Search PubMed⌕ Search

Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 91 records · Page 5Linked to original sources
PubMed1999

[An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to].

A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.

Aged↗
PubMed1999

Anxiolytic 5-hydroxytryptamine1A agonists suppress firing activity of dorsal hippocampus CA1 pyramidal neurons through a postsynaptic mechanism: single-unit study in unanesthetized, unrestrained rats.

Recent behavioral studies indicate that conditioned fear response to contextual stimuli is reduced effectively by anxiolytic 5-hydroxytryptame (5-HT)1A agonists. Since the hippocampus seems to play an essential role in associative fear memories evoked by context, it is important to assess the effect of 5-HT1A agonists on pyramidal cell activity in the hippocampus. We examined the effects of 5-HT1A agonists on the spontaneous firing rate of hippocampal CA1 pyramidal neurons in unanesthetized, unrestrained rats. Systemic administration of selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone, and flesinoxan produced a dose-dependent inhibition of neuronal activity. Putative 5-HT1A antagonists NAN-190 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine and (-)-pindolol did not change neuronal activity of CA1 pyramidal neurons. The suppression of neuronal activity by buspirone was antagonized by NAN-190 but not by (-)-pindolol. Lack of antagonistic activity of (-)-pindolol for the suppression of pyramidal neurons via a postsynaptic mechanism is consistent with the results of recent electrophysiological experiments in anesthetized rats. Pretreatment with parachlorphenylalanine did not change the spontaneous firing rates of hippocampal CA1 pyramidal neurons or abolish the suppressant effects of buspirone on these neurons. Taken together, the present results strongly suggest that suppression of the hippocampal CA1 pyramidal neuronal activity by anxiolytic 5-HT1A agonists in awake rats is mediated by postsynaptic 5-HT1A receptors located on pyramidal neurons.

Animals↗
PubMed1998

Induction of cyclooxygenase-2 by secretory phospholipases A2 in nerve growth factor-stimulated rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechanism independent of their enzymatic functions.

Mast cells exhibit a biphasic (immediate and delayed) eicosanoid-biosynthetic response after stimulation with particular cytokines or Fc epsilonRI (high affinity receptor for IgE) cross-linking. Treatment of rat serosal connective tissue mast cells (CTMC) with nerve growth factor (NGF) induced only the delayed phase of PGD2 generation that depended on inducible cyclooxygenase-2 (COX-2), but not constitutive COX-1, even though the subcellular distributions of these isoforms were similar. Experiments using several phospholipase A2 (PLA2) isozyme-specific probes and inhibitors suggested that both constitutive cytosolic PLA2 and inducible type IIA secretory PLA2 (sPLA2) are involved in NGF-initiated, COX-2-dependent, delayed PGD2 generation in rat CTMC. A type IIA sPLA2 inhibitor, but neither cytosolic PLA2 nor COX inhibitors, reduced, while adding exogenous type IIA sPLA2 augmented, NGF-induced COX-2 expression and its attendant PGD2 generation, indicating that the sPLA2-mediated increase in delayed PGD2 generation was attributable mainly to enhanced COX-2 expression. Type IIA sPLA2 and its close relative type V sPLA2 associated with fibroblastic cell surfaces increased NGF-induced COX-2 expression more efficiently than the soluble enzymes, revealing a particular juxtacrine sPLA2 presentation route. Surprisingly, catalytically inactive type IIA sPLA2 mutants, which were incapable of promoting arachidonic acid release from cytokine-primed cells, retained the ability to enhance COX-2 expression in CTMC, indicating that the COX-2-inducing activities of sPLA2 are independent of their catalytic functions.

Animals↗
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

Long-term reduction of serum bilirubin levels in Gunn rats by retroviral gene transfer in vivo.

Conjugation with glucuronic acid, mediated by bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (bilirubin-UGT), is essential for efficient biliary excretion of bilirubin. Inherited absence of this enzyme activity results in the potentially lethal Crigler-Najjar syndrome type I in humans and lifelong hyperbilirubinemia in Gunn rats. To develop a gene therapy for bilirubin-UGT deficiency, we constructed a high-titer replication-deficient amphotropic recombinant retrovirus (MFG-S hB-UGT1) capable of transferring the gene encoding bilirubin-UGT1, the principal bilirubin-UGT isoform in human liver. To stimulate hepatocyte proliferation, Gunn rats were subjected to 66% hepatectomy. After 24 hours, the portal vein, the hepatic artery, and the inferior vena cava above and below the hepatic vein were clamped, and the portal vein and the isolated segment of the vena cava were cannulated. The liver was perfused with the MFG-S hB-UGT1 preparation through the portal vein at 5 ml/min for 10 minutes, then circulation was restored. Control rat livers were perfused with a recombinant retrovirus expressing Escherichia coli beta-galactosidase. In MFG-S hB-UGT1-perfused rats, but not in controls, expression of human bilirubin-UGT1 was shown by immunotransblotting, bilirubin-UGT assay of liver homogenates, and biliary excretion of bilirubin diglucuronide and monoglucuronide. Mean serum bilirubin levels decreased by 20% to 25% in 3 weeks and remained at that level throughout the study period (18 months). This is the first report of long-term amelioration of inherited jaundice by retrovirus-directed gene therapy in an animal model for Crigler-Najjar syndrome.

Animals↗
PubMed1998

A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is caused by a mutation in the genes encoding the components of the glycine cleavage multi-enzyme system. More than 80% of the patients have defects in the gene encoding P-protein, whereas the rest of the patients have defects in the gene encoding T-protein. We have found a large Israeli-Arab kindred with NKH. At least 14 children were affected, and all the patients had seizures and respiratory failure within 2 days after birth. Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. We screened this family for a mutation in the protein-coding region and exon/intron boundaries of T-protein gene by direct sequencing analysis. A missense mutation was found in exon 2; this resulted in an amino acid substitution from histidine to arginine at position 42 (H42R). Histidine 42 is conserved in human, bovine, chicken, pea, and Escherichia coli, suggesting that it has an important role in catalytic functions. Genotype analyses of 26 family members confirmed that the homozygous H42R mutation was completely associated with the onset of NKH. The availability of DNA testing facilitates the prenatal diagnosis of NKH and the identification of carriers, which is necessary for genetic counseling in the affected families.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Activated hepatic stellate cells participate in liver fibrosis in a patient with transfusional iron overload.

We describe liver fibrosis caused by iron overload after a long history of blood transfusion in a patient with chronic renal failure. Pertinent laboratory data were: serum (s)-Fe 148 microg/dl; unsaturated iron binding capacity (UIBC) 14 microg/dl; s-ferritin 9350 ng/ml; human leukocyte antigen (HLA) A2, A24, B39, B55, Cw1, Cw7. Computed tomography revealed a high density in the liver, and laparoscopy revealed a brown liver. Liver histology showed bridging fibrosis from portal tracts. A heavy iron deposit was seen in Kupffer cells as well as in hepatocytes surrounded by fibrosis around the portal tracts. Immunocytochemistry revealed alpha-smooth muscle actin in many stellate cells distributed along the fibrotic area, and electron microscopy revealed infiltrating myofibroblastic stellate cells coexisting with collagen fibers around degenerated hepatocytes containing iron deposits. The findings are consistent with the notion that stellate cells play an important role in liver fibrogenesis in both genetic and transfusional iron overload hemochromatosis.

Adult↗
PubMed1998

A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia.

Two novel mutations in the gene encoding T-protein, a component of the glycine cleavage system, were identified in a Japanese family with nonketotic hyperglycinemia. The proband had two affected sibs, and enzymatic analysis of the liver sample from the proband revealed the T-protein deficiency. The first mutation, 183delC, was found in exon 1. One of six cytidine residues (base position 183-188) was deleted. The deletion was located in a coding region of the mitochondrial leader peptide and was deduced to create a truncated peptide with 94 amino acids. The second mutation was a base substitution from G to C at position 955 in exon 7. The G955C substitution caused an amino acid change from aspartate to histidine at position 276 (D276H). Aspartic acid at position 276 is evolutionarily conserved among human, bovine, chicken, and pea genes, and replaced by glutamic acid in Escherichia coli, suggesting that the presence of an acidic amino acid at 276 may be crucial for the enzymatic function. No base change other than the 183delC and the G955C was observed in the sequencing analysis. Familial analysis revealed that the 183delC and the D276H mutations were inherited from the father and the mother, respectively. This is the first report of T-protein gene mutation in Oriental patients with nonketotic hyperglycinemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Favorable response to lymphoblastoid interferon-alpha in children with chronic hepatitis C.

BACKGROUND/AIMS: We investigated the efficacy of interferon therapy for the treatment of children with chronic hepatitis C virus infection. METHODS: Twenty-four out of 26 children completed the 6-month treatment with lymphoblastoid interferon-alpha and were followed for 12 months or longer. Response to interferon therapy was defined by assaying for circulating HCV-RNA, using a nested PCR, at 6-month intervals after the end of the therapy. RESULTS: At the end of treatment circulating HCV-RNA was undetectable in 18/24 patients and at 6 months in 12/24. Ten of these 12 primary responders have remained virus free for more than 2 years. One patient remained negative at 12 months. The remaining patient relapsed at 12 months. At 24 months 10 of 18 patients tested negative for HCV-RNA. Serum alanine aminotransferase was normal in 11/24 patients at the end of treatment, at 6 months 12/24 were normal, and at 12 months 11/12 were normal. In eight children with sustained response, repeated liver biopsies revealed a reduction in Knodell's scores for inflammation in the hepatic lobules and in the portal areas. In three of them neither plus nor minus strand of HCV-RNA was detectable in the liver tissue. Responders had a significantly lower level of viremia than non-responders. Side effects of interferon including fever, hair loss, neutropenia, and thrombocytopenia were not serious enough to warrant cessation of interferon treatment. CONCLUSIONS: Interferon therapy in children with chronic hepatitis C may be beneficial as evaluated by sustained loss of viremia as well as by primary response.

Adolescent↗
PubMed1998

Attritional rupture of flexor tendons by the head of the ulna associated with a chronic longitudinal radioulnar dissociation.

A 62-year-old woman sustained multiple attritional ruptures of the flexor tendons at the wrist caused by displacement of the head of the ulna. She had had injuries of the wrist and elbow when she was young, which were thought to have caused chronic longitudinal radioulnar dissociation with palmar dislocation of the head of the ulna. Attrition of the flexor tendons by the dislocated ulnar head during pronation and supination was the major mechanism for the ruptures in this case. She was successfully treated with tendon transfer and resection of the ulnar head.

Chronic Disease↗
PubMed1998

Follow-up study of hypervariable region sequences of the hepatitis C virus (HCV) genome in an infant with delayed anti-HCV antibody responses.

An infant born prematurely and infected with hepatitis C virus (HCV) one month after birth was followed for 4.5 years. The patient did not produce detectable anti-HCV antibodies until two years after the onset of hepatitis. Before seroconversion, a single clone of HCV, as determined by quasispecies of the hypervariable region (HVR) of the HCV genome, was almost exclusively found in the serum. After seroconversion, however, another distinct lineage of HCV clones replaced it within half a year. As HCV infection persisted further in the presence of anti-HCV antibodies, many derivatives of both sequence lineages emerged to exhibit the typical quasispecies feature of HVR sequences. Neither seroconversion nor the changes in HVR sequences influenced the serum aminotransferase titers.

Aging↗
PubMed1998

Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine.

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

Adolescent↗
PubMed1998

Molecular characterization and heterologous expression of the gene encoding a low-molecular-mass endoglucanase from Trichoderma reesei QM9414.

We have isolated the genomic and cDNA clones encoding EG III (a low-molecular-mass endo-beta-1,4-glucanase) gene from Trichoderma reesei QM9414. The nucleotide sequence of the cDNA fragment was verified to contain a 702-bp open reading frame that encodes a 234-amino-acid propeptide. The deduced protein sequence has significant homologies with family H endo-beta-1,4-glucanases. The 16-amino-acid N-terminal sequence was shown to function as a leader peptide for possible secretion. Northern blot analysis showed that the EG III gene transcript, with a length of about 700 bp, was expressed markedly by cellulose but not by glucose. The protein has been expressed as a mature form in Escherichia coli and as secreted forms in Saccharomyces cerevisiae and Schizosaccharomyces pombe under the control of tac, alcohol dehydrogenase (ADH1), and human cytomegalovirus promoters, respectively. The S. cerevisiae and Schizosaccharomyces pombe recombinant strains showed strong cellulolytic activities on agar plates containing carboxymethyl cellulose. The E. coli strain expressed small amounts of EG III in an active form and large amounts of EG III in an inactive form. The molecular masses of the recombinant EG IIIs were estimated to be 25, 28, and 29 kDa for E. coli, S. cerevisiae, and Schizosaccharomyces pombe, respectively, by immunoblot analysis following sodium dodecyl sulfate-polyacryl-amide gel electrophoresis. Parts of the yeast recombinant EG IIIs decreased their molecular masses to 25 kDa after treatment with endoglycosidase H and alpha-mannosidase, suggesting that they are N glycosylated at least partly.

Amino Acid Sequence↗
PubMed1998

Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells.

Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytocidal effect. Accumulating evidence now implicates the nonstructural (NS1) protein of the virus in cytotoxicity, but the mechanism underlying the NS1-induced cell death is not known. Using a stringent regulatory system, we demonstrate that NS1 cytotoxicity is closely related to apoptosis, as evidenced by cell morphology, genomic DNA fragmentation, and cell cycle analysis with the human erythroleukemia cell line K562 and the erythropoietin-dependent megakaryocytic cell line UT-7/Epo. Apoptosis was significantly inhibited by an interleukin-1beta (IL-1beta)-converting enzyme (ICE)/CED-3 family protease inhibitor, Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar inhibitor of ICE (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore, stable expression of the human Bcl-2 proto-oncogene resulted in near-total protection from cell death in response to NS1 induction. Mutations engineered into the nucleoside triphosphate-binding domain of NS1 significantly rescued cells from NS1-induced apoptosis without having any effect on NS1-induced activation of the IL-6 gene expression which is mediated by NF-kappaB. Furthermore, using pentoxifylline, an inhibitor of NF-kappaB activation, we demonstrate that the NF-kappaB-mediated IL-6 activation by NS1 is uncoupled from the apoptotic pathway. This functional dissection indicates a complexity underlying the biochemical function of human parvovirus NS1 in transcriptional activation and induction of apoptosis. Our findings indicate that NS1 of parvovirus B19 induces cell death by apoptosis in at least erythroid-lineage cells by a pathway that involves caspase 3, whose activation may be a key event during NS1-induced cell death.

Apoptosis↗
PubMed1998

Three cases of malignant pheochromocytoma treated with cyclophosphamide, vincristine, and dacarbazine combination chemotherapy and alpha-methyl-p-tyrosine to control hypercatecholaminemia.

We describe 3 cases of malignant pheochromocytoma with multiple metastases which were treated with cyclophosphamide, vincristine and dacarbazine (CVD) combination chemotherapy and alpha-methyl-p-tyrosine. Case 1 was operated on first but hypercatecholaminemia could not be completely controlled. Cases 2 and 3 received chemotherapy, CVD combination chemotherapy and/ or alpha-methyltyrosine and good control of hypercatecholaminemia was attained. In all cases it was possible to control hypercatecholaminemia during most of the time they were administered a-methyltyrosine despite the presence of tumors. None of the patients suffered hypertension crises. In our patients treatment with CVD plus a-methyl-p-tyrosine proved to be safe and ameliorated the clinical course.

Adrenal Gland Neoplasms↗
PubMed1998

Bilirubin binding activity of cytokeratin 18 isolated from the porcine liver.

A porcine liver 40 kDa protein designated SBP40 isolated by affinity chromatography with agarose-linked spermine was identified as a porcine cytokeratin 18 on the basis of partial amino acid sequences of peptides derived by lysylendopeptidase digestion and by its reactivity with two commercially available preparations of monoclonal antibody. Immunohistochemistry revealed that SBP40 is localized at the hepatocyte membranes, preferentially in the bile canalicular area in accordance with the previously reported localization of cytokertain 18 in the murine liver. Affinity chromatography with agarose-linked bilirubin, a solubilization experiment of bilirubin from bilirubin-Sephadex G-10 complex, and gel-filtration of a mixture with bilirubin demonstrated that SBP40 or porcine cytokeratin 18 has binding affinity for bilirubin. These results suggest that cytokeratin 18 may play a role as a membrane reservoir in the event of transport and secretion of bile pigments in the liver.

Amino Acids↗