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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 451 records · Page 25Linked to original sources
PubMed1990

Pharmacological studies on (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)amino] propionyl]-2-oxo-imidazolidine-4-carboxylic acid hydrochloride (TA-6366), a new ACE inhibitor: I. ACE inhibitory and anti-hypertensive activities.

TA-6366 and its active metabolite 6366A inhibited swine renal angiotensin converting enzyme (ACE) activity with IC50s of 9900 and 2.6 nM, respectively. TA-6366 (0.05-0.5 mg/kg, p.o.) inhibited the angiotensin I (AT-I)-induced pressor response in rats. 6366A augmented bradykinin (BK)-induced contraction of guinea pig ileum more potently than captopril. However, when the augmentation on BK-induced hypotension in rats was used as an indicator, TA-6366 was less active than captopril. TA-6366 increased plasma renin activity and plasma AT-I concentration. Oral administration of TA-6366 lowered the blood pressure in two-kidney one-clip renal hypertensive rats at 0.5 to 2 mg/kg and in spontaneously hypertensive rats (SHRs) at 2 to 10 mg/kg. The antihypertensive effect of TA-6366 was approximately 5 times more potent than that of captopril and almost as potent as that of enalapril. In SHRs, the antihypertensive action of TA-6366 was intensified in potency when administered repeatedly. The duration of action was longer than those of captopril and enalapril. However, TA-6366 had no substantial effect on the blood pressure in DOCA/saline hypertensive rats. These results indicate that TA-6366 is a potent and long lasting antihypertensive agent and that its antihypertensive action is attributable to the inhibition of ACE.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

An outbreak of bovine ephemeral fever in Nagasaki Prefecture in 1988.

In October, 1988, bovine ephemeral fever (BEF) occurred in Nagasaki Prefecture and throughout Kyushu island, with the exception Miyazaki Prefecture. The first outbreak occurred in Hirado-shi on October 17. The total number of diseased cattle was 24 in 24 farms in Nagasaki Prefecture. The clinical findings were mainly sudden fever, anorexia, and instability in standing. The serum neutralizing antibodies against BEF virus (BEFV) rose in all infected cattle. Twelve strains of the virus were isolated in HmLu-1 cell cultures made directly from the heparinized blood of 17 infected cattle. The buffy coat was mainly collected from the samples and washed three times with phosphate buffered saline. These isolates were all neutralized by an antiserum against BEFV (Yamaguchi strain). With the aid of an electron microscope, a representative of isolates named Hirado-9 with a length of 150 nm was seen in the sample of infected HmLu-1 cell cultures. Both Hirado-9 and Yamaguchi strains reacted with antisera. The outbreak of BEF in 1988 was the first since 1971 in Nagasaki Prefecture. The result proved that BEFV can be easily isolated in HmLu-1 cell culture from the washed blood cells of infected cattle.

Animals↗
PubMed1990

Hydranencephaly-cerebellar hypoplasia in a newborn calf after infection of its dam with Chuzan virus.

Chuzan virus at 2 to 3 passage levels in cell cultures after isolation was inoculated intravenously into 15 seronegative pregnant cows at 89 to 150 days of gestation. All of the cows developed viremia a few days after inoculation and antibodies 2 weeks after inoculation. No clinical signs, except leukopenia, were observed throughout the experimental period. These 15 cows delivered 15 calves after normal gestation. One of the calves which was born to a dam inoculated at 120 days of gestation, showed impairment of movement, and the remaining 14 were healthy. Postmortem examination revealed that this calf had hydranencephaly- cerebellar hypoplasia (HCH) syndrome and that the remaining calves were normal. Two of the 15 calves, including the one that had HCH syndrome, had antibody to Chuzan virus in their precolostral sera. These findings provide additional evidence that Chuzan virus is the etiological agent of an epizootic of congenital abnormalities with HCH syndrome of calves in Japan, 1985 to 1986. We propose to name the HCH syndrome caused by Chuzan virus infection Chuzan disease.

Anencephaly↗
PubMed1990

[Evaluation of separating X- and Y-sperms by percoll density gradient centrifugation using sperms of transgenic mice carrying a transgene on Y-chromosome].

Using sperms of the transgenic mice carrying a human A gamma/beta-globin gene on Y-chromosome, we attempted to separate X- and Y-bearing sperms by the Percoll density gradient centrifugation. The ratio of X- and Y-sperms was determined by DNA dot blot hybridization procedure with sperm DNA. Sperm suspension collected from cauda epididymidis was loaded on the gradient composed of 7 Percoll concentrations (35-84%) and was centrifuged at 300 x g for 10, 15 or 20 minutes, respectively, at room temperature. After centrifugation, sperms were collected from each gradient fraction and washed with 0.85% saline solution. DNA was extracted from sperms, dotted and fixed on nitrocellulose filter, and was hybridized with the 32P-labeled DNA probe derived from the beta-globin gene. Each DNA spot was cut out, immersed in the liquid scintillator and was counted for radioactivity. There was no difference among the radioactivities in the DNA spots, indicating that the ratio of X- and Y-sperms was the same in all the gradient fractions of three different centrifugal conditions. The results suggests to be difficult to separate X- and Y-sperms by Percoll density gradient centrifugation, at least, using sperms from cauda epididymidis of mouse.

Animals↗
PubMed1990

Anti-inflammatory activity of ginsenoside Ro.

Ginsenoside Ro, an oleanane-type saponin has been screened for activity in experimental models of inflammation. Ginsenoside Ro (10, 50, and 200 mg/kg, p.o.) inhibited an increase in vascular permeability in mice induced by acetic acid and reduced an acute paw edema in rats induced by compound 48/80 or carrageenin. Ginsenoside Ro did not suppress a developing adjuvant-induced edema in arthritic rats. However, ginsenoside Ro was found to be effective in hypercoagulable state, increase of connective tissue in the artery and calcium effluence from the bone in adjuvant-induced arthritic rats.

Animals↗
PubMed1989

Inhibition of purified human postheparin lipoprotein lipase by beta-adrenergic blockers in vitro.

We examined the effects of five beta-adrenergic blockers on the hydrolysis of phosphatidylcholine-stabilized triolein particles by purified human postheparin lipoprotein lipase (PHLpL) in order to evaluate the possible role of direct inhibition as a mechanism of drug-induced hypertriglyceridemia. The relative inhibitory potencies were observed in the following order: propranolol much greater than pindolol greater than metoprolol greater than atenolol greater than nadolol. There was a positive correlation between the octanol/water partition coefficients of these agents and their inhibition of lipoprotein lipase, suggesting that hydrophobicity may be one of the major determinants for PHLpL inhibition. The amount of the beta-adrenergic blockers required to produce 50% inhibition of human PHLpL was much greater than that required to inhibit purified bovine lipoprotein lipase.

Adrenergic beta-Antagonists↗
PubMed1989

Immunohistochemical localization of immunoglobulins in bovine granulomatous lesions.

The immunohistochemical distribution of IgG, IgA and IgM in granulomatous lesions caused by Actinomyces bovis, Actinobacillus lignieresi, Actinomyces (Corynebacterium) pyogenes, Pseudomonas aeruginosa, Staphylococcus aureus and Mycobacterium bovis was studied. Numerous IgG-containing cells (plasma cells) were distributed in the peripheral connective tissue layers, but not in the epithelioid cell layer. A few scattered IgA- and IgM-containing cells were found in all the lesions examined. Mycobacterial granulomas contained fewer IgG-cells than did non-mycobacterial granulomas. Eosinophilic club-shaped bodies were found in A. bovis, A. lignieresi, P. aeruginosa and S. aureus, but they were generally negative for IgG, IgA and IgM.

Actinobacillus Infections↗
PubMed1989

Calmodulin-binding proteins in subcellular fractions of zones of the adrenal cortex.

The guinea pig adrenal cortex consists of a steroidogenic ACTH-responsive outer zone and an ACTH-unresponsive inner zone. It has been suggested that calmodulin plays an important role in ACTH-stimulated steroidogenesis. Thus, in an effort to examine the calmodulin 'system' in the guinea pig adrenal cortex model, Ca2+-dependent binding of calmodulin to proteins in subcellular fractions of the outer and inner zones was examined by the [125I]iodocalmodulin overlay technique and compared to similar studies utilizing pancreas, brain and liver tissue. Although the general pattern of calmodulin-binding proteins was similar for the two adrenocortical zones, quantitatively there was a striking difference with greater binding in the outer zone; this was particularly noteworthy for the mitochondrial fraction. The two most prominent calmodulin-binding proteins isolated from cytosol by calmodulin-Sepharose column chromatography had Mr of 60,000 and 47,000. The size of these two proteins suggested the presence of Ca2+/calmodulin-dependent protein kinase II. Western blot analysis, however, failed to demonstrate calmodulin kinase II in either zone, although it was clearly detectable in brain cytosol. The 60 K calmodulin-binding protein in the adrenal cortex also suggested the presence of the calmodulin-binding A subunit of the Ca2+/calmodulin-stimulated protein phosphatase, calcineurin. Western blot analysis did reveal the presence of calcineurin in the outer adrenocortical zone; it was not detectable, however, in the inner adrenocortical zone. The relation between the striking zonal differential for calmodulin-binding proteins and the zonal differential in ACTH-stimulated steroidogenesis in the guinea pig adrenal cortex will require further investigation.

Adrenal Cortex↗
PubMed1989

Relationship between hypertriglyceridemia and uric acid production in primary gout.

The relationship between uric acid metabolism and lipid levels was analyzed in 148 male subjects with primary gout. The subjects were divided into three groups according to their alcohol consumption: heavy drinkers, moderate drinkers, and nondrinkers or mild drinkers. There was no correlation between urinary uric acid excretion and serum triglyceride (TG) levels in the heavy group, but a marginally significant correlation was shown in the moderate group (P less than .05), and a significant correlation was observed in the nondrinker or mild group (P less than .001). This relationship in the nondrinker or mild group was also found to be significant after adjustment for BMI and age by multiple regression analysis. Serum lipoproteins were analyzed by sequential preparative ultracentrifugation in 21 patients with primary gout who neither drank alcohol nor were obese; VLDL-TG level, but not the VLDL cholesterol level, was found to be significantly correlated with 24-hour urinary uric acid excretion. These results indicate that there is a close correlation between the degree of uric acid production, as judged by 24-hour urinary uric acid excretion, and lipoprotein TG metabolism when the influence of alcohol intake is excluded.

Alcohol Drinking↗
PubMed1989

Studies on angiotensin converting enzyme inhibitors. 4. Synthesis and angiotensin converting enzyme inhibitory activities of 3-acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic acid derivatives.

(4S)-1-Alkyl-3-[[N-(carboxyalkyl)amino]acyl]-2-oxoimidazolidine-4- carboxylic acid derivatives (3) were prepared by two methods. Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed. The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC50 values of 1.1 X 10(-8)-1.5 X 10(-9) M. The most potent compound in this series, monoester 3p, had an ID50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Studies of Panax japonicus fibrinolysis.

The effects of a 70% methanol extract (PMe) obtained from the rhizomes of Panax japonicus C. A. Meyer on experimental thrombosis and fibrinolysis were investigated in vivo and in vitro. PMe showed a promotive effect on the activation of the fibrinolytic system as determined by the euglobulin lysis time (ELT) assay but was inactive to the inhibitory effect against endotoxin-induced disseminated intravascular coagulation (DIC) in rats. PMe and its major components, chikusetsusaponin III, IV, and V, strongly promoted the action of urokinase in fibrin plate. These results suggested that PMe promotes the fibrinolysis and its effective components are chikusetsusaponin III, IV, and V.

Animals↗
PubMed1989

Unidirectional inhibition of early signal transduction of helper T cells by cloned suppressor T cells.

Early intercellular events occurring in cloned T helper (Th) cells following interaction with cloned T suppressor (Ts) cells were studied by stopped-flow fluorometry. It was found that the increase of intracellular Ca2+ ([Ca2+]i) in major histocompatibility complex (MHC)-restricted Th clones induced by the stimulation with antigen and antigen-presenting cells (APC) is inhibited by the incubation with antigen-activated Ts clones. Optimal suppression required that the two cells recognize antigen on the same APC, although the restriction element for recognition could be different. There was an absolute requirement for recognition of the same antigen by these two cell types. The inhibitory effect was unidirectional in that Ts clones could inhibit the increase of [Ca2+]i of Th clones but not vice versa. Ts clones could not suppress the [Ca2+]i response of other Ts clones. If Th and Ts clones do not share the same MHC restriction specificity, a longer co-incubation time for activation of Ts is required for the inhibition of the [Ca2+]i response of the Th clone, suggesting the presence of a non-specific suppressive mediator that selectively acts on Th.

Animals↗
PubMed1989

Modulation of immune response against tumor cells by the in vivo administration of an autoreactive Th clone.

The immunization of C3H mice with irradiated syngeneic MM48 tumor cells induced specific tumor-neutralizing cells (TNC). The TNC activity was mediated by the L3T4+, Ly-2- T cell population, and the generation of TNC coincided with the appearance of delayed-type hypersensitivity response against MM48 antigen. The administration of an auto-I-Ak reactive T helper cell clone MS202 to normal C3H mice resulted in the facilitation of growth of MM48 tumor due to the induction of T suppressor (Ts) cells. Splenic T cells from animals given this T cell clone inhibited the TNC activity of immunized mice resulting in the escape of MM48 from the TNC effect. The surface phenotype of the Ts cells was L3T4+, Ly-2-. The Ts cells induced by the clone MS202 were totally antigen-nonspecific, and were able to suppress both the effector and inductive processes of TNC. The results suggest the presence of a physiological MHC-restricted T cell circuit that regulates immune responses against the growing tumors.

Animals↗
PubMed1989

Insulin secretion in childhood obesity.

In 132 severely obese children (72 boys and 60 girls) who underwent institutional therapy, oral glucose tolerance tests were carried out on admission, and these children were divided into groups with normal and high insulin levels, in terms of the sigma IRI values obtained, on the basis of the reference value + 2SD calculated by Maruhama et al. From these children, those who had diabetes mellitus (DM) and those in whom DM was suspected were distinguished according to the diagnostic criteria of USPHS (Drash et al). The insulin levels were normal in 58 children and high in 64. Ten children were found to have DM, and 19 were suspected to have DM. Metabolism of the glucose load occurred at both normal and high insulin levels in some children. There was also a group of children in whom glucose metabolism was incomplete at high insulin levels and a group of children in whom glucose metabolism was not possible even at high insulin levels, showing an obvious DM reaction. These findings suggest that there is a difference in the sensitivity of the insulin receptors in these children. Age, severe obesity and a family history of DM were considered to be risk factors for DM. Although there was a moderate, positive correlation between sigma IRI and the obesity index and between sigma IRI and age, it seems that the level of insulin secretion varies considerably in obese children.

Adolescent↗