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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 181 records · Page 10Linked to original sources

cDNA and genomic DNA clonings of chalcone synthase from Pueraria lobata.

Four cDNAs encoding chalcone synthase (CHS), the key enzyme in flavonoid biosynthesis, were isolated from Pueraria lobata cells challenged with yeast extract elicitor using bean CHS cDNA as a probe. The longest clone contained a complete open reading frame of 1170 bp which would predict a protein of about 43 kDa. The others were not full-length clones. Using isolated cDNA as a probe, Southern blot hybridization of genomic DNA fragments revealed the presence of multiple CHS genes in the P. lobata genome. We cloned and sequenced one CHS genomic clone, gCHS14, whose 5' untranslated region showed homology with the bean CHS gene CHS15 and included the several reported sequences characteristic of stress response.

Acyltransferases↗

Nine new triterpene saponins, polygalasaponins XXXIII--XLI from the roots of Polygala fallax Hemsl.

Nine new oleanane-type saponins, polygalasaponins XXXIII--XLI, along with seven known saponins were isolated from the roots of Polygala fallax HEMSL. Polygalasaponins XXXIII-XLI were elucidated as 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl- (1-->2)-(4-O-acetyl)-beta-D-fuco-pyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-(4-O-acetyl)-beta-D- fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- alpha-L-rhamnopyranosyl-(1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [(5-O-acetyl)-beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosy l- (1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- (3-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl- (1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-(4-O-acetyl)-beta-D- fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- [alpha-L-rhamnopyranosyl-(1-->3)]-(4-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)- (3,4-di-O-acetyl)-beta-D-fucopyranosyl ester and 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [(5-O-acetyl)-beta-D-apiofuranosyl-(-->3)]-alpha-L-rhamnopyranosyl - (1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, respectively, on the basis of spectroscopic and chemical evidence.

Carbohydrate Sequence↗

A proposal for avoiding toxic interactions of a drug under development to estimate inhibitory ability on the drug metabolizing enzymes in human liver.

Drug interactions can be divided into those involving the pharmacokinetics of a drug and those affecting the pharmacodynamic response to it. Following strategies should be considered for avoiding pharmacokinetic drug interactions of new chemical entities under development. 1. To estimate the major metabolic pathways (including metabolic activation) using human liver preparations. 2. To identify the enzyme systems participating in the major metabolic pathways. 3. To examine metabolic inhibition for other drugs and by other drugs. 4. To confirm a pharmacokinetic effect for the combined drugs in vivo.

Biotransformation↗

[Accuracy of participation rate data for health examination research].

Each local government conducts health examinations based on the Health and Medical Law for the Aged. However, since some residents are able to take health examinations at their own work places, for example, and the local government are allowed to exclude such people from taking the law-mandated health examination, it is difficult to obtain an accurate picture of the examination rate in each area. We investigated the actual participation status for health examination services of all of the 6,080 persons 20 years and over in age in Sakuragawa-mura, Ibaraki Prefecture. A comparative investigation was made on 3,655 non-bedridden/non-hospitalized persons of 40 years and over to ascertain the reliability of responses to questions about participation in lung cancer and gastric cancer examination services given by the village. The rate of valid responses was extremely low in those who had not participated in health examinations (male 54%, female 55% for the lung cancer, and male 53%, female 56% for the gastric cancer). These discrepancies are assumed to be the result of confusing the current health examinations with: (1) the health examination given in the previous year, (2) other kinds of health examinations, or (3) the health examination given in the work place or the like. A comparative investigation through logistic regression analysis, between the responses to the questions in this investigation and the actual health examination participation records, for persons who had not yet taken either lung cancer examinations or gastric cancer examinations (908 males and 938 females for the former, and 1,038 males and 1,187 females for the latter). Results showed that the influence of (1) and (2) were more or less detected in every kind of cancer examination, and the influence of (1) on the gastric cancer examination was particularly clear. No definite result was obtained about (3), because the actual record of the health examination service at the work place, etc. was unavailable. The results of this study suggests the necessity of a careful examination of methods when conducting a comprehensive service investigation for the health examinations.

Female↗

D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.

Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.

Amino Acids↗

Stereoselective pharmacokinetics of dihydropyridine calcium antagonists.

Many dihydropyridine calcium antagonists are widely used for the treatment of angina and hypertension, and many more are under development. Most of these drugs have one or more chiral centre, and the pharmacological activity between the enantiomers for these drugs is known to be markedly different. First, the stereospecific assay methods for these drugs in plasma or serum are reviewed with emphasis on chiral stationary phase high-performance liquid chromatography for their determination. Next, the stereoselective pharmacokinetics of these drugs (nilvadipine, nitrendipine, felodipine, nimodipine, manidipine, benidipine and nisoldipine) in animals, healthy subjects and patients with hepatic disease is reviewed. Enantiomer-enantiomer interaction, enantiomeric inversion and the stereochemical aspects of pharmacokinetic drug interactions in these drugs are also described.

Animals↗

Rat epidermal cathepsin L-like proteinase: purification and some hydrolytic properties toward filaggrin and synthetic substrates.

We have purified cathepsin L-like proteinase from rat epidermis, determined its NH2-terminal amino acid sequence, and investigated its proteolytic activities on an intermediate filament-associated protein filaggrin and several synthetic substrates. The amino acid sequence of its NH2-terminus was determined to be Val-Pro-Asn-Ser-Leu-Asp-Trp-Arg-Glu-Lys-Gly-Tyr-Val-Thr-Pro-, which differed from that of rat cathepsin L and was not found in the amino acid sequence data bank. The enzyme consisted of a single-chain form with M(r) 30,000. Its hydrolytic properties toward synthetic substrates were similar to those of cathepsin L in other tissues. The enzyme effectively proteolyzed rat epidermal filaggrin into small fragments at pH 4.0-6.0 and was inhibited by a specific cysteine proteinase inhibitor, N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)L-leucyl]-agmatin. However, cathepsins D and E from rat epidermis did not hydrolyze filaggrin. This study demonstrated that filaggrin was susceptible to degradation by rat epidermal cathepsin L-like proteinase, suggesting that this proteolytic activity may have relevance to skin differentiation, in which acid proteases are thought to participate.

Amino Acid Sequence↗

A statistical study of calcifying epithelioma, focusing on the sites of origin.

We statistically investigated 396 lesions taken from 355 cases of calcifying epithelioma. The distribution of these lesions did not correlate with the density of the hair follicles, but it was in accord with the distribution of intermediate hairs, such as those in the hair border. This relationship may have etiologic significance.

Adolescent↗

The relationship between serum transaminase activities and fatty liver in children with simple obesity.

To determine hepatic diseases in obese children, biochemically and histologically, 11 obese patients with abnormal serum transaminase activities were subjected to this study. Fat accumulation in the liver was semiquantitatively graded, and histologically the 11 patients were classified into four groups; fatty liver, fatty hepatitis, fatty fibrosis and fatty cirrhosis. All patients had fat deposition in liver specimens, the grade of which did not significantly correlate with the degree of obesity. The grade of fat deposition in the liver specimens also did not significantly correlate with either serum transaminase activities or GOT/GPT ratio. Five patients were grouped into the fatty liver group, three into the fatty hepatitis group, and the remaining three patients into the fatty fibrosis group. However, no significant differences were found among the three histologically classified groups in terms of serum transaminase activities or GOT/GPT ratio. The usefulness of serum transaminase activities and GOT/GPT ratio was limited in predicting the severity of fat deposition or histological abnormality in pediatric obese patients.

Adolescent↗

Pharmacological characterization of alpha 1-adrenoceptor subtypes in rat heart: a binding study.

1. The alpha 1-adrenoceptor subtypes of rat heart were characterized in binding experiments performed with [3H]-prazosin as the radiolabel. The specific binding to the alpha 1-adrenoceptors was determined with 0.3 microM prazosin, because phentolamine (10 microM) was insufficient to inhibit completely the specific binding of high concentrations of [3H]-prazosin. 2. In saturation experiments, [3H]-prazosin bound to two distinct affinity sites (pKD = 10.39 and 8.19). The proportion of the low affinity sites was approximately 84% of total specific binding. Membranes pretreated with chloroethylclonidine (CEC, 10 microM) also showed two distinct affinity sites for [3H]-prazosin, although the maximum numbers of high and low affinity sites were reduced by 86 and 64%, respectively. 3. In competition experiments, [3H]-prazosin (100 pM) binding was inhibited by WB4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane) and 5-methylurapidil. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 10.43 and 8.36 for WB4101, 8.62 and 6.61 for 5-methylurapidil). However, unlabelled prazosin or HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)-ethyl)amin o) propyl)benzeneacetonitrile fumarate) competed for [3H]-prazosin binding monophasically (pKi = 10.34 and 8.28, respectively). In CEC-pretreated membranes, prazosin, WB4101, 5-methylurapidil and HV723 antagonized the [3H]-prazosin (100 pM) binding monophasically (pKi = 9.70, 9.56, 8.60 and 8.82, for each antagonist). 4. On the other hand, 1000 pM [3H]-prazosin binding was inhibited by unlabelled prazosin biphasically (pKi = 10.49 and 8.49). HV723 did not discriminate both prazosin-high and low affinity sites (pKi = 8.18). 5. These results suggest the presence of at least three distinct alpha1-adrenoceptor subtypes in rat hearts(two prazosin-high affinity sites and one prazosin-low affinity site). According to the recent alpha l-adrenoceptor subclassifications, one of the former two sites corresponds to the alpha 1B subtype with low affinities for WB4101 and 5-methylurapidil and sensitive to CEC, while another site with relatively high affinities for WB4101 and 5-methylurapidil may be classical alpha 1A, cloned alpha 1c, alpha 1D subtypes or their mixture. The prazosin-low affinity site corresponds to putative alpha 1L subtype with low affinity for HV723,which may be predominantly involved in the positive inotropic response to phenylephrine.

Adrenergic alpha-1 Receptor Antagonists↗

Left ventricular regional wall motion in the early neonatal period.

To investigate the changes in regional wall motion of the left ventricle in the early neonatal period, serial echocardiography was performed in normal neonates at 2 and 120 hr after birth. Quantitative analysis of the regional wall motion was performed by the centerline method. We measured right ventricular systolic time intervals, left ventricular stroke volume, flow velocity-time integral of the pulmonary artery, and size of the ductus arteriosus. The ductus arteriosus was 4.5 +/- 0.5 mm at 2 hr but was closed in all subjects by 120 hr. At 2 hr, there was hyperkinesis of the interventricular septum which disappeared by 120 hr. The right ventricular systolic time intervals at 2 hr showed a sign of pulmonary hypertension. At 2 hr, the left ventricular stroke volume was at the highest level and the flow velocity-time intervals of pulmonary artery was at the lowest level. Thus the hyperkinesis of the interventricular septum at 2 hr might reflect the circulatory changes that are characteristic of the early neonatal period.

Blood Flow Velocity↗

[A study of the Galvanic Body Sway Test--reproducibility of test results].

Although the Galvanic Body Sway Test (GBST) has been considered useful for differential diagnosis between labyrinthine and retrolabyrinthine lesions, it does not always yield clear wave forms, since the test results are inevitably contaminated by basic body sway in the standing position. In our previous study, in which the effects of duration of stimulation, current intensity and frequency were examined in 13 normal subjects, we found that the clearest GBST wave forms were obtainable when 20 responses to successive monopolar 0.5mA galvanic stimuli for 5 sec at 4 sec intervals were averaged. In the present study, GBSTs were conducted repeatedly in 10 normal subjects using the stimulation conditions mentioned above in order to assess the reproducibility of the test responses. In all of the subjects, monoaural galvanic stimuli were delivered separately to each ear twice on the same day at a fixed intervals and the averaged wave forms were obtained. The same tests were repeated twice more in the following 3 weeks after an interval of at least 7 days. As a result, it was found that very similar responses were obtained from both ears, and there was remarkable reproducibility of both the latency and the amplitude of the GBST response in a given subject. It was also found that while inter-individual differences in latency were minimal, differences in amplitude were fairly large. The results suggest that comparison of response amplitude on both sides in the same subject is significant in evaluating the results of GBST.

Adult↗

Changes in platelet kinetics after a partial splenic arterial embolization in cirrhotic patients with hypersplenism.

We performed a partial splenic arterial embolization in 22 patients with cirrhosis associated with thrombocytopenia and then evaluated the changes in platelet kinetics after undergoing the procedure using 111In-tropolone-labeled platelets. The controls consisted of eight chronic hepatitis patients who showed a normal platelet count and normal spleen size. The mean splenic infarction ratio after the procedure was 54.9%. A platelet kinetics study was performed before and 2 months after the procedure. Before the procedure, the cirrhotic patients showed increases in the splenic volume and the spleen/liver uptake ratio of the 111In-labeled platelets on both the third and seventh days, and a decrease in the platelet recovery compared with the controls, which suggested an increased platelet pool in the spleen. In addition, the platelet survival time in cirrhotic patients was shortened, whereas the platelet-associated immunoglobulin G (PA-IgG) was higher than that of the controls, which suggested the involvement of immunologic mechanisms in the thrombocytopenia. With an increase of the platelet count after a partial splenic arterial embolization, the spleen/liver uptake ratio of the 111In-labeled platelets decreased, whereas the platelet recovery increased. Furthermore, the platelet survival time was prolonged, whereas the PA-IgG decreased. The platelet count showed a positive correlation with the platelet survival time and a negative correlation with PA-IgG before and after the procedure. These results suggest that a transcatheter splenic arterial embolization not only may reduce the increased platelet pool in the spleen but also may improve the thrombocytopenia induced by immunologic mechanisms in patients with cirrhosis.

Adult↗