Biomedical subjects

A Tanaka

Publications and source records attributed to A Tanaka.

At least 19 recordsLinked to original sources

PubMed1999

Vasopressin increases vascular endothelial growth factor secretion from human vascular smooth muscle cells.

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen of vascular endothelial cells which promotes neovascularization in vitro. To determine whether vasopressin induces VEGF secretion in human vascular smooth muscle cells, we performed enzyme-linked immunosorbent assays. Vasopressin potently induced a time-dependent and concentration-dependent (maximal, 10(-7) M) increase in VEGF secretion by human vascular smooth muscle cells that was maximal after 24 h. Furthermore, vasopressin also concentration-dependently caused mitogenic effect, as reflected by total protein content of cells per culture well. These vasopressin-induced VEGF secretion increase and mitogenic effect of these cells were potently inhibited by vasopressin V1A receptor antagonists, confirming this is a vasopressin V1A receptor-mediated event. These results indicate that vasopressin increases VEGF secretion in human vascular smooth muscle cells, the magnitude of VEGF secretion being temporally related to the mitogenic effect of vascular smooth muscle cells and the potency of the growth-promoting stimulus. Vasopressin-induced VEGF secretion by proliferating vascular smooth muscle cells could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium, vasopressin play a more fundamental role in the regulation of vascular function than has previously been recognized.

Antidiuretic Hormone Receptor Antagonists↗

PubMed1999

Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p.

Selenoprotein P is an extracellular protein containing presumably 10 selenocysteines that are encoded by the UGA stop codon in the open reading frame of the mRNA. The function of selenoprotein P is currently unknown, although several indirect lines of evidence suggest that selenoprotein P is a free radical scavenger. We first developed a conventional procedure to isolate selenoprotein P from human plasma. Next, we investigated the reactivities of selenoprotein P against various hydroperoxides in the presence of glutathione. Although selenoprotein P reduces neither hydrogen peroxide nor tertiary butyl hydroperoxide, it does reduce phospholipid hydroperoxide such as 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-3-phosphatidylcholine hydroperoxide. Kinetic analysis demonstrated a tert-uni ping-pong mechanism, similar to those described for classical glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase. Not only glutathione, but also dithiothreitol, mercaptoethanol, cysteine, and homocysteine, were effective as reducing substances, as in the case of phospholipid hydroperoxide glutathione peroxidase. These results show that selenoprotein P functions as a phospholipid hydroperoxide glutathione peroxidase in extracellular fluids.

Amino Acids↗

PubMed1999

Surface Hydroxyl Site Densities on Metal Oxides as a Measure for the Ion-Exchange Capacity.

Hydroxyl groups on metal oxide in water are the sites for ion exchange, and the surface hydroxyl site density on oxides is a measure of the ion-exchange capacity. Here, the Grignard reagent method was applied to determine the surface hydroxyl site density of oxide samples. The results were similar to those reported for different oxides with other methods (dehydration by heating, tritium exchange, crystallographic calculations, etc.), and they are comparable with those calculated from the closest packing of hydroxide ions. A mechanism of hydroxylation is proposed: lattice oxide ions (extremely strong bases) are exposed to aqueous solutions and are neutralized by water to become hydroxide ions. Also, the saturated deprotonation method was applied to hematite, and it was found that all the acid hydroxyl groups on hematite were deprotonated in very high concentrations of alkali solutions ( approximately 5 mol dm-3 NaOH), and from the saturated amount of OH- consumed by deprotonation, the same result as that by the Grignard method was obtained. It is shown that all hydroxyl groups take part in ion exchange and that the unusually small values reported elsewhere with the saturated (de)protonation method may contain errors. Hetero- or homogeneity of hydroxyl groups in contact with water as ion-exchange sites is also discussed. It is suggested that intensely hydrated layers at the oxide/water interface may result in homogeneous discrete sites. The development of microstructures in the oxides was suggested from the measured values of specific surface areas, and the effect of the microstructure environments on the reactivity of internal surface hydroxyl sites is discussed. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Autoepitope mapping and reactivity of autoantibodies to the dihydrolipoamide dehydrogenase-binding protein (E3BP) and the glycine cleavage proteins in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial antibodies (AMA) directed primarily against the E2 subunits of the pyruvate dehydrogenase complex, the branched chain 2-oxo-acid dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, as well as the dihydrolipoamide dehydrogenase-binding protein (E3BP) of pyruvate dehydrogenase complex. The autoantibody response to each E2 subunit is directed to the lipoic acid binding domain. However, hitherto, the epitope recognized by autoantibodies to E3BP has not been mapped. In this study, we have taken advantage of the recently available full-length human E3BP complementary DNA (cDNA) to map this epitope. In addition, another lipoic binding protein, the H-protein of the glycine cleavage complex, was also studied as a potential autoantigen recognized by AMA. Firstly, the sequence corresponding to the lipoic domain of E3BP (E3BP-LD) was amplified by polymerase chain reaction and recombinant protein and then purified. Immunoreactivity of 45 PBC sera (and 52 control sera) against the purified recombinant E3BP-LD was analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Secondly, reactivity of PBC sera was similarly analyzed by immunoblotting against H-protein. It is interesting that preabsorption of patient sera with the lipoic acid binding domain of E3BP completely removed all reactivity with the entire protein by immunoblotting analysis, suggesting that autoantibodies to E3BP are directed solely to its lipoic acid binding domain. Fifty-three percent of PBC sera reacted with E3BP-LD, with the majority of the response being of the immunoglobulin G (IgG) isotype (95%). Surprisingly, there was little IgM response to the E3BP-LD suggesting that the immune response was secondary because of determinant spreading. In contrast, H-protein does not appear to possess (or expose) autoepitopes recognized by PBC sera. This observation is consistent with structural data on this moiety.

Amino Acid Oxidoreductases↗

PubMed1999

Development of an arming yeast strain for efficient utilization of starch by co-display of sequential amylolytic enzymes on the cell surface.

The construction of a whole-cell biocatalyst with its sequential reaction has been performed by the genetic immobilization of two amylolytic enzymes on the yeast cell surface. A recombinant strain of Saccharomyces cerevisiae that displays glucoamylase and alpha-amylase on its cell surface was constructed and its starch-utilizing ability was evaluated. The gene encoding Rhizopus oryzae glucoamylase, with its own secretion signal peptide, and a truncated fragment of the alpha-amylase gene from Bacillus stearothermophilus with the prepro secretion signal sequence of the yeast alpha factor, respectively, were fused with the gene encoding the C-terminal half of the yeast alpha-agglutinin. The constructed fusion genes were introduced into the different loci of chromosomes of S. cerevisiae and expressed under the control of the glyceraldehyde-3-phosphate dehydrogenase promoter. The glucoamylase and alpha-amylase activities were not detected in the culture medium, but in the cell pellet fraction. The transformant strain co-displaying glucoamylase and alpha-amylase could grow faster on starch as the sole carbon source than the transformant strain displaying only glucoamylase.

Agglutinins↗

PubMed1999

AVP-induced mitogenic responses of Chinese hamster ovary cells expressing human V1A or V1B receptors.

Arginine vasopressin (AVP) induces cell proliferation and hypertrophy; however, the human receptor subtype and the intracellular signaling pathways responsible for this mitogenic activity remain unclear. Experiments were conducted to determine which AVP receptor is linked to mitogen-activated protein (MAP) kinase activation and the mitogenic effect seen in Chinese hamster ovary (CHO) cells expressing human V1A or V1B receptors. Adding AVP to CHO cells transfected with human V1A or V1B cDNA significantly and concentration-dependently induced activation of MAP kinase and increased DNA synthesis, as measured by [3H]thymidine incorporation. These effects were inhibited by AVP receptor antagonists and the potency order of antagonists in vitro was similar to that observed in radioligand binding assays. These results suggest that AVP induces the MAP kinase cascade leading to cell proliferation through either human V1A or V1B receptors, and that these cloned, expressed AVP receptors may prove an invaluable tool for probing the physiologic and pathophysiologic effects of AVP.

Animals↗

PubMed1999

Novel mutations, including the second most common in Japan, in the beta-hexosaminidase alpha subunit gene, and a simple screening of Japanese patients with Tay-Sachs disease.

Two novel mutations of the beta-hexosaminidase alpha subunit gene were identified in Japanese patients with the infantile form of Tay-Sachs disease. One mutation was a one-base deletion at nt613C, which generated a stop codon at two codons downstream, in three unrelated patients. The other mutation was a one-base substitution of G-to-A at IVS 5, +1, which caused a splicing abnormality, in one patient. A missense mutation of R170W, which has already been reported in other ethnic groups, was also newly identified in one patient. In 1993, the most common mutation (IVS 5, -1G-->T) in Japanese patients with Tay-Sachs disease was reported as the major mutation in Japan accounting for 80% of 56 mutant alleles from 28 unrelated patients. The deletion of nt613C was the second most common mutation, accounting for 5% of the mutant alleles. The previously reported mutation IVS 5, -1G-->T and the nt613C deletion found in this study together accounted for 85% of the mutations causing Tay-Sachs disease among Japanese. Since these two mutations were located in or close to exon 6 and since they abolish Fok I (IVS 5, -1G-->T) and Sfa NI (nt613C deletion) restriction sites, respectively, they were screened rapidly by single polymerase chain reaction followed by digestion with these enzymes.

Base Sequence↗

PubMed1999

Embryonic form of smooth muscle myosin heavy chain (SMemb/MHC-B) in gastrointestinal stromal tumor and interstitial cells of Cajal.

Myosin heavy chain (MHC) isoform expression was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to clarify a possible link between gastrointestinal stromal tumor (GIST) and interstitial cells of Cajal (ICCs) in the gastrointestinal (GI) tract. Using monoclonal antibodies against MHC isoforms, 18 of 27 GISTs (67%) showed immunoreactivity for non-smooth-muscle myosin or the embryonic form of MHC (SMemb), but only one tumor showed immunoreactivity for smooth muscle cell (SMC)-specific isoforms (SM1 and SM2). Co-expression of KIT or CD34, which is also expressed in GIST and ICCs, was demonstrated in 18 (100%) and 16 SMemb-positive tumors (89%), respectively. Otherwise, the expression of SMemb in GIST was not correlated with the patient's age or sex, tumor size, histological grade of GIST, or expression of mesenchymal cell markers, such as alpha-smooth muscle actin (alpha-SMA) or S100 protein. By double-fluorescence immunostaining of the tunica muscularis of the GI tract wall, co-expression of KIT, CD34, and SMemb was demonstrated in ICCs, which were negative for SM1 and SM2. RT-PCR analysis confirmed that GIST expressed SMemb-mRNA, which lacked neuronal cell-specific inserts of 30 bp. These facts further strengthen the current hypothesis that GIST is a tumor of ICCs.

Adult↗

PubMed1999

Giant fusiform aneurysm of the basilar artery: consideration of its pathogenesis.

BACKGROUND: We tried to determine the pathogenesis of a fusiform aneurysm of the basilar artery based on the findings of two patients who had pontine infarctions due to thrombosis within the aneurysm. CASE REPORT: The patients were female, aged 75 and 62 years. At autopsy of the first case, the dilated basilar artery was filled with fresh and old thrombus. The wall was extremely thin on the left side, where a fresh red thrombus was evident, and thick on the right side, where an old white thrombus appeared. The thick wall had a thickened and hyalinized intima, and a deposition of atheromatous plaque disrupted both the internal elastic lamina and muscle layer. The left vertebral artery was atherosclerotic and its lumen was severely compromised, but the right vertebral artery was hypoplastic. On angiogram of the second case, the dilated basilar artery presumably was filled with thrombus on the left side, contralateral to the dilated and tortuous vertebral artery. The left vertebral artery was hypoplastic. CONCLUSION: Atherosclerosis may be the essential factor in the pathogenesis of a fusiform aneurysm of the basilar artery in elderly patients. The disrupted internal elastic lamina and muscle layer may be susceptible to mechanical injury by hemodynamic strain, causing progressive attenuation of the arterial wall. Stenosis of the vertebral artery on the dominant side probably produces a jet stream within the basilar artery on the stenotic side and a stagnant zone on the opposite side, promoting the initial thrombus formation.

Aged↗

PubMed1999

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗

PubMed1999

Exposed peptide core of IgA1 hinge region in IgA nephropathy.

BACKGROUND: The human IgA1 hinge region is a very unique O-linked glycopeptide, and its sialylation and galactosylation recently were reported to be defective in the serum IgA1 derived from patients with IgA nephropathy (IgAN). This study was performed to examine the underglycosylation of the IgA1 hinge region and consequent exposure of the peptide core in IgAN. METHODS: A polyclonal antibody against a synthetic human IgA1 hinge peptide, PVPSTPPTP SPSTPPTPSPS, (anti-sHP ab) was raised in rabbits and shown specifically to recognize the IgA1 which was treated with neuraminidase, beta-galactosidase and alpha-N-acetylgalactosaminidase. The reactivity of the anti-sHP ab against the purified serum IgA1 was compared among the following three groups: 39 patients with IgAN, 30 patients with other renal diseases (ORD) and 21 healthy controls (HC) using an enzyme-linked immunosorbent assay. RESULTS: The reactivity was significantly higher in the IgAN group (mean +/- SD of OD 490 nm: 0.327 +/- 0.059) than in the ORD group (0.274 +/- 0.043, P=0.0002) and in the HC group (0.265 +/- 0.037, P<0.0001). No significant difference was observed between the latter two groups. The frequency of positive cases (> mean +/- 2SD of HC) was 46.2% (18/39) in the IgAN group, 6.7% (2/30) in the ORD group and 0% (0/21) in the HC group. CONCLUSIONS: It was suggested that the peptide core of the IgA1 hinge region is exposed aberrantly by a defective N-acetylgalactosaminylation and plays a possible role in the pathogenesis of IgAN.

Adolescent↗

PubMed1999

The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis.

Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism.

Alleles↗

PubMed1999

Synchrotron microangiography reveals configurational changes and to-and-fro flow in intramyocardial vessels.

In 8 dogs, in situ microangiography using synchrotron radiation visualized penetrating transmural arteries (PTAs) with a diameter of >60 micrometers and allowed quantitation of vessel diameters of >140 micrometers. Myocardial contraction reduced the vascular short-axial diameters to 87 +/- 17% (n = 62, P < 0.001, paired t-test) of the end-diastolic values and increased the longitudinal dimension to 129 +/- 5% (n = 45, P < 0.001). The diameter reduction in the subendocardial PTA segments was significantly more marked than that in the subepicardial PTA segments (60 +/- 12 vs. 88 +/- 12%, n=13, P < 0.001, paired t-test). Intracoronary administration of dobutamine (0.1 micrograms. kg-1. min-1) increased, and in contrast, partial clamping of the coronary artery (ischemia) decreased, the configurational changes. To-and-fro blood flow was clearly observed in PTAs with visual identification of capacitive backflow, resistive forward flow during ischemia on coronary arteriography, and even under baseline conditions in coronary venography. Thus this method advances our understanding of mechanical influences on the coronary circulation.

Animals↗

PubMed1999

Decrease of serum levels of soluble CD23 during immunotherapy in patients with perennial allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating the synthesis of human IgE and is likely involved in the expression of allergic diseases. Our study has aimed at investigating whether serum sCD23 is elevated in patients with perennial allergic rhinitis as compared to nonatopic controls, whether sCD23 in perennial allergic rhinitis fluctuates during the natural course in untreated patients, and whether sCD23 is decreased by immunotherapy. This study included 139 patients with perennial allergic rhinitis due to Dermatophagoides farinae who gave informed consent to participation. They were divided into 2 groups--an untreated group and an immunotherapy group--according to their treatment background. Thirty-one nonallergic, healthy volunteers were included to serve as controls. Symptom scores and serum concentrations of IgE specific to D. farinae and sCD23 were examined twice in each patient: at enrollment (first evaluation) and on a variant time course after enrollment (second evaluation). Serum concentrations of sCD23 were measured by a sandwich enzyme-linked immunosorbent assay. The level of sCD23 in patients with perennial allergic rhinitis was significantly higher than that in nonatopic controls (p < .0001). The level of sCD23 in perennial allergic rhinitis was correlated with the level of specific IgE against D. farinae. The sCD23 level did not fluctuate during the natural course for a span of 2.8 +/- 2.7 years in untreated patients (p = .1337), but was significantly decreased in patients who received immunotherapy for 2.7 +/- 2.2 years (p < .0001). The rate of decrease in sCD23 was significantly correlated with the rate of decrease in specific IgE (rs = .523, p < .0001) and symptom scores (rs = .450, p < .0001). In conclusion, the reduction in sCD23 during immunotherapy is probably related to the decrease in specific IgE and also plays a role in mediating its clinical effect.

Adult↗

PubMed1999

Isolated primary chylopericardium.

A 16-year-old man was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid. The thoracic duct was easily identified by giving milk and butter and an injection of ethylene blue immediately before the operation. Intraoperative thoracic ductography showed no abnormal findings. Mass ligation of the thoracic duct above the diaphragm and partial pericardiectomy were successfully performed through a right thoracotomy approach. In addition, many of the lymphatics were ligated above the diaphragm. The right thoracotomy approach was a useful method for resection and ligation of the thoracic duct just above the diaphragm. Follow-up showed no accumulation of pericardial fluid or pleural effusion.

Adolescent↗

PubMed1999

[Epidemiology of Japanese cedar pollinosis: result of the survey in Mibu-machi].

The prevalence rate of Japanese cedar pollinosis has increased since 1979. We conducted a survey of the residents of Mibu-mach, Tochigi, in 1988 and 1996 using a questionnaire to determine the prevalence rate of cedar pollinosis. Results showed its rate was 15.6% in 1988, and 25.6% in 1996. Age distribution analysis of patients with Japanese cedar pollinosis showed the highest prevalence in patients between the ages of 10 to 49 years in 1988, and between the ages of 10 to 59 years old in 1996. Within these age groups, the majority of the patients were females, but males were more prevalent than females in the age group under 19 years old. The prevalence rate of patients by age group revealed the same pattern as the age distribution of the patients. Age distribution of cedar pollinosis showed a peak in patients in their thirties both in 1988 and 1996. In conclusion, the numbers of patients with Japanese cedar pollinosis has been increasing remarkably in Mibu-mach. As climate or environmental conditions are varied in different geographical regions in Japan, further epidemiological studies in various regions of the country are required to clarify the actual prevalence rate of cedar pollinosis.

Adolescent↗

PubMed1999

[A case in which palatal squamous cell carcinoma responded to UFT therapy].

We administered UFT to a 70-year-old female with squamous cell carcinoma of the palatal mucosa (T1 N0 M0) who had not consented to radical surgical treatment. The tumor disappeared grossly and histopathologically after 1 month, and no adverse reaction to oral administration of UFT was noted. The patient remains under observation.

Administration, Oral↗

PubMed1999

The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis.

Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf phenotypes in plants. Understanding the regulation of BR biosynthesis demands continued isolation and characterization of mutants corresponding to the genes involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results from feeding studies with 13C-labeled mevalonic acid and compactin show that the defective step is specifically the Delta7 sterol C-5 desaturation, suggesting that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7.

Alleles↗