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Control of West Nile virus, Rhode Island, 2003.

Thanks largely to systematic larviciding by the State's 39 municipalities, and aided by the public's destruction of "backyard" mosquito habitats and adoption of personal protective measures (clothing, repellant), Rhode Island minimized the potential human burden of WNV during the 2003 mosquito season (six serious WNV cases, one death, and no reports of WNV-tainted blood donations). The potential burden of WNV on domestic animals was also reduced through immunization. Nonetheless, the State's first WNV death reminds us of the danger this disease poses for the very young, for elders, and for people of all ages who are immune-compromised. Similarly, the widespread location of birds positive for WNV signifies the ubiquity of risk. All mosquitoes must be avoided. Based on its experience with WNV control over the past few years, the State will continue and enhance its surveillance and control efforts in 2004. Once again, systematic larviciding by municipalities and continuing public education through multiple channels will form the backbone of control, supported by active surveillance for the virus in the wild, in domestic animals, and in humans. For the latter effort, the vigilance of the health care community is of signal importance to the protection of the public. Every human case is investigated thoroughly, to establish as accurately as possible the time and place of exposure. DEM and HEALTH use this information to assess potential weaknesses in WNV control efforts, and to take corrective action, as necessary. Health care providers also play an essential role in public education, reminding patients (all patients, but especially the very young, elders, and the immune-compromised) to avoid mosquito bites. Discussing the avoidance of mosquito bites with patients who engage in regular outdoor activity is especially important. School physicians and the medical directors of nursing homes are well-positioned to keep mosquito control and avoidance on the agenda of their respective institutions. Together, we can control the burden of this disease among domestic animals and humans, if we continue to pursue mosquito control and personal protection aggressively. If we don't, the potential for tragedy is tremendous, as evidenced by the recent experience of other regions of the country.

Animals↗

From finch to fish to man: role of aquaporins in body fluid and brain water regulation.

Charles Darwin, in his Origin of the Species, noted that different species of finches on the Galapagos Islands had adapted their beak size based on where they sought their food. Homer Smith, in his book From Fish to Philosopher, discussed the evolution of the nephron from a single conduit in salt water vertebrates, to nephrons with large glomerular capillaries and proximal and distal tubules in fresh water vertebrates, to smaller glomerular capillaries in amphibians, to nephrons with loops of Henle to allow for urinary concentration and dilution in mammals. The kidney with its million nephrons has emerged as the vital organ for regulating body fluid composition and volume. With the recent discovery of aquaporin water channels, our understanding of volume regulation has been greatly enhanced. This article reviews current knowledge regarding: 1) the unifying hypothesis of body fluid volume regulation; 2) brain aquaporins and their role in pathophysiologic states; and 3) function and regulation of renal aquaporins in the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Animals↗

Construction of two YAC contigs in human Xp11.23-p11.22, one encompassing the loci OATL1, GATA, TFE3, and SYP, the other linking DXS255 to DXS146.

We have constructed two YAC contigs in the Xp11.23-p11.22 interval of the human X chromosome, a region that was previously poorly characterized. One contig, of at least 1.4 Mb, links the pseudogene OATL1 to the genes GATA1, TFE3, and SYP and also contains loci implicated in Wiskott-Aldrich syndrome and synovial sarcoma. A second contig, mapping proximal to the first, is estimated to be over 2.1 Mb and links the hypervariable locus DXS255 to DXS146, and also contains a chloride channel gene that is responsible for hereditary nephrolithiasis. We have used plasmid rescue, inverse PCR, and Alu-PCR to generate 20 novel markers from this region, 1 of which is polymorphic, and have positioned these relative to one another on the basis of YAC analysis. The order of previously known markers within our contigs, Xpter-OATL1-GATA-TFE3-SYP-DXS255146- Xcen, agrees with genomic pulsed-field maps of the region. In addition, we have constructed a rare-cutter restriction map for a 710-kb region of the DXS255-DXS146 contig and have identified three CPG islands. These contigs and new markers will provide a useful resource for more detailed analysis of Xp11.23-p11.22, a region implicated in several genetic diseases.

Animals↗

Effects of toxic extracts and purified borbotoxins from Prorocentrum borbonicum (Dinophyceae) on vertebrate neuromuscular junctions.

Benthic dinoflagellates of the genus Prorocentrum are common in tropical and subtropical water and several species produce phycotoxins potentially involved in human toxic outbreaks. The toxic dinoflagellate Prorocentrum borbonicum collected at La Réunion Island (France) was cultured in laboratory. A crude extract of the organism displayed significant toxicity in mice characterized by progressive limb paralysis, severe dyspnea, and death, and the toxicity was retained, after partition, in the extract's butanol-soluble fraction (BSF). Electrophysiological experiments characterizing the fraction's effect on isolated vertebrate neuromuscular preparations revealed that it depolarizes the muscle membrane and reduces the driving force for endplate potentials (EPPs) evoked by nerve stimulation, blocking directly- and indirectly-elicited muscle twitches. The depolarization induced by P. borbonicum BSF was not due to Na(+) influx through voltage-dependent Na(+) channels, since tetrodotoxin neither prevented nor suppressed the depolarization. However, ouabain, a specific ligand of the Na/K ATPase, reduced the depolarization. These results suggest the presence of palytoxin-like compounds in the fraction. HPLC-MS and MS/MS analysis showed the presence of several toxins having identical UV absorbance, among which two new isomeric toxins, borbotoxin-A and -B, of molecular mass of 1037.6 Da were isolated. The purified borbotoxin-A, had no effect on the resting membrane potential of muscle fibers and did not affect directly-elicited muscle twitches. However, the toxin reduced nerve-evoked muscle twitches, in a dose-dependent manner, reduced EPPs' amplitudes and completely blocked miniature endplate potentials. These observations suggest that the main action of borbotoxin-A is to block post-synaptic nicotinic ACh receptors.

Animals↗

Increasing participation in cancer research: insights from Native Hawaiian women in medically underserved communities.

The cancer burden falls heavily on Native Hawaiian women, and of particular concern are those living in medically underserved communities where participation in potentially helpful clinical studies may be limited. Difficulty in accrual of Native Hawaiian women to a culturally-grounded intervention led researchers to conduct focus groups aimed at exploring attitudes towards research, use of a traditional Hawaiian practice for family discussion, and study promotion. Social marketing theory guided the development of discussion questions and a survey. Through purposive sampling, 30 women from medically underserved communities were recruited. Content analysis was used to identify major discussion themes. Findings indicate that lack of informational access may be a major barrier to participation. Study information disseminated through community channels with targeted outreach to social and religious organizations, promotion through face-to-face contact with researchers, and culturally tailored messages directed to families were preferred. Community oriented strategies based on linkages with organizational networks may increase participation.

Biomedical Research↗

Virulence factors of Helicobacter pylori.

To date a number of virulence factors have been identified and characterised from the gastric pathogen Helicobacter pylori. The vacuolating toxin (VacA) is a major determinant of H. pylori-associated gastric disease. In non-polarised cells, VacA alters the endocytic pathway, resulting in the release of acid hydrolases and the reduction of both extracellular ligand degradation and antigen processing. The toxin forms trans-membrane anion-specific channels and reduces the transepithelial electrical resistance of polarized monolayers. Localization of the VacA channels in acidic intracellular compartments causes osmotic swelling which, together with membrane fusion, leads to vacuole formation. The neutrophil-activating protein of H. pylori (HP-NAP) induces the production of oxygen radicals in human neutrophils via a cascade of intracellular activation events which may contribute to the damage of the stomach mucosa. This protein has recently been shown to be an important antigen in the human immune response to H. pylori infection. In addition, mice vaccinated with recombinant HP-NAP were protected against H. pylori challenge. H. pylori strains that are associated with severe tissue damage and inflammation possess the cag pathogenicity island that contains several genes encoding factors involved in the induction of proinflammatory cytokines/chemokines and of a type IV secretion system involved in the delivery of a highly immunogenic protein, CagA, into eukaryotic cells. Recent advances in our understanding of the involvement of VacA, HP-NAP and the CagA/Type IV secretion system in the H. pylori-associated disease process are discussed in this review.

Animals↗

Molecular phylogeny of the Ceratosolen species pollinating Ficus of the subgenus Sycomorus sensu stricto: biogeographical history and origins of the species-specificity breakdown cases.

The 14 species of Ficus of the subgenus Sycomorus (Moraceae) are invariably pollinated by Ceratosolen species (Hym. Chalcidoidea), which in turn reproduce in the fig florets. They are distributed mostly in continental Africa, Madagascar, and the Mascarene and Comoro Islands, but 1 species extends its geographical range all over the Oriental region. Fig-pollinator relationships are usually strictly species specific, but exceptions to the 'one-to-one' rule occur within the group we studied. In order to understand both the biogeographical history of the Ceratosolen species associated with Ficus of the subgenus Sycomorus and the origins of the specificity breakdown cases, we have used cytochrome b sequences to reconstruct a phylogeny of the fig wasps. The results show that the pollinators from the Malagasy region and those from continental Africa form two distinct clades, which probably diverged after the crossing of the Mozambique Channel by an ancestral population. The Oriental wasp species show strong affinities with the African species. The two species-specificity exceptions are due to different evolutionary events. The occurrence of the two West African pollinators associated with F. sur can be explained by successive speciation events of the mutualistic partner without plant radiation. In contrast, we hypothesize that C. galili shifted by horizontal transfer from an unknown, presumably extinct, Ficus species to F. sycomorus after this native Malagasy fig species colonized Africa.

Animals↗

Modeling the water balance of a small Pinus radiata catchment.

An hourly biophysical model was used to calculate the water balance over a period of one year for an 8.7-ha catchment with a closed-canopy, 13-year-old Pinus radiata D. Don forest in the central North Island, New Zealand. Components of the model are transpiration from the dry tree canopy, evaporation from the partially wet tree canopy and stems, evaporation from the understory and soil, and drainage from a single-layer root zone. The model requires input of hourly weather data (net radiation, air and wet bulb temperatures, windspeed, and rainfall), tree stand characteristics (average height, tree number, leaf area index), physical characteristics of the site (root zone depth, relationship between root zone matric potential and volumetric water content, the relationship between the rate of drainage from the root zone and volumetric water content, and the area of open-stream channels). A submodel of the response of stomatal conductance to air saturation deficit and root zone matric potential is also required. Tree transpiration (704 mm year(-1) or 50% of annual rainfall) was a dominant component of the catchment water balance. Estimated evaporation from the wet tree canopy was 203 mm year(-1) (15%). Evaporation from the understory was much less, amounting to 94 mm year(-1) (7%) and an increase in water storage for the 3.5 m root zone depth was estimated to be 53 mm year(-1) (4%). Estimated daily rates of drainage generally agreed well with measurements of streamflow, although estimated annual drainage (349 mm year(-1), 24%) exceeded measured streamflow (234 mm year(-1)). The significance of the results is discussed in relation to closure of the hydrologic balance.

Journal Article↗

Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2'-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome.

The aim of the present study was to investigate the possibility that ductal cells, which preferentially survive and/or proliferate in Sjögren's syndrome (SS) salivary glands of patients with SS, could acquire the functional expression of membrane water channel aquaporin-5 (AQP5). Thus, in this study, we demonstrate that an immortalized normal human salivary gland ductal cell (NS-SV-DC) line, lacking the expression of AQP5, acquires AQP5 gene expression in response to treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA demethylating agent. Confocal microscopic analysis revealed the localization of AQP5 expression mainly at the apical and lateral sides of the plasma membrane. The expressed AQP5 protein was functionally active because AQP5 expression resulted in a significant increase in the osmotically directed net fluid rate across monolayers of NS-SV-DC cells. By the analysis of bisulfite sequencing of CpG islands in the AQP5 promoter, hypermethylation within the consensus Sp1-binding sites was commonly observed in parental cell clones, whereas demethylation at the CGs, one in the second consensus Sp1 element and the other outside of the third consensus Sp1 element in the AQP5 promoter, was detected in NS-SV-DC cells after treatment with 5-Aza-CdR. By analyzing the luciferase activity of transfected AQP5 promoter vectors, it became evident that demethylation at the CGs cooperatively functions between these two sites to induce AQP5 expression. Our data, therefore, suggest that treatment of ductal cells with 5-Aza-CdR could result in the expression of the AQP5 gene, thereby leading to increased fluid secretion from ductal cells in SS salivary glands.

Aquaporin 5↗

The islet beta-cell.

The beta-cell is one of four major types of cells present in the islets of Langerhans, which are islands of cells distributed throughout the endocrine pancreas in most mammals. The beta-cell synthesizes and secretes the hormone insulin mainly in response to glucose but also in response to several nutrients, hormones and nervous stimuli. In adult rodents the beta-cell has a slow mitotic rate. Recent studies provide novel insights into the functions of the beta-cell. The presence of functional insulin-like growth factor-1 and insulin receptors and components of their signaling pathway indicate an important role for insulin/IGF-1 signaling in the regulation of beta-cell function. Further, the recent discovery of glucokinase (GK) and the ATP-dependent potassium channels on insulin secretory granules, the detection of AMP-protein kinase in the beta-cell and the identification of a new beta-cell transcription factor, mMafA, are some exciting new areas of research currently underway to further understand the complex pathways that regulate the functions of beta-cells.

Animals↗

The prevalence, aetiology and treatment of congestive cardiac failure in Antigua and Barbuda.

A retrospective review of the cases of congestive heart failure admitted to Holberton Hospital in Antigua in 1995 and 1996 was undertaken. Two hundred and ninety-three (293) patients were identified by International Statistical Classification of Diseases, 10th revision (ICD-10) coding as having congestive cardiac failure in the period but only 138 charts were either available or fitted the definition of congestive cardiac failure and these provided the basis for this analysis. The average age of patients admitted for congestive cardiac failure was 69 years (range: 5 months to 99 years), and 63% were female. the aetiology of congestive cardiac failure was hypertension (41%), ischaemia (33%), valvular (12%), alcohol related (2%), idiopathic (5%) and mixed (7%). Treatment included diuretics (95%), angiotensin converting enzyme inhibitors (78%), digoxin (75%), nitrates (34%), calcium channel blockers (25%), other vasodilators (7%) and antiarrhythmics (5%). Of those with congestive heart failure, diabetes was present in 38%, atrial fibrillation in 19%, renal insufficiency in 17%, elevated cholesterol in 11%, obesity in 9% and tobacco use in 7%. The in-hospital mortality in the 2-year period was 17.4% (females 15%, males 22%, 11% < 65 years, 20% > 65 years, 14% for those with 1 to 3 admissions and 83% for those with > 3 admissions, 19% for those with atrial fibrillation and 16% for those without). The prevalence of congestive cardiac failure utilizing the data analysed in this study (138 patients) was 0.21% of the population of the island state but based on the discharge diagnosis using ICD-10 coding it was 0.5%; it was 1% in the 40 to 65-year-age group and 4% in those > 65 years of age. The patients in this study represented only those with New York Heart Association (NYHA) classes III and IV, hence the true prevalence would be higher than recorded here. Congestive cardiac failure is emerging as a significant health problem in Antigua and Barbuda.

Adolescent↗

Changing trends in antihypertensive therapy in two New England communities during the 1980s.

The prevalence rates and correlates of antihypertensive drug use among individuals with hypertension were determined using data derived from five biennial population-based surveys conducted between 1981 and 1990 in two New England communities. Point prevalence estimates were determined for nine categories of antihypertensive agents at five time points, and were analyzed by age and sex using multiple logistic regression. In the first cross-sectional survey, the prevalence of use per 1000 individuals with hypertension was 235.4 for diuretics, 57.1 for beta-blockers, 65.5 for combination products, 29.2 for central alpha-agonists, 2.8 for peripheral alpha-antagonists, and 8.4 each for adrenergic blockers and direct vasodilators. The prevalence rates for calcium channel blockers and angiotensin-converting enzyme inhibitors increased sharply between the third and fourth survey cycles. Significant age- and sex-related differences in antihypertensive use were detected.

Adrenergic alpha-Agonists↗

Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome.

BACKGROUND: Specific ion channel mutations underlie the congenital long-QT syndrome (LQTS). However, the mechanisms by which dysfunction at the molecular level translates into functional electrical instability leading to torsade de pointes (TdP) in LQTS are poorly understood. METHODS AND RESULTS: The cellular basis of TdP was investigated using a novel approach of transmural optical imaging in the canine wedge preparation (n=14). The spatial organization of repolarization and arrhythmogenesis were determined in a surrogate model of LQT2. Action potentials were recorded simultaneously from 128 sites spanning the transmural wall of the left ventricle. In LQT2, QT interval prolongation was paralleled by an abrupt rise in transmural dispersion of repolarization (DOR) from 2.7 plus/minus 0.9 ms/mm (controls) to 12.2 plus/minus 2.1 ms/mm (LQT2). Islands of midmyocardial (M) cells formed zones of increased refractoriness in LQT2, producing steep spatial gradients of repolarization that were directly responsible for conduction block and self-sustained intramural reentrant circuits underlying TdP. CONCLUSIONS: These data provide direct evidence supporting the functional expression of M cells in intact myocardium and a central role for M cells in the development of reentrant TdP arrhythmias in LQTS.

Action Potentials↗

Piper methysticum (kava kava).

Piper methysticum (kava kava) is a plant native to the Pacific Island region, and has been used ceremonial for thousands of years. The active ingredients are a group of substances know as kava lactones (AKA kava pyrones). Four lactones in kava have been found to have significant analgesic and anesthetic effects via non-opiate pathways. Kava's most popular application is as a natural anxiolytic, comparing favorably in several studies to a number prescription medications, including benzodiazepines. CNS effects seem to be mediated by several mechanisms. Studies have been conflicting regarding its GABA-receptor-binding capacity, although this has been found to occur in some studies. In vitro kava has been found to block norepinephrine uptake. It also has some anti-convulsant capabilities, which appear to be mediated by Na+ channel receptor sites. The therapeutic dosage is in the range of 50-70 mg kava lactones three times daily. The most common side effect, usually seen only with long-term, heavy usage of the herb, is a scaly skin rash called "kava dermopathy." It has also been know to potentiate other medications such as barbiturates and Xanax.

Anti-Anxiety Agents↗

Durably controlling bovine hypodermosis.

Cattle hypodermosis, due to insect larvae, is widely spread over the northern hemisphere. Very efficient insecticides are available and their use in most countries are done on an individual level but never cover the whole cattle population of a country. Untreated animals remain the reservoir of the disease and annually re-infest the cattle population. The economic effects of this disease on animal production (meat, milk and the leather industry) but also on the general cattle health status, have led many European countries to launch organised control programs. The first example of definitive hypodermosis control goes back one hundred years ago when Danish farmers eradicated hypodermosis from the Danish islands by manual elimination of the warbles. Since then, more and more European countries have considered the feasibility and economic returns of such programs. The various factors which foster these programs are related to (i) biological factors, (parasite cattle specificity, synchronous biological cycles of both species of insects involved), (ii) the development of more and more efficient insecticides used only once a year by systemic application, with high efficiency at very low dosages against the first larval stage of Hypoderma spp., (iii) the development of acute techniques of detection of the disease for the monitoring of hypodermosis free countries and (iv) the durable successful results obtained in more and more European countries. Although the programs were imposed by different partners of the livestock channel production (farmers, dairy industry, leather industry) and have been engaged within the last 50 years in many European countries (Denmark, The Netherlands, Ireland, the United Kingdom, the Czech Republic, Germany, France and Switzerland) common features have emerged among these different eradication programs. They all need a preliminary statement of the economic impact of this pest and the farmers' awareness of the economic returns of such programs. The programs' efficacy depends: (i) on a good knowledge ofthe epidemiology of the parasites, (ii) on the simultaneous implementation of the control program on the whole national cattle population whatever the structure monitoring the treatments (veterinary services, farmers association), (iii) on a national Warble fly legislation making the treatments compulsory and (iv) on an acute epidemiological survey as soon as the status of a hypodermosis free country is reached and the treatments are suspended. The sanitary and financial returns of such programs are a benefit to all the partners of livestock production, to the quality of the environment and to the consumers.

Animals↗

Vascular adrenal cysts: a clinicopathologic and immunohistochemical study of six cases and a review of the literature.

The clinical, histologic, and immunohistochemical features of six cases of hemorrhagic adrenal pseudocysts are reported together, with a review of the English literature on this topic since 1950. The mean age at presentation was 57 years (range, 30-72 yr). There were four men and 2 women. The average cyst size was 9.2 cm (range, 6-16 cm). In four patients, the hemorrhagic adrenal pseudocysts were incidental findings. The remaining two patients presented with an abdominal mass and hypertension, respectively. The hemorrhagic pseudocysts were unilocular cystic masses surrounded by a fibrous capsule and containing abundant amorphous material, blood, and fibrin. Numerous dilated, thin-walled, vascular channels that stained strongly for Factor VIII-related antigen, collagen IV, laminin, Ulex europaeus agglutinin I lectin, and CD34 were present within the fibrous capsule, cyst contents, and surrounding residual adrenal gland. These findings support a vascular origin for these lesions, and they are thought, therefore, to be related to endothelial adrenal cysts. The literature review of 111 vascular adrenal cysts (85 hemorrhagic pseudocystic type and 26 endothelial type) showed similar clinical features. The mean age at presentation was 44.5 years (range, 5 d-95 yr), with a female predominance (62%). The most common clinical presentation was abdominal pain (35%), followed by incidental findings (32%). There were no significant clinical differences between hemorrhagic and endothelial type cysts. In some cases, the presence of intracystic islands of cortical cells can cause diagnostic confusion with adrenal cortical tumors. The presence, however, of a rich intracystic and capsular vascular network, normal-appearing islands of cortical cells, and abundant thrombotic fibrinous material, rather than necrotic tumor cells, should rule out the possibility of a degenerating adrenal cortical neoplasm.

Adrenal Gland Diseases↗

Energetics of swimming of a sea turtle.

Young (mean mass 735 g) green turtles (Chelonia mydas) were able to swim in a water channel at sustained speeds between 0-14 and 0-35 m.s-1. Oxygen consumption at rest was was 0-07 l.kg-1.h-1; at maximum swimming speed oxygen consumption was 3-4 times greater than at rest for a given individual. In comparison with other animals of the same body mass the cost of transport for the green turtle (0.186lO2.kg-1.km-1) is less than that for flying birds but greater than that for fish. From drag measurements it was calculated that the aerobic efficiency of swimming was between 1 and 10%; the higher efficiencies were found at the higher swimming speeds. Based upon the drag calculations for young turtles, it is estimated that adult turtles making the round-trip breeding migration between Brazil and Ascension Island (4800 km) would require the equivalent of about 21% of their body mass in fat stores to account for the energetic cost of swimming.

Aerobiosis↗

High-resolution mapping of the gamma-aminobutyric acid receptor subunit beta 3 and alpha 5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients.

The gamma-aminobutyric acid (GABAA) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABAA receptor beta 3 subunit gene (GABRB3) and alpha 5 subunit gene (GABRA5) in chromosome 15q11-q13, we have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. We have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints--in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion--are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region.

Angelman Syndrome↗