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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 343 records · Page 19Linked to original sources
PubMed1997

Effects of [Ca2+]i, SR Ca2+ load, and rest on Ca2+ spark frequency in ventricular myocytes.

In heart, spontaneous local increases in cytosolic Ca2+ concentration ([Ca2+]i) called "Ca2+ sparks" may be fundamental events underlying both excitation-contraction coupling and resting Ca2+ leak from the sarcoplasmic reticulum (SR). In this study, resting Ca2+ sparks were analyzed in rabbit and rat ventricular myocytes with laser scanning confocal microscopy and the fluorescent Ca2+ indicator fluo 3. During the first 20 s of rest after regular electrical stimulation, both the frequency of Ca2+ sparks and SR Ca2+ content gradually decreased in rabbit. When rabbit SR Ca2+ content was decreased by reduction of stimulation rate. the initial resting spark frequency was also decreased, even though resting [Ca2+]i was unchanged. The rest-dependent decrease in spark frequency in rabbit cells was prevented by inhibition of Na+/Ca2+ exchange (which also prevents SR Ca2+ depletion during rest). These results suggest that elevation of SR Ca2+ content can increase Ca2+ spark frequency. In contrast to rabbit cells, 20 s of rest produced a gradual increase in spark frequency in rat cells, although SR Ca2+ content was constant and Ca2+ influx was completely prevented. This indicates that there is a time-dependent increase in spark probability during rest that is independent of [Ca2+]i or SR Ca2+. This effect was also apparent in rabbit cells when SR Ca2+ depletion was prevented by blocking Na+/Ca2+ exchange. Stimulation of Ca2+ extrusion via Na+/Ca2+ exchange in the rat (by Ca2+-free superfusion, which slowly depletes SR Ca2+ content) converted the normal rest-dependent increase in spark frequency to a decrease. The amplitude of individual Ca2+ sparks increased with increasing SR Ca2+ content. In the Ca2+-overloaded state, fusion of sparks or long-lasting localized increases of [Ca2+]i were observed with increased spark frequency. We conclude that the resting frequency of Ca2+ sparks can be independently affected by changes in SR Ca2+ content, [Ca2+]i, or rest period. The latter may reflect recovery of the SR Ca2+ release channels from inactivation or adaptation.

Animals↗
PubMed1997

Cardiac myocyte volume, Ca2+ fluxes, and sarcoplasmic reticulum loading in pressure-overload hypertrophy.

Alterations in cellular Ca2+ transport and excitation-contraction coupling may contribute to dysfunction in cardiac hypertrophy. Left ventricular myocytes were isolated from rat hearts after 15-18 wk of suprarenal abdominal aortic banding to evaluate the hypothesis that hypertrophy alters the relationship between Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ load during steady-state voltage-clamp depolarization. Mean arterial pressure (MAP) and heart weight-to-body weight ratio of banded (B) animals were significantly higher than in control or sham-operated animals (C). Isolated myocyte dimensions and volume increased in parallel with whole heart hypertrophy and elevation in MAP. However, the relationship between membrane surface area (measured by capacitance) and cell volume (measured by laser scanning confocal microscopy) was unaltered (C: 8.9 +/- 0.3; B: 8.5 +/- 0.4 pF/pl). No differences in the voltage dependence of ICa activation, steady-state inactivation, or recovery from inactivation were detected between C and B myocytes. Maximal ICa density for the two groups was also not different either under basal conditions (C: 4.28 +/- 0.98; B: 4.57 +/- 0.60 pA/pF) or in the presence of 1 microM isoproterenol (C: 16.6 +/- 2.3; B: 16.5 +/- 2.3 pA/pF). The fraction of Ca2+ released from the SR by a single twitch was 55.4 +/- 9.4% in C and 37.1 +/- 6.9% in B (not significantly different). Steady-state Ca2+ influx during a twitch was calculated in units of micromoles per liter of nonmitochondrial volume from the integral of ICa (C: 13.4 +/- 0.7 microM; B: 13.3 +/- 0.8 microM). The SR Ca2+ load was similarly calculated by integration of Na+/Ca2+ exchange current induced by rapid caffeine application (C: 140 +/- 9 microM; B: 169 +/- 18 microM). We conclude that significant cellular hypertrophy is associated with proportional increases in sarcolemmal ICa influx, SR Ca2+ loading, and the amount of SR Ca2+ released in this model of pressure overload.

Animals↗
PubMed1997

A proposed nomenclature of the domestic cat karyotype.

High-resolution G- and Q-band patterns of cat (Felis catus) prometaphase chromosomes with more than 450 numbered bands are presented. This number represents approximately twice the number of bands per haploid set exhibited by feline chromosomes at mid-metaphase. A diagrammatic representation of G-banded cat chromosomes has already been described (O'Brien and Nash, 1982); however, precise numbering of bands and landmarks, as in the human karyotype and in the karyotypes of other domestic and laboratory animals, has not yet been available for the domestic cat karyotype, except for the RBG-banded ideograms constructed by Shibasaki et al. (1987) and Rønne and Storm (1995). In this report, we propose a numbering system for the G-banded ideogram reported previously (O'Brien and Nash, 1982) and an extended ideogram at the high-resolution level (473 numbered bands) as a contribution to the future standardization of the feline karyotype.

Animals↗
PubMed1997

Production of cytokeratin 19 fragment by human squamous lung cancer cell lines.

Cytokeratins form part of the cytoskeleton of both normal and malignant epithelium. A novel tumor marker measuring cytokeratin 19 (CK-19) fragment has been introduced and proven to be suitable for monitoring therapy and following cases of non-small cell lung cancer, squamous cell lung cancer in particular. However, whether the serum level of CK-19 fragment reflects the number of proliferating tumor mass remains unknown. We studied the CK-19 fragment produced by two human squamous cell lung cancer cell lines. In Western blotting analysis, culture supernatants of both cell lines displayed bands of 37 and 40 kDa, which represented the CK-19 fragment and the intact CK-19, respectively. Gel filtration demonstrated that a part of soluble CK-19 was released as a large complex form in culture supernatants. The level of CK-19 fragment in culture supernatants increased during the exponential growth phase. CK-19 level decreased by an addition of a cytotoxic agent to non-significant level though the transient release of CK-19 fragment occurred during the first 2 days. After all, soluble CK-19 fragments were detected in culture supernatants of human lung cancer cell lines and its level reflected proliferating cancer cells though it was not determined whether CK-19 fragments were released directly from live cells.

Carcinoma, Squamous Cell↗
PubMed1997

Urokinase-type plasminogen activator in carcinomatous pleural fluid.

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are involved in its accumulation. Using an enzyme-linked immunosorbent assay, we quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous pleural fluid compared with the level in transudative pleural fluid from patients with CHF (p<0.0001). The levels of u-PA were not statistically different between patients with cancer and tuberculosis, or between patients with cancer and pneumonia. The levels of u-PA in patients who did not respond to chemical pleurodesis were significantly higher than those who had complete response (p=0.0001). In immunocytochemical and immunoblotting studies, cancer cells in pleural fluids as well as mesothelial cells contained u-PA. u-PA was detected in the culture supernatants of viable pleural cells in the majority of patients with carcinomatous pleuritis. Our results suggest that local release of urokinase-type plasminogen activator by viable cells, including cancer cells and mesothelial cells, may affect the levels of urokinase-type plasminogen activator in pleural fluids.

Adenocarcinoma↗
PubMed1997

Prevention of gastric ulcer relapse induced by indomethacin in rats by a mutein of basic fibroblast growth factor.

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H2-receptor antagonists (H2-RAs) on ulcer relapse in this model. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starting 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

Acetic Acid↗
PubMed1997

New ulcerative colitis model induced by sulfhydryl blockers in rats and the effects of antiinflammatory drugs on the colitis.

We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.

Animals↗
PubMed1997

Role of endogenous basic fibroblast growth factor in the healing of gastric ulcers in rats.

Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580) may be involved in its effect on ulcer healing.

Animals↗
PubMed1997

FR149175, a beta 3-adrenoceptor-selective agonist, is a possible therapeutic agent for non-insulin-dependent diabetes mellitus.

We examined whether FR149175 (ethyl-[(S)-8-[(R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-6,7,8,9 - tetrahydro-5H-benzocyclohepten-2-yloxy]acetate monohydrochloride monohydrate), a selective agonist for the beta 3-adrenoceptor, is a possible therapeutic agent for non-insulin-dependent diabetes mellitus (NIDDM). FR149175 had hypoglycemic effects with an increase in the level of plasma insulin in normal rats. In Zucker fatty rats, an animal model of NIDDM, repeated administration of the drug improved hyperinsulinemia and showed a tendency to decrease the area under the curve (AUC) for plasma glucose levels in the glucose tolerance test. Moreover, FR149175 decreased plasma triglyceride, free fatty acid and total cholesterol levels in the rats. Body weight gain in the rat was suppressed by FR149175 as well. These results suggest that FR149175 has antiobesity and antidiabetic effects and that this drug may be useful for treating NIDDM.

Adrenergic beta-Agonists↗
PubMed1997

Predictive value of home blood pressure measurement in relation to stroke morbidity: a population-based pilot study in Ohasama, Japan.

We investigated the utility of home blood pressure measurements for determining the risk of stroke. We also analyzed the relationship between home blood pressure and the incidence of stroke. Home blood pressure and screening blood pressure measurements were obtained from 1,789 residents (aged 40 yr or older) of a rural Japanese community. Blood pressure was measured at home with a semiautomatic device. A mean (+/-SD) of 23.0 +/- 7.5 measurements were made for each subject. Subjects without a history of stroke and who were not receiving medication for hypertension (n = 1,256) were prospectively followed up for 4.4 +/- 2.1 yr. Subjects were subdivided into quintiles according to their baseline blood pressure. The association between the baseline blood pressure and the incidence of the first-ever stroke was examined with the Cox proportional hazards regression model, adjusted for age and sex. The lowest risk of stroke morbidity occurred in the subjects in the third quintile for home systolic blood pressure (117-123 mmHg) and in those in the second quintile for home diastolic blood pressure (66-70 mmHg). The subjects in the fifth quintiles for home systolic (> or = 133 mmHg) and diastolic blood pressure (> or = 81 mmHg) had a significantly increased risk of stroke morbidity. The subjects in the first and the second quintiles for home systolic blood pressure and those in the first quintile for home diastolic blood pressure tended to have an increased risk as compared with subjects in the lowest risk groups, although this increase was not statistically significant, indicating two possibilities: a trend toward a J-shaped relationship or no-decrease in risk of the first-ever stroke in subjects with home blood pressure level less than 123/70 mmHg. This relationship was not observed for screening blood pressure. We conclude that home blood pressure measurements can provide additional prognostic information to that obtained from blood pressure measurement in a medical environment.

Adult↗
PubMed1997

Magnetic resonance imaging of rat head with a high-strength (4.7 T) magnetic field.

This study was designed to seek the appropriate scanning parameters for T1 and T2 weighted images of rat head by use of a high (4.7 T) magnetic field strength magnetic resonance imaging unit. The optimum values of variables for T1 weighted images were considered to be a time of repetition of 1,000 msec, and for T2 weighted images, 8 echoes. When the sagittal images of a healthy rat head were scanned using these optimum values, the cerebrum, cerebellum, olfactory bulb, pituitary gland, pineal gland, spinal cord, tongue, nasopharynx, nasal conchae, vermis and cerebrospinal fluid were clearly observed in either T1 or T2 weighted images. Moreover, a primary brain tumor induced by ethylnitrosourea was depicted as a high signal intensity mass in T2 and contrast-enhanced T1 weighted images.

Animals↗
PubMed1997

Acute mercury poisoning by intentional ingestion of mercuric chloride.

A 26-year-old woman ingested 0.9 g of mercuric chloride in a suicide attempt and developed hematemesis, melena and acute renal failure. Anuria persisted for 14 days. She was treated by plasma exchange, hemodialysis and peritoneal dialysis in combination with continued dimercaprol chelation. While hemodialysis was ineffective in removing the mercury, plasma exchange effectively eliminated mercury. After two plasma exchange therapies, mercury concentration in the blood decreased linearly on a log scale with half-lives of 23.1 days for whole blood and 19.1 days for plasma, using first-order kinetics. One month after ingestion, renal function recovered to normal as judged by serum creatine and blood urea nitrogen levels, although the beta 2-microglobulin level in urine was still elevated. At a follow-up examination four months later, renal function was found to be completely normal. This indicates that the renal damage caused by acute mercuric chloride poisoning may not be permanent.

Adult↗