Search PubMed⌕ Search

Biomedical subjects

K Miyoshi

Publications and source records attributed to K Miyoshi.

At least 127 records · Page 7Linked to original sources
PubMed1993

MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action.

We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties. After intraarterial injection, MPC-1304 was 3 times less potent than other dihydropyridines (nitrendipine, nifedipine, nicardipine and nisoldipine) in increasing femoral blood flow. After infusion of these drugs, however, MPC-1304 was the most potent in increasing femoral blood flow. The onset and recovery of the effect of MPC-1304 on femoral blood flow were slower than for nifedipine. Higher doses of Bay K 8644 were needed to antagonize the stimulating activity of MPC-1304 than for nifedipine. In a competition assay of [3H]nitrendipine binding, MPC-1304 and its metabolites bound to the dihydropyridine receptor with lower affinity than the other dihydropyridines. The binding affinity of [3H]MPC-1304 was lower than that of [3H]nitrendipine, consistent with the potency of this drug to increase femoral blood flow by bolus injection. The association and dissociation of [3H]MPC-1304 was slower than those of [3H]nitrendipine, which is consistent with the slow onset and long-lasting vasodilating effects of MPC-1304 on femoral blood flow. Moreover, diltiazem reduced a part of [3H]MPC-1304 binding in a competitive manner. In ex vivo binding assays with serum and aorta obtained after oral administration of the drug in spontaneously hypertensive rats, MPC-1304 inhibited [3H]nitrendipine binding to membrane preparations less potently than nifedipine. From these results, we conclude that MPC-1304 is a different type of dihydropyridine possessing the most potent vasodilating action of the representative dihydropyridines tested. Its activity cannot be explained solely by a slow interaction with voltage-dependent Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Cardiovascular profile of MPC-1304, a novel dihydropyridine calcium antagonist: comparison with other calcium antagonists.

The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG). The ratio of negative chronotropic/negative inotropic effect of MPC-1304 was 23 times higher than that of nifedipine in paced left and spontaneously beating right atria of guinea pigs. MPC-1304 and nifedipine did not change atrial-His (AH) conduction time or His-ventricular (HV) conduction time at hypotensive doses in open-chest dogs, whereas diltiazem prolonged AH time. MPC-1304 increased coronary blood flow, and strongly decreased myocardial oxygen consumption (MVO2) by decreasing blood pressure (BP) and heart rate (HR) in open-chest dogs. Left ventricular pressure (LVP) was not changed. Contractile force (dp/dt) was slightly increased by its action on afterload. MPC-1304 and nifedipine did not dilate the large coronary artery, but NTG did. MPC-1304 increased blood flow of the peripheral arteries, especially vertebral and CBF in anesthetized dogs. Cerebral blood flow (CBF) also increased. MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits. Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris.

Animals↗
PubMed1993

[Development of bladder capacity, nocturnal urinary volume and urinary behavior in nonenuretic and enuretic children].

Bladder capacity, nocturnal urinary volume and nocturnal urinary behavior were investigated in 1751 nonenuretic and 282 enuretic children in two primary schools and four kindergartens. The results were as follows: 1. A statistically significant linear correlation was observed between the age and the bladder capacity in the morning and daytime, as well as nocturnal urinary output, in nonenuretic children. 2. The bladder capacity of enuretic children was smaller in the ages below 6 but larger in the ages over 7 than that of noneuretic children. It was not likely from this evidence that an immature bladder capacity was a primary cause of enuresis. 3. For the estimation of the maximum bladder capacity in the study of enuresis, urinary output in the morning immediately after awakening with sufficient urinary sensation was thought to be more reasonable than that in the daytime, because output in the morning was approximately 50% more than that of the daytime. 4. Ten to 15% of nonenuretic children showed nocturnal polyuria with nocturnal urination after complete awakening more than one time every week. It was also not likely from this evidence that polyuria was a primary cause of enuresis. 5. The overall occurrence rate of enuresis was 14%, higher in males up to the ages of 9, and almost equal in males and females after the ages of 10. 6. The average age for the spontaneous disappearance of enuresis was 7.3 y.o., therefore, adequate treatments for enuresis should be instituted after the age of 8.

Child↗
PubMed1993

Effect of a high-fat meal on the bioavailability of phenytoin in a commercial powder with a large particle size.

The effect of a high-fat meal on the bioavailability of free acid phenytoin (DPH) from Hydantol powder with a large particle size (mean particle size, 190 microns) was investigated in four healthy male subjects. The drug was administered as a single oral 5 mg/kg dose of free acid DPH in the fasting state, with a low-fat meal, or with a high-fat meal using a crossover study design. Seven blood samples were collected over a 34-h period following drug administration, and the drug plasma concentrations were determined by GLC. In comparison with the fasting state results, the mean area under the plasma concentration-time curve up to infinity after administration (AUC0-infinity) and the peak plasma concentration (Cmax) of DPH from Hydantol powder significantly increased about 2-fold with the intake of the high-fat meal and about 1.5-fold with the intake of the low-fat meal. The elimination rate constant was not significantly different among the three treatments. The increased bioavailability with the high-fat meal probably resulted from accelerated dissolution of the poorly soluble Hydantol powder due to the stimulation of bile flow or delay of the gastric emptying time caused by the fat intake.

Adult↗
PubMed1993

[Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog].

The antitumor activity of navelbine (vinorelbine ditartrate, KW-2307) against murine and human transplantable tumors was compared with those of other vinca alkaloids, vindesine (VDS), vincristine (VCR) or vinblastine (VLB). KW-2307 and VDS increased the life span of mice bearing ascitic tumors (P 388 leukemia, L 1210 leukemia, EL-4 lymphoma, Colon 26, FM 3 A mammary carcinoma and M 5076 sarcoma) slightly more than VCR or VLB. A significant difference was not found in the antitumor activities against 6 murine solid tumors (B 16 melanoma, Colon 26, FM 3 A mammary carcinoma, Lewis lung carcinoma, M 5076 sarcoma and Sarcoma 180). However, a remarkable difference was observed in the antitumor activities against 11 human tumors inoculated into nude mice. The activity of KW-2307 was more than those of other 3 drugs against 4 human non-small cell lung carcinomas (Lu-65, Lu-99, LC-6 and L-27) and 2 stomach carcinomas (St-4 and St-40). KW-2307 and VDS were also effective in inhibiting the growth of 2 human breast carcinomas (MX-1 and Br-10).

Animals↗
PubMed1992

Synthesis and inotropic activity of pyrazolo[4,3-c]pyridine-4-ones and related compounds.

Two series of 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-ones (5-9) and 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-thiones (11-13) were prepared from dehydroacetic acid as starting material and evaluated for positive inotropic activity in vitro. Moreover, the activity of the synthesized compounds was compared with that of mirlinone as a reference. Among these compounds, the positive inotropic activity of 8a, 11a, and 12 were approximately 1.24, 1.77, and 1.11 times more potent, respectively, than that of mirlinone.

Animals↗
PubMed1992

Ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific monoclonal antibody delays the onset of acute rejection.

In the following study, we investigated whether ex vivo perfusion of canine pancreaticoduodenal allografts prior to transplantation using a class-II-specific monoclonal antibody (MoAb) OKIa1) could prevent acute rejection. Untreated grafts were rejected within 6 days after transplantation, and all of these recipients suffered severe hyperglycemia. In contrast, in recipients who received grafts which underwent ex vivo class-II-specific MoAb perfusion treatment, the mean urinary amylase levels were sustained significantly higher (11,733 +/- 4493 vs. 3274 +/- 2108 U/L on day 7, P < 0.005), and mean fasting blood glucose (FBG) levels remained within the normal range (13.4 +/- 5.8 vs. 23.4 +/- 3.9 mM on day 7, P < 0.0005). Low doses of cyclosporin A (CsA) were necessary in order to maintain lower FBG levels. Histopathology analysis on day 7 after transplantation showed that endotheliitis and necrosis were much less prominent in the MoAb-treated grafts. In the light of our results, we conclude that ex vivo perfusion of canine pancreaticoduodenal allografts using a class-II-specific MoAb is effective in delaying the onset of acute rejection, and low doses of CsA could extend this effect.

Animals↗
PubMed1992

A case of ileus caused by a spiruroid nematode.

A 34-year-old male living in Aichi Prefecture, Japan, complained of lower abdominal pain. Ileus was suspected based on his clinical history and symptoms, and a laparotomy was performed. Four sections of a nematode were found in a large eosinophilic granuloma in the intestinal wall, and were identified as the larva of a spiruroid nematode. This is the third reported case of a spiruroid nematode infection found in the ileum.

Adult↗
PubMed1992

Detection of herpes simplex and varicella-zoster virus DNA by field-inversion gel electrophoresis from clinical materials.

A simple method using field-inversion gel electrophoresis (FIGE) was applied to detect herpes simplex virus (HSV) and varicella-zoster virus (VZV) genomes in clinical specimens. The whole genomes of these viruses could be detected in small vesicle tissues by the FIGE method regardless of their clinical stages of skin lesions. And the sensitivity of the FIGE method was equivalent to that of an immunofluorescent (IF) method. These data indicated usefulness of the FIGE method to detect the whole genomes of HSV and VZV in clinical specimens.

DNA, Viral↗
PubMed1992

Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics.

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of five compounds, A, B1, B2, C1 and C2, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC50 value of 6 pM against human uterine cervix carcinoma HeLa S3 cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [3H]-TdR into macromolecules of HeLa S3 cells as compared with that of [3H]UR or [3H]leucine. DNA strand breaks were detected in DUMB1-treated HeLa S3 cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.

Animals↗
PubMed1992

[Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients].

We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases.

Ambulatory Care↗
PubMed1991

Reversal of learning impairment in ventral globus pallidus-lesioned rats by combination of continuous intracerebroventricular choline infusion and oral cholinergic drug administration.

The effects of separate or combined oral administration of THA (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate hydrochloride) and intracerebroventricular choline infusion using an osmotic minipump were investigated by observing locomotor activity, shock sensitivity, passive avoidance response and cerebral choline and acetylcholine contents in the bilateral ventral globus pallidus-lesioned rat. Evaluation of locomotor activity and shock sensitivity revealed no sensorimotor disturbances caused by combined administration. Intracerebroventricular choline infusion (100 mumol/day) and oral THA or NIK-247 administration (0.5 mg/kg) had no effect on the acquisition of the passive avoidance response, while the combination of oral THA or NIK-247 administration (0.5 mg/kg) and intracerebroventricular choline infusion (100 mumol/day) elicited good acquisition of passive avoidance learning and produced a significant increase of choline and acetylcholine in the cerebral cortex of the bilateral ventral globus pallidus-lesioned rat. These findings suggest that continuous intracerebroventricular choline infusion may intensify the ameliorating effect of THA or NIK-247 on learning disturbance.

Acetylcholine↗
PubMed1991

Combined photic and nonphotic electro-oculographic responses in the clinical evaluation of the retinal pigment epithelium.

In an attempt to simplify the recording technique in electrophysiologic evaluation of the retinal pigment epithelium, we combined the electro-oculographic light rise, hyperosmolarity and acetazolamide responses in a single recording session. Recordings were performed in six normal subjects and in seven patients with diabetic retinopathy or retinitis pigmentosa. In the patients with background diabetic retinopathy, the hyperosmolarity responses were slightly reduced, while the acetazolamide response and the light rise was normal. In the patients with proliferative diabetic retinopathy, the hyperosmolarity response and light rise were remarkably reduced, while the acetazolamide response was normal. In the patients with retinitis pigmentosa, the hyperosmolarity response and light rise were decreased, while the acetazolamide response was normal. Despite a small study population, we concluded that the clinical results from our combined recording protocol were essentially the same as those reported for each response separately. Because this recording technique simplifies electrophysiologic evaluation of the retinal pigment epithelium, it may help clarify the mechanisms or localization of retinochoroidal and pigment epithelial diseases.

Adolescent↗