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Biomedical subjects

S Takami

Publications and source records attributed to S Takami.

At least 19 recordsLinked to original sources
PubMed2000

Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA.

To elucidate the sites of and mechanisms of analgesic effect of centrally injected calcitonin, we examined expression of calcitonin receptor mRNA in the mouse brain by in situ hybridization techniques. Calcitonin receptor mRNA was expressed in various brain regions, including the preoptic area, dorsomedial hypothalamic nucleus, lateral hypothalamic area, periaqueductal gray, dorsal raphe nucleus, locus coeruleus, lateral parabrachial nucleus, gigantocellular reticular nucleus alpha part, lateral paragigantocellular nucleus, raphe magnus nucleus and solitary tract nucleus, which are known to play important roles in pain modulation. In addition, a double in situ hybridization technique demonstrated the intense expression of calcitonin receptor mRNA on serotonergic neurons in some raphe nuclei and the lateral paragigantocellular nucleus, suggesting the involvement of central serotonergic pathways in analgesic effect of calcitonin.

Animals↗
PubMed2000

Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure.

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Adult↗
PubMed2000

Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama study.

The polymorphism of the angiotensin-converting enzyme gene is considered to be associated with increased risk for stroke, but there is a diversity in the results obtained. The genetic involvement of the renin-angiotensin system in stroke also remains unclear. To predict the genetic risk of lacunar infarction, we conducted an association study in an Ohasama population, which is the cohort in a rural region of northern Japan. A total of 134 subjects without major neurological, cardiovascular, or metabolic disorders were recruited. Using brain magnetic resonance imaging, the number of lacunae in each of four brain regions were calculated, and periventricular hyperintensity was classified into five grades. We used the following four candidate gene polymorphisms: angiotensin converting enzyme (ACE)/Insertion(I)-Deletion(D), angiotensinogen (AGT)/M235T, angiotensin II type 1 receptor (AT1)/ A1166C, type 2 receptor (AT2)/C3123A, to examine the association between polymorphisms and the severity of lacunar infarction. AGT/M235T was significantly associated with the number of lacunae in the brain stem, the basal ganglia (P < .05), and whole brain (P < .005) regions. The AT1 polymorphism was also significantly associated with the number of lacunae in the basal ganglia and whole brain regions (P < .05), and with periventricular hyperintensity grade (P < .005) in the younger population. However, ACE and AT2 polymorphisms failed to show an association with either the number of lacunae or the PVH grade. We concluded that AGT and AT1 polymorphisms are independent genetic risk factors for lacunar infarction.

Aged↗
PubMed1999

Structural organization of the 5'-end and chromosomal assignment of human placental leucine aminopeptidase/insulin-regulated membrane aminopeptidase gene.

Placental leucine aminopeptidase (P-LAP) which is identical with cystine aminopeptidase as oxytocinase was found to be a homologue of rat insulin-regulated membrane aminopeptidase (IRAP) by cDNA cloning. In this study, we confirmed 5'-end cDNA sequence of P-LAP and isolated genomic clones containing the upstream region of human P-LAP gene. The transcription initiation sites determined by primer extension located 478 and 480 bp upstream of the initiation methionine codon, 38 bp downstream of TATA box-like motif. The 5'-flanking region of human P-LAP gene contained DNA-binding motifs for several ubiquitous transcription factors such as SP1 and AP2. Chromosomal localization by fluorescence in situ hybridization showed that the gene was assigned to 5q14.2-q15 of the human chromosome. This study establishes the genetic basis for P-LAP gene research, thereby leading to better understanding of the molecular mechanism underlying the P-LAP gene.

Aminopeptidases↗
PubMed1999

Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure.

OBJECTIVE: Endothelial nitric oxide exerts important effects on the regulation of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hypertension. To examine whether the region encoding the eNOS gene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population. DESIGN: In healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotypes, with both parametric and non-parametric and single-locus and multi-point methods. METHODS: We selected 260 families comprising mother and father (aged 40-70 years) and two natural offspring (aged 18-30 years) from the Victorian Family Heart Study. After standardized measurement of clinical data and extraction of DNA, all family members were genotyped at five microsatellite loci including the CA repeat in the eNOS gene by a PCR method. The quantitative linkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS. RESULTS: With both linkage analyses, we found no linkage between any of the loci on chromosome 7q35-36 and the phenotypes systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, pulse rate, weight, height and body mass index. CONCLUSION: Based on these results, we conclude that in this population the eNOS gene is not linked to the physiological variation of blood pressure and other related phenotypes.

Adult↗
PubMed1999

Linkage analysis of glucocorticoid and beta2-adrenergic receptor genes with blood pressure and body mass index.

Glucocorticoids and catecholamines exert important effects on cardiovascular physiology and metabolism. Variants of the glucocorticoid receptor gene (GRL) and the beta2-adrenergic receptor gene (ADRB2) have been associated with high blood pressure and obesity. These genes are close on human chromosome 5q31-5q32, and we undertook a linkage analysis of this region in 264 families from the general population in relation to systolic and diastolic blood pressure, body mass index, weight, height, and pulse rate. All family members were genotyped at four microsatellite loci (D5S207, D5S210, D5S519, and D5S119) located on chromosome 5q31-5q33.3. Using quantitative identity-by-descent sibling pair linkage analysis, we found that at no loci was genetic similarity associated with phenotypic similarity for systolic and diastolic blood pressure, body mass index, weight, height, or pulse rate. Although it is not possible to exclude the influence of specific combinations of certain GRL and ADRB2 polymorphisms, the absence of significant linkage in our population argues against a role for GRL or ADRB2 in physiological variation of blood pressure and body mass index.

Adult↗
PubMed1999

[Detection of TT virus in healthy volunteer].

A novel DNA virus, TT virus(TTV), has been reported in Japanese patient with non A to G posttransfusion hepatitis. We sought to determine whether TTV infection occurs in healthy volunteer, and to compared with DNA extraction methods and polymerase chain reaction(PCR) primer for TTV in diagnostic system. Using a nested PCR assay, serum sample of healthy volunteer serve our laboratory in Japan were examined for the presence of TTV DNA. Twenty of 90(22%) healthy volunteer were detected to have TTV sequences in their serum. Also, we found that DNA extraction methods with a modified phenol-chloroform method. Our result suggested that detection of TTV DNA are high ratio of adults in Japan and were necessary to take care of selected using diagnostic systems.

Adult↗
PubMed1999

[Detection of numerical aberrations in chromosomes by fluorescence in situ hybridization in fine needle aspirates in the preoperative diagnosis of cancer].

Fine needle aspiration (FNA) samples were obtained from 176 breast tumors suspected of malignancy, which were then subjected to conventional cytological and fluorescence in situ hybridization (FISH) analyses using the centromeric probes for chromosomes 1, 11, and 17. Histological examination revealed 157 breast cancers and 19 benign diseases (ten fibroadenomas, six intraductal papillomas, one intracystic papilloma, and two ADH). Sensitivity, specificity, and diagnostic accuracy were 85.4% 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. These results demonstrate that FISH diagnosis of FNA samples has a diagnostic accuracy comparable to that of conventional cytology.

Biopsy, Needle↗
PubMed1998

A hyperalgesic effect of intracerebroventricular cytokine-induced neutrophil chemoattractant-1 in the rat paw pressure test.

Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a member of the chemokine superfamily. The effect of intracerebroventricular (i.c.v) injection of CINC-1 on the mechanical nociceptive threshold in the rat was examined using the paw-pressure test. An i.c.v. injection of CINC-1 at doses of 1 and 10 pg/rat tended to decrease the nociceptive threshold for mechanical stimuli at 15 min after the injection, and significantly lowered the threshold at 30 min. The threshold stayed at these lowered level over 180 min after the injection. Lower (100 fg/rat) and higher (30 and 100 pg/rat, and 1 and 10 ng/rat) doses of CINC-1 had no effect on the mechanical nociceptive threshold. The present results suggest that CINC-1 facilitates mechanical nociception in the central nervous system (CNS).

Animals↗
PubMed1998

Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells.

The expression of the mRNAs for stromal cell-derived factor-1alpha and -1beta (SDF-1alpha and -1beta) and their receptor CXCR4 in cultured rat glial and neuronal cells was examined. SDF-1alpha mRNA was expressed intensely in astrocytes and weakly in neurons, but not in microglia. SDF-1beta mRNA was expressed weakly in these three types of cells. The expressions of SDF-1alpha and -1beta mRNAs in astrocytes were decreased by treatment with LPS (100 ng/ml) for 1-6 h but markedly increased by that for 24-72 h, whereas the expression of SDF-1beta mRNA in microglia was hardly changed by the treatment for 0.5-6 h, and was decreased by that for 24-48 h. The expression of CXCR4 mRNA was observed in astrocytes, microglia and neurons, and was not altered by LPS treatment.

Animals↗
PubMed1998

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Amino Acid Sequence↗
PubMed1998

Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells.

BACKGROUND: We reported an increase in serum lipoprotein(a) [Lp(a)] levels in patients with thromboangiitis obliterans, suggesting that Lp(a) could also contribute to the pathogenesis of cardiovascular diseases by a mechanism different from atherosclerosis. Adhesion molecules were shown to contribute to the development of not only atherosclerotic but also inflammatory vascular diseases. METHODS AND RESULTS: We evaluated the effect of Lp(a) on the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in human umbilical vein endothelial cells by a cell ELISA. Lp(a) dramatically enhanced the levels of ICAM-1 in a dose-dependent manner. A discernible increase in ICAM-1 expression was observed at a physiological concentration of 0.26 mmol cholesterol/L Lp(a) after 48-hour incubation. A 1.8-fold increase in ICAM-1 expression was observed 48 hours after the addition of Lp(a) (1.04 mmol cholesterol/L). Northern blot analysis demonstrated that the amount of ICAM-1 mRNA was increased after treatment with Lp(a). In contrast to ICAM-1, the expression of VCAM-1 and E-selectin was not significantly affected by Lp(a). Lp(a-) [apolipoprotein(a)- removed Lp(a) by reduction with dithiothreitol] and LDL had no significant effect on the expression of ICAM-1. In contrast, recombinant apolipoprotein(a) protein alone significantly enhanced ICAM-1 expression. Lp(a) decreased the level of active transforming growth factor (TGF)-beta in the conditioned medium. Furthermore, recombinant TGF-beta significantly decreased the Lp(a)-induced ICAM-1 expression. These findings suggested that Lp(a) may enhance the ICAM-1 expression by decreasing active TGF-beta level. CONCLUSIONS: Lp(a) could contribute to the development of cardiovascular diseases by enhancing the expression of ICAM-1 in endothelial cells.

Antibodies↗
PubMed1998

A novel vascular modulator, hepatocyte growth factor (HGF), as a potential index of the severity of hypertension.

HGF (hepatocyte growth factor), a member of endothelium-specific growth factors, might contribute to protection and/or repair of vascular endothelial cells injured by high blood pressure (BP). If so, serum HGF level might be elevated in response to endothelial cell damage. To test this hypothesis, we measured serum levels of HGF in hypertensive and normotensive patients. Serum HGF concentration in hypertensive patients without any complication was significantly higher than normal subjects (p < 0.001). Serum HGF concentration showed a significant positive correlation with BP (p < 0.01). Interestingly, serum HGF concentration in hypertensive patients with complications was significantly higher than that in hypertensive patients without complication and normotensive subjects (p < 0.01). Of importance, hypertensive patients treated with antihypertensive drugs showed the same level of serum HGF concentration as normotensive subjects (p < 0.001). The present study demonstrated that serum concentration of HGF is significantly elevated dependent on the severity of hypertension, suggesting that HGF may be a new index of the severity of hypertension.

Antihypertensive Agents↗
PubMed1998

High concentration of glucose induces the expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells.

Atherosclerosis is known to be accelerated in patients with diabetes mellitus. We have examined the effect of glucose on the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and the adhesion of cells of monocyte-like cell line, THP-1, to HUVEC. HUVEC exposed to a high glucose concentration (16.7 mM) showed a 1.4-fold increase in the adhesion of THP-1 cells and a 1.3-fold increase in cell surface expression of ICAM-1 after 6 h exposure compared with those cultured in medium with a low glucose concentration (5.6 mM). ICAM-1 expression began to increase after 3 h exposure, was maximal at 6 h and gradually decreased afterwards. At 16.7 mM, raffinose stimulation produced a significantly lower expression of ICAM-1 on HUVEC than glucose, furthermore it caused a significantly lower expression than low glucose stimulation (5.6 mM). We conclude that a high concentration of glucose can induce ICAM-1 in endothelial cells and that this effect may play an important role in atherogenesis in patients with diabetes mellitus.

Cell Adhesion↗
PubMed1998

Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension.

A genetic epidemiologic approach is useful to elucidate the genes responsible for hypertension. Genetic analyses of the components of the renin-angiotensin system have succeeded in showing an association between their polymorphism and hypertension. Recently, two types of angiotensin II receptor were cloned and characterized. To examine the genetic contribution of angiotensin II type 1 receptor (AT1) and type 2 receptor (AT2) genes in human essential hypertension, a case-control study was performed in Japanese subjects. The study comprised 321 subjects with hypertension who satisfied the criteria for essential hypertension, together with 215 age and sex matched controls. The significance of the differences in genotype distribution between hypertensive and normotensive subjects was examined by chi2 analysis. Neither AT1 nor AT2 gene variants were associated with human essential hypertension in the Japanese subjects. However, the AT1 receptor gene polymorphism was associated with left ventricular mass index in normotensive subjects. The study results suggest that gene polymorphisms of both angiotensin II receptors are not directly involved in the increase of genetic risk for hypertension, but that the AT1 receptor gene might contribute genetically to the increase of left ventricular mass.

Aged↗
PubMed1998

No association between alpha-adducin 460 polymorphism and essential hypertension in a Japanese population.

Many unknown genetic factors are involved in the pathogenesis of hypertension. Recently, the reverse genetic approach revealed that some genetic variants, such as angiotensinogen, lipoprotein lipase, and alpha-adducin gene polymorphisms, increase the risk for hypertension. Both in rat and human, the genetic predisposition to hypertension was confirmed only for angiotensinogen and alpha-adducin genes. Adducin is a membrane cytoskeletal protein, which is thought to regulate sodium transport. Abnormalities of membrane sodium transport in the kidney play an important role in hypertension. A recent report by Cusi et al showed that the Trp allele of alpha-adducin polymorphism (Gly 460 Trp) is associated with an increased risk of hypertension in whites, which led us to carry out a case-control study to examine whether the same association is observed in the Japanese population. We recruited 170 hypertensive and 194 normotensive Japanese subjects and compared the genotype distribution of alpha-adducin 460 polymorphism between cases and controls and between whites and Japanese. Trp allele frequency of controls in the Japanese subjects was twice as high as in the whites. However, no association was observed between alpha-adducin polymorphism and hypertension. Furthermore, alpha-adducin 460 polymorphism was not associated with any clinical characteristics. Accordingly, we concluded that alpha-adducin 460 polymorphism is not a major genetic risk for hypertension in Japanese people.

Alleles↗
PubMed1998

Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease.

Hyperhomocysteinemia is reported to be associated with an increase in the incidence of ischemic heart disease and cerebrovascular disease. Genetic aberrations in methylenetetrahydrofolate reductase (MTHFR) may account for reduced enzyme activity and elevated plasma homocysteine level. A recent report revealed that a common mutation (677C to T; Ala to Val) in the MTHFR gene is associated with decreased specific MTHFR activity and with increased risk for coronary artery disease in the homozygous state (Val/Val). In the present study, we investigated whether the MTHFR gene is a genetic risk factor for cerebrovascular disease (CVD). To undertake a case-control study, we selected the patients with cerebral infarction (n = 48) or cerebral hemorrhage (n = 35) and examined the association between MTHFR gene polymorphism and CVD. The genotype distribution of the MTHFR gene was not significantly different between cases and controls. Because the possibility of matching the morbidity of the effects of hypertension, the lack of association could not be excluded in the first study; however, we also examined whether the MTHFR mutation was associated with any clinical risk factor for CVD or with hypertension. It turned out that the subjects with the Val allele of the MTHFR gene had significantly lower blood pressure than the subjects with other genotypes in the general population (P = .02), and that the frequency of the Val/Val genotype in hypertensive subjects (n = 173) was significantly lower than in control subjects (n = 184) (P = .03). From these results, we conclude that the Val/Val homozygous state of the MTHFR gene increased the risk of thrombosis, but reduced the blood pressure, which resulted in the lack of increased risk for CVD.

Cerebrovascular Disorders↗