Antiphospholipid Syndrome: A Seronegative Case at Ho Teaching Hospital, Ghana.

Antiphospholipid syndrome is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. The finding of individuals who present a clinical picture highly suggestive of antiphospholipid syndrome, but who are persistently negative for "criteria" of antiphospholipid antibodies has led physicians to refer to this patient population as having "seronegative" Antiphospholipid syndrome. We present a case of a 35-years old patient with strong clinical suspicion of antiphospholipid syndrome, with a history of recurrent pregnancy loss and one episode of deep vein thrombosis, but serologically negative, who was admitted and successfully managed and discharged.

Le syndrome des antiphospholipides est une maladie autoimmune systémique caractérisée par une thrombose et/ou une morbidité de la grossesse en présence d'anticorps antiphospholipides positifs persistants. La découverte d'individus qui présentent un tableau clinique hautement évocateur du syndrome des antiphospholipides, mais qui sont constamment négatifs pour les « critères ¼ des anticorps antiphospholipides a conduit les médecins à qualifier cette population de patients de syndrome des antiphospholipides « séronégatifs ¼. Nous présentons le cas d'une patiente de 35 ans avec une forte suspicion clinique de syndrome des antiphospholipides, avec des antécédents de fausses couches à répétition et un épisode de thrombose veineuse profonde, mais sérologiquement négative, qui a été admise et prise en charge avec succès et sortie de l'hôpital.

Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination.

Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

Microplastic pollution in waters of the Antarctic coastal environment of Potter Cove (25 de Mayo Island/King George Island, South Shetlands).

Plastic pollution in the Southern Ocean around Antarctica is a growing concern, but many areas in this vast region remain unexplored. This study provides the first comprehensive analysis of marine microplastic (MPs) concentrations in Potter Cove, located near the Argentinian Carlini research station on 25 de Mayo/King George Island, Antarctica. Water samples were collected at 14 sites within the cove, representing various influences from the station's activities. Two sampling methods were used: a 5 L Niskin bottle and an in-situ filtering device called Microfilter, allowing for large water volumes to be filtered. MPs were found in 100 % of the samples. Microfilter samples ranged from 0.02 to 2.14 MPs/L, with a mean concentration of 0.44 ± 0.44 MPs/L. Niskin bottle samples showed concentrations from 0.40 to 55.67 MPs/L, with a mean concentration of 19.03 ± 18.21 MPs/L. The dominant types of MPs were anthropogenic black, transparent, and pink microfibers (MFs) measuring between 0.11 and 3.6 mm (Microfilter) and 0.06 to 7.96 mm (Niskin bottle), with a median length of 0.01 mm for both methods. Transparent and black irregular microfragments (MFRs) with diameters from 0.10 to 5.08 mm and a median diameter of 0.49 mm were also prevalent. FTIR-spectroscopy revealed the presence of 14 types of polymers. Cellulose-based materials and polyethylene terephthalate were the most abundant in MFs, while polyurethanes and styrene-based copolymers dominated in MFRs. MPs were more abundant near the Carlini station. Compared to other coastal Antarctic areas, the MPs in the cove were relatively abundant and mostly smaller than 1 mm. Local activities on the island were identified as the primary source of MPs in the cove, and the cyclonic water circulation likely affects the distribution of small-sized particles. To protect the ecosystem, reducing plastic usage, improving waste management, regulating MPs debris, and enhancing wastewater practices are essential.

Preparedness, Hurricanes Irma and Maria, and Impact on Health in Puerto Rico.

OBJECTIVES: Only few studies evaluated whether hurricane preparedness impacts health. The PREPARE study addresses this gap. METHODS: We recruited participants who had pertinent pre-hurricane data from the San Juan Overweight Adults Longitudinal Study (SOALS: n=364) and 125 patients with diabetes from Federally Qualified Health Center (COSSMA) in Puerto Rico. Participants aged 42-75 years completed interviews 20-34 months after Hurricanes Irma and Maria. We evaluated associations between self-reported hurricane preparedness and health and other related associations using logistic regression controlling for age, location, education and interview date. RESULTS: Only 41% of participants reported high pre-hurricane preparedness; 25% reported gaps (moderate/low availability) in information and 48% reported gaps in resources for hurricane preparedness. Participants reporting lower pre-hurricane preparedness had higher reported hurricane-related detrimental health impact (OR=1.96; 95% CI: 1.31, 2.95) and higher odds (OR=2.07; 95% CI: 0.92, 4.68) of developing new non-communicable disease (NCD) compared to others. Post-hurricane drinking water disruption for ≥ 3 months versus none or less (OR=2.76; 95% CI: 1.39, 5.47) and similarly diet changes due to cooking/refrigeration access (OR=1.96; 95% CI: 1.24, 3.07), and diet changes for ≥ 20 months due to finances/access to shops (OR=2.83; 95% CI: 1.85, 4.32) were also associated with detrimental health impact. CONCLUSION: Lower preparedness was associated with higher detrimental impact of the hurricanes on overall health, and marginally significant impact on NCD. Future preparedness efforts could especially target means of coping with disruption of water services and regular diet, as these were also associated with detrimental health impact.

Characterization of motifs which are critical for activity of the cyclic AMP-responsive transcription factor CREB.

Cyclic AMP mediates the hormonal stimulation of a number of eukaryotic genes by directing the protein kinase A (PK-A)-dependent phosphorylation of transcription factor CREB. We have previously determined that although phosphorylation at Ser-133 is critical for induction, this site does not appear to participate directly in transactivation. To test the hypothesis that CREB ultimately activates transcription through domains that are distinct from the PK-A site, we constructed a series of CREB mutants and evaluated them by transient assays in F9 teratocarcinoma cells. Remarkably, a glutamine-rich region near the N terminus appeared to be important for PK-A-mediated induction of CREB since removal of this domain caused a marked reduction in CREB activity. A second region consisting of a short acidic motif (DLSSD) C terminal to the PK-A site also appeared to synergize with the phosphorylation motif to permit transcriptional activation. Biochemical experiments with purified recombinant CREB protein further demonstrate that the transactivation domain is more sensitive to trypsin digestion than are the DNA-binding and dimerization domains, suggesting that the activator region may be structured to permit interactions with other proteins in the RNA polymerase II complex.

Regulation of cAMP-inducible genes by CREB.

A large number of neuropeptides and neurotransmitters stimulate neuronal cells through the second messenger cAMP. These synaptic signals often cause profound changes in neuronal function by altering basic patterns of gene expression. Cyclic AMP, in turn, regulates a number of these genes through a conserved cAMP response element (CRE). Recently, a nuclear CRE-binding protein, CREB, has been shown to bind to the CRE and stimulate the transcription of cAMP-responsive genes. This article reviews recent progress towards understanding the mechanism by which cAMP modulates the activity of CREB to stimulate gene transcription.

Composite tissue (limb) allografts in rats. III. Development of donor-host lymphoid chimeras in long-term survivors.

Eight LEW rat recipients possessing long-term-surviving (206-701 days) LBN vascularized hind limb allografts (CTAs) were tested for donor-host lymphoid chimerism. The recipients received various cyclosporine (CsA) treatment protocols in order to induce indefinite CTA acceptance. Histological examination of long-term-surviving CTAs demonstrated normal-appearing bone marrow in the donor limb. Lymphocytes isolated from host hemopoietic tissues (peripheral blood and/or spleen) by ficoll-hypaque density gradient centrifugation were tested against LEW-anti-BN antisera. Comparisons were made to standard curves employing various known concentrations of LBN and LEW cell combinations. The level of lymphocyte agglutination (dependent variable) showed a significant (P less than 0.025-0.005) linear relationship to the concentration of LBN donor cells (independent variable) present. Lymphocyte suspensions isolated from long-term CTA host peripheral blood and/or spleen showed a mean of 19.7% (+/- 9.7-95% confidence interval) donor LBN mononuclear cells present. Thus, it appeared that lymphoid cells originated from, and/or were released from LBN donor bone marrow into the circulation, resulting in chimeric repopulation of hemopoietic tissues. The presence of donor immunocytes in these limb allograft recipients may have been beneficial, and thus could have helped contribute to the long-term CTA survival observed.

Cyclic AMP mediated gene expression in bovine corneal endothelial cells.

PURPOSE: Agents that increase intracellular levels of cAMP mediate gene expression associated with cellular morphology, growth, and/or differentiation via the cAMP response element (CRE). The cAMP element binding protein (CREB) is a transcriptional activator that binds and stimulates gene expression from the CRE in the promoters of cAMP responsive genes. This study was designed to characterize the cyclic AMP (cAMP) transcription apparatus in bovine corneal endothelial cells (BCE). METHODS: CRE transcriptional activity was determined by transient transfection assays using the CRE-chloramphenicol acetyl transferase gene (CRE-CAT) fusion reporter construct. Western blot analyses were performed to determine whether CREB was present in BCE. Mobility shift DNA-binding assay using gel electrophoresis and DNase I protection assays were performed to exclude the possibility of other CRE-binding factors. RESULTS: The authors identified the transcription factor, CREB, in nuclear extracts from BCE by Western blot analysis and showed that its DNA-binding characteristics are identical to the previously characterized CREB protein by DNase I protection and mobility shift DNA-binding studies. Transient transfection studies using the CRE-CAT reporter constructs revealed that the beta-adrenergic receptor agonist, isoproterenol, stimulates gene expression to levels similar to those induced by forskolin, a direct activator of adenylate cyclase (6.0- and 7.2-fold, respectively). CONCLUSIONS: The results suggest that agents that modulate receptors coupled to adenylate cyclase may effect the corneal endothelium by altering gene expression through the second messenger, cAMP.

Characteristics of the cAMP response unit.

Cyclic AMP (cAMP) mediates the hormonal stimulation of numerous cellular processes by regulating the phosphorylation of critical target proteins. In this report, we review current work suggesting that cAMP regulates transcription of eukaryotic genes through the reversible phosphorylation of a target nuclear protein called CREB. As CREB is currently the only transcription factor that is regulated by a well-defined cytoplasmic kinase-kinase-A, these studies may help to elucidate the general mechanisms underlying signal transduction.

Simulations of transport regime in electrodeposition in different viscosity scenarios.

In this work we study the effects of viscosity variations in thin-layer electrochemical deposition (ECD) under galvanostatic conditions through experimental measurements and theoretical modeling. The theoretical model, written in terms of dimensionless quantities, describes diffusive, migratory and convective ion transport in a fluid under galvanostatic conditions. Experiments reveal that as viscosity increases, convection decreases when the cell resistance remains constant. Our numerical model predicts that as viscosity increases, electroconvection becomes less relevant and concentration and convective fronts slow down. The time scaling of this phenomenon is studied and compared to previously reported low viscosity solution studies.

FiltraCheck-UTI, a rapid, disposable system for detection of bacteriuria.

The initial evaluation of the FiltraCheck-UTI bacteriuria detection system is described. The colorimetric test, which utilizes a disposable filter disk and a stable reagent system, does not require instrumentation. The test procedure is simple and may be performed in less than 1 min. Results obtained with the FiltraCheck-UTI system were compared with those obtained by conventional semiquantitative culturing. Of 1,198 urine specimens evaluated, 202 (16.9%) were determined to be significant positives at greater than or equal to 10(5) CFU/ml by the culture method. The sensitivity and specificity of the FiltraCheck-UTI system were 96.5 and 79.7%, respectively, and the negative predictive value was 99.1%. The high sensitivity, rapidity, simplicity, and unique disposable format of the FiltraCheck-UTI system offer significant advantages over other commonly used screening methods.

Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.

In this paper, we demonstrate that phosphorylation of CREB at Ser-133 is induced 6-fold in vivo, following treatment of PC12 cells with forskolin. By contrast, no such induction was observed in the kinase A-deficient PC12 line A126-1B2 (A126). Using F9 teratocarcinoma cells, which are unresponsive to cAMP, we initiated a series of transient expression experiments to establish a causal link between phosphorylation of CREB and trans-activation of cAMP-responsive genes. Inactivating the kinase A phosphorylation site by in vitro mutagenesis of the cloned CREB cDNA at Ser-133 completely abolished CREB transcriptional activity. As CREB mutants containing acidic residues in place of the Ser-133 phosphoacceptor were also transcriptionally inactive, these results suggest that phosphorylation of CREB may stimulate transcription by a mechanism other than by simply providing negative charge.