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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 433 records · Page 24Linked to original sources

Combination of high-performance affinity chromatography and specific detection of proenzyme applicable to the analysis of the fibrinolytic system of human plasma.

A procedure for the analysis of the fibrinolytic system in human blood was devised by combining high-performance affinity chromatography (HPAC) and specific detection of proenzyme. Components of the fibrinolytic system were separated by HPAC using Asahipak GS gel coupled with p-aminobenzamidine, and they were specifically detected by means of an on-line enzyme assay system. This system made it possible to quantitate not only Glu-plasminogen (Glu-Plg) but also Lys-plasminogen (Lys-Plg) in human plasma in a short time without pre-treatment. The effect of urokinase on the state of components of the fibrinolytic system in blood was studied. It was clearly shown that Lys-Plg is more susceptible to activation by urokinase than Glu-Plg (both in vitro and in vivo).

Chromatography, Affinity↗

Determination of ascorbic acid in human urine by high-performance liquid chromatography coupled with fluorimetry after post-column derivatization with benzamidine.

High-performance liquid chromatography on two Asahipak GS-320 hydrophilic gel columns (50 X 0.76 cm I.D.), connected in series, with 0.015 M tartrate buffer (pH 3.0), containing 2 mM ethylenediaminetetraacetate and 0.05% beta-thiodiglycol as eluent allowed the separation of glucose, diketogulonic acid + diketogluconic acid, dehydroisoascorbic acid, dehydroascorbic acid, ascorbic acid, and isoascorbic acid within 55 min. Ascorbic acid in a urine sample was stabilized by the addition of an equal volume of 5% metaphosphoric acid solution, containing 0.5% of beta-thiodiglycol. Filtration of the mixture through a column of Dowex 50W-X8 (H+) facilitated the determination of ascorbic acid and isoascorbic acid in human urine. Samples could be analyzed every 20 min.

Ascorbic Acid↗

Unique cell surface phenotypes of proliferating lymphocytes in mice homozygous for lpr and gld mutations, defined by monoclonal antibodies to MRL/Mp-lpr/lpr T cells.

In mice bearing the autosomal recessive gene of either lpr or gld, generalized T-cell proliferation and autoimmunity occurs. The surface antigen profiles of these proliferating cells were analyzed using two-color flow cytometry analysis with two newly established rat monoclonal antibodies (ALP-1, ALP-2) directed to lpr cells. The Lp-1 antigen, defined by ALP-1, is expressed exclusively on approximately one-half of proliferating lpr and gld lymph node cells. The Lp-2 antigen, like B 220, is expressed on 80-90% of lpr and gld lymph node cells, the cells in B-cell lineage and a small population of Ly-2+ T cells from normal mice. Thus, the lpr and gld lymph node cells were classified into three subsets, Lp-1+/Lp-2+, Lp-1-/Lp-2+ and Lp-1-/Lp-2-. After stimulation with Con A or a combination of IL-2 and phorbol ester, a small population of T cells from normal mice became Lp-1+. The same treatment increased Lp-2+/Ly-2+ and induced Lp-2+/L3T4+ T-cell populations. Therefore, it seems likely that these phenotypically unique T cells are generated at some stage during the proliferation and differentiation of certain normal T-cell subpopulations. The aberrant T cells in mice with lpr and gld mutations may even be normal regulatory T cells, if they are not proliferating abnormally.

Animals↗

Effects of nipradilol on myocardial ischaemia produced by coronary stenosis in dogs.

Effects of nipradilol which is a new beta-adrenoceptor blocking agent endowed with nitroglycerin-like vasodilator actions, its denitrated derivative (denitro nipradilol) and propranolol on abnormalities of regional myocardial shortening produced by partial occlusion of the left circumflex coronary artery (LCX) were studied in anaesthetized open-chest dogs. In the presence of LCX stenosis, nipradilol (0.1 mg kg-1, i.v.) produced marked decreases in heart rate and LVdP/dt without a significant increase in left ventricular end-diastolic pressure (LVEDP). It improved impaired myocardial segment shortening and restored normal cardiac lactate metabolism. Denitro nipradilol (0.2 mg kg-1 i.v.) and propranolol (0.2 mg kg-1 i.v.) both caused similar haemodynamic changes to nipradilol but also produced a significant increase in LVEDP. However, improvement by these two agents of regional dysfunction in the ischaemic myocardium was comparable to those seen with nipradilol. All three agents markedly inhibited isoprenaline-induced tachycardia, but vehicle did not. Atrial pacing abolished the beneficial effect of nipradilol on myocardial shortening in the ischaemic region without affecting other haemodynamic parameters. These results indicate that nipradilol alleviates acute myocardial ischaemia produced by coronary stenosis with similar efficacy to denitro nipradilol and propranolol suggesting, that a major part of the beneficial effect of nipradilol may be attributable to its beta-adrenoceptor blocking action.

Adrenergic alpha-Antagonists↗

Responses of renal, coronary and vertebral vasculatures to MC-838 and captopril in anesthetized dogs.

The regional hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, and captopril at equidepressor doses were examined in the anesthetized dog by simultaneously measuring renal (RBF), coronary (CBF), vertebral (VBF) arterial and aortic blood flow (AoF). Hemodynamic responses to angiotensin I (AI), AII and noradrenaline were compared before and after the administration of each inhibitor. MC-838 (3 mg/kg i.v.) lowered gradually aortic pressure (AoP) and increased moderately AoF and RBF up to 60 min after the administration. Captopril (0.1 mg/kg i.v.) lowered AoP immediately after the administration and increased AoF and RBF more shortly than MC-838. Neither inhibitor produced a marked change in VBF or CBF. The effects of the inhibitors in the renal vascular bed was much greater than that in vertebral and coronary vascular beds, although vascular resistance in all of them was significantly reduced. Each of the drugs inhibited the pressor and renal vasoconstrictor responses to AI. These results indicate that the renal vasculature is more sensitive to both MC-838 and captopril than vertebral and coronary vasculature, but MC-838 has a slower and longer-lasting action than does captopril.

Angiotensin-Converting Enzyme Inhibitors↗

Identification of inhibin secreted by cynomolgus monkey Sertoli cell cultures.

An inhibin was identified in the media of primary Sertoli cell-enriched cultures from the cynomolgus monkey, Macaca fascicularis, and some of its biochemical properties were studied. Conditioned monkey Sertoli cell culture medium (m-SCCM), when added to pituitary cells from 6-week-old male rats, inhibited the basal secretion of FSH but not that of LH. This specificity was lost after the addition of GnRH; mSCCM inhibited not only FSH but also LH release, determined by both RIA and mouse interstitial cell bioassay, from pituitary cells exposed for 6 h to 10 nM GnRH. FSH-inhibiting activity persisted when m-SCCM was boiled for 30 min, but activity was lost after incubation for 1 h at 37 C with 0.1% trypsin. m-SCCM inhibin activity was completely retained by Concanavalin A-Sepharose and could be eluted with 0.2 M alpha-methyl-D-glucoside. Gel filtration high pressure liquid chromatography with a Superose-12 column revealed inhibin activity between 20-60K, with the greatest activity at 40K. Our results indicate that primate Sertoli cells produce an inhibin-like factor which could play a role in controlling gonadotropin secretion in males.

Animals↗

A rapid and sensitive analytical procedure for human plasminogen subspecies. Combination of high-performance affinity chromatography and specific monitoring of proenzymes.

Human plasminogens specifically separated by high-performance affinity chromatography were specifically detected by a newly devised, on-line monitoring system, in which the proenzymes were activated by urokinase and plasmin activity thus generated was assayed. Presence of Lys-plasminogen as a constituent in the blood was demonstrated by both chromatographic patterns and biochemical experiments. This system made it possible to estimate rapidly not only Glu-plasminogen but also Lys-plasminogen in the plasma without any pretreatment. Its utility as a tool for clinical analysis of fibrinolytic system was suggested.

Chromatography, High Pressure Liquid↗

[Lymphocyte subsets and response of breast cancer and benign mammary disease to PHA].

The lymphocyte counts, subsets and response to PHA in the peripheral blood of patients with breast cancer (stage I-III) and with a benign mammary disease have been evaluated. In the breast cancer cases, the lymphocyte counts and stimulation index of PHA increased gradually as the stages advanced but there was no statistical significance. The ratio and number of OKT 4 positive lymphocytes were significantly lower in patients with breast cancer (stage I) between 40 and 59 years old than in patients with benign mammary diseases between the same ages. This impairment of OKT 4 in breast cancer (stage I) cases was considered as either a cause of the carcinoma or as a reflection of the environment of steroid hormones.

Antigens, Surface↗

Effects of Chrysanthemum indicum Linn. on coronary, vertebral, renal and aortic blood flows of the anesthetized dog.

The hemodynamic effects of the water extract of flower of Chrysanthemum indicum Linn. (CIL) and adenosine were examined in anesthetized open-chest dogs by measuring simultaneously and continuously coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flows (AoF). Intravenous administration of CIL (5-20 mg/kg) as well as adenosine (10-50 micrograms/kg) produced decreases in aortic blood pressure (AoP) and RBF, and increases in AoF, VBF, CBF and left ventricular dP/dt (LVdP/dt). Calculated coronary, vertebral and total peripheral resistances were decreased by CIL or adenosine in a dose-dependent manner. The ratio (1.69 +/- 0.27) of decrease in coronary vascular resistance to that in total peripheral resistance by CIL (10 mg/kg) was apparently smaller than that (4.03 +/- 0.48) by adenosine (10 micrograms/kg). After beta-adrenergic blockade, increases in AoF and LVdP/dt were inhibited, but decreases in AoP and coronary, vertebral and total peripheral resistances and increase in renal vascular resistance were not changed. These results indicate that CIL directly and uniformly produces coronary and systemic vasodilation with renal vasoconstriction, and that adenosine directly produces vasoconstriction in renal vasculature and vasodilation which is more potent in coronary vasculature than in systemic ones.

Adenosine↗

Requirement of H-2 heterozygosity for autoimmunity in (NZB X NZW)F1 hybrid mice.

In the F1 hybrid of autoimmune New Zealand Black (NZB) and phenotypically normal New Zealand White (NZW) mice, there occurs a severe systemic lupus erythematosus (SLE)-like autoimmune disease more fulminant than that found in the parental NZB mice. To determine the role of the H-2 complex in the pathogenesis of autoimmune disease of the (NZB X NZW)F1 hybrid, we developed H-2-congenic NZB (NZB.H-2z) and NZW (NZW.H-2d) strains, and compared the degree of autoimmune features between congenic H-2d/H-2d and H-2z/H-2z homozygous F1 hybrids and the original H-2d/H-2z heterozygous (NZB X NZW)F1 hybrid. We found that autoimmune features such as productions of IgG class anti-DNA antibodies and retroviral gp70 immune complexes and the development of renal disease were to a great extent reduced in both H-2 homozygous F1 hybrids, as compared with the H-2 heterozygous (NZB X NZW)F1 hybrid. It would thus appear that the heterozygosity of H-2d haplotype derived from NZB and H-2z from NZW is essential for the autoimmune disease characteristic of the (NZB X NZW)F1 hybrid.

Animals↗

Vasodilating effects of nicorandil and nitroglycerin in anaesthetized open-chest dogs.

Vasodilating effects of intravenous administrations of nicorandil (SG-75) and nitroglycerin were analyzed in anaesthetized open-chest dogs by measuring simultaneously, and continuously, coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flow (AoF). Nicorandil 10-300 micrograms/kg i.v. and nitroglycerin 1-30 micrograms/kg i.v. decreased aortic blood pressure and increased CBF in a dose-dependent fashion. The doses of nicorandil and nitroglycerin which reduced coronary vascular resistance to about 60% of the predrug value were 100 micrograms/kg and 10 micrograms/kg, respectively. Nicorandil 100 micrograms/kg i.v. significantly increased AoF and heart rate, significantly decreased left ventricular end-diastolic pressure and did not significantly change VBF, RBF and left ventricular dP/dt. Nitroglycerin 10 micrograms/kg i.v. significantly increased VBF and heart rate, significantly decreased left ventricular end-diastolic pressure and produced an initial increase followed by a decrease in AoF and RBF. When compared with these doses of both drugs, the ratio of percent decrease in coronary vascular resistance to that in total peripheral resistance was over 1.0 in both drugs and the value of this ratio in nicorandil was significantly larger than that in nitroglycerin. The duration of increase in CBF produced by nicorandil 10-300 micrograms/kg i.v. was dose-dependent, but was not changed by nitroglycerin 1-30 micrograms/kg i.v. The results indicate that nicorandil and nitroglycerin dilate coronary vasculature more markedly than other vascular beds and that the potency of selective coronary vasodilatation and the duration of action are more significant in nicorandil than in nitroglycerin.

Anesthesia↗

Effects of habu (Trimeresurus flavoviridis) venom on isolated and perfused hearts of rats.

Crude habu venom decreased coronary perfusion pressure and produced a small increase in myocardial tension of isolated and perfused rat hearts. Indomethacin infusion depressed the fall in perfusion pressure caused by the venom, without affecting the increase in tension. Heated venom decreased perfusion pressure, but did not increase myocardial tension. These results suggest that crude habu venom has coronary vasodilating and positive inotropic effects, possibly through actions of a phospholipase A2 and a heat-labile component, respectively.

Animals↗

Prolonged treatment of hyperthyroidism with sodium tyropanoate, an oral cholecystographic agent: a re-evaluation of its clinical utility.

To re-evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1.5 g daily) alone for 14 weeks, and six patients (TP + MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an 'escape' occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment. In the TP + MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4-14 weeks (7.3 +/- 5.0 weeks on the average), TP was withdrawn and replaced by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗