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Biomedical subjects

K Nomura

Publications and source records attributed to K Nomura.

At least 19 recordsLinked to original sources
PubMed1996

An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression.

Stress-inducible 72-kDa heat shock proteins (HSP70) were encoded on genes in multiple chromosomes. The expression of mRNA transcribed from the gene (HSP70-1) on chromosome 6 was studied using reverse transcript polymerase chain reaction in peripheral blood mononuclear cells of patients with different diseases. The deletion of 29 bp occurred in 5' noncoding and subsequent 133 bp in coding sequences of HSP70 mRNA in patients with major depression (n = 18), while normal subjects (n = 10) and patients with schizophrenia (n = 5), essential hypertension (n = 3), rheumatoid arthritis (n = 7), and Graves' disease (n = 3) had normal mRNA. No such deletion occurred in genomic DNA and no protein was translated from deleted mRNA. The allel-specific abnormal transcript of the HSP70 gene on chromosome 6 thus may underlie the altered stress and/or immune response in major depression.

Alleles↗
PubMed1996

Activation of glutathione transferase P gene by lead requires glutathione transferase P enhancer I.

Glutathione transferase P (GST-P) is specifically induced in rat liver and kidney by lead cation. The increase of GST-P mRNA after lead administration is blocked by actinomycin D, suggesting that GST-P production by lead is regulated at the transcriptional level. To further determine which part of the flanking region of the GST-P gene has the lead-responsive cis-element in vivo, we utilized transgenic rats with five different constructs having GST-P and/or chloramphenicol acetyl-transferase coding sequence. We studied the effect of lead on these transgenic rats and on transfected NRK (normal rat kidney) cells and found that GST-P induction by lead is indeed regulated at the transcriptional level and that the GST-P enhancer I (GPEI) enhancer is an essential cis-element required for the activation of the GST-P gene by lead. GPEI consists of two AP-1 (c-Jun/c-Fos heterodimer) site-like sequences that are palindromically arranged and can bind AP-1, c-jun mRNA in the liver increased after lead administration and GST-P, and c-Jun had patchy expression in the same hepatocytes 24 h after lead exposure. These results suggest that activation of the GST-P gene by lead is mediated in major part by enhancer GPEI and that AP-1 may be involved at least partially. GPEI has been shown to have essential sequence information for the trans-activation of the GST-P gene during chemical hepatocarcinogenesis of the rat (Morimura, S., Suzuki, T., Hochi, S., Yuki, A., Nomura, K., Kitagawa, T., Nagatsu, I., Imagawa, M., and Muramatsu, M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2065-2068; Suzuki, T., Imagawa, M., Hirabayashi, M., Yuki, A., Hisatake, K., Nomura, K., Kitagawa, T., and Muramatsu, M. (1995) Cancer Res. 55, 2651-2655). The present study establishes that the same enhancer element does operate in the activation of the GST-P gene by lead regardless of the trans-activators involved.

Animals↗
PubMed1996

A novel clonality assay for the mouse: application to hepatocellular carcinomas induced with diethylnitrosamine.

A polymerase chain reaction-based clonality assay was developed for mouse tumors and cellular proliferations of the mouse. This assay was based on a polymorphism of the phosphoglucokinase-1 (Pgk-1) gene on the X chromosome between two different mouse subspecies and the different methylation patterns of active and inactive X chromosomes. All 15 tumor cell lines examined showed one of the two allelic bands on gel electrophoresis, which is consistent with the theory that tumor cell lines are monoclonally derived. This suggests that the Pgk-1 system is useful for clonality studies that will give insight into cancer development. With this method, nine hepatocellular carcinomas were examined, and eight showed monoallelic patterns. The remaining tumor exhibited a biallelic pattern, which is suggestive of polyclonal origin; however, other possibilities are discussed.

Animals↗
PubMed1996

Role of insulin resistance in decreasing lipoprotein lipase activity in tumor-bearing rats.

The role of insulin resistance in the tumor-induced decrease in tissue lipoprotein lipase (LPL) activity was studied in vivo and vitro in methylcholanthrene-induced sarcoma-bearing rats. Intraperitoneal (i.p.) injection of 2U of regular insulin resulted in high-adipose LPL activity in control rats (CTR) of 122.0 +/- 42.4 U/mg tissue, but it had little effect on tumor-bearing rats (TBR), which showed a value of only 9.6 +/- 5.5 U/mg tissue (P = 0.002). When adjusted for serum insulin concentrations, adipose LPL activity remained significantly different between the TBR and CTR at 0.19 +/- 0.17 and 0.78 +/- 0.29 U/mg tissue, respectively (P = 0.02). Following the in vitro incubation with either 1.44 g/l glucose of 1 x 10-8 U insulin of adipose tissue fragments obtained from the TBR and the CTR, measurable LPL activity was maintained in the tissue from the CTR for 2 h but not in that from the TBR. These results suggest that the decreased LPL activities seen in the tumor-bearing state may be mediated by insulin resistance.

Animals↗
PubMed1996

The possible role of TNF-alpha and IL-2 in inducing tumor-associated metabolic alterations.

This study was conducted to investigate the role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4 x 10(4) IU of human recombinant TNF-alpha per rat per day subcutaneously (sc) for 5 consecutive days (n = 5), 3.5 x 10(5) U human recombinant IL-2 per rat per day sc for 14 consecutive days (n = 5), or normal saline (n = 5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF-alpha or IL-2 alone. Thus, it is unlikely that IL-2 or TNF-alpha is the sole mediator of cancer cachexia in this tumor and rat model.

Animals↗
PubMed1996

Triple primary malignant neoplasms including a malignant brain tumor: report of two cases and review of the literature.

BACKGROUND: Two rare cases of triple primary malignant neoplasms (PMN), including malignant brain tumors, which were glioblastoma multiformes, are described. METHODS: The clinical characteristics and underlying genetic alterations in triple or more PMN, including malignant brain tumors are discussed with intensive review of the literature. RESULTS: The first patient, a 77-year-old male, suffered metachronously from tubular adenocarcinoma of the stomach, transitional cell carcinoma of the bladder, and glioblastoma in the brain. This glioblastoma had loss of heterozygosity in exons 7-8 in p53 gene. The second patient, a 68-year-old male, developed papillary adenocarcinoma of the lung, adenocarcinoma of the rectum, and glioblastoma in the brain during a period of 7 years. In 42 such cases described in the literature, age distribution demonstrated two characteristic peaks, one in the third decade and the other over 50 years of age. The younger group consisted mainly of Turcot's syndrome, and of a case of Li-Fraumeni familial cancer syndrome. On the other hand, neither of these hereditary cancer syndromes were contained in the elder group. Regarding the site of PMN, colorectal cancers were associated most frequently with malignant brain tumors, followed by stomach cancers, and thyroid cancers. Malignant brain tumors, mostly glioblastoma multiforme, tend to occur as the last tumor of triple or more PMN. CONCLUSIONS: These results suggest that genetic background might play an important role in tumorigenesis of PMN in the younger group, whereas epigenetic factors would be more important in the older group. Characteristic organ association and factors influencing carcinogenesis, such as aging, environmental carcinogens, and underlying genetic alterations in these tumors are further discussed.

Adenocarcinoma↗
PubMed1996

Establishment of a hepatocyte cell line producing growth-promoting factors for liver-colonizing tumor cells.

A hepatocyte-derived cell line designated MLE-15A2 was established from a primary culture of mouse hepatocytes. The MLE-15A2 cells appeared to retain the basic nature of hepatocytes in that they showed morphology of an epithelial cell type and secreted albumin into the culture medium. These cells were grown on collagen-coated plates and could be easily expanded to a large-scale culture. Therefore, MLE-15A2 cells may provide a more useful model for studying liver microenvironments than primary cultures of hepatocytes. We found that conditioned media from MLE-15A2 cells, as well as from primary cultures of hepatocytes, promoted the proliferation of highly liver-colonizing colon 26 NL-17 cells better than the poorly liver-colonizing colon 26 NL-4 cells. Moreover, the conditioned media stimulated the growth of some human colon cancer cell lines. These results indicate that MLE-15A2 cells secrete growth factors that selectively stimulate certain tumor cell types. Hepatocyte-derived growth factors may regulate selective survival and colonization of tumor cells in the process of liver metastasis. The growth-promoting activity was unaffected by dialysis, was stable at 80 degrees C for 30 minutes and was bound to a heparin-Sepharose column. The major activity was eluted from the column with 0.7-0.75 M NaCl, and some minor activities eluted with lower concentrations of NaCl. These results suggest that the active components are heterogeneous heparin-binding proteins with lower affinity to heparin than platelet-derived and fibroblast growth factors.

Animals↗
PubMed1996

Radiographical and histological evaluation of canine decidual reaction induced by intralumenal injection of bouillon solution mixed with or without barium sulfate.

Radiographical examination of the canine uterus intralumenally injected with barium solution revealed that barium was gradually condensed, segmented and distributed equally along the lumen like embryos in early pregnant uterus. Histological examination of the uterus intralumenally injected with bouillon solution alone showed a remarkable fish net- or tree branch-like growth of superficial glands towards the uterine lumen. The uterus injected with barium in bouillon solution induced two different histological changes: One consisted of cystic glandular hyperplasia in the whole endometrium, which was a so-called Swiss cheese endometrium, and the other was composed of a fish net- or tree branch-like growth in the superficial layer accompanied with cystic glandular hyperplasia in the basal layer. The latter represented endometrial differentiation into spongy layer, supraglandular layer and basal glandular layer, being similar to that during normal early placentation. These findings suggest that clotted barium in bouillon solution has stimulating effects on the uterus similar to those of embryos.

Animals↗
PubMed1996

Canine deciduoma induced by intralumenal insertion of uterine grafts.

This report deals with evaluation of histological characteristics of the canine deciduoma induced by insertion of the uterine grafts as a biological stimulus. Autografts induced severe uterine cystic endometrial hyperplasia, and the grafts were organized by maternal endometrium. On the other hand, allografts induced more severe hyperplasia of the uterine endometrium with stronger inflammation than autografts. Almost all allografts became necrotic and lytic in the uterine lumen. These results suggest that uterine grafts could induce deciduoma and that the maternal endometrium, though under the functional corpora lutea, recognized the uterine grafts to be a stimulant and showed severe cystic endometrial hyperplasia.

Animals↗
PubMed1996

[A case report of Darling's classification Ib total anomalous pulmonary venous return with an unusual left pulmonary vein].

A radical correction involving Vargas's method and a direct anastomosis between the left pulmonary vein (PV) and left atrium (LA) was performed in a 29 day-old infant with supracardiac type Ib total anomalous pulmonary venous return (TAPVR) and an unusual form of the left PV. the left upper and lower PVs drained into a left "common" PV that was just behind the LA, and then into the right pleural cavity. The left common PV was located cephalad to the normal course and received blood from the right lower and upper PVs and drained into the supra-vena cava (SVC). The junction of the SVC and the right PV was slightly stenotic. Vargas's method is a useful technique for Darling's classification Ib TAPVR even in cases without the common PV situated behind the LA. But this patient had a left common PV and it was possible either to anastomose the common PV and LA directly or to perform Vargas's technique. We performed both procedures to prevent left PV obstruction (PVO). Cineangiography performed 2 months after surgery showed that a large amount of blood from the right and left PV drained into the LA through the common PV-LA route. These procedures, which create a dual PV channel, reduce the risk of PVO, so they are useful for radical correction of Darling's Ib type TAPVR.

Cardiac Surgical Procedures↗
PubMed1996

Inhibition of lipid hydroperoxidation of low density lipoprotein by the Ca(2+)-channel and alpha 1-adrenoceptor antagonist monatepil maleate.

The antioxidative effect of monatepil maleate (CAS 103379-03-9, AJ-2615), a new antihypertensive agent, was investigated by measuring its ability to inhibit copper-induced lipid hydroperoxidation of low density lipoprotein (LDL) and was compared with those of diltiazem (Ca(2+)-channel antagonist), prazosin (alpha 1-adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to inhibit copper-induced lipid hydroperoxidation of LDL by 50% (IC50) was 28 mumol/l. The IC50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, > 1 mmol/l, and 17 mumol/l, respectively. These results indicate that AJ-2615 has the same potent antioxidative effect as probucol and suggest that a previously reported ability of AJ-2615 to inhibit the progression of atherosclerosis may be due to this antioxidative property. In addition, the dihydrodibenzothiepine ring of AJ-2615 may have an antioxidative functions.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Opposite effects on cholesterol metabolism and their mechanisms induced by dietary oleic acid and palmitic acid in hamsters.

The effects of dietary oleic acid on cholesterol metabolism were investigated and compared with those of palmitic acid in hamsters. Addition of 5% oleic acid to a 0.1% cholesterol-supplemented diet decreased plasma total cholesterol, very low density lipoprotein (VLDL) cholesterol, and low density lipoprotein (LDL) cholesterol, increased hepatic LDL receptor activity, and decreased plasma cholesteryl ester transfer protein (CETP) activity in comparison with 0.1% cholesterol alone. In contrast, addition of 5% palmitic acid to a 0.1% cholesterol-supplemented diet increased total cholesterol and LDL-cholesterol, increased plasma CETP activity, and suppressed hepatic LDL receptor activity to a greater extent than 0.1% cholesterol alone. Neither oleic acid nor palmitic acid altered hepatic microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, but oleic acid increased hepatic microsomal cholesterol 7 alpha-hydroxylase activity. These results suggest that dietary oleic acid inhibits the increases in total, VLDL-, and LDL-cholesterol induced by dietary cholesterol by preventing both LDL receptor suppression and increased CETP activity, whereas dietary palmitic acid augments the cholesterol-induced increases in total and LDL-cholesterol by both further suppression of LDL receptor activity and further stimulation of CETP activity.

Animals↗
PubMed1995

Frequent development of pancreatic carcinomas in the Rana nigromaculata group.

In 1979, 2 species of pond frogs (Rana nigromaculata and Rana plancyi plancyi) were imported from China, and hybrids were made between these and Japanese, Korean, and Taiwanese pond frogs (R. nigromaculata, Rana plancyi fukienensis and Rana brevipoda) that had been kept for a number of years in the Laboratory for Amphibian Biology of Hiroshima University. From 1982, development of tumors, especially in the peritoneal cavity, was noticed frequently in the hybrids and also later, although rarely, in the Japanese pond frogs. Such tumors had never previously been observed among pond frogs in the laboratory. Histological and immunohistochemical studies identified the i.p. tumors to be pancreatic carcinomas with occasional production of insulin and/or somatostatin. Ultrastructural investigation revealed both endocrine and exocrine secretion granules together with C-type retrovirus particles in the carcinoma cells. Other tumors included a retroperitoneal rhabdomyosarcoma, liver adenomas, and an unclassifiable mesenchymal tumor of the foot pad.

Animals↗
PubMed1995

Identification of an enhancer responsible for tumor marker gene expression by means of transgenic rats.

The glutathione transferase P (GST-P) gene is known for its specific expression during chemical hepatocarcinogenesis of the rat and is used as a tumor marker for hepatocellular carcinoma. We have shown recently that the upstream 2.9-kb region of the GST-P gene is sufficient for conferring tumor-specific expression of the gene in vivo (S. Morimura et al., Proc. Natl. Acad. Sci. USA, 90: 2065-2068, 1993). To further identify crucial sequence elements regulating the unique expression of this gene, we have established six independent lines of transgenic rats bearing distinct areas of the GST-P gene that are connected to the chloramphenicol acetyltransferase coding region and analyzed changes of the chloramphenicol acetyltransferase activity during the course of chemical hepatocarcinogenesis. We demonstrate here that the enhancer, glutathione transferase P enhancer I, that is located 2.5 kb upstream of the GST-P gene is required and sufficient for its tumor-specific expression of the gene among other controlling elements. This approach to transgene expression could be used to define other enhancers, the activity of which is dependent on cellular changes such as carcinogenesis, development, and differentiation.

Animals↗