Molecular cloning and characterization of ficolin, a multimeric protein with fibrinogen- and collagen-like domains

We have previously identified and purified transforming growth factor-beta 1 (TGF-beta 1)-binding proteins from porcine uterus membranes (Ichijo, H., R?nnstrand, L., Miyagawa, K., Ohashi, H., Heldin, C.-H., and Miyazono, K. (1991) J. Biol. Chem. 266, 22459-22464). One of these TGF-beta 1-binding proteins, with a molecular weight of 40,000, was purified to homogeneity and subjected to amino acid sequence analysis. The amino acid sequences obtained were used to isolate two closely related cDNA clones from a porcine uterus cDNA library. The deduced amino acid sequences revealed that both cDNAs encoded proteins that were mainly composed of fibrinogen-like and collagen-like domains. Therefore, they were denoted ficolin-alpha and ficolin-beta. Expression of ficolin-alpha and -beta cDNA in mammalian cells revealed that ficolin forms dimers, trimers, and several higher order of oligomers, whose molecular weights fit well with those of the purified TGF-beta 1-binding proteins from porcine uterus. Moreover, immunoblotting analysis using a peptide anti-serum against ficolin indicated that the TGF-beta 1-binding proteins identified in porcine uterus are ficolin-alpha, -beta, and their oligomers or closely related molecules. However, recombinant ficolin-alpha and -beta did not bind TGF-beta 1, despite the similarities in molecular weights and immunoreactivity with the material from the natural source. It is possible that a specific posttranslational modification of ficolin or interaction with another component is needed for TGF-beta 1 binding. Analysis by Northern blotting revealed that the expression of ficolin-alpha mRNA is relatively restricted and most abundant in placenta and lung. On the other hand, ficolin-beta was mainly expressed in skeletal muscle. The in vivo functions of ficolin will be discussed.     

A prospective four-year follow-up of neuropsychological function in HIV seropositive and seronegative methadone-maintained patients

The evolution of central nervous system (CNS) impairments associated with human immunodeficiency virus (HIV) infection was assessed by a prospective, longitudinal study of patients in a methadone maintenance clinic. At a mean of 47 months after baseline testing, which included physical exams, HIV antibody testing and a neuropsychological (NP) screening battery, 121 subjects received a second NP assessment. Forty subjects (33%) who were seropositive at baseline showed statistically significant declines in NP function over the 4 years compared with 81 seronegatives, on the Finger Tapping and Trail Making B tests. This relatively long-term follow-up suggests that subtle cognitive deficits develop over time and can be identified early, but their course is slow and appears generally to parallel that of non-CNS symptoms/signs of HIV infection.     

Intake of trans fatty acids and risk of coronary heart disease among women

Trans isomers of fatty acids, formed by the partial hydrogenation of vegetable oils to produce margarine and vegetable shortening, increase the ratio of plasma low-density-lipoprotein to high-density-lipoprotein cholesterol, so it is possible that they adversely influence risk of coronary heart disease (CHD). To investigate this possibility, we studied dietary data from participants in the Nurses' Health Study. We calculated intake of trans fatty acids from dietary questionnaires completed by 85,095 women without diagnosed CHD, stroke, diabetes, or hypercholesterolaemia in 1980. During 8 years of follow-up, there were 431 cases of new CHD (non-fatal myocardial infarction or death from CHD). After adjustment for age and total energy intake, intake of trans isomers was directly related to risk of CHD (relative risk for highest vs lowest quintile 1.50 [95% Cl 1.12-2.00], p for trend = 0.001). Additional control for established CHD risk factors, multivitamin use, and intakes of saturated fat, monounsaturated fat, and linoleic acid, dietary cholesterol, vitamins E or C, carotene, or fibre did not change the relative risk substantially. The association was stronger for the 69,181 women whose margarine consumption over the previous 10 years had been stable (1.67 [1.05-2.66], p for trend = 0.002). Intakes of foods that are major sources of trans isomers (margarine, cookies [biscuits], cake, and white bread) were each significantly associated with higher risks of CHD. These findings support the hypothesis that consumption of partially hydrogenated vegetable oils may contribute to occurrence of CHD.     

Method for treatment of finite-sized dichroic structures using asurface impedance approach

The possibility of using an impedance boundary condition to treat scattering from the edges of dichroic surfaces is discussed. Preliminary results and measurements indicate that this approach may be a viable alternative to the more rigorous element by element methods     

Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses' health study

BACKGROUND: Some studies have suggested that the use of calcium channel blockers may increase the risk of cancer. A possible association of the use of calcium channel blockers with cancer incidence and cancer mortality was addressed using data from the Nurses' Health Study. METHODS: In this study, a total of 18,635 female nurses reported regularly taking at least 1 of 4 cardiovascular medications in 1988: diuretics, beta-blockers, calcium channel blockers, and/or angiotensin-converting enzyme (ACE) inhibitors. Cancer incidence and cancer deaths were ascertained until 1994. RESULTS: During 6 years of follow-up, 852 women were newly diagnosed with cancer and 335 women died of cancer. Women who reported the use of calcium channel blockers had no increased risk of newly diagnosed cancer compared with those taking other cardiovascular drugs (relative risk=1.02; 95% CI 0.83-1.26). The relative risk of dying from cancer associated with the self-reported use of calcium channel blockers was 1.25 (95% CI 0.91-1.72). Relative risks were adjusted for the following self-reported factors: age; weight; height; cholesterol level; systolic and diastolic blood pressure; smoking; alcohol intake; physical activity; menopausal status; postmenopausal hormone use; aspirin use; and history of diabetes, cancer, stroke, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina, and hypertension. Regarding site specific cancer incidence and mortality, only lung cancer incidence was somewhat increased (RR=1.61; 95% CI 0.88-2.96). CONCLUSIONS: These data suggest no important increase in overall cancer incidence or cancer mortality related to the self-reported use of calcium channel blockers.