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Biomedical subjects

E Tsuchiya

Publications and source records attributed to E Tsuchiya.

At least 73 records · Page 4Linked to original sources
PubMed1993

Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma.

Frequent losses of heterozygosity observed at several chromosomal loci in primary lung cancers have indicated the existence of several tumor suppressor genes associated with this type of cancer. We have examined loss of heterozygosity on chromosomal arm 8p in 49 cases of non-small cell lung carcinoma, using 14 restriction fragment length polymorphism markers. Of 42 cases informative with at least one marker, 21 showed allelic loss, including 15 of 32 adenocarcinomas and 5 of 9 squamous cell carcinomas. The frequency of allelic loss on 8p was similar at all clinical stages. Deletion mapping defined a single common region of deletion in these tumors within an 8 cM interval at 8p21.3-p22 flanked by the loci defined by cMSR-32 and cC18-245.

Adenocarcinoma↗
PubMed1993

Immunophenotypic and molecular analysis of a case of lymphocytic interstitial pneumonia.

A case of lymphocytic interstitial pneumonia was studied immunophenotypically and with molecular methods in order to clarify its lymphocytic clonality. The patient, a 43 year old Japanese female, underwent lobectomy for a suspected malignant lymphoma as no clear diagnosis could be made from the biopsy specimen. An ill-demarcated, yellowish and elastic firm lesion measuring 60 x 35 x 20 mm in size was located in the peripheral part of the middle lobe of the right lung. Histologically, the alveolar, peribronchial-vascular and subpleural interstitia within the lesion were thickened markedly with severe cellular infiltration largely composed of small lymphocytes with germinal centers. Immunostaining revealed immunoglobulin (Ig) kappa and Ig lambda-bearing cells to be evenly distributed, suggestive of polyspecificity. Immunoglobulin gene analysis further demonstrated the unrearranged germ-line DNA but no rearranged band. These results strongly indicated a reactive process rather than a neoplastic nature for the lesion.

Adult↗
PubMed1993

Mucosal spreading adenocarcinoma at the hilar portion of the lung.

The first case of mucosal spreading adenocarcinoma at the hilum of the lung is presented. The patient was a 72 year old Japanese male smoker. The carcinoma was located at the right main bronchus with involvement of the apical, posterior and anterior segmental bronchi. The tumor consisted of stratified oval or polygonal cells and signet ring cells spreading along the bronchial mucosa in an in situ fashion with extension down the bronchial gland ducts and acini. Only a small micro-invasive focus not extending beyond the bronchial cartilage was seen. Immunohistochemically, the tumor was positive for lysozyme but negative for lactoferrin and PE-10 indicating that this tumor was possibly showing goblet cell differentiation.

Adenocarcinoma↗
PubMed1992

Frequent somatic mutations of the APC gene in human pancreatic cancer.

The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas.

Base Sequence↗
PubMed1992

Lung cancers associated with thorotrast exposure: high incidence of small-cell carcinoma and implications for estimation of radon risk.

The widely accepted concept that the alpha-emitting radionuclide radon (222Rn, 220Rn) induces lung cancers in humans has been based on the excess of lung tumours observed in underground miners extracting uranium or other substances. However, this poses the important question of whether radon is the only carcinogenic factor because such miners are also heavily exposed to mine dusts including silicates, diesel exhaust, etc. in their working environment. Patients to whom Thorotrast was administered continuously exhale radon (220Rn) derived from 232Th deposits in the body and therefore provide a good model for lung carcinogenesis by radon without concomitant dust exposure. We therefore investigated lung-cancer incidence in our epidemiological follow-up series, analysing the histological types of 11 lung cancers which were found among 359 Thorotrast autopsy cases and measuring radioactivity in the breath of living Thorotrast patients. The study revealed that, while the proportion of small-cell lung cancers considered to be related to alpha-particles was significantly increased, the overall lung cancer incidence was not significantly higher than in controls, in spite of the high level of 220Rn in the patients' breath. This result suggests that radon in the lung does induce cancers (particularly small-cell carcinomas) but that the induction rate is not as high as expected from risk factors associated with mining. Thus, excess lung cancers among the miners might be related to the combined effects of exposure to radon and mine dusts, and not solely to radon.

Aged↗
PubMed1992

Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer.

Frequent loss of heterozygosity at chromosomal loci in a specific tumor type may indicate the presence of a tumor suppressor gene. We have examined loss of heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346 patients representing seven different types of human cancer. Frequent allelic losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35, 40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%) and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120 hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers along the short arm of chromosome 8 defined commonly deleted regions within the same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor suppressor genes for both cancers may be present in that region.

Alleles↗
PubMed1992

Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma.

We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.

Adenocarcinoma↗
PubMed1992

Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarcinoma of the lung.

We examined loss of heterozygosity in 49 adenocarcinomas and 18 squamous cell carcinomas of the lung with 19 RFLP markers on the short arm of chromosome 3. Although no interstitial deletions were observed in any squamous cell carcinomas, interstitial or partial deletions were detected in 23 adenocarcinomas. Identification of two common regions of deletion in adenocarcinomas, at 3p21.3 and 3p14.1-21.1, suggested the presence of at least two tumor suppressor genes on 3p within the same regions commonly deleted in renal cell carcinomas. Correlation between the frequency of loss of heterozygosity on 3p and histopathological grade of adenocarcinoma also was observed. These results imply an etiological difference between two major types of non-small cell lung cancers, adenocarcinoma and squamous cell carcinoma.

Adenocarcinoma↗
PubMed1992

The Saccharomyces cerevisiae NPS1 gene, a novel CDC gene which encodes a 160 kDa nuclear protein involved in G2 phase control.

We have cloned the gene NPS1 (nuclear protein of Saccharomyces) which encodes a nuclear protein of mol. wt 156 735 Daltons (1359 amino acids) essential for cell growth. NPS1 contains a 2 kb sequence that is highly homologous to the S. cerevisiae SNF2/GAM1 gene known as a transcriptional regulator for multiple genes. However, the NPS1 gene was found to have a distinct function from SNF2/GAM1. The growth of the cells carrying a nps1 delta :: URA3 deletion allele and galactose-inducible NPS1 on a plasmid was arrested under NPS1-repressed conditions with a cell cycle arrest phenotype, being arrested at the large-bud stage with a single nucleus that had a DNA content of G2/M phase. When the arrested cells were further incubated under NPS1-repressed conditions, re-replication of DNA occurred in some of the arrested cells without passage through mitosis. In the predicted amino acid sequence of NPS1, sequences homologous to the catalytic domain of protein kinases were found. We constructed a mutation which results in the substitution of a highly conserved lysine residue (Lys792) in the presumed ATP-binding site of this kinase-like domain with a glutamic acid codon. The mutant gene failed to rescue the growth defect caused by NPS1 disruption, suggesting that Lys792 is essential for the function of NPS1.

Amino Acid Sequence↗
PubMed1992

Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation to histological subtypes of lung cancer.

The incidence of atypical bronchioloalveolar cell hyperplasia (ABH) of the lung was investigated to evaluate the possibility of this lesion being a precancerous stage in the histogenesis of adneocarcinoma. Lobectomy and pneumonectomy specimens of 165 primary and 45 metastatic tumour cases were step-sectioned horizontally and examined histologically. An average of 51 blocks were taken in each case. Sixty-seven ABHs up to 10 mm in diameter were detected, only 2 lesions being associated with scar tissue. Age was one factor apparently related to ABH development, although not the major one. There was no correlation between smoking index and ABH occurrence. In males, the incidence was highest in association with adenocarcinoma (25.5% of cases, 0.8% of sections), followed by large cell carcinoma (25.0% of cases), squamous cell carcinoma (10.5% of cases) and metastatic tumours from other sites (4.8% of cases). In females, ABH was also more common together with adenocarcinoma (8.3% of cases) than with metastatic tumours (4.0% of cases). The differences in male incidences by case and by section between the adenocarcinoma and metastatic tumour categories were statistically significant (P less than 0.05, P less than 0.01 respectively) indicating that ABH may be a precancerous lesion capable of transformation of adenocarcinoma.

Adenocarcinoma↗
PubMed1992

Surgical treatment of pulmonary metastases from uterine cervical cancer. Operation method by lung tumor size.

Between 1959 and 1986, 32 patients with pulmonary metastatic tumors from squamous cell carcinoma of the uterine cervix underwent pulmonary resection. The method of pulmonary resection was correlated with the pathology of the metastases. In 20 patients with pulmonary metastatic lesions 3 cm in diameter or larger, secondary lymph node involvement was observed in 65% and microscopic satellite lesions around the main metastatic lesion were seen in 50%. On the other hand, in none of 12 patients having metastatic lesions smaller than 3 cm was there accompanying lymph node involvement, and microscopic satellite lesions were observed in only one patient among them. Consequently, we concluded that wedge resection with a disease-free margin of 2 cm or a little more from the tumor edge was appropriate for lesions smaller than 3 cm in diameter, and lobectomy with lymph node dissection was necessary for lesions 3 cm in diameter or more.

Adult↗
PubMed1991

The Saccharomyces cerevisiae genes (CMP1 and CMP2) encoding calmodulin-binding proteins homologous to the catalytic subunit of mammalian protein phosphatase 2B.

Saccharomyces cerevisiae genomic clones that encode calmodulin-binding proteins were isolated by screening a lambda gt11 expression library using 125I-labeled calmodulin as probe. Among the cloned yeast genes, we found two closely related genes (CMP1 and CMP2) that encode proteins homologous to the catalytic subunit of phosphoprotein phosphatase. The presumed CMP1 protein (62,999 Da) and CMP2 protein (68,496 Da) contain a 23 amino acid sequence very similar to those identified as calmodulin-binding sites in many calmodulin-regulated proteins. The yeast genes encode proteins especially homologous to the catalytic subunit of mammalian phosphoprotein phosphatase type 2B (calcineurin). The products of the CMP1 and CMP2 genes were identified by immunoblot analysis of cell extracts as proteins of 62,000 and 64,000 Da, respectively. Gene disruption experiments demonstrated that elimination of either or both of these genes had no effect on cell viability, indicating that these genes are not essential for normal cell growth.

Alleles↗
PubMed1991

Inhibition of membrane Ca2(+)-ATPase of Saccharomyces cerevisiae by mating pheromone alpha-factor in vitro.

Plasma membrane Ca2(+)-ATPase of Saccharomyces cerevisiae was solubilized and partially purified by calmodulin-affinity chromatography. The activity of Ca2(+)-ATPase isolated from MATa cells was inhibited by physiological concentrations of the mating pheromone alpha-factor in a dose-dependent manner. The enzyme prepared from a receptor-deficient sterile mutant cells (delta ste-2) was similarly inhibited by alpha-factor, but the enzyme from MAT alpha cells was resistant to the mating pheromone. We suggest that the inhibition may be involved in the alpha-factor-induced increase of Ca2+ uptake reaction of MATa cells.

Bacterial Proteins↗
PubMed1990

Calmodulin-binding proteins of Saccharomyces cerevisiae.

The subcellular distribution of calmodulin-binding proteins in the soluble, plasma membrane, and nuclear fractions of Saccharomyces cerevisiae was analyzed with a gel binding assay using 125I-labeled calmodulin. Over 20 binding proteins were detected. The calmodulin-binding protein profiles were markedly different among the fractions. Calmodulin-binding proteins were most abundant in the nuclear fraction, followed by the membrane fraction and the soluble fraction in decreasing order. The amounts of certain calmodulin-binding proteins increased after treatment with alpha-mating factor.

Calmodulin↗
PubMed1989

Pulmonary sclerosing hemangioma of the lung. A type II pneumocytoma by immunohistochemical and immunoelectron microscopic studies.

Three cases of pulmonary sclerosing hemangioma were studied by immunohistochemical and immunoelectron microscopic methods using a panel of antibodies. Six cases of adenocarcinoma of the lung, three cases of normal mesothelium, and three cases of mesothelioma were used as controls. The cytoplasm of some of the sclerosing hemangioma tumor cells was positive for the anti-lung surfactant apoprotein monoclonal antibody (PE-10). These cells were the pale cells of the solid areas, the cells covering the papillary projections, and the cells lining the cleft-like spaces. These cells also were positive for conventional epithelial cell markers. Some cells also were positive for vimentin. Electron microscopic study showed that the predominant cell was a poorly differentiated pneumocyte. Immunoelectron microscopic study also demonstrated that PE-10 existed in the rough endoplasmic reticulum of some of the cells in the solid areas, in the same way as normal type II pneumocytes. We concluded that the sclerosing hemangioma is an epithelial tumor with differentiation towards type II pneumocytes.

Aged↗
PubMed1989

Identification of a wheat germ agglutinin-sensitive ATPase in yeast nuclei.

We have found that wheat germ agglutinin (WGA), a lectin that specifically binds to N-acetylglucosamine residues inhibits the in vitro transport of plasmid DNA, pJDB219, into yeast nuclei. Histochemical staining of the isolated nuclei with biotinylated WGA and streptavidin-biotinylated peroxidase complex revealed the presence of WGA-binding materials around the nuclear pore under an electron microscope. Using WGA-agarose column chromatography of yeast nuclear extracts, a novel Mg2+-dependent ATPase was isolated. Its activity was highly sensitive to WGA and stimulated by Nonidet P-40 or phosphatidylserine. We suggest that the WGA-sensitive ATPase plays a role in yeast nuclear transport of DNA.

Adenosine Triphosphatases↗
PubMed1989

Saccharomyces cerevisiae protein kinase dependent on Ca2+ and calmodulin.

A Ca2+- and calmodulin (CaM)-dependent protein kinase of Saccharomyces cerevisiae was partially purified by CaM affinity chromatography of the soluble fraction, and the properties of the enzyme were investigated. The protein kinase activity of the affinity-purified preparation was stimulated at least eightfold by the simultaneous presence of Ca2+ and CaM. The enzyme stimulation was strongly inhibited by trifluoperazine (TFP), a CaM antagonist. When the kinase was incubated in the presence of ATP, Ca2+, and CaM before the assay, the enzyme showed activity even in the presence of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and TFP. The conversion to this Ca2+- and CaM-independent form occurred very rapidly under the incubation conditions required for protein phosphorylation by the kinase. At the highest level of conversion, Ca2+- and CaM-independent kinase activity, which was measured in the presence of EGTA and TFP, was nearly equal to the total kinase activity, which was measured in the presence of Ca2+ and CaM. A protein with a molecular weight of 58,000 was the major species that was phosphorylated in a Ca2+- and CaM-dependent manner by incubation of the CaM affinity-purified proteins with [gamma-32P]ATP. The protein kinase activity of the protein with the same molecular weight was demonstrated by in situ protein phosphorylation in sodium dodecyl sulfate-polyacrylamide gels by using casein as the substrate, after removal of the detergent from electrophoresed CaM-binding proteins. These data indicate that phosphorylation of the kinase is responsible for the conversion of enzyme activity. Enzyme regulation by this mode may play an important role in integrating cellular functions during the cell cycle. A possible role for the Ca2+-and CaM-dependent protein kinase in the signal transduction of the mating pheromone alpha factor is also discussed.

Calcium↗