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Biomedical subjects

A Oshima

Publications and source records attributed to A Oshima.

At least 127 records · Page 7Linked to original sources

Human beta-galactosidase gene mutations in morquio B disease.

Three different beta-galactosidase gene mutations--a 273Trp----Leu (mutation F) in both families, 482Arg----His (mutation G) in one family, and 509Trp----Cys (mutation H) in the other family--were identified in three patients with Morquio B disease who were from two unrelated families. Restriction-site analysis using StuI, Nsp(7524)I or RsaI confirmed these mutations. In human fibroblasts, mutation F expressed as much as 8% of the normal allele's enzyme activity, but the other mutations expressed no detectable enzyme activity. We conclude that the unique clinical manifestations are specifically associated with mutation F, a common two-base substitution, in this disease.

Amino Acid Sequence↗

Galactosialidosis: simultaneous deficiency of esterase, carboxy-terminal deamidase and acid carboxypeptidase activities.

Esterase and deamidase activities at pH 7.0 and carboxypeptidase activity at pH 5.7 were markedly low or deficient in seven galactosialidosis fibroblast strains with deficient activity of "protective protein" for lysosomal beta-galactosidase and neuraminidase. No simultaneous deficiency of these three enzyme activities was observed in other lysosomal disease fibroblasts examined in this study. This result strongly suggests that "protective protein" is identical with a multifunctional protein with esterase/deamidase/carboxypeptidase activities and its mutation in galactosialidosis results in deficiency of these three enzyme activities.

Adolescent↗

Natural history of colorectal polyps and the effect of polypectomy on occurrence of subsequent cancer.

To elucidate the natural history of colorectal polyps and to observe the influence of endoscopic polypectomy on the incidence of colorectal cancer, we conducted a retrospective cohort study of all patients who had undergone colonoscopic examination at the Center for Adult Diseases, Osaka, between April 1974 and December 1985. The study subjects consisted of a control group (760 non-polyp patients) and a polyp group (648 polyp patients, including 136 treated by polypectomy at the initial examination). These subjects were followed up until the end of 1987 by record linkage with the Osaka Cancer Registry's file to observe the occurrence of colorectal cancer. The O/E (observed/expected numbers derived from the general population) was 5.1 (95% confidence interval = 2.5-9.4) and 1.0 (0.1-3.6) for the polyp and control group, respectively. When subjects in the polyp group were categorized into polypectomy and non-polypectomy sub-groups, the O/E was 2.3 (0.1-12.6) and 8.0 (3.4-15.8) respectively. The relative risk of undergoing polypectomy to developing subsequent cancer was estimated at 0.3 (0.1-2.1). These results suggest an increased risk of developing cancer among polyp patients and the possibility of prophylactic effect of polypectomy against subsequent cancer. A large-scale and long-term follow-up study is required to confirm these findings.

Age Factors↗

Partial deletion of human alpha-galactosidase A gene in Fabry disease: direct repeat sequences as a possible cause of slipped mispairing.

A partial deletion involving exon 3 associated with a single base change (A to C) was found in the alpha-galactosidase A gene of a hemizygous male Fabry patient and his mother, a heterozygous proband. This 402-bp deletion was flanked by 6-bp direct repeat sequences, and the intervening portion was found to have unique complementary sequences. These specific structures may have promoted "slipped mispairing" in this family.

Base Sequence↗

Expression, glycosylation, and intracellular distribution of human beta-galactosidase in recombinant baculovirus-infected Spodoptera frugiperda cells.

A full-length cDNA encoding human acid beta-galactosidase was inserted into the baculovirus genome under transcriptional regulation of the viral polyhedrin gene promoter. The Spodoptera frugiperda cells infected with the recombinant virus expressed the beta-galactosidase activity 300-fold higher than human fibroblasts. Immunoblot analysis revealed an 82-kDa protein band, which was modified in molecular size by deglycosylating enzymes; an 80-kDa band appeared after N-glycanase digestion, and two bands (80-kDa and 81-kDa) appeared after endoglycosidase H digestion. This result suggested that the enzyme molecule was glycosylated, partly with high-mannose type oligosaccharides. The intracellular distribution of the enzyme observed by indirect immunofluorescence staining was perinuclear or diffusely cytoplasmic, and not characteristic of lysosomes; the enzyme was secreted to the culture medium in large quantities, and not translocated to lysosomes. Possible application of this expression system to the studies of the structure and function of normal and mutant human beta-galactosidases was discussed.

Animals↗

Estimation of validity of mass screening program for gastric cancer in Osaka, Japan.

To assess the validity of mass screening tests for gastric cancer conducted with three types of radiographic techniques, i.e., photofluorography by a mirror camera, photofluorography by an image intensifier, and direct radiography, 105,122 persons who underwent a total of 272,667 screening tests during 1970 through 1982 were followed through December 31, 1983 by means of a record linkage to the Osaka Cancer Registry, Osaka, Japan. The results of 1 year's follow-up from screening were defined as the gold standard and test performance values were calculated. Sensitivity of screening with photofluorography by a mirror camera, photofluorography by an image intensifier, and direct radiography was 90%, 89%, and 91%, and specificity was 86%, 92%, and 91%, respectively. The receiver operating characteristics curve for screening with photofluorography by an image intensifier resembled that for direct radiography and these two curves were located somewhat to the left of the curve for screening with photofluorography by a mirror camera. The authors conclude that the validity of screening with photofluorography by an image intensifier is almost equivalent to that of screening with direct radiography and both are superior to that of screening with photofluorography by a mirror camera.

Adult↗

A case-control study of hepatocellular carcinoma in Osaka, Japan.

A case-control study was undertaken to evaluate the roles of hepatitis B virus (HBV), blood transfusion, alcohol drinking and cigarette smoking in the etiology of hepatocellular carcinoma (HCC) in Osaka, Japan. A total of 229 cases and 266 hospital controls were included in our study. The relative risks of HCC obtained after adjustment for age, sex and other important variables were 14.3 (95% confidence interval (CI): 5.7-36.3) for HBsAg positives, 4.3 (95% CI: 1.9-9.6) for blood recipients and 3.2 (95% CI: 2.0-5.1) for heavy drinkers. A statistically significant dose-response relationship was observed between the risk of HCC and total alcohol consumption. The overall risk for HCC was also significantly elevated among smokers; however, there was no consistent dose-response relationship between the risk and cigarette consumption. We conclude that HBV, blood transfusion and excessive alcohol drinking play important roles in the etiology of HCC in Osaka, Japan. Further investigation is needed to clarify the possible etiological role of smoking.

Adult↗

Beta-galactosidase-deficient human fibroblasts: uptake and processing of the exogenous precursor enzyme expressed by stable transformant COS cells.

COS-1 cells were transfected by electroporation with a cDNA for human acid beta-galactosidase cloned in our laboratory and stable transformants expressing the enzyme activity were selected. The precursor form of the enzyme was secreted in large quantities into the culture medium. The fibroblasts from patients with GM1-gangliosidosis or Morquio B disease showed a remarkable increase of enzyme activity, up to the normal level, after culture in this medium for 2 days; the amount of uptake was essentially the same as that for the precursor form in human fibroblasts. After endocytosis, the precursor molecules were processed normally to the mature form and remained as stable as those produced by human fibroblasts. On the other hand, cells from galactosialidosis patients did not show any increase of enzyme activity in a similar experiment. It was concluded that the transformants are useful as the source of precursor proteins for the study of intracellular turnover of enzyme molecules in mutant cells.

Animals↗

Does glucagon improve the viability of ischemic intestine?

The effects of glucagon, heparin, urokinase, thromboxane synthetase inhibitor (OKY-046), and the free radical scavengers, superoxide dismutase and catalase (SOD + CAT), on the viability of ischemic intestine were evaluated based on various parameters measured. The mucosal blood flow, the fluorescence pattern, and the histopathological findings in a rabbit model with 3.5 hr total vascular occlusion of a short small intestine indicated that glucagon improved the ischemic intestine. Glucagon increased, tremendously, the mucosal blood flow by 112% in the ischemic intestine compared with that of 25% in the nonischemic intestine. This indicated that vascular spasm, not reperfusion injury or thrombosis, played the initial role in the progression of transmural bowel necrosis. In addition, the outcome in the viability of the ischemic intestine was not detected by the fluorescence technique but was able to be detected through the mitochondrial morphology under the electron microscope.

Animals↗

Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study.

Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells.

Animals↗

The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model.

The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation.

Animals↗

The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis.

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.

Adolescent↗

[A socio-medical study of adult diseases related to life style--comparison of foreigners living in Japan and Japanese].

The purpose of this study was to investigate the relationship between life style factors and adult diseases among three ethnic groups, Chinese living in Japan, Koreans living in Japan and Japanese. The mortalities of major cancers and other adult diseases of Chinese and Koreans in Japan were compared with those of Japanese by calculating Standardized Mortality Ratios (SMR) of the two groups using death rates in the Japanese population as the standard. Life style data on smoking, drinking and dietary habits of the three groups were collected by self-administered questionnaire surveys, and age-adjusted proportions were calculated with the truncated world population as the standard. The results are summarized as follows: 1. The mortality rates for liver cancer, lung cancer, diabetes mellitus, heart disease, hypertensive disease, cerebrovascular disease and liver cirrhosis for Koreans of both sexes in Japan were significantly higher than those for Japanese, but the mortality rates of stomach cancer, pancreatic cancer and breast cancer for Korean females were lower than those for Japanese females. 2. The mortality rates for heart disease, diabetes mellitus, hypertensive disease, liver cirrhosis, rectum cancer, liver cancer, lung cancer (females), breast cancer (females) and cerebrovascular disease (females) for Chinese in Japan were higher than those for Japanese, but the rates for stomach cancer, pancreatic cancer (both sexes), uterus cancer (females) and cerebrovascular disease (males) were lower than those for Japanese. 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease.

Efforts were directed to identify the specific mutations in the alpha-galactosidase A (alpha-Gal A) gene which cause Fabry disease in families of Japanese origin. By polymerase-chain-reaction-amplification of DNA from reverse-transcribed mRNA and genomic DNA, different point mutations were found in two unrelated Fabry hemizygotes. A hemizygote with classic disease manifestations and no detectable alpha-Gal A activity had a G-to-A transition in exon 1 (codon 44) which substituted a termination codon (TAG) for a tryptophan codon (TGG) and created an NheI restriction site. This point mutation would predict a truncated alpha-Gal A polypeptide, consistent with the observed absence of enzymatic activity and a classic Fabry phenotype. In an unrelated Japanese hemizygote who had an atypical clinical course characterized by late-onset cardiac involvement and significant residual alpha-Gal activity, a G-to-A transition in exon 6 (codon 301) resulted in the replacement of a glutamine for an arginine residue. This amino acid substitution apparently altered the properties of the enzyme such that sufficient enzymatic activity was retained to markedly alter the disease course. Identification of these mutations permitted accurate molecular heterozygote diagnosis in these families.

Adult↗

[Liver cancer and life style--drinking habits and smoking habits].

Japan is one of the endemic area of liver cancer in the world with its incidence rate of more than 30 per 100,000 population for males in Osaka. It is well known that Hepatitis B virus is closely related with hepatocellular carcinoma, however, its prevalence is moderately high (2-3%) in Japan. The relationship between drinking and liver cancer is examined by 3 different type of studies. First, more than 13,000 male alcoholics were followed for 9.9 years in average. Their incidence rate of liver cancer was 1.4 times higher than that of general population. Second, the case-control study of liver cancer among HBs antigen positives revealed that drinking habit was related with liver cancer even after adjusted with smoking habits. Lastly hospital based case-control study also showed the positive relationship between drinking habit and liver cancer. The relationship between smoking and liver cancer is still unclear.

Adult↗

[Life-style and cancer prevention. Activities of the Department of Cancer Prevention, Osaka Cancer Prevention and Detection Center].

The role of the Department of Cancer Prevention, Osaka Cancer Prevention and Detection Center which was established in 1987 is to conduct practical research works in the area of primary prevention of cancer through life-style modification. We have so far examined the applicability and efficacy of such tools as population-based smoking cessation contest, nicotine gum, health risk appraisal and "Know Your Body" program. The outline of our activities and future plans are introduced.

Alcohol Drinking↗

[Estimation of the long-term risks of death from smoking--application to public health education].

We calculated the long-term risks of death from smoking-related diseases for individuals of various smoking status using the health risk appraisal system based on Japanese epidemiologic and statistic data. For a 35-year-old man who had started to smoke at age 20 and smoked 20 cigarettes per day, the estimated probability of dying of lung cancer before reaching age 85 was 7.1 per cent, and 6.7, 7.3, 14.2 per cent for stomach cancer, coronary heart disease, and cerebrovascular disease respectively. If this same person had smoked 40 cigarettes per day, the corresponding probabilities were 9.4, 7.0, 14.3, 16.5 per cent respectively. If this same 35 year old man had never smoked, the probability of dying of lung cancer before age 85 was only 0.8 per cent and 5.0, 3.8, 12.5 per cent for the other smoking-related diseases. If this same person had started to smoke at age 20 and stopped smoking at the age of 35 or 55, the corresponding probabilities were nearly the same as those for a nonsmoker.

Adult↗

[Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements].

The aims in this study were designed to clarify the contents of calcium (Ca), phosphorus (P) and aluminum (Al) in central nervous system (CNS), liver and kidney of rabbits with atherosclerosis experimentally induced by cholesterol-rich diet, and investigate scavenger effect of 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine) on the deposition of these elements in CNS and soft tissues of experimental atherosclerosis. Sixteen male rabbits were divided into 4 groups. Each group was fed with standard diet (Group A), standard diet containing 1.5% cholesterol (Group B), standard diet containing 1.5% cholesterol plus oral administration of 3 mg/kg/day vinpocetine (Group C), and standard diet containing 1.5% cholesterol plus administration of 10 mg/kg/day vinpocetine (Group D). After 3 months' feeding, experimental atherosclerosis was produced with a modified method of Kritchevsky et al in rabbits of Groups B, C and D. Blood was collected by cardiocentesis under the anesthesia of ether and then rabbits sacrificed to remove CNS and other tissues. The blood was stood for 1 hour at room temperature and separated by centrifugation at 3000 rpm for 10 min to determine serum total cholesterol, phospholipids, HDL-cholesterol, peroxide lipid, NEFA and calcium levels. Ca, P and Al contents in the frontal lobe, pons, cerebellum, spinal cord, liver and kidney were determined by neutron activation analysis. Ca contents of CNS, liver and kidney in Group B significantly increased than those of Group A (p less than 0.01), and significantly decreased in Groups C and D compared with those of Group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗