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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 541 records · Page 30Linked to original sources
PubMed1993

Nipradilol inhibits rat mesangial cell mitogenesis through the activation of soluble guanylate cyclase.

Nipradilol is a beta-adrenoreceptor blocking agent, whose structure contains an NO2 group. Thus, it is possible that it modulates the function of glomerular mesangial cells through the activation of soluble guanylate cyclase. To prove this hypothesis, we examined the effect of nipradilol on soluble guanylate cyclase, intracellular cyclic guanosine monophosphate (cGMP) accumulation, and the mitogenesis of cultured rat glomerular mesangial cells. Nipradilol increased intracellular cGMP accumulation in a dose-dependent manner through the activation of soluble guanylate cyclase. Furthermore, nipradilol inhibited the incorporation of [3H]thymidine into the mesangial cells stimulated by 2.5% fetal bovine serum in a dose-dependent manner. These results indicate that nipradilol may modulate mesangial cell function through an increase in intracellular cGMP resulting from the activation of soluble guanylate cyclase.

Adrenergic beta-Antagonists↗
PubMed1993

Cyclic-AMP-dependent Ca2+ influx elicited by prostaglandin D2 in freshly isolated nonchromaffin cells from bovine adrenal medulla.

We previously reported that prostaglandin D2 (PGD2) specifically elevates intracellular cyclic AMP in nonchromaffin cells isolated from bovine adrenal medulla (Biochim. Biophys. Acta (1989) 1011, 75-80). Here we again found that PGD2 increased intracellular Ca2+ concentration ([Ca2+]i) in freshly isolated nonchromaffin cells and investigated the cellular mechanisms of PGD2-induced [Ca2+]i increase using the Ca2+ indicator fura-2 and a fluorescence microscopic imaging system. Treatment of the cells with PGD2 receptor agonists BW245C and ZK110841 resulted in both marked stimulation of cyclic AMP formation and an increase in [Ca2+]i. The [Ca2+]i response was also induced by bypassing of the receptor with forskolin, a direct activator of adenylate cyclase, but not by PGE2 or PGF2 alpha both of which are devoid of the ability to generate cyclic AMP in the cells. These cyclic AMP and [Ca2+]i responses induced by PGD2 were completely blocked by the PGD2 receptor antagonist BWA868C. The time-course of cyclic AMP production stimulated by PGD2 coincided with that of the [Ca2+]i increase. While the Ca(2+)-mobilizing hormone bradykinin stimulated a rapid inositol phosphate accumulation in nonchromaffin cells, PGD2 did not stimulate it significantly. Removal of extracellular Ca2+ markedly reduced the Ca2+ response to PGD2 in magnitude and duration, but did not alter the peak [Ca2+]i response to bradykinin. These results demonstrate that PGD2 receptor activation induces the increase in [Ca2+]i via cyclic AMP mainly by increasing the Ca2+ influx from the outside, unlike inositol trisphosphate which causes release of Ca2+ from internal stores.

Adrenal Medulla↗
PubMed1993

Aggressive osteoblastoma of the calcaneus.

Aggressive osteoblastoma of the left calcaneus in 29-year-old Japanese woman is reported. Her initial symptom was heel pain while walking. This was a primary calcaneal tumor, initially diagnosed as a benign osteoblastoma. After a 5-year follow-up (from the initial curettage), there was local recurrence. The histologic findings of aggressive osteoblastoma were confirmed after right lower leg amputation. The recurrent tumor was mildly aggressive to the talocalcanean joint and the retrocalcaneal area, without distant metastasis. The characteristics of the primary and recurrent tumors were examined by the radiologic, histologic, and electron microscopic procedures. Although there are questions about aggressive osteoblastoma, the authors believe that there are osteoblastic tumors of borderline malignancy between benign osteoblastoma and low-grade osteosarcoma. The current case was an example compatible with an aggressive osteoblastoma with the proposed name of Dorfman classification Group 4.

Adult↗
PubMed1993

Gene expression of CD24 core peptide molecule in developing brain and developing non-neural tissues.

CD24 is a signal transducing molecule on the surface of most human B cells, murine immature T cells, myeloid and erythroid lineage cells. We isolated rat CD24 gene from embryonic brain cDNA library and characterized the gene expression during rat embryogenesis. Rat CD24 cDNA is homologous to murine and human CD24 gene with respect to the structure of signal peptide, N-glycosylation sites, and possible glycosyl phosphatidylinositol (GPI) linker attaching site, suggesting that rat CD24 is a transducing glycoprotein anchoring membrane via GPI linker. In the developing embryo, in situ hybridization analyses revealed that CD24 transcript was detected in primitive ectoderm, mesoderm, and ventral endoderm of day 9 postcoitum (p.c.) embryo. In central nervous systems CD24 transcript was strongly expressed in postmitotic cells of spinal cord, hindbrain, midbrain, and forebrain from day 11 p.c. embryo to day 21 p.c. embryo but was dramatically down regulated in adult brain. Furthermore, expression was also detected in epithelium during development of non-neural tissues, such as intestinal mucosal epithelium, nasal epithelium, ductal epithelium of salivary gland, bronchial epithelium, renal tubular epithelium, and hair follicles. In tooth development, where correct epithelium requires epithelial-mesenchymal interactions, CD24 mRNA was specifically induced in mesenchymal cells differentiating into odontoblast in dental papilla, suggesting the pivotal role of CD24 molecule in cell differentiations in vivo. We suggest that CD24 gene may encode the core peptide molecule of 31 kDa GPI linked molecule which has been known to be important in the migration of neurons on astroglial processes during development.

Amino Acid Sequence↗
PubMed1993

Effects of diltiazem and cimetidine on theophylline oxidative metabolism.

The effect of diltiazem or cimetidine pretreatment on the inhibition of theophylline oxidative metabolism was investigated in nine healthy male nonsmokers. Diltiazem 60 mg, cimetidine 400 mg, or placebo was given orally three times daily for 3 days in a randomized three-way crossover manner. Both diltiazem and cimetidine pretreatment decreased the mean theophylline clearance (0.702 on placebo versus 0.641 on diltiazem, P < .05, and 0.542 mL/minute/kg on cimetidine, P < .01), resulting in prolonged mean theophylline half-life (7.58 on placebo versus 8.59 on diltiazem, P < .05, and 10.08 hours on cimetidine, P < .01) with no change in volume of distribution. The mean metabolic clearances for three major theophylline metabolites, 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), and 3-methylxanthine (3-MX), were reduced significantly by cimetidine (28%; P < .05, 32%; P < .01, and 33%; P < .01, respectively). Conversely, diltiazem significantly reduced only the mean metabolic clearance of 1,3-DMU by 21% (P < .05) without changes in that of 1-MU or 3-MX. These results suggest that cimetidine inhibited both N-demethylation and 8-hydroxylation of theophylline, whereas diltiazem exerted little influence on N-demethylation in spite of inhibition in 8-hydroxylation.

Adult↗
PubMed1993

The influence of pretreatment periods with diltiazem on nifedipine kinetics.

The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration-time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P < .05) and decreased the total body clearance (CL) an average of 24.0% (P < .05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P < .01), 188.0% (P < .05) of control values, and decreased CL to 58.2% (P < .01), 63.9% (P < .05) of control values, respectively. The elimination half-life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simultaneously.

Administration, Oral↗
PubMed1993

The effect of nifedipine on the pharmacokinetics and dynamics of diltiazem: the preliminary study in normal volunteers.

To evaluate the influence of nifedipine on the pharmacokinetics and the pharmacodynamics of diltiazem, five healthy subjects received 60 mg diltiazem orally on two occasions, diltiazem alone or after nifedipine pretreatment (10 mg three times daily for 3 days). After nifedipine pretreatment, the maximum concentration (Cmax) of diltiazem was increased and the time of Cmax was shortened, and the area under the concentration curve (AUC) tended to be increased. Although heart rate was increased, the corrected PQ interval tended to be prolonged after the nifedipine pretreatment. Both a decreased hepatic clearance and an increased bioavailability of diltiazem probably accounts for the increase in the Cmax and AUC of diltiazem after nifedipine pretreatment, and that might affect the pharmacodynamics of diltiazem.

Administration, Oral↗
PubMed1993

The effect of maternal exercise on somatic growth and lung development of fetal rats: morphologic and morphometric studies.

Our study was aimed at elucidating the effect of strenuous maternal exercise (running at a speed of 20 m/min) on fetal somatic growth and lung development. Dams were separated into three groups: (1) exercising during the entire course of pregnancy; (2) exercising from the 16th to the 20th gestational day; and (3) controls treated in the same manner as the exercising animals, but not exercised. There were no differences in the mother's body weight (mother's body weight--total body weight of the fetuses) among the three groups. Overall growth and lung development in fetuses from mothers that exercised during the entire course of pregnancy showed markedly decreased size and weight of body and lung, smaller air spaces and thicker future alveolar walls, and fewer osmiophilic lamellated bodies in alveolar type II cells. The morphometric data of fetuses from mothers that had exercised only during late gestation were similar to those of control animals. The ratio of fetal lung volume to body weight was the same in all three groups. These findings indicate that long-term strenuous maternal exercise induces retardation of fetal lung development, possibly accompanied by a disturbance of overall growth. Maternal exercise represents another means of manipulating lung development.

Animals↗
PubMed1993

Cranial MRI and MR angiography in Menkes' syndrome.

We report two boys with Menkes' syndrome who underwent cranial MRI and MR angiography (MRA). In both, CT and MRI revealed progressive cerebral atrophy with a subdural haematoma or effusion. Delayed myelination or dysmyelination of the white matter was suggested. Tortuosity of the cervical and intracranial vessels was well demonstrated by MRA, obviating more invasive conventional angiography should it be thought necessary to demonstrate the characteristic systemic vascular changes of this syndrome.

Atrophy↗
PubMed1993

An experimental model for unilateral ischaemic acute renal failure in dog.

We determined the recovery of unilateral ischaemic acute renal failure in both ischaemic and non-ischaemic canine kidneys. Split renal clearance studies were repeated for seven weeks after 90 minutes of left renal artery clamping. Clearance of inulin and para-aminohippuric acid in the ischaemic kidneys dropped significantly for 3 weeks. Significant increase of the fractional excretion of sodium in those kidneys was observed at only 1 week after ischaemia. In the contralateral non-ischaemic kidneys, these indices did not change significantly throughout the experiments. This animal model of acute renal failure would be helpful in testing possible preventive measures and therapy for human acute renal failure.

Acute Kidney Injury↗
PubMed1993

Evaluation of critically perfused area in acute ischemic stroke for therapeutic reperfusion: a clinical PET study.

To evaluate critically perfused areas in the acute ischemic brain, 9 patients were studied by positron emission tomography (PET) within 7-32 hours after the onset. The cerebral blood flow (CBF) and oxygen metabolic rate (CMRO2) were evaluated and compared with sequential change in CT findings. In all the regions developing subsequent necrosis on CT, CBF dropped below 17 ml/100 g/min. But in some of these lesions, CMRO2 remained above the minimum value for regions in which infarction did not develop, and the tissue density on CT obviously remained normal for several hours after PET scan. The mean CBF in these lesions (14.0 ml/100 g/min, range: 9.9-17.3 ml/100 g/min) was significantly higher than that in ischemic areas with low density on CT before or just after PET study (approximately 10 ml/100 g/min, range: 7.7-14.1 ml/100 g/min). These findings suggest that a part of the tissue with CBF between 10-17 ml/100 g/min is still viable at least 7 hours after the onset of ischemia, but becomes non-viable in a longer period of ischemia. These lesions should respond to effective treatment, including therapeutic reperfusion.

Aged↗
PubMed1993

Suppressive effect of low dose total body irradiation on lung metastasis: dose dependency and effective period.

The dose dependency and effective period of suppressive effects by low dose total body irradiation (TBI) in both artificial and spontaneous lung metastasis were investigated using murine squamous cell carcinoma. In the artificial lung metastasis of the tumour cells injected through a tail vein, the TBI of 0.15-0.20 Gy resulted in significant net suppression of lung colony formation. With this dose range, the effective period lasted for 12 h ranging from 9 h before to 3 h after the tumour cell injection. Similar suppressive effect was also observed in the spontaneous lung metastasis. These data suggest that careful assessment of effective dose and duration of low dose TBI on human metastasis could provide a new therapy to suppress clinical metastasis.

Animals↗
PubMed1993

The complete nucleotide sequence of African horsesickness virus serotype 4 (vaccine strain) segment 4, which encodes the minor core protein VP4.

The complete sequence of RNA segment 4 of African horsesickness virus serotype 4 (AHSV-4) vaccine strain was determined from the full-length cDNA clone inserted into pBR322. The RNA is 1978 bp long (M(r) 1.27 x 10(6)) and contains an open reading frame encoding a protein of 642 amino acids (M(r) 75826) with a net charge of +10 at neutral pH. The 5' and 3' termini of AHSV-4 segment 4,5'GTTTAT... and ...CCTTAC3', were different from orbivirus characteristic terminal sequences, being 5'GTTAAA... and ...ACTTAC3'. A comparison of the sequence of AHSV-4 segment 4 with that of bluetongue virus (BTV) serotype 10 revealed 55.4% nucleotide similarity and 48.5% amino acid similarity. In addition, Northern blot hybridization showed that the full-length AHSV-4 segment 4 cDNA cross-hybridized well with the corresponding genes of serotype 1, 2, 3, 4 and 7 but slightly with serotype 5, 6 and 8 of attenuated AHSV.

African Horse Sickness Virus↗
PubMed1993

Effect of diethyldithiocarbamate on diabetogenic action of alloxan in rats.

To determine whether alloxan action is mediated by hydroxyl radicals in vivo, we assayed methane sulfinic acid (MSA), a product of the trapping reaction of dimethyl sulfoxide (DMSO) with hydroxyl radicals. In DMSO-treated rats, the plasma levels of MSA were increased after injection of alloxan (75 mg/kg). This supports the hypothesis that the diabetogenic action of alloxan is mediated by hydroxyl radicals in vivo. The role of cytosolic superoxide dismutase (SOD) in protecting B cells against chemically induced diabetes was studied in rats injected intraperitoneally with diethyldithiocarbamate (DDC). When rats were injected intraperitoneally with DDC (750 mg/kg), the SOD activity at 2.5 h was decreased by 44% in the whole pancreas. The decreased SOD activity was affected by DDC but not by alloxan. Intraperitoneal injection of rats with DDC (750 mg/kg) increased diabetogenic susceptibility to a nondiabetogenic dose of alloxan (20 mg/kg). Subcutaneous injection of vitamin E, prior to administration of both DDC and alloxan, provided partial protection to the rats against the diabetogenic action. These findings suggest that the susceptibility to diabetogenic action of alloxan in B cells is augmented when the cellular SOD activity is inhibited. Thus, cellular SOD may play an important role in the maintenance of B cell function.

Alloxan↗
PubMed1993

Biotransformation of 18 beta-glycyrrhetinic acid by ginseng hairy root culture.

On administration of 18 beta-glycyrrhetinic acid to hairy root cultures of Panax ginseng, three new biotransformation products, 30-O-[beta-D-glucopyranosyl-(1-->2)-beta-D- glucopyranosyl]18 beta-glycyrrhetinic acid, 30-O-(6- O-malonyl-beta-D-glucopyranosyl)18 beta-glycyrrhetinic acid and 3-O-[6-O- malonyl-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]18 beta-glycyrrhetinic acid, were isolated together with three known compounds. Ginseng hairy roots showed the biotransformation abilities of glycosylation and malonylation to 18 beta-glycyrrhetinic acid.

Biotransformation↗
PubMed1993

Prostacyclin production in cultured endothelial cells is highly sensitive to low doses of ionizing radiation.

In an attempt to detect if low doses of ionizing radiation affect the physiological function of blood vessels, the effect of prostacyclin production was examined using cultured endothelial cells. Irradiation with 5 cGy suppressed the production to 53% of the levels in unirradiated control cells. The PGI2 production decreased with an increase in the dose, showing a maximal decrease at 100 cGy without further decrease at 200 cGy. The suppressive effect lasted for 15 min after irradiation and disappeared later. Preincubation with alpha-tocopherol abrogated the suppressive effect completely, although preincubation with ascorbic acid showed little effect. These results suggest that low dose irradiation inhibits the prostacyclin production by changing the cellular membranes transiently.

Animals↗
PubMed1993

Evaluation of a new test for colorectal neoplasms: a prospective study of asymptomatic population.

In a recent pilot study, we have suggested of potential usefulness of a new test (Shams' test) for screening colorectal (CR) cancer in Japan. Although the sensitivity of this test was remarkably high, its accurate specificity was unclear. The purpose of our present study is to evaluate the incidence of non-specific reaction of Shams' test in the normal Japanese populations. We analyzed 330 asymptomatic individuals, who were seen for annual health checkup, for the presence of the tumor marker D-Gal-B (1- > 3)-D-GalNAc in their rectal mucin. The rectal mucin was smeared on nitrocellulose membrane filter and developed by a sequential reaction of B-D-galactose oxidase and Schiff's reagent. Immunological fecal occult blood test (FOBT) was done in parallel. Extensive study by barium enema/total colonoscopy was indicated only for those who showed positive results with Shams' test or FOBT. A total of 271 individuals were negative, while 50 and 9 had positive and equivocal (+/-) results, respectively. Subsequent barium enema and fiberoptic proctocolonoscopic examinations, which were available on 32 of 59 cases, revealed 6 adenomatous polyps, one villous adenoma with focal severe atypia, and 4 cases of diverticular disease. Except for one patient with polyp, 6 other patients harboring polyps were negative with immunological FOBT. The overall specificity of Shams' test was 92.2% (271/294). Based on these results and preceding reports, we concluded that Shams' test could be a useful tool in our strategy for early detection of CR neoplasms and precancerous lesions.

Adult↗