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Biomedical subjects

R Sasaki

Publications and source records attributed to R Sasaki.

At least 91 records · Page 5Linked to original sources
PubMed1998

Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.

Asian People↗
PubMed1998

Synthesis of human erythropoietin in vivo in the oviduct of laying hens by localized in vivo gene transfer using electroporation.

In order to synthesize human erythropoietin protein in the oviduct of laying hens, localized in vivo gene transfer was attempted by using electroporation. In Experiment 1, transcriptional activities were compared by using four viral and cellular promoters, i.e., the 1.35-kbp long ovalbumin promoter, SV40 early promoter, Rous sarcoma virus long terminal repeat (RSV LTR), and the miw promoter, which is a hybrid of RSV LTR and chicken beta-actin promoter. These promoters were fused immediately upstream to the chloramphenicol acetyltransferase reporter gene. The results of chloramphenicol acetyltransferase activity showed that the miw promoter was the strongest, followed by SV40, RSV LTR, and the ovalbumin promoter in decreasing order. The intensity of the miw promoter was 250 times as high as that of the ovalbumin promoter. In Experiment 2, plasmid DNA containing the human erythropoietin gene, driven either by the ovalbumin promoter or the miw promoter, was transfected in vivo, and the production of human erythropoietin protein was detected by ELISA. The results indicated that the synthesis of human erythropoietin protein was attained in the chicken oviduct, and its concentration was higher when driven by the miw promoter than the ovalbumin promoter.

Animals↗
PubMed1998

Correlation between initial potentials on a signal-averaged P-wave and indice of electrophysiologic measurements in the right atrium.

The aim of this study was to determine whether initial potentials of the P-wave on a signal-averaged electrocardiogram (SAE) during sinus rhythm reflect indices of electrophysiologic measurements in the high lateral right atrium. A total of 67 patients underwent P-wave signal averaging during electrophysiologic testing. The correlation between root mean square voltages for the initial 10 and 20 msec of the P-wave on the SAE and indices of electrophysiologic measurements, sinus node recovery time (SRT) and sinoatrial conduction time (SACT), obtained from programmed stimuli, was evaluated. It was found that the initial potentials of the P-wave on the SAE correlated negatively with SRT and SACT (-0.37 < or = r < or = -0.30). It was concluded that the initial potentials correlated with indices of electrophysiologic measurements, although the statistical significance was weak.

Adolescent↗
PubMed1998

Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer.

We investigated expression of the vascular endothelial growth factor (VEGF) gene and its receptor gene (flt-1) in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder by Northern blot hybridization analysis. The VEGF transcript was observed in all of the tumors and the normal mucosae. Of the 20 tumors in which a comparative study was done, eight (40.0%) overexpressed the gene with a tumor versus normal ratio of equal to and greater than 3.0. Invasive TCCs expressed significantly more VEGF gene than superficial TCCs. Cytoplasm of tumor cells was positively stained by immunohistochemistry with an anti-VEGF monoclonal antibody, while the intratumoral endothelial cells and the vascular smooth muscle cells were weakly positive for the staining. TCCs, normal mucosae and human umbilical endothelial cells expressed flt-1 gene, while leucocytes from peripheral blood did not. The expression level of flt-1 gene significantly correlated with that of the VEGF gene in the tumor. These results indicate that the VEGF gene is frequently overexpressed in TCC of the urinary bladder, especially in muscle invasive tumors, and that a paracrine system including VEGF and flt-1 exists between the TCC cells and the adjacent endothelial cells so as to regulate the angiogenesis in this tumor.

Adult↗
PubMed1998

[Radiation therapy for non-small cell lung cancer with postoperative intrathoracic recurrence].

We reviewed patients with intrathoracic recurrence of non-small cell lung cancer after surgery, with reference to the feasibility of radiotherapy. The series consisted of 46 patients (39 males and 7 females) treated by radiotherapy from 1982 to 1995. Histology included squamous cell carcinoma (28 patients), adenocarcinoma (17), and large cell carcinoma (1). Clinical stage by UICC classification (1987) was as follows: stage I(2 patients), stage II(1), stage IIIa(13), stage IIIb(23), and stage IV(7). Recurrences were noted in bronchial stump (18 patients) and surgical scar (4). Metastases occurred in hilar-mediastinal lymphnodes (15), lung fields (7), and pleuropericardium (2). The mean interval from surgery to recurrence was 27 months. Delivered dose ranged from 45 to 80 Gy, and 19 patients received combined chemotherapy. Therapeutic results were as follows: complete response in 16 patients, partial response in 27, no response in 12 and progressive disease in 1, Overall 2- and 5-year survival rates were 17% and 11%, respectively, and 10 months in MST. On univariate analysis, significant prognostic factors were sex, stage at recurrence, recurrence pattern, performance status and initial response to radiotherapy, while multivariate analysis showed sex and initial response. From these data, we are encouraged by effective radiotherapy for postoperative intrathoracic recurrence of non-small cell lung cancer, especially in patients with stump or lymphnode recurrence.

Adenocarcinoma↗
PubMed1998

Functional outcome after hip fracture in Japan.

One thousand one hundred sixty-nine elderly Japanese patients who sustained a hip fracture were observed prospectively. Ninety-two percent had operative fracture treatment. Hospital length of stay averaged 67 days; 81% of patients were discharged to their place of residence where they resided before sustaining the fracture. Mortality rates at 120 days, 1 year, and 2 years after injury were 6%, 11%, and 19%, respectively. At 1-year followup, ambulatory status was recovered to that of the level experienced before injury in 67% of patients.

Activities of Daily Living↗
PubMed1997

Release of opioid peptides, gluten exorphins by the action of pancreatic elastase.

The release of opioid peptides, gluten exorphins A, which have been isolated from the pepsin-thermolysin digest of wheat gluten, with gastrointestinal proteases was examined. High levels of gluten exorphin A5 (Gly-Tyr-Tyr-Pro-Thr) immunoreactive materials were detected in the pepsin-pancreatic elastase digest by a competitive ELISA. From this digest, gluten exorphin A5, B5 and B4 were isolated. This means that these peptides are released in the gastrointestinal tracts after ingestion of wheat gluten. The yield of gluten exorphin A5 in the pepsin-elastase digest was larger than that in the pepsin-thermolysin digest. The gluten exorphin A5 sequence is found 15 times in the primary structure of the high molecular weight glutenin. The region from which gluten exorphin A5 was released by the action of pancreatic elastase was identified using synthetic fragment peptides.

Cross Reactions↗
PubMed1997

Insulin-like growth factors and insulin stimulate erythropoietin production in primary cultured astrocytes.

Erythropoietin (EPO) is established as a major regulator of erythropoiesis. However, we and others have shown that neurons express erythropoietin receptor (EPO-R), that astrocytes produce EPO and that EPO may act as a neurotrophic factor in the CNS. We also found that EPO production is activated by insulin and insulin-like growth factors (IGFs) in astrocytes in a dose-dependent manner and that IGF-I was the most potent activator. The concentrations required for half-maximal activation were 3 nM IGF-I, 10 nM IGF-II and 100 nM insulin. The oxygen concentration regulates EPO production; hypoxia stimulates EPO production in astrocytes. The stimulatory effect of IGFs and insulin on EPO production in astrocytes was not affected by the oxygen concentration of astrocyte culture. Insulin and IGFs did not increase the total protein synthesis of astrocytes but increased EPO mRNA levels, indicating that EPO production is stimulated at the mRNA level. It appeared that the growth factor-induced accumulation of EPO mRNA in astrocytes was caused by activation of the tyrosine kinase-signal transduction pathway, because tyrosine phosphorylation of receptors for IGF-I and insulin was activated when astrocytes were stimulated by these growth factors.

Animals↗
PubMed1997

Identification of casoxin C, an ileum-contracting peptide derived from bovine kappa-casein, as an agonist for C3a receptors.

Casoxin C (Tyr-Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg) is a bioactive peptide that was isolated from a tryptic digest of bovine kappa-casein as an anti-opioid peptide in longitudinal strips of guinea pig ileum. Casoxin C also evokes contraction of the ileal strips, and we found that this process was biphasic with rapid and slow components. The contractile profile was very similar to that of human complement C3a(70-77), which is the COOH-terminal octapeptide of C3a and has, although less potent, qualitatively the same biological activities as C3a. Casoxin C also has homology with C3a(70-77). The rapid contraction was mediated by histamine release and the slow contraction was mediated by a prostaglandin E2-like substance, judging from the effects of various pharmacological inhibitors and antagonists on the ileal contraction. Casoxin C had affinity for C3a receptors (IC50 = 40 microM) in the radioreceptor assay. In addition, casoxin C showed phagocyte-stimulating activities. Casoxin C is therefore the first milk-derived peptide identified, that acts through complement C3a receptors.

Amino Acid Sequence↗
PubMed1997

Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death.

Recently, erythropoietin has been shown to be produced by astrocytes and its production is hypoxia-inducible. In the present study, we demonstrated, using a reverse transcription-polymerase chain reaction assay and immunostaining of the cells, that the erythropoietin receptor was expressed in cultured hippocampal and cerebral cortical neurons of day 19 rat embryo. Erythropoietin protected the cultured neurons from glutamate neurotoxicity. Neurons cultured for seven to 10 days were exposed to glutamate for 15 min and after culture for a further 24 h in the absence of glutamate the neuron survival was assayed. Significant protection was observed with erythropoietin from 3 pM (c. 100 pg/ml) in a dose-dependent manner. The protection was completely reversed by co-application of a soluble erythropoietin receptor, an extracellular domain capable of binding with erythropoietin. For exhibition of the neuroprotective effect, exposure of neurons to erythropoietin approximately 8 h prior to exposure to glutamate was required. Experiments with the inhibitors indicated that RNA and protein syntheses were necessary for the protection. However, exposure to erythropoietin for a short period (5 min or less) was sufficient to elicit the protective effect. The protective effect of erythropoietin was blocked by the simultaneous addition of EGTA. These findings and the previous finding that erythropoietin induces a rapid and transient increase in intracellular Ca2+ concentration in neuronal cells suggest that erythropoietin plays a neuroprotective role in brain injury caused by hypoxia or ischemia and that erythropoietin-induced Ca2+ influx from outside of the cells is a critical initial event yielding an enhanced resistance of the neurons to glutamate toxicity.

Animals↗
PubMed1997

Structural changes of immunoglobulin G oligosaccharides with age in healthy human serum.

Age-related changes of IgG N-linked oligosaccharides isolated from normal human serum are reported for 403 individuals (male 227 and female 176), varying in age from 0 to 85 years. The IgG N-linked oligosaccharides were released from the protein by digestion with a glycoamidase and reductively aminated with the fluorescent reagent, 2-aminopyridine. The mixture of pyridylaminated oligosaccharides was separated at high resolution by HPLC using a reverse-phase column. From the results of neutral oligosaccharide analysis, agalactosyl glycoform and bisecting GlcNAc-containing glycoform were shown to increase with increasing age. Spearman's correlation coefficients were 0.503 and 0.473, respectively. Thus, in healthy people, an increase of both types of glycoforms correlates weakly with age. In addition, differences were demonstrated between male and female groups in their twenties. The quantity of agalactosyl glycoform was found to be lower in females than in males. No significant differences, however, were observed in the quantity of bisecting GlcNAc-containing glycoforms between males and females.

Adolescent↗
PubMed1997

Survival in long-term haemodialysis patients: results from the annual survey of the Japanese Society for Dialysis Therapy.

The prognosis for haemodialysis patients is reported to be more favourable in Japan than in Europe or North America. Consequently, evaluation of the death predictors for haemodialysis patients in Japan is of considerable interest outside Japan. The Patient Registration Committee of the Japanese Society for Dialysis Therapy annually surveys the individual patient case mix, laboratory data and important events occurring in the previous years. Thus, using case mix data and laboratory data (including Kt/V and protein catabolic rate) from the 1993 questionnaire survey and the individual patients' life/death statistics from the 1994 questionnaire survey, a logistic regression analysis was conducted on 53867 patients. The analysis indicated that important death risk predictors were: (i) advanced age, (ii) occurrence of diabetes mellitus, (iii) male sex, (iv) Kt/V lower than 1.8, (v) haemodialysis time less than 5 h, (vi) protein catabolic rate less than 0.9 g/kg/day, and (vii) percentage body weight decrease less than 4% and more than 8% during the first haemodialysis session of the week.

Adult↗
PubMed1997

Current status of renal replacement therapy in Japan: results of the annual survey of the Japanese Society for Dialysis Therapy.

Beginning in 1966, the Patient Registration Committee of the Japanese Society for Dialysis Therapy has conducted a survey once a year on renal replacement therapy in Japan. As of 1983, the survey covered the life/death of patients in the survey years, as well as the case mix of individual patients. In 1990 several laboratory variables were added to the survey items. The present report summarizes the data from the 1993 and 1994 surveys. The Committee mailed out questionnaire forms at the end of the survey year to the heads of all dialysis facilities. Survey forms were returned from 99.6% of the dialysis facilities in the 1993 survey, and from 99.8% of the facilities in the 1994 survey. Some 143709 patients were treated by renal replacement therapy in 1994 (7509 were treated by CAPD, and 131016 by extracorporeal haemopurification). The gross mortality rate was 9.5% in the same year. The mean values of the laboratory variables among 88693 patients undergoing thrice weekly haemodialysis were as follows in 1993: Kt/V, 1.31 +/- 0.30; protein catabolic rate, 1.04 +/- 0.30 g/kg/day; haemodialysis time, 4.12 +/- 0.50 h. In 1994, the variables were: predialysis serum creatinine concentration, 11.54 +/- 2.85 mg/dl; predialysis serum albumin concentration, 3.91 +/- 0.55 g/dl; predialysis haematocrit, 28.69 +/- 4.36%.

Aged↗
PubMed1997

Secretory production of erythropoietin and the extracellular domain of the erythropoietin receptor by Bacillus brevis: affinity purification and characterization.

Bacillus brevis secretes a large amount of cell wall proteins into the culture medium. For construction of Bacillus brevis expression-secretion vectors of human erythropoietin (EPO) and the extracellular domain of mouse erythropoietin receptor (sEPOR), cDNA for each mature form was inserted into a plasmid containing the promoter region and the signal-peptide encoding region of a cell wall protein. Culture supernatants of transformants were affinity purified using a monoclonal antibody-fixed gel for EPO and and EPO-fixed gel for sEPOR. The affinity purification efficiently removed unwanted proteins, giving samples with sufficiently high purity to analyze amino acid sequences of N-terminal regions and biological activities. Combination of this secretory production and affinity purification may facilitate isolation of a large amount of pure EPO and sEPOR, and is useful for further understanding the molecular mechanism of interaction between EPO and EPOR.

Amino Acid Sequence↗
PubMed1997

Use of the body surface recovery time for detection of coronary artery disease.

We explored the relationship between body surface recovery time (RT), the interval between the QRS onset and the time of maximum derivative in the T-wave on a 16 precordial lead system electrocardiogram (ECG), and monophasic action potential (MAP) duration of the left ventricular endocardium in 9 patients in whom electrophysiologic testing was indicated. The usefulness of RT measurement on body surface ECG for the detection of coronary artery disease was evaluated in 98 patients who had chest pain. The RT located in the right clavicular or upper sternal area showed a very high positive correlation (r = 0.91, p < 0.001) with MAP duration from the left ventricular endocardium and showed specific shortening in patients with one-vessel disease of the left anterior descending coronary artery. With a criterion of the RT located in the right clavicular or upper sternal area corrected by Bazett's formula < 380 msec1/2, a sensitivity of 81% and a specificity of 80% were achieved for detection of one-vessel disease of the left anterior descending coronary artery.

Action Potentials↗
PubMed1997

Relationship between serum carotenoid levels and cancer death rates in the residents, living in a rural area of Hokkaido, Japan.

The relationship between serum carotenoid levels and cancer death in rural Japanese residents, aged more than 39 years, was examined epidemiologically. The follow-up subjects participated in the comprehensive health examinations, every August from 1986 to 1989, were 929 males and 1424 females, living in a rural area of Hokkaido, Japan. During 2-8 years to December 1994, the ninety-eight deaths were observed among the cohort; that is, deaths from all causes were 67 males and 31 females, and cancer deaths were 34 males and 10 females. Serum samples at fasting were collected at the entry of the cohort and serum levels of beta-carotene, alpha-carotene and lycopene were measured by the HPLC method. The relation between the mortality rates and serum carotenoid levels was estimated statistically using the Cox's proportional hazard model. The results were as follows; the hazard ratio with the overall on high serum beta-carotene levels to those of lower was 0.46 (95% C.I.: 0.27-0.78) for all causes and 0.33 (95% C.I.: 0.14-0.75) for cancer deaths. This result suggested that high levels of serum beta-carotene may play some roles on preventing cancer death.

Adult↗