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Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 307 records · Page 17Linked to original sources
PubMed1995

Effect of compression temperature on the consolidation mechanism of chlorpropamide polymorphs.

The effect of environmental temperature on the compression mechanism of chlorpropamide (CPM) polymorph, forms A and C, was investigated with an eccentric type tabletting machine with two load cells and a noncontact displacement transducer. The temperature of the die was controlled at 0 and 45 degrees C by a thermocontroller. Sample powders (200 mg), which were also controlled at 0 and 45 degrees C by a thermocontroller, were compressed at almost 230 MPa. The tabletting dynamic processes of CPM forms A and C at 0 and 45 degrees C were evaluated by Cooper and modified Heckel analyses. The results suggest that particle brittleness or plasticity was affected by compression at different temperatures. The higher tablet hardness of form A at 45 degrees C was thought to be caused by the increased plasticity of primary particles, whereas that of form C at 45 degrees C was ascribed to the decreased size of the secondary particles.

Chemistry, Pharmaceutical↗
PubMed1995

Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, major metabolites of phenytoin, on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study.

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 microgram.ml-1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.

Adult↗
PubMed1995

Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine.

Serum (+)- and (-)-nicardipine concentrations were determined after oral administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blood pressure was investigated. Serum concentrations of (+) and (-)-nicardipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrometry (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg x ml(-1) for both enantiomers of nicardipine with correlation coefficients of greater than 0.999. A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertension. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administration. The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in systolic blood pressure, the correlation being statistically significant 1 and 2 h after drug administration, and also inversely correlated with the percentage change in diastolic blood pressure 1, 2 and 3 h after drug administration. However, the logarithmically transformed value of serum (-)-nicardipine showed no significant correlations with the percentage change in either systolic or diastolic blood pressure.

Administration, Oral↗
PubMed1995

Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for oxidative metabolism of ethanol, exist in multiple, genetically determined molecular forms. Widely different kinetic properties in some of these isozymes account for the individual differences in alcohol sensitivity. In this study we used the polymerase chain reaction/restriction fragment length polymorphism method to determine the genotypes of the ADH2 and ALDH2 loci of alcoholic and nonalcoholic Chinese living in Shanghai. We also investigated the subjects' drinking patterns by means of semistructured interviews. The alcoholics had significantly lower frequencies of the ADH2(2) and ALDH2(2) alleles than did the nonalcoholics, suggesting the inhibitory effects of these alleles for the development of alcoholism. In the nonalcoholic subjects, ADH2(2) had little, if any, effect, despite the significant effect of the ALDH2(2) allele in decreasing the alcohol consumption of the individual. Taken together, these results fit the proposed hypothesis for the development of alcoholism, i.e., drinking behavior is greatly influenced by the individual's genotypes of alcohol-metabolizing enzymes, and the risk of becoming alcoholic is proportionate with the ethanol consumption of the individual.

Adult↗
PubMed1995

Elongation of the side chain of analogs of 1 alpha,25-dihydroxyvitamin D3 prevents osteopenia in a rat model.

Five analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] [1], 26,27-dimethyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Me)2D3] [2], 26,27-dimethyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Et)2D3] [3], 26,27-dipropyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Pr)2D3] [4], 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3], and [5] 24a-homo-24,24-difluoro-1 alpha,25- dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3] were investigated to clarify the possibility that prevents osteopenia induced in rats by ovariectomy and sciatic neurotomy. The objective of our studies was to determine whether these analogs may be effective for treatment of subjects with osteoporosis. 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3 prevented decreases in bone mineral density (BMD) of the femur, as measured by dual energy X-ray absorptiometry (DXA). The potency of 1,25(OH)2(Me)2D3 in this test was higher than that of 1,25(OH)2D3. The potencies of 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3 were similar to that of 1,25(OH)2D3. On the other hand, though 1,25(OH)2(Et)2D3 and 1,25(OH)2(Pr)2D3 had a preventive effect on the decrease in BMD, the potency of two analogs was lower than that of 1,25(OH)2D3. Decreases in cortical and trabecular bone areas of the femur were prevented by three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3. Serum calcium (Ca) concentration was elevated at the last administration of three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2-(Me)2D3 and 24aF2-homo-1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier.

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.

Base Sequence↗
PubMed1995

Polymorphisms of dopamine receptor and transporter genes and Parkinson's disease.

Disturbances of the dopamine system are involved in the pathogenesis of idiopathic Parkinson's disease (PD). Although genetic factors may play a role in the etiology of PD, there is little direct evidence implicating a specific gene. We conducted a study to test the hypothesis that allelic variations of the dopamine receptors (D2, D3, D4) and the dopamine transporter (DAT) contribute to the susceptibility to PD. Association analyses of 70 Japanese PD patients and the same number of age-matched controls did not reveal any association between alleles of the D2, D3 or D4 receptor genes or the DAT gene and PD. Thus, our results suggest that factor(s) other than allelic variations of these key proteins in the dopamine system contribute to the susceptibility to PD.

Aged↗
PubMed1995

Relation of emotional behaviors to urine catecholamines and cortisol.

We examined changes of epinephrine, norepinephrine, and cortisol levels in 24-h urine accompanying emotional behavior in cats such as restlessness, threat, and quiet biting attack elicited by electrical stimulation of specific sites within the hypothalamus. Although norepinephrine remained unchanged with restlessness but increased with threat, elevation of epinephrine and cortisol levels was common to restlessness and threat. No significant changes in these hormonal levels were seen with quiet biting attack and control. Therefore, it was suggested that emotional behaviors such as restlessness and threat are more closely related to emotional stress than quiet biting attack in cats.

Animals↗
PubMed1995

Properties of glutamate dehydrogenase and its involvement in alanine production in a hyperthermophilic archaeon, Thermococcus profundus.

Thermococcus profundus, a hyperthermophilic archaeon, did not exhibit detectable glutamine synthetase activity, although the organism possessed an extraordinarily high level of glutamate dehydrogenase (GDH), the content of which reached over 10% of total soluble proteins. This GDH was purified to homogeneity. The enzyme had a molecular weight of 263,000 and was composed of six homogeneous subunits of molecular weight 43,000. The enzyme was extremely thermostable with a half life of 1 h at 90 degrees C. Circular dichroism (CD) spectra of the enzyme revealed gradual unfolding of alpha-helices upon exposure to increasing temperature. The enzyme reaction was strongly biased toward glutamate formation. T. profundus excreted L-alanine into the medium, and the concentration reached mM. High activity of alanine aminotransferase (AAT) was present in the cells, while no alanine dehydrogenase activity was detected. The alanine formation may be initiated by ammonia uptake by GDH followed by aminotransfer from glutamate to pyruvate by AAT.

Alanine↗
PubMed1995

Pharmacokinetic study of valproic acid sustained-release preparation in patients undergoing brain surgery.

Pharmacokinetics of valproic acid sustained-release preparation (VPA-SR) were studied in nine patients undergoing surgery for brain tumor. Total (t) and free (f) serum concentrations were analyzed in samples drawn during the day of brain surgery and compared with levels from a postoperative day. The area under the curve (AUCt) and clearance (CLt) of the total concentration did not differ on these occasions. In contrast, statistically significant differences were observed in AUCf and CLf between the two occasions; increased AUCf and decreased CLf were observed on the day of surgery. A significant relation was found between the average free fraction (AUCf/AUCt on operation day per AUCf/AUCt on postoperative day) and estimated blood loss during operation (r = 0.82; p < 0.001). In addition, a significant relation was found between simple free fraction and the intraoperative albumin level in serum (r = -0.68; p < 0.001). These findings indicate that the increased VPA free concentration is due to low serum albumin level secondary to blood loss and that there has been a decrease in intrinsic clearance during operation.

Adolescent↗
PubMed1995

Characterization of antineutrophil antibodies in patients with neutropenia associated with nutritional copper deficiency.

Six antineutrophil antibody (ANA)-positive patients with copper deficiency were classified into two groups; those with (group A, n = 3) and those without (group B, n = 3) neutropenia. The percent binding of ANA for normal peripheral neutrophils was similar in both groups (83.5 +/- 7.2 vs. 79.1 +/- 10.5%). The percent binding of sera to cultured promyelocytic leukemia cells (HL-60) was increased in group A (from 3.7 +/- 3.2 to 12.2 +/- 2.3%) but not in group B (from 65.3 +/- 21.7 to 40.7 +/- 6.3%) after stimulation of HL-60 with DMSO. The stimulated HL-60 cells expressed CD 16 and CD 11b antigens. In the presence of monoclonal antibody for CD 16, the titer of ANA was nil in group A and unchanged in group B. Thus, ANA of patients with neutropenia may recognize mainly the CD 16 antigen, the Fc gamma receptor III of neutrophils.

Adolescent↗
PubMed1995

Alcohol and aldehyde dehydrogenase polymorphisms and the risk for alcoholism.

OBJECTIVE: The authors studied a large number of Japanese alcoholic patients and comparison subjects to establish the genotype frequencies of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) and to quantify the relative risk for alcoholism from the results. METHOD: The subjects were 655 alcoholic patients and 461 comparison subjects. ADH2 and ALDH2 were genotyped by the combination of polymerase chain reaction and hybridization methods. RESULTS: Active ALDH2 and usual ADH2 were significantly more frequent in the alcoholic patients. Inactive ALDH2 was not always associated with a low risk of alcoholism, and active ALDH2 was not always associated with high risk. In individuals with heterozygous inactive ALDH2 and usual ADH2, the odds ratio for alcoholism was high. CONCLUSIONS: The risk for alcoholism in Japanese has been accurately estimated on the basis of the genotype frequencies of ADH2 and ALDH2. Many Japanese may be protected from alcoholism by inactive ALDH2 and by higher frequencies of atypical ADH2.

Alcohol Dehydrogenase↗
PubMed1995

Development of Babesia gibsoni in the salivary glands of the larval tick, Rhipicephalus sanguineus.

The development of Babesia gibsoni in the salivary glands of larval Rhipicephalus sanguineus ticks was morphologically studied for 4 days of feeding of tick on rabbits. Babesia gibsoni showed two forms (sporont and sporozoite) in the budding process. Sporozoites were formed in the acinar cells of salivary glands and released from the hollow cytoplasmic area of these cells by day 4 of feeding. The morphology of B. gibsoni in the salivary glands of R. sanguineus shows a close similarity to those of B. gibsoni in Haemaphysalis longicornis.

Animals↗
PubMed1995

[The first case of Sjögren's syndrome with anti-Wa antibody].

A 42-year-old woman presented in 1992 with Raynaud's phenomenon, polyarthralgia and morning stiffness and next year developed xerostomia and xerophthalmia. Investigations revealed 20 mm/hr of ESR, positive test for RAPA (1 : 320), ANF (1 : 1280), anti-SS-A antibody and anti-Wa antibody, and positive Schirmer tear test. A biopsied specimen of minor salivary gland of lip showed lymphocytic infiltration around the ducts and fibrotic changes and a sialogram demonstrated diffuse dilatations of the peripheral ducts. Resulting from the data shown above, the diagnosis of Sjögren's syndrome was made. Anti-Wa antibody, which recognizes a 48 kD tRNA associated protein was identified in serum from a patient with systemic sclerosis by Yamagata in 1985. So far the antibody has been specific for systemic sclerosis, because all of six patients with anti-Wa antibody previously reported were diagnosed as having systemic sclerosis. However, we here described the first case of Sjögren's syndrome with anti-Wa antibody.

Adult↗
PubMed1995

Pharmacokinetics of barnidipine hydrochloride, a new dihydropyridine calcium channel blocker, in the rat, dog and human.

1. The pharmacokinetics of a new calcium antagonist barnidipine hydrochloride, a stereochemically pure enantiomer, was studied after intravenous and oral dosing to the rat and dog, and oral to man. 2. After intravenous dosing, plasma concentrations of barnidipine hydrochloride declined bi-exponentially with the terminal half-lives of 0.6 h in the rat and 4.1 h in the dog. The blood clearance was 5.2 l/h/kg in the rat and 3.3 l/h/kg in the dog, and was comparable with hepatic blood flow in both species. 3. After oral dosing, plasma concentrations of barnidipine hydrochloride peaked rapidly (0.3-0.4 h in the rat and dog, 1.0-1.6 h in man). Cmax and AUC rose non-linearly with increasing doses in all three species. 4. The absolute bioavailability was low (11-18% in the rat and 6-9% in the dog), suggesting a marked first-pass metabolism.

Administration, Oral↗
PubMed1995

[Alcohol beverage advertisements--survey of weekly magazines].

This paper presents an analysis of alcohol beverage advertisements appearing in weekly magazines and comics. Few studies have be undertaken on this sector of the mass media in Japan. The results are compared with those of a similar study in the United States. We also review alcohol advertisements on television and the drinking scenes shown in comics. On the average, Japanese magazines tend to contain fewer alcohol advertisements than American magazines. However, 18 (53%) in 34 weekly magazines contained alcohol advertisements showing that such magazines are an important medium for alcoholic beverage advertising in Japan. There were also alcohol advertisements targeting to particular populations, youths and women, which may be connected with the increase in drinking in these groups. Alcohol advertisements in the mass media should be monitored continuously as public health issue.

Advertising↗