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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 109 records · Page 6Linked to original sources

Preparation of a monoclonal antibody specific for human stanniocalcin.

Stanniocalcin (STC) is a glycoprotein hormone that was first identified in fish, where it regulates the calcium level in the body fluid. The cDNA which encodes human STC has recently been reported but the function has not been completely elucidated. We have prepared a monoclonal antibody against human STC using an analogous peptide of the putative antigenic domain in human STC; it was conjugated with keyhole limpet hemocyanin (KLH). The monoclonal antibody specifically stained the distal convoluted tubules in human kidney which is a putative target organ of STC. The ELISA was established using the monoclonal antibody and recombinant human STC as a standard antigen. The monoclonal antibody prepared in this study provides a useful tool for clinical studies of STC in human.

Amino Acid Sequence↗

Reconstruction of the coronoid for chronic dislocation of the elbow. Use of a graft from the olecranon in two cases.

Persistent dislocation of the elbow after a fracture of the coronoid process is a difficult problem. We have performed an open reduction with reconstruction of the coronoid by an osteocartilaginous graft from the ipsilateral olecranon for two patients. Both achieved a painless, stable joint with a functional range of movement. The joint surface of the graft has a similar curve to that of the coronoid giving good congruency and stability. The technique is simple and the graft is obtained through the same incision.

Adult↗

Cavity adaptation of resin composite in canine cavity in vivo.

The efficacy of four commercial and two experimental dentin bonding systems was examined by observing the cavity adaptation of commercial light-cured resin composites restored in the dogs scheduled to be sacrificed after a medical experiment. Before being sacrificed, a cylindrical class V cavity was prepared in each canine, and the cavity wall was treated with one of four commercial dentin bonding systems according to the manufacturers instructions followed by resin composite filling. The maximum contraction gap widths at the occlusal, gingival and axial cavity wall were measured on the cavity section 30 min after the polymerization of the resin composite under a light microscope. Contraction gap formation was completely prevented in only one of the experimental groups in which the cavity wall was primed with 35 vol% glyceryl mono-methacrylate (GM). In addition, observation of cavity adaptation in the canine in vivo was useful to estimate consistently the efficacy of the bonding systems.

Alkanes↗

[A tuberculosis epidemic among four relatives who live in the neighborhood of index case].

A tuberculosis epidemic occurred among 4 relatives who live in the neighborhood of the index case. A thirty-three year old female was admitted to a hospital in July 1994 with high fever and cervical lymphoadenopathy. Culture examination of her sputum was positive for acid-fast bacilli and her chest X-ray showed diffuse small nodules. During the following sixteen months, five new patients with pulmonary tuberculosis were found among the relatives who lived in the neighborhood of the index case. The contact examination was first limited in her own family members, however, after detection of the second case, the examination was extended to other relatives living nearby, and another four patients were found. The results of PPD skin test of ten contact children showed strongly positive reaction, and chemoprophylaxis was indicated. Contacts examination is very important especially for patients with highly infectious tuberculosis.

Adolescent↗

[MPO-ANCA related diffuse alveolar hemorrhage].

The purpose of this study was to elucidate the clinical features characterizing patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA) related diffuse alveolar hemorrhage (DAH). Seventeen MPO-ANCA-positive patients were evaluated. Nine patients (52.9%) had pulmonary involvement; of those, 6 (35.3%) had DAH, and 4 (23.5%) had interstitial pneumonia (1 patient had both pulmonary diseases). Three of the patients with DAH demonstrated only mildly bloody sputum. All patients with DAH had increased peripheral white blood cell counts, high titers of C-reactive protein and MPO-ANCA, and marked microscopic hematuria. DAH was diagnosed in all cases by fiberoptic bronchoscopy with bronchoalveolar lavage. All patients with DAH were treated with three pulses of methylprednisolone, and 5 were treated with cyclophosphamide. Three of the patients with DAH required mechanical ventilation for respiratory insufficiency, but 2 were relieved of that need by immunosuppressive therapy. In spite of intensive care, 1 patient died of respiratory failure and 2 died of complications related to therapy. The prognosis for patients with DAH is poor. We emphasize the importance of prompt and accurate diagnoses and aggressive care, including immunosuppressive therapy, mechanical ventilation, and hemodialysis. In addition, extra precautions should be taken against opportunistic infections such as Pneumocystis carinii pneumonia.

Aged↗

A novel mutation of the down-regulated in adenoma gene in a Japanese case with congential chloride diarrhea. Mutations in brief no. 198. Online.

Congenital chloride diarrhea (CLD) is an autosomal recessive disease characterized by excretion of watery stool with a high chloride content. Pathogenesis of CLD is a deficient absorption of chloride in exchange for bicarbonate in the ileum and the colon. In 1996, it was reported that 36 patients with CLD had mutations in the down-regulated in adenoma (DRA) gene; 32 Finnish patients had a three base deletion (951delGGT), 2 Polish patients had a one base mutation (371AtoT) and 2 Polish patients had a one base deletion (344delT). In this study we analyzed the DRA gene in a Japanese boy patient with CLD and in members of his family. The patient was found to have a two base deletion (TT) at nucleotide 1526-1527 within codon 509 which results in a frameshift leading to a permature stopping at codon 517. The patient was homozygous for the deletion, his parents and brother were heterozygous, and his sister was normal. This is the first case of CLD identified to carry a mutation of the DRA gene in Asia.

Adenoma↗

Association study between the -141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism.

Dopamine D2 receptors have been implicated in the biology of alcohol preference. We examined the -141 C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and the DRD2 TaqI A polymorphisms in 209 Japanese alcoholics and 152 age- and sex-matched Japanese controls. The Ins allele was significantly increased in the alcoholics, compared with the controls (p < 0.002, odds ratio = 1.82). The TaqI A1 allele tended to be more frequent in the alcoholics than in the controls (p < 0.04). Linkage disequilibrium between these two polymorphisms was weak (a maximum delta value = 0.13). The -141 C Ins/Del polymorphism may affect the vulnerability for alcoholism presumably through different expression of DRD2 in the Japanese.

Adult↗

Nutrient regeneration in coastal seas by Noctiluca scintillans, a red tide-causing dinoflagellate.

Ammonium nitrogen, phosphate, and silicate contents in Noctiluca scintillans cell fluid were estimated at 2470, 183, and 54 pmol per individual, respectively. Ammonium nitrogen and phosphate concentrations at the surface layer of the water column seemed to be related to cell abundance of N. scintillans at the sampling location. Patches of N. scintillans provided 16 and 25 times greater concentrations of ammonium nitrogen and phosphate in the uppermost layer (0-10 cm depth) of the water column than those in the ambient seawater, respectively. Silicate concentration within patches, however, was close to that in surrounding water. The morphology of fecal pellets of N. scintillans fed on the diatom, Thalassiosira sp., was examined with a scanning electron microscope. The fecal pellet was composed entirely of visible structural diatom cells. It could be inferred that N. scintillans excretes silica from the diatom undigested in its fecal pellets and thus no remarkably high silicate concentration within red tide patches was observed.

Journal Article↗

Detection of secretory phospholipase A2s related but not identical to type IIA isozyme in cultured mast cells.

We previously reported that BALB/cJ mouse-derived bone marrow-derived mast cells (BMMC) exhibited two sequential phases of prostaglandin D2 (PGD2) generation in response to Fc(epsilon) receptor I (Fc(epsilon)RI) crosslinking and cytokine stimulation, the late phase of which was suppressed by an antibody raised against type IIA secretory phospholipase A2 (sPLA2). Here we report that BMMC derived from C57BL/6J mice, which are genetically deficient in type IIA sPLA2, display both immediate and delayed PGD2 generation normally. Lysates of C57BL/6J-derived BMMC contained a Ca2+-dependent PLA2 that was absorbed to a column conjugated with anti-type IIA sPLA2 antibody and had a similar molecular mass of 14 kDa, as assessed by immunoblotting. Therefore we speculate that a sPLA2 similar to, but distinct from, type IIA sPLA2 would compensate for type IIA sPLA2 deficiency in C57BL/6J-derived BMMC. We found that the two type IIA-related sPLA2 family members, type V and type IIC sPLA2s, were expressed in BMMC as well as in rat mastocytoma RBL-2H3 cells.

Animals↗

Massive repopulation of rat liver by transplantation of hepatocytes into specific lobes of the liver and ligation of portal vein branches to other lobes.

An important consideration in application of hepatocyte transplantation is whether the number of engrafted hepatocytes is sufficient to achieve the desired effect. Here we have evaluated the proliferative potential of transplanted primary hepatocytes during regeneration of hepatic lobes. Two million hepatocytes isolated from congeneic normal Wistar-RHA rats were injected into the main portal vein of deficient, jaundiced Gunn rats. The right branch of the portal vein was ligated 24 hr before hepatocyte transplantation (group A) or transiently clamped during hepatocyte injection (group B) or 24 hr after hepatocyte injection (group C). In these groups, the three lobes supplied by the right branch of the portal vein rapidly atrophied and disappeared in 4 days, whereas the remaining lobes proliferated, as shown by size increase and 5-bromo-2-deoxy-uridine uptake. Two control groups received 2 million (group D) or 20 million hepatocytes (group E) without ligation. Hepatocyte engraftment occurred in all groups. The greatest hypobilirubinemic effect was observed in group A, in which serum bilirubin concentrations were reduced to 1.7+/-0.45 mg/dl from pretransplantation levels of 6.9+/-1.2 mg/dl. This effect was even greater than that observed after transplantation of 20 times more hepatocytes without ligation (group E). Specific endonuclease digestion of a polymerase chain reaction-amplified segment of the ugt1 gene from hepatic DNA showed that up to 25% of the DNA was of donor origin. This paralleled the hepatic bilirubin-UDP-glucuronosyltransferase activity, which was above 50% of normal. The results indicate that the transplanted hepatocytes proliferate preferentially within the regenerating lobes, replacing more than 20% of the liver mass with the progeny of the transplanted phenotypically normal hepatocytes.

Animals↗

Cyclooxygenase-2-dependent delayed prostaglandin D2 generation is initiated by nerve growth factor in rat peritoneal mast cells: its augmentation by extracellular type II secretory phospholipase A2.

When rat serosal connective tissue mast cells (CTMC) were stimulated with nerve growth factor (NGF), the immediate prostaglandin D2 (PGD2) generation was followed by delayed PGD2 generation that occurred between 2 and 24 h, reaching levels as high as 50 ng and 260 ng/10(6) cells in the absence or presence of lysophosphatidylserine (lysoPS), respectively. This delayed PGD2 generation was accompanied by de novo induction of cyclooxygenase (COX)-2, with NGF and lysoPS acting as inducer and enhancer, respectively. COX-2 induction and the attendant delayed PGD2 generation in CTMC were modestly induced by c-kit ligand, but not by Fc epsilonRI cross-linking. This indicated that the stimulus specificity differed from that observed in the immediate phase, in which NGF, c-kit ligand, and Fc epsilonRI cross-linking, either in combination with each other or with lysoPS as a cofactor, elicited comparable levels of PGD2 generation within 10 min, reaching 10 to 20 ng/10(6) cells. Addition of type II secretory phospholipase A2 (sPLA2), a PLA2 isoform that is detected in microg/ml levels in inflammatory exudates, to NGF-stimulated CTMC significantly augmented delayed, but not immediate, PGD2 generation, and this augmentative effect was mediated in part by the enhancement of COX-2 expression by sPLA2. These results suggest that CTMC have the capacity to produce PGD2 over a prolonged period in the presence of tissue-derived cytokines and sPLA2 in a COX-2-dependent manner.

Animals↗

Depletion of cerebral D-serine in non-ketotic hyperglycinemia: possible involvement of glycine cleavage system in control of endogenous D-serine.

Tissue concentrations of D-serine and other chiral and non-chiral amino acids were measured post-mortem in the cerebral cortex of the neonatal or infantile individuals with (three cases) or without (seven cases) non-ketotic hyperglycinemia (NKH) using high performance liquid chromatography with fluorometric detection. In the cortical tissues of the NKH patients lacking activity of glycine cleavage system, there was a marked reduction and elevation of the contents of D-serine and glycine, respectively, compared to non-NKH controls. Systemic administration of an inhibitor of glycine cleavage system (GCS), cysteamine, mimicked the changes in the cortical concentrations of these amino acids in the 8-day-old rats. Augmentation of brain glycine levels by means of intraperitoneal injection of glycine itself resulted in an increase in cortical D-serine contents in the neonatal rats with normal activity of GCS. These findings provide the first evidence that GCS might be implicated in the biosynthesis or content regulation of endogenous D-serine in the mammalian brain.

Amino Acid Oxidoreductases↗

Nicotinamide derivatives as a new class of gastric H+/K(+)-ATPase inhibitors. 1. Synthesis and structure-activity relationships of N-substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides.

A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7 and 8 were synthesized. Upon acid activation in the acidic environment of the parietal cell, these compounds are converted into their active forms, 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K(+)-ATPase. Inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration in vivo were evaluated, and the structure-activity relationships were examined. Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in vivo equivalent to those of omeprazole, a typical H+/K(+)-ATPase inhibitor. Moreover, 8b was much more stable at neutral and weakly acidic pH than omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a promising agent for treating acid-related gastrointestinal disorders.

Aminopyrine↗

Transplantation of Gunn rats with autologous fibroblasts expressing bilirubin UDP-glucuronosyltransferase: correction of genetic deficiency and tumor formation.

The end product of the breakdown of the heme group of hemoglobin and other heme-containing proteins is bilirubin. Bilirubin is hydrophobic and cannot be excreted as such. Therefore, mammals have a liver enzyme bilirubin UDP-glucuronosyltransferase (B-UGT), which conjugates bilirubin with glucuronic acid, thereby making the molecule much more water soluble. Bilirubin glucuronides are secreted into bile. Patients with Crigler-Najjar (CN) disease have a deficiency in bilirubin UDP-glucuronosyltransferase and accumulate high serum levels of bilirubin. An animal model for CN disease is the Gunn rat. The obvious target for gene therapy for CN disease is the liver, but because liver cells do only divide infrequently, they are difficult to transduce. To investigate whether cells that are easily transduced can be used to develop gene therapy for CN disease, we have transduced Gunn rat fibroblasts with B-UGT, using a recombinant retrovirus. Gunn rat fibroblasts expressing B-UGT were able to glucuronidate bilirubin present in cell culture media. In this study, we describe the intraperitoneal transplantation of Gunn rats with Gunn rat fibroblasts expressing B-UGT. Transplantation of the fibroblasts corrected the genetic deficiency of the Gunn rats, serum bilirubin concentrations of the transplanted Gunn rats were reduced to normal, and bilirubin glucuronides appeared in bile. However, due to the prolonged period of cell culture, the transplanted fibroblasts were transformed, and the experimental animals developed tumors after transplantation.

Animals↗

Nonketotic hyperglycinemia: biochemical, molecular, and neurological aspects.

Nonketotic hyperglycinemia (NKH) is a metabolic disorder with autosomal recessive inheritance, causing severe, frequently lethal, neurological symptoms in the neonatal period. The metabolic lesion of NKH is in the glycine cleavage system (GCS), a complex enzyme system with four enzyme components; P-, T-, H-, and L-protein. The enzymatic analysis revealed that 86% of the patients with NKH are deficient of P-protein activity. The cDNA clones encoding all four components were isolated and their primary structures were determined. Several mutations have been identified in P- and T-protein genes: One missense mutation, S564I, in P-protein gene accounts for 70% of the mutant alleles in Finland where the incidence of NKH is unusually high. The immunochemical and in situ hybridization analyses revealed that the strong GCS expression was observed in rat hippocampus, olfactory bulbus, and cerebellum. The distribution resembled that of N-methyl-D-aspartic acid (NMDA) receptor which has binding site for glycine. It is, therefore, suggested that the neurological disturbance in NKH may be caused by excitoneurotoxicity through the NMDA receptor allosterically activated by high concentration of glycine. Based on the hypothesis the NMDA antagonists such as ketamine and dextromethorphan were administered to the patients. We treated three neonatal case with dextromethorphan and it ameliorated their findings on electroencephalogram and behavior in two out of three patients. Thus the GCS is suggested to play a role in regulation of glycine level around the NMDA receptor.

Amino Acid Metabolism, Inborn Errors↗