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Biomedical subjects

M Hirai

Publications and source records attributed to M Hirai.

At least 91 records · Page 5Linked to original sources
PubMed2000

Comparative FISH mapping of the ancestral fusion point of human chromosome 2.

It is known that human chromosome 2 originated from the fusion of two ancestral primate chromosomes. This has been confirmed by chromosome banding and fluorescence in-situ hybridization (FISH) with human chromosome-2-specific DNA libraries. In this study, the order of 38 cosmid clones derived from the human chromosome region 2q12-q14 was exactly determined by high-resolution FISH in human chromosome 2 and its homologous chromosomes in chimpanzees (Pan trogrodydes, 2n=48) and cynomolgus monkeys (Macacafascicularis, 2n = 42). This region includes the telomere-to-telomere fusion point of two ancestral ape-type chromosomes. As a result of comparative mapping, human chromosome region 2q12-q14 was found to correspond to the short arms of chimpanzee chromosomes 12 and 13 and cynomolgus monkey chromosomes 9 and 15. It is noted that no difference was detected in the relative order of the cosmid clones between human and chimpanzee chromosomes. This suggests that two ancestral ape-type chromosomes fused tandemly at telomeres to form human chromosome 2, and the genomic organization of this region is thought to be considerably conserved. In the cynomolgus monkey, however, the order of clones in each homologue was inverted. In addition to cosmid mapping, two chromosome-2-specific yeast artificial chromosome (YAC) clones containing the fusion point were identified by FISH.

Animals↗
PubMed2000

Prevalence and characteristics of muscle cramps in patients with varicose veins.

BACKGROUND: It has been suggested that limb circulation may be disturbed in patients with muscle cramps due to leg venous hypertension. The aim of this study was to examine the incidence and characteristics of muscle cramps from venous insufficiency. PATIENTS AND METHODS: The incidence and characteristics of muscle cramps, which were investigated by a questionnaire, were compared between 288 patients with incompetence of the long or short saphenous vein and 550 age-matched individuals from the general population. RESULTS: The patient group showed a significantly higher incidence of muscle cramps in the last year than the general population group, 67% and 53%, respectively (p < 0.001). The incidence of calf cramps was significantly higher in the patient group than in the general population group, 91% and 75%, respectively (p < 0.001). Although most subjects reported symptoms occurring only at night, the incidence was significantly higher in the patient group than in the general population group, 78% and 52%, respectively (p < 0.001). There was no significant difference in the duration or severity of muscle cramps between the groups. The patient group showed a significantly higher incidence of more than 12 episodes per year than the general population group (p < 0.001). CONCLUSIONS: Muscle cramps in patients with varicose veins occur more frequently and more often at night and in the calf in comparison with those from the general population.

Adult↗
PubMed2000

Teratocarcinosarcoma of the nasal cavity. Report of a case showing favorable prognosis.

We report a very rare case of teratocarcinosarcoma of the nasal cavity showing a favorable prognosis. The patient was a 66-year-old man with a mass completely obstructing the right nasal cavity. Subsequently, extirpation of the mass and Denker-Watsuji operation were performed, and the patient was treated with a combination of radiation therapy and chemotherapy. Neither recurrence nor distant metastasis was observed during follow-up lasting 30 months. Histologic examination of the resected mass revealed several tissue elements including columnar and squamous epithelia with atypia, smooth muscle cells with rare mitotic activity, and neuroectodermal tissue. The glandular epithelium and smooth muscle cells were reminiscent of a primitive intestinal organoid structure, suggestive of teratomatous tumorigenesis. Our case and a review of the literature indicate that the absence of invasiveness to the stroma or surrounding tissue is closely related to a favorable prognosis.

Aged↗
PubMed2000

Purging of human breast cancer cells from stem cell products with an adenovirus containing p53.

Tumor cell contamination of stem cell products can contribute to tumor relapse following high-dose chemotherapy and stem cell rescue. Numerous techniques have been used to remove the tumor cells from stem cell products with the objective of prolonging relapse-free survival. However, to date these techniques have been relatively ineffectual and/or toxic to hematopoietic stem and progenitor cells. The differential infectivity of adenovirus (Adv) vectors for breast cancer cells, compared with hematopoietic cells, has suggested that Adv-p53 might provide an effective purging strategy. To facilitate the use of Adv-p53 as a clinical strategy, we undertook studies to determine the parameters necessary for optimal stem cell product purging. The parameters studied were the particle number to nucleated cell ratio, the duration of coincubation, the incubation volume, and the presence or absence of hematopoietic progenitor cells. We have found that these parameters are interdependent and conclude that a 4-hour coincubation with an Adv-p53 particle to nucleated cell ratio of 2000:1 with 2 x 10(8) nucleated cells/mL is optimal for tumor cell purging. Furthermore, this appeared to be a safe procedure, with total loss of clonogenic growth of breast cancer cells as well as no significant effect on progenitor cell function as determined by granulocyte-macrophage colony-forming unit assays.

Adenoviridae↗
PubMed2000

Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder.

A high association between type 2 diabetes mellitus and depressive illness has been reported. Insulin resistance during depressive illness might contribute to the linkage between depression and type 2 diabetes. To determine whether the genetic polymorphisms of the tyrosine hydroxylase ([TH] HUMTH01) and insulin (INS-VNTR) genes contribute to insulin resistance in depressive illness, we analyzed the association between the polymorphisms and insulin resistance in 41 Japanese patients with depressive disorder, 204 normal control subjects, 161 cohort subjects with normal glucose tolerance (NGT) and without depressive symptomatology, and 59 NGT subjects with depressive symptomatology. The depressive patients had a significantly lower insulin sensitivity index (SI) than the control subjects (P= .016). Depressive NGT subjects had a significantly higher homeostasis model assessment (HOMA) insulin resistance index [HOMA(R)] than the nondepressive NGT subjects (P < .0001). The depressive patients and NGT subjects had more HUMTH01 allele 7 (TH7) than the controls and nondepressive NGT subjects. SI was significantly lower in patients with the TH7/7 homozygote versus patients with the other genotypes and the controls. TH7 was associated with higher HOMA(R) as compared with the other alleles in the NGT subjects. Insulin resistance was associated with depressive disorders. The HUMTH01 and INS-VNTR were associated with insulin resistance and depressive symptoms.

Adult↗
PubMed2000

Haemodynamic evaluation of cerebral arteriovenous malformations by quantification of transit time using high speed digital subtraction angiography: basic considerations.

It is important to evaluate the haemodynamics of cerebral arteriovenous malformations (AVMs) in order to predict and avoid complications following surgical intervention. This study measured the transit time of each component of AVMs by high-speed digital subtraction angiography (DSA) to understand the haemodynamics and to evaluate which parameter is an appropriate indicator for the monitoring. Eleven cases of cerebral AVMs were studied. Haemodynamics were evaluated by analysis of tracer transit using DSA. Tracer transit parameters including transit time and peak time were calculated by application of gamma fitting to time density curve, and measured in the following compartments; feeding artery, nidus and draining vein. Significant correlations of tracer transit parameters were present among compartments. Although there was no significant correlation of nidus volume and tracer transit parameters, the peak time was shorter in haemorrhage cases than in non-haemorrhage cases. Measurements of tracer transit parameters by high-speed DSA may be a useful tool for characterising and monitoring the haemodynamics of AVMs following surgical intervention.

Adolescent↗
PubMed2000

Suppression of cellular immunity by surgical stress.

BACKGROUND: Suppression of cellular immunity is one of the host responses to surgical stress. In cancer patients this immunosuppression may accelerate the growth and metastasis of residual cancer cells, so it is desirable to restrict immunosuppression by surgical stress to a minimum. However, the extent and duration of immunosuppression caused by operations on gastrointestinal cancer, as well as the mechanisms involved, have not been determined. METHODS: To clarify these points, we investigated immunocyte function and measured the blood levels of hormones, cytokines, and acute phase reactants from before to after operation in 20 patients with stage I gastrointestinal cancer. RESULTS: In patients exposed to surgical stress, peripheral blood lymphocyte numbers and function were suppressed until at least 2 weeks postoperatively. This immunosuppression was mainly due to a decrease of helper-inducer T cells, cytotoxic T cells, natural killer cells, and interleukin-2 receptor-positive cells, as well as an increase of suppressor T cells. In addition, hypersecretion of cortisol and overproduction of immunosuppressive acidic protein were observed. CONCLUSIONS: Cellular immunosuppression by surgical stress was mainly due to an increase of lymphocyte subsets that depress cellular immunity coupled with a decrease of the subsets that promote it. Overproduction of cortisol and immunosuppressive acidic protein in response to surgical stress may play an important role in the development of immunosuppression.

Acute-Phase Proteins↗
PubMed2000

Acute effects of a single low oral dose of pimobendan on left ventricular systolic and diastolic function in patients with congestive heart failure.

A recent long-term multicenter trial has shown that pimobendan is more effective when administered in low doses. However, no data are available concerning the effect of a low dose of pimobendan on the systolic and diastolic pressure-volume relations in patients with heart failure. Therefore we examined the effects of a single low dose of oral pimobendan, a calcium sensitizer, on systolic and diastolic hemodynamics in patients with cardiomyopathy and congestive heart failure. We measured the left ventricular (LV) pressure-volume relations using a conductance catheter with a micromanometer tip in 10 patients with chronic congestive heart failure resulting from idiopathic cardiomyopathy before and 45 and 90 min after administration of a single oral dose of 2.5 mg of pimobendan. End-systolic elastance was used as an index of LV contractility and was measured during transient occlusion of the inferior vena cava. End-systolic elastance increased significantly by 25% at 45 min (p < 0.05) and by 55% at 90 min (p < 0.01) without an increase in myocardial oxygen consumption. The inotropic effect was accompanied by improved ventriculoarterial coupling. This effect was attenuated in patients with severely impaired myocardial contractility. LV relaxation, assessed by the time constant of isovolumic pressure decay (T(1/2)), was significantly shortened at 90 min (from 47.7 +/- 1.9 to 41.2 +/- 1.7 ms; p < 0.01), although it remained unchanged at 45 min. The diastolic pressure-volume relation showed a leftward and downward shift in all patients. These results indicate that low-dose oral pimobendan had favorable short-term inotropic and lusitropic effects in patients with congestive heart failure caused by idiopathic dilated cardiomyopathy, and may thus be a useful alternative to traditional agents. Further study in a large-scale trial is merited.

Administration, Oral↗
PubMed2000

Comparative genome analysis of the mouse imprinted gene impact and its nonimprinted human homolog IMPACT: toward the structural basis for species-specific imprinting.

Mouse Impact is a paternally expressed gene encoding an evolutionarily conserved protein of unknown function. Here we identified IMPACT, the human homolog of Impact, on chromosome 18q11. 2-12.1, a region syntenic to the mouse Impact locus. IMPACT was expressed biallelically in brain and in various tissues from two informative fetuses and in peripheral blood from an informative adult. To reveal the structural basis for the difference in allelic expression between the two species, we elucidated complete genome sequences for both mouse Impact ( approximately 38 kb) and human IMPACT ( approximately 30 kb). Sequence comparison revealed that the two genes share a well-conserved exon-intron organization but bear significantly different CpG islands. The mouse island lies in the first intron and contains characteristic tandem repeats. Furthermore, this island serves as a differentially methylated region (DMR) consisting of a hypermethylated maternal allele and an unmethylated paternal allele. Intriguingly, this intronic island is missing from the nonimprinted human IMPACT, whose sole CpG island spans the first exon, lacks any apparent repeats, and escapes methylation on both chromosomes. These results suggest that the intronic DMR plays a role in the imprinting of Impact.

Alleles↗
PubMed2000

Efficient production of artificially designed gelatins with a Bacillus brevis system.

Artificially designed gelatins comprising tandemly repeated 30-amino-acid peptide units derived from human alphaI collagen were successfully produced with a Bacillus brevis system. The DNA encoding the peptide unit was synthesized by taking into consideration the codon usage of the host cells, but no clones having a tandemly repeated gene were obtained through the above-mentioned strategy. Minirepeat genes could be selected in vivo from a mixture of every possible sequence encoding an artificial gelatin by randomly ligating the mixed sequence unit and transforming it into Escherichia coli. Larger repeat genes constructed by connecting minirepeat genes obtained by in vivo selection were also stable in the expression host cells. Gelatins derived from the eight-unit and six-unit repeat genes were extracellularly produced at the level of 0.5 g/liter and easily purified by ammonium sulfate fractionation and anion-exchange chromatography. The purified artificial gelatins had the predicted N-terminal sequences and amino acid compositions and a solgel property similar to that of the native gelatin. These results suggest that the selection of a repeat unit sequence stable in an expression host is a shortcut for the efficient production of repetitive proteins and that it can conveniently be achieved by the in vivo selection method. This study revealed the possible industrial application of artificially designed repetitive proteins.

Amino Acid Sequence↗
PubMed2000

Molecular cloning and characterization of a mouse homolog of human TNFSF14, a member of the TNF superfamily.

A member of the tumor necrosis factor (TNF) superfamily, human TNFSF14 (hTNFSF14)/HVEM-L (herpes virus entry mediator ligand) was isolated as a cellular ligand for HVEM/TR2 and human lymphotoxin beta receptor (LTbetaR). TNFSF14 induces apoptosis and suppresses tumor formation. We have isolated a cDNA clone for a mouse homologue of hTNFSF14 by signal sequence trap (SST) screening which we recently developed. The deduced amino acid sequence of the mouse TNFSF14 (mTNFSF14) cDNA comprised 239 amino acid residues and was 77% identical to the hTNFSF14 protein. In Northern blot analysis, 2.1 kb and 4.2kb mTNFSF14 transcripts were detected in spleen and lung, and in heart, respectively. Fluorescence in situ hybridization analysis localized the mTNFSF14 gene Tnfsf14 to chromosome 17 which is tightly linked with Tnf, Lta, and Ltb.

Amino Acid Sequence↗
PubMed2000

Cloning, expression analysis and chromosome mapping of human casein kinase 1 gamma1 (CSNK1G1): identification of two types of cDNA encoding the kinase protein associated with heterologous carboxy-terminal sequences.

Casein kinase 1 gamma1(CK1 gamma1) is known to be involved in the growth and morphogenesis of eukaryotic cells. We have isolated two types of cDNA for human casein kinase 1 gamma1 (hCK1 gamma1). One of them (hCK1 gamma1S) was found to encode a polypeptide consisting of 393 amino acids, which is highly homologous with already reported rat CK1 gamma1 (rCK1 gamma1). The other type of cDNA (hCK1 gamma1L) encodes a polypeptide consisting of 422 amino acids, which is quite identical in the kinase domain, but different in the C-terminal sequence from hCK1 gamma1S. Namely, hCK1 gamma1L has a characteristic sequence of 50 amino acids at the C-terminal end and this motif was shown to be shared by the casein kinase gamma2 and gamma3 from rat and human, suggesting that it is a signature sequence of the gamma-isoforms. In this sense, newly isolated hCK1 gamma1L might be the original form of CK1 gamma1 subspecies rather than rCK1 gamma1 and hCK1 gamma1S. RT-PCR analysis revealed that hCK1 gamma1S mRNA is predominantly present in the testis, whereas the abundance of hCK1 gamma1L mRNA was nearly the same in the twelve tissues examined. These results suggest that novel hCK1 gamma1L may have a unique functional role different from that of hCK1 gamma1S and rCK1 gamma1. The human hCK1 gamma1 gene (CSNK1G1) was mapped to chromosome 15q22.1-->q22.31 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed2000

Neointima formation in a restenosis model is suppressed in midkine-deficient mice.

Neointima formation is a common feature of atherosclerosis and restenosis after balloon angioplasty. To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation. MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery. Neointima formation in a restenosis model was strongly suppressed in MK-deficient mice. Continuous administration of MK protein to MK-deficient mice restored neointima formation. Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice. Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro. These results indicate that MK plays a critical role in neointima formation at least in part owing to its ability to mediate leukocyte recruitment.

Angioplasty, Balloon↗
PubMed2000

Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance.

The locus of the vitamin D-binding protein (DBP; also known as group-specific component protein or Gc) gene, chromosome 4q12, has been reported to be associated with glucose metabolism in several ethnic groups, including Pima Indians. We have recently reported the association of the DBP genotype with type 2 diabetes mellitus in Japan. The aim of this study was to investigate whether genetic variations of DBP have any influence on glucose metabolism without secondary effects of hyperglycemia or diabetes mellitus using 82 Japanese with normal glucose tolerance. The variations of the DBP gene (Gc 1F, 1S, and 2) were determined by PCR-restriction fragment length polymorphism. Fasting plasma insulin concentration and homeostasis model assessment, an index of insulin resistance, were significantly different based on the DBP genotype (P < 0.01 and P < 0.05, respectively). The people with Gc 1S-2 (5.73 +/- 2.57 microU/mL) and 1S-1S (5.30 +/- 3.46 microU/mL) had significantly higher fasting plasma concentrations than those with 1F-1F (2.84 +/- 1.67 microU/mL) (P < 0.01 and P < 0.03, respectively). There was no significant difference in plasma glucose concentration, body mass index, total cholesterol, triglyceride, and blood pressure. In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes.

Asian People↗
PubMed2000

Characterization and affinity purification of juvenile hormone esterase from Bombyx mori.

Juvenile hormone esterase (JHE) from hemolymph of the silkworm moth Bombyx mori was characterized for substrate specificity and inhibitor sensitivity. B. mori JHE hydrolyzed the juvenile hormone surrogate substrate methyl n-heptylthioacetothioate (HEPTAT) more efficiently than p-nitrophenyl acetate and 1-naphthyl acetate substrates widely used to assay total carboxylesterase activity. B. mori JHE was sensitive to 3-octylthio-1,1,1-trifluoro-2-propanone (OTFP), which was developed as a selective inhibitor for lepidopteran JHE, and relatively insensitive to diisopropyl fluorophosphate (DFP), an inhibitor of serine esterases but not of all JHEs. Affinity purification with a trifluoromethyl ketone ligand was more efficient for purification of B. mori JHE than DEAE ion exchange chromatography.

Acetates↗
PubMed2000

Comparison of vectorcardiographic and 12-lead electrocardiographic detections of abnormalities in repolarization properties due to preexcitation in patients with Wolff-Parkinson-White syndrome: proposal of a novel concept of a "remodeling gradient".

Repolarization abnormalities after radiofrequency ablation in patients with manifest Wolff-Parkinson-White syndrome (WPW) have been attributed to cardiac memory of pre-existing changes in repolarization properties. We compared spatial ventricular gradient (VG) from vectorcardiograms with QRST values of 12-lead ECG in 41 patients with WPW (group A, manifest WPW due to left-sided accessory pathway (n = 20); group B, manifest WPW due to right-sided accessory pathway (n = 12); group C, concealed WPW (n = 9)) before and after ablation. Group N (n = 607) served as control. In groups A and B, the abnormalities of spatial VG and QRST values of 12-lead ECG that existed before and 1 day after ablation significantly decreased 1 week after ablation. In group C, spatial VG and QRST values of 12-lead ECG showed no significant changes. The diagnostic ability of spatial VG is almost equivalent to that of the QRST value of ECG in detecting repolarization abnormalities in patients with WPW before and after ablation. We propose a new concept of a "remodeling gradient" directing from the preexcited area to the opposite side of the ventricle as a result of preexcitation-induced electrical remodeling.

Adolescent↗
PubMed2000

[RAPD-markers linked to the locus for resistance to the race 4 pathogen for black rot, Xanthomonas campestris pv. campestris (Pamm.) Dow., in Brassica rapa L].

Association between the RAPD markers and the resistance to race 4 of the black rot causative agent was studied in Brassica rapa L. Experiments were carried out using doubled haploid lines, obtained via crosses between the race 4-susceptible fodder turnip and resistant pak-choi, and the F2 progeny of the crosses between the doubled haploid lines with contrasting resistance. The WE(22)980 RAPD marker inherited from the pak-choi and associated with the clubroot susceptibility was also linked to the locus responsible for the resistance to race 4 of Xanthomonas campestris pv. campestris. The two other RAPD markers were linked to susceptibility to black rot. Simultaneous association of the same DNA markers with the resistance/susceptibility to two different obligate pathogens favored the hypothesis on cluster organization of the resistance genes in plants. The markers described can be used in plant breeding and in further investigation of the genetic bases of resistance in plants.

Base Sequence↗