Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 145 records · Page 8Linked to original sources

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↗

PubMed1999

A novel polymorphism (-357 G/A) of the ALDH2 gene: linkage disequilibrium and an association with alcoholism.

BACKGROUND: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. METHODS: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. RESULTS: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2*2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2*1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A chi2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (chi2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. CONCLUSION: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.

Adult↗

PubMed1999

[Lithium carbonate].

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Antipsychotic Agents↗

PubMed1999

Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics.

BACKGROUND: Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. METHODS: To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. RESULTS: The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*I (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 heterozygotes with ADH2*1/ 2*1, compared with 92.3% of those with ALDH2*1/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. CONCLUSION: Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.

Adult↗

PubMed1998

Sensitive and specific method for the determination of josamycin in human plasma by liquid chromatography-mass spectrometry.

A highly sensitive and specific method for the determination of josamycin in human plasma by LC-MS was developed and validated. Josamycin was extracted from human plasma by a single-step liquid-liquid extraction and analyzed by LC-MS via an electrospray ionization interface. Selected ion monitoring was used to detect josamycin and its internal standard. The intra-day precision and accuracy, expressed as C.V. and R.E., ranged from 2.8% to 13.5% and -10.3% to 7.6%, respectively. The lower limit of detection was 0.1 ng/ml and the lower limit of quantitation was set at 1 ng/ml when 0.5 ml of plasma was used. No endogenous interference was observed in human plasma obtained from drug-free volunteers.

Anti-Bacterial Agents↗

PubMed1998

Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for barnidipine in human plasma.

A sensitive and specific LC-MS-MS assay has been developed and validated for barnidipine (1-benzyl-3-pyrrolidinyl)methyl-2,6-dimethyl-4(m-nitrophenyl)-1,4-dihydr opyridine-3,5-dicarboxylate). The assay involves a simple and rapid solid-phase extraction procedure. Sample analysis was on a Spherisorb S3ODS2 100 mmX2 mm I.D. column, with a Finnigan TSQ 7000 mass spectrometer, using an electrospray interface and selective reaction monitoring (SRM). The intra- and inter-day precision and accuracy, determined as the coefficient of variation and relative error, respectively, were 11.8% or less. The limit of quantitation was 0.03 ng/ml, and the calibration was linear between 0.03 and 3.0 ng/ml. The method has been used successfully for the measurement of over two thousand human plasma samples from pharmacokinetic clinical trials.

Calcium Channel Blockers↗

PubMed1998

Familial neuronal migration disorder: subcortical laminar heterotopia in a mother and pachygyria in the son.

We describe clinical manifestations and magnetic resonance imaging (MRI) findings in a man and his mother who were diagnosed as having a neuronal migration disorder. The son had severe psychomotor retardation and the mother had intractable seizures and mild psychomotor retardation. MRI demonstrated moderate pachygyria in the son and subcortical heterotopia in the mother. In both patients, the frontal parts of the brain were characteristically more affected than any other areas. A dominant pattern of inheritance in the family suggests a genetic role in the underlying cause of the migration disorder. The difference in severity between the two patients also suggests an X-linked dominant inheritance. Our family fits the condition of X-linked lissencephaly.

Adult↗

PubMed1998

Purification and characterization of a kinin-releasing and fibrinogen-clotting serine proteinase (KN-BJ) from the venom of Bothrops jararaca, and molecular cloning and sequence analysis of its cDNA.

Two forms of a proteinase, KN-BJ 1 and 2, were purified to homogeneity from the venom of Bothrops jararaca. In SDS/PAGE reduced KN-BJ 1 and 2 migrated as single bands with molecular masses of 38 kDa and 39 kDa. The two enzymes have similar N-terminal amino acid sequences and specific activities on synthetic chromogenic substrates, and both release bradykinin from bovine low-molecular-mass kininogen. KN-BJ 1 and KN-BJ 2 clot fibrinogen with specific activities of 245 NIH U/mg and 219 NIH U/mg, releasing only fibrinopeptide A. The amidolytic, kinin-releasing and coagulant activities are inhibited by phenylmethylsulfonyl fluoride, demonstrating that KN-BJ is a serine proteinase. Benzamidine derivatives, which are competitive inhibitors of trypsin-like proteinases, also inhibited the amidolytic activity of KN-BJ. A cDNA clone (HS104, 2.2 kb) has been isolated from a cDNA library of B. jararaca venom glands with an ORF of 771 bp. The deduced amino acid sequence contains segments that are identical to the sequences of the N-terminus and three tryptic peptides of KN-BJ 2. Therefore, the cDNA is believed to represent the gene of KN-BJ 2. The deduced amino acid sequence indicates that KN-BJ 2 is synthesized as a prezymogen of 257 amino acids with a putative signal peptide of 18 amino acids and an activating peptide of six amino acid residues. The sequence of 233 amino acids representing the mature enzyme exhibits high similarity to sequences of serine proteinases isolated from crotalid venoms.

Amino Acid Sequence↗

PubMed1998

Structure-activity characterization of an H2-receptor antagonist, 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione hydrochloride (T-066), involved in the insurmountable antagonism against histamine-induced positive chronotropic action in guinea pig atria.

IT-066 (3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino]-3-cyclobutene-1,2-dione hydrochloride), an H2-receptor antagonist, shows highly potent, time-dependent, and irreversible antagonism at H2-receptors. We identified the structurally important parts of IT-066 involved in its interaction with the H2-receptor, and explored its unique mode of action by investigating the H2-receptor blocking action of IT-066 and related compounds in guinea pig isolated atria. IT-066 is structurally divided into three different parts: a tertiary amine and hydrophobic group, a connecting carbon chain, and a polar group. Though the replacement of its pyridine ring with a benzene ring maintained the mode of the H2-receptor blocking action of IT-066, the oxidation of the piperidine ring completely attenuated this blocking action. By replacing the connecting carbon chain of IT-066, cis-2-butene, with butane, trans-2-butene, or 2-butyne, the irreversible antagonism disappeared and the potency was reduced. On the other hand, BMY25368, whose connecting carbon chain is trimethylene, showed irreversible antagonism comparable to that of IT-066. Hydrolysis of the polar group of IT-066 completely attenuated the H2-receptor blocking activity. Among the compounds tested, only the compound that had 3,4-diamino-3-cyclobutene-1,2-dione as a polar group showed time-dependent and insurmountable H2-receptor blocking action. These data suggest the importance of the following structural features of IT-066: the piperidine ring of IT-066 and -NH2 in its polar group are essential for the interaction with the H2-receptor; and the 3,4-diamino-3-cyclobutene-1,2-dione group and the connecting carbon chain of IT-066 are crucial for determining the irreversibility of H2-receptor blocking action, though the connecting carbon chain is replaceable with another chain with appropriate length and configuration.

Animals↗

PubMed1998

Absence of association of alpha1-antichymotrypsin polymorphisms with Alzheimer's disease: a report on autopsy-confirmed cases.

alpha1-Antichymotrypsin (ACT) polymorphisms were examined in 79 cases with autopsy-confirmed Alzheimer's disease (AD) as well as in 28 cases with autopsy-confirmed nonneurological diseases to test the hypothesis that ACT polymorphisms confer a risk to an individual to develop AD. Neither ACT genotype frequency nor ACT allele frequency in the AD group was significantly different from the control group. The ACT polymorphic pattern was essentially the same among apolipoprotein E (apoE) epsilon4 carriers and noncarriers. The age at onset of AD was not significantly affected by the inherited dose of ACT/A allele. Taking together, our observations do not confirm the effect of the ACT/A allele as a risk factor for developing AD in addition to the ApoE epsilon4 allele.

Adolescent↗