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Biomedical subjects

K Uchino

Publications and source records attributed to K Uchino.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method.

An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma. The improved method was selective and made it possible to determine precisely glycyrrhizin at levels as low as 500 ng/mL. The pharmacokinetic behavior of glycyrrhizin and its metabolites after oral and intravenous administration of glycyrrhizin to normal subjects was investigated. After oral administration of glycyrrhizin (100 mg) to three normal subjects, the major metabolite of glycyrrhizin (glycyrrhetic acid) appeared in plasma (less than 200 ng/mL), but glycyrrhizin was not found. On the other hand, glycyrrhizin was found in urine, and the amount excreted was 1.1-2.5% of the dose. This finding suggests that glycyrrhizin is partly absorbed in the intact form from the gastrointestinal tract. The concentration of glycyrrhizin in plasma after intravenous administration of glycyrrhizin (40, 80, and 120 mg) showed biexponential profiles during the 24-h period after administration of each dose. The glycyrrhizin metabolites, glycyrrhetic acid and glycyrrhetic acid-3-O-glucuronide, were not detected in either plasma or urine. The terminal half-life of glycyrrhizin, the apparent volume of the central compartment, the steady-state distribution volume, and the total body clearance in three dosing experiments were 2.7-4.8 h, 37-64 mL/kg, 59-98 mL/kg, and 16-25 mL/kg/h, respectively. Glycyrrhizin was not detected in plasma after oral administration of the usual therapeutic dose of glycyrrhizin, and no dose dependency of the drug was observed in the dose range of 40-120 mg.

Administration, Oral↗
PubMed1992

Inhibitory effect of tannic acid sulfate and related sulfates on infectivity, cytopathic effect, and giant cell formation of human immunodeficiency virus.

The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human immunodeficiency virus [HIV (HTLV-III/LAV)]. In this report, we synthesized sulfated plant polyphenols such as tannic acid sulfate, rutin sulfate, ellagic acid sulfate, (-)-epicatechin sulfate, and (-)-epigallocatechin 3-gallate sulfate, and examined the in vitro inhibitory effect on HIV infection using human T-cell lymphotropic virus type-I-carrying MT-4 cells, which are extremely susceptible to HIV infection. Of the compounds tested, tannic acid sulfate was the most effective and had low cytotoxicity. Tannic acid sulfate completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at the concentration of 6 micrograms/ml. In addition, this sulfate inhibited giant cell formation in coculture at the concentration of 5 micrograms/ml.

Cell Line↗
PubMed1992

Effects of alpha 1-adrenergic blockade on intrarenal hemodynamics in heart failure rats.

To investigate intrarenal hemodynamics and effects of alpha 1-adrenergic blockade on glomerular functions in congestive heart failure (CHF), micropuncture studies were performed before and after intravenous injection of terazosin (1 microgram/100 g body wt iv) in eight myocardial infarction (MI) and in nine sham-operated rats after intraperitoneal injection of Inactin (70 mg/kg). CHF was characterized by elevated left ventricular end-diastolic pressure and increased total heart weight. In CHF rats, single nephron glomerular filtration rate (SNGFR), single nephron plasma flow (SNPF), and ultrafiltration coefficient (Kf) were decreased compared with sham-operated rats (SNGFR, 21.9 +/- 1.6 vs. 39.2 +/- 2.9 nl.min-1.g-1, P less than 0.01; SNPF, 66.6 +/- 6.1 vs. 133.8 +/- 10.5 nl.min-1.g-1, P less than 0.01; Kf, 0.019 +/- 0.001 vs. 0.041 +/- 0.004 nl.s-1.mmHg-1.g-1, P less than 0.01). Single nephron filtration fraction (SNFF), glomerular pressure (Pg), and efferent arteriolar resistance (Re) were higher in the CHF-MI rats than in the sham-operated rats (SNFF, 33.4 +/- 1.3 vs. 27.7 +/- 1.0, P less than 0.05; Pg, 60.2 +/- 1.6 vs. 53.3 +/- 0.8 mmHg, P less than 0.01; Re, 3.92 +/- 0.66 vs. 1.62 +/- 0.15 x 10(10) dyn.s.cm-5.g, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

New substances against human immunodeficiency virus: sulfated 5'-nucleotidase inhibitory polyphenols.

Two sulfated polyphenols, NF-86II-S-13.3 and NF-86II-S-6.2, were synthesized from NF-86II without sulfur their inhibitory effect on human immunodeficiency virus (HIV) infection in vitro was examined, using cytopathic effect and an antigen expression assay system in MT-4 cells. NF-86II-S-13.3 (sulfur content, 13.3%) completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at concentrations of more than 6.3 micrograms/ml. The effect of NF-86II-S-6.2 (sulfur content, 6.2%) was much weaker than that of NF-86IIS-13.3. On the other hand, NF-86II without sulfur did not show any activity at all.

5'-Nucleotidase↗
PubMed1991

Selective high-performance liquid chromatographic method for the determination of glycyrrhizin and glycyrrhetic acid-3-O-glucuronide in biological fluids: application of ion-pair extraction and fluorescence labelling agent.

A selective high-performance liquid chromatographic method has been developed for the simultaneous determination of glycyrrhizin and glycyrrhetic acid-3-O-glucuronide in biological fluids of the rat. The procedure is based on the ion-pair formation using tetra-n-amylammonium bromide, extraction with ethyl acetate-n-heptane from the salt-saturated aqueous phase, labelling with 4-bromomethyl-7-methoxycoumarin, followed by chromatographic separation with fluorescence detection. Glycyrrhizin in plasma, bile and urine could be precisely determined in concentrations as low as 1, 1 and 2.5 micrograms/ml, respectively, in a 0.1-ml sample. The equivalent values for the glucuronide were 1, 2.5 and 2.5 micrograms/ml, respectively. The method is applicable in pharmacokinetic studies of glycyrrhizin in small animals.

Animals↗
PubMed1991

Identification of an alpha 2-adrenoceptor in human coronary arteries by radioligand binding assay.

A single high affinity binding site for an alpha 2-adrenoceptor in human coronary arteries was identified by radioligand binding assay. Human coronary arteries were obtained at autopsy within 6 hours of death. A crude membrane solution was incubated with (3H)-rauwolscine at 25 degrees C for 30 min. The binding of (3H)-rauwolscine was rapidly saturable and reversible. Kd was 1.2 +/- 0.2 (SE) nM and Bmax 22 +/- 3 fmol/mg protein. This is the first study which has shown the presence of an alpha 2-adrenoceptor in human coronary arteries using a radioligand binding assay method.

Arteries↗
PubMed1991

Specificity of mutational DNA sequence changes induced by X-rays in the cloned Escherichia coli crp gene.

Plasmid DNA carrying the adenosine 3',5'-cyclic monophosphate receptor protein (crp) gene of Escherichia coli was irradiated, in solution, with X-rays, and the mutations produced in the crp gene were assayed by transforming the recipient E. coli cells. Ninety-six mutant clones were isolated, and mutational changes were determined by DNA sequencing. Of the 92 mutations thus detected, 74 represented base substitution mutations and the remaining 18 were frameshifts. The base substitutions included 56 G:C to A:T transitions, 10 G:C to T:A transversions and 7 G:C to C:G transversions. An A:T to G:C transition was found only once, and neither an A:T to T:A nor an A:T to C:G transversion was detected. The frameshift mutations consisted of 11 one-base deletions and 7 one-base insertions. Accordingly, G:C to A:T transition was the predominant type of mutation, which constituted 76% (56/74) of the total base substitutions and 60% (56/92) of all detected mutations. Furthermore, of the 56 transitions, about three-quarters (41 clones) clustered at an identical site, a cytosine residue at the 706 position, demonstrating that this site is a distinct hot spot for X-ray mutagenesis. These results raise the possibility that radiation-induced mutations may not necessarily occur randomly, at least in certain cases.

Bacterial Proteins↗
PubMed1991

Spontaneously hypertensive rats demonstrate increased renal vascular alpha 1-adrenergic receptor responsiveness.

To determine alpha 1-adrenergic receptor responsiveness of the renal vasculature in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), phenylephrine (2.5 or 5.0 micrograms.kg-1.min-1 iv) or saline was infused. Effective renal blood flow (ERBF) and glomerular filtration rate were determined by p-aminohippuric acid and inulin clearances, respectively. Peritubular capillary, proximal tubular, and stop-flow pressures (SFP) were measured by micropuncture. Phenylephrine decreased ERBF (6.27 +/- 0.48 to 4.55 +/- 0.65 ml.min-1.g-1; P less than 0.05) and increased arterial pressure and SFP (31.5 +/- 0.9 to 34.2 +/- 1.0 mmHg) in SHR. It only increased arterial pressure and ERBF in WKY without changing SFP. Afferent arteriolar resistance (RA) and glomerular capillary pressure (PG) remained unchanged, whereas efferent resistance (RE) decreased in WKY; in contrast, RA, RE, and PG increased in SHR (RA 21.2 +/- 2.0 to 38.1 +/- 7.1 mmHg.ml-1.min.g, RE 6.9 +/- 0.6 to 13.9 +/- 3.8 mmHg.ml-1.min.g; and PG 49.6 +/- 0.9 to 53.7 +/- 1.1 mmHg; all P less than 0.05). These data demonstrated increased SHR afferent and efferent arteriolar responsiveness; WKY efferent arteriolar hyperresponsiveness was not observed. The findings support the concept of augmented intrarenal vascular alpha 1-adrenergic responsiveness in hypertension that may predispose to subsequent glomerular hypertension.

Animals↗
PubMed1991

Alpha 1-adrenergic receptor blockade reduces afferent and efferent glomerular arteriolar resistances in SHR.

To assess the effects of alpha 1-adrenergic receptor blockade on intrarenal hemodynamics of spontaneously hypertensive rats (SHR), terazosin (0.015 or 0.03 mg/kg body wt) or saline was injected into SHR or normotensive Wistar-Kyoto rats (WKY) (age 16-18 wk). Single-nephron glomerular filtration rate (SNGFR) and renal glomerular filtration rate were determined with [3H]inulin infusion; effective renal blood flow was measured with p-aminohippurate. Intrarenal efferent arteriolar, proximal tubular, stop-flow pressures measurements, and tubular fluid and efferent arteriolar samplings were obtained by micropuncture techniques. Terazosin reduced arterial pressure significantly in both rat strains, but only in SHR did alpha 1-inhibition decrease glomerular hydrostatic pressure (from 58.0 +/- 1.5 to 46.6 +/- 1.1 mmHg; P less than 0.05). Terazosin did not change SNGFR or single-nephron blood flow in either strain. As a result, only in SHR did efferent glomerular arteriolar resistances decrease (0.262 +/- 0.021 to 0.193 +/- 0.014 mmHg.ml-1.min; P less than 0.05). Glomerular ultrafiltration coefficient increased only in SHR (0.034 +/- 0.005 to 0.104 +/- 0.01; P less than 0.05). These results provide further support to the concept of alpha 1-adrenergic receptor hyperresponsiveness of efferent glomerular arteriolar in SHR but not WKY.

Adrenergic alpha-Antagonists↗
PubMed1991

The growth inhibition of Streptococcus mutans by 5'-nucleotidase inhibitors from Areca catechu L.

New 5'-nucleotidase inhibitors named NF-86I, NF-86II were recently isolated from the seeds of Areca catechu L. NF-86I and NF86II showed inhibitory effects on the growth of Streptococcus mutans MT8148(c) and Streptococcus mutans MT6715(g), respectively. In addition, these inhibitors could inhibit insoluble glucan formation from sucrose. NF-86I and NF-86II were found to be polyphenolic substances. Some polyphenols such as tannic acid bind non-specifically to proteins (tannic activity). The 5'-nucleotidase inhibitors that we isolated did not show any such activity. However, the growth inhibitory activity and the inhibitory effect on water-insoluble glucan production were equal to tannic acid. It is therefore considered that these inhibitors bind specifically to the bacterial cell surface. Our findings suggest that the 5'-nucleotidase inhibitors NF-86I and NF-86II may be useful anti-plaque preventing agents.

5'-Nucleotidase↗
PubMed1991

New polyphenolic 5'-nucleotidase inhibitors isolated from the wine grape "Koshu" and their biological effects.

New 5'-nucleotidase inhibitors designated as NPF-88BU-IA, NPF-88BU-IB, NPF-88BU-IIA and NPF-88BU-IIB, respectively, were isolated from the seeds and skin of the wine grape "Koshu". They were purified by solvent extraction, dialysis, and reversed-phase high performance liquid chromatography (HPLC). Their physico-chemical properties revealed these compounds to be polyphenolic substances. The average relative molecular masses of the four were estimated by gel permeation chromatography (GPC) analysis to be 7850, 5950, 11900, and 11300, respectively. They strongly inhibited 5'-nucleotidase activities from snake venom and rat liver membrane, and displayed significant therapeutic activity against Ehrlich ascites carcinoma. They also showed inhibitory effects on the growth of Streptococcus mutans MT8148(c), a primary cariogenic bacterium. Furthermore, these 5'-nucleotidase inhibitors inhibited the glucan formation from sucrose. These results suggest that the 5'-nucleotidase inhibitors can prevent the cause of caries of tooth.

5'-Nucleotidase↗
PubMed1991

Change of ras-transformed NRK-cells back to normal morphology by mycalamides A and B, antitumor agents from a marine sponge.

Mycalamide A and mycalamide B, isolated as antiviral and antitumor agents from a New Zealand sponge of the genus Mycale, converted the morphology of ras-transformed NRK-cells to normal morphology at 10 and 1 ng/ml, respectively. The effect on protein synthesis suggests that these agents converted the morphology by preferentially inhibiting the biosynthesis of p21 protein.

Animals↗
PubMed1991

[A case of ventricular septal defect associated with active infective endocarditis which was successfully treated by triple valve replacement and ventricular septal defect patch closure].

A 47-year-old man was hospitalized in May, 1990, because of breathlessness and continuous fever which appeared about 4 weeks after he had had his periodontic tooth removed in December, 1989. He had been diagnosed as having ventricular septal defect (VSD) at the age of 6 years. When he was hospitalized, he was in a condition of class IV by NYHA classification, with a white blood cell count of 17,300/mm3, an increase in CRP, a red blood cell sedimentation rate of 108 mm/hr, and positive alpha-streptococcus in blood culture. His cardiothoracic ratio was 64% with signs of pulmonary congestion on a chest X-ray film. Echocardiography revealed the presence of VSD and huge vegetations on the tricuspid, mitral and aortic valves. He was considered to have active infective endocarditis (AIE) which had presumably been provoked by VSD and the tooth removal. Penicillin G at a daily dose of 20 million units and gentamicin at a daily dose of 80 mg were intravenously administered to treat the alpha-streptococcus infection for about 4 weeks. Furosemide was used for congestive heart failure. Since, although his cardiac function appeared to have been improved, the signs and symptoms of the infection persisted, triple valve replacement for the tricuspid, mitral and aortic valves and patch closure of the VSD were performed 4 weeks after the hospitalization. The operation revealed inflammatory lesions extending from the endocardium of the right ventricle to the mitral valves through the VSD, and huge vegetations on the tricuspid, mitral and aortic valves. The operation was successful and the inflammatory areas gradually disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1989

Intracellular localisation of a subunit of human DNA polymerase alpha affecting primase activity recognised by monoclonal antibody (HDR-854-E4) and its application to distinction between proliferative and non-proliferative lesions.

We have successfully established one murine hybridoma that secretes a monoclonal antibody specific for the 77,000 subunit of human DNA polymerase alpha. The results of immunochemical studies, using HDR-854-E4 monoclonal antibody (MAb) and immunoperoxidase detection methods, demonstrate intranuclear and intracytoplasmic localisation of the subunit in all the human culture cell lines tested. The immunoperoxidase reaction product exhibits a diffuse pattern of distribution within the cytoplasm and nucleoplasm, but nucleoli are clearly negative. In cultured cell lines, HeLa and KATO III, more than 95% of the cells are positive, suggesting that the subunit antigens persist throughout the mitotic cycle. No subunit antigen was recognised in resting mononuclear cells (MNC). Immuno-electron microscopic examination of HeLa cells confirms and extends these observations. We have further examined the expression level of the subunit antigen in various normal and cancerous tissues. Strong reaction was observed in proliferating normal and cancer cells such as cancer cells from the gastrointestinal (GI) tract, thyroid, malignant lymphoma, breast, cells in the germinal centres of lymph nodes, epithelial cells in the GI tract and nephrogenic zones in fetal kidney. Finally, we utilised this antibody as a diagnostic tool in biopsies of the thyroid and GI tract. Thyroid cancer was stained positively with this antibody, while follicular adenoma was not. Gastric cancer was stained strongly and adenomatous polyp and hyperplastic polyp were stained moderately. This antibody is not only specific and powerful for application of a novel approach to the complex biochemical mechanisms of mammalian DNA replication, but also useful for distinction between proliferative and non-proliferative lesions.

Antibodies, Monoclonal↗
PubMed1989

Phosphatase-inhibitory activity and activation of murine macrophages by new 5'-nucleotidase inhibitors, NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB.

New 5'-nucleotidase-inhibitory polyphenols named NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB were isolated from the seeds of Areca catechu L. The ability of the inhibitors to precipitate gelatin was investigated by microturbidimetry. These inhibitors produced weak turbidity. As 5'-nucleotidase is a kind of phosphatase, we examined the effects of these inhibitors on alkaline and acidic phosphatases. While they showed moderate inhibitory effects on the activity of acidic phosphatases, they did not have any significant effect on the activity of alkaline phosphatase. Therefore, they showed a higher inhibitory effect on the 5'-nucleotidase than the other phosphatases, Murine macrophages were directly stimulated by the 5'-nucleotidase inhibitors.

5'-Nucleotidase↗