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Biomedical subjects

H Sano

Publications and source records attributed to H Sano.

At least 523 records · Page 29Linked to original sources
PubMed1990

Inhibition of both etoposide-induced DNA fragmentation and activation of poly(ADP-ribose) synthesis by zinc ion.

Treatment of a human promyelocytic leukemia cell line (HL-60) with etoposide for 3-4 hrs produced an extensive degradation of DNA. Agarose gel electrophoresis showed DNA fragmentation in a nucleosomal ladder pattern. Simultaneous addition of zinc ion (ZnSO4, 1 mM) inhibited DNA fragmentation, although the amount of DNA strand breakage introduced initially by etoposide did not change significantly as measured by the DNA unwinding assay. Furthermore, zinc ion abrogated both the activation of poly(ADP-ribose) synthesis and the morphologic changes characteristic of apoptosis by etoposide. These results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.

Cell Line↗
PubMed1990

Metabolic basis for differential glutamine requirements of human leukemia cell lines.

We compared the ability of human leukemia cell lines of various origins to grow in glutamine-deficient media. The growth of B lymphoblastoid cell lines, including promyelocytic HL-60, is highly dependent on glutamine, whereas T-cell lines are able to proliferate in glutamine-free media. Such glutamine dependency has a good inverse correlation with the activity of glutamine synthetase. Moreover, glutamine synthetase can be induced in glutamine-deficient media, especially in glutamine-independent cells. In HL-60 cells, glutamine deprivation results in the decrease of both ATP and dATP levels. The addition of adenine to the culture medium abolishes these changes without restoring cell growth, indicating that the effects of glutamine deprivation on cell growth cannot be fully explained by the perturbation of adenine nucleotide pools.

Adenine↗
PubMed1990

Thymic stroma-derived T cell growth factor (TSTGF): III. Its ability to promote T cell proliferation without stimulating interleukin 2- or 4-dependent autocrine mechanism.

A thymic stroma-derived cell clone, MRL104.8a produced a T cell growth factor designated as thymic stroma-derived T cell growth factor (TSTGF). This factor that is distinct from previously described T cell growth factors such as interleukin (IL) 2 or 4 was capable of promoting the growth of IL2-dependent, antigen-specific helper T cell clones. While such growth promotion was induced without requirement of the relevant antigen and exogenous IL2, we further investigated whether it depended on activation of an IL2- or IL4-dependent autocrine mechanism. Helper T cell clones, 8-E and 8-5, were able to proliferate in response to stimulation with either antigen or TSTGF. 8-E and 8-5 produced IL2 and IL4, respectively, in cultures following antigenic stimulation, whereas neither IL2 nor IL4 activity was detected in cultures during TSTGF-induced proliferation. The proliferation of these helper T cell clones by antigenic stimulation was almost completely inhibited when anti-IL2 receptor or anti-IL4 antibody was added to the cultures. The addition of cyclosporin A (CsA) to cultures of 8-E and 8-5 clones together with antigen also resulted in the complete inhibition of cellular proliferation in association with the suppression of IL2 and IL4 production. In contrast, TSTGF-induced proliferation was not affected by addition of either type of antibody or CsA. These results indicate that TSTGF is a novel T cell growth factor that can exert its own growth-promoting effect without depending on an IL2- or IL4-operating autocrine mechanism.

Animals↗
PubMed1990

Immune dysfunction expressed selectively on L3T4+ T cells in the tumor-bearing state.

Spleen cells from normal C3H/He or BALB/c mice generate cytotoxic T-lymphocyte (CTL) responses to both trinitrophenyl (TNP)-modified syngeneic cells (TNP-self) and allogeneic cells. In contrast, cells from these strains of mice bearing a syngeneic tumor failed to induce anti-TNP-self-CTL responses, although portions of the same responding cells generated comparable anti-allo-CTL responses to those induced by normal responding cells. Although anti-allo-CTL responses were inducible from only Lyt-2+ T-cell subset of responding cells from normal or tumor-bearing mice, induction of TNP-CTL responses required the participation of L3T4+ T-cell subset as well as Lyt-2+ CTL precursors. In addition, the fact that the addition of concanavalin A-stimulated culture supernatant to cultures of responding cells from tumor-bearing mice resulted in the induction of appreciable anti-TNP-self CTL responses demonstrated the defect of L3T4+ T-cell function in the tumor-bearing state. Such a functional defect was ascribed neither to the loss of L3T4+ T cells nor to the generation of suppressor cells in spleen cells of tumor-bearing mice. It was found on one hand that in vitro stimulation of antigen-presenting cell (APC)-depleted normal responding population with TNP-self prepared from cells of normal or tumor-bearing mice produced comparable anti-TNP CTL responses. On the other hand, APC-depleted responding cells from tumor-bearing mice were unable to induce anti-TNP CTL responses under conditions in which APC-depleted normal responding cells induced an effective TNP-CTL response. These results indicate that selective impairment of L3T4+ T cell-mediated immunity is induced in the tumor-bearing state and that such an impairment is ascribed to the dysfunction of L3T4+ T cells themselves, but not of APC required for the activation of L3T4+ T-cell subset.

Animals↗
PubMed1990

Three cases of syndactyly, polydactyly, and hypoplastic triphalangeal thumb: (Haas's malformation).

Three cases of a complex malformation of the hand involving syndactyly, polydactyly, and hypoplastic triphalangeal thumb are presented. In all three patients, six metacarpal bones and hypoplasticity of the thenar muscles were present. In one patient, both hands, except the most radial digits of the left hand, were completely fused by soft webs as reported by Haas and Ofodile. In two other patients, the extent of the webs differed from Haas's case, but one of them was similar to Ofodile's first case. In all instances the supernumerary digit had a triphalangeal configuration and the thenar muscles were hypoplastic, often associated with some degree of webbing.

Adult↗
PubMed1990

Insulin secretion and glucose uptake in hypomagnesemic sheep fed a low magnesium, high potassium diet.

Hyperglycemic and euglycemic clamp experiments were conducted to evaluate insulin secretion and glucose uptake in the hypomagnesemic sheep fed a low magnesium (Mg), high potassium (K) diet. Five mature sheep were fed a semipurified diet containing 0.24% Mg and 0.56% K (control diet) and five were fed 0.04% Mg and 3.78% K (low Mg/high K diet) for at least 2 weeks. In the hyperglycemic clamp experiment, plasma glucose concentrations were raised and maintained at a hyperglycemic steady-state (approximately 130 mg/100 ml) by variable rates of glucose infusion during the experimental period (120 minutes). The insulin response in the sheep fed the low Mg/high K diet (31.0 microU/ml) were significantly (P < 0.01) lower than those (111.7 microU/ml) of the sheep fed the control diet. In the euglycemic clamp experiment, insulin was infused at rates of 5, 10, 15, or 20 mU/kg/min, each followed by variable rates of glucose infusion to maintain a euglycemic steady-state (basal fasting levels). Hypomagnesemic sheep fed the low Mg/high K diet had significantly (P < 0.01) lower mean glucose disposal (3.72 mg/kg/min) across the insulin infusion rates compared with those of the sheep fed the control diet (5.37 mg/kg/min). These results suggest that glucose-induced insulin secretion and insulin-induced glucose uptake would be depressed in hypomagnesemic sheep and are caused by feeding the low Mg/high K diet.

Journal Article↗
PubMed1990

Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints.

The synovium from patients with rheumatoid arthritis (RA) and LEW/N rats with streptococcal cell wall (SCW) arthritis, an experimental model resembling RA, is characterized by massive proliferation of synovial connective tissues and invasive destruction of periarticular bone and cartilage. Since heparin binding growth factor (HBGF)-1, the precursor of acidic fibroblast growth factor (FGF), is a potent angiogenic polypeptide and mitogen for mesenchymal cells, we sought evidence that it was involved in the synovial pathology of RA and SCW arthritis. HBGF-1 mRNA was detected in RA synovium using the polymerase chain reaction technique, and its product was immunolocalized intracellularly in both RA and osteoarthritis (OA) synovium. HBGF-1 staining was more extensive and intense in synovium of RA patients than OA and correlated with the extent and intensity of synovial mononuclear cell infiltration. HBGF-1 staining also correlated with c-Fos protein staining. In SCW arthritis, HBGF-1 immunostaining was noted in bone marrow, bone, cartilage, synovium, ligamentous and tendinous structures, as well as various dermal structures and developed early in both T-cell competent and incompetent rats. Persistent high level immunostaining of HBGF-1 was only noted in T-cell competent rats like the disease process in general. These observations implicate HBGF-1 in a multitude of biological functions in inflammatory joint diseases.

Animals↗
PubMed1990

Dietary linoleic acid prevents the development of deoxycorticosterone acetate-salt hypertension.

The aim of this study was to elucidate the effect of dietary variations of linoleic acid on the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. All rats were divided into three groups and fed one of the following isocaloric diets with 8% NaCl: a high linoleic acid (HLA) (20% sunflower oil), a moderate linoleic acid (5% lard oil + 15% sunflower oil), or a low linoleic acid (DLA) (20% lard oil). After 4 weeks of feeding, we determined intraerythrocyte sodium, potassium, and magnesium concentrations, intra-aortic and lymphocyte magnesium content, and erythrocyte ouabain-sensitive 22Na efflux rate constant. Cytoplasmic free calcium concentration of lymphocytes from thymus was also determined with quin-2 as a fluorescent indicator. In the HLA group, the elevation of systolic blood pressure was significantly attenuated, and intraerythrocyte sodium concentration was significantly lower than in the DLA group. There were greater intraerythrocyte potassium and magnesium concentrations, intra-aortic and lymphocyte magnesium contents, and erythrocyte ouabain-sensitive 22Na efflux rate constant in the HLA group as compared with other groups. Cytoplasmic free calcium concentration in the HLA group was significantly lower than in other groups. Systolic blood pressure significantly correlated negatively with intraerythrocyte and intra-aortic magnesium concentrations and intraerythrocyte potassium concentration, and correlated positively with cytoplasmic free calcium concentration. Erythrocyte ouabain-sensitive 22Na efflux rate constant significantly correlated positively with intraerythrocyte magnesium concentration. These findings suggest that dietary linoleic acid can attenuate the development of DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of captopril on congestive heart failure.

1) Captopril was orally administered in a dose of 12.5 mg to 12 patients with congestive heart failure to follow changes in its blood concentration and determine changes in clinical test values. 2) The blood concentration of captopril reached its peak in 2 h after medication, the mean value being 274 ng/ml and the half-life 3.16 h. The Tmax and T1/2 were found to be extended as compared with those of normal humans and hypertensive patients that had been reported. No significant differences were noted between Group I of mild cases and Group II of serious cases. 3) Following administration of captopril, a rise in angiotensin I and renin activity and a reduction in aldosterone were noted. These were found to be correlated or inversely correlated with the changes in the blood concentration of captopril. Greater changes were noted in Group II than in Group I. All clinical test values in each group tended to return to the control value 6h after the administration.

Aldosterone↗
PubMed1990

Insulin responsiveness to glucose and tissue responsiveness to insulin over the feeding cycle in sheep.

Insulin responsiveness to glucose and tissue responsiveness to insulin, using the hyperglycemic clamp and the hyperinsulinemic euglycemic clamp techniques, were measured before, during and after feeding in sheep fed an alfalfa hay and commercial concentrate diet. Glucose infusion rate and the plasma insulin increment in the hyperglycemic clamp experiment were higher during the feeding period (0 to 1 h after initiating feeding) than during the pre- and post-feeding periods. The ratio of plasma insulin increment to glucose infusion rate remained unchanged over the feeding cycle. Only a slight increase (P less than .05) in the glucose infusion rate was observed during feeding in the hyperinsulinemic euglycemic clamp experiment. These results suggest that insulin responsiveness to glucose tends to be enhanced during the feeding period but that tissue responsiveness to insulin is not changed over the feeding cycle in sheep.

Animals↗
PubMed1990

The kapurimycins, new antitumor antibiotics produced by Streptomyces. Physico-chemical properties and structure determination.

The kapurimycins A1, A2 and A3 were revealed to be new antitumor antibiotics with molecular formula of C27H26O9, C26H24O9 and C27H24O9, respectively. The structures of the kapurimycins were determined by NMR spectroscopic analysis. The kapurimycins are new class of polycyclic microbial metabolites having the tetrahydroanthra-gamma-pyrone skeleton and the beta, gamma-unsaturated delta-keto carboxylic acid structure. The individual components of the kapurimycins differ from one another in the side chain at the pyrone ring of the molecule.

Anthracenes↗
PubMed1990

Structures of KS-501 and KS-502, the new inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase.

The structures of KS-501 and KS-502, new inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, were determined to be 2-(beta-D-galactofuranosyloxy)-6-heptyl-4-hydroxybenzoic acid 3-heptyl-5-hydroxyphenyl ester and 2-(beta-D-galactofuranosyloxy)6-heptyl-4-hydroxybenzoic acid 4-carboxy-3-heptyl-5-hydroxyphenyl ester, respectively, on the basis of chemical and physico-chemical evidences.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

Structures of the novel anthraquinone antitumor antibiotics, DC92-B and DC92-D.

The structures of the new anthraquinone antitumor antibiotic DC92-B and its photodegradation product DC92-D were determined by their spectral studies. DC92-B and D are pluramycin antibiotics, related to hedamycin which possess a characteristic ring F and a side chain containing a cis-epoxide and terminal dimethyl.

Acetylation↗
PubMed1990

[Studies on acetylspiramycin. II. Biological activities of spiramycin components].

Acetylspiramycin (ASPM) was fractionated using high performance liquid chromatography (HPLC). The peak fractions were named F1 to F7 successively in order of increasing retention times (Rt), i.e., increasing hydrophobicity, and studied for 1) antibacterial activities (MIC), 2) antibacterial potency against Bacillus subtilis ATCC 6633, 3) therapeutic effect on mice infected with Streptococcus pneumoniae III, Staphylococcus aureus Smith, 4) acute toxicity by i.p. administration to mice (LD50) and 5) cytotoxicities to fibroblasts derived from Chinese-hamster lung (CHL), cow pulmonary artery endothelial cells (CPAE) and rat hepatic cells. The results obtained are summarized below. 1. Components F1 and 4'-acetylspiramycin F2 had significantly different biological activities from those of other components: F1 showed the lowest antibacterial potency of 492 micrograms (potency)/mg, F2 showed the highest antibacterial potency of 2,040 micrograms (potency)/mg and correspondingly the lowest LD50 value of 692 mg/kg (the highest toxicity). The therapeutic effect of F2 on infections in mice was found to be the second smallest and was superior only to that of F1. The LD50 value of F1 was 1,200 mg/kg and similar to that of ASPM. 2. Antibacterial potencies of F3, F4, F5 and F6 were 1,165, 1,266, 1,374 and 1,530 micrograms (potency)/mg, respectively; fraction with the higher antibacterial activities corresponded to the longer retention times, i.e., the greater hydrophobicities. The most hydrophobic component, F7, 3-propionyl-3",4"-diacetylspiramycin, however, showed a low antibacterial potency of 1,085 micrograms (potency)/mg, next to the lowest one, F1, a fact which was in contradiction to with the sequential relation between hydrophobicities and potencies from F3 to F6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Long-term follow-up study of alcoholic liver disease].

Two hundred seventy-one patients with various forms of alcoholic liver disease were followed up for an average of 87.9 months. The survival was the lowest for alcoholic cirrhosis (average 10-year survival: 23.8%). Prognosis was grave especially in cirrhotic patients who continued drinking, owing mainly to the increased death due to gastrointestinal bleeding. The development of hepatocellular carcinoma (HCC) was observed during the first six years only in cirrhosis. The average 5-year probability rate of developing HCC for cirrhosis was 16.3%. The rate was significantly higher for the cirrhotic patients who abstained than for those who continued drinking. Serial biopsies were performed on 66 non-cirrhotic patients who continued drinking. The mean duration of histological follow-up 46.0 months. Cirrhosis developed eventually in 30.3% of the cases. In conclusion, the present study indicates that continued drinking causes progressive liver damage and a poor prognosis. Our data also suggest that abstinence is associated with an increased risk of HCC in cirrhosis. Thus, it is important to recover from alcoholism before cirrhosis develops.

Adult↗
PubMed1990

[Studies on acetylspiramycin. 1. Separation and chemical structures of acetylspiramycin components].

1. A macrolide antibiotic acetylspiramycin (ASPM) was separated into seven fractions using high performance liquid chromatography (HPLC) with Lichrosorb RP-8 and mobile phase of a mixed solvent of 0.025M phosphate ammonium (pH 7.4) and acetonitrile at a ratio of 10:18. 2. Five components were purified over 90%, and analyzed using mass spectroscopy, 1H NMR, and 13C NMR, and their chemical structures were determined as 4''-acetylspiramycin I, 4''-acetylspiramycin II, 4''-acetylspiramycin III, 3'',4''-diacetylspiramycin II and 3'',4''-diacetylspiramycin III, respectively. 3. The weight component ratio of the seven fractions of ASPM separated by HPLC was constant throughout several lots of ASPM which had been stocked for nearly 15 years at room temperature, indicating an excellent chemical stability of the antibiotic. 4. Some physicochemical parameters were determined for the five ASPM components. Solubilities in water at 24 degrees C were in a range from 0.14 mg/ml to 4.9 mg/ml, and they were, in the decreasing order, 3'',4''-diacetylspiramycin III, 3'',4''-diacetylspiramycin I 4''-acetylspiramycin III, 4''-acetylspiramycin II, and 4''-acetylspiramycin I. Relationships between solubilities and numbers and positions of acyl substituents in spiramycin molecule are discussed.

Chemical Phenomena↗