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Biomedical subjects

A Oshima

Publications and source records attributed to A Oshima.

At least 163 records · Page 9Linked to original sources

The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells.

We have cloned and sequenced the full-length cDNA for the human cation-independent mannose 6-phosphate receptor from four overlapping clones. The 9104-nucleotide sequence contains 7473 nucleotides which encode a protein of 2491 amino acids. The amino acid sequence includes a putative signal sequence of 40 amino acids, an extracytoplasmic domain consisting of 15 homologous repeat sequences of 134-167 amino acids, a transmembrane region of 23 amino acids, and a cytoplasmic domain of 164 amino acids. The predicted molecular size is greater than 270 kDa. Repeats 7-15 of the extracytoplasmic domain of the human receptor are highly homologous with the sequence recently reported for the partial cDNA for the bovine receptor (Lobel, P., Dahms, N. M., Breitmeyer, J., Chirgwin, J. M., and Kornfeld, S. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2233-2237). The nucleotide sequence for the full-length cDNA and the deduced amino acid sequence for the cation-independent mannose 6-phosphate receptor, which are reported here, are strikingly similar (99.8% identical at the nucleotide level and 99.4% identical at the amino acid level) to those recently reported for the human insulin-like growth factor II receptor from HepG2 hepatoma cells (Morgan, D. O., Edman, J.D., Standring, D. N., Fried, V. A., Smith, M. C., Roth, R. A., and Rutter, W. J. (1987) Nature 329, 301-307). These findings support the suggestion that the cation-independent mannose 6-phosphate receptor for lysosomal enzymes is a multifunctional binding protein which is identical with the insulin-like growth factor II receptor. A cDNA construct containing the full coding sequence for the cation-independent mannose 6-phosphate receptor in the expression vector pSVL was used to transfect COS cells. Expression of the cDNA in transfected COS cells produced a cell-surface protein which co-migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with authentic human receptor, bound to an affinity column and was specifically eluted with mannose 6-phosphate, mediated cell-surface binding and endocytosis of beta-glucuronidase, and targeted the endocytosed enzyme to lysosomes.

Amino Acid Sequence↗

Impairment of gastric microcirculation in stress.

Gastric mucosal blood flow and microvascular patterns were studied in normal and stressed rats. In addition, various regulating factors of gastric mucosal blood flow, such as autonomic nervous system and biogenic amines, were investigated by histochemical procedures. Gastric mucosal blood flow was determined by the hydrogen gas clearance method as well as the hydrogen gas electrolytic method, and the microvascular structure was observed by the infusion method with two-colored silicon rubber. The gastric mucosal blood flow decreased significantly in the early period after induction of burn stress. The incidence of acute gastric mucosal lesions had a highly correlative relation with the decrease in mucosal blood flow. Reduction of mucosal blood flow was consequently due to opening of an arteriovenous shunt and hyperpermeability of true capillaries. This hemodynamic change, regulated by biogenic amines and autonomic nerves, was followed by ischemia and congestion of the gastric mucosa. The results of these studies demonstrated the importance of defensive factors; that reduction of mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesions.

Animals↗

Effects of Ca2+ and a protonophore on growth of an Escherichia coli L-form.

The influence of Ca2+ ions on the growth of an L-form (NC7) derived from Escherichia coli K12 was investigated. In a medium containing NaCl as osmotic stabilizer 1 mM-Ca2+ was required for optimal growth of the L-form, while with KCl as osmotic stabilizer, in a medium containing 0.1 or 1.0 mM-Ca2+, optimium growth was observed at 32 and 37 degrees C, respectively. When the L-form, growing exponentially at 32 degrees C in medium containing KCl and 0.1 mM-Ca2+, was shifted to 37 degrees C growth was strikingly suppressed. In contrast, the suppression of growth in the presence of 1.0 mM-Ca2+ at 32 degrees C was relieved when the culture was shifted to 37 degrees C. When the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), at a final concentration of 10 microM, was added to a medium containing NaCl and sucrose as osmotic stabilizers, together with 10 mM-glucose, the parent strain could grow exponentially. In contrast, growth of the L-form was completely stopped by 10 microM-CCCP under the same conditions. In the presence of 20 microM-CCCP, the L-form accumulated more than twice as much 45Ca as in the absence of the protonophore. Thus, it is suggested that growth of the L-form NC7 is coupled to the protonmotive force. Possible mechanisms for the coupling of calcium to growth of the L-form are discussed.

Calcium↗

[Problems in using survival data of cancer patients as a method of gauging the effectiveness of cancer control efforts].

Survival rates of cancer patients have been widely used as a method of gauging the effectiveness of cancer control efforts. Sometimes, however, they cannot be considered reliable indicators due to many biases, such as a lead time bias, a length bias, a self-selection bias and an overdiagnosis bias. Instead, cancer mortality rates should be used for evaluating screening programs and for assessing the recent progress against cancer, although some problems are encountered in the accuracy of death certificates.

Humans↗

Cloning, sequencing, and expression of cDNA for human beta-glucuronidase.

We report here the cDNA sequence for human placental beta-glucuronidase (beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) and demonstrate expression of the human enzyme in transfected COS cells. We also sequenced a partial cDNA clone from human fibroblasts that contained a 153-base-pair deletion within the coding sequence and found a second type of cDNA clone from placenta that contained the same deletion. Nuclease S1 mapping studies demonstrated two types of mRNAs in human placenta that corresponded to the two types of cDNA clones isolated. The NH2-terminal amino acid sequence determined for human spleen beta-glucuronidase agreed with that inferred from the DNA sequence of the two placental clones, beginning at amino acid 23, suggesting a cleaved signal sequence of 22 amino acids. When transfected into COS cells, plasmids containing either placental clone expressed an immunoprecipitable protein that contained N-linked oligosaccharides as evidenced by sensitivity to endoglycosidase F. However, only transfection with the clone containing the 153-base-pair segment led to expression of human beta-glucuronidase activity. These studies provide the sequence for the full-length cDNA for human beta-glucuronidase, demonstrate the existence of two populations of mRNA for beta-glucuronidase in human placenta, only one of which specifies a catalytically active enzyme, and illustrate the importance of expression studies in verifying that a cDNA is functionally full-length.

Amino Acid Sequence↗

Time trends of the prevalences of hepatitis B e antigen positives among hepatitis B virus carriers in Japan.

In order to examine time trends of the prevalences of HBeAg positives among HBV carriers in Japan, we analysed data on HBeAg of HBsAg positive voluntary blood donors (23,560 males, and 8659 females) at the Osaka Red Cross Blood Centre between January 1977 and March 1984. Age-specific prevalences of HBeAg positives decreased year by year for both sexes, especially for those in their teens and twenties. The prevalences of HBeAg positives decreased with age, but at any given age it was lower for the later than for the earlier birth cohorts. Although reasons for the secular declines are unknown, the findings suggest that the prevalence of HBeAg positives among HBV carriers will continue to decrease in Japan. This, together with the immunization programme implemented this year, may lead to a future reduction in the risk of HBV related liver diseases in Japan.

Adolescent↗

Morphology, growth and reversion in a stable L-form of Escherichia coli K12.

An L-form isolated from Escherichia coli K12 by sequential treatment with N-methyl-N'-nitro-N-nitrosoguanidine and lysozyme was adapted to grow in hyperosmolar liquid cultures. It was stable in the absence of antibiotic when cultured in brain heart infusion (BHI) broth containing NaCl and CaCl2, the optimal concentrations being 0.34 M and 1 mM, respectively. No growth of the L-form was observed when CaCl2 was not added to BHI medium containing 0.34 M-NaCl. On the other hand, when KCl replaced NaCl as the osmotic stabilizer, growth of the L-form was repressed in the presence of CaCl2. Electron microscopy of the L-form confirmed the absence of a cell wall. A revertant strain derived from the L-form grew as a stable bacillary form in BHI medium without osmotic stabilizer. The growth characteristics of the revertant strain resembled those of the parent strain. The revertant strain produced L-forms in the presence of NaCl.

Culture Media↗

Cancer patterns among Koreans in Japan, Koreans in Korea and Japanese in Japan in relation to life style factors.

Cancer incidences for major sites were compared among Koreans in Osaka, Japan, Koreans in Korea and Japanese in Osaka by calculating standardized proportional incidence ratios (SPIR's), in addition to updating the findings on cancer mortality experiences of Koreans and Japanese in Osaka reported before. Compared with Japanese, Koreans in Osaka had significantly higher mortality rates from cancers of the esophagus, liver and lung in males, and liver in females. Mortality rates among Koreans in Osaka were significantly lower for stomach cancer in both sexes and for breast cancer in females. Compared with Korean counterparts in the homeland, Koreans in Osaka had a reduced risk for cancers of the stomach in males and the uterus in females. On the other hand, an elevated risk was observed for cancers of the esophagus, colon, liver and lung among Korean males in Osaka and for cancers of the colon and liver among Korean females in Osaka. The risk for cancer of the breast in females was similar among Koreans in the host and home countries. These different cancer patterns among Koreans in the host and home countries and Japanese are discussed in relation to their life styles, such as smoking, drinking and dietary habits, which have been investigated by means of questionnaire surveys.

Adult↗

Evaluation of a mass screening program for stomach cancer with a case-control study design.

In order to evaluate the effectiveness of a mass screening program for stomach cancer, a case-control study was conducted in Nose town in Osaka, Japan. The case series consisted of all deaths from stomach cancer during the period 1969-1981 (54 in males and 37 in females). For each case, 3 controls of the same sex and from the same precinct as the case, and born within 5 years of the case birth-year, were selected at random from Nose town residents alive at the date of death of the relevant case. We then investigated whether each case and corresponding controls had ever had screening tests before the date of diagnosis of the case. From the matched analysis of the distribution of screening in case-control combination, the odds ratio of screened vs. unscreened among those who died from stomach cancer compared to those who did not was calculated as 0.595 (90% confidence interval: 0.338-1.045) among males and 0.382 (0.185-0.785) among females. When the screening tests conducted within 12 months of diagnosis were ignored on the presumption that they were symptom-related, the odds ratio was calculated as 0.519 (0.297-0.905) among males and 0.486 (0.239-0.986) among females. These data strongly suggest that the mass screening program is effective in reducing stomach cancer mortality.

Adult↗

Pathophysiology of hepatic ischemia in cardiogenic shock.

The hepatic hemodynamic response to cardiogenic shock was investigated in a porcine model produced by pericardial tamponade to better understand the pathophysiology of postshock hepatic insufficiency. Reductions of cardiac output to 50 percent of baseline levels produced marked hepatic ischemia by causing disproportionate reductions in blood flow through the celiac and hepatic arteries and portal vein. These were due to selective vasoconstriction of the splanchnic resistance vessels that was mimicked without tamponade by the infusion of angiotensin II, ablated by angiotensin-converting enzyme blockade, unaffected by alpha-adrenergic ablation, and correlated closely with levels of plasma renin activity. The ischemic liver injury of cardiogenic shock appears to be largely due to an exquisite responsiveness of the splanchnic vascular smooth muscle to endogenously released angiotensin II.

Angiotensin II↗

Mortality among Koreans living in Osaka, Japan, 1973-1982.

The mortality pattern of Koreans living in Osaka, Japan was surveyed by comparing their age-specific and age-adjusted death rates with those among Japanese during 1973-1982. Cancer was the leading cause of death among Korean males, while cerebrovascular disease was most common among Korean females in Osaka. Mortality rates from tuberculosis, cancer, mental disorder, cerebrovascular disease, chronic obstructive pulmonary diseases (COPD), liver cirrhosis, accidents and suicide were significantly higher for Korean males than for Japanese males. COPD, liver cirrhosis and accidents were more frequent for Korean females than for Japanese females. In cancers, liver cancer was most common among Korean males, followed by stomach and lung cancers. Stomach cancer was most frequent among Korean females, followed by uterine and liver cancers. The ratio of cancer mortality rates for Koreans and Japanese was significantly higher than 1.0 for oesophagus, liver and lung among males, and for liver among females. Koreans had considerably higher levels of liver cancer and liver cirrhosis compared with Japanese. Mortality from stomach cancer was significantly lower in both sexes among Koreans in Osaka and the reduction of this disease among Koreans in Japan occurred more rapidly than among Japanese.

Adolescent↗

AccIII, a new restriction endonuclease from Acinetobacter calcoaceticus.

A new site-specific restriction endonuclease, AccIII, was isolated from Acinetobacter calcoaceticus. AccIII recognizes T/CCGGA and cleaves at the position shown by the arrow. AccIII activity was inhibited by adenine methylation at the overlapping dam methylase recognition sequence.

Acinetobacter↗

Occurrence of second primary cancers among patients with cervical cancer in Osaka, Japan.

Using the data accumulated in the Osaka Cancer Registry, we conducted a study on the effect of radiotherapy for cervical cancer in causing second primary cancers. Two groups of patients with cervical cancer, 1,767 who were given radiotherapy and 1,377 who were not, were followed for 7-9 years on average. In the radiotherapy group, 79 women had second primaries, and in the nonradiotherapy group, 23 did. These figures were compared with the expected cancer incidence for all sites. In the radiotherapy group, a significantly high observed-to-expected ratio was noted in cancers of the rectum, lung, and bladder. The nonradiotherapy group showed no site with a significantly high observed-to-expected ratio. Factors causing the increased level of lung cancer were studied. Some evidence indicated the excess was probably not related to smoking but to radiation, although the mechanism is unknown.

Adult↗

Control of gastric vascular resistance in cardiogenic shock.

That local splanchnic ischemia is associated with the acute gastric "stress" erosions seen in shock is well established. The hemodynamic mechanism mediating that ischemia is unknown. Pericardial tamponade was produced in anesthetized pigs while hemodynamic parameters were monitored in the systemic circulation as a whole and in the vascular beds of the celiac and left gastric arteries, respectively. Stepwise increases in pericardial pressure produced progressive decreases in arterial pressure and cardiac output (i.e., reproducible, quantitable, and rapidly reversible levels of cardiogenic shock). This produced a profound reduction in blood flow in the celiac and gastric beds that was significantly disproportionate to the reduction in cardiac output. This was due to significant increases in celiac and gastric vascular resistance that were more than twice as great as those seen in the systemic circulation as a whole (i.e., selective splanchnic vasoconstriction). This response was abolished by ablation of the renin-angiotensin axis, whether by bilateral nephrectomy, captopril, or saralasin, and mimicked, without tamponade, by the infusion of angiotensin II. Levels of celiac artery blood flow and resistance correlated significantly with endogenous levels of plasma renin activity. On the other hand, this response was not abolished by confirmed alpha-adrenergic blockade (phenoxybenzamine) or by sympathectomy. In this model, cardiogenic shock produces regional splanchnic ischemia in the celiac and gastric vascular beds by inducing a severe and disproportionate vasospasm that is mediated primarily by the renin-angiotensin axis.

Animals↗

[Cancer screening in Japan--a critique from the epidemiological viewpoint].

The present status of cancer screening in Japan has been critically reviewed from an epidemiological point of view. Cancer screening programs for stomach cancer and uterine cervical cancer were introduced in the 1960s on the basis of the naive belief of many clinicians that early diagnosis is beneficial: Many studies now show that this belief unfounded. Therefore, before the introduction of screening programs as a general policy, epidemiological evaluation is essential. The general principles involved in evaluation of cancer screening were discussed. In contrast to stomach cancer and uterine cervical cancer, cancers of the lung, breast and colorectum are increasing in Japan. In the case of lung cancer, primary prevention, i.e., smoking control, should be preferred, because lung cancer screening has not yet been shown to be effective. In the case of breast cancer and colorectal cancer, screening trials should be designed and appropriate evaluations should be conducted before their implementation as cancer control measures.

Female↗

Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer.

In order to confirm the close association between chronic hepatitis B virus (HBV) infection and primary hepatocellular carcinoma (PHC) in Japan, 8,646 male hepatitis B surface antigen (HBs Ag)-positive blood donors (GPT less than or equal to 35 Karmen units) were followed up. Twenty liver cancer cases were observed during the follow-up period (average 6.2 years), the expected number calculated on the basis of age-specific incidence rates among the general population being 3.03. Therefore, the observed to expected ratio of liver cancer was 6.60, that is significantly higher than 1.0. During the same follow-up period, a total of 76 deaths were observed, of which 20 were due to liver cancers and 9 to liver cirrhoses, meaning that nearly 40% of deaths among the study subjects due to chronic liver diseases. Drinking and smoking habits in the liver cancer cases were compared with those observed in healthy male HBV carriers. A strong positive association between drinking habits and liver cancer was observed and there was a significant dose-response relationship after adjustment for cigarette smoking habits. A high risk of liver cancer was also observed among heavy smokers, but a significant dose-response relationship could not be found between smoking habits and liver cancer, partly because of the limited number of the study subjects. These findings suggest that HBV is a major etiologic agent of PHC in Japan where the HBs Ag prevalence rate is about 2%, and alcohol drinking and cigarette smoking may promote the process of HB viral hepato-carcinogenesis.

Adolescent↗

Prospective study of "early" gastric cancer.

In order to elucidate the natural history of early gastric cancer, we followed up non-concurrently certain patients who had been diagnosed endoscopically as having "early' gastric cancer and who had histological evidence of cancer by biopsy, but on whom surgical resection had been delayed or had not been conducted. At the Center for Adult Diseases, Osaka, 56 cases were eligible for this study. Out of these, 27 cases progressed to advanced cancer and 16 remained at the early stage during the follow-up period (6-88 months, mean: 29 months). The remaining 13 cases had had neither surgical resection nor examinations. The survivorship function for the duration of "early" gastric cancer was estimated by the life-table method of Kaplan and Meier. The median of the duration was estimated as 37 months. The 5-year survival rate of the 34 cases on whom surgical resection had not been conducted was estimated as 64.5%. These results suggest that early diagnosis and early treatment may lead to a reduction of mortality from stomach cancer.

Adult↗