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Biomedical subjects

H Esumi

Publications and source records attributed to H Esumi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Relationships between the synthesis of N-nitrosodimethylamine and immune responses to chronic infection with the carcinogenic parasite, Opisthorchis viverrini, in men.

This study investigated the relationship between immune responses to infection with the liver fluke, Opisthorchis viverrini, and the synthesis of the carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also examined associations between synthesis of nitric oxide (NO) and nitrosation of amines, in vivo. Antibody and T cell responses to fluke antigens and post-alcohol urinary NDMA excretion were assessed among three groups of 40-50 men with no, moderate and heavy liver fluke infection. Markers of NO synthesis (nitrate, nitrite) and nitrosation (nitrosamino acids) were also measured in biological fluids. Assessments were carried out under controlled conditions which minimised intake of exogenous nitrate and nitrite and were carried out at two time points, namely before and 4 months after elimination of the infection with praziquantel treatment. No statistically significant variation was observed in the amount of NDMA excreted between the 3 groups. However, during active infection, a strong negative association was observed between in vitro lymphoproliferative responses to some liver fluke antigens and NDMA excretion. After treatment this association was reduced. Multivariate statistical models revealed a highly significant relationship between NDMA levels and urinary nitrate, stimulation indices for two T cell responses to two parasite antigens (MW 37 kDa and 110 kDa) and gall bladder dimensions. NDMA levels after treatment were best described by the ratio between parasite-specific IgG2 and IgE, background levels of T cell proliferation, a urinary marker of nitrosation (N-nitrosothioproline) and usual level of alcohol consumption. These results suggest that individual background immunologic activity, parasite-specific responses and/or parasite products and NO synthesis are important determinants of endogenous generation of nitrosamines in O. viverrini-infected humans.

Adult↗
PubMed1998

Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia.

Nitric oxide produced by inducible nitric oxide synthase (iNOS) has been claimed to be involved in gastritis; however, its characteristics are largely unknown. We assessed (1) iNOS expression in the human gastric mucosa in chronic gastritis and (2) the cytokines associated with iNOS expression. Gastric biopsy specimens were obtained from patients with chronic gastritis. Total RNA was isolated and reverse transcription-polymerase chain reaction (PCR) was performed semiquantitatively using specific primer sets for iNOS, interleukin (IL)-1beta, IL-8, IL-6, interferon-y, tumor necrosis factor-alpha (TNF-alpha), TNF receptors, IL-6 receptors, and sucrase, respectively. Helicobacter pylori infection was examined by the PCR assay. Reverse transcription-PCR analysis showed that expression of iNOS was detected in 10 of 23 samples. Expression of iNOS mRNA was closely correlated with expression of TNF-alpha and was observed frequently in subjects with intestinal metaplasia. The Helicobacter pylori gene was detected by PCR assay in all iNOS-positive cases. These results indicate that iNOS is predominantly expressed in the gastric mucosa with intestinal metaplasia and H. pylori infection. TNF-alpha is thought to be an important cytokine associated with iNOS expression.

Adult↗
PubMed1998

Preliminary study of percutaneous alcohol injection into the lung.

Although percutaneous ethanol injection is widely used to treat hepatic tumors, this technique has not been applied to lung tumors. We performed a preliminary experiment with percutaneous ethanol injection into the rabbit lung, and evaluated the local and systemic effects of absolute ethanol injection on pulmonary structures in order to assess the feasibility and safety of this technique as a local treatment for human lung tumors. Percutaneous injection of absolute ethanol into the rabbit lung was performed under CT guidance. The volume of ethanol injected ranged from 0.6 to 1.0 ml (approximately 0.2-0.5 ml/kg). Follow-up CT scans were performed 1, 2, 7 and 30 days after the injection. The animals were killed at intervals (range: 3 h-30 days), and the lung was examined histologically. The ethanol was well tolerated and did not induce significant systemic side-effects. All doses induced necrosis in the injected lung, but none was lethal. Although ethanol spilling into the thoracic cavity induced effusion and pleuritis, these reactions were manageable. Alcohol injection produced an area of necrosis surrounded by pulmonary edema associated with polymorphonuclear cells invasion within 24 h; moreover, granulation change, epithelial regeneration, and alveolar septal fibrosis had appeared by one week. The necrosis was sometimes multifocal, probably due to transbronchial spread of the injected ethanol. In conclusion, the feasibility and safety of absolute ethanol injection were confirmed. Neither severe systemic side effects nor lethal extensive necrosis were observed with injected ethanol; however, an unexpected side effect, multifocal necrosis, was seen. The latter reaction suggests that careful observation and care would be essential after alcohol injection into the lung.

Administration, Cutaneous↗
PubMed1998

Suppression of anti-microtubule agent-induced apoptosis by nitric oxide: possible mechanism of a new drug resistance.

The propensity of a cell to undergo apoptosis has been proposed to be a determinant of sensitivity to anti-microtubule agents. The anti-microtubule agents vincristine and paclitaxel induce key features of apoptosis, such as intranucleosomal DNA fragmentation and changes in nuclear morphology in the human neuroblastoma cell line, NB-39-nu. Nitric oxide (NO) generated from NO-releasing drugs prevented anti-microtubule agent-induced apoptosis in this cell line. The mechanism of suppression of apoptosis by NO appears to be via the inhibition of an interleukin-1beta converting enzyme-like protease cascade. This finding reveals a new biological function of NO, as well as a new molecular insight into resistance to chemotherapy with anti-microtubule agents.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Neoplastic transformation of rat colon epithelial cells by expression of activated human K-ras.

Somatic mutations of the K-ras oncogene play an important role in colorectal carcinogenesis. We determined whether rat colon epithelial cells could be transformed by introducing retroviruses carrying the activated human K-ras oncogene alone. Primary epithelial cells from the rat distal colon were infected with retroviruses carrying wild-type and two types of activated K-ras (asp and val at codon 12) cDNAs. Cells infected with the wild-type K-ras virus showed no change in morphology and died within 3 weeks, whereas the activated K-ras virus-infected cells underwent morphological changes within 3 days and continued to proliferate. From these cells, several cell lines were subsequently established. Epithelial cells transformed by activated K-ras formed colonies in soft agar culture and tumors in athymic nude mice. Multiple copies of human K-ras genes and large amounts of K-ras mRNAs and proteins were found in the transformed cells. These data suggest that overexpression of activated K-ras transforms rat colon epithelial cells.

Animals↗
PubMed1998

Clonal analysis of isolated intestinal metaplastic glands of stomach using X linked polymorphism.

BACKGROUND: Monoclonal precancerous cells undergo successive biochemical and genetic changes during the multistep process of carcinogenesis in the gastrointestinal tract. Despite a high association with intestinal-type stomach cancer (differentiated adenocarcinoma of the stomach), the role of intestinal metaplasia is unclear in stomach carcinogenesis. AIMS: To study the clonality of intestinal metaplasia. METHODS: The clonality of 86 single intestinal metaplastic glands isolated by EDTA treatment from gastrectomy specimens from patients with cancer were investigated. The methylation sensitive restriction enzyme HpaII and polymerase chain reaction (PCR) were used to detect a polymorphic human androgen receptor gene locus linked to an inactive X chromosome. RESULTS: Forty one (48%) intestinal metaplastic glands were heterotypic (mixed cells of different allelic methylation) and 45 (52%) were homotypic (cell population of the same allelic methylation), while almost all the single pyloric glands were homotypic. Eleven of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands that had originated from different cells. There were no strong relationships between clonal type and location or histological type of intestinal metaplasia. CONCLUSION: Intestinal metaplasia in general is not a lesion that arises or proceeds monoclonally.

Clone Cells↗
PubMed1998

Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of the lung.

Sclerosing hemangioma of the lung remains poorly understood, and it is still unclear whether this lesion is neoplastic or not. It consists of two major cell types, pale cells and cuboidal cells. We analyzed the clonality of each cell types from six female cases of surgically resected sclerosing hemangioma. The pale cells and cuboidal cells were separated by microdissection from methanol-fixed sections, and DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor (HUMARA) gene or the phosphoglycerate kinase (PGK) gene. The HUMARA and PGK genes were found to be amplified with or without digestion by the methylation-sensitive restrictive endonuclease HpaII. Five of six cases were informative. Pale cells and cuboidal cells showed the same monoclonality in all of the informative cases, whereas the control cells showed a polyclonal pattern. Our results demonstrated that sclerosing hemangioma is caused by monoclonal expansion of cells, confirming that it is a neoplasia. Moreover, the present data indicate that both pale cells and cuboidal cells are derived from the same cell.

Adolescent↗
PubMed1997

Inhibition of inducible nitric oxide synthase gene expression by glucocorticoid-induced protein(s) in lipopolysaccharide-stimulated J774 cells.

Glucocorticoids inhibit inducible-type NO synthase activity in a variety of cell types. We report here that proteins recovered from the medium of dexamethasone-treated J774 macrophages (1, 10, 100 microg/ml) inhibited lipopolysaccharide-stimulated nitrite generation by 10.0 +/- 3.0%, 32.3 +/- 5.3% and 55.0 +/- 6.0%, respectively, and inducible NO synthase mRNA expression in these cells. Immunoblotting analysis of crude and partially purified glucocorticoid-induced proteins with an anti-lipocortin-1 polyclonal antiserum revealed the presence of lipocortin-1-like immunoreactive species with a molecular mass of 35-37 kDa. Furthermore, inhibition of lipopolysaccharide-induced nitrite production by glucocorticoid-induced proteins in J774 cells was reversed by addition of anti-lipocortin-1 neutralizing polyclonal antibody (1:60 dilution; 4 h before lipopolysaccharide). Comparison of glucocorticoid-induced proteins inhibition of both nitrite production and inducible NO synthase mRNA expression suggests that these effects result mainly from inhibition of lipopolysaccharide-mediated inducible NO synthase gene expression. These results indicate that negative regulation of inducible NO synthase by glucocorticoids is, at least in part, mediated by glucocorticoid-induced proteins that involve also members of the lipocortin-like superfamily.

Animals↗
PubMed1997

Induction of vascular endothelial growth factor by nitric oxide in human glioblastoma and hepatocellular carcinoma cells.

We evaluated the effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression in human A-172 glioblastoma cells and human HepG2 hepatocellular carcinoma cells. The mRNA level of VEGF increased in response to S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) in both cell lines, and increased in mRNA level well coincided with VEGF protein production in A-172 cells. SNAP at 0.5 mM induced maximal stimulation of 4.4 and 3.7 kb VEGF mRNA expression after 6 h about 11 and 8 fold increase, respectively above control level. Similar VEGF mRNA accumulation was observed also with NOR3, another chemical NO generator. To evaluate the effect of SNAP on VEGF mRNA stability, half-lives of VEGF mRNA were measured in A-172 cells cultured with or without 0.5 mM SNAP and treated with actinomycin D (25 microg/ml). Half-life for VEGF mRNA was found to be prolonged about 2.4 fold by SNAP. VEGF expression induced by SNAP was inhibited by guanylate cyclase inhibitors, methylene blue (10 microM) and LY-83583 (1 microM), and by the protein synthesis inhibitor, cycloheximide (25 microg/ml). These results suggest that induction of VEGF gene expression by NO is mediated through guanylate cyclase activity and requires on-going protein synthesis.

Carcinoma, Hepatocellular↗
PubMed1997

Nitric oxide inhibits CPP32-like activity under redox regulation.

The inhibitory effect of nitric oxide (NO) on the enzymatic activity of CPP32-like proteases in the cell extract from vincristine-treated cells was examined in vitro. NO generated from (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-S-hexen eamide (NOR1) inhibited CPP32-like protease, which constitute a family of interleukin-1beta-converting enzyme (ICE)-like proteases in a dose-dependent manner. Moreover, recombinant CPP32beta activity was inhibited by NOR1 at same concentration. Inhibition of CPP32-like activity by NO was reversed in the presence of glutathione in the enzymatic reaction mixture. Thus, CPP32-like activity was regulated by NO under redox regulation. These findings suggest that NO may prevent apoptosis by inhibiting the ICE protease cascade under the influence of cellular redox status.

Apoptosis↗
PubMed1997

TNF-alpha mediates inducible nitric oxide synthase expression in human neuroblastoma cell line by cisplatin.

The human neuroblastoma cell line NB-39-nu expressed inducible nitric oxide synthase (iNOS) mRNA following treatment with a combination of interferon-gamma (IFN-gamma) and cis-diamminedichloroplatinum(II) (cisplatin). The level of iNOS mRNA peaked at 48 hr after treatment, and dexamethasone inhibited the induction of iNOS mRNA expression. Cisplatin induced tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and an anti-TNF-alpha neutralizing antibody inhibited the induction of iNOS expression by a combination of cisplatin and IFN-gamma in NB-39-nu cells. Thus, iNOS expression in NB-39-nu cells by a combination of cisplatin and IFN-gamma involves in the TNF-alpha-mediated signal transduction mechanism.

Antineoplastic Agents↗
PubMed1997

Lesion-induced neuronal nitric oxide synthase in Purkinje cells of the rat cerebellar cortex: histochemical and in situ hybridization study.

Lesion-induced induction of neuronal nitric oxide synthase (nNOS) was examined in the rat cerebellum. The stab-lesioned cerebellar cortex was examined with NADPH-diaphorase (NADPH-d) histochemistry and in situ hybridization using nNOS cRNA probe at 1, 3, 7, 14, 35 days post-lesion. NADPH-d- and nNOS mRNA-positive Purkinje cells appeared adjacent to the lesion by 3 days after the lesion. The area of distribution expanded and the number of positive cells increased at 7 days after the lesion, and at 14 days post-lesion, shrunken NADPH-d-positive Purkinje cells with irregular surface appeared. NADPH-d activity and nNOS mRNA signal could not be detected in Purkinje cells after 35 days post-lesion. Combined NADPH-d histochemistry and in situ hybridization using glutamic acid decarboxylase (GAD) cRNA probe revealed that nNOS-expressing Purkinje cells showed fewer GAD mRNA signals than those in normal Purkinje cells. The atrophic contour and the lower expression of GAD mRNA signals in NADPH-d positive Purkinje cells suggest that nNOS is expressed under a degenerating process.

Animals↗
PubMed1997

Comparative distribution of nitric oxide synthase (NOS) in pancreas of the dog and rat: immunocytochemistry of neuronal type NOS and histochemistry of NADPH-diaphorase.

We investigated the localization of nitric oxide synthase in the pancreas of the dog in comparison to the rat by the methods of immunocytochemistry using antineuronal type nitric oxide synthase serum and histochemistry using NADPH-diaphorase activity. In both species, the most intense staining was observed in neuronal cell bodies and fibers in the pancreas and nitric oxide synthase immunoreactivity was completely colocalized with NADPH-diaphorase activity. However, there were differences of the distribution between the two species. In the dog pancreas, immuno- and NADPH-diaphorase-positive nerve fibers were numerous around pancreatic ducts and moderate around the arteries and the acini but few in the islets. In contrast, in the rat pancreas, immuno- and diaphorase-positive fibers were fewer around the pancreatic ducts and acini and more abundant in the islets. The expression ratio of NADPH-diaphorase in intrapancreatic ganglion cell bodies that were scattered in the interlobular connective tissue was low to moderate (28.1% in the right lobe, 49.5% in the left lobe) in the dog, while the ratio in rat pancreas was very high in both lobes of the pancreas (about 86%). Except for neuronal staining, weak NADPH-diaphorase-positive reactions were detected in the vascular endothelial cells of the pancreas in both species. In rat islet cells, weak neuronal type nitric oxide synthase immunoreactivity was observed; however, in dog islet cells, no immunoreactivity was detected. These results suggest that nitric oxide in the pancreas is derived from vascular endothelium and neuronal tissue in both species and that the neuronal nitrergic regulation of the exocrine and endocrine pancreas is different between the species.

Animals↗
PubMed1997

Association between p53 mutation and clinicopathological features of non-small cell lung cancer.

Genetic alterations in exons 5-8 of the p53 gene, determined by single-strand conformation polymorphism and sequencing analyses, and the clinicopathological characteristics of 108 patients with non-small cell lung cancer were compared. Mutations in this gene were found in 37 of the 108 patients (34%): in 30% (23/76) of those with adenocarcinomas, 46% (12/26) of those with squamous cell, 33% (1/3) of those with large cell and 33% (1/3) of those with adenosquamous carcinomas. No associations between the incidence of p53 mutations and the histological or cytological subtypes of adenocarcinomas were found. The analysis of types of mutations, however, showed that GC transversion was relatively common in papillary and clara subtypes, whereas it accounted for only 17% at most of p53 mutations in tubular and bronchial surface epithelial cell subtypes of adenocarcinomas. Univariate analyses revealed that large tumor size, high nodal stage and positive vascular invasion of non-small cell lung cancers, and high nodal stage and high-grade nuclear atypia of adenocarcinomas were associated significantly with p53 mutations. Multivariate analyses showed that the tumor sizes of non-small cell lung cancer correlated with p53 mutations with marginal significance (P = 0.099) whereas nuclear atypia of adenocarcinomas correlated significantly (P = 0.028). No differences between the overall or relapse-free survival rates of patients with and without p53 mutations in non-small cell lung cancers or adenocarcinomas were found. These findings indicate that p53 mutations in adenocarcinomas of the lung are associated with the malignant phenotype of tumor cells, but not with patient survival.

Adenocarcinoma↗
PubMed1997

Induction of aberrant crypt foci and flat-type adenocarcinoma in the colons of dogs by N-ethyl-N'-nitro-nitrosoguanidine and their sequential changes.

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.

Adenocarcinoma↗
PubMed1997

Microsatellite instability in lung cancer patients 40 years of age or younger.

Lung cancer in the young, which has the characteristics of a higher incidence of adenocarcinoma, lower male-to-female ratio of the patients, and less frequent smoking history in the patients, may possibly be associated with genetic predisposition to cancers. We studied six microsatellite loci (D2S123, D3S659, D3S966, D5S346, WT1, and TP53) in 18 surgically treated lung cancer patients aged 25-40 years and nine control patients aged 62-74 to determine the presence of microsatellite instability (MSI) and to correlate its occurrence with clinicopathological characteristics. Of the 18 patients, 11 were female and seven were non-smokers. There were 15 adenocarcinomas and three squamous cell carcinomas, 15 (83%) of which had vascular invasion. MSI was positive in seven (39%) of 18 young patients and one (11%) of nine control patients. Moreover, MSIs in a half or more of six loci examined were demonstrated in five (28%) young patients, whereas no control patients showed such a high frequency of MSI. We observed no significant differences in clinical or pathologic parameters between cases with and without MSI. This result suggests that genetic factors play an important role in the development of lung cancer in young adults.

Adenocarcinoma↗
PubMed1997

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.

Adenoma↗