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T Hosoya

Publications and source records attributed to T Hosoya.

At least 19 recordsLinked to original sources
PubMed2001

Isolation and characterization of the rat prolactin-releasing peptide gene: multiple TATA boxes in the promoter region.

The prolactin-releasing peptide (PrRP) gene is a novel bioactive peptide expressed in very restricted regions in the brain. To explore the molecular mechanism of PrRP gene expression, we cloned and characterized the gene and its promoter region. The gene spans approximately 2.4 kb and contains three exons and two introns. 3'RACE analysis showed that a polyadenylation signal 103 bp downstream from the stop codon was functional. Primer extension analysis indicated three transcriptional start sites (TSSs) 92, 199, and 325 bp upstream from the translational start site. Interestingly, in addition to the putative binding sites for SP1-1, AP-2, and Oct-2A, three characteristic TATA boxes were identified close to these TSSs. Transient transfection study using a series of deletion mutants revealed that the middle TATA box is important for the promoter activity. Furthermore, the cloned 1.6 kb promoter region was active only in neuron- and pituitary-derived cell lines, and the promoter region -1600 approximately -800 bp worked as a negative regulatory element. We demonstrated for the first time, the genomic organization and promoter function of the PrRP gene, and this knowledge will facilitate elucidation of transcriptional control of the PrRP gene.

3' Untranslated Regions↗
PubMed2000

The effects of sarpogrelate on cardiomyocyte hypertrophy.

Sarpogrelate was developed as an antiplatelet agent antagonizing 5-hydroxytryptamine (5-HT) receptors. It had been reported that 5-HT receptors were expressed in cardiovascular system, and that sarpogrelate had antihypertrophic effects in vascular smooth muscle cells. Cardiac hypertrophy is a major problem in cardiac diseases, so the present study was designed to elucidate the effects of sarpogrelate on cardiac hypertrophy. Cultured rat cardiomyocytes (MCs) and cardiac nonmyocytes (NMCs) were prepared by Percoll gradient and adhesion method and MCs were incubated with (MCs/NMCs) or without NMCs. As an index of protein synthesis of MCs, [3H]-leucine uptake into MCs and MCs/NMCs was measured. Sarpogrelate decreased [3H]-leucine uptake into MCs (maximum 62.6+/-20.6% of control at 10(-4)M, p<0.05 vs. control). Sarpogrelate also significantly attenuated angiotensin-II- and endothelin-1-induced [3H]-leucine uptake. These results indicated that sarpogrelate might have antihypertrophic effects and could be a useful aid for cardiovascular disease.

Angiotensin II↗
PubMed2000

A Drosophila homolog of LIM-kinase phosphorylates cofilin and induces actin cytoskeletal reorganization.

Mammalian LIM-kinases (LIMKs) phosphorylate cofilin and induce actin cytoskeletal reorganization. To elucidate the functional roles of LIMKs in vivo during developmental processes, we attempted to isolate the cDNA encoding a Drosophila homolog of LIMK (DLIMK) and identified two isoforms of DLIMK transcripts coding for proteins with 1235 and 1257 amino acids, possessing the structure composed of two LIM domains, a PDZ domain, a protein kinase domain, and an unusual long C-terminal extension. In situ hybridization analysis in Drosophila embryos detected the uniformly distributed DLIMK mRNA in stages 2 to 5. In vitro kinase reaction revealed that DLIMK efficiently phosphorylates Drosophila cofilin (twinstar) specifically at Ser-3, the site responsible for inactivation of its actin-depolymerizing activity. When expressed in cultured cells, wild-type DLIMK, but not its kinase-inactive form, induced changes in actin cytoskeletal organization. These observations suggest that the LIMK-cofilin signaling pathway for regulating actin filament dynamics is evolutionarily conserved between Drosophila and mammals.

Actin Depolymerizing Factors↗
PubMed2000

Preparation of Hydrophobically Modified Poly(amidoamine) Dendrimer-Encapsulated Gold Nanoparticles in Organic Solvents.

HAuCl(4) in aqueous solution was extracted to toluene or chloroform using a hydrophobically modified poly(amidoamine) dendrimer. Then, by reduction of Au(3+) ions with dimethylamineborane, gold nanoparticles in the size range of 2-4 nm were obtained in toluene or chloroform. It is suggested that gold nanoparticles are encapsulated by the dendrimer. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.

OBJECTIVE: Familial juvenile hyperuricemic nephropathy (FJHN, MIM 162000) is an autosomal-dominant disease characterized by underexcretion-type hyperuricemia, gout, and chronic renal failure. No loci responsible for this disease or any underexcretion-type hyperuricemia/gout have ever been identified. The aim of the study was to localize a gene responsible for FJHN by linkage analysis. METHODS: A single large family with at least 20 affected members was analyzed. DNA was obtained from 13 affected and 18 non-affected members after lymphoblastoid cell lines were established. Initially, polymorphic data were obtained for 343 microsatellite loci covering all chromosomes except the X chromosome. Parametric linkage analysis was performed using the obtained data with LINKAGE package software. RESULTS: Following a genome-wide search using a set of highly polymorphic microsatellite markers, initial evidence for linkage was obtained for a marker on chromosome 16p. We subsequently genotyped the same subjects for 12 additional markers spanning approximately 30 cM on the short arm of chromosome 16. We obtained a maximum 2-point logarithm of odds (LOD) score of 6.04 at theta = 0 with the marker D16S401; multipoint linkage analysis yielded a maximum LOD score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of approximately 9 cM. CONCLUSION: A gene for FJHN was localized to a candidate interval of approximately 9 cM at 16p12. These findings will be useful for the presymptomatic diagnosis of FJHN in some families and for testing genetic heterogeneity of FJHN in general.

Chromosome Mapping↗
PubMed2000

Diffusion- and T2-weighted MRI of the transverse pontine fibres in spinocerebellar degeneration.

Because the transverse pontine fibres degenerate in some subtypes of spinocerebellar degeneration (SCD), demonstration of these fibres may be helpful for radiological diagnosis of SCD. Using multishot diffusion-weighted MRI, we attempted to find a way to show the transverse pontine fibres. We assessed the quality of demonstration of these fibres on DWI and of abnormal high signal in the pons and middle cerebellar peduncles on T2-weighted images. We examined evaluated 24 control subjects and 12 patients with SCD: two with sporadic olivopontocerebellar atrophy (OPCA), five with spinocerebellar ataxia type 1 (SCA1), two with SCA3, and three with SCA6. In all control subjects and patients with SCA6, we succeeded in demonstrating the transverse pontine fibres as clear low-signal bundles using DWI. In two patients with SCA3, these fibres were identified less distinctly. In contrast, in two patients with sporadic OPCA and in four of five patients with SCA1, the fibres were not identified. In both patients with sporadic OPCA, abnormal high-signal foci were seen in the base of the pons and middle cerebellar peduncles on T2-weighted images; no such foci were detected in any patient with SCA1, SCA3 or SCA6. DWI seems to be useful for demonstrating transverse pontine fibres. Abnormal high signal in the pons and middle cerebellar peduncles may provide a clue to differentiation of sporadic OPCA from other types of SCD.

Adult↗
PubMed2000

Presence of sonographically detectable parathyroid glands can predict resistance to oral pulsed-dose calcitriol treatment of secondary hyperparathyroidism.

Oral pulsed-dose calcitriol administration has been shown to be effective therapy for patients with secondary hyperparathyroidism. However, this effect is not consistently observed in the clinical setting. This study was undertaken to examine whether enlarged parathyroid glands can serve as a clinical marker that predicts the suppressive effect of calcitriol. Thirty-five patients undergoing chronic hemodialysis (HD) were examined (age, 51.9 +/- 14.9 years; duration of HD, 72.0 +/- 56.0 months). Based on the volume of parathyroid glands measured using an ultrasonographic scanner, patients were divided into two groups: 15 patients with undetectable parathyroid glands (ND group) and 20 patients with detectable parathyroid glands (D group; mean volume of parathyroid glands, 261. 9 +/- 347.5 mm(3)). No significant differences were found in serum ionized calcium (Ca(++)) or parathyroid hormone (PTH) levels before calcitriol administration between the two groups. For each patient, 8 microg of calcitriol was administered orally at the end of the HD session, and the changes in serum PTH levels were determined 44 hours after dosing. No significant differences were found between the two groups in serum Ca(++) levels. However, a significant decrease in serum PTH levels was observed in the ND group, whereas no significant changes were found in the D group. The results of the study show that the suppressive effect on PTH through calcitriol therapy was reduced in patients with detectable enlarged parathyroid glands. This may indicate that the size of parathyroid glands is one factor determining the therapeutic potential of pulsed-dose calcitriol administration for secondary hyperparathyroidism.

Administration, Oral↗
PubMed2000

Three-dimensional matrix suppresses E2F-controlled gene expression in glomerular mesangial cells.

BACKGROUND: Extracellular matrix (ECM) regulates mitogenesis of glomerular mesangial cells. Currently, however, the molecular mechanisms that mediate the control of cell growth by ECM are not fully elucidated. METHODS: The effects of structurally distinct forms of type I collagen matrix on mesangial cell proliferation and cell cycle distribution were examined. Expressions of the cell cycle-regulatory transcription factor E2F and retinoblastoma susceptibility gene family proteins were also investigated. RESULTS: Mesangial cells cultured on monomeric collagen matrix showed a substantial growth response to serum. In contrast, mesangial cells cultured on polymerized collagen matrix exhibited arrest of the cell cycle in the G0/G1 phase. The induction of the quiescent phenotype was correlated with down-regulation of E2F-1, the prototypal transcription factor that controls cell cycle progression. The suppression of E2F-1 was associated with (1) dephosphorylation of retinoblastoma susceptibility gene proteins, pRB and p130, and (2) accumulation of E2F-pRB and E2F-p130 DNA binding complexes that bind to the E2F consensus sequence located in the E2F-1 promoter. Other E2F regulatory genes, including c-myc, cyclin A, and cdc 2, were also down-regulated in mesangial cells cultured on polymerized collagen matrix. CONCLUSION: These results suggest that a three-dimensional collagen induces cell cycle arrest via suppression of E2F-controlled gene expression in mesangial cells. Dephosphorylation of pRB and p130 and subsequent generation of transrepressor complexes, E2F-pRB and E2F-p130, may be involved in this process.

Carrier Proteins↗
PubMed2000

XDH gene mutation is the underlying cause of classical xanthinuria: a second report.

BACKGROUND: Classical xanthinuria is a rare autosomal recessive disorder characterized by excessive excretion of xanthine in urine. Type I disease results from the isolated deficiency of xanthine dehydrogenase (XDH), and type II results from dual deficiency of XDH and aldehyde oxidase. The XDH gene has been cloned and localized to chromosome 2p22-23. The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iranian-Jewish family. METHODS: The apparently unrelated parents originated from a community in which consanguineous marriages are common. Subtyping xanthinuria was attempted by homozygosity mapping using microsatellite markers D2S352, D2S367, and D2S2374 in the vicinity of the XDH gene. Mutation detection was accomplished by PCR-SSCP screening of all 36 exons and exon-intron junctions of the XDH gene, followed by direct sequencing and confirmation of sequence alteration by restriction analysis. RESULTS: The index case was homozygous for all three microsatellite markers analyzed. The expected frequency of this genotype in a control population was 0. 0002. These results suggested that xanthinuria in the patient is linked to the XDH gene. Consequently, a 1658insC mutation in exon 16 of the XDH gene was identified. The 1658insC mutation was not detected in 65 control DNA samples. CONCLUSION: A molecular approach to the diagnosis of classical xanthinuria type I in a female patient with profound hypouricemia is described. Linkage of xanthinuria to the XDH locus was demonstrated by homozygosity mapping, and a 1658insC mutation, predicting a truncated inactive XDH protein, was identified. These results reinforce the notion that mutations in the XDH gene are the underlying cause of classical xanthinuria type I.

Amino Acid Sequence↗
PubMed2000

Sudden-onset tinnitus associated with arterial dissection of the vertebrobasilar system.

Magnetic resonance (MR) images of 62 patients with tinnitus were reviewed. These included T1-weighted and T2-weighted axial images and three-dimensional spoiled gradient-recalled acquisition in steady-state (3D-SPGR) imaging with gadopentetate dimeglumine. In 49 cases with tinnitus occurring gradually, the MR images of 2 cases (4.1%) suggested arterial dissection of the vertebrobasilar system. One of these patients underwent vertebral angiography (VAG) and no dissection was confirmed. In 13 cases of sudden-onset tinnitus, MR images of 3 cases (23.1%) suggested arterial dissection. Of these three cases, VAG was performed in two, resulting in arterial dissections being confirmed in two cases. It was concluded that the arterial dissection of the vertebrobasilar system was one of the causes of sudden-onset tinnitus. Abnormalities in neurotological examinations in cases with tinnitus caused by the arterial dissection of vertebrobasilar system implied that the tinnitus was caused by inner ear dysfunction.

Acute Disease↗
PubMed2000

High-resolution computed tomography using multiplanar reconstruction for the facial nerve canal.

Multiplanar reconstruction (MPR) images along the facial nerve canal were prepared with high-resolution computed tomography (HRCT) and their clinical usefulness was evaluated. Over a period of 6 years, temporal bone HRCT was performed on 628 cases. Of these cases, 6 patients exhibited facial nerve lesions, including facial nerve schwannoma (n = 3), traumatic facial nerve palsy (n = 2) and congenital facial nerve palsy (n = 1). Thirty patients without facial nerve lesions, such as chronic otitis media, were randomly selected as controls. Two types of MPR image were composed. One was along the labyrinthine and tympanic segment, and the other was along the tympanic and mastoid segment. Other MPR images, such as those along the facial nerve canal and bone fracture line, were composed as needed. All MPR images were prepared with real-time observation of delicate angles. In all cases, MPR images delineated the labyrinthine and tympanic segment in one image, and the tympanic and mastoid segment in another image. In two patients with traumatic facial nerve palsy, the MPR images revealed a relationship between the facial nerve canal and the bone fracture. In conclusion, MPR images of the facial nerve canal are easy to obtain and are useful in detecting facial nerve schwannoma, traumatic facial nerve palsy and congenital facial nerve palsy.

Adolescent↗
PubMed2000

An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might modulate volume-dependent hypertension in patients on hemodialysis.

Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 +/- 1.76 micromol/l) was significantly lower than in those without the a allele (35.6 +/- 0.90 micromol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (deltaBP/deltaBW), patients were divided into high responders (High-R: deltaBP/deltaBW >2.0 mm Hg; n = 90) and low responders (Low-R: deltaBP/deltaBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele (b/a + a/a) was 3.64 (95% confidence intervals: 1.60-8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

Alleles↗
PubMed2000

Circulating adrenomedullin in erythrocopietin-induced hypertension.

Levels of adrenomedullin (AM) have been shown to be elevated in hypertension and chronic renal failure, suggesting that AM plays a role in the pathogenesis of these diseases. The objective of the present study was to investigate whether circulating AM is involved in erythropoietin (Epo)-induced hypertension in patients with renal anemia due to progressive renal disease. Following treatment with 6,000 IU of Epo once a week, the hematocrit (Ht) rose significantly from 25.9+/-4.0 to 33.4+/-3.3% (n=54, p<0.001) with an overall rate of increase in Ht of 0.43+/-0.04%/week. In response to treatment with Epo, a rise in mean blood pressure of >10 mmHg (Epo-induced hypertension) was found in 22% (12/54 cases) of the patients enrolled. There was no difference in the rate of Ht increase between patients with and without Epo-induced hypertension. There was a significant positive correlation between mature AM and serum creatinine (Cr) concentration before treatment with Epo. However, no correlation was found between the plasma concentration of total AM and serum Cr concentration. Long-term treatment with Epo did not influence plasma concentration of either mature AM or total AM in patients developing hypertension during the study period. These results suggest that circulating AM may play a role in the progression of renal disease. However, the present study does not support the notion that circulating AM is associated with the pathogenesis of Epo-induced hypertension. It is too early yet to claim that there is no AM-mediated mechanism in Epo-induced hypertension.

Adrenomedullin↗
PubMed2000

Possible involvement of endothelin-1 in cardioprotective effects of benidipine.

Benidipine hydrochloride has been developed as an antagonist for the L-type calcium channel and is used as an anti-hypertensive drug. But recent studies have reported that benidipine exerts not only antihypertensive actions but also anti-hypertrophic actions on cardiac muscles. Endothelin-1 (ET-1), one of the endogenous pathological humoral factors of cardiovascular diseases such as hypertension and heart failure, has a strong vasoconstrictive action and could induce hypertension and cardiac hypertrophy. So, it is a matter of great interest whether or not calcium antagonists can decrease cardiac hypertrophy induced by the pathological vasoactive substances such as ET-1. Thus, the present study was designed to elucidate the effects of benidipine on cardiac hypertrophy, and particularly on the interaction with ET-1, using neonatal rat cardiac myocytes (MCs) and cardiac non-myocytes (NMCs) culture systems. Cells were cultured with or without ET-1, benidipine, and nifedipine and the effects of calcium antagonists on cardiac hypertrophy were evaluated by incorporations of [3H]-leucine and [3H]-thymidine into MCs and/or NMCs. Benidipine significantly decreased the ET-1-induced increase of [3H]-leucine and [3H]-thymidine uptake into cardiac MCs and NMCs, whereas no significant effects of nifedipine were observed. Furthermore, benidipine (10(-8)M) attenuated ET-1 secretions from NMCs. In summary, benidipine at least partially decreased the cardiac hypertrophy induced by paracrine mechanisms through its attenuation of ET-1 secretions from NMCs. Benidipine could thus be a useful tool for preventing cardiac hypertrophy due to hypertension.

Animals↗
PubMed2000

F-12509A, a new sphingosine kinase inhibitor, produced by a discomycete.

In the course of our screening for inhibitors of sphingosine kinase, we found an active compound from a culture broth of a discomycete, Trichopezizella barbata SANK 25395. The structure of the compound, named F-12509A, was elucidated by a combination of spectroscopic analyses, to be a new sesquiterpene quinone consisting of a drimane moiety and a dihydroxybenzoquinone. Enzyme kinetic analyses showed that F-12509A inhibits sphingosine kinase activity in a competitive manner with respect to sphingosine, with a Ki value of 18 microM.

Animals↗