Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 145 records · Page 8Linked to original sources

PubMed1999

Association of a polymorphism of the 5HT2A receptor gene promoter region with alcohol dependence.

Approximately 10% of Japanese alcoholics develop their disease despite having an inactive form of aldehyde dehydrogenase-2 (ALDH2), known as a genetic deterrent of heavy drinking due to adverse reactions after drinking. Such alcoholics are considered to be advantageous in genetic research because they should show reduced heterogeneity and possess genetic factors conferring susceptibility to alcohol dependence. Examination of the -1438 A/G polymorphism of the serotonin 2A (5HT2A) receptor gene in 225 Japanese alcoholics with inactive ALDH2 revealed the presence of significantly more of the G allele than was found in 361 control subjects. The frequency of the G allele in 282 alcoholics with active ALDH2 fell between the G allele frequencies of controls and subjects with inactive ALDH2. These data suggest that although the effect is relatively small, genetic variability in the 5HT2A receptor is involved in the development of alcohol dependence.

Alcoholism↗

PubMed1999

Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy.

AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. RESULTS: In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients.

Adult↗

PubMed1999

Population analysis for the optimization of digoxin treatment in Japanese paediatric patients.

BACKGROUND AND OBJECTIVES: Information about the pharmacokinetics of digoxin in paediatric patients is limited. We therefore aimed to investigate the effects of physiological factors on the digoxin clearance in Japanese paediatric patients. METHOD: We used routinely collected therapeutic drug monitoring data (n=544), derived from the steady-state serum concentrations of digoxin in 181 hospitalized paediatric patients. RESULTS: Of those physiological factors which have been examined in this study, age and total body weight were most closely correlated with digoxin clearance. Data on neonates within the first postnatal month indicated a tendency towards lower clearance for premature neonates than full-term neonates (P<0.01). Digoxin clearance was reduced by spironolactone in patients younger than 4 months (P<0.05). Patients with congestive heart failure showed a lower digoxin clearance than the others (P<0.001). Serum creatinine and gender did not have a statistically significant effect on digoxin clearance. CONCLUSION: Age and total body weight are important factors influencing digoxin clearance in children. Spironolactone affected digoxin clearance and needs to be considered when dosing paediatric subjects.

Age Factors↗

PubMed1999

Interaction of the new histamine H2-receptor antagonist pibutidine hydrochloride with canine cloned H2-receptor expressed cells.

The effect of a new histamine H2-receptor antagonist, pibutidine hydrochloride ((Z)-3-amino-4-{4-{4-[(piperidinomethyl)pyrid-2-yl]oxy} but-2-enylamino}cyclobut-3-ene-1,2-dione monohydrochloride, CAS 126463-66-9, IT-066 displaced the binding of [3H]tiotidine to cells transfected with the wild-type H2-receptor in a concentration-dependent manner. Compared with the 50% inhibitory concentration values (IC50) among five H2-receptor antagonists tested, the value of IT-066 was lowest. The inhibitory effect of IT-066 was enhanced by preincubation of IT-066 with the cells, and preincubation for 60 min increased potency about 2-fold. Famotidine also has such effects. When H2-receptor transfected cells were treated with IT-066 for 30 min, the inhibitory effect of IT-066 on the [3H]tiotidine binding still remained even after the cells were extensively washed. Scatchard plot analysis supported the non-competitive and irreversible action of IT-066. When the canine mutated H2-receptor-expressed cells were used, which have substituted amino acid of 190Alanine (Ala; position: 190th amino acid) for 190Threonine (Thr) in the fifth transmembrane domain, IT-066 also inhibited [3H]tiotidine binding to the cells concentration-dependently. However, in the case of the 190Ala mutated cells, the inhibitory effect of IT-066 attenuated with a decrease in maximal response after washing of the cells. These results show that IT-066 could tightly bind H2-receptor in a time-dependent manner and suggest the possibility that the irreversible inhibition of IT-066 is important in the interaction with 190Thr in the fifth transmembrane domain of H2-receptor.

Alanine↗

PubMed1999

Alcohol consumption as a major risk factor for the rise in liver cancer mortality rates in Japanese men.

BACKGROUND: Age-adjusted liver cancer mortality rates have been increasing for both men and women in Japan since 1970; however, increases in mortality rates in men are much greater than those in women. Hepatitis C virus infections and heavy alcohol consumption are considered to be the major risk factors of liver cancer deaths in Japanese. The purpose of this study is (1) to examine the pattern of liver cancer mortality by gender and birth year to compare those with the pattern of other alcohol-related mortality and (2) to estimate the attributable risk per cent of heavy alcohol consumption for liver cancer deaths in Japanese men. METHODS: Age-specific liver cancer mortality rates by gender were compared with those of cirrhosis mortality rates. Then male-to-female mortality rate ratios were calculated by birth cohort and compared with cirrhosis mortality rate ratios and oesophageal cancer mortality rate ratios. The attributable risk per cent of alcohol consumption for liver cancer death was calculated, using female liver cancer mortality rates as standard rates. RESULTS: Examination of both gender and birth cohort mortality rates revealed that male-to-female liver cancer mortality rate ratios by birth cohort correspond well with those rate ratios for liver cirrhosis and oesophageal cancer mortality. The attributable risk per cent of alcohol consumption for liver cancer deaths in Japanese men was 70%. CONCLUSION: Alcohol consumption is more important than hepatitis C virus infections as a major cause of liver cancer deaths in Japanese men.

Adult↗

PubMed1999

Predictive performance of equations to estimate creatinine clearance from serum creatinine in Japanese patients with congestive heart failure.

Seven methods using patient's age, weight, gender, and serum creatinine concentration were evaluated for mathematical and clinical predictive performance in estimating the creatinine clearance of Japanese patients. We compared the measured and estimated creatinine clearance in 179 hospitalized heart failure patients. The Gates equation was the most biased (mean prediction error, 17.9 mL/min), and the Yukawa equation was the most precise (mean absolute prediction error, 10.4 mL/min), followed by the Jelliffe, Bjornsson, Cockcroft and Gault, and Mawer equations. For all methods, precision was less when serum creatinine concentrations of <0.6 mg/dL were rounded than when serum creatinine concentrations of >/=0.6 mg/dL were rounded. We conclude that in clinical practice where the renal function can vary widely, any of the published formulas can give satisfactory results. The Yukawa formula is concise and gives better results in Japanese patients.

Adolescent↗

PubMed1999

Crystallization and preliminary x-ray diffraction studies of hyperthermostable glutamate dehydrogenase from Thermococcus profundus.

Recombinant glutamate dehydrogenase from a hyperthermophilic archaeon, Thermococcus profundus, was crystallized in the presence of both polyethylene glycol 8000 and lithium sulfate. Four types of crystals having different morphologies appeared in the crystallization trials; however, only one type was suitable for X-ray crystal structure analysis. The crystal belonged to the monoclinic space group P2(1) and the unit-cell parameters were a = 112.99, b = 163.70, c = 133.07 A, beta = 113.46 degrees at 110 K. The calculated V(M) value of 3.42 A(3) Da(-1) was acceptable when one hexamer of the enzyme, which was the physiological functional unit, occupied a crystallographic asymmetric unit. X-ray diffraction intensity data were collected to a resolution of 2.25 A with good statistics at the BL44B2 beamline of SPring-8.

Crystallization↗

PubMed1999

Genetic association between alcohol withdrawal symptoms and polymorphism of CCK gene promoter.

In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine-related behavior. CCK co-exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant -45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (chi2 = 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (-45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.

Cholecystokinin↗

PubMed1999

Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988-991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 microg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 +/- 132 versus 995 +/- 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% +/- 22.1%) and high at neutrophilia with rhG-CSF therapy (73. 0% +/- 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.

Adjuvants, Immunologic↗

PubMed1999

Pharmacokinetic and pharmacodynamic analysis of subcutaneous recombinant human granulocyte colony stimulating factor (lenograstim) administration.

A total of 72 adult healthy volunteers were administered 1 microgram/kg of rhG-CSF. There was no correlation between Cmax and an increase in peripheral neutrophil count, and there was a negative correlation between AUC and this increase. The mechanism of this is probably based on the correlation between the elimination rate constant (ke) and neutrophil increase. The ke probably has a close relationship with uptake by neutrophil and its progenitor via the G-CSF receptor. An individual with higher ke should therefore show a greater increase in neutrophil count. Therefore, AUC is proportional to the rhG-CSF remainder, that is, the proportion that is not consumed in the course of increasing the neutrophil count. In such a situation, the bioavailability calculated from the AUC is unlikely to indicate the absorbed amount. The authors also analyzed the pharmacokinetics using a two-compartment model with zero-order absorption and first-order elimination. This model was sufficient to obtain a good curve fit, and this demonstrates that the absorption process is not a first-order but a zero-order process. Therefore, there might be an upper limit to the rhG-CSF transfer rate from subcutaneous tissue to blood.

Adjuvants, Immunologic↗

PubMed1999

The complete amino acid sequence of dog beta2-microglobulin.

Dog beta2-microglobulin was purified from the urine of dogs with potassium dichromate induced tubular damage. It was purified by sequential use of anion exchange chromatography, gel filtration chromatography, and reversed-phase high performance liquid chromatography. Comparisons of the amino acid sequence of the dog protein with human, mouse, and rabbit beta2-microglobulin, indicated a high degree of similarity. The dog protein was very similar to human beta2-microglobulin in that it had a molecular weight of 11.8 kDa and contained two half-cystinyl residues. Dog and human beta2-microglobulin were demonstrably different at 24 of the 99 positions compared. The data supported the conclusion that the purified protein was dog beta2-microglobulin and that all four proteins from dog, human, mouse, and rabbit were closely related.

Amino Acid Sequence↗

PubMed1999

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

Studies were made on the development of Babesia gibsoni in the midgut of the larval tick, Rhipicephalus sanguineus. Six hr after repletion, merozoites of B. gibsoni, freed from erythrocytes, were observed in the midgut contents of the tick. After that, within 24 hr, those merozoites were transformed into the ring-forms which were relatively large, 2-3 microns in diameter. Later, the ring forms developed into the spherical forms which were subelliptical in shape and 4-6 microns in diameter. Within 2-4 days, the elongated forms, 5-8 microns in length, were found. At this time, some of the binucleated fusion form has assumed a form intermediate between the spherical and elongated-forms. About 5-6 days after repletion, large round or elliptic zygotes, 8-10 microns in diameter, were observed in the tick gut.

Animals↗

PubMed1999

Development of Babesia gibsoni in the midgut of the nymphal stage of the tick, Rhipicephalus sanguineus.

Studies were made on the development of Babesia gibsoni in the midgut of the nymphal stage of the tick, Rhipicephalus sanguineus. Six hr after repletion, merozoites of B. gibsoni, free of erythrocytes, were observed in the midgut contents of the ticks. After that, within 24 hr, those merozoites were transformed into ring-forms which were relatively large ring 1-2 microns in diameter. Later, the ring forms developed into spherical forms which were somewhat elliptical in shape and 3-4 microns in diameter. Within 2-4 days, bizarre forms (5-6 microns in diameter) developed into elongated forms (5-6 microns in length). About 5-6 days after repletion, large round or elliptic zygotes (7-9 microns in diameter) were observed in the ticks gut.

Animals↗

PubMed1999

Determination of bovine beta2-microglobulin and albumin in urine by a reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (HPLC) was used to analyze beta2-microglobulin and albumin in bovine urine. The urine samples were chromatographed on TSK-gel ODS-120T column with an acetonitrile gradient. Urinary beta2-m and albumin were detected at 220 nm. For the pre-treatment, there were two steps proceeding injection: dialysis of urine with distilled water overnight, followed by concentration by solid-phase extraction method using a Sep-Pak cartridge. The retention times of beta2-microglobulin and albumin were 25.35 +/- 0.85 and 32.20 +/- 0.20 minutes (n=5), respectively. The mean analytical recoveries of beta2-microglobulin and albumin added to 0.1 ml of urine samples were 94.5 and 100.5%, respectively. The within-run coefficients of variation ranged from 1.5 to 5.3% for beta2-microglobulin and from 2.3 to 7.0% for albumin. The sensitivity for quantification of each protein was 0.5 microg in 100 microl injected urine samples. Urine samples from healthy cows and from cows with different types of proteinuria were analyzed by this reversed-phase HPLC. Results revealed albumin was remarkable in the urine from a cow with glomerulonephritis, and beta2-microglobulin was, in the urine from a cow with tubular dysfunction.

Albuminuria↗

PubMed1999

Diffusion-weighted echo planar imaging of acute brain infarction: a preliminary report.

The clinical usefulness of diffusion-weighted echo planar imaging (DW-EPI) was studied in 55 patients with acute brain ischemia. Ischemic lesions were identified on DW-EPI as hyperintense regions in all patients before changes were detected by conventional magnetic resonance imaging techniques in 12 cases studied earlier than 6 hours after onset. The earliest case was verified on DW-EPI at 50 minutes after onset. The ultra-fast imaging technique took less than 2 minutes to perform even for restless patients. Three patients had cardioembolic middle cerebral artery occlusion, and emergent percutaneous transluminal recanalization was carried out. Chronological changes in the signal of brain ischemia on DW-EPI depended on the site and size of the lesion, lacunar infarct of basal ganglia, and/or massive infarct due to major vessel occlusion, and were affected by associated hemorrhagic events. Coronal DW-EPI could more easily demarcate ischemia in the brainstem and/or cerebellum than axial scans when susceptibility artifacts were present. Coronal scans also demonstrated the site and direction of the pyramidal tract and its anatomical correlation with the lesions. DW-EPI has potential for the diagnostic and therapeutic planning of patients with acute brain ischemia.

Aged↗

PubMed1999

Comparison of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 on the resorption of bone explants ex vivo.

26,27-Hexafluoro-1 alpha,25-dihydroxyvitamin D3 [F6-1,25-(OH)2D3] is more potent than 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1,25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1,25(OH)2D3 or 1,25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog/g body weight, was examined. F6-1,25(OH)2D3 was more potent than 1,25(OH)2D3 during each in vivo time period. 1,25(OH)2D3 at 3 h after the injection was more active compared to the control (no injection of 1,25(OH)2D3) but not at 14 and 24 h. The radioactivity of the bones after the injection of [3H]-F6-1,25(OH)2D3 was retained even at 24 h. In the case of [3H]-1,25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1,25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1,25(OH)2D3 and [3H]-26,27-hexafluoro-1 alpha, 23S,25-trihydroxyvitamin D3 [F6-1,23,25(OH)3D3] were detected at 14 and 24 h after the injection. [3H]-1,25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1,23,25(OH)3D3 was less than that of F6-1,25(OH)2D3 but similar to that of 1,25(OH)2D3. The present study indicates that F6-1,25(OH)2D3 is more active and more long-lasting than 1,25(OH)2D3 in the ex vivo method. A higher potency of F6-1,25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1,25(OH)2D3 and its active metabolite, F6-1,23,25(OH)3D3, in the bones are higher than that of 1,25(OH)2D3, and that F6-1,25(OH)2D3 and its metabolite are retained in bones longer than 1,25(OH)2D3.

Animals↗

PubMed1999

[Minimally invasive coronary artery bypass (MIDCAB) for double vessel using Y arterial graft which consists of left internal thoracic artery and right inferior epigastric artery].

MIDCAB is a rapidly evolving technique to revascularize the left anterior descending coronary artery (LAD) with the left internal thoracic artery (LITA). Our case is a 60-year-old female with unstable angina due to restenosis of the proximal LAD following PTCA and proximal stenosis of the large first diagonal branch (D1). She underwent double vessel MIDCAB (LITA-LAD and LITA-RIEA-D1) using Y composite arterial conduit with LITA and right epigastric artery (RIEA), because of chronic renal failure on maintenance hemodialysis. Postoperative course was uneventful and postoperative angiography revealed a patent Y graft. Y graft using IEA appears to be an interesting operative method in double vessel MIDCAB.

Coronary Artery Bypass↗

PubMed1999

Cerebrospinal fluid tau protein levels in demented and nondemented alcoholics.

The tau protein levels in cerebrospinal fluid (CSF-tau) were examined in 27 patients with alcohol dependence (20 demented and 7 nondemented), 36 age and dementia severity-matched patients with Alzheimer's disease (AD), and 23 age-matched normal control subjects. The CSF-tau levels in the demented alcoholic group (alcohol-induced organic brain disorders, 25.4 +/- 10.2 pg/ml) was significantly lower (p < 0.0001) than that in the AD group (96.1 +/- 53.3 pg/ml), but not significantly different from that in the nondemented alcoholics (18.1 +/- 10.2 pg/ml) or the controls (19.2 +/- 12.9 pg/ml). Using a 44.9 pg/ml as a cut-off value (mean + 2 SD of the normal control group), only one patient with alcohol-induced organic brain disorders exceeded the value, whereas 3 of 36 of the AD group showed CSF-tau levels less than this level. These findings suggest that alcohol-induced organic brain disorders are a group of dementias that are characterized by normal CSF-tau levels, and that the CSF examination for tau in combination with other clinical findings may help in differentiating alcohol-induced organic brain disorders from AD.

Adolescent↗