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Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 325 records · Page 18Linked to original sources
PubMed1995

Mechanisms of eosinophilia in mice infested with larval Haemaphysalis longicornis ticks.

Infestation of larval Haemaphysalis longicornis ticks induced a threefold increase of eosinophils in the peripheral blood of normal WBB6F1- +/+ mice 2 days after tick infestation. In genetically mast cell-deficient WBB6F1- W/Wv mice, a threefold increase of blood eosinophils was observed 6 days after the tick infestation. However, marked infiltration of eosinophils was detected in the tick infestation sites of the WBB6F1- +/+ mice but not the WBB6F1- W/Wv mice. When the mast cell deficiency of WBB6F1- W/Wv mice had been rescued locally by intradermal injections of WBB6F1- +/+ mouse-derived cultured mast cells, a rapid increase of blood eosinophils and tissue infiltration of eosinophils were revealed following tick infestation. The intravenous (i.v.) injection of immune spleen or lymph node cells obtained from WBB6F1- +/+ mice 10 days after tick infestation led to significant eosinophilia in naive recipient mice. Treatment with anti-Thy-1.2 or anti-CD4 monoclonal antibody (mAb) and complement (C) completely abolished the eosinophilia; the early response (2 days after tick challenge) is dependent on mast cells at the feeding site, and the late response (6 days after tick challenge) is dependent on T lymphocytes. Since amplified interleukin-5 (IL-5) cDNA was detectable in the spleen cells 4 days after tick infestation, the late response might be mediated by IL-5. The infiltration of eosinophils at the feeding site of skin appeared to be dependent on mast cells.

Animals↗
PubMed1995

[Neutropenia in patient with X-linked hyper-IgM syndrome].

The X-linked form of hyper-IgM syndrome (HIGM1) is a rare disorder characterized by the inability of B cells to undergo isotype switch by a deficiency of CD40 ligand (CD40L) on activated T lymphocytes. The patients suffer from recurrent infections not only due to a lack of B lymphocyte activation but also due to defect of T lymphocyte functions. In addition, neutropenia is frequently accompanied by these symptoms. A patient with HIGM1, we experienced, suffered from recurrent infections and neutropenia. But he had a normal number of hematopoietic stem cell by the in vitro colony forming assay. CD34+ myeloid stem cell has been known to express CD40. We speculated by these facts that myeloid cell numbers are regulated by CD40-CD40L interaction.

Adolescent↗
PubMed1995

Pharmacokinetics of YM175, a new bisphosphonate, in rats and dogs.

We investigated the pharmacokinetics of YM175, a new bisphosphonate, after intravenous and oral administrations in rats and dogs. After intravenous administration at 0.03-0.3 mg/kg, plasma YM175 concentration declined biexponentially with an apparent terminal half-life of 0.37-0.72 hr in rats and 3.30-4.09 hr in dogs. In both species, the area under the plasma concentration vs. time curve increased dose-proportionally, whereas volume of distribution at steady-state and total body clearance changed little among doses, indicating the linear pharmacokinetics of the drug after intravenous administration. After oral administration to rats (3-30 mg/kg) and dogs (0.3-10 mg/kg), maximum concentration and area under the plasma concentration vs. time curve increased more than dose-proportionally at 30 mg/kg in rats and at 3 mg/kg or higher in dogs. Thus, bioavailability increased at higher doses, being 1.0%, 1.2%, and 3.6% at 3, 10, and 30 mg/kg in rats, and being 1.8%, 1.3%, 2.9%, and 11.5% at 0.3, 1, 3, and 10 mg/kg in dogs, respectively. Urinary excretion and bone concentration of radioactivity in rats receiving [14C]YM175 agreed well with those of unchanged drug in both administration routes, and radiochromatograms of rat urine revealed no peaks of metabolites. These findings suggest that YM175 undergoes practically no metabolism and indicate that the increase in bioavailability at higher doses is caused by enhanced drug absorption, and not by any saturation of first-pass metabolism. Finally, concentrations of YM175 in the rib of dogs receiving a 0.3 mg/kg intravenous dose were highest in the epiphyseal costa, followed by the middle costa and cartilage, indicating that the uptake of YM175 into bone is site-dependent. Furthermore, the drug in rib decreased biexponentially with a terminal half-life of 249 days in the epiphyseal costa and 351 days in the middle costa, suggesting that the elimination rate of YM175 from bone is also site-dependent.

Administration, Oral↗
PubMed1995

[Lithium carbonate].

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Antidepressive Agents↗
PubMed1994

Association of structural polymorphism of the dopamine D2 receptor gene and alcoholism.

To examine the possible association between three recently identified structural polymorphisms of the dopamine D2 receptor (DRD2) gene and alcoholism, we compared allele frequencies of these polymorphisms in 280 Japanese alcoholics and 289 normal controls. The results revealed that only one of three variants identified in white individuals existed in the alcoholic and control Japanese. The frequency of the Cys311 variant allele was significantly higher in alcoholics (.063) than in controls (.029). All of the subjects with the variant allele were heterozygous Ser311/Cys311. Patients with Cys311 allele had less severe symptoms of alcoholism than did those with homozygous Ser311, especially symptoms related to loss of control over drinking. The coprevalence of other psychiatric disorders including schizophrenia did not differ between the two patient groups. These results suggest that the D2/Cys311 variant is associated with some type of alcoholism in Japanese.

Age of Onset↗
PubMed1994

Expression of beta-amyloid precursor protein in the developing human spinal cord.

Human fetal spinal cords and other non-neural tissues from cases with gestational age from 6 to 21 weeks were examined with a panel of antibodies to different domains of beta-amyloid precursor proteins (beta-APPs). In the early developmental stages, the beta-APPs were expressed in three distinct layers, i.e., primitive neuroepithelial cell layer, mantle layer and marginal layer. beta-APP immunoreactivity was most prominent in cell bodies of putative neuroblasts located in the outer ventral part of the mantle layer. beta-APP expression diminished as the spinal cord matured and a weak residual immunoreactivity was detected exclusively in a subset of the anterior horn cells by 21 weeks gestational age. Throughout the gestational ages examined, no convincing beta/A4 immunostaining was seen in any of the spinal cord regions. Outside the spinal cord, beta-APP immunostaining was consistently present in (1) cell bodies and proximal nerves of immature neurons of dorsal root ganglia and in (2) myotubules, although these cells were devoid of beta/A4 immunoreactivity. Western blot analysis of fetal spinal cord revealed immunoreactive bands with apparent molecular weight between 100 and 140 kDa in the membrane-associated fraction, while soluble proteins with a molecular mass centered on 115 kDa were detected in the cytosolic fraction. Our results indicate that: (1) one or more isoforms of full length beta-APPs are expressed at very early gestational ages in the developing human spinal cord; (2) the normal metabolism of beta-APPs does not result in accumulations of beta/A4 fragments.

Amyloid beta-Protein Precursor↗
PubMed1994

Sensitive determination of a novel bisphosphonate, YM529, in plasma, urine and bone by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method for the sensitive determination of 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1, 1-bisphosphonic acid monohydrate (YM529) in plasma, urine and bone is described. Plasma obtained in high-dose animal studies is treated 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 dissolution of the precipitate in EDTA. Plasma obtained in low-dose clinical studies is treated by method B, a more sensitive method using 4 ml of plasma, which is based on direct precipitation of the drug prior to the deproteinization in method A. Urine and bone samples are prepared by solid-phase extraction using a Sep-Pak C18 cartridge coupled with method A. The drug is separated with a reversed-phase column using a mobile phase at pH 7, and detected with a fluorescence detector following postcolumn alkalization of the mobile phase to enhance fluorescence intensity. The limit of determination is 0.2 ng/ml for method A and 0.05 ng/ml for method B in plasma, 0.05 ng/ml in urine, and 5 ng/g in bone.

Animals↗
PubMed1994

Bulimia nervosa with and without alcoholism: a comparative study in Japan.

To characterize females with bulimia nervosa and alcoholism, this study compared the social and family backgrounds, as well as the clinical symptoms of alcoholics with bulimia and patients with bulimia only. The subjects were 22 Japanese female patients with both bulimia nervosa and alcoholism; the comparison group comprised 22 age-matched female patients with bulimia nervosa but without alcoholism. Patients with both bulimia and alcoholism had more borderline personality disorders and pathological symptoms such as stealing, suicide attempts, and liver injuries than the nonalcoholic comparison group. The subjects' average body weight was significantly less than that of the comparison group. Whereas the clinical characteristics of females with bulimia and alcoholism differ in many respects from those with bulimia only, it is suggested that alcoholic bulimia patients form a distinct clinical subgroup among patients with bulimia nervosa.

Adult↗
PubMed1994

Apolipoprotein E epsilon 4 allele distribution in alcoholic dementia and in Alzheimer's disease in Japan.

The apolipoprotein E epsilon 4 allele has been associated with both familial and sporadic Alzheimer's disease (AD). Given its possible role in nerve repair and growth, it is plausible that apolipoprotein E may be a common denominator in the pathogenesis of several dementing diseases. Therefore, we investigated epsilon 4 frequencies in demented and nondemented alcoholics, as well as in patients with sporadic AD and controls in Japan. No significant differences in allele frequencies was found between demented and nondemented alcoholics and controls, while a significant association was demonstrated between AD and the epsilon 4 allele. These results support a specific role of epsilon 4 in the pathogenesis of AD, rather than a more general role for epsilon 4 in dementing illnesses.

Aged↗
PubMed1994

A family of selective immunodeficiency with normal immunoglobulins: possible autosomal dominant inheritance.

We report here our findings in two Japanese siblings who experienced recurrent bacterial and viral infections since early infancy. Recent symptoms included diarrhoea, conjunctivitis, rashes, headache, sore throat, joint pain, vomiting and vertigo, all similar to those seen in toxic shock syndrome, except for shock. These symptoms improved following gammaglobulin treatment. Staphylococcus aureus with coagulase type IV was continuously isolated from nasal smears producing toxic shock syndrome toxin-1 (TSST-1). Serum antibodies did not or only poorly responded to TSST-1, diphtheria toxoid, varicella virus and rubella virus, whereas total and subclass levels of serum immunoglobulin and in vitro DNA synthesis of lymphocytes stimulated by TSST-1, Staph. aureus, varicella vaccine and mitogens were normal. In the family, ten other members in three generations (five males: five females) including the mother had similar clinical symptoms. Thus, the disease may be inherited in an autosomal dominant fashion.

Antibodies, Bacterial↗
PubMed1994

NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro.

NS-398 is a novel anti-inflammatory and analgesic agent which produces much fewer gastrointestinal lesions in rats. Recently, two forms of cyclooxygenase have been identified: a COX-1 first purified from ram seminal vesicles and a newly discovered mitogen-inducible form (COX-2). Effects of NS-398 on activities of these two distinct forms of COX were investigated. COX-1 purified from ram seminal vesicles and COX-2 isolated from sheep placenta (purity was 70%) were used. The COX-1 activity was completely unaffected by 10(-4) M NS-398, whereas the COX-2 activity was concentration-dependently inhibited, the IC50 value being 3.8 x 10(-6) M. Indomethacin inhibited both COX-1 and COX-2 activity to the same degree, the IC50 values being 7.4 x 10(-7) M and 9.7 x 10(-7) M, respectively. The anti-inflammatory and analgesic effects of NS-398 were almost as potent as indomethacin, the effective dose range being 0.3 approximately 5 mg/kg in rats. The gastrointestinal lesions related to NS-398 were not significant following a dose of 1000 mg/kg given orally. NS-398 is the first documented agent to have selective inhibition for COX-2, which may result in the less gastrointestinal toxicity.

Animals↗
PubMed1994

Application to cows and horses of Spotchem, a dry-chemistry blood analyzer for use in veterinary clinics.

The usefulness of a dry-chemistry blood analyzer, Spotchem SP-4410 (SP-4410) in a veterinary clinic for analysis of bovine and equine blood chemistry was studied. We quantitated total protein (TP), albumin (Alb), total bilirubin (T-Bil), blood urea nitrogen (BUN), total cholesterol (T-Cho), glucose (Glu), calcium (Ca), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatinine phosphokinase (CPK), and alkaline phosphatase (ALP) in bovine sera. Each sample was assayed with both the SP-4410 and an automated blood analyzer which served as a wet-chemistry reference system, and the data were analyzed with regression analysis. The correlation coefficient for AST was 0.997 being the highest for all the parameters, and all the correlation coefficients were 0.93 or higher. The coefficients of variation were lower than 5.0 except in the case of bovine T-Bil where it was 5,756. The ranges of normal reference values measured by SP-4410 were the same as those reported by other investigators in most cases, but those for GGT and CPK were slightly higher. The strongest interference was observed with hemoglobin. It seems that dry-chemical-analysis of blood serum using the SP-4410 is useful for analysis of bovine and equine blood.

Animals↗
PubMed1994

Relationship between age and drinking patterns and drinking problems among Japanese, Japanese-Americans, and Caucasians.

Comparing alcohol consumption patterns by age and gender among Japanese in Japan and Japanese-Americans and Caucasians in the United States, this study examined the associations between age and both heavy drinking and social problems using logistic regression for each ethnic group of male current drinkers. As reported in previous studies of Caucasians, men drink more alcohol than women, older respondents are more likely than younger ones to be abstainers, and the percentages of heavier drinkers and problem drinkers are higher among the young than among older people. Although Japanese-Americans reported consuming less alcohol than Caucasians, their drinking patterns by age were similar: among both United States populations, younger respondents are at higher risk for drinking problems than older respondents, even when alcohol consumption and sociodemographic variables are controlled by logistic regression. However, this association of age and drinking patterns and drinking problems is not universal. Japanese men consumed more alcohol and had a higher proportion of heavier drinkers in the middle age groups; the association between age and drinking problems also varied in this group. In addition to aging, sociocultural factors such as drinking norms probably account for the differences in drinking behavior among different age groups. This study may stimulate further cross-cultural comparison of drinking patterns and problems.

Acculturation↗
PubMed1994

Development of Babesia ovata in the salivary glands of the nymphal tick, Haemaphysalis longicornis.

The development of Babesia ovata in the salivary glands of nymphal Haemaphysalis longicornis ticks was morphologically studied for 4 days of feeding of tick on rabbits. Babesia ovata 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.

Animals↗