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Biomedical subjects

H Uchida

Publications and source records attributed to H Uchida.

At least 379 records · Page 21Linked to original sources
PubMed1992

Identification of urinary metabolites of 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in rat, rabbit and dog.

The metabolism of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) in rat, rabbit and dog was studied. The urine of animals dosed with 14C-KC-764 was extracted with ethyl acetate after treatment with beta-glucuronidase and arylsulfatase. The metabolites were purified by TLC and HPLC from the extract. Unchanged KC-764 and 16 metabolites were isolated and their structures were identified or proposed by NMR and MS spectrometry. The metabolism of KC-764 took place by the oxidation of the tetrahydropyridine ring, 6,7-position and 2-methyl group of the pyrazolopyridine ring, and their combinations. The oxidation of the tetrahydropyridine ring was predominant in dog, whereas the oxidation of the pyrazolopyridine ring was more important in rabbit. Rat produced the various metabolites by their combination. 6-Oxo and 6-ureido derivatives of the tetrahydropyridine ring were common major metabolites in all animal species studied.

Animals↗
PubMed1992

Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in laboratory animals.

KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo [1,5-a]pyridine CAS 94457-09-7) and its metabolites in serum and urine were determined after intravenous and oral administration in mice, rats, rabbits and dogs at a dose of 5 mg/kg. KC-764 was rapidly eliminated from serum in all species. The biological half-lives of unchanged KC-764 after intravenous administration in mice, rats, rabbits and dogs were 1.31, 0.29, 1.94 and 1.20 h, respectively. 2-Methyl-3-(1,4,5,6-tetrahydro-6-oxonicotinoyl)pyrazolo-[1,5-a]pyr idine was a common major metabolite in serum of all species, although 6,7-dihydro-6,7-dihydroxy-2-methyl-3-(1,4,5,6- tetrahydro-6-oxonicotinoyl) pyrazolo-[1,5-a]pyridine (M-8) was more abundant in rabbits. Urinary recovery of unchanged KC-764 was as low as 0.4-2.2% in all species. The major urinary metabolite was 2-methyl-3-(1,4,5,6-tetrahydro-6-ureidonicotinoyl)pyrazolo-[1,5-a] pyridine in mice, rats and dogs, but M-8 was in rabbits. KC-764 was rapidly and well absorbed by oral administration, and extensively metabolized in all species tested.

Administration, Oral↗
PubMed1992

Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects.

The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC-764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration.

Adult↗
PubMed1992

[Application of an expandable metallic Z-type stent for stenosis of the left main bronchus following tuberculosis--a case report].

A 32-year-old man had been suffering from dyspnea on exertion and stridor, which were due to stenosis of the left main bronchus as a complication of bronchial tuberculosis. A three-connection stent, 1.2 cm in diameter and 4.5 cm in length was placed at the site of the bronchial stenosis. Dyspnea disappeared 2 days after the procedure, and the pulmonary function 3 weeks later showed considerable improvements in %FVC, FEV1 and MMF.

Adult↗
PubMed1992

[Improvement of bone marrow hematopoiesis in idiopathic myelofibrosis with prednisolone].

A 64 year-old female patient of idiopathic myelofibrosis (IMF), who had had rapidly progressing massive splenomegaly and severe pancytopenia refractory to blood transfusion, was treated with PSL 0.6 mg/kg/day for a month, being significantly improved not only symptomatically and hematologically but also in bone marrow hematopoiesis. Although the effectiveness of PSL to restoration of bone marrow hematopoiesis has been almost unknown, long term oral PSL should be tried for a certain phase of IMF.

Bone Marrow↗
PubMed1992

Dental fear in Japan: Okayama Prefecture school study of adolescents and adults.

A total of 3,041 students and staff in middle school in Okayama Prefecture, Japan, were surveyed regarding dental fear. Over 88% reported fear, with 42.1% classified as having high fear. Almost 70% reported acquiring dental fear prior to junior high school. A majority reported being hurt at the last appointment. Delay of dental work was also reported for over 50% of the sample. Coping, pattern of physiological upset, nondental fears, and sex and age differences were also reported. Results suggest intervention is needed to address the major dental public health problems associated with dental fear.

Adolescent↗
PubMed1991

Immunobiological activities of synthetic peptide segments of fimbrial protein from Porphyromonas gingivalis.

Several oligopeptide segments of fimbrial subunit protein (fimbrilin) of Porphyromonas gingivalis strain 381 were synthesized and tested for immunobiological activities. Peptides F3(31-50; amino acid residue numbers 31 to 50, based on the amino acid sequence of the fimbrilin proposed by Dickinson et al., Infect. Immun., 170, 1658, 1988), F12(212-231) and F17(312-331) were found to be immunodominant epitopes of this fimbrial protein as revealed by ELISA. Furthermore, peptides F5(71-90) and F17(312-331) were demonstrated to agglutinate rabbit erythrocytes, and were mitogenic for BALB/c spleen cells but not thymocytes. These peptides enhanced the number of fimbria-specific antibody-secreting cells in BALB/c spleen cell cultures, and induced cytokines such as tumor necrosis factor-alpha and interleukin-6 production in human monocyte/macrophage cultures. The data demonstrate that these defined peptide segments are responsible for the immunostimulating portions within the fimbrial protein molecule.

Amino Acid Sequence↗
PubMed1991

Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies.

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.

Animals↗
PubMed1991

Fluctuating CPAP (F-CPAP) versus conventional CPAP (C-CPAP) in dogs with blood aspiration.

Fluctuating CPAP(F-CPAP) is a combination of spontaneous ventilation and fluctuating PEEP, in which end-expiratory pressure (EEP) is periodically changed within a certain range. In a dog model with localized lung injury induced by the aspiration of non-heparinized blood (2 ml.kg(-1) body weight), we carried out a comparative study of the effects of F-CPAP in which the EEP was cyclically changed from 4 to 12 cmH(2)O with periods of 10 min and those of conventional CPAP with a fixed EEP of 8 cmH(2)O (C-CPAP), on hemodynamics and pulmonary oxygenation. The blood aspiration produced significant increases in the intrapulmonary shunt (Qsp/Qt), the alveolar-arterial difference of partial pressure of oxygen (A-aD o(2)), and the respiratory rate (RR). Although both F-CPAP and C-CPAP reduced Qsp/Qt and A-aD o(2) and RR, 7 dogs treated with F-CPAP showed a significantly greater recovery of Qsp/Qt and A-aD o(2) than 7 dogs treated with C-CPAP. There were no significant differences in hemodynamic variables between the two groups. These results suggest that F-CPAP is more useful in the treatment of some kinds of hypoxic respiratory failure due to uneven distribution of lung injury.

Journal Article↗
PubMed1991

Synergistic coronary vasoconstriction produced by endothelin-1 in combination with 5-hydroxytryptamine.

The present study was undertaken to examine the action of endothelin-1 (ET-1) per se, or the combined effects of ET-1 with vasoconstrictor agonists such as acetylcholine (ACh), histamine (His), and 5-hydroxytryptamine (5-HT), all of which have been implicated in the genesis of coronary spasm. Isometric tension development and the cytosolic Ca2+ concentration [( Ca2+]i) in a ring segment of porcine coronary artery loaded with fura-2 were measured simultaneously with a mechanoelectric transducer and a fluorometer, respectively. ET-1 (30-100 pM) specifically potentiated the 5-HT-induced contraction without causing a significant increase in [Ca2+]i. This effect of the peptide seems to be qualitatively similar to that produced by the tumor-promoting phorbol ester, DPB. These results suggest that the combined stimulation of ET-1 and 5-HT augments the Ca2+ sensitivity of the contractile elements through the possible activation of protein kinase C.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Potentiation by endothelin-1 of 5-hydroxytryptamine-induced contraction in coronary artery of the pig.

1. In order to elucidate the physiological and potential pathological roles of endothelin-1 (ET-1) in coronary artery contraction and relaxation, we undertook the present study to examine the action of ET-1 itself, and the combined effects of ET-1 with vasoconstrictor agonists such as acetylcholine (ACh), histamine, and 5-hydroxytryptamine (5-HT), all of which have been implicated in the genesis of coronary spasm. 2. Isometric tension and cytosolic Ca2+ concentration ([Ca2+]i) in a ring segment of porcine coronary artery loaded with fura-2 were measured simultaneously. 3. ET-1 contracted the artery in a concentration-dependent manner; and nisoldipine, a Ca2+ channel blocking drug of the 1,4-dihydropyridine type, antagonized the ET-1 action non-competitively. A radio-receptor binding assay also indicated the mutually exclusive binding of ET-1 and (+)-[3H]-PN200-110, a Ca2+ channel ligand, to the membrane fraction of porcine coronary artery. 4. ET-1 (10-100 pM) increased tension and [Ca2+]i in a parallel manner, while at higher concentrations (1-10 nM) it produced further contraction with a small increase in [Ca2+]i. 5. ET-1 (30-100 pM) selectively potentiated the 5-HT-induced contraction 1.5 to 2 times over the control without causing a significant increase in [Ca2+]i, which seems to be qualitatively similar to a tumour promoting phorbol ester, 12-deoxyphorbol 13-isobutylate (DPB). Bay K 8644 (10 nM), on the other hand, potentiated the contraction in response to practically all agonists used and affected a concomitant increase in [Ca2+]i.6. A Ca2+ channel blocking drug such as diltiazem abolished the increase in [Ca2+]i and partially attenuated the mechanical potentiation produced by a small amount of ET-1 in combination with 5-HT.7. The results suggest that ET-1 and 5-HT interact functionally at the cellular or subcellular level and modulate the Ca2 + sensitivity of the contractile elements through the possible activation of protein kinase C.

Animals↗
PubMed1991

Increase in tumor necrosis factor alpha- and interleukin-6-secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis.

We detected and quantified tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) from monocytes/macrophages (M phi) in the peripheral blood of subjects from three different population groups, i.e., tuberculin-negative healthy subjects, tuberculin-positive healthy subjects, and patients with active pulmonary tuberculosis. TNF-alpha or IL-6 activity in the culture supernatant of these cells was determined by the cytotoxicity of murine L-929 cells or by enzyme-linked immunosorbent assay, respectively. Detection and enumeration of cells secreting either TNF-alpha or IL-6 were performed by an adaptation of the enzyme-linked immunospot assay. Monocytes/M phi from tuberculin-positive healthy subjects or patients with tuberculosis showed higher TNF-alpha- and IL-6-producing activities than those from tuberculin-negative healthy subjects. The number of TNF-alpha- and IL-6-secreting cells in either lipopolysaccharide- or muramyl dipeptide-stimulated mononuclear cells from tuberculin-positive healthy subjects and patients was significantly higher than that in cells from the tuberculin-negative healthy subjects.

Adult↗
PubMed1991

Transcription and initiation of ColE1 DNA replication in Escherichia coli K-12.

By S1 nuclease protection mapping, we characterized RNA transcripts and nascent ColE1 DNA synthesized in wild-type Escherichia coli cells after infection with lambda-mini-ColE1 hybrid bacteriophages. Transcription of the RNA II region of ColE1 DNA in vivo starts mostly from the RNA II promoter, which was identified by in vitro experiments, and ends at or near the ori site. Synthesis of the leading strand of ColE1 DNA was found to start at the ori site. Nevertheless, the molar ratio of the nascent DNA to the synthesized transcripts ending at the ori site was less than 0.05. In bacterial rnh mutants whose RNase H activities were less than 0.06% of that of the wild type, transcription patterns, as well as nascent DNA synthesis, were still similar to those in rnh+ cells. However, in bacteria whose rnh gene was interrupted by insertion of a drug resistance gene, the number of transcripts ending at the ori site was much reduced and that of transcripts reading through the ori site was definitely increased relative to that observed in wild-type bacteria. These results suggested that cleavage of the RNA transcript at the ori site in vivo is dependent on RNase H activity, as demonstrated in the in vitro system, but most of the cleaved RNA is unable to prime initiation of ColE1 DNA synthesis efficiently.

Bacteriocin Plasmids↗
PubMed1991

Identification of pre- and postcentral gyri on CT and MR images on the basis of the medullary pattern of cerebral white matter.

The authors illustrate a new method to identify the pre- and postcentral gyri on computed tomographic (CT) and magnetic resonance (MR) images of the brain on the basis of the pattern of the medullary branches of the cerebral white matter. The most commonly used method to identify the gyri depends on recognition of the central sulcus by surface arrangement of the sulci. The two methods were compared by analysis of CT images of 104 subjects who had normal findings (age range, newborn to 60 years; 57 males and 47 females). The usefulness of the new method was also determined in angiographic studies of nine patients with space-occupying lesions. The method is especially helpful for identification of gyri on the lower level of the centrum semiovale and if space-occupying lesions are present that may result in a blurred depiction of sulci. Since MR imaging depicts the medullary branches more clearly than does CT, this new method should facilitate identification of the gyri with either modality.

Adolescent↗
PubMed1991

Low-dose clonidine enhances pregnancy-induced analgesia to visceral but not somatic stimuli in rats.

This is one of a series of experiments designed to examine the possible pharmacologic basis for analgesia normally associated with pregnancy. The antinociceptive effects of low-dose (0.1 mg/kg) subcutaneous clonidine on analgesia associated with pregnancy were evaluated in rats. Colorectal distention thresholds and tail-flick latencies were determined in timed pregnant rats (n = 27) before mating, on days 7 and 21 of gestation, and on postpartum day 7. Immediately after baseline testing on each of those days, animals received 0.1 mg/kg clonidine subcutaneously and were retested 30 min later. On day 21 of gestation, 20 micrograms/kg naloxone (n = 9) and 0.2 mg/kg yohimbine (n = 5) were intravenously administered after clonidine testing, and animals were retested 15 min later. In the absence of clonidine, pregnant animals demonstrated a statistically significant increase in their tolerance of colorectal distention pressures and longer latencies to tail-flick withdrawal on day 21 of gestation. Clonidine produced a further significant increase in distention thresholds on day 21 of gestation but did not change these thresholds on any other day, nor did it change tail-flick latencies. Naloxone and yohimbine reversed the effect of clonidine on the distention thresholds on day 21. Systemic clonidine, at a dose lower than that required to produce antinociception in nonpregnant rats, enhanced pregnancy-induced analgesia to visceral stimulation late in pregnancy, an effect that was reversed by naloxone and yohimbine. These results suggest a synergistic antinociceptive effect of clonidine due to an interaction with an endogenous opiate system that is only activated late in pregnancy.

Analgesia, Obstetrical↗
PubMed1991

Advantages of triple therapy with mizoribine, cyclosporine and prednisolone over other types of triple and/or double therapy including cyclosporine for renal transplantation.

Mizoribine (Mz) is an analogue of azathioprine (Az) with less hepatotoxicity, being extensively used as immunosuppressant in place of the latter agent especially in Japan. However, careful comparative studies of mizoribine (Mz), cyclosporine (Cy), and prednisolone (Pr) versus azathioprine (Az), Cy and Pr or Cy and Pr in renal allotranspalnt patients have not been reported. Retrospectively we compared triple therapy with Mz, Cy, and Pr (group I, n = 50) to triple therapy with Az, Cy and Pr (group II, n = 13) and/or double therapy with Cy and Pr (group III, n = 11) in one-haplotype-identical living related renal transplantations performed between Oct. 1984 through March 1989. Initial and maintenance doses of Cy in groups I and II were largely two thirds of those in group III. Patient and graft survival rates at 3 years in each group are 100% and 92% (group I), 100% and 91% (group II), and 91% and 82% (group III). There were no statistical differences in patient and graft survival rates between these three groups. The incidences of miscellaneous complications were the same in the groups. Bone marrow suppression, however, was significantly less in group I than in group II (P less than 0.005). Cy related nephrotoxicity was apparently less in groups I and II than in group III. Estimated US $5,000 in a year can be saved by immunosuppressive treatment in a patient of group I as compared to a patient in group III. Therefore, we conclude that triple therapy with Mz, Cy and Pr is superior to those with Az, Cy and Pr, and/or double therapy with Cy and Pr.

Cyclosporine↗