Correlates of mutagen sensitivity in patients with upper aerodigestive tract cancer.

Although tobacco and alcohol use are the major determinants of upper aerodigestive tract carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens. One explanation may be differences in mutagen sensitivity (as measured by the in vitro bleomycin-induced mutagen sensitivity assay) in patients with squamous cell carcinoma of the upper aerodigestive tract.

Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue.

We have determined the role of cholesteryl ester transfer protein (CETP) in selective uptake of high density lipoprotein (HDL)-derived cholesteryl esters (CE) by human adipose tissue, using organ culture or collagenase-digested adipocytes. Incubation of the fresh tissue fragments with HDL containing [3H]CE or 125I-apoprotein (apo) A-I resulted in significant uptake of HDL-CE-derived label. Addition of recombinant CETP (rCETP) increased CE uptake in a dose-response fashion.

Activity of plasma membrane-recruited Raf-1 is regulated by Ras via the Raf zinc finger.

Ras recruits Raf to the plasma membrane for activation by a combination of tyrosine phosphorylation and other as yet undefined mechanism(s). We show here that the Raf zinc finger is not required for plasma membrane recruitment of Raf by Ras but is essential for full activation of Raf at the plasma membrane. Membrane targeting cannot compensate for the absence of the zinc finger.

Herpes zoster ophthalmicus and the immunocompromised host: a case report and review.

Background: Herpes zoster is the secondary form of varicella zoster virus disease, caused by the reactivation of the dormant virus in the sensory ganglia. It manifests as a unilateral cutaneous dermatitis with a prodromal fever and malaise. Herpes zoster ophthalmicus occurs when the ophthalmic division of the trigeminal nerve becomes afflicted.

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps.

Background & Aims: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps.

Methods: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls.

Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat.

Dexmedetomidine (Dex) is an alpha 2-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is unclear whether cerebral vasoconstriction is mediated by a local effect on cerebral vessels or by a remote neural mechanism. In the present study, we compared the pial arteriole responses to locally and systemically administered Dex with and without local application of the specific alpha 2-adrenergic antagonist atipamezole.

Liver Cell Estrogen Receptor Binding in Prespawning Female LargemouthBass, Micropterus salmoides, Environmentally Exposed toPolychlorinated Biphenyls.

Estrogen-receptor-like binding was partiallycharacterized in liver tissue of prespawning female largemouth bass,Micropterus salmoides (LMB). Saturation and Scatchard analysesexhibited estrogen binding activity with high affinity (Kd in the10(-9) M range) and limited capacity (nuclear = 37.4fmol/g tissue; cytosol = 234 fmol/g tissue).

Dietary surveillance for states and communities.

Information about dietary behaviors, attitudes, and knowledge is important for state and local health agencies because national monitoring lacks the local representativeness and timeliness necessary to catalyze community interest and to design, target, and evaluate dietary intervention programs. Currently, however, both methods and resources are limited for surveying diet in the population of a state or community. Brief assessments are included in the Youth Risk Behavior Surveillance System for adolescents, which is conducted by state departments of education, and in the Behavioral Risk Factor Surveillance System for adults, which is operated by state departments of health.

Colorectal cancer in Egyptian patients under 40 years of age.

Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypt's 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid-Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo.

Plasma kinetics of cholesteryl ester transfer protein in the rabbit. Effects of dietary cholesterol.

The plasma kinetics of recombinant human cholesteryl ester transfer protein (rCETP) were studied in six rabbits before and after cholesterol feeding (0.5% wt/wt). The rCETP, labeled with the use of the Bolton Hunter reagent, was shown to retain neutral lipid transfer activity.

Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogs.

We tested the hypothesis that a centrally administered alpha 2-receptor agonist could alter the cerebrovascular response to hypoxia, without evidence of systemic absorption of the drug. Beagle dogs were anesthetized with 1.4% isoflurane and exposed to hypoxic hypoxia (Pao2 approximately 22 mm Hg) before and after ventricular-cisternal perfusion with mock cerebrospinal fluid (CSF group, n = 5) or dexmedetomidine (100 micrograms/mL; total dose 300 micrograms; DEX group, n = 6).

Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls.

Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester transfer from the HDL-containing plasma fraction to lipoproteins of lighter densities (apo B-containing LP) and plasma cholesteryl ester transfer protein concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n = 11) and normal controls (n = 10) both in the fasting state and 4 h after a standard milk-shake test meal (50g of fat/m of body surface). The percent of [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL containing preparation incubated for 30 min and the [3H]cholesteryl ester transfer was measured upon precipitation of apo B-containing lipoproteins with dextran sulphate/MgCl2 following a 2 h period of plasma incubation with [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma triglyceride concentration and to a similar extent in diabetics and in normal controls.

Intrastriatal AP5 differentially affects behaviors induced by local infusions of D1 vs. D2 dopamine agonists.

Using bilateral infusions into the rat striatum, the effects of the competitive NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5) on behaviors induced by the dopamine (DA) D1 receptor agonist SKF 82526 (fenoldopam) or the D2 receptor agonist quinpirole were determined. These effects were tested in DA-replete (intact) rats and in rats that were receiving injections of the monoamine-depleting drug reserpine. In both intact and reserpinized rats, fenoldopam induced significant sniffing.

Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer. Studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy.

The two major subclasses of HDL contain apo A-I only (Lp A-I) or both apo A-I and apo A-II (Lp A-I/A-II). We have carried out experiments to quantify the participation of Lp A-I and Lp A-I/A-II in the neutral lipid transfer reaction in normal and hypertriglyceridemic subjects. Thirteen hypertriglyceridemic subjects were studied before and after fenofibrate therapy.

Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states.

Hypercholesterolemic women (n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides.

Allelic variation in the gene encoding the cholesteryl ester transfer protein is associated with variation in the plasma concentrations of cholesteryl ester transfer protein.

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins. Mutations that abolish CETP function are associated with very high levels of HDL cholesterol, but the effect of more common allelic variation at this locus is less clear. In this study, we have measured plasma CETP concentration and plasma HDL cholesterol concentrations in 694 individuals from 106 nuclear families.

Association of diet and colorectal adenomatous polyps: dietary fiber, calcium, and total fat.

We conducted a case-control study to investigate the relation between dietary fiber, calcium, and total fat and the risk of colorectal adenomatous polyps. We used a food frequency questionnaire to assess the usual diet for 157 cases and 480 controls. In multivariate analyses, dietary fiber was inversely associated with risk of adenomatous polyps.

Calcium supplementation modifies the relative amounts of bile acids in bile and affects key aspects of human colon physiology.

Use of calcium supplements has increased dramatically in recent years yet little is known about the effect of calcium supplementation on colon physiology. We supplemented 22 individuals with a history of resected adenocarcinoma of the colon, but currently free of cancer, with 2000 or 3000 mg calcium for 16 wk. The effects of supplementation on duodenal bile acids and important fecal characteristics including total fecal output, wet and dry weight, pH, bile acids (in solids and in fecal water), and concentrations and total excretion of calcium, magnesium, phosphates (organic and inorganic), unesterified fatty acids and total fat were determined.

Analysis of cholesteryl ester transfer activity in adipose tissue.

Transfer of cholesteryl ester (CE) between lipoproteins is mediated by a plasma glycoprotein called cholesteryl ester transfer protein (CETP) which plays an important role in reverse cholesterol transport between peripheral tissues and the liver. Adipose tissue is a major site of cholesterol storage and lipoprotein interactions. CE transfer activity in cultured adipose tissue from several species was analyzed by using a CE transfer assay in vitro.

Visual recovery under glare conditions following laser capsulotomy.

The purpose of this study was to look at the changes in Snellen visual acuity and contrast sensitivity under standard and glare conditions before and after Nd:YAG laser capsulotomy. Contrast sensitivity was measured with a Pelli-Robson chart; a Brightness Acuity Tester was used as a glare source. Seventeen pseudophakic patients with no other ocular disease underwent a capsulotomy.

The antihyperglycemic agent englitazone prevents the defect in glucose transport in rats fed a high-fat diet.

The effects of englitazone in male Wistar rats fed a high-fat diet (59% of calories as fat) were compared with control rats fed a high-carbohydrate diet (69% of calories as carbohydrate) (5-15 animals per group). Insulin-stimulated (17 nmol/l) 2-deoxy-D-glucose (2-DG) uptake was inhibited 31% in adipocytes isolated from rats on the high-fat diet for 3 weeks, but englitazone (50 mg/kg for the last 7 days) normalized the response. There was a selective decrease in GLUT4 (54 +/- 5% of high-carbohydrate) in epididymal fat from rats on the high-fat diet for 3 weeks, but englitazone treatment did not reverse the defect in GLUT4 (43 +/- 8% of high-carbohydrate) or increase GLUT1 (81 +/- 12% of high-carbohydrate).

Cholesteryl ester transfer protein (CETP) mRNA abundance in human adipose tissue: relationship to cell size and membrane cholesterol content.

Cholesteryl ester transfer protein (CETP) has a well-defined role in plasma neutral lipid transport. CETP synthesized by human adipose tissue may contribute to the plasma CETP pool. CETP mRNA abundance increases in subcutaneous adipose tissue in response to cholesterol feeding and we have hypothesized that CETP gene expression is regulated by a specific pool of cellular sterol.

Ethical issues in screening and testing for genetic diseases.

New analytic techniques coupled with detailed knowledge of the entire human genome soon will make possible testing of all genes in every person. Concepts of disease will change, and predisease states will be identified for genetic therapies. Patients, physicians, and laboratory personnel will be confronted with ethical and moral issues in the performance of genetic testing.