Investigating the role of imprinted genes in pediatric sporadic brain arteriovenous malformations

Arteriovenous malformation AVM is a vascular congenital defect affecting microvasculatu re of both brain and peripheral o rga ns.Arteriovenous malformation of the brain(bAVM,OMIM#108010),in particular,affects up to 15 per100,000 persons with no sex predominance.Almost 50%of the patients manifest intracerebral hemorrhage and epileptic seizures,as main clinical symptoms.     

A factor secreted by human embryo stimulates cytokine release by uterine mast cell

The existence of a biochemical network of embryo-maternal communicationimplies that various secreted molecules constitute a signal-responsemechanism, important for the process of embryo implantationin mammals. Here we report the purification of a protein withan apparent molecular weight of 136 kDa, responsible for a 2000-foldincrease in embryo-derived histamine-releasing factor (EHRF)activity. This protein, purified from medium from the in-vitroculture of 2–8-cell human embryos, by means of affinitychromatography, was capable of binding immunoglobulin (lg)Eas demonstrated by immunoblotting and enzyme-linked immunosorbentassays. We found that EHRF was capable of inducing release ofhistamine and cytokines in vitro from rat uterine tissue, collectedon day 4 of pregnancy (preimplantation stage of embryo development).When EHRF was used as a secretagogue, granulocyte macrophage-colonystimulating factor (GM-CSF) release increased from 3 to 55 pg/g(P <0.01) and tumour necrosis factor-     

Endothelin-1 concentrations in cord blood of neonates with meconium-stained amniotic fluid

BACKGROUND: The effects of meconium-stained amniotic fluid (MSAF) on cord blood endothelin-1 (ET-1) concentrations have not been explored. OBJECTIVE: The aim of this study was to verify whether MSAF influences ET-1 cord blood concentrations in healthy term neonates. METHODS: Using an enzyme-linked immunosorbent assay, plasma ET-1 concentrations were determined in 30 healthy term neonates with MSAF, and in 15 healthy term neonates without MSAF. The two groups were of the same gestational age, weight, Apgar score, cord blood pH, base excess, and hematocrit values, as well as systolic and diastolic blood pressures. RESULTS: ET-1 plasma concentrations were not significantly different between the two groups and did not correlate with cord blood pH or base excess values. CONCLUSION: Our data demonstrate that meconium passage does not induce ET-1 secretion.     

Renal plasma flow, filtration fraction and microalbuminuria in hypertensive patients: effects of chronic smoking

INTRODUCTION: Albumin excretion rate is usually increased in people who smoke, but the physiological basis of this phenomenon is not fully understood. METHODS: The effect of chronic smoking on renal haemodynamics was studied in a cohort of 66 men. Twenty-seven were smokers and 36 were hypertensive. In all subjects, the albumin excretion rate was evaluated; in hypertensive patients, a renoscintigraphic evaluation of renal plasma flow and glomerular filtration were carried out and the filtration fraction was calculated. RESULTS: The hypertensive smoking population presented an increased urinary albumin excretion rate in comparison with hypertensive non-smoking patients. No significant differences were found for the mean values of renal plasma flow, the glomerular filtration rate and the filtration fraction between hypertensive smokers and hypertensive non-smoking patients. CONCLUSIONS: In hypertensive patients, smoking does not modify typical renal haemodynamic changes of arterial hypertension; however, it significantly increases the albumin excretion rate.     

Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors

Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia.At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2)-positive tissues, both D(2) isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisol-secreting carcinomas, in which only the D(2long) isoform was expressed. D(2)-like receptor expression was confirmed at receptor-ligand binding study. At immunohistochemistry, D(2) was mainly localized in the zona glomerulosa and reticularis of the adrenal cortex and, to a lesser extent, in the zona fasciculata and medulla of normal and hyperplastic adrenal tissue. In the positive tumors, D(2) was localized in the tumoral cells. At the in vitro study, a significant inhibition of both baseline and ACTH-stimulated aldosterone secretion was found after high-dose cabergoline, but not bromocriptine, administration; and a significant inhibition of angiotensin-II-stimulated aldosterone secretion was found after both bromocriptine and cabergoline administration in the adrenal hyperplasias. In conclusion, the current study demonstrated that both D(1)-like and D(2)-like receptors are expressed in the normal adrenal gland and in a percentage of adrenal adenomas or carcinomas. Bromocriptine and cabergoline induce only a minor inhibition of the secretion of adrenal hormones in the nontumoral adrenal gland in vitro, not excluding, however, the possible effective use of dopamine agonists in vivo in the treatment of adrenal tumors.     

Identification of HBV DNA sequences that are predictive of response to lamivudine therapy

Numerous studies have shown that resistance to long-term lamivudine therapy occurs in as many as (2/3) of hepatitis B virus (HBV) chronic carriers. Additional studies have shown that reversion of HBV mutations in the precore/core promoter region conferring an HBeAg-negative phenotype/genotype can occur in up to 30% of lamivudine-treated patients. In this study, sequences of the HBV polymerase and precore/core coding regions in 26 HBV-infected patients (24 with HBeAg-negative virus infection, 25 genotype D, 1 genotype A) treated for 27 to 53 months with lamivudine were analyzed to determine the relationship between pretreatment HBV DNA sequence patterns and long-term treatment response, and the effect of therapy on the status of HBV precore mutations. Reversions of precore mutations A1762T/G1764A and G1896A were observed in 29% and 25% of patients, respectively, but none became HBeAg-positive. These data are consistent with previously published reversion frequencies for 2 other groups of lamivudine-treated patients. Two naturally-occurring DNA polymorphisms at aa91 and aa256 of the HBV polymerase were observed in the pretreatment serum samples, which correlated with extended treatment failure. In conclusion, reversion of mutations conferring an HBeAg-negative phenotype occur relatively frequently under lamivudine therapy. Furthermore, at least in HBeAg-negative patients infected predominantly with HBV genotype D, specific viral DNA sequences which are present before therapy appear to be useful as predictors of long-term response to lamivudine treatment.     

Knowledge discovery in databases of biomechanical variables: application to the sit to stand motor task

Background  

The interpretation of data obtained in a movement analysis laboratory is a crucial issue in clinical contexts. Collection of such data in large databases might encourage the use of modern techniques of data mining to discover additional knowledge with automated methods. In order to maximise the size of the database, simple and low-cost experimental set-ups are preferable. The aim of this study was to extract knowledge inherent in the sit-to-stand task as performed by healthy adults, by searching relationships among measured and estimated biomechanical quantities. An automated method was applied to a large amount of data stored in a database. The sit-to-stand motor task was already shown to be adequate for determining the level of individual motor ability.     

<Emphasis Type="Italic">In vitro</Emphasis> modulation of the multiple sclerosis (MS)-associated retrovirus by cytokines: Implications for MS pathogenesis

Multiple sclerosis (MS)-associated retrovirus (MSRV) is a component of the human endogenous retrovirus (HERV)-W family, with gliotoxic and superantigenic properties, related to MS clinical progression, and transactivated by viral agents. The authors studied MSRV modulation by cytokines involved in vivo in MS course, utilizing peripheral blood mononuclear cells from MSRV-positive and MRSV-negative individuals. Cultured cells from MSRV-negative subjects did not produce virus, whereas spontaneous MSRV release was detected in cultures from MSRV-positive donors; virus release was increased by interleukin (IL)-4 and IL-6 and, to a greater extent, by the detrimental cytokines interferon gamma and tumor necrosis factor (TNF)alpha. Interferon beta, used in MS therapy, inhibits MSRV release. A parallel between the effects of these cytokines on MSRV production in vitro and on MS disease in vivo is observed, which deserves further elucidations.