Search PubMed⌕ Search

Biomedical subjects

M Nishiwaki

Publications and source records attributed to M Nishiwaki.

At least 37 records · Page 2Linked to original sources

Usefulness of K-ras gene mutation at codon 12 in bile for diagnosing biliary strictures.

Point mutations of the K-ras gene at codon 12 are often detected in the pancreatic juice of patients with pancreatic cancer. Detection of these mutations may, thus, have diagnostic implications. K-ras mutations may also have diagnostic potential for other biliary tumors. We sought to detect K-ras mutations in DNA obtained from bile in patients with biliary tract cancers, pancreatic cancer and benign biliary disease but who had obstructive jaundice. In 35 patients, bile was collected during percutaneous transhepatic choledocal drainage (PTCD) catheters. K-ras gene mutations at codon 12 in the samples were examined using mutant-allele-specific-amplification (MASA). We compared these results with cytological analyses of bile. K-ras mutations at codon 12 in bile were detected in 11 of 14 (79%) of the patients with biliary duct cancer, 3 of 9 (33%) with pancreatic cancer but not in patients with gallbladder cancer (n=3), papilla of Vater's cancer (n=3) or benign biliary diseases (n=6). In the patients, where cytological evaluation did not reveal malignant cells, K-ras mutations in bile were detected in 5 of 7 (71%) patients with biliary duct cancer and 2 of 5 (40%) with pancreatic cancer. This approach, when used in conjunction with bile cytology, may improve the yield in diagnosing suspected malignant tumors of the pancreatic-biliary system.

Aged↗

[Effective mechanisms of ATX-S10, a new photosensitizer, on HeLa tumors in nude mice].

Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser generated light. PDT is effective for oncologic applications. Many cancer patients have undergone a hematoporphyrin derivative (HpD)-mediated PDT. The HpD showed a side effect causing prolonged cutaneous photosensitivity. But ATX-S10, a new photosensitizer, provides rapid plasma and tissue clearance, comparable photoactivation efficiency, and superior light absorption of visible red. In this study, the tumor rejection mechanisms of PDT using ATX-S10 on HeLa tumors in nude mice were investigated with morphological and fluorometric methods. The mice were intracutaneously inoculated with HeLa cells, 5 x 10(5) or 1 x 10(7) cells. When tumors grew to about 10-12 mm in diameter, mice were intraperitoneally administered ATX-S10, 30 mg/kg, and 2 hours later the ATX-S10 in tumors was indirectly measured by a fluorometric machine, PMA-10 (Hamamatsu Photonics K. K.) and the tumors were irradiated by Optical Parametric Oscillator (Hamamatsu Photonics K. K.) tuned to a wave length at 670 nm, 5 mJ/pulse, 100 J/tumor. Before and after the irradiation, the effective mechanisms of PDT with ATX-S10 were studied by histological and ultrastructural approaches. The results showed occlusive thrombi in the microvasculature of the tumors and tumor cell death. These occlusive thrombi were observed within one hour after PDT at both light and electron microscopy levels, and were more remarkable as time passed after PDT. Therefore, the morphological studies of PDT with ATX-S10 suggested that the rejection mechanisms occurred mainly as a result of the destructive changes of the microvasculature in the tumors first, and secondly or simultaneously, tumor cells were destroyed through necrosis, and finally the tumors were rejected.

Animals↗

Remnant-like very-low-density lipoprotein isolated from hypertriglyceridemic patients by immunoaffinity chromatography suppressed 3-hydroxy-3-methylglutaryl coenzyme A activity of cultured human skin fibroblasts.

It has been previously reported that VLDL unbound to monoclonal antibody against apoB-100 was rich in apoE, thus resembling remnant particles (J Lipid Res, 1993:33;369-380). In the current study, we have further analyzed the unbound VLDL fraction in plasma from hypertriglyceridemic patients using a mixture of monoclonal antibodies against apoB-100 and apoA-1. The unbound VLDL isolated from the plasma of hypertriglyceridemic patients was found to be rich in apoE, apoB-48, and triglyceride compared with the bound VLDL. Furthermore, these unbound VLDL, but not bound VLDL, significantly suppressed HMG CoA reductase activity of cultured human skin fibroblasts (-20 to -25%, P = 0.0022). The degree of suppression is significantly correlated with the apoE content of unbound VLDL (r = -0.769, P < 0.05). Unbound VLDL failed to suppress the activity of HMG CoA reductase of LDL receptor negative fibroblasts. These observations indicate a potential atherogenicity of remnant-like unbound VLDL by delivering more cholesterol through the LDL receptor dependent pathway with apoE as a ligand. In conclusion, this new immunoaffinity chromatography system is a useful method for directly quantifying atherogenic remnants in plasma.

Adult↗

An evaluation of splenopancreatic disconnection as a modification of the distal splenorenal shunt, studied in nonalcoholic patients by sequential angiography.

To evaluate the validity and complications of modifying the distal splenorenal shunt (DSRS) by performing splenopancreatic disconnection (SPD), hemodynamic changes in the portal system were assessed by visceral angiography in 93 patients with nonalcoholic portal hypertension during early postoperative follow-up after DSRS. There were 40 patients who underwent DSRS alone and 53 who underwent DSRS plus SPD. Early follow-up angiography showed that portal vein perfusion was well maintained, and that the diameter of the portal vein had decreased significantly by the same degree in both groups. Hepatofugal collaterals for the shunt had developed to a greater extent in the DSRS group, while they were almost completely absent in the DSRS with SPD group. Nevertheless, partial portal vein thrombosis was not detected in the DSRS group, although it was seen in seven (13.2%) of the patients who underwent DSRS plus SPD, in whom the left proximal splenic vein was not visible. The proximal splenic vein was seen in significantly less of the DSRS with SPD patients (47.2%) than the DSRS group patients (85%). In conclusion, SPD more effectively prevented the early postoperative development of collateral pathways for the shunt compared with standard DSRS; however, the possible stagnation of blood flow in the left proximal splenic vein may predispose to a risk of partial portal vein thrombosis developing during the early postoperative period after DSRS with SPD.

Adult↗

Red cell survival in patients with nonalcoholic liver cirrhosis before and after distal splenorenal shunt.

We previously reported severe hemolysis in one patient immediately after distal splenorenal shunt (DSRS). The purpose of the present study was to evaluate changes in red cell survival after DSRS. In ten patients with nonalcoholic cirrhosis in whom DSRS was performed for esophageal varices, red cell survival and splenic quantitative hemodynamic studies were performed before and after DSRS. The splenic venous blood flow per unit volume (flow/volume ratio) was calculated. The red cell survival was significantly (P < 0.05) shortened after DSRS; the apparent half-life survival time (T 1/2) before and after DSRS was 24.6 +/- 5.9 (mean +/- SD) and 16.3 +/- 8.5 days, respectively. After DSRS, the spleen volume was significantly (P < 0.05) decreased, whereas the splenic venous blood flow was slightly increased. The spleen flow/volume ratio was significantly (P < 0.05) increased after DSRS. There was a significant and negative correlation (r = -0.684, P < 0.05) between the postoperative percentage change in T 1/2 and the spleen flow/volume ratio. These findings suggest that the red cell survival period is significantly decreased, after DSRS in patients with nonalcoholic cirrhosis, and that the increased splenic blood flow per unit spleen volume after DSRS may play an important role in the hemolytic reaction in the spleen after this procedure.

Adult↗

Effect of tea flavonoid supplementation on the susceptibility of low-density lipoprotein to oxidative modification.

Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of tea flavonoids in the prevention of atherosclerosis, we investigated the effects of tea flavonoids on the susceptibility of low-density lipoprotein (LDL) to oxidative modification. In an in vitro study, catechins or theaflavins (25-400 mumol/L) were added to plasma and incubated for 3 h at 37 degrees C. Then, the LDL fraction was separated by ultracentrifugation. The oxidizability of LDL was estimated by measuring conjugated diene, thiobarbituric acid-reactive substances (TBARS), and lipid peroxides after cupric sulfate was added. TBARS and lipid peroxides in the supernates were also measured after incubation with macrophages. Catechins significantly (P < 0.01 by ANOVA) and dose-dependently prolonged the lag time before initiation of oxidation. Among the catechins, epigallocatechin gallate exerted the most marked effect, prolonging the oxidation lag time more than vitamin E at the same molar concentration. Theaflavins exerted stronger inhibitory effects than catechins. Macrophage-mediated LDL oxidation was also inhibited by adding these tea flavonoids to the plasma samples. In an in vivo study, 14 healthy volunteers consumed 750 mL black tea/d for 4 wk. After the subjects had consumed tea for 4 wk, the lag time before LDL oxidation was significantly (P < 0.01) prolonged from 54 to 62 min. This minor prolongation occurred despite much lower plasma flavonoids than were used in vitro. No significant change was observed in eight control volunteers. LDL exposed to tea flavonoids in vitro or in vivo reduced oxidizability. We speculate that tea flavonoids may have a role in ameliorating atherosclerosis.

Adult↗

Beneficial effects of alcohol withdrawal on LDL particle size distribution and oxidative susceptibility in subjects with alcohol-induced hypertriglyceridemia.

LDL subclass pattern B, reported to have a higher prevalence in hypertriglyceridemics (HTGs), is considered to be associated with an increased risk for coronary artery disease, and the small dense LDL characteristic of this pattern is susceptible to oxidative modification. Alcohol is considered one of the most frequent causes of increases in plasma triglyceride (TG) levels. We investigated the effects of alcohol withdrawal on LDL subclass distribution and oxidizability in drinkers with different plasma TG levels. Thirty-seven male subjects with relatively heavy alcohol-consumption habits were divided into four groups; normotriglyceridemic (NTG)/withdrawal (n = 11), NTG/control (n = 8), hypertriglyceridemic (HTG)/withdrawal (n = 10), and HTG/control (n = 8). Both withdrawal groups abstained form alcohol for 4 weeks, while the control subjects maintained their usual intake of alcohol. Peak LDL particle diameter (PPD) was smaller in the combined HTG groups than in the combined NTG groups before abstinence, although PPD increased significantly (P < .01) from 25.5 to 26.1 nm in the HTG/withdrawal group. Before abstinence, lag times preceding LDL oxidation in the combined HTG groups were shorter than in the combined NTG groups; after withdrawal, lag time was prolonged significantly (P < .01) from 49.9 to 57.3 minutes in the HTG-withdrawal group. No significant changes in PPD and lag time were observed in the other three groups. Significant correlations (P < .05) were observed between the change (delta) in the lag time and delta TG and between delta lag time and delta PPD. We conclude that in alcohol-induced HTG subjects, alcohol withdrawal has beneficial effects on the LDL profile by shifting the particle size from smaller to larger and decreasing its susceptibility to oxidation.

Adult↗

Characterization of high-density apolipoprotein particles A-I and A-I:A-II isolated from humans with cholesteryl ester transfer protein deficiency.

The cholesteryl ester transfer protein (CETP) plays an important role in metabolism of high-density lipoprotein and reverse cholesterol transport in humans. The two major classes of high-density lipoprotein particles are those containing apolipoprotein A-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). We isolated and characterized the apoA-I-containing lipoprotein particles from three subjects with homozygous CETP deficiency (CETP-D) and compared the results with those from normolipidemic control subjects. Plasma concentrations of apoA-I in both LpA-I and LpA-I:A-II were significantly elevated in CETP-D subjects. Both LpA-I and LpA-I:A-II from these subjects were larger and contained more cholesteryl ester per particle than control particles. In CETP-D, subpopulations of LpA-I and LpA-I:A-II with an unusually large size (Stokes diameters 13.8 nm and 12.6 nm, respectively) not detected in normal subjects were isolated. The molar ratio of apoA-I to apoA-II in LpA-I:A-II isolated from CETP-D subjects was higher (mean 2.4) than those of controls (mean 1.4). ApoE was primarily associated with LpA-I:A-II in CETP-D subjects. A subclass of LpA-I with pre-beta migration on agarose electrophoresis was increased in CETP-D subjects. Both LpA-I and LpA-I:A-II from CETP-D subjects bound with higher affinity but less capacity to HepG2 cells compared with control particles, and were internalized to a lesser extent than control particles. These data suggest that the absence of CETP in humans significantly affects the plasma concentration, size, composition, and cellular interaction of both major classes of apoA-I-containing lipoprotein particles.

Adult↗

Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency.

The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.

Adult↗

CETP and LCAT activities are unrelated to smoking and moderate alcohol consumption in healthy normolipidemic men.

To distinguish between the effects of smoking and drinking on lipid metabolism, we conducted a cross-sectional study using 52 healthy normolipidemic subjects who either smoked or drank, but not both. The subjects were divided into three groups: Group S, smokers who did not drink (n = 20); Group D, drinkers who did not smoke (n = 12); and Group C, controls (n = 20), who neither drank nor smoked. High density lipoprotein cholesterol (HDL-C) levels and plasma cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activities were measured in all of the subjects, and the values obtained in Group S and Group D were compared to those of controls. Group S had lower (p < 0.01) HDL2-C and HDL3-C levels, and Group D had higher (p < 0.05) HDL2-C and HDL3-C levels than the controls, but there were no significant differences between groups with respect to CETP and LCAT activities. Thus, in healthy normolipidemic men, both smoking and drinking affect HDL-C levels as expected, but do not affect plasma CETP or LCAT activity levels.

Adult↗

Effects of Ca-antagonists on oxidative susceptibility of low density lipoprotein (LDL).

Twelve adults (age 32-61 years) with essential hypertension were recruited from the outpatient clinics of National Defense Medical College hospital to serve as subjects in the present study. They were treated with nilvadipine, a Ca-antagonist, 4 mg b.i.d. for 4 weeks. LDL samples were isolated by ultracentrifugation at the beginning (week 0) and at the end (week 4) of the treatment regimen. The formation of conjugated dienes was measured by incubating 100 micrograms of LDL protein with 2 mumol CuSO4 in 2 ml phosphate buffered saline (PBS). There were no significant differences between lipids levels, composition and anti-oxidant levels of LDL at weeks 0 and 4. The lag time of LDL oxidation was 71.1 +/- 11.3 min at week 0 and 81.3 +/- 13.2 min at week 4 (p < 0.05). In vitro studies of LDL oxidation, evaluated by thiobarbituric acid reactive substances (TBARS) and by agarose electrophoretic mobility, indicated that nilvadipine inhibited the oxidative modification of LDL while amlodipine, used as control, did not. Nilvadipine, a lipophilic Ca-antagonist, significantly prolonged the lag time of conjugated diene formation of LDL by 12.6% but amlodipine, a hydrophilic Ca-antagonist, had no major effect on LDL oxidation. These results suggest that Ca-antagonists are effective for the prevention of atherosclerosis but the effect is dependent upon the lipophilicity of the drugs.

Adult↗

[A case of type A acute aortic dissection successfully treated with a ringed intraluminal graft: a new technique of graft insertion].

A-77-year old woman was hospitalized at our hospital presenting with severe chest and back pain. A computed tomographic scan revealed acute type A aortic dissection and intraoperative ultrasound showed an entry near the brachiocephalic artery. Selective cerebral perfusion using flexible 12 Fr balloons was performed for brain protection. The distal aorta was trimmed just proximal to the entry using felt strips and a 24 mm ringed intraluminal graft (ILG) was inserted under it successfully. The patient did well after the operation. Insertion of a ringed ILG is a simple and easy technique, however if an entry is located near the aortic arch, insertion is difficult because of intimal retraction to the arch. And an additional intimal tear sometimes occurs at the site of tape ligation. The method which we presented seemed to provide safer insertion of the proximal ring without these problems.

Acute Disease↗

The efficacy of non-clamping selective cerebral perfusion in distal aortic arch aneurysm repair: report of a case.

Successful repair of a distal aortic arch aneurysm without aortic cross-clamping was carried out in a 74-year-old man, using a combination of special separate cerebral perfusion and retrograde coronary perfusion, termed non-clamping selective cerebral perfusion. We believe that satisfactory results following aortic arch surgery in elderly patients can only be achieved through the prevention of emboli derived from an aortic cross-clamping site, and shortened ischemic time of the vital organs.

Aged↗

Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation.

The mechanism whereby alcohol increases high-density lipoprotein cholesterol (HDL-C) levels is unclear. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) act on lipoprotein metabolism. The purpose of the present study is to determine which one or what combination of these factors is responsible for the rise in HDL-C levels following alcohol ingestion. After 3 weeks of abstinence, 12 men consumed 0.5 g/kg bw of alcohol per day for 4 weeks; 13 abstaining men served as controls. Mean plasma total cholesterol (TC) levels were unchanged in either group throughout the study. Among the alcohol consumers, plasma triglycerides (TG), HDL-C, apolipoprotein (apo) A-I and A-II levels increased significantly after 3 weeks of alcohol loading but were unchanged in the control group. High-density lipoprotein3 cholesterol (HDL3-C) levels increased significantly in the alcohol consumers after 4 weeks of alcohol loading whereas high-density lipoprotein2 cholesterol (HDL2-C) levels were unaffected. In the controls, neither HDL2-C nor HDL3-C changed significantly. Post-heparin plasma (PHP) LPL activity and mass increased significantly (P < 0.01) after the alcohol ingestion (controls remained unchanged) without changing LPL specific activity. HL, CETP and LCAT activities were unaffected in both groups. We conclude that of the factors considered, LPL contributed the most to the alcohol-induced rise in HDL-C.

Adult↗