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Biomedical subjects

N Kimura

Publications and source records attributed to N Kimura.

At least 19 recordsLinked to original sources
PubMed1992

T-cell receptor beta chain gene rearrangement in acute myeloid leukemia always occurs at the allele that contains the undermethylated J beta 1 region.

The epigenetic phenomenon could play a role in the interaction between chromatin and DNA-binding enzymes, allowing us to consider an association between the phenomenon and gene rearrangement. The correlation between methylation status and rearrangement of the T-cell receptor (TCR) beta chain gene in leukemia cells obtained from patients with acute myeloid leukemia (AML) was examined. All of the AML patients with a TCR-beta rearrangement had hypomethylated CCGG sequences within the J beta 1 region on the rearranged allele, while the germline allele had completely methylated CCmeGG sequence in this region, indicating a strong association between hypomethylation status and rearrangement of the TCR beta chain gene. In the DNA from AML patients with or without a TCR-beta rearrangement, the C beta 2 region contained completely methylated CCmeGG sequences, even though they express T-cell-associated antigens, including CD7; this pattern is quite different from that observed in T-cell neoplasias. Moreover, some AML patients showed a TCR-beta rearrangement without the presence of immunoglobulin heavy-chain gene rearrangement, suggesting that TCR beta chain gene involvement in AML is required for unknown factors other than common recombinase activity.

Adolescent↗
PubMed1992

Expression of human regenerating gene mRNA and its product in normal and neoplastic human pancreas.

BACKGROUND: Localization of human regenerating gene (reg) mRNA and its product was investigated in normal and neoplastic human pancreas with the in situ hybridization method and immunohistochemical studies. METHODS: Both reg mRNA and reg protein were observed in acinar cells of the pancreas, but neither was found in ductal or islet cells. Immunoreactive reg was observed in an acinar cell carcinoma, a pancreatoblastoma, a solid and cystic tumor, and 5 of 20 duct cell carcinomas, but it was not found in 15 endocrine tumors and 2 microcystic adenomas. RESULTS: For comparison with reg, alpha-1-antitrypsin (AAT), lysozyme, chromogranin A (CMG), CA 19-9, carcinoembryonic antigen (CEA), cytokeratin, vimentin, and alpha-fetoprotein (AFP) were assessed in those tumors. An acinar cell carcinoma and a pancreatoblastoma had positive results for AAT, lysozyme, cytokeratin, and AFP but negative results for vimentin. An acinar cell carcinoma showed cells focally immunoreactive for CMG and CEA. A solid and cystic tumor had strongly positive results for AAT and vimentin and focally positive results for CMG and pancreatic hormones. Microcystic adenomas had abundant glycogen and strong immunoreactivity for cytokeratin. Ductal cell carcinomas showed cells focally positive for AAT, lysozyme, CMG, CA 19-9, and CEA. CONCLUSIONS: The localization of reg protein was not consist with that of any other proteins examined in the current study. Thus, reg protein was considered a useful marker for acinar cell differentiation; however, ectopic expression of reg also was observed in ductal cell carcinomas. In ductal cell carcinomas, expression of reg immunoreactivity was considered as one of phenotypic heterogeneity, as seen in AAT, lysozyme, and CMG immunoreactivity.

Calcium-Binding Proteins↗
PubMed1992

Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product.

BACKGROUND: Expression of nucleoside diphosphate (NDP) kinase, which is highly homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential in human breast cancer. PURPOSE: The present study was conducted to clarify the association of NDP kinase expression with metastatic potential in human hepatocellular carcinoma. METHODS: The immunohistochemical expression of NDP kinase was analyzed in 30 patients with histopathologically proven hepatocellular carcinoma. These patients included nine with distant metastases and 21 without distant metastases. Tissue specimens were reacted with rabbit anti-rat NDP kinase antibody and stained by the biotin-streptavidin complex method. The relative staining intensities were evaluated by comparing primary tumor sites with adjacent nontumorous liver tissue or with metastatic sites, RESULTS: The expression of NDP kinase in primary sites in patients with distant metastases was significantly less intense than that in patients without distant metastases (P = .018). NDP kinase was expressed significantly less intensely in metastatic sites than in primary sites (P = .005). The intensity of NDP kinase expression did not statistically correlate with tumor size or number of lesions in the liver, histopathological classification of tumor, associated liver diseases, hepatitis virus markers, or tumor markers. CONCLUSION: These results suggest that the reduced expression of NDP kinase is closely associated with distant metastatic potential in hepatocellular carcinoma. IMPLICATIONS: It is possible that both NDP kinase and the nm23 gene product may be active in the progression and differentiation of tumor cells and that their reduced expression induces a high metastatic potential in tumor cells. Studies using Northern blotting or in situ hybridization should be planned to confirm our findings.

Adult↗
PubMed1992

Isolation and characterization of a gene encoding rat nucleoside diphosphate kinase.

Two overlapping genomic clones for a rat nucleoside diphosphate kinase (NDP kinase) have been isolated and characterized. Complete sequencing of the genomic segment including the whole coding region for the enzyme revealed that the gene consists of four exons spanning 5.5 kilobase pairs. Primer extension analyses and ribonuclease protection assays indicated that the transcription may start from multiple sites with the major initiation site at 3 base pairs upstream from the translation initiation site, Met-1. Neither CAAT-box nor TATA-box could be assigned for each transcription initiation site, whereas five putative Sp1-binding sites (GC-boxes) were present in the 5'-flanking region. These features of the NDP kinase gene represent those of housekeeping genes. In genomic Southern blotting using a full-length rat NDP kinase cDNA as a probe, many positively hybridized fragments were detected. In support of this, five possible processed pseudogenes were identified in different DNA segments although many other NDP kinase-related genomic fragments remained to be characterized. These results demonstrate that the NDP kinase gene may consist of a multiple gene family.

Amino Acid Sequence↗
PubMed1992

Activation of nucleoside diphosphate kinase by mastoparan, a peptide isolated from wasp venom.

We have previously reported that GDP-bound alpha beta gamma-trimeric GTP-binding (G) proteins can be converted into the active GTP-bound form with nucleoside diphosphate (NDP) kinase and ATP, although its exact activation mechanism still remains to be resolved. In the present study, we investigated whether NDP kinase activity was modified by mastoparan, a wasp venom peptide that is known to activate G proteins as an agonist-receptor complex. The activity of NDP kinase measured by the formation of GTP from ATP and GDP was markedly stimulated, when the kinase was incubated with mastoparan. The concentration of mastoparan required for the activation was much lower than that observed for the peptide-induced activation of G proteins under similar assay conditions. There was also an increase in the phosphorylated intermediate of NDP kinase as well as the catalytic activity upon its incubation with mastoparan. These results suggest that mastoparan not only activates G proteins directly via guanine nucleotide exchange reaction but also stimulates NDP kinase activity.

Animals↗
PubMed1992

Human T-cell leukemia virus type I associated lymphadenitis.

Histopathologic changes in lymph nodes were examined from ten patients with mild lymphadenopathy, a few atypical lymphocytes in their peripheral blood, skin lesions, and proviral DNA of human T-cell leukemia virus type I (HTLV-I) in their nodes. The proviral DNA of HTLV-I was detected by southern blot analysis, in situ hybridization, and/or polymerase chain reaction techniques. The lymph nodes showed preserved nodal architecture with diffuse infiltration of small to intermediate-sized lymphocytes in association with scattered transformed lymphocytes and a few immunoblast-like cells in the enlarged paracortex. The infiltrating lymphocytes were positive for CD4, but neither rearrangement nor deletion of T-cell receptors and immunoglobulin heavy chain genes was detected. Eight of ten patients received no therapy, and all patients were alive and healthy more than 5 months after the biopsies. The histologic findings resembled those of a viral infection and could be distinguished from HTLV-I associated lymphomas.

Adult↗
PubMed1992

Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma.

Immunohistochemical localization of the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), was investigated in 70 cases of functioning and non-functioning phaeochromocytomas comprising 52 of adrenal and 18 of extra-adrenal origin. Of 59 functioning tumours, 30 were mixed epinephrine and norepinephrine-producing (mixed type) and 29 were norepinephrine-producing tumours. TH, AADC and DBH were detected in all functioning phaeochromocytomas, but PNMT was limited to the mixed-type phaeochromocytomas. Non-functioning phaeochromocytomas were divided into two groups, comprising a complete type, which induced neither elevated plasma catecholamines nor their metabolites in urine, and an incomplete type which exhibited no elevated plasma catecholamines, but showed a slightly high urinary vanillylmandelic acid level. In the non-functioning complete-type tumours, immunoreactive TH was negative, but the incomplete tumours of the adrenal medulla had all four enzymes, and corresponded to a mixed-type phaeochromocytoma. AADC and DBH were present universally in all functioning and non-functioning tumours, including TH-negative tumours. TH is a rate-limiting enzyme of catecholamine biosynthesis and deficiency of TH is an important feature of extra-adrenal non-functioning phaeochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1992

Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay.

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.

Bucladesine↗
PubMed1992

Immunohistochemical analysis of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma: lack of prognostic value.

Levels of nm23 gene product/nucleoside diphosphate kinase (NDP kinase) expression have been demonstrated to correlate inversely with metastatic potential in several tumours, indicating that this could be a useful tool as a prognostic indicator. Using an antibody to NDP kinase, levels of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma were examined immunohistochemically. Of 88 patients tested, 39 (44%; Group B) showed strong immunoreactivity for NDP kinase in most of cancer cells within the tumour tissues, while 49 (56%; Group A) contained few or no NDP kinase-positive cancer cells. Nm23 gene product/NDP kinase was expressed independently of clinicopathological factors, and unexpectedly, no correlation of survival rates between both Groups could be demonstrated. Thus, in pulmonary adenocarcinoma, levels of nm23 gene product/NDP kinase expression may lack prognostic value.

Adenocarcinoma↗
PubMed1992

The effect of dobutamine on hepatic blood flow and oxygen supply-uptake ratio during enflurane nitrous oxide anesthesia in humans undergoing liver resection.

Liver surgery is often accompanied by hepatic hypoperfusion and hypoxia, and it is controversial whether catecholamines increase hepatic blood flow and oxygen supply. The effects of 3 micrograms.kg-1.min-1 dobutamine on hepatic circulation and oxygen balance were examined in patients anesthetized with enflurane, nitrous oxide, and oxygen for liver surgery. Dobutamine did not cause a significant increase in hepatic arterial blood flow. However, total hepatic blood flow and portal venous blood flow were increased, resulting in an increase in hepatic oxygen delivery (HDO2). The increase in HDO2 was not associated with an improvement of hepatic oxygen supply-uptake ratio, since hepatic oxygen uptake (HVO2) also increased. After hepatectomy, the increases in portal venous blood flow and HDO2 were not accompanied by an increase in HVO2. The stimulation of hepatocellular oxygen metabolism by dobutamine and depressed responsiveness of adrenoceptors on hepatocytes in which metabolism was already augmented are the likely explanation for the different reactions before and after hepatectomy.

Adult↗
PubMed1992

Transcription of a recombinant influenza virus RNA in cells that can express the influenza virus RNA polymerase and nucleoprotein genes.

A new transfection system for influenza virus was developed using the clone 76 cell line, in which the viral RNA polymerase and nucleoprotein (NP) genes can be expressed in response to dexamethasone. Ribonucleoprotein (RNP) complexes were reconstituted by expressing proteins from a chimeric NS-chloramphenicol acetyltransferase (CAT) RNA consisting of the full-length negative-strand RNA of the CAT gene positioned between the 5'- and 3'-terminal sequences of influenza virus RNA segment 8, and purifying NP from an NP gene-expressing Escherichia coli strain. When the reconstituted RNP was transfected into clone 76 cells, CAT was produced only when the synthesis of the three RNA polymerase subunits and NP was induced by treatment with dexamethasone.

Animals↗
PubMed1992

Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and invasive components of human breast cancers.

Expression of the c-erbB-2 oncoprotein (ErbB-2) and the nm23 anti-metastatic gene product (nucleoside diphosphate [NDP] kinase) was examined in the intraductal and invasive components of 63 fresh human breast cancer tissues. The expression of estrogen receptor (ER) as a marker of hormone dependency and the Ki-67 protein as a proliferative cell marker was also examined. ErbB-2 and ER were positive in 77.8% (28/36) and 64.7% (22/34) of the intraductal components, and in 43.6% (27/62) and 57.1% (36/63) of the invasive components, respectively. NDP kinase was positive in 58% (18/31) of intraductal, and in 30.9% (17/55) of invasive areas. The average Ki-67-positive cell rates were 5.9% in the intraductal, and 10.7% in the invasive components. Thus, the cells within the intraductal component of breast cancer appear to have different characteristics from the invasive component, not only in markers of proliferative ability, but also in the expression of oncogenes and hormone receptors.

Biomarkers, Tumor↗
PubMed1992

Experimentally produced fractures of articular cartilage and bone. The effects of shear forces on the pig knee.

Experimental injuries of cartilage and bone were produced by applying shear force to the articular surfaces of the lateral femoral condyles of six-month-old pigs under various loading conditions. The lesions were divided into two groups, 'open' or 'closed', depending on the presence of a crack on the articular surface. Each was further divided into four types according to the depth of penetrating injury: (1) splitting of uncalcified cartilage; (2) splitting at the subchondral plate; (3) subchondral fracture; and (4) intra-articular fracture. When shear force was applied at high speed but with low energy, the articular cartilage surface was the first to crack. At low speed and low energy, splits occurred in the deeper layers first. As the energy increased, both loading conditions eventually resulted in similar open lesions. Experimentally produced shear injuries are useful models for clinical osteochondral fracture, osteochondritis dissecans, and chondromalacia patellae.

Animals↗
PubMed1992

[Analysis of T-cell receptor delta chain gene in hematological malignancies].

We analyzed the rearrangement of T-cell receptor (TcR) delta chain gene in 196 cases of hematological malignancies. This rearranged band (s) was observed in 15% of the total cases investigated. All T-ALL patients and cell lines, except for P30/Okubo, had a new band (s) or deletion of J delta 1 gene locus, indicating the gamma delta T-cell type or the alpha beta T-cell type. In the other T-cell malignancies, the delta rearranged band (s) was recognized in 5% of T-cell lymphomas, 20% of AILD but not in ATL, Hodgkin's disease, T-CLL. Inappropriate delta rearrangement was frequently recognized in 63% of B-ALL and 50% of CML-BC but none or few (5% less) in B-CLL, B-lymphoma and AML. Southern blotting, using J delta 1 and V delta gene probes or Pst I enzyme digestion, indicated that the inappropriate delta rearranged band in B-ALL and CML-BC is V delta 2D or DD without a J delta locus. The rearranged band (s) involved J delta locus, was mostly recognized in 5/6 cases of CD7 (+) stem cell leukemia. Therefore, the TcR delta gene is useful in evaluating clonality for the most immature T-cell neoplasms, not showing rearrangement of the other TcR genes. Moreover, this delta gene may be a useful tool for distinguishing T-lineage from the other lineages, using the characteristic rearrangement pattern (V delta 2D as a inappropriate pattern, or (D) DJ and V (D) DJ as the T-lineage pattern (s)).

Chromosome Deletion↗
PubMed1992

[Clinical analysis of 10 patients with chronic lymphoid leukemia].

Ten patients with chronic lymphoid leukemia were analyzed for clinical characteristics, morphology and phenotype of leukemic cells. There were 3 patients with T-chronic lymphocytic leukemia (CLL), 2 with T-prolymphocytic leukemia (PLL), 2 with B-CLL, 1 with B-PLL, 1 with non-T-non-B-CLL and 1 with Waldenström's macroglobulinemia. Although chronic lymphoid leukemia is usually characterized by proliferation of B-lymphocytes, our study revealed that 5 of 10 patients had T-cell phenotype. A peripheral blood specimen of T-CLL showed small lymphocytes with a mature appearance and an irregular nuclear margin. Most of the cells lacked large azurophilic granules in the cytoplasm and nucleoli were also inconspicuous in the nucleus by light and electron microscopic examinations. In PLL, a majority of the cells were large lymphocytes with a prominent nucleolus and abundant basophilic cytoplasm which were more clearly observed by transmitted electron microscopic examination. The patients were treated with cyclophosphamide and prednisolone, but response to treatment was transient. The median survival time was 7 months for all patients, while that of T-cell lineage cases was only 1 month. Therefore, new modalities of treatment must be investigated in the future.

Aged↗
PubMed1992

[A case report of an acute promyelocytic leukemia patient showing remarkable thrombopoiesis prior to granulopoiesis by hM-CSF treatment after chemotherapy].

We report a case of an acute promyelocytic leukemia patient who showed remarkable thrombopoiesis prior to granulopoiesis by human macrophage colony-stimulating factor (hM-CSF) treatment after chemotherapy. A 50 year-old man was diagnosed as acute promyelocytic leukemia (FAB classification: M3) with t(15;17). He received two courses of induction therapy with daunorubicin and cytarabine followed by consolidation therapy with cytarabine and mitoxantrone. After each course of chemotherapy. hM-CSF (8 x 10(6) units, daily) was given for 14 days. After each treatment with hM-CSF, the increase in number of platelets preceded increase of granulocytes and reticulocytes. When serum levels of granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony simulating factor (G-CSF), interleukins-3 (IL-3) and -6 (IL-6) were measured, only that of G-CSF was increased after hM-CSF treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Clinical evaluation of bone marrow fibrosis in non-Hodgkin's lymphomas].

A study was performed in 62 patients with non-Hodgkin's lymphoma (ATL included) who were hospitalized between 1985 and 1991 and who underwent bone marrow aspiration and biopsy before or after treatment or at the time of recurrence. The relationships between the extent of bone marrow fibrosis and other prognostic factors as well as the effects of chemotherapy and bone marrow fibrositic prognosis were examined. The results were as follows: 1) The periods of survival in patients with high degree of fibrosis in bone marrow were significantly shortened. 2) The extent of bone marrow fibrosis significantly correlated with the presence or general symptoms, bone marrow invasion, and blood levels of LDH and Ca on blood biochemical examinations. 3) Effective therapy reduced collagen fibers as well as reticulin fibers in bone marrow. 4) Sixty-four percent of relapsing cases showed increase of bone marrow fibrosis. These results suggest that understanding the state of bone marrow fibrosis over the clinical course may give a good guide of indication the prognosis of malignant lymphoma.

Bone Marrow↗