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Biomedical subjects

H Shibuya

Publications and source records attributed to H Shibuya.

At least 127 records · Page 7Linked to original sources
PubMed1999

Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling.

BACKGROUND: Members of the TGF-beta superfamily of ligands bind to and activate surface serine/threonine-kinase receptors. Transduction of these signals requires the Smad proteins, which transiently interact with the activated receptor complex and are phosphorylated on their C terminus, SSXS site, by the type I receptor. Smad8 is a downstream signalling mediator of ALK2/ActRIA. RESULTS: We have cloned a splice variant of Smad8, designated Smad8B. The Smad8 and Smad8B cDNAs are identical in sequence, except that Smad8B lacks a portion encoding 47 amino acids, including the SSXS phosphorylation site, in the C-terminal MH2 region. Both Smad8 and Smad8B were expressed in many of the same cell types. Smad8B was capable of specific complex formation with either Smad8 or Smad4 in mammalian cells. In cells expressing constitutively activated ALK2, Smad8B was localized to the cytoplasmic region, whereas Smad8 was translocated into the nucleus. In mammalian cells, Smad8B acted as a dominant inhibitor of BMP signalling. CONCLUSIONS: Smad8B, a splice variant of Smad8, was isolated and found to specifically associate with both Smad8 and Smad4. Smad8B inhibited BMP signalling. Smad8 and Smad8B thus represent novel signal transduction proteins that may regulate the BMP signalling pathway.

Alternative Splicing↗
PubMed1999

Invasion of the lacrimal system by basal cell carcinoma.

BACKGROUND: The rate of recurrence of basal cell carcinoma (BCC) in the periorbital region is higher than that in other areas because of the spread of the tumor along barrier structures. OBJECTIVE: A better understanding of the biological behavior of BCC in this area, in particular as it relates to the lacrimal system, should improve the outcome of surgery. METHODS: A study was made of two cases of BCC that developed in the periorbital region and invaded the lacrimal system. RESULTS: The tumors were found to have invaded the lacrimal system along the mucosal epithelium. Magnetic resonance imaging (MRI) did not suggest any abnormalities in this area. In one patient, the tumor had infiltrated the nasal cavity without destruction of the periorbital bone and nasal cartilage. A preoperative fiberscopic examination clearly demonstrated the involvement of the nasal cavity in this case. CONCLUSION: The lacrimal system is often invaded by BCC that originates from the periorbital region. Physicians and surgeons need to be well aware of the possibility of such aggressive infiltration by BCC.

Aged↗
PubMed1999

Perfusion and blood pool scintigraphy for diagnosing soft-tissue arteriovenous malformations.

PURPOSE: Six arteriovenous malformations were assessed to determine the effectiveness of perfusion and blood pool scintigraphy to diagnose arteriovenous malformations of soft tissue. METHODS: After injection of Tc-99m RBC or Tc-99m DTPA-HSA, dynamic perfusion and early and delayed blood pool images were analyzed. RESULTS: Four of six arteriovenous malformations showed increased activity on perfusion images and slightly increased activity on blood pool images; the remaining two arteriovenous malformations showed increased activity on perfusion and normal activity on blood pool studies. CONCLUSIONS: This expansion of the authors' previous studies of hemangiomas shows that perfusion and blood pool scintigraphy are useful methods to differentiate arteriovenous malformations from various types of hemangiomas.

Adult↗
PubMed1999

67Ga whole-body scintigraphy in the evaluation of head and neck squamous cell carcinoma.

The diagnostic accuracy of 67Ga-citrate whole-body scintigraphy for the evaluation of primary tumours, local recurrences, cervical node metastases and distant metastases was investigated in patients with head and neck squamous cell carcinoma (SCC). Altogether, 102 67Ga-citrate whole-body scans were performed on 83 patients with head and neck SCC using a dual-headed gamma camera. The results were compared with those of computed tomography (CT) and final diagnosis. 67Ga scintigraphy correctly diagnosed 28 of 29 primary lesions, a sensitivity of 97% (CT = 97%). For tumour recurrence, 67Ga scintigraphy correctly diagnosed 13 of 15 recurrences and 53 of 58 instances of no recurrence, giving a sensitivity of 87% and a specificity of 91% (CT = 80 and 62%, respectively). Scintigraphy correctly diagnosed 23 of 31 metastatic sides of the neck and all 173 negative sides of the neck, giving a sensitivity of 74% and a specificity of 100% (CT = 90 and 84%, respectively). Finally, scintigraphy correctly diagnosed all 12 distant metastases as well as 86 of 90 cases of no metastasis, resulting in a sensitivity of 100% and a specificity of 96%. Furthermore, in five patients, distant metastases were initially detected on 67Ga scintigraphy. In conclusion, 67Ga whole-body scintigraphy with a dual-headed camera resulted in a high sensitivity and specificity for the detection of primary lesions, recurrences and distant metastases of head and neck SCC. Although the sensitivity for detecting neck node metastases was relatively low, the specificity was high. Thus, 67Ga scintigraphy is an effective technique for the evaluation of head and neck SCC, especially tumour recurrence and distant metastases.

Adolescent↗
PubMed1999

Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with intravoxel incoherent motion echo-planar MR imaging.

PURPOSE: To determine the true diffusion coefficients of abdominal organs and hepatic lesions with intravoxel incoherent motion (IVIM) echo-planar magnetic resonance (MR) imaging. MATERIALS AND METHODS: Seventy-eight patients suspected of having hepatic lesions were examined with IVIM echo-planar MR imaging at 1.5 T. There were 77 hepatic masses (27 hepatocellular carcinomas, 10 metastatic tumors, eight hemangiomas, and 32 cysts) in the 78 patients. The true diffusion coefficient D and the perfusion fraction f were calculated and compared with the apparent diffusion coefficient (ADC). RESULTS: Specific values of D were found for abdominal organs (liver, 0.72 x 10(-3) mm2/sec; spleen, 0.80 x 10(-3) mm2/sec; kidney, 1.38 x 10(-3) mm2/sec; gallbladder, 2.82 x 10(-3) mm2/sec) and for hepatic lesions (hepatocellular carcinoma, 1.02 x 10(-3) mm2/sec; metastasis, 1.16 x 10(-3) mm2/sec; hemangioma, 1.31 x 10(-3) mm2/sec; cysts, 3.03 x 10(-3) mm2/sec). The ADCs of solid organs and solid lesions were significantly higher than their D values, indicating a high contribution of perfusion to the ADCs. CONCLUSION: Perfusion contributes to the ADCs of abdominal organs and hepatic lesions. The D and f values are useful for the characterization of hepatic lesions.

Abdomen↗
PubMed1999

Moyamoya disease: evaluation with diffusion-weighted and perfusion echo-planar MR imaging.

PURPOSE: To determine the clinical efficacy of diffusion-weighted and perfusion echo-planar magnetic resonance (MR) imaging in the evaluation of moyamoya disease. MATERIALS AND METHODS: Seventeen patients with moyamoya disease were examined prospectively with diffusion-weighted and perfusion echo-planar MR imaging and conventional angiography. The change in the effective transverse relaxation rate (delta R2*) peak value, delta R2* peak time, and delta R2* integral were calculated to assess regional cerebral perfusion. The MR images were compared with angiographic images. RESULTS: Of the 34 posterior cerebral arteries (PCAs) of the 17 patients, 14 PCAs (41%) in 11 patients showed stenosis or occlusion. The delta R2* peak value ratio in the cerebral hemispheres decreased significantly, and the delta R2* peak time ratio increased significantly, with PCA stenosis and occlusion. However, no correlation was apparent between perfusion and extent of the stenotic or occlusive lesions of the internal carotid artery bifurcation. The frequency of cerebral infarctions was significantly increased in patients with stenotic or occlusive PCA lesions. For three acute infarctions, a decrease in the apparent diffusion coefficient was significantly correlated with a decrease in the delta R2* peak value, an increase in the delta R2* peak time, and a decrease in the delta R2* integral. CONCLUSION: Regional cerebral perfusion in moyamoya disease is decreased and delayed with PCA stenosis, with greater decrease and delay with PCA occlusion. Diffusion-weighted and perfusion imaging are useful for evaluating cerebral ischemia in moyamoya disease.

Adult↗
PubMed1999

Antihypertensive actions of methylripariochromene A from Orthosiphon aristatus, an Indonesian traditional medicinal plant.

Methylripariochromene A (MRC) was isolated from the leaves of Orthosiphon aristatus (Lamiaceae) and subjected to the examination of several pharmacological actions related to antihypertensive activity. The following four findings were revealed from the present study: 1) MRC caused a continuous decrease in systolic blood pressure and a decrease in heart rate after subcutaneous administration in conscious male SHRSP, 2) MRC exhibited the concentration-dependent suppression of contractions induced by high K+, l-phenylephrine or prostaglandin F2alpha in endothelium-denuded rat thoracic aorta, 3) MRC showed a marked suppression of contractile force without a significant reduction in the beating rate in isolated bilateral guinea pig atria, and 4) MRC increased urinary volume and the excretion of Na+, K+ and Cl- for 3 h after oral administration with a load of saline in fasted rats. These findings indicate that MRC possesses some actions related to a decrease in blood pressure, i.e. vasodilating action, a decrease in cardiac output and diuretic action. Furthermore, it is presumed that the traditional use of this plant in the therapy of hypertension may be partially supported by these actions with MRC.

Animals↗
PubMed1999

Successful interstitial treatment for bilateral tongue cancer.

We report three cases of bilateral tongue cancer who received interstitial brachytherapy successively for each tumour. Tumour control following treatment are as good as that for unilateral tongue cancer and there have been no severe complications in, or around, the tumour area after using a mandibular protective spacer and dose reduction for the second treatment.

Adult↗
PubMed1999

Purification and characterization of recombinant Mortierella vinacea alpha-galactosidases I and II expressed in Saccharomyces cerevisiae.

The cDNAs coding for Mortierella vinacea alpha-galactosidases I and II were expressed in Saccharomyces cerevisiae under the control of the yeast GAL10 promoter. The recombinant enzymes purified to homogeneity from the culture filtrate were glycosylated, and had properties identical to those of the native enzymes except for improving the heat stability of alpha-galactosidase II and decreasing the specific activities of both enzymes.

Bacterial Proteins↗
PubMed1999

Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population.

BACKGROUND: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder. METHODS: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls. RESULTS: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01). CONCLUSIONS: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.

Adult↗
PubMed1999

Quantitative evaluation of salivary gland scintigraphy in Sjörgen's syndrome.

UNLABELLED: This study compared the quantitative characteristics of salivary gland scintigraphy in patients with Sjogren's syndrome with the histopathologic grading of labial biopsy. METHODS: Thirty-nine patients with Sjögren's syndrome were studied by salivary gland scintigraphy and labial biopsy. Twelve normal volunteers were also studied as a control group for scintigraphic parameters. After injection of 370 MBq 99mTc sodium pertechnetate, dynamic salivary scintigraphy with lemon juice stimulation was performed for 50 min. Functional parameters for the parotid and submandibular glands were calculated, and scintigraphic and histopathologic results were compared. RESULTS: With the progression of histopathologic grades 1-4, the velocity of tracer secretion decreased in the parotid gland (P < 0.05), and the quantity of tracer accumulation decreased in the submandibular gland (P < 0.05). The histopathologic grade in patients with Sjögren's syndrome was correlated with these scintigraphic parameters (P < 0.05): Histopathologic grade = 2.304 - 0.014 x (submandibular gland maximum accumulation) + 0.196 x (parotid gland time interval of tracer secretion). CONCLUSION: Decreased secretion velocity in the parotid gland and decreased accumulation in the submandibular gland were sensitive indicators of salivary gland disease in Sjögren's syndrome. The histopathologic grade was correlated with these scintigraphic parameters.

Adult↗
PubMed1998

Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia.

Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).

Adolescent↗
PubMed1998

Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism.

Tyrosine hydroxylase is the rate-limiting step in the biosynthesis of catecholamines. To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing. Source DNAs for sequencing were from 88 Japanese patients comprised of 17 schizophrenics, 21 with mood disorders, and 50 alcoholics. Two novel variants, T-229A and Val468Met, were identified. Case-control comparisons demonstrated that distribution of these two variants were similar in the controls and the three psychiatric groups. Distributions of the previously reported Val81Met polymorphism alleles and the intron 1 TCAT repeat polymorphism alleles were similar in the four subject groups. Our study indicates that the TH gene is not likely to play a major role in the genetic predisposition to schizophrenia, mood disorders, or alcohol dependence.

Adult↗
PubMed1998

Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese.

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.

Female↗
PubMed1998

Factors affecting mandibular complications in low dose rate brachytherapy for oral tongue carcinoma with special reference to spacer.

PURPOSE: To evaluate the efficacy of a spacer in the prevention of mandibular complications in low dose rate (LDR) brachytherapy (BRT) for oral tongue carcinoma. METHODS AND MATERIALS: A retrospective analysis was conducted using 103 patients with T1 or T2 tongue carcinoma treated by a single plane implantation of iridium (192Ir) pins between 1979-1994. Of these patients, 60 were treated by BRT alone, and the rest were combined with external irradiation (Ext) and/or chemotherapy (CHT). Forty-eight and 55 patients were given BRT with and without a spacer, respectively. Spacers were individually made of acrylic resin according to a prosthetic technique so as to obtain the thickness of 7-10 mm at the lingual part of the implanted side. Variables, including a spacer, which may be associated with the development of osteoradionecrosis (ORN) of the mandible, were analyzed by the Cox proportional hazards regression analysis. RESULTS: Our spacer reduced about 50% of the absorbed dose at the lingual side surface of the lower gingiva (LSG) to that in the absence of a spacer. Absolute incidence of ORN was 2.1% (1 of 48) and 40.0% (22 of 55), with and without a spacer, respectively, and the difference was statistically significant by univariate analysis (p = 0.0004). It was revealed by the Cox analysis that the spacer (p = 0.0247), combined CHT (p = 0.0295), and combined Ext (p = 0.0279) were significant independent factors associated with the development of ORN. The spacer was shown to be a significant factor by univariate analysis (p = 0.0037), but not by multivariate analysis when analysis was restricted to the patients who did not receive CHT. The absorbed dose, dose rate, and biological effective dose (BED) reflecting early or late response were estimated at the LSG, and prognosticators associated with the incidence of ORN were also determined by the Cox analysis. Particularly, BED for late response by BRT, the total absorbed dose, and any BED by Ext plus BRT were highly significant factors in the whole population. Essentially similar results were obtained in the patients without receiving CHT. CONCLUSIONS: It was clarified that our spacer effectively prevents mandibular complications in LDR BRT by 192Ir for oral tongue carcinoma. Furthermore, introduction of a spacer provided novel information concerning the development of ORN, where BED particularly for late response given by BRT, the total absorbed dose, and any BED by Ext plus BRT could be good prognostic factors only when estimated at the LSG.

Adult↗
PubMed1998

Coding sequence and exon/intron organization of the canine CLN3 (Batten disease) gene and its exclusion as the locus for ceroid-lipofuscinosis in English setter dogs.

Hereditary ceroid-lipofuscinosis in English setters has been proposed to be the canine equivalent of human juvenile ceroid-lipofuscinosis, which results from defects in the CLN3 gene. Analyses were performed to determine whether the disease in English setters is also the consequence of a CLN3 gene mutation. Canine CLN3 cDNA was found to contain a 1,314-bp open reading frame predicting a derived amino acid sequence which is 89%, 85%, and 84% identical to the predicted amino acid sequences for the human, mouse, and rabbit CLN3 proteins, respectively. The canine gene has sixteen exons. No differences were detected when cDNA nucleotide sequences from an English setter with ceroid-lipofuscinosis and from a normal dog were compared. Moreover, alleles of the canine CLN3 gene distinguished by an intragenic marker segregated independently from the disease in an English setter family, eliminating CLN3 as the locus for the canine disease. A ceroid-lipofuscinosis-affected Tibetan terrier was homozygous for a Gly70Glu CLN3 variant; however, this allele is common in dog breeds considered free of ceroid-lipofuscinosis.

Amino Acid Sequence↗
PubMed1998

Role of TAK1 and TAB1 in BMP signaling in early Xenopus development.

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.

Adaptor Proteins, Signal Transducing↗