Absolute mass limits of the gaugino-Higgsino sector in the minimal supersymmetric model from data from the CERN collider LEP and the Fermilab Tevatron.
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Biomedical subjects
Publications and source records attributed to K Hidaka.
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We report a rare case of secondary involvement of the gallbladder by metastatic renal cell carcinoma. A 71-year-old man was diagnosed as having a polypoid mass within the gallbladder when he underwent right nephrectomy for a renal cell carcinoma. A preoperative diagnosis of simultaneous carcinoma of the gallbladder was made, and extended cholecystectomy with regional lymphadenectomy was performed five months after the initial operation. Postoperative histological examination of the polypoid mass within the gallbladder and a pancreatic mass excised during the second surgery revealed these resected tumors to be identical to the clear cell type of renal cell carcinoma. We feel that this case presents synchronous involvement of the gallbladder and pancreas by metastatic renal cell carcinoma of the right kidney.
This study examined the effects of simvastatin, an inhibitor of HMG-CoA reductase, on the metabolism of labelled human low density lipoprotein (LDL) in animal models. Administration of 10 mg/kg per day simvastatin for 2 weeks reduced the levels of total cholesterol, LDL-cholesterol and triglycerides by 5.7 mg/dl (16%), 8.8 mg/dl (36%) and 4.9 mg/dl (13%), respectively in guinea pigs. High density lipoprotein-cholesterol levels rose 0.8 mg/dl (29%) by simvastatin treatment. Measurements of turnover of LDL were determined between simvastatin-treated guinea pigs and untreated guinea pigs using intravenous injection of 131I-labelled LDL and 125I-labelled galactose-treated LDL to quantify the LDL receptor pathway. Simvastatin significantly increased the fractional catabolic rate (FCR) of the LDL receptor-dependent pathway. In contrast, the FCR of the LDL receptor-independent pathway was not altered by simvastatin therapy. The FCR for LDL isolated from simvastatin-treated subjects compared to that from control subjects was very similar in both control and simvastatin-fed guinea pigs. These findings suggest that simvastatin mainly reduced serum cholesterol levels by accelerated FCR of LDL receptor mediated pathway.
In this study, we asked whether cholesterol contents were specifically correlated with cellular sensitivity to hyperthermia. To examine this possibility, we employed two isogenic mammalian cell lines, Chinese hamster V79 cell line and its amphotericin B-resistant (AMBr) cell line. AMBr cells had a decreased content of membrane sterols in comparison with V79 cells. Clonogenic assays showed that AMBr cells were more sensitive to hyperthermic treatment at 45 degrees C than V79 cells. Cholesterol contents were increased in AMBr cells by exposure to liposomes containing 1:1 lecithin-cholesterol, and the sterol level was comparable to that of V79 cells. In comparison with untreated AMBr cells, AMBr cells were more resistant to hyperthermia at 45 degrees C when incubated with liposomes containing cholesterol. Treatment of V79 cells with oxygenated sterol, a potent inhibitor of endogeneous sterol synthesis, sensitized the hyperthermic cytotoxicity. Our present data present the hypothesis that cellular cholesterol contents are closely correlated with cellular heat toxicity.
Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.
A new technique of intra-arterial catheterization through the inferior epigastric artery using a subcutaneously-implanted silicon reservoir was tried for arterial infusion chemotherapy in patients with cancer located in specific lesions. Eight surgically uncontrollable tumors, consisting of 6 hepatic metastasis, one surgically incurable gastric cancer and one recurrent rectal cancer, were treated by continuous arterial infusion of cis-diamminedichloroplatinum (CDDP) using this new method. Clinical antitumor effect was evaluated by CT scan, sonography or operation. CR, PR and NC were observed in 3, 3 and 2 patients, respectively. No significant difference in CDDP levels in serum was found between CR plus PR and NC cases. Since this method can be done without laparotomy, more patients may benefits from arterial infusion chemotherapy.
We measured expression of the MDR1 gene (also known as the PGY1 gene) in the human gastrointestinal tract. MDR1 messenger RNA (mRNA) levels were elevated in 13 of 15 colorectal carcinoma specimens and in six of 13 gastric carcinoma specimens. Well-differentiated colorectal carcinomas contained significantly higher concentrations of MDR1 mRNA than moderately differentiated colorectal carcinomas. Similarly, moderately differentiated gastric carcinomas contained higher concentrations of MDR1 mRNA than poorly differentiated gastric carcinomas. MDR1 gene expression in normal colorectal and gastric tissues adjacent to carcinomas was similar to that in the carcinomas. MDR1 gene expression in xenografts of colorectal and gastric carcinomas in nude mice was also investigated. Elevated expression of the MDR1 gene was seen in only four of 18 xenografts of colorectal carcinoma and was not seen in any xenografts of gastric carcinoma. P-glycoprotein was distributed over the luminal surface of the colorectal carcinoma. These results imply that the higher levels of MDR1 mRNA found in well-differentiated carcinomas derived from colorectal tissues are the results of increased expression of the MDR1 gene in the luminal surface cells. The level of expression of the MDR1 gene in colorectal and gastric carcinomas appears to correlate with the degree of differentiation and also appears to be affected by transplantation into nude mice.
We have investigated the pharmacological profiles of the novel muscarinic agonists, 1-oxa-8-azaspiro[4.5]decane derivatives, YM796 (2,8-dimethyl-3-methylene) and YM954 (2-ethyl-8-methyl-3-oxo). These compounds, like the putative M1 agonists, RS86 and AF102B, inhibited [3H]pirenzepine binding to cerebral cortical membranes in the micromolar range and weakly inhibited [3H]quinuclidinyl benzylate binding to cerebellar membranes. Their (-) isomers had Hill coefficients lower than 1.0. (+/-)-YM796, (+/-)-YM954 and RS86, but not AF102B, stimulated phosphoinositide hydrolysis in hippocampal slices, an effect which is mainly linked to M1 receptors. (+/-)-YM796 (0.031 mg/kg p.o.) and (+/-)-YM954 (0.016 mg/kg p.o.) reversed the cognitive impairment in nucleus basalis magnocellularis-lesioned rats in a passive avoidance task more effectively than did RS86 and AF102B. Similar results were obtained in scopolamine-treated rats. Finally, (+/-)-YM796 was weaker than (+/-)-YM954 and RS86 in the induction of tremor, hypothermia and contraction of isolated ileum, which are mainly mediated by M2 and/or M3 receptors. These results suggest that (+/-)-YM796, (+/-)-YM954 and RS86 have M1 agonistic activity in central nervous system and that (+/-)-YM796 has relatively weak M2 and/or M3 agonistic activity.
Hb Fukutomi [alpha 126(H9)Asp----Val], a new hemoglobin variant with a high affinity for oxygen (log P50 = 0.201 at pH 7.0, normal = 1.087) was detected in a Japanese male during a screening survey. The amino acid substitution is located in the alpha 1 beta 1 contact of the tetramic molecule. Like other variants of the high oxygen affinity type Hb Fukutomi showed increased resistance to auto-oxidation. The tryptic peptide alpha T-13, that usually forms part of the trypsin-resistant core of the alpha chain, was cleaved off by trypsin in the new variant and released into the soluble fraction.
The Kd value of [3H]YM-09151-2, a potent and highly selective dopamine D-2 antagonist, for binding to rat striatum was about 20 pM (half of that for [3H]spiperone and one-fiftieth of that for [3H]raclopride). The Bmax of [3H]YM-09151-2 binding was about 30% higher than that of [3H]raclopride or [3]spiperone. The ratio (bout 3%) of non-specific to specific binding of [3H]YM-09151-2 was smaller than that of [3H]spiperone and [3H]raclopride. The Hill coefficient values of dopamine D-2 antagonists, SCH23390, mianserin and phentolamine for the inhibition of binding of [3H]YM-09151-2 were near 1.0, and their Ki values with [3H]YM-09151-2 were consistent with those for inhibiting [3H]raclopride and [3H]spiperone binding to D-2 receptors. Thus, [3H]YM-09151-2 may be the most suitable ligand for the labelling of dopamine D-2 receptors in the brain.
Plasma high density lipoproteins (HDL) and their major protein, apolipoprotein (apo) A-I, are deficient in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. As the pathophysiology of subnormal HDL-apo A-I is unclear, we examined kinetic parameters of HDL-apo A-I in WHHL rabbits and normolipidemic Japanese White (control) rabbits. The total plasma mass of HDL-apo A-I was significantly smaller (P less than 0.01) in WHHL rabbits than in controls (less than one-third). Mean fractional catabolic rates (FCR) computed from the specific radioactivity decay curves of HDL-apo A-I were significantly greater (P less than 0.01) in WHHL rabbits than in controls (0.874 +/- 0.052 vs. 0.502 +/- 0.060/day, respectively). Mean synthetic rates of HDL-apo A-I were significantly lower (P less than 0.01) in WHHL rabbits than in controls (8.67 +/- 0.59 vs. 18.14 +/- 3.75 mg/kg body weight/day, respectively). We conclude that the deficiency of plasma HDL-apo A-I in the WHHL rabbits resulted from an increase in FCR and a decrease in apo A-I synthesis.
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Permeability of the blood-brain barrier (BBB) of methylmercury chloride (MMC) intoxicated rat brain was studied in vivo by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). MMC intoxicated rat brain showed the prolonged T1 in the cerebral white matter and prolonged T2 in the cerebellar cortex. After Gd-DTPA administration, T1 of cerebral and cerebellar white matter shortened from 1.647 to 1.344 sec., and 1.290 to 1.223 sec. respectively. On the contrary, T2 showed no change after Gd-DTPA injection. It was concluded that, although the shortening of T1 after Gd-DTPA enhancement was rather little when compared with experimental brain ischemia, the shortening of the relaxation time of the MMC intoxicated rat brain was caused by the increased permeability of BBB.
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Biliary and urinary concentrations and recoveries of 3 different antibiotics (piperacillin (PIPC), cefbuperazone (CBPZ) and cefoperazone (CPZ], after intravenous bolus injection were studied using the crossover method with external cholecystostomies done in order to treat obstructive jaundice due to complete obstruction of the lower biliary tract; the concentrations of antibiotics in bile and urine were determined by means of a high performance liquid chromatography method. Drug concentrations and recoveries in the bile after intravenous injection of these antibiotics were at levels in the order of CPZ greater than CBPZ greater than PIPC. Since our patients were inflicted with various malignancies which made them impaired in terms of biliary excretion of antibiotics, the concentrations of those drugs in the bile were lower than those previously reported by several investigators. However, CBPZ and CPZ showed sufficient levels of excretion into the bile and their amounts were high enough when compared to the value of MIC 80% reported recently against Escherichia coli and Klebsiella pneumoniae, which are known to be main pathogens of biliary system infections. The excretion of CPZ into the bile was invariably found to be 2 times or more as high as the other 2 drugs tested. Concentrations and recoveries of the 3 antibiotics excreted into urine were similar to the cefotaxime excretion, of which into urine had been reported to be excellent. Thus, CBPZ and CPZ appeared to be effective against biliary system infections, even with blockage of antibiotics excretion into the bile.
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