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Biomedical subjects

S Sumi

Publications and source records attributed to S Sumi.

At least 163 records · Page 9Linked to original sources

[Clinical analysis and treatment of carcinoma of the prostate with bone metastasis].

We carried out a clinical analysis of carcinoma of the prostate with bone metastasis in 141 cases of prostatic cancer treated between 1965 and 1984. Among these, there were 64 cases of stage D, 45.4% and 55 cases of bone metastasis at the first visit. Stage D cases were mainly treated with estrogen. Poorly differentiated adenocarcinoma was observed in 62% of the stage D cases. Elevated pretreatment levels of serum acid phosphatase in the cases of bone metastasis were found in 47.8-71.4% of patients with poorly differentiated adenocarcinoma. Elevated acid phosphatase levels were also normalized by estrogen administration in over 60% of cases, regardless of the degree of differentiation. Also, clinical efficacy of estrogen was observed in more than 80% of stage D cases with any degree of differentiation. The most frequent clinically observed metastatic site was bone. Pain-relieving effects of estrogen, radiation and ifosfamide were observed in 76.3%, 92.3% and 70%, of patients, respectively. The cause of death in stage D patients was mainly aggravation of metastatic lesions. The period for which estrogen was effective was 45 months on average in cases who died at stage D. The period from reactivation to death averaged 16 months, while the period from the beginning of treatment to death in cases unresponsive to estrogen was only 11 months on average.

Adenocarcinoma↗

Renal hypouricaemia in a patient with 48,XXYY syndrome.

Studies on hypouricaemia observed in a patient with 48,XXYY syndrome revealed an abnormality in renal urate handling. His renal urate clearance was abnormally increased. Inosine administration and provocative tests using probenecid and pyrazinamide identified an isolated renal tubular abnormality with increased urate secretion. Since the serum urate in his brother with a normal sex chromosome constitution was also low, the association of renal hypouricaemia and 48,XXYY syndrome in this patient is probably coincidental. Although the brother was not investigated, these siblings may be a previously unreported case of familial hypouricaemia due to isolated renal hypersecretion.

Adult↗

In vitro degradation of oxytocin by pregnancy serum, placental subcellular fractions and purified placental aminopeptidases.

The degradation of oxytocin (formula; see text) by human placental particulate and soluble fractions, pregnant and non-pregnant sera, and purified enzymes such as microsomal placental leucine aminopeptidase (P-LAP), retroplacental serum P-LAP and placental post-proline endopeptidase, was studied by measuring liberated amino acids with a high performance liquid chromatograph (HPLC). While the placental particulate fraction degraded oxytocin almost completely into single amino acid and amide, the placental soluble fraction did not liberate any amino acid and amide. Purified retroplacental P-LAP liberated Tyr2, Ile3, Gln4 and Asn5 from the cyclic structure of oxytocin actively. Pregnancy serum containing the retroplacental P-LAP liberated also these amino acids and amides. Purified microsomal P-LAP liberated Leu8 in addition to these amino acids and amides. Although purified placental post-proline endopeptidase or porcine kidney leucine aminopeptidase (LAP) could not liberate any amino acid and amide from oxytocin, the combination of the post-proline endopeptidase with porcine kidney LAP or with placental microsomal P-LAP actively liberated all amino acids and amides detectable by HPLC. When the ratio of amino acid liberation velocity to LAP activity measured with leu-p-nitroanilide was calculated, the ratios for cyclic amino acids such as Tyr2 and Ile3 were high with the placental particulate fraction, the mixture of post-proline endopeptidase and microsomal P-LAP, retroplacental P-LAP, and pregnancy serum. The ratio for Leu8 was high with the placental particulate fraction and the mixture of post-proline endopeptidase and microsomal P-LAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Excess purine degradation in exercising muscles of patients with glycogen storage disease types V and VII.

To investigate purine catabolism in exercising muscles of patients with muscle glycogen storage disease, we performed ischemic forearm exercise tests and quantitated metabolites appearing in cubital venous blood. Two patients with glycogen storage disease type V and three with glycogen storage disease type VII participated in this study. Basal lactate concentrations lowered in every patient with glycogen storage disease type V or type VII. Two patients with glycogen storage disease type VII, who had markedly elevated concentrations of serum uric acid (14.3 and 11.9 mg/dl, respectively), showed high basal concentrations of ammonia (118 and 79 mumol/liter, respectively; 23 +/- 4 mumol/liter in healthy controls) and of hypoxanthine (23.4 and 20.4 mumol/liter, respectively; 2.0 +/- 0.4 mumol/liter in healthy controls). Other patients showed near normal measurements of these metabolites. After forearm exercise, ammonia, inosine, and hypoxanthine levels increased greatly in every patient studied, in contrast with the lack of increase in lactate levels. The incremental area under the concentration curves for venous ammonia was 13-fold greater in the glycogen storage disease group than in controls (1,120 +/- 182 vs. 83 +/- 26 mumol X min/liter). The incremental areas of inosine and hypoxanthine were also greater in the glycogen storage disease group (29.2 +/- 7.2 vs. 0.4 +/- 0.1 and 134.6 +/- 23.1 vs. 14.9 +/- 3.2 mumol X min/liter, respectively). The incremental areas of ammonia in controls and in glycogen storage disease patients strongly correlated with those of hypoxanthine (r = 0.984, n = 11, P less than 0.005). These findings indicated that excess purine degradation occurred in the exercising muscles of patients with glycogen storage disease types V and VII, and suggested that the ATP pool in the exercising muscles may be deranged because of defective glycogenolysis or glycolysis.

Adult↗

Purification and properties of human placental dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (EC 3.4.14.5; Gly-Pro-p-nitroanilidase) was purified 1840-fold from human placenta and characterized. The enzyme was solubilized from membrane fractions with Triton X-100 and subjected to zinc acetate fractionation, hydroxylapatite chromatography, Sephacryl S-300 chromatography and then affinity chromatographies with Lentil Lectin-Sepharose 4B and Gly-Pro-NH-(CH2)6-NH-Sepharose 4B. Dipeptidyl peptidase IV was completely separated from leucine aminopeptidase by the final affinity chromatography. The apparent molecular weight of the enzyme was estimated to be 350,000 by gel filtration. The purified enzyme gave a single band with a weight of 124,000 with sodium dodecyl sulfate (SDS) gel-electrophoresis, suggesting that the enzyme consists of three subunits. The isoelectric point of the enzyme was 4.4. The purified enzyme was most active at pH 8.0 with Gly-Pro-p-nitroanilide as substrate and the Km value for this substrate was 2.27mM.

Chromatography, Affinity↗

Post-proline endopeptidase in human placenta.

Post-proline endopeptidase (EC 3.4.21.26) was found in human placenta, purified 3390-fold from it and briefly characterized. The post-proline endopeptidase could be completely separated from dipeptidyl peptidase IV (EC 3.4.14.5) by hydrophobic phenyl-Sepharose chromatography. The pH optimum of the enzyme was 6.7. The Km values for 7-(Succinyl-Gly-Pro)-4- methylcoumarinamide was 1.0 mM. The molecular weight of this enzyme was estimated to be 140 000 by gel filtration and 67 000 by dodecyl sulfate gel electrophoresis, indicating its dimeric structure. Human placental post-proline endopeptidase was suggested to be a thiol proteinase by inhibition studies.

Electrophoresis, Polyacrylamide Gel↗

Decreases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in diabetic mice: a close relationship to the development of ketosis.

Hyperglycemic mice with streptozotocin diabetes were divided into two groups according to the presence or absence of ketosis. No difference in blood glucose level between two groups was observed in this experiment. However, hepatic fructose-2,6-P2 level and fructose-6-P,2-kinase activity were decreased only in ketotic diabetic mice. Similar decreases in those indices were observed in 48-h starved normal mice. In ketotic diabetes, insulinization for 24 h was required to normalize fructose-2,6-P2 level and fructose-6-P,2-kinase activity, while glucose administration normalized altered fructose-2,6-P2 metabolism in starvation only in 30 min. Hepatic cyclic AMP was increased neither in ketotic nor in non-ketotic diabetic mice. These results indicate that the decrease in hepatic fructose-2,6-P2 level in diabetes is apparently related to the occurrence of ketosis, but not to hyperglycemia. The mechanisms of the decrease in fructose-6-P,2-kinase activity in ketotic diabetes and starvation are discussed.

Animals↗

A comparative study on glucagon effect between McArdle disease and Tarui disease.

Pretreatment with glucagon relieved patients with McArdle disease from muscular symptoms during exercise and enhanced exercise performance, though it did not produce any improvement in patients with Tarui disease. The difference in glucagon effect between the two diseases was clearly demonstrated in the bicycle ergometer exercise tests. In addition, the semi-ischemic forearm exercise tests performed after glucagon injection showed that increased lactate production was significantly induced by exercise in McArdle disease, but it was not the case in Tarui disease. In McArdle disease, the augmentation in exercise-induced lactate production was also observed after administration of glucose, or glucose plus insulin, but it was neither observed after administration of insulin alone nor after arginine or epinephrine administration. These findings suggest that the beneficial effect of glucagon in McArdle disease is due to the enhanced utilization of circulating glucose through the muscular glycolytic pathway realized in the coexistence of hyperglycemia and hyperinsulinemia.

Adult↗

Kinetic properties of erythrocyte phosphofructokinase in patients with type VII glycogenosis from two families--close similarity to liver type phosphofructokinase.

The kinetic properties of phosphofructokinases (PFKs) from normal human liver, muscle and erythrocytes, and from erythrocytes of two unrelated patients with type VII glycogenosis (muscle PFK deficiency, McKusick 23280) were analysed in this study. Sensitivity to inhibition by ATP and to inhibition by 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate and citrate were quite different for muscle and liver PFKs. The kinetic characteristics of normal erythrocyte PFK were intermediate between those of muscle and liver PFKs. The kinetic constants of erythrocyte PFK of a patient in one family were indistinguishable from those in the other family. In addition, kinetic behaviour of residual PFK activity in erythrocytes from patients in the two families were quite similar to those of normal liver PFK. These results of kinetic analyses provide convincing evidence for the concept that normal erythrocyte PFK consists of muscle and liver type subunits. Residual erythrocyte PFK activity in type VII glycogenosis is thus concluded to reflect the activity of liver type PFK existing in patient's erythrocytes.

Adolescent↗

Upside-down presentation of the Johansson moving light-spot pattern.

In a film produced by Johansson, a group of moving spots, corresponding to lights attached to the main joints of a walker or a runner, gives instantly a vivid impression of a person walking or running. Even when this film was inverted and run backward, some sort of human movement was still perceived. It was perceived more frequently as an upright image of a person moving forward in a very strange manner than as an inverted image of a person moving backward. Such strangeness seemed to arise from the fact that the actor's arms were perceived as legs and vice versa. The phase relations typical of the Johansson pattern are therefore still present when the film is inverted and run backward, leading to the perception of biological motions though these motions are very strange.

Animals↗

Metabolic basis of improved exercise tolerance: muscle phosphorylase deficiency after glucagon administration.

A 26-year-old girl with muscle phosphorylase deficiency had exercise intolerance and experienced an occasional "second wind" phenomenon. Muscle glycogen concentration was about three times the normal level, whereas each glycolytic intermediate below the phosphorylase step was equivalent to only 10% of a normal level. Semi-ischemic forearm exercise tests disclosed no elevation of the venous lactate or pyruvate level, but they showed remarkable increases of serum creatine kinase and ammonia. Glucagon administration markedly augmented exercise tolerance. Forearm exercise after glucagon injection significantly increased venous lactate. Thus, the beneficial effect of glucagon is attributable to blood glucose utilization by muscle.

Adult↗

Insulin and epidermal growth factor stimulate glycolysis in quiescent 3T3 fibroblasts with no changes in key glycolytic enzyme activities.

In order to study the effect of insulin and epidermal growth factor (EGF) on glycolysis in quiescent 3T3 fibroblasts and their mechanisms of action, lactic acid produced by cells and activities of key glycolytic enzymes in cell extracts were determined. Insulin increased lactic acid production; the maximal stimulation occurred at the concentrations above 250 ng/ml and the half-maximal dose was 50 ng/ml. This effect of insulin appeared as early as one hour, and lactic acid production in the presence of insulin linearly increased up to 4 h. The 24-h pretreatment with insulin exhibited no significant effect on the production by cells afterward incubated either with or without insulin. Lactic acid production decreased as the concentration of phloridzin increased. However, insulin stimulation of the production still remained in the presence of phloridzin. Parahydroxymercuribenzoate reduced production only by the equivalent of the increase due to insulin. EGF also increased lactic acid production; this effect occurred at 1 ng/ml and was maximal at 100 ng/ml. The activities of hexokinase, phosphofructokinase and pyruvate kinase in quiescent cells were not increased by insulin, and the affinities for substrates of these enzymes remained unaltered. These findings suggest that glucose uptake is a rate-limiting step in glycolysis in quiescent 3T3 fibroblasts and that the stimulatory effect of insulin on glycolysis is mediated by enhanced glucose entry.

Animals↗

Purification and properties of a human placental post-proline endopeptidase.

Post-proline endopeptidase (EC 3.4.21.26) was found in human placenta, purified 3,390-fold and characterized. The post-proline endopeptidase was able to be completely separated from dipeptidyl peptidase IV (EC 3.4.14.5) by hydrophobic phenyl Sepharose chromatography. The pH optimum of the enzyme was 6.7. The Km value for 7-(succinyl-Gly-Pro)-4-methylcumarineamide was 1.0mM. The molecular weight of this enzyme was estimated to be 140,000 by gel filtration and 67,000 by sodium dodecyl sulfate gel electrophoresis, indicating its dimetric structure. Human placental post-proline endopeptidase appeared to be a thiol protease in view of the results of inhibition studies.

Chromatography↗

Prevalence of diabetic retinopathy and distribution of its severity among patients of a university clinic of diabetes in Osaka.

We have been following longitudinal changes of diabetic retinopathy by periodic fundoscopy in patients at our out-patient clinic for diabetes mellitus. In this study, we reviewed the prevalence of diabetic retinopathy and the distribution of its severities. Funduscopic examinations for retinopathy were performed on 242 patients. They ranged in age from 13 to 84 years (52.9 +/- 0.9, mean +/- s.e.). Duration of diabetes ranged from 1 to 31 years (10.7 +/- 0.4). Forty patients were treated with diet alone, 112 with oral hypoglycemic agents and 90 with insulin administration. No retinopathy was found in 83 patients (34%), background retinopathy in 113 (47%), preproliferative retinopathy in 24 (10%) and proliferative retinopathy in 17 (7%). Five patients (2%) were blind. Twenty-seven patients (60%) of 45 with a less than 5-year duration of diabetes were apparently without retinopathy, while the incidence of proliferative retinopathy increased in proportion to the duration. Fasting plasma glucose and glycosylated hemoglobin levels were higher in the patients with proliferative retinopathy than in any other group. All of the blind patients had a long history of untreated diabetes. Whether diabetic control assessed by glycosylated hemoglobin influences the progression of retinopathy could not be demonstrated by a 2-year observation. Further analysis based on a longer duration is needed in this respect.

Adolescent↗

Production in Escherichia coli of biologically active secretin, a gastrointestinal hormone.

A synthetic gene for porcine secretin was ligated with Pst I-cleaved pBR322 by its flanking synthetic Pst I linkers to produce a fused protein consisting of an amino-terminal portion of beta-lactamase and an entire secretin molecule. The hybrid plasmid was transferred into competent Escherichia coli cells. The plasmids, which were proved in our investigation to contain the secretin gene in the desired orientation, were then screened for the production of secretin. This was shown by radioimmunoassay and gel electrophoretic analysis of the polypeptides that were synthesized in E. coli minicells transformed with the hybrid plasmids. Secretin so produced, whose carboxy terminal residue may not be amidated in contrast with natural porcine secretin, showed the same activity in stimulating pancreatic secretion in a bioassay with anesthetized rats as does natural secretin.

DNA Restriction Enzymes↗