Organochlorine exposure and risk of breast cancer

BACKGROUND: Some organochlorine compounds may have weak oestrogenic effects and are, therefore, suspected of increasing the risk of breast cancer. We assessed prospectively the risk of breast cancer in relation to serum concentrations of several organochlorine compounds. METHODS: In 1976, serum samples from 7712 women were obtained from participants in the Copenhagen City Heart Study as part of physical examinations and interviews about lifestyle factors. During 17 years of follow-up, 268 women developed invasive breast cancer. Each woman with breast cancer was matched with two breast-cancer-free women from the remaining cohort. We analysed in 1996-97 the serum samples from 240 women with breast cancer and 477 controls. FINDINGS: Dieldrin was associated with a significantly increased dose-related risk of breast cancer (adjusted odds ratio 2.05 [95% CI 1.17-3.57], p for trend 0.01). Beta-hexachlorocyclohexane increased risk slightly but not significantly (p for trend 0.24). There was no overall association between risk of breast cancer and p,p'-dichlorodiphenyltrichloroethane or metabolites or for polychlorinated biphenyls. Exclusion of women with breast cancer diagnosed within 5 years of blood sampling strengthened the result for dieldrin, but did not affect the other results. INTERPRETATION: These findings support the hypothesis that exposure to xeno-oestrogens may increase the risk of breast cancer.     

Correction of hypoalphalipoproteinemia in LDL receptor-deficient rabbits by lecithin:cholesterol acyltransferase

Familial hypercholesterolemia (FH), a disease caused by a variety of mutations in the low density lipoprotein receptor (LDLr) gene, leads not only to elevated LDL-cholesterol (C) concentrations but to reduced high density lipoprotein (HDL)-C and apolipoprotein (apo) A-I concentrations as well. The reductions in HDL-C and apoA-I are the consequence of the combined metabolic defects of increased apoA-I catabolism and decreased apoA-I synthesis. The present studies were designed to test the hypothesis that overexpression of human lecithin:cholesterol acyltransferase (hLCAT), a pivotal enzyme involved in HDL metabolism, in LDLr defective rabbits would increase HDL-C and apoA-I concentrations. Two groups of hLCAT transgenic rabbits were established: 1) hLCAT+/LDLr heterozygotes (LDLr+/-) and 2) hLCAT+/LDLr homozygotes (LDLr-/-). Data for hLCAT+ rabbits were compared to those of nontransgenic (hLCAT-) rabbits of the same LDLr status. In LDLr+/- rabbits, HDL-C and apoA-I concentrations (mg/dl), respectively, were significantly greater in hLCAT+ (62 +/- 8, 59 +/- 4) relative to hLCAT- rabbits (21 +/- 1, 26 +/- 2). This was, likewise, the case when hLCAT+/ LDLr-/- (27 +/- 2, 19 +/- 6) and hLCAT-/LDLr-/- (5 +/- 1, 6 +/- 2) rabbits were compared. Kinetic experiments demonstrated that the fractional catabolic rate (FCR, d(-1)) of apoA-I was substantially delayed in hLCAT+ (0.376 +/- 0.025) versus hLCAT- (0.588) LDLr+/- rabbits, as well as in hLCAT+ (0.666 +/- 0.033) versus hLCAT- (1.194 +/- 0.138) LDLr-/- rabbits. ApoA-I production rate (PR, mg x kg x d(-1)) was greater in both hLCAT+/LDLr+/- (10 +/- 2 vs. 6) and hLCAT+/LDLr-/- (9 +/- 1 vs. 4 +/- 1) rabbits. Significant correlations (P < 0.02) were observed between plasma LCAT activity and HDL-C (r = 0.857), apoA-I FCR (r = -0.774), and apoA-I PR (r = 0.771), while HDL-C correlated with both apoA-I FCR (-0.812) and PR (0.751). In summary, these data indicate that hLCAT overexpression in LDLr defective rabbits increases HDL-C and apoA-I concentrations by both decreasing apoA-I catabolism and increasing apoA-I synthesis, thus correcting the metabolic defects responsible for the hypoalphalipoproteinemia observed in LDLr deficiency.     

52 Gb/s 16:1 transmitter in 0.13 μm SiGe BiCMOS technology

A52-Gb/s 16:1 quarter-rate clocking transmitter for high-speed serial data transmission is designed to utilise 0.13-mum SiGe bipolar complementary metal-oxide-semiconductor (BiCMOS) technology. The quarter-rate transmitter consists of a 16:1 multiplexer (MUX), a voltage-controlled ring oscillator, a phase-locked loop (PLL), a pseudorandom data generator and an output amplifier. The voltage-controlled ring oscillator has a wide tuning range from 11 to 22 GHz with feedforward loop and delay interpolation. A continuous model of a third-order PLL is developed and used to optimise loop filter parameters and to estimate the PLL performance in a simulation. The PLL achieves a low phase noise of -124.6 dBc/Hz at 1 MHz offset. The 16:1 MUX features quarter-rate clock multiplexing with multi-phase voltage-controlled oscillator clocks. In the design of a 16:1 MUX, an edge-channelling 4:1 MUX is used to alleviate a duty cycle and a jitter problem.     

Limb girdle muscular dystrophy: a pathological and immunohistochemical reevaluation

We investigated the involvement of IL-8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL-8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8 inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the time-course of which preceded that of LPS-induced delayed VP. Production of IL-8 in LPS-pleurisy was inhibited with anti-tumor necrosis factor alpha (TNF-alpha), whereas the production of TNF-alpha was not affected with anti-IL-8. Injection of IL-8 did not induce TNF-alpha production and anti-TNF-alpha had no effect on IL-8-induced VP. Injection of homologous TNF-alpha induced IL-8 production and VP, and TNF-alpha-induced delayed VP was blocked with anti-IL-8. These results indicate important roles of IL-8 in LPS-induced delayed VP and that TNF-alpha causes the delayed VP through the production of IL-8.     

Laboratory evaluation of molluscicidal activity of extracts from Cotula cinerea (L) and Quercus lusitania var. infectoria galls (Oliv.)

In this work, we have studied the molluscicidal activity of different extracts obtained from Cotula cinerea and Quercus lusitania var. infectoria galls. The hydroalcoholic extract of Cotula cinerea, acetonic extract and gallotanin of Quercus infectoria galls have presented high activity against Bulinus truncatus. The hydroalcoholic extract of Cotula cinerea was fractionated by chromatography on silica gel column. We have isolated two very active fractions at concentrations respectively of 52.5 and 27.5 ppm.     

Identification of ultradilute dopants in ceramics

The properties of ceramic materials are strongly influenced by the presence of ultradilute impurities (dopants). Near-edge X-ray absorption fine structure (NEXAFS) measurements using third-generation synchotron sources can be used to identify ultradilute dopants, provided that a good theoretical tool is available to interpret the spectra. Here, we use NEXAFS analysis and first-principles calculations to study the local environments of Ga dopants at levels of 10 p.p.m in otherwise high-purity MgO. This analysis suggests that the extra charge associated with substitutional Ga on a Mg site is compensated by the formation of a Mg vacancy. This defect model is then confirmed by positron lifetime measurements and plane-wave pseudopotential calculations. This powerful combination of techniques should provide a general method of identifying the defect states of ultradilute dopants in ceramics.     

Embryo deadenylation element-dependent deadenylation is enhanced by a cis element containing AUU repeats

The deadenylation of maternal mRNAs in the Xenopus embryo is a sequence-specific process. One cis element that targets maternal mRNAs for deadenylation after fertilization is the embryo deadenylation element (EDEN). This element, composed of U/R repeats, is specifically bound by a protein, EDEN-BP. In the present study we show that the rate at which an RNA containing an EDEN is deadenylated can be increased by the presence of an additional cis element composed of three AUU repeats. This effect was observed for a natural EDEN (c-mos) and two synthetic EDENs. Hence, the enhancement of EDEN-dependent deadenylation conferred by the (AUU)3 motif is not due to an interaction with a particular EDEN sequence. Mutation of the (AUU)3 motif abrogated the enhancement of EDEN-dependent deadenylation. These data indicate that the rate at which a specific maternal mRNA is deadenylated in Xenopus embryos is probably defined by a cross talk between multiple cis elements.     

Esophageal replacement for atresia without fistula

Rectal excision for non-malignant conditions using a posterior sagittal approach is described in three patients. The technique allows excellent exposure of the rectum, meticulous haemostasis, minimal risk of pelvic nerve injury and accurate reconstruction of the pelvic floor without the need for drainage.