Body weight and risk of myocardial infarction and death in the adult population of eastern Finland.

Body mass index (weight (kg) divided by height squared (m2] and its association with the risk of myocardial infarction and death from all causes were studied prospectively in a randomly selected population sample in eastern Finland aged 30-59 at outset in 1972. The study population consisted of 3786 men and 4120 women. The participation rate in the survey in 1972 was over 90%. All deaths and admissions to hospital in the sample were obtained from the National Death Certificate and Hospital Discharge Registers. During the seven years of follow up until 1978, 170 men and 52 women had acute myocardial infarction, and during the nine years up to 1980, 223 men and 92 women died. Independent of age, men with a body mass index of 28.5 or more had a significantly higher incidence of acute myocardial infarction. This effect was also independent of smoking but not independent of biological coronary risk factors--that is, serum cholesterol concentration and blood pressure. In the analysis stratified for smoking in men the body mass index total mortality curve was J shaped among non-smokers, whereas smoking entirely outweighed body mass index as a predictor of death. Body mass index did not contribute significantly to the risk of either acute myocardial infarction or death in women. It is concluded that a body mass index of around 29.0-31.0 or more is not only a marker for coronary risk factors but is also a predictor of acute myocardial infarction in men.     

Attractiveness of women's body odors over the menstrual cycle: the role of oral contraceptives and receiver sex

It is a long held assumption that women have concealed ovulation,which means that men do not know when women's menstrual cyclesare in their most fertile phase. Recent empirical results haveprovided evidence that ovulation may not be totally concealedfrom pair-bonded males, but the generality and the mechanismsof the finding demand further study. To examine the possibleadaptive value of the phenomenon, it is necessary to study whetherthe ability to detect ovulation is confined to males. We studiedthese questions in an experiment in which male and female ratersrated the sexual attractiveness and intensity of T-shirts' odorsworn by 42 women using oral contraceptives (pill users) andby 39 women without oral contraceptives (nonusers). Males ratedthe sexual attractiveness of nonusers highest at midcycle. However,female raters showed only a nonsignificant trend for this relationship.Neither sex rated attractiveness of the odors of pill usersaccording to their menstrual cycle. The results indicate thatmen can use olfactory cues to distinguish between ovulatingand nonovulating women. Furthermore, the contrasting resultsbetween pill users and nonusers may indicate that oral contraceptivesdemolish the cyclic attractiveness of odors. Together, thesefindings give more basis for the study of the role of odorsin human sexual behavior.     

HrpN of Erwinia amylovora functions in the translocation of DspA/E into plant cells

The type III secretion system (T3SS) is required by plant pathogenic bacteria for the translocation of certain bacterial proteins to the cytoplasm of plant cells or secretion of some proteins to the apoplast. The T3SS of Erwinia amylovora, which causes fire blight of pear, apple and other rosaceous plants, secretes DspA/E, which is an indispensable pathogenicity factor. Several other proteins, including HrpN, a critical virulence factor, are also secreted by the T3SS. Using a CyaA reporter system, we demonstrated that DspA/E is translocated into the cells of Nicotiana tabacum'Xanthi'. To determine if other T3-secreted proteins are needed for translocation of DspA/E, we examined its translocation in several mutants of E. amylovora strain Ea321. DspA/E was translocated by both hrpW and hrpK mutants, although with some delay, indicating that these two proteins are dispensable in the translocation of DspA/E. Remarkably, translocation of DspA/E was essentially abolished in both hrpN and hrpJ mutants; however, secretion of DspA/E into medium was not affected in any of the mentioned mutants. In contrast to the more virulent strain Ea273, secretion of HrpN was abolished in a hrpJ mutant of strain Ea321. In addition, HrpN was weakly translocated into plant cytoplasm. These results suggest that HrpN plays a significant role in the translocation of DspA/E, and HrpJ affects the translocation of DspA/E by affecting secretion or stability of HrpN. Taken together, these results explain the critical importance of HrpN and HrpJ to the development of fire blight.     

Calpain 1 and 2 are required for RNA replication of echovirus 1

Calpains are calcium-dependent cysteine proteases that degrade cytoskeletal and cytoplasmic proteins. We have studied the role of calpains in the life cycle of human echovirus 1 (EV1). The calpain inhibitors, including calpeptin, calpain inhibitor 1, and calpain inhibitor 2 as well as calpain 1 and calpain 2 short interfering RNAs, completely blocked EV1 infection in the host cells. The effect of the inhibitors was not specific for EV1, because they also inhibited infection by other picornaviruses, namely, human parechovirus 1 and coxsackievirus B3. The importance of the calpains in EV1 infection also was supported by the fact that EV1 increased calpain activity 3 h postinfection. Confocal microscopy and immunoelectron microscopy showed that the EV1/caveolin-1-positive vesicles also contain calpain 1 and 2. Our results indicate that calpains are not required for virus entry but that they are important at a later stage of infection. Calpain inhibitors blocked the production of EV1 particles after microinjection of EV1 RNA into the cells, and they effectively inhibited the synthesis of viral RNA in the host cells. Thus, both calpain 1 and calpain 2 are essential for the replication of EV1 RNA.     

Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion

Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.     

The energy charge in wild-type and respiration-deficient chinese hamster cell mutants

High pressure liquid chromatography was used to determine the base, nucleoside, and nucleotide levels in wild type and a series of respiration-deficient Chinese hamster cell mutants. From this analysis the size of the total adenylate pool and the energy charge could be calculated for each cell line. We find a constant energy charge, as expected, but the adenylate pool seems to be considerably lower in the respiration-deficient mutants.     

Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration--a novel role for alphaIIb integrin and tirofiban

The expression of collagen XVII (BP180), a transmembrane hemidesmosomal component, is upregulated in invasive areas of epithelial tumors. The collagenous ectodomain of collagen XVII is cleaved from the plasma membrane of keratinocytes and malignant epithelial cells. The released ectodomain is predicted to regulate cell detachment, differentiation, and motility. We report that the cell adhesion domain of collagen XVII, Col15, is able to chemotactically attract invasive HSC-3 SCC cells but not keratinocytes. Analysis of integrin expression revealed that HSC-3 cells, unlike keratinocytes, express alphaIIb integrin, a platelet-specific fibrinogen receptor. We show that this novel chemotactic function is mediated by the known Col15-binding integrins alpha5beta1 and alphav and the platelet integrin alphaIIb. Moreover, we report that tirofiban, a FDA-proved alphaIIb integrin-blocking drug widely used for the therapy of acute coronary ischaemic syndrome and the prevention of thrombotic complications, inhibits the Col15 chemotaxis of HSC-3 carcinoma cells. Together, these data demonstrate a novel interaction between collagen XVII and alphaIIb integrin and also suggest a possibility to use tirofiban to inhibit the invasion and progression of alphaIIb expressing SCC tumors.     

Change in risk factors for coronary heart disease during 10 years of a community intervention programme (North Karelia project).

A comprehensive community based programme to control cardiovascular diseases was started in North Karelia, Finland, in 1972. Reductions in smoking, serum cholesterol concentrations, and blood pressure were among the central intermediate objectives. The effect of the programme during the 10 year period 1972-82 was evaluated by examining independent random population samples at the outset (1972) and five (1977) and 10 (1982) years later both in the programme and in a matched reference area. Over 10 000 subjects were studied in 1972 and 1977 (participation rate about 90%) and roughly 8000 subjects in 1982 (participation rate about 80%). Analyses were conducted of the estimated effect of the programme on the risk factor population means by comparing the baseline and five year and 10 year follow up results in the age range 30-59 years. The effect of the programme (net reduction in North Karelia) at 10 years among the middle aged male population was estimated to be a 28% reduction in smoking (p less than 0.001), a 3% reduction in mean serum cholesterol concentration (p less than 0.001), a 3% fall in mean systolic blood pressure (p less than 0.001), and a 1% fall in mean diastolic blood pressure (p less than 0.05). Among the female population the reductions were respectively, 14% (NS), 1% (NS), 5% (p less than 0.001), and 2% (p less than 0.05). During the first five years of the project (1972-7) the programme effectively reduced the population mean values of the major coronary risk factors. At 10 years the effects had persisted for serum cholesterol concentrations and blood pressure and were increased for smoking.     

Predominance of outcrossing in Lymnaea stagnalis despite low apparent fitness costs of self-fertilization

We have quantified the natural mating system in eight populations of the simultaneously hermaphroditic aquatic snail Lymnaea stagnalis, and studied the ecological and genetic forces that may be directing mating system evolution in this species. We investigated whether the natural mating system can be explained by the availability of mates, by the differential survival of self- and cross-fertilized snails in nature, and by the effects of mating system on parental fecundity and early survival. The natural mating system of L. stagnalis was found to be predominantly cross-fertilizing. Density of snails in the populations had no relationship with the mating system, suggesting that outcrossing rates are not limited by mate availability at the population densities observed. Contrary to expectations for outcrossing species, we detected no evidence for inbreeding depression in survival in nature with inferential population genetic methods. Further, experimental manipulations of mating system in the laboratory revealed that self-fertilization had no effect on parental fecundity, and only minor effects on offspring survival. Predominance of cross-fertilization despite low apparent fitness costs of self-fertilization is at odds with the paradigm that high self-fertilization depression is necessary for maintenance of cross-fertilization in self-compatible hermaphrodites.