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Biomedical subjects

K Yamasawa

Publications and source records attributed to K Yamasawa.

At least 19 recordsLinked to original sources

Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The Bcl-2 can work to protect cells from apoptosis, which is induced by p53 gene. These facts suggest the significant role of these genes in the genesis and progression of various tumors. The present study was designed to assess the significance of p53 and Bcl-2 protein (pBcl-2) expression on resectable invasive ductal carcinoma (IDC) of the pancreas. METHODS: The present study included 63 IDCs, which were resected between 1982 and 1998. pBcl-2 and p53 were stained immunohistochemically with monoclonal antibodies. RESULTS: pBcl-2 was expressed in 16 (25.4%), and p53 was positively expressed in 32 out of 63 IDCs (50.8%); however, expression of pBcl-2 did not necessarily correlate with that of p53. Although p53 expression did not show any significant influence on the patients' survival, pBcl-2(+) patients showed a higher survival than pBcl-2(-) patients for both p53(+) and p53(-) patients, which suggested that pBcl-2 expression had a more significant effect on the survival of patients than p53 expression. On the other hand, there were no differences in the survival curve between the adjuvant chemotherapy (ACT) group and the surgery alone (SA) group. pBcl-2 expression had no influence on the effect of ACT, the ACT group showed a significantly better survival than the SA group for p53(+) IDC patients. CONCLUSIONS: pBcl-2 expression is a beneficial prognostic factor for patients with IDC, whereas p53 expression may be beneficial in the prediction of the effects of adjuvant chemotherapy on patients with IDC. J. Surg. Oncol. 2001;76:188-196.

Adult↗

Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas.

The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis, pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI. pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.

Adult↗

[A case of recurrent pancreatic cancer brought into a complete response by a multimodal treatment with intraarterial chemotherapy and radiotherapy].

We achieved a complete response of recurrent pancreatic cancer using a multimodal treatment with intravenous, oral and intraarterial chemotherapies and radiotherapy. A 55-year-old female patient had a recurrent pancreatic cancer, which had invaded the portal vein, 2 years after pancreatoduodenectomy. Angiography demonstrated prominent stenosis of the portal vein, which was enlarged by the insertion of a metalic stent to maintain blood flow to the liver. Chemotherapy included intravenous mitomycin C, 5-FU and 4'-epirubicin (EPI), oral UFT and cyclophosphamide, and intraarterial cisplatin, 5-FU and EPI through a catheter inserted into the celiac artery. Furthermore, the patient received a total of 50 Gy radiotherapy. Four months after the initiation of therapy, a computed tomography image demonstrated a complete disappearance of the recurrent tumor and a prominent decrease in the serum CA19-9 level. At present, 11 months have passed after the initiation of therapy, and she has been followed at our outpatient department without any symptoms of recurrence.

Adenocarcinoma↗

Effects of aging on alpha 1-adrenoceptor mechanisms and the inhibitory effect of diltiazem on noradrenaline maximum response in isolated rat aortic preparation.

The effects of aging on alpha 1-adrenoceptor mechanisms in aortic preparations isolated from 3-, 6-, 10-, 18-, and 40-week-old rats were studied and compared with serotonin receptor mechanisms in the same preparations. The potency (pD2 value) of noradrenaline increased with age from 3 to 10 weeks, but decreased thereafter with age from 10 to 40 weeks. The affinity (pKA value) of noradrenaline and of prazosin (pA2 value) did not alter with aging. The change in potency or the pD2 value of noradrenaline was proportional to receptor reserve (pD2-pKA value) for noradrenaline, suggesting that the change of potency of noradrenaline with age was due to a change of receptor reserve, but not to change of drug affinity to alpha 1-adrenoceptors. The potency (pD2 value) and affinity (pKA value) of serotonin, and the affinity (pA2 value) of ketanserin, did not alter with aging, suggesting that serotonin receptor mechanisms in rat aorta did not change with age. The inhibitory effect of diltiazem on noradrenaline maximum response decreased with age from 3 to 10 weeks, but increased with age from 10 to 40 weeks. An inverse relationship between changes of diltiazem inhibition and receptor reserve of noradrenaline was found. Diltiazem's inhibitory effect on serotonin maximum response did not alter with aging.

Aging↗

[Pharmacokinetic and clinical studies of cefuzonam in obstetric and gynecologic infections].

Cefuzonam (CZON, L-105), a new semisynthetic cephem antibiotic, was studied in the field of obstetrics and gynecology, pharmacokinetically and clinically. Following is a summary of the results. 1. Concentrations of CZON in serum and genital organs following intravenous drip infusion of 1 g of the drug over 60 minutes were measured. Samples were taken during 40 to 190 minutes after the end of the infusion. Ratios of concentrations of the drug transferred into genital organs to the concentration in the cubital venous serum were 0.5 to 1.5 in many cases. Levels of the drug in the genital organs examined well exceeded MICs for common causative organisms in obstetric and gynecologic infections. 2. Therapeutic effects of 1 g or 2 g of CZON by drip infusion twice daily were evaluated in 8 patients. Overall clinical efficacy was 62.5% (5/8). No side effects or abnormal laboratory findings due to the drug were noted. The results suggest that CZON is a useful antibiotic for obstetric and gynecologic infections.

Adolescent↗

Uptake and oxidation of acetaldehyde by intact human erythrocytes.

Human erythrocytes were examined for acetaldehyde-oxidizing capacity of intact cells, in comparison with its uptake under various conditions. The oxidation was found to be predominant over other possible acetaldehyde-metabolizing pathways, particularly with low concentrations of acetaldehyde. Further investigation using three media which differed in the initial pyruvate level showed an independence of acetaldehyde oxidation rate up to the high cellular lactate/pyruvate concentration ratio. The apparent non-oxidative acetaldehyde uptake obtained by subtraction of oxidation from the total uptake, was reduced when pretreating the erythrocytes with pyridoxal but not with pyridoxal 5'-phosphate. Though N-ethylmaleimide also inhibited the non-oxidative uptake, another sulfhydryl blocking reagent, p-chloromercuribenzoate was without effect. Thus, in addition to the oxidation, acetaldehyde may be involved in a reaction such as binding to the red cell components, as the minor metabolizing pathway in the erythrocytes.

Acetaldehyde↗

Comparative study of phenotypes on activity and plasma concentration in the genetic system of plasminogen.

Plasma antigen concentration of plasminogen was approximately 11-13 mg/100 ml in all phenotypes. Specific activities of common PLG 1-1 and second common PLG 2-1 were 16.52 +/- 1.43 U/mg (caseinolytic activity/milligram antigen concentration, mean +/- SD) and 17.22 +/- 2.14 U/mg, respectively. Caseinolytic activity, antigen concentration and specific activity of PLG 1-B were 0.80 +/- 0.23 U/ml, 11.39 +/- 2.44 mg/100 ml and 6.95 +/- 0.96 U/mg. Plasma plasminogen levels of three rare phenotypes (PLG 3-1, PLG 1-C and PLG 1-M) were at least in the normal ranges by immunological and biological assay.

Alleles↗

Effect of disulfiram and its reduced metabolite, diethyl-dithiocarbamate on aldehyde dehydrogenase of human erythrocytes.

Inhibition of human erythrocyte aldehyde dehydrogenase (ALDH) activity was studied using disulfiram and its reduced metabolite, diethyldithiocarbamate (DDC). The enzyme was rapidly inactivated by disulfiram and the inhibition was protected by reduced glutathione (GSH), in a concentration dependent manner when the enzyme premixed with GSH was reacted with disulfiram. Higher reactivity of the thiol group of the enzyme than that of GSH to disulfiram was suggested from the observation that half of the enzyme activity was inhibited when the ratio of disulfiram to GSH was 1:10. Although DDC alone showed no inhibitory effect on the enzyme, inactivation was mediated by a low concentration of heme-containing peroxidases, but not by methemoglobin. Under this condition, the inhibition potential was not protected, even with a high concentration of GSH. The constant reoxidation system of DDC is probably directly related to the enzyme inactivation.

Aldehyde Dehydrogenase↗

Two new slow-moving variants of human serum albumin.

Two new slow-moving variants of human serum albumin were found in members of two unrelated Japanese families. These variants, different from each other and from the slow-moving variants described previously, were designated albumin "Okinoerabu' and albumin "Akasaka'. The mode of inheritance of each variant was consistent with an autosomal codominant trait. A very rare type, homozygote for a variant, albumin "Okinoerabu', was also detected. The segregation data of albumin and Gc showed no discrepancy from the postulation of a linkage between these two loci.

Electrophoresis, Agar Gel↗

Three new variants in the plasminogen system.

Three new phenotypes of plasminogen system, named PLG 3-1, PLG 1-M and PLG 1-C, were found in sera from healthy Japanese persons by the agarose gel isoelectric focusing followed by the methods of immunofixation and caseinolysis. The present study indicates that at least the PLG 3 component is genetically determined. The existence of another PLG3 allele is postulated.

Adult↗

Correlation between human erythrocyte aldehyde dehydrogenase activity and sensitivity to alcohol.

Young healthy Japanese men were given 0.48 g ethanol/kg body weight orally. Those responding with a marked increase in heart rate after alcohol also exhibited facial flushing and had higher acetaldehyde levels than those not responding, in spite of similar blood alcohol levels. The activity of aldehyde dehydrogenase in erythrocytes was found to correlate significantly (r=-0.73, p < 0.01) with the increase in heart rate after alcohol drinking. It is suggested that erythrocyte aldehyde dehydrogenase activity affects or reflects blood acetaldehyde levels and physiological response to alcohol, and may prove useful as a marker for alcohol sensitivity in Orientals.

Acetaldehyde↗

Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes.

Human erythrocyte aldehyde dehydrogenase (aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) was purified to apparent homogeneity. The native enzyme has a molecular weight of about 210,000 as determined by gel filtration, and SDS-polyacrylamide gel electrophoresis of this enzyme yields a single protein and with a molecular weight of 51,500, suggesting that the native enzyme may be a tetramer. The enzyme has a relatively low Km for NAD (15 microM) and a high sensitivity to disulfiram. Disulfiram inhibits the enzyme activity rapidly and this inhibition is apparently of a non-competitive nature. In kinetic characteristic and sensitivity to disulfiram, erythrocyte aldehyde dehydrogenase closely resembles the cytosolic aldehyde dehydrogenase found in the liver of various species of mammalians.

Aldehyde Oxidoreductases↗