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Biomedical subjects

A Oshima

Publications and source records attributed to A Oshima.

At least 109 records · Page 6Linked to original sources
PubMed1993

Protective protein gene mutations in galactosialidosis.

Four different protective protein cDNA mutations, 146A-->G (Q49R), 193T-->C (W65R), 268-269TC-->CT (S90L), and 1184A-->G (Y395C), were identified in six Japanese galactosialidosis patients with various phenotypic manifestations, and another mutation, 746T-->A (Y249N), in a patient of French-German origin with an atypical clinical course. Y395C was a common mutation in four Japanese patients in infancy and childhood; two juvenile patients were compound heterozygotes of Y395C and another common mutation, SpDEx7, and the other two infants were compound heterozygotes of Y395C and mutant alleles other than SpDEx7. We confirmed these mutations in genomic DNA by direct-sequence analysis or restriction-site analysis. The mutant cDNA clones, transiently expressed in a transformed galactosialidosis cell line, did not restore the secondarily deficient beta-galactosidase or alpha-neuraminidase activity except for the Y249N mutation that expressed some carboxypeptidase activity and restored the two lysosomal enzyme activities. Pulse-chase analysis detected a small amount of the mature form, as well as the precursor, in the cells transfected with the Y249N cDNA. Only precursor proteins were detected, mature proteins not appearing for the other mutant cDNAs.

Adolescent↗
PubMed1993

[Some problems of TS measurement after administration of fluoropyrimidines in colorectal cancer. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma].

A joint multicenter comparative study of carmofur (HCFU) alone or HCFU+dipyridamole (DP) concurrent administration was conducted by the Kinki Colorectal Cancer Chemotherapy Society. In this study, the drugs were administered five days prior to surgery, and thymidylate synthetase (TS) inhibition rate at the primary lesion of colorectal cancer was determined. In addition, the effect of time after resection of the primary lesion before specimen cooling on the TS inhibition rate was investigated. The subjects were 87 registered patients who received colorectal cancer surgery during 4 months from October 1991 to January 1992. The time before postsurgical cooling was divided into four group; within 10 min (n = 67), 11-20 min (n = 8), 21-30 min (n = 7), and 31 min or longer (n = 5). The TS inhibition rates (mean +/- SD) were 0.45 +/- 0.22, 0.38 +/- 0.19, 0.30 +/- 0.21, and 0.04 +/- 0.05 respectively. The longer the time after resection of the primary lesion before specimen cooling, the more TS inhibition rate decreased. When the time before specimen cooling exceeds 30 min, the major part of TS combined with FdUMP exists in a free state. Therefore, it was considered not suitable as the material for the measurement.

Adult↗
PubMed1993

[Smoking restrictions in medical schools in Japan].

The theme of the 6th WHO World Non-Smoking Day in 1993 was "Health services: our window to a tobacco-free world". A survey of the public health departments of all medical schools and universities was conducted in April, 1992 in order to investigate the state of smoking restrictions in those departments responsible for training in health services. Responses were received from 76 schools out of 80. The results were as follows: 1) In school cafeteria: Smoking prohibited (17.8%), Separate smoking/non-smoking areas (21.9%), Unrestricted smoking (60.3%), In student lounges: Smoking prohibited (2.9%), Separate Smoking/non-smoking areas (7.1%), Unrestricted smoking (90.0%), 2) The number of schools with tobacco vending machines: 59 schools (77.6%), 3) In medical faculty meetings: Smoking prohibited--32 schools (42.1%), Unrestricted smoking--22 schools (28.9%), No rules but no smokers--22 schools (28.9%), A total of 54 schools (71.0%) have established non-smoking meetings. 4) The number of school that give no attention to raking students aware of smoking risks: 6 schools As a result of this investigation, one national and one private medical school initiated prohibition of smoking at medical faculty meetings. In order to stimulate consciousness of the health hazards of smoking in future medical professionals, freshmen orientation should be utilized for teaching about the risks of both tobacco and "chug-a-lugging" of alcoholic beverages. In addition, the elimination of tobacco vending machines from all medical department area is strongly indicated.

Humans↗
PubMed1993

[Influence of homologous serum on endothelial cell growth factor withdrawal].

In examined the influence of endothelial cell growth factor (ECGF) withdrawal upon the growth and PGI2 production of human endothelial cells (HECs) maintained in either fetal bovine serum (FBS) or human serum (HS). For the study of growth, enzymatically harvested cells were passed twice, divided into seven groups and maintained in medium containing 20% FBS with ECGF (0, 0.1, 1, 10, 100 micrograms/ml) or 20% HS with ECGF (0, 100 micrograms/ml) (n = 8). Growth curve was generated from daily cell counts for ten days. Cells were dead in medium containing FBS with ECGF in concentration of 1 micrograms/ml or less, however, cells were sustained and grew in HS without ECGF. For the study of PGI2 production, harvested HECs were divided into 2 groups and cultured in medium containing 20% FBS or HS (ECGF: 100 micrograms/ml) (n = 12). Second passage cells were divided into 3 groups respectively and cultured in different ECGF concentration (0, 1, 100 micrograms/ml) for 48 hours. Cells were stimulated with thrombin(2U/ml) and PGI2 production was measured by radioimmunoassay. Cells cultured in medium containing HS produced more amount of PGI2 than in FBS in any concentration of BCGF (19 +/- 11 pg/10(5) cells in FBS v.s. 89 +/- 80 pg/10(5) cells in HS: p < 0.05, ECGF: 100 micrograms/ml) Second passage HECs cultured in medium containing HS were viable and maintained the ability of PGI2 production even without ECGF.

Animals↗
PubMed1992

GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients.

Clinical findings were compared with the results of molecular analysis in 16 Japanese patients from 10 unrelated families with the adult/chronic form of GM1 gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian manifestations were commonly seen. Cerebellar signs, myoclonus, severe intellectual impairment, dysmorphism, or visceromegaly were not observed. A common single-base substitution, 51Ile(ATC)----Thr(ACC), reported in a previous study of ours, was confirmed in 14 patients by the Bsu36I restriction site analysis; one was a compound heterozygote with another mutation (457Arg[CGA]----Gln[CAA]) and the others were homozygotes of this mutation. Clinically, the compound-heterozygous patient showed more severe neurological manifestations and a more rapid clinical course than those of homozygotes. The homozygotes showed considerable variations in the age of onset and subsequent clinical course. The 51Ile----Thr mutant allele expressed a significant amount of beta-galactosidase activity, whereas the 457Arg----Gln mutant allele expressed extremely low activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene mutations causing different residual enzyme activities are related to the severity of clinical manifestations, but some other genetic or environmental factors contribute to clinical heterogeneity. The Bsu36I restriction site analysis was performed in 7 families and provided clear results for the diagnosis of heterozygotes as well as homozygotes of this specific clinical form of GM1 gangliosidosis. The technique is applicable to prenatal diagnosis and genetic counseling.

Adult↗
PubMed1992

Optimal seeding conditions for human endothelial cells.

An in vitro model of endothelial cell seeding has been developed to individually evaluate the steps required for seeding arterial prostheses. Human saphenous vein endothelial cells are radiolabeled with tritiated thymidine and seeded onto 4 mm polytetrafluoroethylene grafts. Grafts are then placed into a perfusion circuit for determination of cellular retention. Using this model, the following variables were studied: (1) graft coating (fibronectin versus serum versus plasma); (2) time of incubation of cells with graft (0, 20, 90 minutes); (3) density of the initial seeding solution (4 x 10(3)-6 x 10(5) cells/cm2). The data suggest that incubation of a graft with plasma provides an adhesive surface that is as effective as fibronectin for enhancing cell retention. With this particular model, seeding densities between 1 and 2 x 10(5) cells/cm2 produce a confluent monolayer with optimal utilization of cells. A shorter 20 minute incubation period resulted in the retention of only half of the seeded cells, while postperfusion attachment increased significantly with a 90 minute incubation period. Data derived from this system can be used to construct a protocol that may be useful for clinical in vivo seeding trials.

Blood Vessel Prosthesis↗
PubMed1992

Effect of Ca2+ and K+ on the intracellular pH of an Escherichia coli L-form.

The L-form NC7, derived from Escherichia coli K12, grew in a complex medium containing 0.2 M-CaCl2 as osmotic stabilizer, but not at pH values above 7.8. The cessation of growth at alkaline pH was not due to cell death. In complex media containing K+ or Na+, the L-form grew ove a wide pH range. Growth at alkaline pH was inhibited by 1 mM-amiloride, indicating that Na+/H+ antiport activity was required for growth at alkaline pH. The internal pH (pHi) of the L-form in media containing K+, Na+ or Ca2+ was constant at about 7.8 to 8.0 at external pH (pHo) values of 7.2 and 8.2. The rates of O2 consumption by intact cells, lactate oxidation by membrane vesicles from cells grown in Ca(2+)-containing medium, and cell division were all strongly repressed under alkaline conditions.

Amiloride↗
PubMed1992

Diagnostic validity of fecal occult blood tests for detecting gastroenterological cancers.

In order to estimate the diagnostic validity of chemical fecal occult blood tests, i.e. orthotolidine (Shionogi A) and guajac (Shionogi B) slides for detecting cancers of the esophagus, stomach and colorectum, the authors followed up all the examinees (n = 3,449) of comprehensive medical check-ups at the Center for Adult Diseases, Osaka, by means of record linkage to the Osaka Cancer Registry's files. Then, diagnostic validity was calculated based on the results of two years' follow-up. Sensitivity for the respective cancers was 20.0%, 11.8% and 62.5% for Shionogi A, and 20.0%, 5.9% and 43.8% for Shionogi B slides. Likelihood ratio for the respective cancers was 1.4, 0.8 and 4.5 for Shionogi A, and 3.3, 1.0 and 7.5 for Shionogi B. Specificity was analogous among the three cancer sites, being 86% for Shionogi A and 94% for Shionogi B. These results suggest that the diagnostic validity of chemical occult blood tests for detecting cancers of the esophagus and the stomach is very poor, and therefore imply that close examinations of these sites for screening positives is unnecessary in mass screenings for colorectal cancer.

Adult↗
PubMed1992

GM1-gangliosidosis: tandem duplication within exon 3 of beta-galactosidase gene in an infantile patient.

A 23-nucleotide tandem duplication (GGACCTTGAAAGTACTC-GGGACC) was found within exon 3 of the beta-galactosidase gene in a patient with infantile-form GM1-gangliosidosis, which generated a premature stop codon after translation of 36 amino acids. Homologous sequences at the area of duplication suggested that the mutation resulted from an unequal crossover. A single base substitution 316Trp----Cys was found in the other allele. Family study showed that the duplication was transmitted from his father and the base substitution from his mother.

Base Sequence↗
PubMed1992

Resistance of Trypanosoma cruzi to blood clearance induced by acute-phase immune mouse serum.

To investigate functional changes in Trypanosoma cruzi parasites induced during their interaction with the vertebrate host, we compared the blood clearance profiles of blood forms isolated from infected normal mice (Reg-Tc) or from infected mice immunodepressed after treatment with cyclophosphamide (Cy-Tc). Parasite blood numbers were measured at various time intervals in animals injected intravenously (i.v.) with 1-2 x 10(6) T. cruzi of either isolate. In the absence of added immune sera (spontaneous clearance), Reg-Tc and Cy-Tc were cleared from blood at similar rates. However, when acute immune mouse serum (Ac-IMS) was injected i.v. 2 min after inoculation of parasites, a significant proportion of Cy-Tc only was cleared from the blood an hour later, whereas Reg-Tc were not, their clearance profile being identical to that observed in mice injected with normal mouse serum. Cy-Tc susceptibility to Ac-IMS was not the result of a toxic effect of cyclophosphamide over T. cruzi as parasites recovered from animals immunodepressed by irradiation before infection were cleared similarly by acute serum. Contrary to Ac-IMS, chronic immune mouse serum induced similar rates of disappearance of Reg-Tc and Cy-Tc from blood. Our results suggest the occurrence of T. cruzi selection or modification during the acute phase, which leads to an increased parasite resistance to the clearance properties of acute-phase antibodies.

Acute-Phase Reaction↗
PubMed1991

Acid carboxypeptidase deficiency in galactosialidosis.

Carboxypeptidase activity with an optimal pH at 5.7 was found to be deficient in cultured lymphoblastoid cells and skin fibroblasts from 16 galactosialidosis patients of Japanese origin. The amounts of residual enzyme activities did not correlate with clinical phenotypes (early infantile and juvenile/adult). Four parents of the patients from different families showed enzyme activities at an intermediate level between the patients and normal controls. It was concluded that this enzyme deficiency is closely connected to the genetic defect of "protective protein." Further characterization with various protease inhibitors indicated that the enzyme deficient in galactosialidosis cells is a serine carboxypeptidase with histidine and cysteine residues at or near the active site.

Adolescent↗
PubMed1991

Gastric microcirculation and its regulating factors in stress.

Gastric mucosal blood flow and its regulating factors were studied in normal and stressed rats. In addition, vascular regulating factors and the role of CoQ10 anion radical and SOD (superoxide dismutase) level in gastric mucosa were also investigated as well as the influence of 5-HT (5-hydroxytryptamine) on gastric mucosal blood flow. Gastric mucosal blood flow was measured by the hydrogen gas clearance method. The vascular pattern of the stomach was investigated by the infusion method with two-colored silicon rubber. CoQ10 anion radical and SOD levels in gastric tissue were assayed by electron spin resonance (ESR) and radioimmunoassay. The gastric mucosal blood flow decreased significantly early after the induction of stress. Impairment of gastric mucosal blood flow was highly correlated with 5-HT and CoQ10 anion radical and SOD levels. Reduction in gastric mucosal blood flow was consequently due to opening of arteriovenular shunt and hyperpermeability of true capillaries influenced by 5-HT. These results demonstrate that ischemia and reperfusion after reduction of the gastric mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesions.

Animals↗
PubMed1991

Hypertrophic cardiomyopathy in late-onset variant of Fabry disease with high residual activity of alpha-galactosidase A.

A new variant form of Fabry disease with hypertrophic cardiomyopathy of late onset is reported. Two unrelated male hemizygotes of this disease first presented with signs and symptoms of cardiomyopathy after 50 years of age. Cultured lymphoblastoid cells showed significantly higher residual alpha-galactosidase A activities than in the patients with classical phenotypic expressions.

Cardiomyopathy, Hypertrophic↗
PubMed1991

Clinical and molecular heterogeneity in hereditary beta-galactosidase deficiency.

Results of a molecular analysis of GM1-gangliosidosis and galactosialidosis in our laboratory are briefly reviewed. A common single base substitution was found in adult/chronic form of GM1-gangliosidosis among heterogeneous beta-galactosidase gene mutations, and restriction site analysis was successfully performed for diagnosis of homozygotes and heterozygotes. All adult galactosialidosis patients had a common mutation at a splice junction which caused skipping of an exon of the protective protein/carboxypeptidase gene. An artificial restriction site was introduced in this case and applied to diagnosis of this disease. The heterogeneous gene mutations were compared and correlated with phenotypic manifestations in these two diseases.

Adolescent↗
PubMed1991

[Smoking and alcohol drinking behavior among Japanese adolescents--results from "Japan Know Your Body Study"].

The "Japan Know Your Body Study" (JKYB) is an example of collaborative activities of technology transfer carried out in Japan in several phases. The first phase is a needs assessment and data collection survey and it was administered during 1989. A survey was conducted throughout 9 prefectures in Japan with participation by 49 schools. Subjects were students in elementary, junior and senior high schools who ranged in age from 6 to 18 years. Participants, 12,892 in total, completed a survey on knowledge, attitude and behavior regarding cigarette smoking, alcohol drinking, diet, exercise and so on. The main results concerning cigarette smoking and alcohol drinking behavior were as follows: 1) The percentage of monthly male smokers rose remarkably from 8% in the third grade of junior high school to 37% in the third grade of senior high school, while that of female smokers showed a slow rise from 3% to 15%. The sex difference for smoking behavior was clear among senior high school students. 2) Smoking rates increased in proportion to the numbers of parents, siblings and friends who smoked. Above all, smoking behavior of friends was strongly related. Among senior high school students, for example, 50% of males and 46% of females who had two or more smoking friends were smokers, as compared to 5% of males and 2% of females with no smoking friends. 3) The percentage of monthly drinkers rose at a steady pace from 13% of males and 7% of females in the fifth grade of elementary schools to 59% of males and 50% of females in the third grade of senior high schools. The sex difference for alcohol drinking behavior among senior high school students, while statistically significant, was not as pronounced as that for smoking behavior. These results suggest that tobacco- and alcohol-use prevention programs should be introduced in elementary schools and those programs should include components relating to the social influences of parents, siblings and friends.

Adolescent↗
PubMed1991

Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases.

Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnormally large mRNA; one patient was probably a homozygote, and the other was a heterozygote of this mutation. The other two infantile patients had different mutations; a 123 Gly(GGG)----Arg(AGG) mutation in one patient and a 316 Tyr(TAT)----Cys(TGT) mutation in the other. A 201 Arg(CGC)----Cys(TGC) mutation, eliminating a BspMI site, was detected in a late-infantile/juvenile patient; the restriction-site analysis of amplified genomic DNA confirmed his heterozygosity for this mutation. A 51 Ile(ATC)----Thr(ACC) mutation was found in all five adult/chronic patients examined in this study. It created a SauI site, and restriction-site analysis confirmed that four patients were homozygous mutants. The other was a compound heterozygote for this mutation and another 457 Arg(CGA)----Gln(CAA) mutation. These mutant genes expressed markedly decreased or completely deficient enzyme activities in beta-galactosidase-deficient human fibroblasts transformed by adenovirus-SV40 recombinants. We conclude that gene mutations are heterogeneous in GM1-gangliosidosis but that the 51 Ile(ATC)----Thr(ACC) mutation is common among the Japanese adult/chronic cases. Genotype-phenotype correlations in GM1-gangliosidosis are briefly discussed.

Adolescent↗