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T Sugimura

Publications and source records attributed to T Sugimura.

At least 325 records · Page 18Linked to original sources
PubMed1993

Biplane transesophageal echo-Doppler studies of atrial septal defects: quantitative evaluation and monitoring for transcatheter closure.

Forty-four patients with atrial septal defects, aged 7 months to 18 years (median 8.9), underwent biplane transesophageal (TEE) and transthoracic (TTE) echocardiography. The size of the defect and the shunt flow volume were measured by TEE and compared with the actual size at surgery (N = 14) or the shunt volume measured by the Fick method (N = 34), respectively. In all cases the location and morphology of the defect were clearly demonstrated by TEE; on the other hand, two patients with sinus venosus-type and multiple-type defects, respectively, and one with a small ostium primum defect did not have a complete diagnosis by TTE. The defect size determined by TEE correlated well with the surgical measurement. Similarly a significant correlation was demonstrated between the shunt volume measured by TEE and that obtained by the Fick method. In three patients transcatheter closure of the atrial septal defect by means of a clamshell device was accomplished successfully with TEE monitoring. We conclude that biplane TEE provides a better appreciation of cardiac anatomy and hemodynamic evaluation than TTE in this setting, and TEE is essential for monitoring during transcatheter closure.

Adolescent↗
PubMed1993

Carcinogenic factors in food with relevance to colon cancer development.

The diet contains various mutagens and carcinogens that can be classified into three groups: naturally occurring chemicals, synthetic compounds and compounds produced by cooking. The first group includes mycotoxins and plant alkaloids while the second is exemplified by food additives and pesticides. The third includes polycyclic aromatic hydrocarbons and heterocyclic amines (HCAs). HCAs are mutagenic to microbes and eukaryotes and their precursors are creatine or creatinine, sugars, and amino acids in meat and fish. Among 10 HCAs so far examined for carcinogenicity in rodents, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced colon cancer in rats. PhIP is an especially interesting compound inducing colon tumors specifically in male F344 rats and only very rarely in females, which develop mammary carcinomas at high frequency instead. Since induced DNA adduct levels, determined by the 32P-postlabeling method, were found to be almost the same in male and female F344 rats adduct formation in itself is not directly responsible for carcinogenesis. We established, however, that PhIP causes increased cell proliferation in colon mucosa but not in the non-target liver or kidney of male rats. Induction of cell proliferation is therefore possibly an additional important factor determining carcinogenic organ specificity. In terms of molecular alteration ras family gene mutations are very rare and no mutations are evident in the p53 gene in colon tumors induced by HCAs. Their development due to HCAs can thus be considered an appropriate experimental model for human colon tumors in which ras or p53 gene activation is not involved. Since HCAs are genotoxic compounds, a causal role in some stage of human colon carcinogenesis is plausible. Exposure to HCAs should accordingly be avoided as far as possible.

Animals↗
PubMed1993

Okadaic acid, a protein phosphatase inhibitor, induces sister-chromatid exchanges depending on the presence of bromodeoxyuridine.

Okadaic acid (OA), a potent tumor promoter and an inhibitor of protein phosphatase 1 and 2A, induced sister-chromatid exchanges (SCEs) in human lymphoblastoid cells and Chinese hamster ovary cells at low concentrations of 2-10 nM, when the cells were grown for two cell cycles in the presence of OA and bromodeoxyuridine (BrdUrd). Prolonged treatment with OA prior to addition of BrdUrd did not induce SCEs, indicating an essential role of BrdUrd. A similar important role of BrdUrd in SCE induction has been reported in the cases of benzamide (BA) (Natarajan et al., 1981) and camptothecin (CPT) (Zhao et al., 1992), which are inhibitors of poly(ADP-ribose)polymerase and DNA topoisomerase I (topo I), respectively. Unlike many DNA-damaging agents, they are required to be present during S phase along with BrdUrd in the medium and/or in the parental DNA as BrdUMP. Thus OA, like BA and CPT, is a new type of SCE inducer. Exposing cells to a combined treatment with OA, BA and CPT, a significantly higher level of SCEs was induced than that expected if the numbers of SCE caused by these three inhibitors were additive, while no such synergistic increase was seen in every combination of two agents. Since both phosphorylation and poly(ADP-ribosyl)ation have been known to modify topo I activity, the results suggest a common involvement of topo I for SCE formation by OA, BA and CPT. In addition to SCE induction, OA resulted in an increase of mitotic cells which were characterized by a marked chromosome condensation. OA also induced chromosome fragmentation/pulverization in human lymphoblastoid cells and fragmented nuclei in Chinese hamster cells.

Animals↗
PubMed1993

Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.

The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) is widely distributed in cooked foods. The nuclease P1 method increased the sensitivity of the standard 32P-postlabeling analysis about 1000-fold for detection of MeIQx-DNA adducts. The recovery of MeIQx-DNA adducts by the nuclease P1 method was determined to be about 50% using liver DNA of a rat treated with [14C]MeIQx intragastrically. By the nuclease P1 method five adducts were detected in the liver DNA of rats fed MeIQx and two of them, including the most abundant one, were identified as MeIQx-deoxyguanosine adducts by comparison with the adducts formed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with the four 2'-deoxyribonucleotides. The most abundant adduct in vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate (3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissues could be determined by the nuclease P1 modification of the 32P-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.

Animals↗
PubMed1993

Dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) carcinogenicity in rats.

The dose-dependence of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) carcinogenicity was investigated in F344 rats of both sexes administered the heterocyclic amine in the diet at concentrations of 25 or 100 p.p.m. for up to 104 weeks. Incidences of mammary adenocarcinomas were 7% (2/30) for 25 p.p.m. and 47% (14 of 30 rats) for 100 p.p.m. in females and those of colon adenocarcinomas were 43% (13/30) for males and 13% (4/30) for females of the 100 p.p.m. groups. No mammary adenocarcinomas were induced in males and no colon carcinomas were observed in the 25 p.p.m. groups of either sex. Furthermore, development of lymphocytic leukemia was apparently enhanced by PhIP in males. In a separate experiment, dose-dependent induction of aberrant crypts in the large intestine, considered as preneoplastic lesions, was evident after 8 weeks feeding of PhIP-supplemented diet at doses of 25, 100 or 400 p.p.m. Thus a clear dose-dependency was demonstrated for both colon and mammary carcinogenesis. Since PhIP is a particularly abundant heterocyclic amine and its carcinogenic organotropism overlaps with the types of neoplasias most commonly observed in western countries, the compound may be extremely important with respect to human cancer development.

Adenocarcinoma↗
PubMed1993

High frequency and low specificity of ras gene mutations in rat Zymbal's gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline.

The activating mutations of all three ras genes in rat Zymbal's gland tumors induced by a food mutagen, 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) were analyzed. DNA fragments of the Ha-ras, Ki-ras and N-ras oncogenes were amplified from formalin-fixed and paraffin-embedded tissues by the polymerase chain reaction (PCR) and analyzed for activating mutations involving codons 12, 13 and 61 by oligonucleotide differential hybridization. All nine Zymbal's gland tumors examined, including three papillomas, were found to contain either an Ha-ras or Ki-ras mutation. These mutations were located in either codon 13 or 61 of Ha-ras, and in either codon 12 or 13 of Ki-ras. Of the nine mutations, three were G-->T, three were G-->C, two were G-->A and one was A-->T. Of the nine mutations, eight occurred at guanine bases and seven were transversions. There was no correlation between the types of mutations and the histological types of the tumors. These results suggest that ras gene activation is an important early event in the tumorigenesis induced by IQ in rat Zymbal's gland and that mutations at guanine bases are frequent, though the locations and types of the mutations are not highly specific.

Animals↗
PubMed1993

Multiple steps in carcinogenesis involving alterations of multiple tumor suppressor genes.

Recent advances in molecular genetics have made it possible to understand the molecular mechanisms of human cancer progression. The results indicate that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration occurs during tumor progression. It is widely accepted that tumor suppressor genes play a central role in the genesis and progression of human cancers, as frequent alterations of tumor suppressor genes have been found in a variety of human cancers. Molecular analyses of various stages of human cancers, from precancerous lesions to advanced or metastatic tumors, indicate that sequential accumulation of genetic alterations correlates with more malignant phenotypes of tumor cells. Furthermore, biological studies of tumor suppressor genes have revealed that a single gene defect is not sufficient for the cells to gain growth advantage and start clonal expansion in vivo. These results are consistent with the concept of human multistage carcinogenesis, indicated by experimental animal models and epidemiological studies. Although it is supposed that there are more than 20 tumor suppressor genes in the human genome, only a few tumor suppressor genes have been identified to date. Thus, further studies should focus on the identification and characterization of novel tumor suppressor genes, and molecular analysis of those genes in human cancer would be of great help in clarifying the multiple steps in the process of human carcinogenesis.

Animals↗
PubMed1993

Strong inhibition of 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole-induced mutagenesis and hepatocarcinogenesis by 1-O-hexyl-2,3,5-trimethylhydroquinone.

The effects of 3-O-dodecylcarbomethylascorbic acid (3-O-DAsA), 3-O-ethylascorbic acid (3-O-EAsA) and 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) on 2-amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole (Glu-P-1)-induced mutagenesis and hepatocarcinogenesis were examined. In a Salmonella assay, addition of 2.5 to 20.0 mg of HTHQ to Salmonella TA 98 in the presence of S-9 mixture dose-dependently inhibited Glu-P-1-induced mutagenesis. The highest dose showed a 99% reduction in revertants. 3-O-DAsA and 3-O-EAsA were without effect. In an animal study using the medium-term bioassay system for the detection of hepatocarcinogens or hepatopromoters in F344 male rats, treatment with Glu-P-1 alone was associated with a significant increase in the number and area of GST-P-positive foci (47.5 +/- 8.9 and 11.1 +/- 4.7, respectively). Combined treatment with 1.0% HTHQ significantly reduced the number and area of GST-P-positive foci (to 8.1 +/- 2.1 and 0.6 +/- 0.2) while 3-O-DAsA exerted marginal inhibition and 3-O-EAsA had no effect. On the other hand, all three of these compounds slightly enhanced the numbers and areas of foci when given alone. The results indicate that HTHQ is a potent chemopreventer of Glu-P-1-induced hepatocarcinogenesis.

Animals↗
PubMed1993

Effects of chronic administration of low doses of 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline on glutathione S-transferase placental form-positive foci development in the livers of rats fed a choline-deficient diet.

Effects of chronic administration of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) at the very low doses of 0.4 and 4 ppm, respectively 1000- and 100-fold less than the dose shown to be carcinogenic (400 ppm), on the liver of rats fed a choline-deficient (CD) diet were examined in terms of glutathione S-transferase placental form (GST-P)-positive foci. Male F344 rats were given CD diet containing 0, 0.4 or 4 ppm MeIQx for 20 or 40 weeks. As controls, rats received choline-supplemented (CS) diet in the same manner. MeIQx at 4 ppm in the CD diet significantly increased both the number and area of GST-P-positive foci, the values being 2.3- and 2.1-fold at 20 weeks and 2.0- and 3.3-fold at 40 weeks, respectively, compared with those observed for CD diet alone. MeIQx at 0.4 ppm in CD diet did not affect the development of GST-P-positive foci. No influence of the heterocyclic amine was found in the CS groups, where only very small numbers of minute lesions were observed. The level of MeIQx-DNA adducts in rats given the CD diet containing 4 ppm MeIQx was 2- to 3-fold lower than that in rats given the CS diet containing 4 ppm MeIQx at 20 and 40 weeks. This result indicates that DNA adduct formation and cell proliferation are both required for the increase of GST-P-positive foci in rats fed 4 ppm MeIQx in a CD diet. The above findings strongly suggest that MeIQx could be carcinogenic even at 4 ppm under CD conditions, where liver cell regeneration is continuously occurring.

Animals↗
PubMed1993

Helicobacter pylori may be transmitted through gastrofiberscope even after manual Hyamine washing.

Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash-out samples from the biopsy-suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy-suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential.

Base Sequence↗
PubMed1993

Current issues in Kawasaki disease.

The most important clinical aspect of Kawasaki disease is the cardiovascular problems. This article reports on the cardiovascular spectrum in acute Kawasaki disease, analysis of myocardial infarction and fatal cases, a follow-up study on the natural history of coronary artery lesions, long-term cardiovascular problems including premature atherosclerosis, problems in the adult cardiology and the treatment of acute Kawasaki disease. The etiology and pathogenesis of this disease are still unknown. Current hypotheses and leading studies on the etiology and the pathogenesis of Kawasaki disease are also reviewed.

Adult↗
PubMed1993

Exposure to heterocyclic amines.

Many mutagenic heterocyclic amines (HAs) have been isolated from cooked foods and pyrolysates of amino acids and proteins, and the carcinogenicity of 10 of these HAs in rodents and of 1 in monkeys has been reported. Quantification of these carcinogenic HAs in various kinds of cooked foods indicated that the level of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was highest (0.56-69.2 ng/g), that of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was second highest (0.64-6.44 ng/g), and those of other HAs were 0.03-2.50 ng/g. Heterocyclic amines were found in urine samples of 10 healthy volunteers consuming a normal diet, but HAs were not detectable in urine samples of three patients receiving parenteral alimentation. These results strongly suggest that humans are continuously exposed to HAs derived from food in the normal diet. Based on quantitative data on the levels of HAs in cooked foods and urine samples, the daily exposures to PhIP and MeIQx were estimated to be 0.1-13.8 micrograms and 0.2-2.6 micrograms per person, respectively. These levels of carcinogenic HAs are in the same range as those of other carcinogens such as N-nitrosodimethylamine and benzo[a]pyrene to which humans are exposed.

Adolescent↗
PubMed1993

Immunohistochemical localization of an inducible form of nitric oxide synthase in various organs of rats treated with Propionibacterium acnes and lipopolysaccharide.

Immunohistochemical localization of an endotoxin-inducible form of nitric oxide synthase was examined using rabbit polyclonal antibody against the enzyme purified from rat liver. In rats treated with Propionibacterium acnes and lipopolysaccharide, immunostaining was observed in macrophages, occasional lymphocytes, neutrophils and eosinophils in red pulp of spleen, Kupffer cells, endothelial cells and hepatocytes in liver, alveolar macrophages in lung, macrophages and endothelial cells in adrenal glands, and histiocytes, eosinophils, mast cells and endothelial cells in colon. Immunoreactivity was also evident in the following tissues: histiocytes and endothelial cells in kidney; histiocytes and neutrophils in esophagus; macrophages and eosinophils in duodenum; macrophages, some lymphocytes and mast cells in ileum; histiocytes in thymus; and endothelial cells in heart and aorta. Immunoreactivity was not detected in these organs from untreated rats. Positively staining cells in these rat organs appeared within 2.5 h after lipopolysaccharide administration; their number dramatically increased within the next 2.5 h, remained at high levels for a further 19 h, and then decreased over the following 24 h. The number of positive cells appearing correlated well with the nitric oxide synthase activity biochemically determined in the same organs.

Adrenal Glands↗
PubMed1993

Defective secretion of albumin encoded by exon-skipped mRNA found in aged analbuminemic rat liver.

Remarkable increases in the amount of exon H-skipped (delta H), exons G and H-skipped (delta GH), and exons H and I-skipped (delta HI) mRNAs of rat albumin have been found in the livers of aged or mutagen-treated analbuminemic rats (Kaneko, T., H. Shima, H. Esumi, M. Ochiai, S. Nagase, T. Sugimura, M. Nagao: Proc. Natl. Acad. Sci. USA 98, 2707-2711 (1991)), in association with increases in numbers of immunohistochemically albumin-positive hepatocytes and the accumulation of albumin(s) in the cells. To determine which type of mRNA is responsible for the accumulation of albumin(s), expression vector systems for intact mRNA and three kinds of exon-skipped albumin mRNAs were constructed and transfected into COS-1 and HepG2 cells. Transient expression and secretion of albumins were examined in these cells. delta HI albumin and intact albumin were efficiently expressed by both types of transfected cells. The delta HI albumin expressed had a similar molecular weight to the major albumin isolated from the microsome fraction of the liver of aged analbuminemic rats, as judged by SDS-PAGE. The rate of secretion of delta HI albumin was very low in both types of transfected cells, whereas those of delta H and delta GH albumins were normal. Immunocytochemical analyses of the transfected COS-1 cells with antiserum against rat albumin showed that the distribution of intact albumin had a compact Golgi-like pattern, whereas that of delta HI albumin had a diffuse endoplasmic reticulum-like pattern. These distribution patterns were similar to those in aged analbuminemic rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Dynamic response of the adult monkey maxilla to occlusal forces.

We investigated the magnitude of various maxillary occlusal forces and the direction in which such forces were propagated. Adult monkeys were anesthetized and forced to occlude on sticks of 3, 5 and 7 mm thickness at the canines, second premolars and second molars. Electrical stimulation was applied to the masseter and temporalis muscles, and measurements of magnitude, direction and character of principal strains were recorded. Readings for the surface of the maxilla indicated that bone sutures and adjacent cavities are intimately and functionally related to the buffering of these occlusal forces. The maxilla deformed as the premaxilla was pushed out in the region of the premaxillomaxillary suture. The nasal bone was stretched anteroposteriority in the region of the nasomaxillary suture as the space that arose due to contraction of the masseter muscle was filled in the region of the zygomaticomaxillary suture. In addition, when occlusal forces were imparted on the maxilla, the surfaces of this bone bulged out due to the effect on adjacent bone cavities. Results demonstrated that the maxilla dispersed occlusal force well by these mechanisms. Accordingly, there were very few regions in this bone where stresses concentrated.

Animals↗
PubMed1993

[Helicobacter pylori infection in gastric cancer].

The relationship between Helicobacter pylori (H. pylori) infection and gastric cancer becomes the topics in the world, since some reports thereon in 1991. The purpose of this study was to know the prevalence of H. pylori infection in many patients with gastric cancer. We examined the H. pylori IgG antibody in 507 patients with gastric cancer resected surgically in our hospital from 1989 to 1991, retrospectively. For the test of H. pylori IgG antibody, HM-CAP EIA kit (Italy, ENTERIC PRODUCTS Co.) was used. The overall detection rate of H. pylori IgG antibody was 75% (378/507). H. pylori infection was significant significantly frequent in early cancer (80%, 231/288) than advanced cancer (67%, 147/219). But, the other clinicopathological features such as sex, age, histological type, location and the degree of intestinal metaplasia were not significantly correlated with H. pylori infection. To evaluate the risk of H. pylori infection for gastric cancer, we are going to plan a matched-pair case-control study.

Aged↗
PubMed1992

Multistep carcinogenesis: a 1992 perspective.

Cancer is the leading cause of death in Japan. Recent changes in cancer incidence patterns may reflect the trend toward a more Western diet and life-style. Among the dietary factors that contribute to carcinogenesis are the heterocyclic amines, a group of mutagenic compounds present in cooked meat and fish. Carcinogenesis is a multistep process in which cells accumulate multiple genetic alterations as they progress to a more malignant phenotype. Recognition of the growing number of interacting factors that contribute to carcinogenesis may force reconsideration of current methods of risk assessment.

Amines↗