Strongyloides stercoralis infection as a cause of acute granulomatous appendicitis in an HIV-positive patient in Athens,Greece

A case of acute granulomatous appendicitis due to Strongyloides stercoralis infection in an HIV-positive patient is described. To our knowledge this is the first case presented in the literature.     

Fas signaling in thyroid carcinomas is diverted from apoptosis to proliferation.

PURPOSE: The death receptor Fas is present in thyroid carcinomas, yet fails to trigger apoptosis. Interestingly, Fas has been reported to be actually overexpressed in papillary thyroid carcinomas, suggesting that it may confer a survival advantage. EXPERIMENTAL DESIGN: We investigated the expression and activation status of Fas pathway mediators in thyroid carcinoma cell lines and tumor specimens. RESULTS: All cell lines tested express Fas-associated death domain, procaspase-8, procaspase-9, and procaspase-3; resistance to Fas-mediated apoptosis could not be attributed to lack of any of these apoptosis mediators. Moreover, Fas death domain mutations were not found in our study. The proteasome inhibitors MG132 and PS-341 (bortezomib, Velcade), which lead to accumulation of the nuclear factor kappaB (NF-kappaB) inhibitor IkappaB, did not sensitize SW579 cells to Fas-mediated apoptosis, suggesting that resistance to Fas-mediated apoptosis is not due to proteasome or NF-kappaB activity. Cross-linking of Fas in vitro induced recruitment of Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) instead of procaspase-8. Inhibition of FLIP expression with a FLIP antisense oligonucleotide resulted in significant sensitization to Fas-mediated apoptosis. Fas cross-linking promoted BrdUrd incorporation; activated the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase, NF-kappaB, and activator protein-1 pathways in thyroid carcinoma cells in vitro; and protected cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. We also found that good prognosis papillary thyroid carcinoma specimens exhibited higher immunoreactivity for cleaved (activated) caspase-8 than poor prognosis tumors. CONCLUSIONS: In thyroid carcinomas, the proteolytic cleavage and activation of caspase-8 depends on the balance between expression levels for procaspase-8 and FLIP and correlates with favorable clinical prognosis. Fas may actually stimulate proliferation and confer a survival advantage to thyroid cancer cells.     

A common hormone-sensitive lipase i6 gene polymorphism is associated with decreased human adipocyte lipolytic function

Hereditary factors may be involved in the pathogenesis of type 2 diabetes. A polymorphism in the hormone-sensitive lipase (HSL) gene (HSLi6) is associated with obesity and diabetes, although it is unknown whether the polymorphism is functional and thereby influences lipolysis. We genotyped 355 apparently healthy nonobese male and female subjects for the HSLi6 polymorphism. Allele 5 was found to be the most common allele (allele frequency 0.57). In 117 of the subjects, we measured abdominal subcutaneous fat cell lipolysis induced by drugs acting at various steps in the lipolytic cascade. The lipolysis rate induced by norepinephrine isoprenaline (acting on beta-adrenoceptors), forskolin (acting on adenylyl cyclase), and dibutyryl cyclic AMP (acting on HSL) were all decreased by approximately 50% in allele 5 homozygotes, as compared with noncarriers. Heterozygotes showed an intermediate lipolytic rate. The difference in lipolysis rate between genotypes was more pronounced in men than in women. We conclude that allele 5 of the HSLi6 polymorphism is associated with a marked decrease in the lipolytic rate of abdominal fat cells. This may in turn contribute to the development of obesity.     

Pathogenic BRCA1 mutations may be necessary but not sufficient for tissue genomic heterogeneity: Deep sequencing data from ovarian cancer patients

Background

Tissue genomic heterogeneity (t-HET) in patients with epithelial ovarian cancer (OVCA) is related to tissue plasticity, i.e., flexibility to adapt to adverse molecular environments. Here, we interrogated the presence and clinical relevance of OVCA t-HET.

Clinical and laboratory effects of long-term administration of hydroxyurea to patients with sickle-cell/β-thalassaemia

Hydroxyurea (HU), a widely used cytostatic, has been given over a long period of time to 14 adult Caucasian compound heterozygotes for β^s and various β-thalassaemia genes. All patients had severe pain crises and other complications prior to receiving the drug. After 4-8 weeks on high 'sub-toxic'doses of HU all patients responded with a multifold increase of fetal haemoglobin (HbF) and a marked increase of MCV and MCH; they also felt significantly better and ceased having pains or other complaints. Haematological toxicity was minimal and rapidly reversible. Follow-up of the patients has now exceeded 100 weeks and goes up to 180 weeks in two of them. Pain crises have never recurred. Maintenance of high levels of HBF requires continuous administration of high doses of HU; whenever the latter were decrease in various attempts to avoid potential long-term toxicity, the observed changes gradually faded. The effect of HU in HbS/β-thalassaemia may be better than that reported for homozygous HbS disease because the synthesized λ-chains not only inhibit the sickling process but they also neutralize the noxious effects of the excess α-chains and cut down the ineffective erythropoiesis of the patients.     

Insights into the origin of postmortem ethanol

Accurate interpretation of the blood ethanol (EtOH) concentration at the time of death presents a difficult task since the origin of detected EtOH in postmortem cases (either in corpses or in specimens after sample collection) may vary. Headspace gas chromatography is the choice method for detecting EtOH in blood or other specimens, due to the accuracy and sensitivity it provides. Possible sources of postmortem EtOH have been the ante-mortem ingestion, the ante-mortem endogenous production and the postmortem microbial neo-formation, which has been considered the most critical factor that could complicate the results. It has been reported that EtOH could be formed postmortem in variable and non-predictable amounts, as a function of the type and number of microorganisms present either in corpses or specimens collected at autopsy. The presence of other volatiles-mostly n-propanol-has been correlated to microbial EtOH production, although the quantitative pattern between them and EtOH still remains obscure. The factors most frequently implicated in the mechanism of postmortem EtOH production in corpses have been considered the number and nature of microbes present, the availability of various types of substrates, the temperature and the time. Complication in the interpretation of blood alcohol concentration could arise due to the atypical distribution of EtOH in the body compartments after death. Specimens to blood EtOH ratios reported in the literature are presented. All the aforementioned aspects are discussed in a comprehensive way, providing a deep insight into this essential problem.     

Evaluation of the methods used for carboxyhemoglobin analysis in postmortem blood

Numerous methods have been described in the literature for the determination of carboxyhemoglobin (COHb) in whole blood. The most popular and widely used have been (1) the spectrophotometric methods, which could be performed either by using a conventional spectrophotometer or by using specialized automated instruments known as CO-oximeters; (2) the gas chromatographic methods, with variable detection systems, which have been considered as the reference methods for every carbon monoxide analysis. The authors have critically reviewed previously reported comparative studies on these methods, considering statistical and analytical matters, in order to propose the best method for the determination of COHb in postmortem blood, that could be utilized in forensic toxicology laboratories where such analyses are limited in number (less than 20 per year). Criteria for evaluation have been accuracy, reliability, simplicity, time, and cost. The authors' concluding statement has been that the manual spectrophotometric method could be the method of choice for COHb determination in postmortem blood samples. It is simple, rapid, and reliable and fulfills the forensically acceptable accuracy. It is performed by the use of a conventional spectrophotometer, which is considered a basic instrument in every analytical laboratory.     

Loss of E-cadherin and p27 expression is associated with head and neck squamous tumorigenesis

BACKGROUND: In neoplastic head and neck lesions, it has been found that the loss or reduction in E-cadherin expression is a late event and is associated with invasion. Low p27 levels have been associated with a poor prognosis in many different tumors, including laryngeal carcinoma. The authors investigated p27 and E-cadherin protein expression in the early stages of head and neck tumorigenesis and evaluated their predictive roles individually and in association with carcinogenesis. METHODS: Tissue biopsies from 46 patients who were participants in 3 chemoprevention trials were analyzed for E-cadherin expression, and 40 samples were analyzed for p27 expression using immunohistochemistry. RESULTS: The data suggested that loss of both E-cadherin expression and p27 expression occurred early during the preneoplastic steps of head and neck carcinogenesis, and loss of p27 protein expression alone (P=0.02) and in combination with loss of E-cadherin expression (P=0.04) was a significant predictor of the risk for head and neck carcinoma. CONCLUSIONS: The loss of p27 expression may be useful in the construction of a risk model for head and neck carcinogenesis and may represent a potential target for chemopreventive interventions. Longer follow-up of the high percentage of low-risk preneoplastic lesions in the current study and validation in a larger sample size may be required to establish the predictive role of these abnormalities.     

Hypoparathyroidism in a patient presenting with severe myopathy and skin rash. Case report and review of the literature

A 47-year old man with idiopathic hypoparathyroidism (IHP), presented as severe myopathy and skin rash is described. The serum muscle enzymes were increased. After treatment with calcium and vitamin D, the clinical condition improved, the skin rash gradually disappeared, and the muscle enzymes decreased and remained within the normal range thereafter.