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Biomedical subjects

A Hata

Publications and source records attributed to A Hata.

At least 73 records · Page 4Linked to original sources
PubMed1996

A human Mad protein acting as a BMP-regulated transcriptional activator.

The TGF-beta/activin/BMP cytokine family signals through serine/threonine kinase receptors, but how the receptors transduce the signal is unknown. The Mad (Mothers against decapentaplegic) gene from Drosophila and the related Sma genes from Caenorhabditis elegans have been genetically implicated in signalling by members of the bone-morphogenetic-protein (BMP) subfamily. We have cloned Smad1, a human homologue of Mad and Sma. Microinjection of Smad1 messenger RNA into Xenopus embryo animal caps mimics the mesoderm-ventralizing effects of BMP4. Smad1 moves into the nucleus in response to BMP4. Smad1 has transcriptional activity when fused to a heterologous DNA-binding domain, and this activity is increased by BMP4 acting through BMP-receptor types I and II. The transactivating activity resides in the conserved carboxy-terminal domain of Smad1 and is disrupted by a nonsense mutation that corresponds to null mutations found in Mad and in the related gene DPC4, a candidate tumour-suppressor gene in human pancreatic cancer. Additionally, we show that DPC4 contains a transcriptional activation domain. The results suggests that the Smad proteins are a new class of transcription factors that mediate responses to the TGF-beta family.

Amino Acid Sequence↗
PubMed1996

Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.

Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.

Adult↗
PubMed1996

Angiographic findings of Takayasu arteritis: new classification.

Having proposed a new classification on angiographic findings of patients with Takayasu arteritis, we evaluated the angiographic findings of 80 Japanese patients and 102 Indian patients according to this classification. Japanese patients showed a higher frequency of involvement of the ascending aorta, aortic arch and its branches than did the Indians (P < 0.01). On the other hand, the frequency of involvement of the abdominal aorta and/or renal arteries was higher in Indian patients (P < 0.01). Type III cases of the new classification which involves the thoracic descending aorta, abdominal aorta and/or renal arteries were observed in 3% of the Indian patients, but not at all in the Japanese. In conclusion, in Japanese patients, vascular lesions tend to occur primarily in the ascending aorta, aortic arch and/or its branches and extend into the abdominal aorta. On the other hand, in Indian patients, the tendency is primarily in the abdominal aorta including renal arteries and extending into the thoracic aorta.

Adolescent↗
PubMed1996

Four years follow-up study in patients with Takayasu arteritis and severe aortic regurgitation; assessment by echocardiography.

We prospectively performed the follow-up study in 11 female patients with Takayasu arteritis and severe aortic regurgitation by echocardiography. A mean follow-up period was 4 years. The inflammatory state was controlled in all patients. Antihypertensive agents including beta-blocker were administered in nine patients. Heart failure did not progress in all patients except one. No candidate for cardiac surgery appeared during the follow-up period. Aortic root diameter, left atrial, left ventricular end-diastolic and end-systolic dimensions, wall thickness, left ventricular mass, and percent fractional shortening of the left ventricle showed no significant change in echocardiography. These data indicate that left ventricular disturbance might be slowly progressive in patients with Takayasu arteritis and severe aortic regurgitation. Systemic hypertension and the inflammatory state should be well controlled in managing the patients. beta-blocker might be useful in some patients with Takayasu arteritis and severe aortic regurgitation. Further follow-up is necessary for the decision of the cardiac surgical indication.

Adrenergic beta-Antagonists↗
PubMed1996

Identification and analyses of glycoprotein B of human herpesvirus 7.

The gene for the human herpes virus 7 (HHV-7) glycoprotein B (gB) has been identified by sequencing a molecularly cloned HHV-7 DNA fragment. A 2.5-kb open reading frame (ORF) encoded a protein of 822 amino acids with characteristics of a transmembrane glycoprotein, and showed the strongest similarity (56.5%) with the human herpesvirus 6 (HHV-6) gB. The genes for the transport/capsid assembly protein (tp/cap) and the DNA polymerase (pol) existed upstream and downstream of the gB gene, respectively. This arrangement was the same as that of HHV-6. Antisera were generated by immunizing mice with a glutathione S-transferase-carboxy terminal gB fusion protein. Immunofluorescent tests demonstrated that the antisera reacted specifically with HHV-7 antigens in cytoplasm of infected cells. The antisera immunoprecipitated proteins with apparent molecular masses of 51, 63 and 112 kDa from HHV-7 infected cells by pulse-chase analysis. In the presence of tunicamycin, the protein with a molecular mass of 112 kDa was replaced by a protein with a molecular mass of 88 kDa, and this size was consistent with the predicted size of the primary translation product of the HHV-7 gB gene. These results suggested that the protein with a molecular mass of 112 kDa was a glycoprotein synthesized by addition of N-linked oligosaccharides to a non-glycosylated precursor of the protein with a molecular mass of 88 kDa and then cleaved into the proteins with molecular masses of 51 and 63 kDa in HHV-7 infected cells.

Amino Acid Sequence↗
PubMed1996

Identification of a Gly862 to Ser substitution in the type I collagen gene from a single spermatozoon.

Individual spermatozoa from the father of two affected infants with osteogenesis imperfecta were separated by dilution and micromanipulation. A segment of the type I collagen gene containing the mutant region was amplified by nested polymerase chain reaction and sequenced. Among 40 individual spermatozoa, 15 specimens were identified as mutants with a substitution of guanine3208 to adenine (glycine862 to serine) while 18 and seven specimens were of the wild and mixed types respectively. Through this study, we have established a molecular procedure that can be considered as prerequisite for preimplantation diagnosis of genetic disorders with a single point mutation.

Collagen↗
PubMed1996

Event-related potential correlates of functional hearing loss: reduced P3 amplitude with preserved N1 and N2 components in a unilateral case.

A female patient exhibiting functional hearing loss in her left ear demonstrated reduced amplitude of P3 component in event-related potentials (ERP) to left monaural stimulation, with preserved N1 and N2 components to stimulation of either ear. This result suggested that stimuli in the affected ear were conducted successfully up to the auditory cortex but that further processing in higher brain regions was 'repressed'. Event-related potential examination for such hysterical disorders could be useful in clarifying their brain mechanism and offer a useful diagnostic clue to its nature.

Adult↗
PubMed1996

Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult.

In five different Japanese families, we identified six male hemizygotes (aged 6, 9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution at nucleotide 119 in exon 2 generating histidine in place of arginine. OTC activity in the necropsied liver tissue was reduced to approximately 12% of the control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/- 1.8% of the control transfected with wild type OTC cDNA. Clinical features ranged from death during a hyperammonaemic attack (a 9 year old) to a 65 year old asymptomatic man. We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manifestation of this disease.

Adolescent↗
PubMed1995

Role of angiotensinogen in the genetics of essential hypertension.

Although essential hypertension has long been recognized to involve a strong genetic predisposition, the genes that increase susceptibility remain virtually unknown. With recent advances in molecular biology and statistical methods, it has become feasible to study candidate genes which may contribute to the pathogenesis of essential hypertension in humans. Recently, the angiotensinogen (AGT) locus was demonstrated to exhibit genetic linkage and association to essential hypertension and to preeclampsia. While the statistical evidence that mutations of the AGT gene or a neighboring gene contribute to the development of hypertension is strong, the exact mechanism(s) by which these mutations affect the regulation of blood pressure (BP) is unknown. Increasing attention is now being focused on elucidating this mechanism(s).

Amino Acid Sequence↗
PubMed1995

Magnetic resonance imaging of vascular changes in Takayasu arteritis.

We studied the thoracic aorta in 42 female patients with Takayasu arteritis by magnetic resonance imaging (MRI) with a 1.5-T superconducting instrument and compared the findings with those in 10 healthy female controls. Images in the transaxial and oblique sagittal planes were acquired by cardiac gating using a spin-echo pulse sequence. Images in the oblique plane were also obtained with cine MRI. Vascular changes were found in 41 (98%) of the patients. Dilatation of the ascending aorta was observed in 20 patients (48%), while stenotic changes were more characteristic in the descending aorta (16 patients, 38%). Moderate signal-intensity masses on the aortic wall were encountered in 21 patients (50%), suggesting mural thrombi. Turbulent blood flow was observed around all masses by cine MRI. HLA analysis revealed that patients carrying HLA-B52 typing showed these masses more frequently than those without this typing (P < 0.05). Cine MRI demonstrated aortic regurgitation in 20 patients (48%), all of whom showed dilated ascending aorta; furthermore, 14 (70%) of them were confirmed as carrying HLA-B52. Thus, MRI was a useful non-invasive tool not only for the evaluation of the morphological changes in the aorta and its branches, and of the hemodynamic disturbance in Takayasu arteritis, but also for follow-up of the morbid condition.

Adult↗
PubMed1995

Template-switching during DNA synthesis by Thermus aquaticus DNA polymerase I.

Recombinant DNA molecules are often generated during the polymerase chain reaction (PCR) when partially homologous templates are available [e.g., see Pääbo et al. (1990) J. Biol. Chem. 265, 4718-4721]. It has been suggested that these recombinant molecules are a consequence of truncated extension products annealing to partially homologous templates on subsequent PCR cycles. However, we demonstrate here that recombinants can be generated during a single round of primer extension in the absence of subsequent heat denaturation, indicating that template-switching produces some of these recombinant molecules. Two types of template-switches were observed: (i) switches to pre-existing templates and (ii) switches to the complementary nascent strand. Recombination is reduced several fold when the complementary template strands are physically separated by attachment to streptavidin magnetic beads. This result supports the hypothesis that either the polymerase or at least one of the two extending strands switches templates during DNA synthesis and that interaction between the complementary template strands is necessary for efficient template-switching.

Base Sequence↗
PubMed1995

What effect does controlling platelets have on atherosclerosis?

Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets.

Adenylyl Cyclases↗
PubMed1995

Seroprevalence of hepatitis C virus infection and its genotype in Lanzhou, western China.

The seroprevalence of hepatitis C virus (HCV) infection in Lanzhou, Western China was studied. HCV genotypes in 20 patients with HCV infection was determined by genotype-specific primer for polymerase chain reaction (PCR) based on HCV core region and compared with the genotype assigned by sequence comparison and molecular evolutionary analysis based on the same region. Antibody to HCV (anti-HCV) was present in 2.5% of volunteer blood donors and in 35.0% of paid blood donors (P < 0.01). HCV infection is uncommon in patients with liver disease who attended liver clinics in this locality; 4.0% with acute hepatitis and 4.0% with chronic hepatitis, 10.0% with liver cirrhosis, and none with hepatocellular carcinoma were seropositive for anti-HCV. Genotype 1b and 2a were both found to be prevalent. Together, they accounted for 19 of 20 (95%) patients with HCV infection. Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype-specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis. These data showed that HCV is present in Western China, HCV infection is more common in paid blood donors, and HCV genotypes 1b and 2a are both prevalent in Western China.

Amino Acid Sequence↗
PubMed1995

Recurrence of osteogenesis imperfecta because of paternal mosaicism: Gly862-->Ser substitution in a type I collagen gene (COL1A1).

We determined that two siblings with type III osteogenesis imperfecta (OI) had the same single base substitution that converted the codon for glycine (Gly) 862 to a codon for serine (Ser) in exon 44 of the alpha 1 chain of the type I (alpha 1(I)) collagen gene (COL1A1). The mutation was also detected in various paternal tissues; the mutant allele accounted for approximately 11% of the COL1A1 alleles in blood, 24% of those in fibroblasts, and 43% of those in sperm determined by allele-specific colony hybridization using amplified genomic sequences. These findings demonstrate that germ-line mosaicism in the phenotypically normal father is responsible for the recurrence. There is a cluster of serine substitutions for Gly (Gly832, Gly844 and Gly901) which is associated with nonlethal phenotypes and which is located between two lethal clusters. In the cases studied here, a Gly862-->Ser mutation was identified that is located inside the nonlethal cluster.

Adult↗
PubMed1995

p53 protein expression and p53 gene mutation in thymic epithelial tumors. An immunohistochemical and DNA sequencing study.

p53 protein expression in 34 thymic epithelial tumors was examined immunohistochemically, and p53 gene mutation was detected in selected cases by DNA sequencing, using formalin-fixed and paraffin-embedded tissues. The tumors comprised 12 noninvasive thymomas, 9 invasive/metastatic thymomas, and 13 thymic carcinomas. All the tumors were immunoreactive for p53 protein. The p53-positive tumor cells in noninvasive thymoma were less than 10% (low expressor) in 7 cases and 10% to 50% (moderate expressor) in 5 cases. In invasive/metastatic thymoma, two were low expressors and seven were moderate expressors. In thymic carcinomas, there were nine moderate expressors and four high expressors (with > 50% positive cells). There was significant difference in p53 protein immunopositivity between thymic carcinoma and each of the noninvasive or invasive/metastatic thymomas. The DNA sequencing study confirmed the presence of p53 gene point mutation in all 10 cases examined, including three low expressors. These results suggest that p53 gene mutation is an early event in thymic tumorigenesis, and the p53 protein-positive cells increase with the progression of the tumor. Immunostaining reactivity of p53 may be a useful adjunct to differentiate thymic carcinoma from thymoma.

Adult↗
PubMed1995

Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.

It has been reported that individuals with the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene are at greater risk for myocardial infarction (MI), especially among subjects normally considered to be at low risk. However, little is known about the mechanism by which the ACE polymorphism affects the risk of MI. Coronary artery spasm (CAS) is considered to be one possible mechanism for developing MI. We therefore examined the ACE polymorphism relation to CAS to determine if this was the mechanism by which the DD genotype influences MI. We studied 150 angiographically assessed Japanese males, all more than 60 yr old. CASs were detected using intracoronary injection of ergonovine maleate. Subjects were divided into three groups: those with CAS (group 1), those without CAS, but with fixed organic stenosis (group 2); and those without CAS and no organic stenosis (group 3). DD subjects were significantly represented in group 1 when compared with groups 2 (P = 0.002) and 3 (P = 0.026). These results suggest that the DD genotype relates to the greater risk for MI in the patients with CAS.

Aged↗
PubMed1995

Synchronous fluctuation of interleukin-6 and platelet count in cyclic thrombocytopenia and thrombocytosis.

We describe a case of cyclic thrombocytopenia and thrombocytosis, whose cytokine levels, granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6) in plasma, fluctuated in synchrony with platelet count. The levels of the two cytokines correlated significantly with the platelet count for 11 observations over an 8-month period (r = 0.79, p < 0.01 for GM-CSF and r = 0.87, p < 0.001 for IL-6). No inverse relationship between platelet-associated immunoglobulin G (PAIgG) and platelet count was observed (r = 0.39, p > 0.20). These findings suggest that the fluctuation of platelet count in this case may result from an aberration of the cytokine network regulating megakaryopoiesis and platelet formation.

Adult↗