Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 19 recordsLinked to original sources

PubMed1992

Determination of a new bisphosphonate, YM175, in plasma, urine and bone by high-performance liquid chromatography with electrochemical detection.

A high-performance liquid chromatographic method for the determination of disodium dihydrogen(cycloheptylamino)methylene-bisphosphonate monohydrate (YM175) in plasma, urine and bone is described. Plasma obtained in high-dose animal studies is pretreated by Method A, a simple method using 1 ml of plasma, which is based on deproteinization of plasma followed by coprecipitation of the drug with calcium phosphate and removal of excess calcium ions by AG 50W-X8 resin. Plasma obtained in lower-dose clinical studies is treated by Method B, a more sensitive method using 10 ml of plasma, which is based on solid-phase extraction using a Sep-Pak C18 cartridge coupled with Method A. Urine and bone are treated similarly to Method B. The chromatographic system consists of a mobile phase at pH 11, an alkali-stable column and an electrochemical detector operating in the oxidation mode. The determination limit is 5 ng/ml for Method A and 0.5 ng/ml for Method B in plasma, 1 ng/ml in urine, and 25 ng/g in bone.

Animals↗

PubMed1992

Molecular cloning of a calmodulin-dependent phosphatase from murine testis: identification of a developmentally expressed nonneural isoenzyme.

A unique isoform of the catalytic subunit of calmodulin-dependent protein phosphatase (CaM-PrP) was cloned from a murine testis library. The cDNA sequence of 1964 base pairs contained an open reading frame encoding a protein of 513 amino acids (Mr approximately 58,706), the predicted isoelectric point of which (pI 7.1) was much more basic than those of brain isoforms (pI 5.6-5.8). The deduced amino acid sequence was 77-81% identical to two other murine CaM-PrP genes and displayed a distinct Southern blot hybridization pattern, indicating that it was derived from a separate gene (type 3). High amounts of a 2800-nucleotide mRNA transcript were observed in testis, whereas mRNA species were not detectable in brain; thus, it seems likely that this CaM-PrP represents a nonneural isoenzyme. Measurements of CaM-PrP mRNA during testicular development showed a dramatic increase in expression during weeks 4-6, correlating with the later stages of spermatogenesis. These data suggest that this phosphatase isoform may be involved in germ-cell function and are consistent with the report of a flagellum-associated form of CaM-PrP that may regulate sperm motility [Tash, J. S., Krinks, M., Patel, J., Means, R. L., Klee, C. B. & Means, A. R. (1988) J. Cell Biol. 106, 1625-1633].

Amino Acid Sequence↗

PubMed1992

Influence of food on serum ambenonium concentration in patients with myasthenia gravis.

Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non-fasting state. The AUC (0-3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the nonfasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC.

Adult↗

PubMed1992

Calcium regulating activity of 26,27-dialkyl analogs of 1 alpha,25-dihydroxyvitamin D3.

A series of analogs of 1 alpha,25-dihydroxyvitamin D3[1,25(OH)2D3] with alkyl substitutions in 26- and 27-positions were tested for calcium (Ca) regulating activity. The potencies of dialkyl analogs in stimulating bone resorption in neonatal mouse calvaria cultures were the highest in 1 alpha,25-dihydroxy-26,27-dimethylvitamin D3[1,25(OH)2-(Me)2D3], followed by 1,25(OH)2D3, 1 alpha,25-dihydroxy-26,27-diethylvitamin D3[1,25(OH)2(Et)2D3], and 1 alpha,25-dihydroxy-26,27-dipropylvitamin D3[1,25(OH)2(Pr)2D3] in that order. A similar order of potential regarding formation of osteoclast-like cells in mouse bone marrow cell cultures and on bone Ca mobilization with long-term vitamin D-deficient rats was observed in the same series. The relative potencies of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 1,25(OH)2(Et)2D3, and 1,25(OH)2(Pr)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptors were 1:1:0.16:0.036. A similar order of potential in case of intestinal Ca transport in situ was observed in the same series. The potencies of dialkyl analogs in competing with 25-hydroxy-vitamin D3 for binding to rat serum vitamin D binding protein were much lower than that of 1,25(OH)2D3. Effect of 1,25(OH)2(Me)2D3 on osteopenia in rats induced by ovariectomy and right sciatic neurotomy was higher than that of 1,25(OH)2D3. From these results, the lengthening by one carbon at 26- and 27-positions was shown to maintain the Ca regulatory activity of 1,25(OH)2D3.

Animals↗

PubMed1992

Effects on cultured neonatal mouse calvaria of 1 alpha,25-dihydroxyvitamin D3, 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,26,26,27,27,27-hexafluoro-1 alpha,23S,25-trihydroxyvitamin D3.

The potency of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) to enhance bone calcium (Ca) mobilization in vitro was higher than that of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In a 48-h organ culture system using fetal rat limb bones, effects of 26,27-F6-1,25(OH)2D3 on bone resorption were similar to those of 1,25(OH)2D3. Thus, we attempted to clarify whether or not the potency of 26,27-F6-1,25(OH)2D3 in bone resorption in vitro would be higher than that of 1,25(OH)2D3. Calvarial bones from neonatal mice were used as explants and the culture period was extended to 144 from 48 h. In cultures of 0 to 48 h, both drugs increased the release of prelabeled 45Ca from cultured calvariae, in a dose-dependent manner. In cultures of 48 to 144 h, 26,27-F6-1,25(OH)2D3 was much more effective than 1,25(OH)2D3 regarding indices of bone resorption. 26,26,26,27,27,27-F6-1 alpha,23S,25-trihydroxyvitamin D3 (26,27-F6-1,23,25(OH)3D3), a main metabolite of 26,27-F6-1,25(OH)2D3 in rats, stimulated 45Ca release equipotently to 1,25(OH)2D3. In mouse bone marrow cells cultured for 7 days, the potency of 26,27-F6-1,25(OH)2D3 on osteoclast formation was much higher than 1,25(OH)2D3. These results suggest that the higher potency of 26,27-F6-1,25(OH)2D3 in bone resorption may be due at least in part to both the higher potency of 26,27-F6-1,25(OH)2D3 in osteoclast formation and the larger retention of 26,27-F6-1,23,25(OH)3D3 in calvariae.

Acid Phosphatase↗

PubMed1992

Determination of glutathione isopropyl ester in rat, dog and human blood by high-performance liquid chromatography with fluorescence detection.

A HPLC method is developed for the determination of glutathione isopropyl ester, a drug for the treatment of cerebral vascular disease, in rat, dog and human blood. The blood is deproteinized with sulphosalicylic acid and the clear supernatant treated with a thiol-specific fluorogenic reagent, ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD-F) in borate buffer pH 7.5 at 30 degrees C. The derivatization of glutathione isopropyl ester with SBD-F is markedly enhanced by the addition of dimethyl sulphoxide, and is complete in 30 min. The fluorescent derivatives of glutathione isopropyl ester and the internal standard, glutathione ethyl ester are separated from those of endogenous thiols such as cysteine and glutathione on a reversed-phase column. The method is simple and selective with a detection limit of 0.05 micrograms ml-1. Blood concentrations of glutathione isopropyl ester in rats, dogs and humans after intravenous administration are determined using the method.

Animals↗

PubMed1992

The association of drinking levels and drinking attitudes among Japanese in Japan and Japanese-Americans in Hawaii and California.

This study examined cross-cultural differences in drinking attitudes and drinking levels and their correlation among Japanese in Japan and Japanese-Americans in Hawaii or California. In most situations, an increase in drinking levels was associated with more tolerant drinking attitudes in all three groups. Abstainers were less likely to say that getting drunk is sometimes all right, whereas the reverse was true for heavier drinkers. Drinking levels among Japanese, especially among Japanese women, were not highly associated with how much drinking was perceived as acceptable in each situation, whereas among Japanese-Americans, drinking levels were highly associated with drinking attitudes. Although the Japanese had generally tolerant attitudes toward drinking, they indicated higher abstention rates before driving than Japanese-Americans regardless of their drinking levels. This may reflect the impact of public education on drunken driving in Japan.

Adolescent↗

PubMed1992

Molecular and phylogenetic analysis of calmodulin-dependent protein phosphatase (calcineurin) catalytic subunit genes.

In the mammalian brain, there are multiple catalytic subunits for the Ca(2+)- and calmodulin-dependent protein phosphatase [also called protein phosphatase 2B (PP-2B) and calcineurin] that are derived from two structural genes. The coding sequences of these two genes are distinguished by the absence (PP2B alpha 1) or the presence (PP2B alpha 2) of an amino terminus containing polyproline. Both of these genes can produce intragenic isoforms through alternative splicing. In the present study, a potential phylogenetic relationship of these genes was inferred from analysis of genomic DNA and from studies of mRNA and protein expression. Southern blot analysis showed unique restriction fragments for both genes in seven mammalian species; however, in organisms from two nonmammalian vertebrates (chicken and lizard), hybridization was observed only for PP2B alpha 1. In agreement with these results, Northern blots of mammalian brain RNA showed transcripts for both genes, with about two to three times more of the PP2B alpha 1 mRNAs, whereas in chicken and lizard, only PP2B alpha 1 transcripts were detected. An analysis of protein expression by two-dimensional electrophoresis was also consistent with these findings. For the purified mammalian brain protein, eight to ten variants were observed with isoelectric points of 5.2-5.8; immunoblot analysis using anti-peptide antibodies indicated that the majority of these were PP2B alpha 1 forms. In chicken brain, multiple isoforms were recognized by antibodies against the PP2B alpha 1 forms, but no reactivity was seen with those against the PP2B alpha 2 forms. Taken together, these findings suggest that: (i) in mammals, the predominant catalytic subunit isoforms in brain are PP2B alpha 1 products and (ii) the gene for the polyproline-containing catalytic subunit of calmodulin-dependent phosphatase (PP2B alpha 2) may have evolved after the avian/reptilian branching point, perhaps to carry out a role(s) of particular significance in mammals.

Animals↗

PubMed1992

Influence of age and co-medication on steady-state carbamazepine serum level-dose ratios in Japanese paediatric patients.

The effects of age and co-medication on steady-state carbamazepine (CBZ) level-dose (L/D) ratios were evaluated retrospectively in 370 paediatric patients. The CBZ L/D ratio increased significantly with age up to 15 years in patients on monotherapy (L/D = 0.051 x AGE + 0.334, n = 111, r = 0.593, P less than 0.001). Associated anti-epileptic therapy affected the CBZ L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy. The study therefore suggests that routine monitoring of CBZ serum levels is extremely useful, especially in the paediatric age group, and in patients who require associated anti-epileptic medication.

Adolescent↗

PubMed1992

Influence of age and co-medication on steady-state phenobarbital serum level-dose ratios in Japanese paediatric patients.

The effects of age and co-medication on steady-state phenobarbital (PB) level-dose (L/D) ratios were evaluated retrospectively in 539 paediatric patients. The PB L/D ratio increased significantly with age up to 15 years. Associated anti-epileptic therapy affected the PB L/D ratio, which was significantly increased in patients on polypharmacy as compared to patients on monopharmacy. Therefore, routine monitoring of PB serum levels is extremely useful, particularly in the paediatric age group, and in patients who require associated anti-epileptic medication.

Adolescent↗

PubMed1992

Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with chronic benign granulocytopenia and congenital agranulocytosis (Kostmann's syndrome).

Seven patients with chronic benign granulocytopenia and nine patients with congenital agranulocytosis, received consecutive seven-day courses of recombinant human granulocyte-colony stimulating factor at a starting dose of 50 micrograms/m2/day, subcutaneously. If there was no response the doses were increased to 300 micrograms/m2. All patients with chronic benign granulocytopenia responded rapidly at the minimum dose within 1-3 days after administration. By contrast, only three of the nine patients with congenital agranulocytosis responded within 1-7 days at this dose. Four patients with congenital agranulocytosis showed a response between days 7-19 at a dose of granulocyte-colony-stimulating factor 100-200 micrograms/m2 but in the remaining two cases no response was obtained. The administration of granulocyte-colony-stimulating factor was shown to be safe and effective also in reducing infectious episodes in these patients. Previously it was reported that granulocyte-colony-stimulating factor 10-30 micrograms/kg/day was effective for patients with congenital agranulocytosis. These results indicate that patients with congenital agranulocytosis may require much higher doses of recombinant human granulocyte-colony-stimulating factor than patients with chronic benign granulocytopenia and that the response to ordinary doses of recombinant human granulocyte-colony-stimulating factor may be useful in differentiating between chronic benign granulocytopenia and congenital agranulocytosis.

Adolescent↗

PubMed1992

Phenobarbitone population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens.

Routine clinical pharmacokinetic data collected from patients receiving phenobarbitone have been analysed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of phenobarbitone was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicated a nonlinear function of total body weight as the optimum adjustment of phenobarbitone clearance. Concomitant administration of phenobarbitone and other antiepileptic drugs showed a decrease of phenobarbitone clearance in young children. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.

Adolescent↗

PubMed1992

Digoxin population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens.

Routine clinical pharmacokinetic data collected from patients receiving digoxin have been analysed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of digoxin was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicate that digoxin clearance was influenced by the demographic variables of age, total body weight, serum creatinine and sex. The interindividual variability in digoxin clearance was modelled with additive error with an estimated standard deviation of 46.15 L day-1 and the intraindividual variability, or residual error was 0.209 ng mL-1. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.

Aged↗

PubMed1992

Clinical management of boric acid ingestion: pharmacokinetic assessment of efficacy of hemodialysis for treatment of acute boric acid poisoning.

Seven hours after suicidal ingestion of about 21 g of boric acid, a 26-year-old female admitted to our hospital in a state of slightly impaired consciousness, with frequent vomiting, shivering, fever and skin flush. Immediately, gastric lavage, followed by administration of activated charcoal and laxative (MgSO4), was performed. In order to ensure her urination, fluid infusion therapy was conducted with the aid of diuretics (furosemide). Since the serum concentrations of boric acid was very high, hemodialysis was carried out twice during the first 39 h. She responded well to the above mentioned treatment and was discharged 12 d post-admission without any sequelae. The concentrations of boric acid in serum and urine were measured in appropriate intervals with our modified Miyamoto's method, and the pharmacokinetics of boric acid were analyzed. The concentration of boric acid in serum and urine at the beginning of treatment was 465 micrograms/ml and 3.40 mg/ml, respectively. The half-life of boric acid in serum was 13.46 h, whereas it was shortened to 3.76 h during hemodialysis. The total body clearance was 0.99 l/h, while it increased to 3.53 l/h by hemodialysis. The additional removal of boric acid by hemodialysis was estimated to be about 5 g. It was concluded that the hemodialysis was very useful in the treatment of boric acid poisoning, because it accelerated the elimination of boric acid about four times faster than with conventional treatment.

Acute Disease↗

PubMed1992

Pharmacoepidemiological study on adverse reactions of antiepileptic drugs.

The relationship between the occurrence of side effects (SEs) and drug factors, such as antiepileptic drugs (AEDs), daily dose, duration of treatment, drug combination pattern, total and free serum concentrations, metabolite per parent level ratio as an index of metabolism ability, and co-medicated drugs except AEDs were evaluated in 227 outpatients with epilepsy. The possible influences of certain physiological and/or the pathophysiological factors were also evaluated. SEs with 19 clinical signs were observed in 66.1% of all patients. There was no definite dose- or serum concentration-dependent increase in the incidence of SEs. Stepwise discriminant function analysis revealed that benzodiazepines (BZN) polytherapy with AEDs produced a higher incidence of somnolence and general fatigue than did any other AED or drug combination. The effects of various drug combination patterns on the incidence of SEs were also evaluated on the basis of observed frequencies. The incidence of somnolence was significantly higher in patients taking phenytoin (PHT) plus carbamazepine (CBZ) therapy, and in patients taking BZN plus either PHT, phenobarbital (PB) or CBZ therapy compared with patients taking either PHT, PB or CBZ therapy. Other responsible drug combination patterns were PHT plus valproic acid (VPA) therapy for mental function impairment, acetazolamide (AZM) polytherapy with PB or PHT for dry mouth, and CBZ plus BZN therapy for constipation. In this study, the stratifying points (occurrence limits) of SEs were detected in various variables such as the number of prescribed drugs, daily dose and serum concentrations. Interestingly, these limits are within the commonly accepted "therapeutic range" or "usual daily dose," and some of these limits shifted down when another AED was co-medicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

The relationship between low Km aldehyde dehydrogenase phenotype and drinking behavior in Japanese.

The relationship between the low Km aldehyde dehydrogenase (ALDH2) phenotype determined by the isoelectric focusing of hair root lysates, facial flushing and alcohol drinking patterns in Japanese (N = 282) was examined. Men who had inactive ALDH2 drank significantly less alcohol than those with active ALDH2. Although the effect was less noticeable, a similar relationship was detected in women. Two types of flushing responses were determined: one due to the inactive ALDH2, the other unrelated to this variant form of the isozyme. A striking difference between these flushing types, in terms of the inhibitory influence over drinking patterns, was noted. Nearly 86% of the subjects who reported always flushing in the face were shown to have inactive ALDH2, whereas infrequent flushing and absence of flushing were associated with active ALDH2. Thus, facial flushing may be used as an indicator of ALDH2 phenotype.

Adolescent↗

PubMed1992

The effect of acculturation on drinking attitudes among Japanese in Japan and Japanese Americans in Hawaii and California.

Data from a joint Japan-U.S. collaborative study were examined to determine the relationship of acculturation to drinking attitudes among Japanese in Japan and Japanese Americans in Hawaii and California. Drinking attitudes (i.e., self-reported acceptable or appropriate levels of drinking) among ethnic groups differed significantly for the nine situations studied: (1) at a bar with friends, (2) at a party at someone else's house, (3) as a parent, spending time with small children, (4) during working hours, (5) visiting in-laws, (6) with friends at home, (7) with friends after work, (8) with people at sports events and (9) before driving a car. Factor analysis was used to determine the differences in drinking attitudes among these ethnic groups. Japanese and Japanese Americans differentiated drinking situations into different categories. The major difference between the two groups was that the Japanese associated spending time with small children with a situation appropriate for drinking, such as being with friends at home, whereas Japanese Americans associated spending time with small children with a situation inappropriate for drinking, such as before driving.

Acculturation↗

PubMed1992

The relationship between three subtypes of the flushing response and DSM-III alcohol abuse in Japanese.

This study examined the relationship between the flushing response and drinking patterns and DSM-III alcohol abuse among Japanese using data collected in the joint U.S.-Japan collaborative study. The flushing response was classified into the following three subtypes: typical flushing (always flushed in the face after drinking), atypical flushing (sometimes) and nonflushing (never). This study of male current drinkers showed that typical flushers drank less alcohol than did atypical and nonflushers, but there was no observed difference between the drinking patterns of atypical flushers and nonflushers. Although the relationship was less pronounced, a similar association was found for female current drinkers. The 12-month prevalence of DSM-III alcohol abuse was estimated to be highest among atypical flushers and lowest among typical flushers, with nonflushers in between for both genders. When daily alcohol consumption and other pertinent sociodemographic variables were controlled, logistic regression analyses revealed that the risk for alcohol abuse by men was approximately 3.0 times higher among atypical flushers and 1.7 times higher among nonflushers than among typical flushers. The corresponding risks for abuse by women were 7.8 (atypical flushers) and 2.8 (nonflushers) times higher. Possible explanations for these differences in drinking patterns and the risk for alcohol abuse among the three flushing subtypes and between genders are discussed.

Adolescent↗