Search PubMed⌕ Search

Biomedical subjects

T Miyahara

Publications and source records attributed to T Miyahara.

At least 145 records · Page 8Linked to original sources
PubMed1993

Metabolism of mephentermine and its derivatives by the microsomal fraction from male Wistar rat livers.

1. The N-demethylation of mephentermine (MP), p-hydroxymephentermine (p-hydroxy-MP) and N-hydroxymephentermine (N-hydroxy-MP), to produce phentermine (Ph), p-hydroxyphentermine (p-hydroxy-Ph) and N-hydroxyphentermine (N-hydroxy-Ph), and the p-hydroxylation of MP and Ph, to produce p-hydroxy-MP and p-hydroxy-Ph, were examined using rat liver microsomal preparations containing NADPH. Microsomal reduction of N-hydroxy-Ph to Ph was also examined using various cofactors. In addition, enzymic system for the N-demethylation and p-hydroxylation were examined using various inhibitors. 2. N-Hydroxy-MP demethylation to N-hydroxy-Ph proceeded at a rate almost 10-fold faster than other reactions. MP demethylation to Ph, MP oxidation to P-hydroxy-MP, Ph oxidation to p-hydroxy-Ph proceeded at similar rates, whilst p-hydroxy-MP demethylation to p-hydroxy-Ph was catalysed at the slowest rate. Microsomal reduction of N-hydroxy-Ph to Ph required NADH, and the activity was similar to that of MP oxidation to p-hydroxy-MP. 3. N-Demethylation of MP, p-hydroxy-MP and N-hydroxy-MP were inhibited not only by inhibitors of cytochrome P450, but also by methimazole, an inhibitor of the FAD-monooxygenase system. p-Hydroxylations of MP and Ph were inhibited only by inhibitors of cytochrome P450.

Aerobiosis↗
PubMed1993

Metabolism of phentermine and its derivatives in the male Wistar rat.

1. Urinary metabolites of the male Wistar rat dosed i.p. and orally with phentermine (Ph), N-hydroxyphentermine (N-hydroxy-Ph) and p-hydroxyphentermine (p-hydroxy-Ph) were examined by g.l.c. and g.l.c.-mass spectroscopy. 2. N-hydroxy-Ph which accounted for about 3% dose was identified in the urine of rat dosed i.p. and orally with Ph. The major urinary metabolite of Ph dosed i.p. and orally was a p-hydroxy-Ph conjugate (51% dose). 3. The major urinary metabolite of N-hydroxy-Ph dosed i.p. and orally was a p-hydroxy-Ph conjugate (40% dose). A N-hydroxy-Ph conjugate (12% dose) was identified following i.p. administration of N-hydroxy-Ph, but was not detected following oral administration. Small amounts of Ph (< 10% dose) and p-hydroxy-Ph (3% dose) were also identified after i.p. and oral administration of N-hydroxy-Ph. 4. The only urinary metabolite of p-hydroxy-Ph after either i.p. or oral dosing was a p-hydroxy-Ph conjugate (65% dose). 5. These results indicate that N-hydroxy-Ph is a urinary metabolite of Ph in rat; p-hydroxy-Ph is produced by the hydroxylation of Ph itself and partly by the hydroxylation of Ph formed from N-hydroxy-Ph; the p-hydroxy-Ph conjugate is the major and final metabolite of Ph dosed i.p. and orally.

Animals↗
PubMed1993

[Analysis of bronchoalveolar lavage fluid in a case of high altitude pulmonary edema].

A 29-year-old male climber developed high altitude pulmonary edema (HAPE), progressing from headache and dyspnea to disturbance of consciousness in the Japan Alps. He was admitted to Shinshu University Hospital. Physical examination on admission revealed a cyanotic patient with coarse crackles and wheezes in bilateral lungs. Chest X-ray film showed bilateral patchy infiltrates. Arterial blood gases indicated severe hypoxemia, and respiratory alkalosis; pH 7.452, PO2 35.5 Torr, PCO2 31.6 Torr. Right heart catheterization showed noncardiogenic pulmonary edema, analysis of bronchoalveolar lavage (BAL) fluid was as follows; cells 2.05 x 10(5)/ml (alveolar macrophages 61.5%, neutrophils 25.5%, lymphocytes 13.0%), protein concentration 91 mg/dl. Cellular and protein analysis of BAL has been shown to be of value to clarify the pathogenesis of the permeability edema in patients with HAPE.

Adult↗
PubMed1992

Alterations in cellular calcium handling as a result of systemic calcium deficiency in the developing chick embryo: I. Erythrocytes.

Chick embryos rendered calcium (Ca) deficient by shell-less (SL) culture develop hypertension and tachycardia. Since hypocalcemia is accompanied by hypernatremia systemically but not by lower cellular Ca (Koide and Tuan, 1989), we speculate that cellular Ca handling may be altered in the SL embryo, perhaps involving Na transport. Using erythrocytes (RBC) from day-14 SL and normal (NL) embryos as the experimental cell, cellular Ca handling was studied under varying extracellular osmotic and ionic conditions by analyzing 45Ca uptake and cell volume regulation. Two agents, p-chloromercuriphenylsulfonate (PCM), and inosine/iodoacetamide (INI) were used to treat the RBCs to modify plasma membrane ion permeability and to deplete cellular ATP, respectively. Other cellular functions and activities related to Ca homeostasis, including ATP content and Ca(2+)-ATPase activity, were also analyzed. These analyses showed: (1) in NaCl, Ca uptake was similar in NL and SL cells, except after INI treatment, which resulted in slower Ca uptake by the SL cells, (2) in choline and sucrose, Ca uptake by SL RBCs was higher, (3) Ca uptake by RBCs of both embryos changed depending on the osmotic agent (Na < K < or = choline < sucrose), (4) Ca(2+)-ATPase activity was higher in SL RBC, although there was no change in the size or charge of the enzyme, and (5) in any osmotic agent, cellular Na was significantly lower, whereas cellular K was higher, in SL RBC. Based on these results, three features of RBC Ca handling were apparent: (1) Na-Ca exchange was functional and was more active in SL RBCs, (2) Ca uptake was dependent on the total ionic electrochemical gradient but not on bulk H2O movement, and (3) Ca pumping out capacity was directly correlated with Ca(2+)-ATPase activity. Elevated Ca uptake in sucrose-treated SL RBC is therefore indicative of its greater ion permeability. Taken together, these findings indicate that cellular Ca handling of the RBCs of SL chick embryos is characterized by a more active Na-Ca exchange system, greater ion permeability, and higher Ca pumping out capacity, thereby suggesting an up-regulated Ca handling function in the SL RBCs. The abnormal cellular Ca handling may be a direct result of the systemic Ca deficiency of the SL chick embryo and may be functionally related to its hypertension and tachycardia.

Adenosine Triphosphate↗
PubMed1992

Alterations in cellular calcium handling as a result of systemic calcium deficiency in the developing chick embryo: II. Ventricular myocytes.

We have previously shown that cardiovascular anomalies, such as hypertension and tachycardia, develop in Ca(2+)-deficient, shell-less (SL) chick embryos cultured ex ovo, accompanied by elevated circulating catecholamines and higher alpha-adrenergic sensitivity of cardiovascular functions. Results described in the preceding work, using erythrocytes as an experimental system, show that cellular Ca2+ handling properties are also altered as a result of long-term calcium deficiency. To examine the relevance of these findings to cells of the cardiovasculature, we have analyzed and compared the Ca2+ handling characteristics of the heart cells of SL and normal (NL) embryos. For this study, isolated and cultured ventricular myocytes of SL and NL embryos were loaded with Fura-2 via transient membrane damage with glass beads. Compared to Fura-2/AM, bead loading yielded similar values and kinetic profiles of [Ca2+]i-dependent differential fluorescence and, in addition, did not affect cell viability and beating activity. The Fura-2 loaded ventricular myocytes were washed in Ca(2+)-free buffer and then analyzed by ratiometric fluorescence (350 nm/380 nm) microscopy for kinetic changes in [Ca2+]i (R350/380 values) as a function of [Ca2+]o and adrenergic modifiers. At 0.5 and 1.0 mM [Ca2+]o, SL cells showed significantly higher [Ca2+]i, higher beating rates, and faster rate of increase in [Ca2+]i compared to NL cells. At higher [Ca2+]o (3.5 mM), there was no significant difference in [Ca2+]i and beating rate between NL and SL cells. Treatment with norepinephrine (NE; 0.01-1 microM) at 1 mM [Ca2+]o substantially increased [Ca2+]i in both NL and SL cells. In the former, the NE effect was completely inhibited by beta-blockade (1 microM propranolol). In contrast, in SL cells, NE remained effective after beta-blockade, and combined alpha-blockade (1 microM prazosin) and beta-blockade was needed to inhibit completely the NE effect. In both NL and SL cells, treatment with NE substantially increased beating rates in a similar manner. Taken together, these findings suggest that Ca2+ handling and adrenergic regulation of the heart cells are significantly altered in the SL embryos, and that these alterations may be related to the development of impaired cardiovascular functions resulting from systemic Ca2+ deficiency.

Animals↗
PubMed1992

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer.

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.

Aged↗
PubMed1992

Hemodynamic changes after resection of thoracic duct for en bloc resection of esophageal cancer.

An en bloc resection of esophageal cancer is one of the most radical forms of esophagectomy, and includes the resection of the thoracic duct, but a relatively high hospital mortality rate has been reported. There is very little knowledge on the pathophysiological changes after resection of the thoracic duct. We examined 24 patients who underwent en bloc resection. Some patients developed severe tachycardia or shock postoperatively which subsided after a massive infusion of plasma. Analysis of the fluid balance revealed that much more fluid was necessary during surgery and the postoperative 24 h than in patients treated by a standard esophagectomy. Postoperative lymphangiography or CT revealed abnormal collateral lymphatics around the kidneys or in the pelvic cavity. This suggests the development of the lymphaticovenous shunts, which differed depending on the anatomy of each patient. One patient with chronic hepatitis developed uncontrollable ascites. These are important findings which can hopefully reduce the high rate of hospital death after this operation.

Aged↗
PubMed1992

Calcium regulating activity of 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3.

A series of analogs of 1 alpha,25-dihydroxyvitamin D3[1,25(OH)2D3] with alkyl substitutions in 26- and 27-positions were tested for calcium (Ca) regulating activity. The potencies of dialkyl analogs in stimulating bone resorption in neonatal mouse calvaria cultures were the highest in 1 alpha,25-dihydroxy-26,27-dimethylvitamin D3[1,25(OH)2-(Me)2D3], followed by 1,25(OH)2D3, 1 alpha,25-dihydroxy-26,27-diethylvitamin D3[1,25(OH)2(Et)2D3], and 1 alpha,25-dihydroxy-26,27-dipropylvitamin D3[1,25(OH)2(Pr)2D3] in that order. A similar order of potential regarding formation of osteoclast-like cells in mouse bone marrow cell cultures and on bone Ca mobilization with long-term vitamin D-deficient rats was observed in the same series. The relative potencies of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 1,25(OH)2(Et)2D3, and 1,25(OH)2(Pr)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptors were 1:1:0.16:0.036. A similar order of potential in case of intestinal Ca transport in situ was observed in the same series. The potencies of dialkyl analogs in competing with 25-hydroxy-vitamin D3 for binding to rat serum vitamin D binding protein were much lower than that of 1,25(OH)2D3. Effect of 1,25(OH)2(Me)2D3 on osteopenia in rats induced by ovariectomy and right sciatic neurotomy was higher than that of 1,25(OH)2D3. From these results, the lengthening by one carbon at 26- and 27-positions was shown to maintain the Ca regulatory activity of 1,25(OH)2D3.

Animals↗
PubMed1992

Effects on cultured neonatal mouse calvaria of 1 alpha,25-dihydroxyvitamin D3, 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,26,26,27,27,27-hexafluoro-1 alpha,23S,25-trihydroxyvitamin D3.

The potency of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) to enhance bone calcium (Ca) mobilization in vitro was higher than that of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In a 48-h organ culture system using fetal rat limb bones, effects of 26,27-F6-1,25(OH)2D3 on bone resorption were similar to those of 1,25(OH)2D3. Thus, we attempted to clarify whether or not the potency of 26,27-F6-1,25(OH)2D3 in bone resorption in vitro would be higher than that of 1,25(OH)2D3. Calvarial bones from neonatal mice were used as explants and the culture period was extended to 144 from 48 h. In cultures of 0 to 48 h, both drugs increased the release of prelabeled 45Ca from cultured calvariae, in a dose-dependent manner. In cultures of 48 to 144 h, 26,27-F6-1,25(OH)2D3 was much more effective than 1,25(OH)2D3 regarding indices of bone resorption. 26,26,26,27,27,27-F6-1 alpha,23S,25-trihydroxyvitamin D3 (26,27-F6-1,23,25(OH)3D3), a main metabolite of 26,27-F6-1,25(OH)2D3 in rats, stimulated 45Ca release equipotently to 1,25(OH)2D3. In mouse bone marrow cells cultured for 7 days, the potency of 26,27-F6-1,25(OH)2D3 on osteoclast formation was much higher than 1,25(OH)2D3. These results suggest that the higher potency of 26,27-F6-1,25(OH)2D3 in bone resorption may be due at least in part to both the higher potency of 26,27-F6-1,25(OH)2D3 in osteoclast formation and the larger retention of 26,27-F6-1,23,25(OH)3D3 in calvariae.

Acid Phosphatase↗
PubMed1992

Stimulative effects of cadmium on bone resorption in neonatal parietal bone resorption.

Effects of cadmium on bone resorption were investigated using neonatal mouse parietal bone culture system. Cadmium at 0.5 microM and above stimulated hydroxyproline release as well as 45Ca release. As cadmium-stimulated bone resorption was inhibited by calcitonin, bone resorption induced by cadmium is osteoclast-mediated bone resorption. CI-1, collagenase inhibitor, depressed cadmium-stimulated bone resorption in a dose-dependent manner. Osteoblasts are also involved in cadmium-induced bone resorption. Indomethacin-inhibited cadmium-stimulated bone resorption and cadmium-treated bones released prostaglandin E2 to a greater extent than untreated bones. Cadmium-stimulated bone resorption was shown to be dependent on the production of prostaglandin E2. 3-Isobutyl-1-methylxanthine potentiated cadmium-stimulated bone resorption and verapamil depressed it. It is possible that an increase in levels of cAMP and calcium ion in bone cells is involved in cadmium-induced bone resorption. From these results, cadmium was found to stimulate osteoclast-mediated bone resorption which is dependent on prostaglandin E2. Second messengers in cadmium-induced bone resorption may be cAMP and calcium ion.

Animals↗
PubMed1992

Clinical use of new video-endoscopes (EVIS 100 and 200).

The authors report on their clinical experience with two new videoendoscopes developed in cooperation with Olympus Co. One of them is an instantaneous image method videoendoscope (EVIS 100), the other produces sequential images (EVIS 200). EVIS 100 is as compact as a fiberscope; EVIS 200 has the special advantages of electronic magnification, the use of infrared rays and image display of hemoglobin concentration in the tissue. In clinical application in 245 patients examined with EVIS 100 and 30 cases with EVIS 200, both instruments were found to be satisfactory in terms of daily use; EVIS 200 could be applied in further endoscopic research. In our opinion videoendoscopes will replace conventional fiberscopes in the future.

Endoscopes, Gastrointestinal↗
PubMed1992

The number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with cisplatin at its mean lethal concentration.

HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37 degrees C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 microgram/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of D0 values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 x 10(4), 5.71 x 10(4) and 1.03 x 10(5) nucleotides for 1, 2 and 3 h treated cells, respectively.

Cell Survival↗
PubMed1992

Effects of sodium L-lactate and sodium racemic lactate on intraoperative acid-base status.

Lactated Ringer's solution is frequently used to avoid metabolic acidosis during fluid resuscitation. The standard lactated Ringer's solution contains racemic lactate, an equal mixture of the D- and L-stereoisomers. We investigated whether sodium L-lactate or sodium racemic lactate (DL-lactate) is more effective for increasing buffering capacity in body fluids. For the purpose of this comparison, Ringer's solutions containing no lactate, sodium L-lactate, or racemic lactate at a concentration of 84 mEq/L (three times more than the ordinary level) were infused in patients under general anesthesia during tympanoplasty. Although differences occurred among the three groups in blood concentrations of L-lactate, D-lactate, and the L-lactate/pyruvate ratio, no differences occurred between the two lactate groups in either bicarbonate ion concentration or base excess. The amount of buffering capacity increased significantly in both lactate groups, compared with preinfusion levels, and was more than the values in the nonlactated Ringer's solution group. We conclude that sodium racemic lactate is metabolized at nearly the same rate as that of sodium L-lactate.

Acid-Base Equilibrium↗
PubMed1992

Intestinal metabolism of mephentermine and its biliary metabolites in male Wistar rats.

1. Intestinal metabolites produced in the incubation (0-24 h) of mephentermine (MP), phentermine (Ph), N-hydroxymephentermine (N-hydroxy-MP), N-hydroxyphentermine (N-hydroxy-Ph), p-hydroxymephentermine (p-hydroxy-MP) and p-hydroxyphentermine (p-hydroxy-Ph) with male Wistar rat intestinal contents under N2 were examined by g.l.c. and g.l.c.-electron impact (EI) mass spectrometry. Metabolites produced in the anaerobic incubation of bile from rats given MP, with the intestinal contents were also examined. In addition, urinary and biliary metabolites of p-hydroxy-MP and p-hydroxy-Ph dosed orally to rat were examined. 2. Metabolites in the anaerobic incubation of N-hydroxy-MP and N-hydroxy-Ph were MP and Ph, and Ph, respectively. No metabolites were detected in the incubation of MP, Ph, p-hydroxy-MP and p-hydroxy-Ph. 3. p-Hydroxy-MP and p-hydroxy-Ph (major), and MP and Ph (minor) were detected when bile from rats given MP was incubated with intestinal contents. 4. Unchanged p-hydroxy-MP, and conjugates of p-hydroxy-MP and p-hydroxy-Ph, were detected in the 24-h urine of rats dosed with p-hydroxy-MP, which accounted for about 3, 72 and 1% dose, respectively. Unchanged p-hydroxy-Ph and conjugated p-hydroxy-Ph were detected in the 24-h urine of rats dosed with p-hydroxy-Ph, which accounted for about 4 and 68% dose, respectively. 5. Conjugated p-hydroxy-MP and conjugated p-hydroxy-Ph, which accounted for about 3% doses, were detected in the 24-h bile of rats dosed with p-hydroxy-MP and p-hydroxy-Ph.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗