How inbreeding affects productivity in Europe.
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Biomedical subjects
Publications and source records attributed to M Soler.
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The relation between various types of fiber and oral, pharyngeal and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in Italy. Cases were 271 hospital patients with incident, histologically confirmed oral cancer, 327 with pharyngeal cancer and 304 with esophageal cancer. Controls were 1,950 subjects admitted to the same network of hospitals as the cases for acute, nonneoplastic diseases. Cases and controls were interviewed during their hospital stay using a validated food frequency questionnaire. Odds ratios (OR) were computed after allowance for age, sex, and other potential confounding factors, including alcohol, tobacco consumption, and energy intake. The ORs for the highest vs. the lowest quintile of intake of oral, pharyngeal and esophageal cancer combined were 0.40 for total (Englyst) fiber, 0.37 for soluble fiber, 0.52 for cellulose, 0.48 for insoluble non cellulose polysaccharide, 0.33 for total insoluble fiber and 0.38 for lignin. The inverse relation were similar for vegetable fiber (OR = 0.51), fruit fiber (OR = 0.60) and grain fiber (OR = 0.56), and were somewhat stronger for oral and pharyngeal cancer than for esophageal cancer. The ORs were similar for the two sexes and strata of age, education, alcohol and tobacco consumption, and total non-alcohol energy intake. Our study indicates that fiber intake may have a protective role on oral, pharyngeal and esophageal cancer.
The aim of this study was to analyze the effects of a polyunsaturated n-6 high-fat diet on rat DMBA-induced breast cancer at different stages of the carcinogenesis and to investigate if changes in the tumor fatty acid composition are one of the mechanisms by which dietary lipids could exert their effects. 14 fatty acids were evaluated in 6 lipid fractions. The results firstly showed that this high-fat diet stimulated the malignant mammary tumor growth, mainly all in the promotion group. The tumor lipid analysis indicated: 1) that each lipid fraction presented distinct major fatty acids (>5%) which were not the most abundant in the diet, except in the case of the triacylglicerides, suggesting the different resistance to dietary fatty acid modification of the tumor lipid fractions; 2) a higher arachidonic acid content in the fractions with less linoleic acid, above all in phospholipids, particularly in the phosphatidylethanolamine, indicating a different efficiency of conversion; 3) the three most abundant fatty acids in the dietary lipid (18:2n-6, 18:1n-9 and 16:0) were those which essentially displayed the differences between groups; thus, the high-fat diet changed the tumor lipid profile, increasing the 18:2n-6 relative content and decreasing that of the 18:1n-9; differences were significant in phosphatidylcholine, free fatty acids and triacylglycerides. Any change was obtained in the phosphatidylinositol. The greatest number of differences was found in the promotion group. Taken as a whole, our results suggest the different roles of lipid fractions in breast cancer cells and an association between cancer malignancy and the content of linoleic and oleic acids.
Asthma is a major public health problem, with variable trends in several countries. We analysed mortality trends from asthma in Italy and Spain between 1980 and 1996. Overall asthma-related mortality at all ages increased between 1980 and 1987 in both sexes in Italy, from 16.6 in 1980-1981 to 29.0 in 1986-1987 per million males, and from 8.0 in 1980-1981 to 13.8 in 1986-1987 per million females, but decreased thereafter to reach 14.6 per million in males and 8.7 in females in 1996. The downward trends after 1987 were consistent in middle age and elderly population, but asthma mortality tended to rise in children and young adults over the last few years. In Spain, overall age-standardized mortality rates from asthma declined in men from 37.8 in 1980-1981 to 10.1 in 1996, and from 19.5 in 1980-1981 to 13.2 per million females in 1996. In women, the fall in mortality rates was smaller, and overall mortality was higher than in males since early 1990s. Trends of asthma mortality in Italy and Spain were favourable over the last decade.
BACKGROUND: Prostaglandin H2 (PGH2) is the precursor of the other prostanoids and exhibits a vasoconstricting activity. Glomerular mesangial cells are an important source of vasoactive prostanoids in kidney. Hence, the present investigation focused on the release of untransformed PGH2 by rat glomerular mesangial cells (RGMCs). METHODS: Synthesis of prostanoid by resting and interleukin-1beta (IL-1beta)-treated (overnight) RGMCs from exogenous or endogenous arachidonic acid (AA) was assessed by high-performance liquid chromtography or enzyme immunoassay, respectively. Cyclo-oxygenase isoforms were determined by Western blotting. Release of untransformed PGH2 from exogenous AA was evaluated in RGMCs and intact glomeruli as the difference of PGF2alpha formed in the incubations performed in the presence and in the absence of SnCl2 or measuring the ability of aspirin-treated platelets to form thromboxane B2 (TXB2) in mixed incubations of platelets and RGMCs or glomeruli. RESULTS: The prostanoids formed by RGMCs were PGE2, PGF2alpha, PGI2 and PGD2. SnCl2 totally deviated formation of PGE2 and PGD2 toward PGF2alpha in resting RGMCs, whereas PGE2 was only partially deviated toward PGF2alpha in IL-1beta-treated RGMCs. The PGE2/PGD2 ratio in resting RGMCs was similar to that expected for nonenzymatic isomerization of PGH2, whereas this ratio was higher in IL-1beta-treated RGMCs, suggesting the induction of PGE synthase by IL-1beta. Aspirin-treated platelets formed TXB2 when either RGMCs or intact glomeruli were present in the incubation and formation of TXB2 was approximately fourfold higher with IL-1beta-treated RGMCs or glomeruli. CONCLUSIONS: RGMCs and intact glomeruli released substantial amounts of untransformed PGH2, which was enhanced following exposure to IL-1beta.
The effect of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), a nitric oxide (NO) scavenger that yields nitrogen dioxide (NO(2)) in a rat endotoxemia model was investigated. Endotoxin (lipopolysaccharide [LPS]) increased NO synthase (NOS) activity and inducible NOS expression measured in lung and plasma levels of nitrite/nitrate, 6-oxo-prostaglandin (PG) F(1alpha), thromboxane B(2), and PGF(2alpha). Infusion of cPTIO significantly reduced LPS-induced mean arterial blood pressure decline and mortality and selectively reduced LPS-induced 6-oxo-PGF(1alpha) plasma levels and prostacyclin synthase (PGIS) activity measured in the lung and aorta. In vitro, PGIS activity in aorta rings was not modified by SNAP (NO donor), cPTIO slightly inhibited the enzyme but not in the presence of L-N(G)-monomethyl arginine, and SNAP in combination with cPTIO significantly inhibited PGIS. Thus, cPTIO may be beneficial in endotoxic shock because of NO scavenging and PGIS inactivation, which could be mediated by NO(2).
In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [(14)C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH(2) released by the cells was evaluated as the difference in the formation of PGF(2alpha) in the incubations performed in the presence and in the absence of SnCl(2). Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha formed PGE(2) and PGI(2) (evaluated as 6-oxo-PGF(1alpha)), and in the presence of SnCl(2) only a small amount of PGE(2) was deviated toward PGF(2alpha). In contrast, resting and stimulated HUVECs produced PGI(2), PGE(2), PGF(2alpha), and PGD(2), and SnCl(2) completely diverted PGE(2) and PGD(2) toward PGF(2alpha). Reverse transcriptase-polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1beta and TNF-alpha, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE(2) and PGI(2) but not of untransformed PGH(2), stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH(2).
The ratio between the length of the 2nd and 4th digit (2D:4D) is sexually dimorphic, with mean male 2D:4D lower than mean female 2D:4D. It recently was suggested that 2D:4D is negatively correlated with prenatal testosterone and positively correlated with prenatal estrogen. It is argued that high prenatal testosterone and low estrogen (indicated by low 2D:4D) favors the male fetus and low prenatal testosterone and high estrogen (indicated by high 2D:4D) favors the female fetus. The patterns of expression of 2D:4D are interpreted in terms of sexually antagonistic genes.We report data on the following. (a) reproductive success and 2D:4D from England, Germany, Spain, Hungary (ethnic Hungarians and Gypsy subjects), Poland, and Jamaica (women only). Significant negative associations were found between 2D:4D in men and reproductive success in the English and Spanish samples and significant positive relationships between 2D:4D in women and reproductive success in the English, German, and Hungarian samples. The English sample also showed that married women had higher 2D:4D ratios than unmarried women, suggesting male choice for a correlate of high ratio in women, and that a female 2D:4D ratio greater than male 2D:4D predicted high reproductive success within couples. Comparison of 2D:4D ratios of 62 father:child pairs gave a significant positive relationship. This suggested that genes inherited from the father had some influence on the formation of the 2D:4D ratio. Waist:hip ratio in a sample of English and Jamaican women was negatively related to 2D:4D. (b) Sex and population differences in mean 2D:4D in samples from England, Germany, Spain, Hungary (including ethnic Hungarians and Gypsy subjects), Poland, Jamaica, Finland, and South Africa (a Zulu sample). Significant sex and population differences in mean 2D:4D were apparent.
BACKGROUND/AIMS: Alpha interferon administration is quite disappointing as a single therapy in chronic hepatitis C. A brief course of corticosteroid therapy might increase the effectiveness of subsequent alpha interferon administration, but data on this issue are controversial. METHODS: One hundred and fifty-six consecutive patients with chronic hepatitis C were randomly assigned to be treated blind with tapering doses of oral prednisolone or placebo for 4 weeks. Two weeks after cessation of therapy, patients received alpha interferon (3 MU t.i.w.) for 48 weeks and were followed for 24 additional weeks. Response was defined by the presence of normal alanine aminotransferase (ALT) and negative HCV-RNA in serum. RESULTS: ALT activity decreased during prednisolone administration and rebounded upon withdrawal in 38% of the patients treated with this drug. Significant changes in serum bilirubin were not observed. HCV-RNA serum concentration tended to increase during prednisolone administration and to decrease upon withdrawal. ALT and HCV-RNA did not change during administration of placebo. At the end of interferon administration, 33% of patients treated with prednisolone and 25% of those treated with placebo presented biochemical and virological response. At the end of post-treatment follow-up, response was maintained in 12% and 13% of patients treated with prednisolone or placebo respectively. Response was not related to ALT or HCV-RNA changes observed during the pre-interferon phase of the study. No adverse events related to prednisolone administration were observed. CONCLUSIONS: Prednisolone administration and withdrawal induced a rebound in ALT activity and a decrease in HCV-RNA serum concentration in about one third of the patients with chronic hepatitis C. However, these changes did not enhance the effectiveness of subsequent alpha interferon therapy.
BACKGROUND: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. METHODS: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus. RESULTS: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. CONCLUSIONS: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.
The stability of fireballs in a recent model of ball lightning is studied. It is shown that the balls shine while relaxing in an almost quiescent expansion, and that three effects contribute to their stability: (i) the formation in each one during a process of Taylor relaxation of a force-free magnetic field, a concept introduced in 1954 in order to explain the existence of large magnetic fields and currents in stable configurations of astrophysical plasmas; (ii) the so called Alfven conditions in magnetohydrodynamics; and (iii) the approximate conservation of the helicity integral. The force-free fields that appear are termed "knots" because their magnetic lines are closed and linked.
In human cultured monocytic cells stimulated by cytokines, CD43 was demonstrated to exhibit a modification of sialylated epitopes (dys-sialylation) [Soler et al: Leukoc Biol 1997;61:609-618]. Therefore, we chose to investigate CD43 behavior on patients who present pathological status implicating monocytes after renal graft (KTR). We performed flow cytometry after immune staining using monoclonal antibodies to CD43 sialic acid-dependent (L60) and -independent (L10) epitopes. Compared to normal controls, mean fluorescence intensity was never altered on lymphocytes. Conversely, on monocytes, we found different profiles with L60: 26% of patients having normal CD43 expression, 54% displayed decreased values and 20% had a double population of monocytes, the major one being normal and the minor one with a very low staining. Decreased values were more frequent among KTR during the first 3 months following transplantation. L10 immunostaining was not altered on monocytes in patients with low values of CD43 staining by L60, confirming that the mechanism involved was a CD43 dys-sialylation. We investigated a possible role of cyclosporin (CsA) on human monocytic (THP-1) and lymphoid (Jurkat) cell lines. CsA decreases CD43 expression in monocytic and not in lymphoid cell lines and could be responsible for the specific dys-sialylation of KTR monocytes. Whatever, CD43 dys-sialylation might lead to functional abnormalities of monocytes in KTR, possibly involving the adhesion process.
Here we present experimental evidence that phagocytic cells use modulation of specific components of their glycocalyx to regulate their binding capacity. Particles coated with antibodies specific for the CD32 medium affinity IgG receptor were driven along human monocytic THP-1 cells (expressing CD32) in a flow chamber operated at low shear rate. Surprisingly, only minimal adhesion was observed. However, when cells were activated by exposure to fibronectin-coated surfaces and/or soluble &ggr; interferon, adhesion efficiency was dramatically increased, whereas the apparent glycocalyx thickness displayed 20% decrease, and the surface density of CD43/leukosialin carbohydrate epitopes displayed 30-40% decrease on activated cells. The existence of a causal link between adhesion increase and glycocalyx alteration was strongly supported by the finding that (i) both phenomena displayed similar kinetics, (ii) an inverse relationship between THP-1 cell binding capacity and glycocalyx density was demonstrated at the individual cell level, and (iii) adhesion enhancement could not be ascribed to an increased binding site density or improved functional capacity of activated cells. Additional experiments revealed that cell-to-particle adhesion resulted in delayed (i.e. more than a few minutes) egress of CD43/leukosialin from contact areas. Since the time scale of particle attachment was less than a second, surface mobility should not affect the potential of CD43 to impair the initial step of adhesion. Finally, studies performed with fluorescent lectins suggested that THP-1 cell activation and increased adhesive potential were related to a decrease of O-glysosylation rather than N-glycosylation of surface glycoproteins.
The most important molecular techniques used in the diagnosis of Aspergillus spp. and typing of the most pathogen species of this genus are described and discussed. The former, are mainly based in PCR amplification of a concrete DNA fragment and posterior confirmation with Southern-blot; RAPD techniques and less frequently microsatellite markers analysis and DNA-DNA hybridization to a moderately repeated, inactive, retrotransposon-like DNA Afut1 are used in typing clinical isolates.
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BACKGROUND/AIMS: A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other countries. METHODS: Using hemi-nested-PCR amplification to detect TTV-DNA sequences in serum, we investigated TTV infection in blood donors and in patients with liver diseases of varied etiology. RESULTS: The prevalence of TTV infection was 13.7% in blood donors (23/168), 18.6% in chronic hepatitis C (19/102), 28.6% in chronic hepatitis B (16/56), 29.9% in hepatocellular carcinoma (20/67), 9.1% in cryptogenic chronic liver disease (2/22) and 39.6% in fulminant hepatitis (19/48). The prevalence of TTV infection in patients with virus-induced or idiopathic fulminant hepatitis was similar. Comparison of TTV-infected and non-infected patients did not reveal significant differences concerning demographic, epidemiological or histopathological features. In patients with hepatitis C, response to interferon therapy was not related to TTV infection. Phylogenetic analysis of TTV isolates showed that at least three different types of TTV are present in Spain. CONCLUSIONS: Our data suggest that TTV infection is frequent among blood donors and patients with acute liver disease. However, pathogenic effects associated with TTV infection were not observed.
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