Tamoxifen down-regulates CD36 messenger RNA levels in normal and neoplastic human breast tissues

Tamoxifen (TAM) exerts a long-term suppressive effect on human breast cancer cell proliferation. To determine whether the effects of TAM are mediated by specific gene activation or repression, normal and tumoral human breast tissues obtained before and during TAM treatment were analyzed by differential display technique. Total RNA for differential display analysis was obtained from breast tissues from two women with the diagnosis of estrogen receptor-positive stage II (T2N1M0) infiltrating ductal carcinoma, made by incisional biopsy, followed by modified radical mastectomy performed after a 30-day treatment with TAM (20 mg/day). One 202-bp cDNA band, AP5-1, was present in normal and tumoral biopsy samples, but was absent in breast tissue obtained during TAM treatment, and was confirmed by Northern hybridization, which showed a 2.7-kb band in both patients. The differentially expressed cDNA fragment showed 99% homology to Homo sapiens CD36 gene, a glycoprotein that acts as a receptor for the extracellular matrix proteins thrombospondin-1, collagen types I and IV, and oxidized low-density lipoprotein. These results indicate that the down-regulation of CD36 induced by TAM might represent alternative or additional mechanisms of action of this drug affecting the functions of thrombospondin-1, which is involved in hematogenous tumor spread, invasion and angiogenesis, and oxidized low-density lipoprotein, playing a role in inhibition of arteriosclerosis. The multiple functions affected by the down-regulation of CD36 by TAM warrant the need for additional studies.     

Anomalies in coral reef community metabolism and their potential importance in the reef CO2 source-sink debate

It is not certain whether coral reefs are sources of or sinks for atmospheric CO2. Air-sea exchange of CO2 over reefs has been measured directly and inferred from changes in the seawater carbonate equilibrium. Such measurements have provided conflicting results. We provide community metabolic data that indicate that large changes in CO2 concentration can occur in coral reef waters via biogeochemical processes not directly associated with photosynthesis, respiration, calcification, and CaCO3 dissolution. These processes can significantly distort estimates of reef calcification and net productivity and obscure the contribution of coral reefs to global air-sea exchange of CO2. They may, nonetheless, explain apparent anomalies in the metabolic performance of reefs close to land and reconcile the differing experimental findings that have given rise to the CO2 debate.     

Application of physicians' predictions of meal and exercise effects on blood glucose control to a computer simulation

Our aim was to develop a computer simulator program that allows patients to practise insulin dose and dietary adjustment on a day of planned exercise, and shows the resulting blood glucose response in an average diabetic patient. The degree of blood glucose change predicted by the program was determined from changes predicted by five local specialists in seven hypothetical scenarios involving exercise +/- dietary or insulin dose adjustments. The program was then tested against 18 outside specialists' responses in 7 different scenarios. The program simulates the 24 h glycaemic response after 45 min mild or moderate exercise starting 2 h after meals, as well as changes to this response induced by alterations in dietary carbohydrate and/or insulin dose. Coefficients of variation of specialists' blood glucose predictions were greater for exercise (35% local, 31% outside specialists) than dietary change (7% local, 10% outside specialists; p = 0.002-0.04). The program's predicted change in blood glucose levels in the seven scenarios correlated well with the outside specialists' corresponding mean predictions (r = 0.97; p = 0.0001). We conclude that specialists are less consistent in predicting glycaemic change with exercise than with dietary alteration. Nevertheless it is possible to represent their predictions in a computerized simulator for diabetic patient education.     

Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance

HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndrome's pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome.     

Multi-element, multi-media method for the determination of airborne elemental emissions by inductively coupled plasma atomic emission spectrometry

BACKGROUND AND OBJECTIVE: A number of lasers are available for cutaneous periorbital surgery, yet not all eye shields are appropriate for all applications. We tested a variety of commercially available eye shields to assess their safety features. STUDY DESIGN/MATERIALS AND METHODS: Six commercially available eye protectors were studied. A focused laser was incident upon the shield, and the intensity and exposure duration required for visible damage to the shield were measured. We then measured the temperature on the underside of the eye shield during exposure from the laser. Time-dependent temperature measurements were made with a type-T thermocouple fixed to the eye shield with silicon grease. RESULTS: Thermal response curves and rates of warming for each of the six eye shields were generated. Plastic shields showed significant thermal damage with most of the lasers tested. The metallic shields warmed more slowly and to a lesser degree. CONCLUSION: Overall, the metallic eye shields had the most acceptable safety profile. Many of the plastic shields exhibited significant thermal damage, and therefore we discourage their use in periorbital laser surgery.     

An automated reasoning problem associated with proving claims about programs using Floyd-Hoare inductive assertion methods

Proving claims about behavior of software is essential for the qualification of computer-based systems used in the control of nuclear reactors. For this Problem Corner, we select one of the verification conditions for a C program that initializes an array to zero. We add assertions about the initial conditions and state of the program and about the expected behavior of the program in terms of its state. The modeling and specification technique is the inductive assertion technique of Floyd-Hoare. The program with assertions is then transformed by the source-to-source program transformation system TAMPR into a set of separate verification conditions to be proven by the automated reasoning system. Our experience with this program demonstrates the typical automated reasoning problems we have encountered and illustrates how we have approached solutions to the problems.Work supported by the Civilian Reactor Development Program and the Applied Mathematical Sciences Research subprogram of the Office of Energy Research, U.S. Department of Energy, under Contract No. W-31-109-ENG-38.