that under selected conditions, the enzyme can also be stimulated by cGMP as well as some other nucleotide derivatives. The maximum cGMP-dependent stimulation was observed when the enzyme in Fraction P-2 was incubated with 10 microM cGMP for 5-20 min at 37 degrees C in the presence of Mg2+, washed, and then assayed in the absence of added cGMP. The level of this stimulation was close to, but less than, that achieved by insulin in intact cells. The actions of the cGMP- and insulin-stimulated enzymes to hydrolyze labeled cAMP were inhibited in an identical manner by cilostamide (Ki = 0.10 microM), griseolic acid (Ki = 0.19 microM), unlabeled cAMP (Km = 0.20 microM), and cGMP (Ki = 0.16 microM), all added to the assay system. Also, the basal, insulin-stimulated, and cGMP-activated enzymes were identically inhibited by a polyclonal antibody raised against a purified membrane-bound low Km phosphodiesterase from bovine adipose tissue. When the same antibody was used for the Western blot analysis of Fraction P-2, it immunoreacted with a single band of protein (165 kDa). These observations indicate that the insulin-sensitive phosphodiesterase in rat adipocytes can be stimulated with 10 microM cGMP and that this stimulation is detectable only after the nucleotide has been eliminated since the enzyme would be strongly inhibited by the nucleotide if the latter exists in the assay system. It is proposed that the insulin-sensitive phosphodiesterase, which is often referred to as a Type IV enzyme, is functionally similar to the Type II enzymes that are known to be stimulated by a low concentration of cGMP and inhibited by higher concentrations of the same nucleotide.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Descending projections to the mammillary nuclei in the rat, as studied by retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase.

The cells of origin and projection fields of the descending afferents to the mammillary nuclei were studied in the rat with retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. The subiculum projects bilaterally to the entire medial mammillary nucleus (MM) in a topographic fashion along the two axes: 1) the proximal part of the subiculum along the presubiculo-CA1 axis projects to the caudal and lateral regions of the MM whereas the more distal part of the subiculum projects to the medial region; 2) the septal part of the subiculum projects to the caudodorsal region of the MM whereas the more temporal part projects progressively to the more rostroventral regions. The ventral subiculum also projects ipsilaterally to the ventral and lateral margin of the lateral mammillary nucleus (LM). The presubiculum projects bilaterally to the dorsolateral region of the pars posterior of the MM and ipsilaterally to the LM. The infra-limbic cortex projects bilaterally to the rostrodorsal region of the MM, whereas the retrosplenial cortex (areas 29a and 29b) projects bilaterally to the medial region at the midrostrocaudal and middorsoventral levels of the MM. The nucleus of the diagonal band projects bilaterally to the caudomedial region of the MM, whereas the lateral septal nucleus projects bilaterally to the pars mediana and the mammillary fiber capsule. A part of the anterior hypothalamic area ventromedial to the fornix projects predominantly ipsilaterally to the rostroventral part of the MM, whereas other basal forebrain regions such as the bed nucleus of the stria terminalis, the medial preoptic and anterior hypothalamic areas, and the area of the tuber cinereum send fibers predominantly ipsilaterally to the mammillary fiber capsule. The results reveal a complex organization of the descending projections to the mammillary nuclei, which may reflect the complex functions of these nuclei within the limbic circuitry.

Afferent Pathways↗