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Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 253 records · Page 14Linked to original sources

Roles of Ca and cAMP on C1 channel activity in cystic fibrosis sweat clear cells as studied by microsuperfusion and cell volume analysis.

In an attempt to study regulation of C1 channels in intact sweat secretory coils in cystic fibrosis and controls in the least invasive manner, isolated secretory coils were superfused with various drugs and K-efflux was determined as an indirect measure of C1 movement. C1 channel activity was also determined from the drug-induced cell volume increase in gramicidin (GC)-treated dissociated eccrine clear cells. We observed that while MCh-induced K-efflux from the CF secretory coils was entirely normal, K-efflux in the presence of isoproterenol (ISO), forskolin (FK), or IBMX was absent in CF, suggesting that these agents failed to stimulate C1 movement. C1 channel activity of dissociated CF clear cells, as studied by cell volume analysis, was entirely normal when stimulated by Ca-elevating agents but was defective when stimulated by cAMP-elevating agents. TPA (phorbol ester) does not appear to stimulate C1 channel activity nor does it modify the effect of other agents. The following observations from the present and previous studies are not necessarily consistent with the traditional thesis that the observed C1 movement is due to cAMP: CT-cAMP had no effect on cell swelling or on K-efflux; ISO is more potent in accumulating tissue cAMP than IBMX yet the latter is more potent in stimulating K-efflux; IBMX increases cytoplasmic [Ca] yet is unable to stimulate K-efflux in CF; K-efflux stimulated by cAMP-elevating agents was inhibited by removal of Ca from the bath; and, cell swelling of GC-treated cells in response to cAMP elevating agents was inhibited by removal of Ca. The inability of IBMX to stimulate C1 channels in the face of elevated cytoplasmic [Ca] and cAMP in CF cells deserves further scrutiny.

1-Methyl-3-isobutylxanthine↗

Intracellular ion concentrations and cell volume during cholinergic stimulation of eccrine secretory coil cells.

Methacholine (MCh)-induced changes in intracellular concentrations of Na, K, and Cl [( Na]i, [K]i, and [Cl]i, respectively) and in cellular dry mass (a measure of cell shrinkage) were examined in isolated monkey eccrine sweat secretory coils by electron probe X-ray microanalysis using the peripheral standard method. To further confirm the occurrence of cell shrinkage during MCh stimulation, the change in cell volume of dissociated clear and dark cells were directly determined under a light microscope equipped with differential interference contrast (DIC) optics. X-ray microanalysis revealed a biphasic increase in cellular dry mass in clear cells during continuous MCh stimulation; an initial increase of dry mass to 158% (of control) followed by a plateau at 140%, which correspond to the decrease in cell volume of 37 and 29%, respectively. The latter agrees with the MCh-induced cell shrinkage of 29% in dissociated clear cells. The MCh-induced increase in dry mass in myoepithelial cells was less than half that of clear cells. During the steady state of MCh stimulation, both [K+]i and [Cl]i of clear cells decreased by about 45%, whereas [Na]i increased in such a way to maintain the sum of [Na] i + [K]i constant. There was a small (12-15 mM) increase in [Na]i and a decrease in [K]i in myoepithelial cells during stimulation with MCh. Dissociated dark cells failed to significantly shrink during MCh stimulation. The decrease in [Cl]i in the face of constant [Na]i + [K]i suggests the accumulation of unknown anion(s) inside the clear cell during MCh stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Effects of vitamin D2 analogs on calcium metabolism in vitamin D-deficient rats and in MC3T3-E1 osteoblastic cells.

The effects of 1 alpha-hydroxyvitamin D2 on calcium metabolism in vivo and of 1 alpha, 25-dihydroxyvitamin D2, which is an active metabolite of 1 alpha-hydroxyvitamin D2, on bone metabolism in vitro was studied and compared with that of 1 alpha-hydroxyvitamin D3 or 1 alpha,25-dihydroxyvitamin D3. 1 alpha-Hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3 was equally potent in stimulating intestinal calcium transport by using the everted sac method and of calcium mobilization from bone in vitamin D-deficient rats. On the other hand, the hypercalcemic activity of 1 alpha-hydroxyvitamin D2 was much lower than that of 1 alpha-hydroxyvitamin D3 in normal mice and rats. 1 alpha,25-Dihydroxyvitamin D2 and 1 alpha,25-dihydroxyvitamin D3 stimulated alkaline phosphatase activity in osteoblastic MC3T3-E1 cells and bone resorption in newborn mouse calvaria maintained in organ culture. These results show that 1 alpha-hydroxyvitamin D2 as well as 1 alpha-hydroxyvitamin D3 promote calcium absorption and may accelerate bone remodelling via direct action on osteoblasts. In addition, they suggest that 1 alpha-hydroxyvitamin D2 may be more useful than 1 alpha-hydroxyvitamin D3 for the treatment of senile osteoporosis, because hypercalcemia is one of the major side effects of 1 alpha-hydroxyvitamin D3.

Alkaline Phosphatase↗

2-Chlorodeoxyadenosine inhibits the repair of DNA double-strand breaks and does not inhibit the repair of DNA single-strand breaks in X-irradiated Chinese hamster V79 cells.

The exposure of log-phase Chinese hamster V79 cells to 2-chlorodeoxyadenosine (CdA) for 3 h after X irradiation enhanced the lethal effects of X-rays in a concentration-dependent manner. The enhancement of the killing efficiency of X-rays by CdA was mainly observed in the reduction of quasi-threshold doses (Dq) of the dose-response curves. When the ability of CdA to inhibit the repair of X-ray-induced double- and single-strand breaks (dsb and ssb) of DNA was investigated by neutral- and alkaline-filter elution techniques, respectively, it was observed that 90% of dsb were rejoined in the absence of CdA within 30 min after X irradiation and 15-40% of dsb rejoining was suppressed by co-incubation of the cells with 5-10 microM of CdA for 3 h after X irradiation, whereas almost 100% of ssb were rejoined within 15 min regardless of the presence or absence of CdA. From these results it was concluded that CdA interfered exclusively with the repair of DNA dsb in X-irradiated Chinese hamster V79 cells and thereby increased the lethality of X-rays.

2-Chloroadenosine↗

Eosinophilia caused by administration of L-tryptophan to animals with adrenal dysfunction.

We have investigated an animal model of eosinophilia-myalgia syndrome (EMS), a disease that occurred in various parts of the United States in 1989, with a view to determining its cause. We speculated that adrenal dysfunction might have potentially contributed to the occurrence of EMS and studied the effects of adrenal dysfunction on the eosinophil count in peripheral blood by using rats and mice whose adrenals had been excised or that had been metyrapone-treated, and giving them L-tryptophan. As a result, a significant increase in the eosinophil count was observed in both animal species. The results suggest that EMS may have been caused, not by L-tryptophan alone, but by the combined effects of adrenal dysfunction and L-tryptophan ingestion.

Administration, Oral↗

A new class of calcium antagonists. Synthesis and biological activity of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo [b,e]thiepin derivatives.

A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11- octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*,10aR*,11R*)-11-[[4-[4-(4-fluorophenyl)-1- piperazinyl]butyryl] amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31,pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.

Animals↗

A new class of calcium antagonists. 2. Synthesis and biological activity of 11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,11- dihydrodibenzo[b,e]-thiepin maleate and related compounds.

A series of [(epsilon-aminoalkanoyl)amino]-6,11- dihydrodibenzo[b,e]thiepins and -5H-dibenzo[a,d]cycloheptenes and related compounds were synthesized and evaluated for calcium antagonistic activity by calcium-induced constriction of potassium-depolarized rat aorta. Semiempirical molecular orbital calculations of the dibenzotricyclic systems indicated that calcium antagonistic activity increased with a decrease of the angle between the planes of the two phenyl rings. AM1 net charge calculations showed that a neutral or positive charge distribution in the bridge portion was necessary for activity. 11-[[4-[4-(4-Fluorophenyl)-1- piperazinyl]butyryl]amino]-6,11-dihydrodibenzo[b,e]thiepin maleate (16, AJ-2615) showed a more gradual and longer lasting antihypertensive effect than diltiazem and nifedipine in spontaneously hypertensive rats (SHR) administered orally. Compound 16 also possessed antianginal effects in methacholine-induced ST elevation and vasopressin-induced ST depression tests in rats. The alteration of the dibenzotricyclic system of 16 to 5H-dibenzo[a,d]cycloheptene (19, 5-[[4-[4-(4-fluorophenyl)-1-piperazinyl]-butyryl]amino]-5H- dibenzo[a,d]cycloheptene) resulted in selectivity for cardiac tissue over vascular tissue, thereby conferring antianginal activity without an effect on blood pressure. Antianginal potencies of 16 and 19 were equal to or somewhat more potent than those of diltiazem.

Animals↗

Characterization of free radicals in gamma-irradiated polycrystalline uridine 5'-monophosphate: a study combining ESR, spin-trapping and HPLC.

Free radicals generated in gamma-irradiated polycrystalline uridine 5'-monophosphate (5'-UMP) were studied by ESR, spin-trapping and high-performance liquid chromatography (HPLC). After gamma-irradiation at 0 degree C (70kGy), poly-crystalline 5'-UMP was dissolved in an anaerobic aqueous solution of 2-methyl-2-nitrosopropane as a spin trap at room temperature. Since an ESR spectrum consisting of several components was observed immediately after irradiation, these components were separated with reverse-phase HPLC in the ion-suppression mode and again analysed by ESR spectrometry. Although HPLC ultimately gave four spin-adducts, one component that was originally present disappeared during HPLC. Spin adducts due to two types of C6 radicals were identified. One of these was thought to be formed by electron addition and subsequent protonation at the C6 position, and the other was presumed to be produced by electron addition and subsequent protonation at the O4 position. The spin adducts derived from the C5 and C5' radicals were also identified. The spin adduct that disappeared during HPLC was thought to correspond to the C4'-centred radical. Computer simulation of ESR spectra was carried out to estimate the hyperfine splitting constants.

Chromatography, High Pressure Liquid↗

Movement of cellular ions during stimulation with isoproterenol in simian eccrine clear cells.

The ionic mechanism of beta-adrenergic sweating is unknown. In isolated rhesus eccrine secretory coils, K efflux was determined by an extracellular K electrode and cellular monovalent ions by X-ray microanalysis. Isoproterenol (Iso) induced a small (dose-dependent propranolol-inhibitable) K efflux followed by net K reuptake. Similar K response was seen with forskolin, theophylline, or isobutyl-methylxanthine (IBMX). The net K uptake often exceeded the net K efflux, causing a small net accumulation of K. Bumetanide (BT) and ouabain not only abolished the Iso (with or without IBMX) -induced net K uptake but increased the Iso-induced initial K efflux about threefold. BT and ouabain drastically decreased K and Cl concentrations in the clear cell (by X-ray microanalysis) only in the presence of Iso plus IBMX, suggesting that adenosine 3',5'-cyclic monophosphate (cAMP) may simultaneously stimulate both KCl efflux (by unknown mechanisms) and K reuptake (presumably by BT-sensitive cotransporters and ouabain-sensitive Na pumps). Thus the cAMP-mediated ion movement is different from the cholinergic mechanism that is characterized by the net KCl loss, cell shrinkage (Saga et al., J. Membr. Biol. 107: 13-24, 1989; Takemura et al., J. Membr. Biol. In press), and no augmentation of methacholine-induced K efflux by BT or ouabain.

1-Methyl-3-isobutylxanthine↗

Effects of clomiphene citrate on serum hormone levels and endometrial thickness in an in vitro fertilization and embryo transfer program.

Hormonal alterations and pregnancy rates were compared between the clomiphene citrate (CC)-hMG combination cycle and the hMG cycle alone in an in vitro fertilization and embryo transfer program. In the CC-hMG cycle, the numbers of follicles developed, oocytes recovered and embryos transferred were higher than those in the hMG cycle (p less than 0.01, p less than 0.01 and p less than 0.05, respectively). Pregnancy rates of the CC-hMG cycle (6.7%/operation, 7.1%/embryo transfer), however, were lower than those of the hMG cycle (25%/operation, 31.6%/embryo transfer). PRL levels in the hMG cycle increased according to estradiol levels. In the CC-hMG cycle, CC might inhibit estradiol-induced hyperprolactinemia and the increase was lower even if the estradiol level was much higher than that of the hMG cycle until day 2. On day 4, the PRL level in the CC-hMG cycle further increased. The thickness of endometrium on day -2 in the hMG cycle alone was much thicker than that in the CC-hMG cycle (9.8 +/- 0.4 vs. 6.8 +/- 0.4 mm, mean +/- SEM).

Clomiphene↗

Effect of age on coronary circulation after imposition of pressure-overload in rats.

We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.

Aging↗

Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders.

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.

Animals↗

Longitudinal observation of cementum regeneration through multiple fluorescent labeling.

The assessment of new attachment after periodontal treatment has been the focus of continuous research. An approach to longitudinally examine the deposition of cementum was devised by using fluorescence microscopy (FL), contact microradiography (CMR), and toluidine blue staining (TBS) after the injection of three labeling agents known to be incorporated within newly mineralized tissues with different tones: tetracycline, calcein, and alizarin complexion. Three adult Japanese monkeys (male, 6.0 to 8.3 Kg weight) were used for this experiment. Bone defects were surgically created in 24 mandibular sites and a copper plate was inserted for a period of 4 weeks to promote microbial colonization to form periodontal pockets. Scaling and root planing (baseline) were then performed, and the fluorescent agents were administered twice weekly leaving a 1 week interval between the different agents. The mandibular specimens were fixed in neutralized formalin and embedded in polyester resin. Undecalcified sections were prepared 3, 6, and 9 weeks after baseline. Cementum regeneration was confirmed in 18 out of 24 sites; in 6 samples only epithelial proliferation was observed. Regeneration could be seen as early as 2 weeks after debridement. Cementum was identified by observation under FL of a labeled structure, discrimination in the degree of mineralization of dentin by CMR, and by the presence of functional collagen fibers and location of the epithelial border by TBS. In this study the use of three different labeling agents using the three observation techniques was shown to be effective for the longitudinal assessment of cementum regeneration.

Alveolar Bone Loss↗

[Non-supervised home exercise programs in a convalescent phase of acute myocardial infarction: their effectiveness and the usefulness of the heart rate at the anaerobic threshold].

The effectiveness of 2 different exercise programs in the convalescent phase of acute myocardial infarction (AMI) was assessed. One hundred and five patients with AMI were enrolled for one of these 2 non-supervised home exercise programs immediately after discharge from the hospital. Before discharge and one month later, they underwent submaximal graded treadmill exercise tests with the application of expiratory gas analysis. All patients were assigned to perform 2 km of walk-jog exercise daily for one month. The heart rate during exercise, duration of exercise and the total steps during 24 hrs were measured. Eighty patients (group A) underwent the exercise program in which their heart rates were maintained at 100-110 beats/min during exercise; while 25 patients (group B) underwent the other program in which their heart rates were maintained at 90-100% of those obtained at their anaerobic threshold (AT). The ventilatory AT was calculated by the standard technique using the Horizon System. In group A, AT increased from 13.4 ml/min/kg to 15.1 ml/min/kg (p < 0.01) after the exercise program and in group B, from 12.8 ml/min/kg to 14.9 ml/min/kg (p < 0.01). In group B, AT increased in all patients, while it remained unchanged in 30% of the patients in group A (p < 0.01). In conclusion, a non-supervised home exercise program can be effective and easily instituted for rehabilitation in a convalescent phase of AMI. The program using 90-100% of the heart rates at the anaerobic threshold seemed to be more suitable for obtaining better effects on exercise tolerance than that using 100-110/min heart rate.

Aged↗

[A case report of Buschke-Lowenstein tumor (giant condyloma)].

A 28-year-old woman with diabetes mellitus and alcoholic hepatitis presented a rare case of Buschke Lowenstein tumor, or giant condyloma of vulva. HPV DNA of this tumor was detected by in situ hybridization using tritium labeled HPV 6 b, 16 and 18 DNA. This tumor appeared to harbour HPV 6 b DNA, but other HPV DNAs were negative. The distribution of HPV 6 b DNA was detected in the nucleus of the squamous epithelium showing koilocytosis. Total vulvectomy and resection of the clitoris were done. The postoperative course was uneventful and there has been no recurrence of tumor so far.

Adult↗