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Biomedical subjects

M C Lin

Publications and source records attributed to M C Lin.

At least 235 records · Page 13Linked to original sources

5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells.

5'-Guanylylimidodiphosphate (Gpp(NH)-p) stimulates adenylate cyclase [ATP-pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes isolated from frog and salmon erythrocytes, from rat adrenal, hepatic, and fat cells, and from bovine thyroid cells. The nucleotide acts cooperatively with the various hormones (glucagon, secretin, ACTH, thyrotropin, and catecholamines) that stimulate these adenylate cyclase systems with resultant activities that equal or exceed those obtained with hormone plus GTP or with fluoride ion. In the absence of hormones, Gpp(NH)p is a considerably more effective activator than GTP, and, under certain conditions of incubation, stimulates rat fat cell adenylate cyclase to levels of activity (about 20 nmoles of 3',5'-adenosine monophosphate mg protein per min) far higher than reported hitherto for any adenylate cyclase system examined. The nucleotide activates frog erythrocyte adenylate cyclase when the catecholamine receptor is blocked by the competitive antagonist, propranolol, and activates the enzyme from an adrenal tumor cell line which lacks functional ACTH receptors. In contrast, Gpp(NH)p does not stimulate adenylate cyclase in extracts from Escherichia coli B. Gpp(NH)p appears to be a useful probe for investigating the mechanism of hormone and nucleotide action on adenylate cyclase systems in eukaryotic cells.

Adenylyl Cyclases↗

The inhibition of plant and animal adenosine 3':5'-cyclic monophosphate phosphodiesterases by a cell-division-promoting substance from tissues of higher plant species.

One member of a new class of cell-division-promoting factors, that has been given the trivial name of cytokinesin I, is a potent inhibitor of adenosine 3':5'-cyclic monophosphate phosphodiesterases of both plant and animal origin. Since an adenylate cyclase has been demonstrated in this study to be present in plant cells, the results suggest that cytokinesin I may be exerting its biological effects in promoting division in cells of higher plant species as a regulator of adenosine 3':5'-cyclic monophosphate.

Adenylyl Cyclases↗

Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites.

Diallyl sulfide, a major flavor ingredient from garlic, was previously shown to inhibit chemically induced carcinogenesis and cytotoxicity in animal model systems. It modulated cytochrome P-450 compositions by inactivating P-450 2E1 and inducing P-450 2B1. The present studies examined the inhibition of P-450 2E1 mediated p-nitrophenol hydroxylase activity by diallyl sulfide and its putative metabolites diallyl sulfoxide and diallyl sulfone (DASO2). Each compound displayed competitive inhibition of p-nitrophenol hydroxylase activity in incubations using liver microsomes from acetone-pretreated male Sprague-Dawley rats. Preincubation of the microsomes with DASO2 inactivated p-nitrophenol hydroxylase activity in a process that was time- and NADPH-dependent and saturable, exhibited pseudo-first-order kinetics, was protected by alternate substrate, was accompanied by a loss of microsomal P-450-CO binding spectrum, and was unaffected by exogenous nucleophile. The Ki value for DASO2 was 188 microM and the maximal rate of inactivation was 0.32 min-1. DASO2 was ineffective in the inactivation of ethoxyresorufin dealkylase, pentoxyresorufin dealkylase, or benzphetamine demethylase activity. Purified P-450 2E1 in a reconstituted system was inactivated in a time- and NADPH-dependent manner by DASO2. The metabolic conversion of diallyl sulfide to the sulfoxide and sulfone was observed in vivo and in vitro. The results suggest that diallyl sulfide inhibits the metabolism of P-450 2E1 substrates by competitive inhibition mechanisms and by inactivating P-450 2E1 via a suicide-inhibitory action of DASO2.

Allyl Compounds↗

Intravascular hematocrit effect in cross-sectional CT imaging.

Venous fluid-fluid levels were seen on CT or MR of three patients being evaluated for possible thrombosis. In all three cases, further investigation (by ultrasonography, venography, or surgery) revealed the cause of the fluid-fluid level to be slowly flowing blood without thrombosis. On CT done after intravenous contrast medium administration, the nondependent half of the vessel was denser than the dependent half. In an attempt to confirm this MR and CT picture and, particularly, to explain the dense upper half on CT, we conducted an in vitro study. Our study confirmed that when blood with diatrizoate sodium is not clotted and allowed to settle, a similar fluid-fluid level is observed by CT imaging. Our results indicate that an intravascular fluid-fluid level seen on cross-sectional images represents slowly flowing blood, not thrombosis.

Adult↗

Recovery of motile sperm using the osmolality-gradient technique.

A simple, effective method for collecting motile sperm from ejaculates is developed. One hundred semen samples were obtained from both fertile and infertile men. Following initial semen dilution (1: 1) to 4 mL in a hypoosmotic medium (210 mOsm/kg), the mixture was layered into the specially designed tube filled with 1 mL recovery medium in the bottom and 1 mL isolation medium in the second layer to form three discrete layers. During the next hour the highly motile sperm out-distanced the other seminal contents to reach the bottom of the tube. Compared with the parent ejaculates, the recovered specimens exhibited an increased percentage of motile sperm with significantly enhanced sperm velocity and linearity (p less than .001). This method isolated motile sperm with higher velocity than those obtained using the swim-up technique.

Humans↗

Concomitant splenectomy for hypersplenic thrombocytopenia in hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: Resection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis and hypersplenic thrombocytopenia (HSTC) is risky. Controversy exists concerning the role of concomitant splenectomy for HSTC in cirrhotic patients undergoing hepatectomy for HCC. METHODOLOGY: During the past 10 years, 294 patients have undergone hepatic resection for HCC in our department. Among them, 11 cirrhotic patients with severe HSTC (platelet count < or = 80000/mm3) underwent splenectomy simultaneously. The clinical outcomes were retrospectively reviewed. RESULTS: The resected spleen weighed 479 +/- 242 g. The post-operative mortality and morbidity were 9.1% and 27.3%, respectively. In all patients, the platelet count was elevated to above 100000/mm3, and serum total bilirubin was significantly lowered within 1 week of operation. The overall 5-year actuarial and disease-free survival rates were 66.7%. None of the patients developed severe infectious complications during the follow-up period. CONCLUSIONS: Concomitant splenectomy for severe HSTC in cirrhotic patients undergoing hepatectomy for HCC is justified as the benefits of concomitant splenectomy by far surpass the adverse effects.

Aged↗

Is hepatic resection absolutely contraindicated for hepatocellular carcinoma in Child-Pugh class C cirrhotic patients?

BACKGROUND/AIMS: Liver resection for hepatocellular carcinoma (HCC) in Child-Pugh class C cirrhotic patients is considered to be high risk and even contraindicated. This study examined our results of hepatectomy for HCC in such cirrhotic patients. METHODOLOGY: A retrospective review of the clinicopathological features, as well as early and late resection results of Child-Pugh class A (n = 181) and class C patients (n = 13) were compared. The extent of hepatectomy was based on the pre-operative liver function test and indocyanine-green (ICG) clearance rate. RESULTS: The tumor size in class C patients was smaller than that in class A patients. There were no significant differences with regard to operative blood loss, amount of blood transfusion, operative morbidity or mortality. The surgical margins of class C patients were narrower (p = 0.003). The tumors of class C patients had higher incidences of well-formed capsules and absence of satellite nodules. The 5-year disease-free and actuarial survival rates of class A and C patients were 35.4% and 40.7% (p = 0.28), and 48% and 50% (p = 0.13), respectively. CONCLUSIONS: Not all HCCs in Child-Pugh class C cirrhotic patients are contraindicated for liver resection. In the absence of uncontrollable ascites, marked jaundice and encephalopathy, surgical resection is still justified in some selected cases, in spite of a narrow surgical margin.

Actuarial Analysis↗