128 research outputs found
GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis
Objective:
To describe the findings of histopathology and genotyping studies in affected brain tissue from
an individual with phacomatosis pigmentovascularis (PPV). /
Methods:
A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV
cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology
findings, and genotyping studies in his affected brain tissue are summarized. /
Results:
The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the
setting of status epilepticus. A somatic pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys)
was detected in his skin tissue but not in blood (previously published). He underwent an urgent
left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain
tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the
exact pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys), previously isolated from his skin
tissue but not blood, was detected in his resected brain tissue. /
Conclusions:
The finding of this variant in affected skin and brain tissue of our patient with PPV supports
a unifying genetic diagnosis of his neurocutaneous features
Cost-effectiveness analysis of PCR for the rapid diagnosis of pulmonary tuberculosis
<p>Abstract</p> <p>Background</p> <p>Tuberculosis is one of the most prominent health problems in the world, causing 1.75 million deaths each year. Rapid clinical diagnosis is important in patients who have co-morbidities such as Human Immunodeficiency Virus (HIV) infection. Direct microscopy has low sensitivity and culture takes 3 to 6 weeks <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. Therefore, new tools for TB diagnosis are necessary, especially in health settings with a high prevalence of HIV/TB co-infection.</p> <p>Methods</p> <p>In a public reference TB/HIV hospital in Brazil, we compared the cost-effectiveness of diagnostic strategies for diagnosis of pulmonary TB: Acid fast bacilli smear microscopy by Ziehl-Neelsen staining (AFB smear) plus culture and AFB smear plus colorimetric test (PCR dot-blot).</p> <p>From May 2003 to May 2004, sputum was collected consecutively from PTB suspects attending the Parthenon Reference Hospital. Sputum samples were examined by AFB smear, culture, and PCR dot-blot. The gold standard was a positive culture combined with the definition of clinical PTB. Cost analysis included health services and patient costs.</p> <p>Results</p> <p>The AFB smear plus PCR dot-blot require the lowest laboratory investment for equipment (US 5,635,760 versus US 50,773 and US 374,778,045 and US$ 110,849,055, respectively.</p> <p>Conclusion</p> <p>AFB smear associated with PCR dot-blot associated has the potential to be a cost-effective tool in the fight against PTB for patients attended in the TB/HIV reference hospital.</p
Smear plus Detect-TB for a sensitive diagnosis of pulmonary tuberculosis: a cost-effectiveness analysis in an incarcerated population
Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain
Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population
Transgenic Overexpression of Active Calcineurin in β-Cells Results in Decreased β-Cell Mass and Hyperglycemia
BACKGROUND:Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+) influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+) signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes. METHODOLOGY/PRINCIPAL FINDINGS:To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP)). To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP) mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis. CONCLUSIONS:Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes
A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model
Women in nursing teams: organizational identification and experiences of pleasure and suffering
The genome of the sea urchin Strongylocentrotus purpuratus
We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus
purpuratus, a model for developmental and systems biology. The sequencing strategy combined
whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones,
aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome.
The genome encodes about 23,300 genes, including many previously thought to be vertebrate
innovations or known only outside the deuterostomes. This echinoderm genome provides an
evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
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