A haplotype in the human Sur2 gene is associated with essential hypertension.
Explore the source record for details and available documents.
ATP-Binding Cassette Transporters↗
Biomedical subjects
M Soma
Publications and source records attributed to M Soma.
The microsatellite alleles on chromosome 1 associated with essential hypertension and blood pressure levels.
Essential hypertension (EH) is thought to be a polygenic disease. Several candidate genes of this disease have been investigated in studies using polymorphic genetic markers, but some studies have failed to show any association of EH with these genes. In this experiment, we used microsatellite markers on chromosome 1, and performed an association study between EH and control subjects. Genomic DNA was amplified with fluorescently labelled primers from the Applied Biosystems PRISM linkage mapping set HD-5 comprising 63 highly polymorphic microsatellite markers with an average spacing of 4.5 cM. We isolated three loci showing significant differences: D1S507, D1S2713 and D1S2842. The P-values of the allele with the greatest post hoc contributions in D1S507, D1S2713 and D1S2842 were 0.0008, 0.0062 and 0.0084, respectively. All these values were significant after Bonferroni correction. Furthermore, we found that the three microsatellite alleles were associated with the levels of systolic blood pressure. These data suggest that there are at least the three susceptibility loci for EH on chromosome 1, and that a case-control study using microsatellite markers on genomewide basis is a useful method for isolating the susceptibility loci of multifactorial disorders.
Alleles↗
Congenital arachnoid cyst mimicking meningocele.
The subject of this report is a rare case of a 5-year-old girl who developed an arachnoid cyst with a bony and dural defect in the parietal convexity. She had no history of head trauma or infection. Surgical exploration revealed the bulging lesion to consist of cerebrospinal fluid-containing spongy subcutaneous tissue and to extend into the bony and dural defect. The arachnoid cyst cavity was found beneath the subcutaneous lesion and was not connected to the adjacent subarachnoid space. Histologically, the subcutaneous tissue contained a complex of sinusoidal channels formed by an abundance of migrating arachnoidal cells, thus mimicking meningocele.
Arachnoid Cysts↗
Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease.
Serum amyloid P component (SAP) is a major acute-phase reactant in mice. Recently, it was reported that SAP-deficient mice spontaneously developed anti-nuclear antibodies and severe glomerulonephritis. Because the SAP-deficient mice we generated display no obvious phenotypic abnormalities, we investigated whether our SAP-deficient mice would also spontaneously develop autoimmune responses. In accordance with the report, our mice produced high titers of anti-nuclear antibody but did not develop severe glomerulonephritis. On the other hand, it was recently reported that SAP bound to gram-negative bacteria via lipopolysaccharide (LPS) prevented LPS-mediated activation of a classical complement pathway. Thus, we asked if SAP-deficient mice would show altered responses to an intraperitoneal injection of LPS from Salmonella typhimirium. SAP-deficiency did afford resistance to lethality induced by high-dose LPS. Our experiments clearly showed that contrary to documented data, SAP-deficient mice do not develop serious autoimmune disease and we suggest that SAP has a critical role in LPS toxicity.
Animals↗
Changes in Ca2+-dependent protein kinase C isoforms induced by chronic ethanol treatment in mice.
Protein kinase C (PKC) has been shown to regulate ethanol sensitivity. The goal of the present study was to ascertain whether chronic in vivo ethanol treatment could affect PKC isoforms in the mouse brain. We measured the protein level of membrane-bound PKC isoforms following chronic ethanol treatment using Western blotting. The protein level of membrane-bound PKCalpha and PKCgamma isoforms, which are defined as Ca2+-dependent PKC isoforms (cPKC), in the limbic forebrain during chronic ethanol treatment was significantly increased, whereas the levels of both were significantly decreased in the frontal cortex. By contrast, there was no change in PKCepsilon, a Ca2+-independent PKC isoform, in both areas. These findings suggest that the change in membrane-bound cPKC in the limbic forebrain and frontal cortex may play substantial roles for the development of ethanol dependence.
Alcohol-Induced Disorders, Nervous System↗
Polymorphism of the promoter region of prostacyclin synthase gene is not related to essential hypertension.
An impaired synthesis of prostacyclin has been implicated in the development of essential hypertension (EH). We therefore investigated whether there is an association between the prostacyclin synthase (PGIS) gene and EH using a variable number of tandem repeats (VNTR) polymorphism in the promoter region that influences transcriptional activity of this gene. A total of 125 patients with EH and 125 age-matched subjects with normal blood pressure were studied. The number of VNTR of the five alleles ranged from 3 to 7 repeats in the 250 unrelated Japanese subjects. The allele frequency distribution in the two groups were not significantly different. Thus, this VNTR polymorphism in the PGIS gene is not associated with EH.
Cytochrome P-450 Enzyme System↗
Systematic screening of type B human natriuretic peptide receptor gene polymorphisms and association with essential hypertension.
C-type natriuretic peptide (CNP) dilates arteries, lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the type B natriuretic peptide receptor (NPRB). The CNP-NPRB system may play a crucial role in the development of cardiovascular disease. We recently determined the structure of the human NPRB gene. In the present study, our objectives are to identify the polymorphisms of the NPRB gene and investigate the association of this gene with essential hypertension (EH). We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to study the NPRB gene polymorphism, and conducted an association study using a novel polymorphic marker. PCR-SSCP analysis of all 22 exons was done in 90 subjects, and abnormally-migrating bands were observed in the analyses of exon 11 and intron 18. Direct sequencing of these DNA fragments revealed the following sequence alterations: a C to T transition at nucleotide (nt) 2077 in exon 11 and a 9-bp insertion/deletion (I/D) in intron 18. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition. PCR-RFLP analyses of healthy subjects revealed that the C2077T polymorphism had complete linkage to GT repeats in intron 2 reported previously. The I/D polymorphism was identified by polyacrylamide gel electrophoresis, and it was not linked to any known polymorphic alleles of this gene. Therefore, the possible association between the I/D polymorphism and EH was investigated. A total of 123 individuals with EH and 123 age-matched normotensive control subjects were studied. Overall distributions of allele frequencies in the two groups were not significantly different. Although the I/D polymorphism in intron 18 of the NPRB gene was not associated with EH, the results of this study, which identified two novel polymorphisms in the human NPRB gene, will facilitate further genetic analysis of this gene and cardiovascular disease.
Adult↗
Protocol to prevent shoulder-hand syndrome after stroke.
OBJECTIVE: To determine the effectiveness of a protocol designed to restrict passive movement of affected upper extremity on the incidence of shoulder-hand syndrome (SHS) after stroke. DESIGN: Before-and-after trial: follow-up duration of subject group and historical control group 231.6 and 257.2 days, respectively. SETTING: Rehabilitation medicine department in a hospital in Japan. PARTICIPANTS SUBJECTS: 81 stroke patients treated with the protocol from 1994 to 1996 who were followed for at least 4 months from the onset of stroke; controls: 71 stroke patients treated without the protocol from 1991 to 1994 who were followed for same length of time. INTERVENTION: Use of a set protocol for controlled passive movement by trained therapists and restriction of passive movement by the patients for 4 months after stroke. The SHS criterion used to detect early signs of SHS has not yet been validated. Corticosteroids were given to all subjects diagnosed with SHS. MAIN OUTCOME MEASURES: Swelling index, SHS diagnostic criteria applied in physical exam, Brunnstrom stage, and sensory disturbance evaluations. RESULT: The incidence of SHS in the subject group was 18.5% (n = 15), whereas the incidence of SHS in the control group was 32.4% (n = 23). The difference between the 2 groups was statistically significant (chi(2) = 3.885, p < .05). CONCLUSION: The protocol helped to prevent development of SHS.
Chi-Square Distribution↗
Association study between the variants of the human ANP gene and essential hypertension.
Variants of atrial natriuretic peptide (ANP) are reported to be more common in blacks with hypertension than in normotensive controls and constitute an independent risk factor for cerebral infarction. The purpose of the present study was to investigate the role of ANP in the pathogenesis of essential hypertension (EH) in the Japanese. We investigated 2 previously reported ANP gene markers, G1837A and T2238C, for their possible associations with EH. A total of 233 individuals with EH and 213 age-matched normotensive (NT) control subjects were studied. The frequencies of the G and A alleles were 0.09 (42/466) and 0.91 (424/466), respectively, for the NT group and 0.11 (47/426) and 0.89 (379/426), respectively, for the EH group. These frequencies did not differ significantly between the two groups. The frequencies of the T and C alleles were 0.024 (11/466) and 0.97 (455/466), respectively, for the NT group and 0.03 (13/426) and 0.97 (413/426), respectively, for the EH group. These frequencies also did not differ significantly between the two groups. Neither G1837A nor the T2238C polymorphism of the ANP gene was associated with EH. Our findings do not support the hypothesis that the G1837A and T2238C polymorphisms of the ANP gene are markers for EH in the Japanese.
Adult↗
A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia.
Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.
Adult↗
Implications of the NR2B subunit-containing NMDA receptor localized in mouse limbic forebrain in ethanol dependence.
The present study was designed to further investigate the direct involvement of the NR2B-containing NMDA receptor in ethanol dependence. Using the liquid diet method, mice were chronically treated with skimmed milk containing 5% ethanol for 5 days. After the discontinuation of ethanol, mice revealed tremor, handling-elicited convulsion and death. Treatment with a selective NR2B-containing NMDA receptor antagonist, ifenprodil, significantly suppressed the expression of ethanol withdrawal signs. The protein level of NR2B subunits in the limbic forebrain, but not the cerebral cortex, during chronic ethanol treatment was markedly increased with respect to the levels in control mice. The significant up-regulation of NR2B subunits lasted for at least 9 h after the discontinuation of ethanol and returned to the basal level by 48 h after the withdrawal. These findings suggest that the up-regulation of NR2B subunits during chronic ethanol exposure may be implicated in the initial development of physical dependence on ethanol.
Animals↗
Functional deletion mutation of the 5'-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese.
The natriuretic peptide (NP) family is involved in the regulation of blood pressure and fluid volume. We isolated the 5'-flanking region of the type A human NP receptor gene and identified an insertion/deletion mutation in this region. We then assessed whether there is a genetic association between this mutation and essential hypertension (EH). The deletion allele lacks 8 nucleotides and alters binding sites for the activator protein-2 (AP-2) and Zeste transcriptional factors. We genotyped 200 EH and 200 normotensive (NT) individuals and found 9 subjects with the deletion (8 in the EH group and 1 in the NT group). All 9 individuals were heterozygous. The NT subject with the mutation had left ventricular hypertrophy without hypertension. Transcriptional activity of the deletion allele was <30% that of the wild-type allele. The plasma levels of brain NP in EH patients with the deleted allele were significantly higher than the levels in the EH patients with the wild-type allele, and plasma brain NP levels were significantly higher in subjects with the deleted allele than in subjects with the wild-type allele, despite comparable blood pressures. These findings suggest that in Japanese individuals, this deletion in the human NP receptor gene reduces receptor activity and may confer increased susceptibility to developing EH or left ventricular hypertrophy.
Adult↗
Effect of hypoxia on nitric oxide production and its synthase gene expression in rat smooth muscle cells.
It has not been clarified yet as to whether hypoxia and inflammation affect NO synthesis. In this study, we investigated the transcription of inducible nitric oxide synthase (iNOS) mRNA and the production of nitric oxide (NO) in rat smooth muscle cells (SMCs) cultured under hypoxic conditions in the presence and absence of proinflammatory cytokine interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). We found that hypoxia inhibited the production of NO but did not affect the transcription of iNOS mRNA in rat SMCs treated with IFN-gamma, LPS, or both. These results indicate that O(2) is involved in the regulation of NO synthesis in inflammatory tissues.
Animals↗
Association of 5' upstream promoter region of prostacyclin synthase gene variant with cerebral infarction.
The aim of this study was to investigate whether there is an association between the promoter region of the prostacyclin synthase gene and cerebral infarction (CI). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we found a variable-number tandem repeat polymorphism in the 5'-upstream promoter region of the prostacyclin synthase gene. This region contains transcriptional factors-binding sites of Spl (CCCGCC) and AP-2 (CCGCCAGCCCC). The alleles varied in size from three to seven repeats of nine base pairs (bp). We performed an association study using the polymorphism in 111 patients and 152 control subjects. The transcriptional activity of the abnormal promoter region allele was determined by luciferase assay. The overall distribution of alleles differed significantly between both groups. Logistic linear regression analysis revealed the small number repeat allele to be found more frequently with CI. Transcriptional activity increased with increasing numbers of repeats. This study provides consistent support for the association between CI and the PGIS gene.
Aged↗
Angiotensin II upregulates transforming growth factor-beta type I receptor on rat vascular smooth muscle cells.
Angiotensin II (Ang II) and transforming growth factor-beta (TGF-beta) modulate cell growth and metabolism. Our objective was to evaluate the effect of Ang II on the characteristics and expression of TGF-beta receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats. The addition of TGF-beta1 elicited a biphasic response on DNA synthesis in cultured VSMC in the absence of Ang II, but TGF-beta1 did not stimulate DNA synthesis in the presence of Ang II. TGF-beta binding data showed that Ang II increased the specific binding of 125I-TGF-beta1 by enhancing the expression of lower affinity receptors and increasing the number of binding sites. Ang II alone did not stimulate DNA synthesis in these cultures. However, Ang II significantly stimulated DNA synthesis after the inhibition of endogenous TGF-beta with a neutralizing antibody. The DNA synthesis stimulated by phorbol ester milisterol (PMA) was not affected by the TGF-beta neutralizing antibody. Affinity labeling data revealed receptor-ligand complexes of 280, 85, and 70 kDa, corresponding to TGF-beta type III, II, and I receptors, respectively. Incubation of VSMC with Ang II but not with PMA markedly increased the expression of the TGF-beta type I receptor. Reverse transcription and polymerase chain reaction data also indicated that Ang II, but not PMA, significantly increased the expression of TGF-beta type I receptor mRNA. Results suggest that Ang II increases the binding of TGF-beta with upregulation of TGF-beta type I receptor via a C-kinase-independent pathway. The enhanced expression of the TGF-beta type I receptor may counteract Ang II-promoted growth of VSMC.
Activin Receptors, Type I↗
Upregulation and activation of Stat6 precede vascular smooth muscle cell proliferation in carotid artery injury model.
The role of signal transducers and activators of transcription (STAT) proteins in modulating proliferation and differentiation of various cell types in the hematopoietic system and the central nervous system has been well established. In contrast, the pathophysiological role of these proteins in vascular proliferative diseases has remained unproven, despite in vitro observations emphasizing the involvement of the STAT system in mediating vascular smooth muscle cell (VSMC) proliferation. On the basis of our previous observations demonstrating the occurrence of a specific modulation of Stat6 protein during the proliferative, migratory, and differentiation phases of the developing brain, we investigated whether Stat6 protein is present and modulated in arterial tissue challenged by perivascular injury. The time course of expression and localization of Stat6 after arterial injury was analyzed by immunohistochemistry, Western blot analysis, and confocal microscopy. Six hours after injury, the expression of Stat6 was markedly increased. This overexpression preceded the onset of VSMC proliferation and was downregulated starting from 7 days after injury, coincident with the decline of VSMC proliferation. Moreover, early after injury, Stat6 was predominantly localized at the nuclear level, denoting its functional activation. Conversely, Stat6 staining at later time points was largely cytosolic, suggesting silencing effects of this signaling pathway. These data indicate that Stat6 signaling may contribute to the modifications of gene expression underlying VSMC activation in the context of acute vascular proliferative diseases.
Animals↗
Dopamine D1 receptor gene polymorphism is associated with essential hypertension.
Dopamine has been shown to influence renal sodium excretion through a direct interaction with the dopamine receptor (DR). The dopamine D1 receptor (DRD1) has been localized to the proximal tubules and is known to increase sodium excretion by inhibiting Na-H exchanger and Na,K-ATPase activity. Defective renal dopamine production and/or DR function have been reported in essential hypertension (EH) as well as in genetic models of animal hypertension. With a restriction fragment length polymorphism of the DRD1 gene, we performed an association study in patients with EH. One hundred thirty-one subjects with EH and 136 age-matched normotensive (NT) controls were studied. Polymerase chain reaction was used to amplify the A-48G polymorphic site in the DRD1 gene, and restriction analysis of the polymerase chain reaction product was used to score the A and G alleles. The allele frequencies in the EH group and NT group were then compared. The G allele was observed more frequently in the EH group than in the NT group, and the allele frequencies in the 2 groups differed significantly (chi(2)=6.5, P=0.01). Multiple logistic linear regression analysis revealed that the genotype frequencies of A/A, A/G, and G/G differed significantly (odds ratio=2.1; 95% CI=1.19 to 3.66) between the EH and NT groups. EH patients who possess the G allele had a higher diastolic blood pressure than those lacking the G allele (P<0.01). Thus, the alleles detected by this restriction fragment length polymorphism in the DRD1 gene are associated with EH, and they appear to influence the diastolic blood pressure of Japanese EH patients.
Adult↗
An insertion/deletion polymorphism in intron 18 of the type B human natriuretic peptide receptor gene is not associated with cerebral infarction.
The natriuretic peptide (NP) system may play a crucial role in the development of cardiovascular and renal diseases. C-type NP dilates arteries and lowers blood pressure, and it inhibits the proliferation of vascular smooth muscle cells via the type B NP receptor (NPRB). We determined and analyzed the structure of the NPRB gene and found an insertion/deletion (I/D) polymorphism in intron 18. In this experiment, we studied this I/D polymorphism in the NPRB gene in 241 subjects, including 118 patients with cerebral infarction (the CI group) and 123 control subjects (the non-CI group). Our goal was evaluate the association of this polymorphism with cerebral infarction. Our findings showed that genotype frequencies of the I/D polymorphism were in Hardy-Weinberg equilibrium. The frequencies for the II, ID, and DD alleles were 0.569, 0.374, and 0.057, respectively, in the non-CI group and 0.576, 0.356, and 0.068, respectively, in the CI group. No association was found between this polymorphism and cerebral infarction. These results suggest that this polymorphism in the NPRB gene is not linked to a pathogenic CI gene.
Aged↗