Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.     

Affordances, perceptual complexity, and the development of tool use.

Perceiving the affordance of a tool requires the integration of several complementary relationships among actor, tool, and target. Higher order affordance structures are introduced to deal with these forms of complex action from an ecological-realist point of view. The complexity of the higher order affordance structure was used to predict the difficulty of perceiving the tool function. Predictions were tested in 3 experiments involving children between 9 mo and 4 yrs old. In a classical tool use task dating back to W. K?hler (1921), a desirable target was obtained by using a hook as a tool. The relative positions of the hook and the target were systematically varied to obtain structures differing in complexity. The observed difficulty of the task was found essentially in accordance with the theoretical complexity of the higher order affordance structures involved in perceiving the tool function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The association of leukocytes with secondary brain injury

Shock increases mortality from brain injuries, but the mechanism is poorly understood. We hypothesized that brain injury followed by shock and resuscitation leads to a secondary reperfusion injury mediated in part by polymorphonuclear leukocytes (PMNs). To validate this hypothesis, we studied cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebral blood flow (CBF), cortical water content (CWC), and hemodynamic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock. Cerebral PMN accumulation (CPMN) in the injured and uninjured hemispheres was determined histologically from the total PMNs in five high-power fields (400x). Twenty-nine mature swine were randomized to four groups. Group 1, the control group, was instrumented only. Group 2 animals had a brain injury alone and were studied for 24 hours. Group 3 animals had a brain injury and hemorrhagic shock. Group 4 animals had hemorrhagic shock alone. Brain injury followed by shock caused a significantly greater ICP and a significantly lower CBF than brain injury or shock alone. There was no significant difference in CPP between groups after resuscitation. The CWC of the lesioned area was similar in both brain-injured groups but was significantly increased when compared with the controls and the shock-only group. The CWC of the nonlesioned hemisphere was higher in group 3 than in group 2. The CPMN in both hemispheres in group 3 was significantly greater than in either group 2 or group 4. There was a significant positive correlation between CPMN and both ICP and CWC, and a significant negative correlation between CPMN and CBF. These data suggest an association between CPMN accumulation and secondary brain injury.     

Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group

26 previously treated patients with progressive recurrent small cell lung cancer (SCLC) were given vinorelbine (Navelbine), 30 mg/m2 weekly. All patients had responded to first-line chemotherapy and were off therapy for at least 3 months. Partial response was observed in 4 out of 25 eligible patients (16%; 95% confidence interval 4-36%), stable disease in 7 patients and progression in 12 patients. The limiting toxicity was a non-cumulative leucopenia (80%, 32% WHO grade 3-4). Reaction at the site of injection was observed in 5 patients, causing treatment discontinuation in 2 cases. Other non-haematological toxicities were moderate. These results suggest acceptable toxicity and some antitumour activity of vinorelbine in pretreated SCLC patients.     

The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.     

Gel-entrapment of perfluorocarbons: a fluorine-19 NMR spectroscopic method for monitoring oxygen concentration in cell perfusion systems

Oxygenation is a major determinant of the physiological state of cultured cells. 19F NMR can be used to determine the oxygen concentration available to cells immobilized in a gel matrix by measuring the relaxation rate (1/T1) of perfluorocarbons (PFC) incorporated into the gel matrix. In calcium alginate gel beads without cells the relaxation rate (1/T1) of the trifluoromethyl group of perfluorotripropylamine (FTPA) varies linearly with oxygen concentration, with a slope of 1.26 +/- 0.15 x 10(-3) s-1 microM-1 and an intercept of 0.50 +/- 0.04 s-1. During perfusion with medium equilibrated with 95%/5% O2/CO2, changes in PFC T1s indicate that the average oxygen concentration was reduced from 894 +/- 102 microM in the absence of cells to 476 +/- 65 microM and 475 +/- 50 microM in the presence of 0.7 x 10(8) EMT6/Ro and RIF-1 murine tumor cells per milliliter of gel, respectively. The presence of 0.2 microliters of FTPA/ml of gel had no effect on the energy status of the cells as indicated by 31P NMR spectra. To calculate oxygen gradients within the beads from the average PFC T1 of the sample, a mathematical model was used assuming that oxygen is the limiting nutrient for cell metabolism and that the cellular oxygen consumption rate is independent of oxygen concentration. Data for EMT6/Ro cells were fit using experimentally determined perfusion parameters together with literature values for cell volume and oxygen consumption rate.(ABSTRACT TRUNCATED AT 250 WORDS)