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Antenna size dependent exciton dynamics in the chlorosomal antenna of the green bacterium Chloroflexus aurantiacus.

Using picosecond fluorescence spectroscopy, we demonstrated antenna size dependent exciton dynamics in chlorosomal antenna, measured for intact cells of different cultures of the green bacterium Chloroflexus aurantiacus with different chlorosomal antenna size determined by electron microscopic examination of ultrathin sections of the cells. The measured bacteriochlorophyll (BChl) c excitation lifetimes show a quasilinear dependence on chlorosome size as predicted in our model for cylindrical exciton migration within the three-dimensional chlorosomal antenna. The migration model was developed for the proposed exciton model of chlorosomal BChl c aggregation. The data predict the time constant values for excitation energy transfer between BChl c aggregates as well as to BChl a of the baseplate.

Bacteria↗

Are seasonalities in suicide dependent on suicide methods? A reappraisal.

In general, suicide frequencies peak in spring and early summer and depict a low in autumn and winter months. Suicide seasonality is a ubiquitous phenomenon; however, recent studies have indicated that it is related particularly to violent suicide methods. We investigated differences in suicide seasonalities by suicide methods using Swiss mortality data. The suicide data were extracted from the Swiss cause of death statistics and cover the period 1969-1994. In this period 37,518 suicides (ICD-8 codes 950-959) were registered in the mortality statistics. The data were analysed by the Edwards' method, which examines unimodal sinusoidal patterns in aggregated monthly data, and by spectral analysis with disaggregated monthly data. Overall, Swiss suicide data in 1969-1994 depict the expected pattern with a peak in May and June and a low in December. However, analyses by suicide methods show that there is no common pattern. Suicide seasonalities are absent or weak in some violent as well as non-violent methods (firearms, cutting, crashing, poisoning). Even if clearly present (hanging, drowning, jumping from high places, unspecified/other), the seasonalities show distinct patterns and cycles. Apart from sinusoidal patterns, there are also outliers: in overall data as well as in most method-specific data, the December frequencies fall more than 10% below the neighbouring months. The decrease of the frequencies culminates at Christmas/New Year and then returns to average levels. Hence, the seasonality of the overall Swiss suicide frequencies is but a compound seasonality. It largely depends on specific suicide methods and different cyclical dynamics.

Accidents, Traffic↗

Inhibitory effect of the leaf extract of Ginkgo biloba L. on oxidative stress-induced platelet aggregation.

The effect of the leaf extract of Ginkgo biloba L. on platelet aggregation induced by oxidative stress was studied. The extract caused a dose-dependent inhibition of platelet aggregation stimulated with tert-butyl hydroperoxide (t-BHP) and Fe2+. Similar inhibitory activity was observed when platelets were exposed to H2O2 and Fe2+. Synergistic aggregation induced by a combination of t-BHP and Fe2+ or H2O2 and Fe2+ in association with suboptimal concentration of collagen or U46619, was prevented by the extract. However, the extract failed to inhibit aggregation in response to collagen, thrombin or U46619. Ginkgolides A, B and C inhibited platelet-activating factor-induced aggregation, but not oxidant-induced aggregation. These data suggest that the suppressive effect of the extract is specific on platelet aggregation stimulated by oxidative stress, and that this effect is involved in the mechanism related to its protective effect upon cerebral or myocardial injuries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Asian and Pacific Islander mortality differences in Hawaii.

In the United States, national health status data pertaining to Asian and Pacific Islander (API) Americans are rarely disaggregated. By aggregating API data, however, the poor health status of some API groups is often masked by the favorable health status of others. The purpose of this paper is two-fold: (1) to compare mortality rates of the five major ethnic groups in Hawaii (Caucasians, Chinese, Filipinos, Japanese, and Hawaiians) and (2) to explore methodological issues related to comparative studies of API health indicators. Standardized and age-specific mortality rates and 95 per cent confidence intervals for major causes of death were estimated for 1990 based on Hawaii vital records and population data. In general, death rates were highest for Hawaiians and lowest for Japanese and Chinese, illustrating the importance of API data disaggregation and suggesting that special attention be paid to improving the health of Hawaiians. Methodologically, the study demonstrated that, while some compromises in analysis are required, legitimate comparisons across API groups can be made if data sets are available.

Adolescent↗

Psychological changes in hundred-day remote Antarctic field groups.

Psychological adaptation to extreme environments has been examined from several perspectives. In this study, two Australian teams, each consisting of six male crew members, completed computer-administered questionnaires twice weekly during 100-day traverses around the Lambert Glacier Basin, Antarctica. Only small trends were noted when data were aggregated at the group level, which is consistent with the findings of others. Data were then analyzed using pooled time-series regression. These analyses incorporated personality characteristics, environmental factors, and interpersonal factors as predictors of Group Tensions, Personal Morale, Emotional State, Cognitive Readiness, and the Team's Work Life. Most of the psychological discomfort and problems that occurred appeared to be within the individual or between individuals. They did not affect all members of the group equally.

Adaptation, Psychological↗

The ovarian insulin-like growth factors, a local amplification mechanism for steroidogenesis and hormone action.

The importance of the ovarian insulin-like growth factors (IGFs) has been suggested by data from numerous laboratories and several approaches in the last several years. In the aggregate, these data indicate that this system could function as an important local amplification mechanism for steroidogenesis and gonadotropin action. Studies supporting this hypothesis have described several interacting components of this autocrine/paracrine system. First, the several types of ovarian cells possess an IGF-response system, which includes receptors for IGFs and an effective intracellular transduction system. The IGFs can promote growth and/or differentiation of ovarian cells, and their predominant actions depend on the nature of the cells and the presence of additional modulating factors. The biochemical events leading to enhanced steroidogenesis are now understood in considerable detail and include induction of several steps in the cAMP-dependent steroidogenic cascade. The second component of the ovarian IGF system comprises hormone-responsive local production of IGFs. Both IGF-I and IGF-II may be secreted; gonadotropins, gonadal steroids and locally produced growth factors can regulate the IGF system at this level. Finally, ovarian cells secrete a heterogeneous and complex family of IGF-binding proteins (IGFBPs). These proteins can impact on multiple ovarian functions in a manner which is generally opposite to that of the IGFs themselves. As is the case for the IGFs, the secretion of these proteins by ovarian cells is regulated by gonadotropins and locally produced ovarian factors. Collectively, these several components provide an integrated, synergistically cooperative local network to promote gonadotropin-dependent growth and differentiation in the ovary.

Female↗

An 'Honest Broker' mechanism to maintain privacy for patient care and academic medical research.

PURPOSE: From the Hippocratic Oath to the World Medical Association's Declaration of Geneva, physicians have sworn to protect patients' privacy. However, as systems move to more integrated architectures, protecting this medical data becomes more of a challenge. The increase in complexity of IT environments, the aggregation of data, and the desire of other entities to access this data, often 24 h/day x 7 day/week x 365 day/year, is putting serious strains on our ability to maintain its security. This problem cuts across all electronic record sources from patient care records to academic medical research records. APPROACH: In order to address this issue, we are rethinking the way we store, transmit, process, access, and federate patient data from clinical and research applications. Our groups at the University of Michigan are developing a system called the "Honest Broker" to help manage this problem. The Honest Broker will offload the burden of housing identifiable data elements of protected health information (PHI) (e.g., name and address) as well as manage data transfer between clinical and research systems. Lab results and other non-identifiable data will be stored in separate systems with either a research study ID or clinical ID number. This two-component architecture increases the burden on attackers who now need to compromise two systems, one of which is seriously hardened, in order to match health data with a patient's actual identity. CONCLUSIONS: While no security system is truly intrusion-proof, this architecture provides a high security choke point reducing the likelihood of a breach. By redesigning the method of integrating clinical care and research, we have enabled projects that would be cost prohibitive to conduct otherwise. The scalability of this mechanism is dependant on nature of the heterogenous nature of the clinical systems serving patients.

Biomedical Research↗

Lack of correlation between the incidence of bloodborne AIDS and overall AIDS incidence in Western Europe.

BACKGROUND: The incidence of bloodborne AIDS and the total incidence of AIDS in various areas of the United States are strongly correlated. STUDY DESIGN AND METHODS: To determine whether the same held true for Western Europe, data for 1985 through 1993 from the World Health Organization's European Non-Aggregate AIDS Data Set and for 1985 through 1992 from the Centers for Disease Control and Prevention's AIDS Public information Data Set were compared. Incidence rates per million population were adjusted for reporting delays in each country and age-standardized (world standard population). RESULTS: In Western Europe, there were no significant correlations between the annual incidence of transfusion-associated (TA)-AIDS (correlation coefficient, r = 0.38) and that of hemophilia-associated AIDS (r = 0.24) and the corresponding incidence of all AIDS cases. Whereas similar age-specific incidence rates for hemophilia-associated AIDS emerged in all countries examined, those for TA-AIDS varied and increased greatly with age in France and the United States. Male-to-female ratios of TA-AIDS ranged between 0.5 in the United Kingdom and > or = 1.5 in Italy, Portugal, Spain, Sweden, and the United States. CONCLUSION: Lack of significant correlation between the incidence of bloodborne AIDS and that of all AIDS in Western Europe points to important, but little-quantified sources of variation by country in the safety of blood and blood derivatives. Higher rates of TA-AIDS in the elderly and in males in some countries suggest international differences in transfusion practices by age and sex.

Acquired Immunodeficiency Syndrome↗

A combined analysis of North American case-control studies of residential radon and lung cancer.

Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10-15% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by a-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with a-track radon measurements within the exposure time window (ETW) 5-30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits (-0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5-30 ETW and who had a-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners.

Adult↗

Activation of platelets in platelet-rich plasma by rotablation is speed-dependent and can be inhibited by abciximab (c7E3 Fab; ReoPro).

BACKGROUND: Rotational atherectomy with the Rotablator catheter has improved percutaneous treatment of certain coronary atherosclerotic lesions, but the "no-reflow" phenomenon remains a serious complication. Because platelet activation by rotablation may contribute to the no-reflow phenomenon, we developed an in vitro system to test the effect of rotablation on platelets in the absence or presence of platelet GP IIb/IIIa receptor blockade with abciximab. METHODS AND RESULTS: Platelet-rich plasma (PRP) was prepared from 28 healthy human volunteers. PRP was divided into 4 samples: (1) no treatment, (2) 6D1 (anti-GP Ib), (3) c7E3 Fab (anti-GP IIb/IIIa+alpha(v)beta3), and (4) c7E3 Fab+6D1. Samples were pumped through a flow chamber containing a 2.5-mm burr rotating at various speeds and then placed in an aggregometer. PRP samples tested in the absence of antibody underwent more rapid and extensive aggregation when rotablated at 150000 and 180000 rpm compared with 0 rpm (P<0.001 at both speeds). Preincubation of platelets with c7E3 Fab decreased the slope of aggregation at each rotablation speed, with 98%, 79%, and 71% reductions at 70000, 150000, and 180000 rpm, respectively (P=0.09 for 70000 and P<0.001 for both 150000 and 180000 rpm). Preincubation of platelets with 6D1 did not decrease the slope of aggregation at any rotablation speed (P>0.5, P=0.99, and P=0.091 for 70000, 150000, and 180000 rpm). Platelet ATP release, a marker of granule release and cell damage, was markedly increased at 180000 rpm (P=0.002 compared with 0 rpm in the control group). Electron microscopy revealed extensive rotablation-induced platelet damage at 150000 and 180000 rpm, and leakage of LDH confirmed platelet lysis at these speeds (P=0.002 and P<0.001 compared with 0 rpm). CONCLUSIONS: High-speed rotablation induces platelet activation of PRP, leading to aggregation; pretreating PRP with abciximab decreases the aggregation. These data suggest that pretreatment of patients with abciximab may decrease rotablation-induced platelet aggregation during rotational atherectomy.

Abciximab↗

[Procoagulant and aggregating platelet activities of human mammary tumor cells].

The ability of tumor cells to initiate coagulation, platelet aggregation and subsequent thrombotic alterations is believed to facilitate metastatic process. The mechanisms by which tumor cells develop thrombotic events in malignancy are discussed. We have examined the procoagulant activity and the modifications of rheologic platelet functions induced by 3 human mammary tumor cell lines (MCF-7, ZR-75-1, BT-20) using a laser-thromborheometer. According to experimental conditions, these 3 tumor cell lines aggregate platelets via a thrombin-dependent mechanism. Moreover, MCF-7 cells also induce ADP-like platelet aggregation. These data suggest the existence of several mechanisms of mammary tumor cell-induced platelet aggregation.

Blood Coagulation↗

cAMP and cell sorting control the spatial expression of a developmentally essential cell-type-specific ras gene in Dictyostelium.

The Dictyostelium ras gene (Dd-ras) is expressed at a low level in vegetative cells, is not expressed between the onset of development and aggregation, and is then re-expressed in the multicellular aggregate stages from the distal, now cAMP-responsive, promoter and from two more proximal promoters. Expression of activated Dd-ras (G12----T12) (Reymond et al. 1986) results in an abnormal developmental phenotype with the formation of aggregates having multiple tips and an inhibition of further development. In this report we investigate the spatial expression of Dd-ras by fusing the 5'-flanking region to the Escherichia coli lacZ gene and by staining aggregates for beta-galactosidase (beta-gal) activity. We show that fusions using 5'-flanking sequences that include all promoters are expressed in approximately 10-20% of the cells randomly scattered within the early aggregate. Our data indicate that these beta-gal-expressing cells migrate to newly formed tips of aggregates and localize in the region that becomes the prestalk zone. Staining is also seen in the very posterior of the organism. The anterior staining appears to be specific for the prestalk A population, and beta-gal activity is subsequently present in stalk cells as developmental proceeds. When only the two more proximal promoters are used to drive lacZ expression, localized staining is seen in the anterior prestalk region, although it is weaker than with the construct carrying all promoters. Moreover, staining is not seen in the posterior domain in the first finger stage, suggesting differences in the spatial expression from the different promoters. Staining is also observed in some cells within the prespore region, which could be anterior-like cells. The pattern of Dd-ras/lacZ staining during tip formation suggests a directed, spiral pattern of cell migration, possibly in response to the proposed spiral gradient of cAMP within the developing aggregate. The pattern of Dd-ras is consistent with the abnormal developmental phenotype caused by expressing an activated Dd-ras Thr12 gene and suggests an essential role for Dd-ras in controlling spatial differentiation.

Amino Acid Sequence↗

Role of fibrinogen alpha and gamma chain sites in platelet aggregation.

Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin alpha IIb beta 3). Peptides containing the amino acid sequence RGD derived from the alpha chain (residues alpha 95-97 and residues alpha 572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the gamma chain of Fbg (residues gamma 400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD-->RGE substitution at either position alpha 97 or alpha 574, and a rFbg gamma'-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the gamma' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the gamma chain of Fbg is essential for optimal platelet aggregation and that the alpha-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.

Amino Acid Sequence↗

Control of organelle transport in melanophores: regulation of Ca2+ and cAMP levels.

Melanophores of the cichlid Tilapia mossambica can be induced to aggregate pigment by addition of epinephrine to the medium, suggesting adrenergic control of this transport. The melanophore response to adrenergic stimulation was examined using agonists and antagonists that are highly specific for each alpha-adrenoceptor subclass. The signal transduction mechanism of each subclass is unique: stimulation of alpha 1 receptors results in a rise in intracellular free Ca2+, while alpha 2 stimulation results in decreased cAMP levels [Exton, 1985: Am. J. Physiol. 248:E633-E647]. Each alpha 1 or alpha 2 specific agonist tested showed a dose dependent ability to induce aggregation and each was able to effect complete aggregation of pigment, suggesting that aggregation can be mediated either by elevating Ca2+ or by lowering cAMP. However, in the presence of either an alpha 1 or an alpha 2 receptor antagonist, none of the agonists were able to induce significant aggregation, suggesting that changes in levels of both messengers are required for pigment aggregation in the melanophores. Moreover, experiments in which intracellular levels of Ca2+ or cAMP were perturbed, using BAPTA and forskolin, respectively, indicated that elevating Ca2+ in the presence of high cAMP is not sufficient to induce aggregation and, conversely, that lowering cAMP levels in the presence of reduced Ca2+ is not sufficient to induce pigment aggregation. These data indicate that the concentrations of both cAMP and Ca2+ are important in regulating pigment aggregation in teleost melanophores, and suggest that maximal aggregation of pigment requires altering the levels of both messengers.

Animals↗

The Atlas of Health and Working Conditions by Occupation. 1. Occupational ranking lists and occupational profiles from periodical occupational health survey data.

In this article, we describe methods which have been applied in the compilation of the Atlas of Health and Working conditions by Occupation. First, we discuss the need for information systems to identify problems concerning working conditions and health. Such information systems have an exploratory purpose, being deployed to identify work risks in companies, groups of occupations and sectors of industry, and can also be a starting point for the generation of hypotheses on the causes of adverse health effects. In the Netherlands, occupational health services gather questionnaire data about work and health as part of periodical occupational health surveys. In the atlas, aggregated questionnaire data for 129 occupations with male employees and 19 occupations with female employees are presented. In this article, we explain the methodology used to compare occupations with regard to each item in the questionnaire. We then discuss applications of these occupational ranking lists. The cross-sectional nature of the data collection, various forms of selection and the limited size of some occupational populations have to be taken into account when interpreting the results. Occupational ranking lists can be applied in the allocation of resources and in the design of scientific research. The overviews for each occupation, presented in the second half of the atlas, provide an occupational profile of existing problems with respect to work and health. These profiles are used as basic information to develop a practical policy on working conditions and health.

Adult↗

The role of Galectin-1 in the interaction between chondrocytes and a lactose-modified chitosan.

Evidences for the involvement of the Galectin-1 in the interaction of pig chondrocytes with a lactose-modified chitosan, namely Chitlac, are reported. The Chitlac glycopolymer has been shown to promote pig chondrocyte aggregation and to induce extracellular matrix production. Highly pure Galectin-1 was obtained from pig spleen by affinity chromatography and its identity was determined by ion spray mass spectrometry analysis of tryptic peptide fragments obtained after in-gel digestion. The complete sequence of pig Galectin-1 CDS was obtained by screening a pig EST database using human Galectin-1 sequence as template. The Galectin-1 cDNA was cloned into a pGEX-4T-1 expression vector and the recombinant protein was purified, characterized and used to produce a rabbit anti-serum. Recombinant Galectin-1 interacts in a dose-dependent manner with Chitlac as determined with ELISA assay. Expression level of galectin-1 gene, quantified by real-time PCR, was significantly higher in chondrocytes cultivated on Chitlac. In the same way, the presence of Chitlac stimulates secretion of Galectin-1 in culture medium that, by immunohistochemical analysis, revealed to be clustered on the surface of Chitlac-induced aggregates. These data indicate the role of Galectin-1 as a bridging agent between Chitlac and chondrocyte aggregates.

Animals↗

ATP-dependent dissociation of non-disulfide-linked aggregates of coagulation factor VIII is a rate-limiting step for secretion.

Deficiency in coagulation factor VIII leads to the bleeding disorder hemophilia A. Previous studies demonstrated that factor VIII secretion is limited due to an ATP-requiring step early in the secretory pathway. In this report, we identified that this ATP-dependent rate-limiting step involves the dissociation of non-disulfide-linked aggregates within the endoplasmic reticulum (ER). In contrast to the numerous examples of interchain disulfide-linked aggregates, factor VIII is the first protein characterized to form non-disulfide-linked high molecular weight aggregates within the ER. Approximately a third of newly synthesized factor VIII was detected in high molecular weight aggregates. These aggregates disappeared over time as functional factor VIII appeared in the medium. The aggregated complexes did not require proteasomal degradation for clearance. Aggregate formation was enhanced by ATP depletion, and upon restoration of metabolic energy, these aggregates were dissociated and secreted. With the coexpression of von Willebrand factor (vWF), a small portion of vWF coaggregated with factor VIII. However, vWF dissociated from the aggregates more rapidly than factor VIII, supporting that these aggregates are dynamic. An increase in the factor VIII expression level elicited a corresponding increase in the fraction of factor VIII that was aggregated. In addition, a 110 amino acid sequence containing a hydrophobic beta-sheet within factor VIII was identified that may predispose factor VIII to aggregation. These data show that formation and ATP-dependent dissolution of nondisulfide-linked factor VIII aggregates is a dynamic, rate-limiting step during the folding process in the early secretory pathway. In summary, we have identified an unprecedented requirement for protein transport out of the ER that involves an ATP-dependent dissociation of non-disulfide-linked aggregates within the ER.

Acetylcysteine↗

Indexing the census: a by-product of the simulation of whole populations by means of SAS and SAR data.

"Amongst the new output formats adopted for the 1991 [U.K.] census were the Small Area and Local Base Statistics tables and the Samples of Anonymised Records. During an attempt to combine these data sources to estimate whole populations, a need was recognised for a computer algorithm to aggregate SAR data flexibly into LBS and SAS table look-alikes. This paper is a report on progress in the development of such an algorithm, including the concomitant development of a meta-database of census tables and variables required as an input to the algorithm. Out of this work a user-friendly, freely disseminable version of the census meta-database has been created, of interest to all census users."

Censuses↗