Distribution and metabolism of leukotriene C4 after cisternal injection in guinea pigs

Following cisternal injection of [3H8]LTC4 into guinea pigs, leukotriene metabolites were identified in the brain, cerebellum, perilymph, blood, liver and kidneys. LTC4 was metabolized into LTD4 and LTE4 in the cerebrospinal fluid and LTE4 was transported into the blood for general circulation and uptake into the liver and kidneys. The excretion of LTE4 from CNS to blood seemed to be the rate-limiting step in the elimination of leukotrienes from the body. Leukotrienes were also transported into the perilymph. The conversion of LTC4 into LTD4 and LTE4 was lower in perilymph as compared to the cerebrospinal fluid, suggesting a rate limiting function of the cochlear aqueduct that can be defined as a cerebrospinal fluid-labyrinth barrier.     

Risk factors and 25 year risk of coronary heart disease in a male population with a high incidence of the disease: the Finnish cohorts of the seven countries study.

OBJECTIVE--To assess the efficacy of high serum cholesterol concentration, raised blood pressure, and smoking as predictors of coronary heart disease. DESIGN--Prospective cohort study of middle aged men conducted over 25 years. SETTING--Finish components of an ongoing international study (seven countries study). PARTICIPANTS--1520 Men who at age 40-59 in 1959 were free of clinically evident heart disease. INTERVENTIONS--At each follow up visit a detailed medical examination including resting electrocardiography was performed, blood pressure and serum total cholesterol concentration were measured, and smoking was assessed. MEASUREMENTS AND MAIN RESULTS--825 Deaths (54% of participants) occurred during follow up, of which 335 were due to coronary heart disease. The hazard ratio for death from coronary heart disease with respect to risk factors at entry were: for serum cholesterol concentrations above 8.4 mmol/l v below 5.2 mmol/l, 2.68 (95% confidence interval 1.62 to 4.42); for systolic blood pressure in the highest quintile v that in the lowest quintile, 2.46 (1.72 to 3.50); and for smoking 10 or more cigarettes daily v never smoking, 1.95 (1.36 to 2.79). The hazard ratios with respect to cholesterol concentrations and blood pressure remained constant during follow up but the ratio with respect to smoking diminished, mainly owing to men giving up the habit. The estimated conditional probability of a 50 year old man dying of coronary heart disease in the next 25 years ranged from 12% among those with the most favourable risk factor profile to 75% among those with the least favourable profile. CONCLUSIONS--High risk factor levels (as determined in this study) in middle aged men may greatly increase the absolute probability of death from coronary heart disease when the period of study is relevant to the human life span.     

Consequences and treatment of ovarian failure after total body irradiation for leukaemia.

OBJECTIVE--To assess the incidence and severity of physical and psychosexual symptoms in young women due to ovarian failure caused by total body irradiation for leukaemia and the women''s response to hormone treatment. DESIGN--Postal questionnaire and interview. SETTING--Leukaemia unit of oncology hospital. PATIENTS--Consecutive series of 46 English speaking women who had developed ovarian failure after total body irradiation and bone marrow transplantation as treatment for leukaemia. RESULTS--Of the 36 responders, 33 reported some symptoms, vaginal dryness being the most common (29). This profoundly affected sexual function. Although 22 women had had sexual intercourse within six months after treatment, 16 were less interested in and 18 experienced difficulties with sexual intercourse. Anxieties about sterility, femininity, and appearance were common and reduced self confidence. Almost half reported that they had changed their social habits and restricted their social activities. Treatment seemed effective in abolishing symptoms in 24 women, but vaginal dryness remained a problem in three. Two women failed to respond and intercourse remained impossible. CONCLUSIONS--Such patients are vulnerable and access to gynaecologists and endocrinologists soon after treatment would be valuable. The optimal treatment regimen and the long term benefits of treatment have yet to be established.     

Economic impact of a nationwide outbreak of salmonellosis: cost-benefit of early intervention.

The recognition and investigation of an outbreak of food poisoning in 1982 due to chocolate contaminated with Salmonella napoli enabled the food that carried the salmonella to be identified and four fifths of the implicated consignment of chocolate to be withdrawn. The economic benefits of prompt intervention in the outbreak have been assessed. The cost of the outbreak was over 0.5 pounds m. It is estimated that five deaths were prevented by the intervention and that 185 admissions to hospital and 29,000 cases of S napoli enteritis were avoided. This successful investigation yielded a 3.5-fold rate of return to the public sector and a 23.3-fold return to society on an investment in public health surveillance. A methodology is described that can be used to estimate the benefits of early intervention in outbreaks of foodborne illness and topics for further research are suggested. It is concluded that public health authorities and industry have much to gain by collaborating in the research into the design of cost effective programmes to prevent foodborne infections.     

Fetal infection after maternal reinfection with rubella: criteria for defining reinfection.

Five cases of asymptomatic maternal reinfection with rubella are described that occurred in England and Wales during 1985-8 and resulted in intrauterine infection. The criteria for diagnosing reinfection are described. In four cases the rubella contact was with the woman''s own children. Two women had therapeutic abortions, rubella virus being recovered from the products of conception, and three were delivered of infants with congenitally acquired disease. Though the risks associated with maternal reinfection with rubella are very small and being measured in a prospective study, it is hoped that the recently introduced augmented programme of rubella vaccination will reduce rubella in the community and therefore this small risk still further.     

The Complex Carbohydrate Structure Database

The Complex Carbohydrate Structure Database (CCSD) and CarbBank, an IBM PC/AT (or compatible) database management system, were created to provide an information system to meet the needs of people interested in carbohydrate science. The CCSD, which presently contains more than 2000 citations, is expected to double in size in the next two years and to include, soon thereafter, all of the published structures of carbohydrates larger than disaccharides.     

The calcium-binding site of clathrin light chains

Clathrin light chains are calcium-binding proteins (Mooibroek, M. J., Michiel, D. F., and Wang, J. H. (1987) J. Biol. Chem. 262, 25-28) and clathrin assembly can be modulated by calcium in vitro. Thus, intracellular calcium may play a regulatory role in the function of clathrin-coated vesicles. The structural basis for calcium's influence on clathrin-mediated processes has been defined using recombinant deletion mutants and isolated fragments of the light chains. A single calcium-binding site, formed by residues 85-96, is present in both mammalian light chains (LCa and LCb) and in the single yeast light chain. This sequence has structural similarity to the calcium-binding EF-hand loops of calmodulin and related proteins. In mammalian light chains, the calcium-binding sequence is flanked by domains that regulate clathrin assembly and disassembly.