75,063 research outputs found

    Hsp-90 and the biology of nematodes

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    BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different free-living or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints.<BR/>RESULTS: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GA-binding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not.<BR/>CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin

    Effect of the Healthy Schools Program on prevalence of overweight and obesity in California schools, 2006-2012.

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    IntroductionThe Alliance for a Healthier Generation's Healthy Schools Program (HSP) is a national evidence-based obesity-prevention initiative aimed at providing the schools in greatest need with onsite training and technical assistance (TTA) and consultation with national experts (HSP national advisors) to create sustainable healthy change in schools' nutrition and physical activity environments. The objective of this study was to evaluate the impact of HSP on the prevalence of overweight and obesity in California schools, from HSP's inception in 2006 through 2012.MethodsWe used statewide body mass index (BMI) data collected annually from 5th-, 7th-, and 9th-grade students to determine whether enrolling in the HSP's onsite intervention reduced the prevalence of overweight and obesity in intervention schools (n = 281) versus propensity-score matched control schools (n = 709) and whether increasing exposure to the program (TTA and contact with HSP national advisors) was associated with reductions in the prevalence of overweight and obesity.ResultsAnalyses showed no difference between HSP schools and control schools in overweight or obesity prevalence. However, program exposure varied widely among participating schools, and each additional contact with TTA or HSP national advisors was associated with a 0.3% decline in overweight and obesity prevalence (P < .05).ConclusionHSP appears to be an important means of supporting schools in reducing obesity. Although participation in HSP alone was not sufficient to improve weight status in California schools, there was a clear dose-response relationship to the program. HSP serves as an effective model for addressing childhood obesity among engaged schools

    Assessment of babA2 and hsp genotype frequency in Helicobacter pylori specimens isolated from digestive disorders patients

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    Background and Objective: Helicobacter pylori is the main gastric pathogen in human. BabA2 and Hsp genotypes are essential for enormous clinical outcomes in gastreodeoneal and dyspepsia. This study was done to determine the assessment of babA2 and hsp genotype frequency in Helicobacter pylori specimens isolated from digestive disorders patients. Method: This descriptive-analytic study was carried out on 80 digestive disorders patients in 5 th hospital, Gorgan, northern Iran. Stomach specimen biopsy was taken by a gastroenterologist. Urease test, histopathologic assessment and DNA extraction were performed. The frequency of babA2 and hsp genotypes was determined using poly merase chain reaction. Results: In 80 affected patients with H.pylori, 36, 18 and 26 patients were found to suffer from gastritis, stomach cancer and stomach ulcer, respectively. 51 specimens (63%) were positive babA2 genotype. 49 specimens (61%) were positive hsp genotype. No significant relationship was found between babA2 and hsp geno types with stomach diseases. Conclusion: In spite of positive babA2 and hsp genotype in isolated Helicobacter pylori speicments from digestive disorders patients, this finding was not correlated with type of digestive disorders

    SPG10 is a rare cause of spastic paraplegia in European families

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    Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date.Objective: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype.Patients and methods: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families.Results: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory--motor neuropathy was detected by neurophysiology studies.Conclusions: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy

    A Case of Henoch-Schonlein Purpura Associated with Rotavirus Infection in an Elderly Asian Male and Review of the Literature.

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    BACKGROUND Henoch-Schönlein purpura (HSP), a small vessel vasculitis mediated by deposition of immune-complexes containing IgA in the skin, gut, and glomeruli, often presents with abdominal pain, purpuric rash in the lower extremities and buttocks, joint pain, and hematuria. The disease most commonly targets children but can affect adults who tend to have a worse prognosis. CASE REPORT We discuss a case of HSP in an elderly Chinese male who presented with severe proximal bowel inflammation, vasculitic rash, and proteinuria; he was found to have positive stool rotavirus and giardia. He improved significantly with high dose steroids. We believe rotavirus may have been a triggering event in this patient. A brief review of the literature is also presented. CONCLUSIONS This is the first case report describing a classic presentation of HSP in an adult following a rotavirus infection. HSP can cause significant morbidity and mortality in adult patients predominantly from progressive renal failure; therefore careful management and monitoring is important. GI infections seem to be a common trigger for HSP and this case report suggests that rotavirus may be part of the spectrum

    Electro-hyperthermia in Oncology

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    Hyperthermia is a rapidly developing treatment method in oncology. The classical effect is based on well-focused energy absorption targeting the malignant tissue. Unfortunately, the heat-shock protein (HSP) synthesis may considerably suppress the treatment’s efficiency, causing cells to adapt and survive the shock. Electro-hyperthermia heats the targeted tissue by means of electricity, producing less HSP in the cells than classical hyperthermia. The main improvement is keeping the energy absorption within the extracellular matrix (ECM). By heating the ECM, ion-mobility increases, metabolic rates increase, and the heat destroys the cells’ membrane before the heat-shock activates the intra-cellular HSP mechanisms

    Service delivery for people with hereditary spastic paraparesis living in the South West of England.

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    PURPOSE: Hereditary Spastic Paraplegia (HSP) is an inherited nervous system disorder characterized by development of leg weakness, spasms and stiffness. While generally acknowledged that health and social care services can minimise symptoms and improve quality of life, there is a lack of research exploring this from the perspective of people affected by HSP. This qualitative study explored the users and providers experience of using rural services. METHOD: Focus groups and interviews were undertaken of people with HSP (n = 14), carers (n = 6) and professionals (n = 12), to describe their experience of service provision and to suggest improvements for care. These were taped, transcribed and analysed. RESULTS: Four themes emerged: (1) Diagnosis, symptoms and finding support; (2) Therapy, treatment and the delivery of care; (3) Managing the disease together; and (4) The way forward. CONCLUSIONS: Rehabilitation and support for self-management is valued by those affected with HSP throughout the disease trajectory from diagnosis onwards. Key to this is the development of a partnership approach which includes carers. Single point, well-informed, gatekeepers may enhance the coordination and delivery of care in rural areas. These findings underline current guidance promoting a holistic approach for people with neurological conditions

    Further supporting evidence for REEP1 phenotypic and allelic heterogeneity.

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    Heterozygous mutations in REEP1 (MIM #609139) encoding the receptor expression-enhancing protein 1 (REEP1) are a well-recognized and relatively frequent cause of autosomal dominant hereditary spastic paraplegia (HSP), SPG31.1 REEP1 localizes in the mitochondria and endoplasmic reticulum (ER) and facilitates ER-mitochondria interactions.2 In addition to the HSP phenotype, REEP1 has been associated with an autosomal dominant spinal type of Charcot-Marie-Tooth disease in 2 families.3 More recently, a patient with homozygous REEP1 mutation with a much more severe phenotype akin to spinal muscular atrophy with respiratory distress type 1 (SMARD1) was reported.4 In this report, we present a patient with a homozygous mutation in REEP1 manifesting a severe congenital distal spinal muscular atrophy (SMA) with diaphragmatic paralysis, expanding the phenotype from mild autosomal dominant HSP through to severe recessive distal SMA pattern
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