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Biomedical subjects

A Oren

Publications and source records attributed to A Oren.

At least 19 recordsLinked to original sources

The cytoskeletal network controls c-Jun translation in a UTR-dependent manner.

The cytoskeleton is a dynamic network that undergoes restructuring during various cellular events, influencing cell proliferation, differentiation, and apoptosis. Here, we report that accumulation of c-Jun, a member of the AP1 family of transcription factors that play a key role in normal and aberrant cell growth, dramatically increases upon depolymerization of the cytoskeleton, and that, unexpectedly, this increase is controlled translationally. Depolymerization of the actin or microtubule network induces an increase in c-Jun accumulation with no corresponding increase in c-Jun mRNA or in the half-life of the c-Jun protein, but rather in the translatability of its transcript. This increase is mediated by the untranslated regions (UTRs) of c-Jun mRNA, and is not dependent on activated mitogen-activated protein kinase pathways. This novel mechanism of c-Jun regulation might be relevant to physiological conditions in which c-Jun plays a pivotal role.

Base Sequence↗

Birth size and coronary heart disease risk score in young adulthood. The Atherosclerosis Risk in Young Adults (ARYA) study.

Data of the Atherosclerosis Risk in Young Adults (ARYA) study were used to investigate the association between birth size and the absolute risk for coronary heart disease in healthy young adults. The cohort study comprises 750 (46.9% men) subjects born between 1970 and 1973. Birth characteristics were obtained from school health records. At young adulthood, blood pressure, anthropometry and fasting lipid levels were measured. Questionnaires were taken about smoking and diabetes. The young adult 10-year risk for coronary heart disease was calculated using the Framingham risk score. The overall 10-year risk for coronary heart disease was 1.6% (standard deviation (SD) 1.9), 3.0% (SD 1.9) in men and 0.3% (SD 0.2) in women. Using linear regression it was shown that a SD lower birth weight (=0.54 kg) was associated with 0.1% greater risk in the overall population (95% confidence interval (CI): -0.19, -0.004). Similarly, a lower ponderal index at birth was associated with an 0.11% higher risk (95% CI: -0.21, -0.002). These relations were stronger in men. Lower birth length was related with an increased risk in women (-0.02% risk/SD birth length; 95% CI: -0.04, 0.0001). These results suggest that small birth size is associated with an increased risk score for coronary artery disease in young adulthood.

Adult↗

Yeast diversity in hypersaline habitats.

Thus far it has been considered that hypersaline natural brines which are subjected to extreme solar heating, do not contain non-melanized yeast populations. Nevertheless we have isolated yeasts in eight different salterns worldwide, as well as from the Dead Sea, Enriquillo Lake (Dominican Republic) and the Great Salt Lake (Utah). Among the isolates obtained from hypersaline waters, Pichia guilliermondii, Debaryomyces hansenii, Yarrowia lipolytica and Candida parapsilosis are known contaminants of low water activity food, whereas Rhodosporidium sphaerocarpum, R. babjevae, Rhodotorula laryngis, Trichosporon mucoides, and a new species resembling C. glabrata were not known for their halotolerance and were identified for the first time in hypersaline habitats. Moreover, the ascomycetous yeast Metschnikowia bicuspidata, known to be a parasite of the brine shrimp, was isolated as a free-living form from the Great Salt Lake brine. In water rich in magnesium chloride (bitterns) from the La Trinitat salterns (Spain), two new species provisionally named C. atmosphaerica - like and P. philogaea - like were discovered.

Biodiversity↗

Determinants of augmentation index in young men: the ARYA study.

BACKGROUND: There is an increasing interest in the augmentation index (AIx), the proportion of the central pulse pressure resulting from peripheral arterial wave reflection, which has been related to cardiovascular disease risk and mortality. Most of the data on the AIx have been collected in patients with established cardiovascular disease. In contrast, data in the young are scarce. However, as AIx might be used to evaluate cardiovascular disease risk already at an early age, we aimed to study determinants of AIx in a population of healthy young men. MATERIALS AND METHODS: Three hundred and thirty males (mean age of 28 years) of the Atherosclerosis Risk in Young Adults study (ARYA-study) were studied in this cross sectional, population-based study. Anthropometrics and risk factors for cardiovascular disease were determined and AIx was estimated by radial applanation tonometry. The data were analysed using linear regression models. RESULTS: Augmentation index was associated with age, height (inverse), heart rate (inverse) and mean arterial pressure (positive). After adjustment for these determinants, smoking (beta = 0.31%/pack years, 95% CI [0.06; 0.55]) and LDL-cholesterol (beta = 1.28%/(mmol L(-1)), 95% CI [0.04; 2.51]) were statistically significant related to AIx. CONCLUSIONS: This study among young adult males shows that smoking and LDL-cholesterol are positively related to AIx. These findings support the view that AIx may be used as a marker for early vascular damage and cardiovascular disease risk.

Adult↗

Survival of filamentous fungi in hypersaline Dead Sea water.

A variety of filamentous fungi have recently been isolated from the Dead Sea (340 g/L total dissolved salts). To assess the extent to which such fungi can survive for prolonged periods in Dead Sea water, we examined the survival of both spores and mycelia in undiluted Dead Sea water and in Dead Sea water diluted to different degrees with distilled water. Mycelia of Aspergillus versicolor and Chaetomium globosum strains isolated from the Dead Sea remained viable for up to 8 weeks in undiluted Dead Sea water. Four Dead Sea isolates (A. versicolor, Eurotium herbariorum, Gymnascella marismortui, and C. globosum) retained their viability in Dead Sea water diluted to 80% during the 12 weeks of the experiment. Mycelia of all species survived for the full term of the experiment in Dead Sea water diluted to 50% and 10% of its original salinity. Comparison of the survival of Dead Sea species and closely related isolates obtained from other locations showed prolonged viability of the strains obtained from the Dead Sea. Spores of isolates obtained from the terrestrial shore of the Dead Sea generally proved less tolerant to suspension in undiluted Dead Sea water than spores of species isolated from the water column. Spores of the species isolated from the control sites had lost their viability in undiluted Dead Sea water within 12 weeks. However, with the exception of Emericella spores, which showed poor survival, a substantial fraction of the spores of Dead Sea fungal isolates remained viable for that period. The difference in survival rate between spores and mycelia of isolates of the same species points to the existence of adapted halotolerant and/or halophilic fungi in the Dead Sea.

Fungi↗

In human epidermis, beta-defensin 2 is packaged in lamellar bodies.

The skin presents a mechanical, as well as an immunological barrier to infection, and displays considerable innate immune capacity. Recently, cultured human keratinocytes were described to produce and export a microbicidal peptide human beta-defensin 2 (HBD-2). Immunogold was used to label ultrathin cryosections of stimulated, cultured human epidermis. HBD-2 was found to be stored in the lamellar bodies (LBs) of the stimulated keratinocytes of the spinous layer of the epidermis. HBD-2 was also found in the intercellular space. These findings suggest that HBD-2 is released with the contents of the LBs. Along with other investigations, our findings indicate that the lipid "permeability" barrier of the skin contains antimicrobial substances.

Anti-Infective Agents↗

The Atherosclerosis Risk in Young Adults (ARYA) study: rationale and design.

INTRODUCTION: Despite recent advances in treatment, cardiovascular disease (CVD) is still health problem number one in western societies. Aiming at specific prevention strategies for high-risk individuals and shifting the available prevention programs towards younger age groups might increase the success of primary prevention. However, before addressing age-specific prevention programs, more insight in the determinants of early vascular damage and increased cardiovascular risk is warranted as well as insight in determinants increased cardiovascular risk, including vascular damage, at an early age. The Atherosclerosis Risk in Young Adults (ARYA) study was specifically designed to address this issue. OBJECTIVES: The ARYA study started off with studies evaluating (1) whether it is possible to predict cardiovascular risk at young adulthood by routinely measured adolescent data, and (2) evaluating the role of birth characteristics and adolescent characteristics to the development of vascular damage at young adulthood. METHODS: The ARYA study comprises of two cohorts of young adults. The Utrecht cohort includes 750 young adults, aged 27-30 years. The Hague-cohort includes 261 young adults born between 1963 and 1968. Data on birth characteristics, growth in early infancy as well as adolescent anthropometry, blood pressure, lipids, body mass index were obtained from the original medical records of the Municipal Health Service. In 1999/2001, the extent of subclinical vascular damage was measured using carotid wall thickness and aortic stiffness. Also, data on adult cardiovascular risk profile, bone density and central blood pressure were assessed, fasting blood was drawn and timed overnight urine samples were collected. CONCLUSION: The ARYA study is aimed to provide data on early determinants of cardiovascular risk, including vascular damage, at an early age. This knowledge enhances the understanding of atherosclerosis development and CVD risk and is needed to improve the available primary prevention programs.

Adolescent↗

Change in body mass index from adolescence to young adulthood and increased carotid intima-media thickness at 28 years of age: the Atherosclerosis Risk in Young Adults study.

UNLABELLED: Obesity has become a major health problem in Western societies by increasing the risk of atherosclerosis and cardiovascular disease. Although data on tracking of body mass index (BMI) are available, little is known about the impact of weight change over time on the development of vascular damage. OBJECTIVE: To evaluate the relationship between adolescent BMI as well as change in BMI from adolescence into young adulthood and cardiovascular risk, as estimated by common carotid intima-media thickness (CIMT). DESIGN: Cohort study. SUBJECTS: A total of 750 healthy young adults, aged 27-30 y, who attended secondary school in Utrecht, the Netherlands. MEASUREMENTS: Data on adolescent weight, height, blood pressure and puberty stage were available from the original school health records of the Municipal Health Service. At young adulthood, a questionnaire on cardiovascular risk factors was completed and fasting blood sample was drawn and common CIMT was measured. RESULTS: One standard deviation (s.d.) increase in adolescent BMI was associated with 2.3 microm [95% confidence interval (CI): 1.3; 3.3] increase in mean common CIMT in young adults after adjustment for gender, adolescent age, adolescent blood pressure, puberty stage and lumen diameter. Further adjustment for adult cardiovascular risk factors did not change the relationship (linear regression coefficient=2.1 microm/s.d.; 95% CI: 1.0; 3.1). Adjustment for adult BMI attenuated the association (linear regression coefficient=0.9 microm/s.d.; 95% CI: -0.3; 2.2) as the majority of overweight and obese adolescents remained overweight or became obese young adults. Subjects who remained in the upper BMI distribution from adolescence into young adulthood had a significantly higher common CIMT compared to those who showed relative weight loss over time (mean difference 14.7 mum; P<0.001). These latter showed similar CIMT values as individuals with constant low BMI. CONCLUSION: Adolescent BMI predicts cardiovascular risk, as estimated by common CIMT in young adulthood. Individuals who experience the largest increase in BMI and those who remain overweight over time have the thickest common CIMT.

Adolescent↗

Aortic stiffness and carotid intima-media thickness: two independent markers of subclinical vascular damage in young adults?

BACKGROUND: Previous reports have shown that carotid intima-media thickness (CIMT) and arterial stiffness are strong predictors of subsequent cardiovascular disease (CVD) morbidity and mortality, and are well related to an unfavourable cardiovascular risk profile in middle-aged and older subjects. These similarities suggest that arterial stiffness may play a role in the development of atherosclerosis or vice versa. However, studies show conflicting results and are limited to elderly subjects. To study this issue further, we evaluated the relation of arterial stiffness to subclinical atherosclerosis in 524 healthy young adults, aged 27-30 years. METHODS AND RESULTS: Aortic stiffness was assessed using pulse wave velocity (PWV) and CIMT was used as measure of subclinical atherosclerosis. The positive crude correlation between for mean arterial pressure adjusted PWV and CIMT (Pearson's correlation coefficient: 0.11; P=0.016) attenuated after adjustment for common determinants of both measurements like gender and age (partial correlation coefficient: 0.03; P=0.512). Furthermore, multivariate linear regression models showed that male gender, age and blood pressure were independent determinants of both CIMT and PWV while body mass index and LDL-cholesterol were independent determinants of CIMT only. CONCLUSIONS: These observations suggest that in healthy young adults arterial stiffness and CIMT reflect two separate entities of vascular damage.

Adult↗

Diversity of halophilic microorganisms: environments, phylogeny, physiology, and applications.

The phylogenetic diversity of microorganisms living at high salt concentrations is surprising. Halophiles are found in each of the three domains: Archaea, Bacteria, and Eucarya. The metabolic diversity of halophiles is great as well: they include oxygenic and anoxygenic phototrophs, aerobic heterotrophs, fermenters, denitrifiers, sulfate reducers, and methanogens. The diversity of metabolic types encountered decreases with salinity. The upper salinity limit at which each dissimilatory process takes place is correlated with the amount of energy generated and the energetic cost of osmotic adaptation. Our understanding of the biodiversity in salt-saturated environments has increased greatly in recent years. Using a combination of culture techniques, molecular biological methods, and chemotaxonomic studies, we have obtained information on the nature of the halophilic Archaea as well as the halophilic Bacteria that inhabit saltern crystallizer ponds. Several halophilic microorganisms are being exploited in biotechnology. In some cases, such as the production of ectoine, the product is directly related to the halophilic behavior of the producing microorganism. In other cases, such as the extraction of beta-carotene from Dunaliella or the potential use of Haloferax species for the production of poly-beta-hydroxyalkanoate or extracellular polysaccharides, similar products can be obtained from non-halophiles, but halophilic microorganisms may present advantages over the use of non-halophilic counterparts.

Adaptation, Physiological↗

Selenihalanaerobacter shriftii gen. nov., sp. nov., a halophilic anaerobe from Dead Sea sediments that respires selenate.

We isolated an obligately anaerobic halophilic bacterium from the Dead Sea that grew by respiration of selenate. The isolate, designated strain DSSe-1, was a gram-negative, non-motile rod. It oxidized glycerol or glucose to acetate + CO2 with concomitant reduction of selenate to selenite plus elemental selenium. Other electron acceptors that supported anaerobic growth on glycerol were nitrate and trimethylamine-N-oxide; nitrite, arsenate, fumarate, dimethylsulfoxide, thiosulfate, elemental sulfur, sulfite or sulfate could not serve as electron acceptors. Growth on glycerol in the presence of nitrate occurred over a salinity range from 100 to 240 g/l, with an optimum at 210 g/l. Analysis of the 16S rRNA gene sequence suggests that strain DSSe-1 belongs to the order Halanaerobiales, an order of halophilic anaerobes with a fermentative or homoacetogenic metabolism, in which anaerobic respiratory metabolism has never been documented. The highest 16S rRNA sequence similarity (90%) was found with Acetohalobium arabaticum (X89077). On the basis of physiological properties as well as the relatively low homology of 16S rRNA from strain DSSe-1 with known genera, classification in a new genus within the order Halanaerobiales, family Halobacteroidaceae is warranted. We propose the name Selenihalanaerobacter shriftii. Type strain is strain DSSe-1 (ATCC accession number BAA-73).

Bacteria, Anaerobic↗

Cancer in children with celiac disease: a survey of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: In adults, the relation between celiac disease (CD) and cancer has been long recognized. In children, only four cases of CD and cancer have been described in Europe. We made a new inventory of cases with CD and cancer in children that were known by the members of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition between 1989 and 1999. METHODS: Postal inquiry was made of all European Society for Paediatric Gastroenterology, Hepatology and Nutrition members mentioned on the society's web page. The members were asked if they had seen a child with CD and cancer between 1989 and 1999 and if so, to supply additional clinical data. Also, information on working place, experience, and number of celiac patients under their care was requested. RESULTS: Fifty-six percent of the members responded. Sixteen members reported 22 cases of cancer and CD in children. One case had been reported in the literature previously. The tumors that were reported originated from the brain, thyroid, larynx, liver, small bowel, adrenal, lymphoreticular system, and the musculoskeletal system. There were no differences between members reporting a case and those who did not. CONCLUSIONS: Twenty-one new cases of cancer and CD in children in Europe were found. Cancer and CD in children are underreported. A remarkable number of thyroid and small bowel cancers were found, suggesting a possible relation with CD. It is important to evaluate whether these findings are coincidental. All cases of cancer and CD in children should be reported to the literature.

Adolescent↗

The contribution of halophilic Bacteria to the red coloration of saltern crystallizer ponds(1).

Analysis of the pigments extracted from solar saltern crystallizer ponds in Santa Pola near Alicante and on the Balearic island of Mallorca, Spain, showed that 5-7.5% of the total prokaryotic pigment absorbance could be attributed to a novel carotenoid or carotenoid-like compound. This unidentified pigment was identical to the sole pigment present in Salinibacter ruber, the only described member of a newly discovered genus of red halophilic Bacteria related to the Cytophaga-Flavobacterium-Bacteroides group. On the basis of fluorescence in situ hybridization experiments it has been shown that Salinibacter is an important component of the microbial community of Spanish saltern ponds. The red color of saltern crystallizer ponds may thus not only be due to red halophilic Archaea and to beta-carotene-rich Dunaliella cells as previously assumed, but may contain a bacterial contribution as well. The Salinibacter pigment was not detected in samples collected from crystallizer ponds of the salterns of Eilat, Israel, and only traces of it may have been present in the Newark, CA, USA, salterns. The community structure of the prokaryote community inhabiting saltern crystallizers thus shows significant geographic variations. Polar lipid analyses of the biomass collected from the Santa Pola salterns showed that the total contribution of Salinibacter and other Bacteria to the total biomass was minor, the most important component of the community being halophilic Archaea.

Journal Article↗

Determinants of Staphylococcus aureus nasal carriage.

Nasal carriage of Staphylococcus aureus has been identified as a risk factor for community-acquired and nosocomial infections. We screened 230 donors of diverse ethnic and socioeconomic backgrounds and identified 62 (27%) whose nasal secretions were colonized by S. aureus. In 18 donors in whom the various regions of the nasal luminal surface were separately sampled, the predominant region of S. aureus colonization was the moist squamous epithelium on the septum adjacent to the nasal ostium. Nasal fluid from carriers was defective in killing endogenous S. aureus and nasal carrier isolates of S. aureus but not a laboratory S. aureus strain. Transmission electron microscopy revealed that S. aureus isolates incubated in nasal fluid from carriers for 2 h at 37 degrees C were less damaged than those incubated in noncarrier fluid and were coated with an electron-dense layer. Compared with that from healthy donors and patients with acute rhinitis, nasal fluid from carriers contained elevated concentrations of the neutrophil-derived defensins human neutrophil peptides 1 to 3 (47- and 4-fold increases, respectively), indicative of a neutrophil-mediated inflammatory host response to S. aureus colonization. The concentration of the inducible epithelial antimicrobial peptide human beta-defensin 2 was also highly elevated compared to that in healthy donors, in whom the level was below the detection limit, or patients with acute rhinitis (sixfold increase). Thus, nasal carriage of S. aureus takes hold in nasal fluid that is permissive for colonization and induces a local inflammatory response that fails to clear the colonizing bacteria.

Body Fluids↗

Halocins: are they involved in the competition between halobacteria in saltern ponds?

Many representatives of the family Halobacteriaceae ("halobacteria") excrete halophilic bacteriocins (halocins) that inhibit the growth of other halobacteria. In spite of the fact that halocin production is widespread among the Halobacteriaceae, no information is available on their ecological significance. To test whether halocins may play a role in the interspecies competition between different types of halobacteria in saltern crystallizer ponds inhabited by dense communities of these red halophiles, we assayed for halocins active against a variety of halobacteria in salterns from different locations worldwide. Detection of halocin activity was based on the inhibition of growth of indicator organisms on agar plates, the decreased incorporation of radiolabeled substrates, and microscopic examinations. No halocin activity was detected in any of the brines examined, in spite of the fact that halocin production was demonstrated in cultures of most microorganisms isolated from these brines. Thus, the contribution of halocins in the competition between different halobacteria in hypersaline aquatic environments is probably negligible.

Archaeal Proteins↗

Comparisons of the polar lipid and pigment profiles of two solar salterns located in Newark, California, USA, and Eilat, Israel.

The whole community pigments and lipids have been examined during a 5-year period in two commercial solar salterns located in the United States and in Israel. There were significant differences in the complexity of the lipid and pigment patterns within the California saltern system, and these differences were not consistent over the sampling period despite examination of ponds with the same salinity. The solar saltern system in Eilat, Israel, showed greater consistency during this sampling period and compared directly with previous studies. The complexity of the saltern in Newark, California, could be explained on the basis of the prevailing weather conditions (cooler and more rainfall) and the nutrient-enriched source water. The Eilat saltern, however, has an oligotrophic water source and has a considerably warmer and drier climate. This difference resulted in more diverse and more complex pigment and lipid patterns and presumably microbial populations in the Newark, California, plant than in the saltern in Eilat, Israel.

Biomass↗

Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome.

OBJECTIVES: To investigate the best approach to screen for celiac disease (CD) in patients with Down syndrome (DS). STUDY DESIGN: One hundred thirty-seven children with DS were followed up longitudinally. CD screening was offered in 1994, 1996, and 1999 by determination of serum immunoglobulin A-anti-endomysium antibodies (AEA). The HLA-DQA1*0501/DQB1*02 allelic combination known to be strongly positively associated with CD was typed. All IgA-AEA-positive children were given the opportunity to undergo a small bowel biopsy: if villous atrophy was found, the diagnosis of CD was established. RESULTS: CD was diagnosed in 11 (8%) children: 8 in 1994 and 3 in 1996. All of them carried the HLA-DQ alleles associated with CD. The presence of symptoms was not useful in discriminating which children could have CD. CONCLUSIONS: Screening once in a lifetime is not enough to detect CD in patients with DS. We propose a new, accurate, and cost-sparing 2-step strategy for screening, based on selection of the individuals with potential CD by HLA-DQ typing and on longitudinal serologic CD screening in this selected group.

Alleles↗