Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia.

We report the case of a child with clinical and haematological features indicative of juvenile myelomonocytic leukaemia (JMML). The patient showed dysmorphic features: high forehead, bilateral epicanthal folds, long eyebrows, low nasal bridge and slightly low-set ears. A 38G>A (G13D) mutation in exon 1 of the NRAS gene was first demonstrated on peripheral blood cells, and then confirmed on granulocyte-macrophage colony-forming units.

Diabetes changes the levels of ionotropic glutamate receptors in the rat retina.

Purpose: Diabetic retinopathy (DR) is a leading cause of vision loss and blindness among adults between the age 20 to 74. Changes in ionotropic glutamate receptor subunit composition can affect retinal glutamatergic neurotransmission and, therefore, contribute to visual impairment. The purpose of this study was to investigate whether diabetes leads to changes in ionotropic glutamate receptor subunit expression at the protein and mRNA level in the rat retina.

The molecular basis for the regulation of the cap-binding complex by the importins.

The binding of capped RNAs to the cap-binding complex (CBC) in the nucleus, and their dissociation from the CBC in the cytosol, represent essential steps in RNA processing. Here we show how the nucleocytoplasmic transport proteins importin-alpha and importin-beta have key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.

Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas.

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment.

Hypereosinophilic syndrome in childhood: clinical and molecular features of two cases.

Hypereosinophilic syndrome (HES) represents a heterogeneous group of diseases, some of which are being clarified by recent advances in molecular genetics. It is very rare in children. Uncertainties in classification and lack of prospective studies make therapeutic decisions difficult.

Neuropeptide Y inhibits [Ca2+]i changes in rat retinal neurons through NPY Y1, Y4, and Y5 receptors.

Neuropeptide Y (NPY) and NPY receptors are widely distributed in the CNS, including the retina, but the role of NPY in the retina is largely unknown. The aim of this study was to investigate whether NPY modulates intracellular calcium concentration ([Ca(2+)](i)) changes in retinal neurons and identify the NPY receptors involved. As NPY decreased the [Ca(2+)](i) amplitudes evoked by 30 mM KCl in only 50% of neurons analyzed, we divided them in two populations: NPY-non-responsive neurons (Delta2/Delta1 > or = 0.

Correlation between morphology and function of the upper lip: a longitudinal evaluation.

In order to evaluate the relationship between the morphology of the upper lip and muscle activity in a sample of 38 subjects (17 males and 21 females) with Angle Class II division 1 malocclusions, cephalometric and electromyographic analyses were conducted. The sample was subdivided into either predominantly nose or mouth breathers. The individuals were evaluated at two different periods, with a 2 year interval.

Evaluation of an antimicrobial silver foam dressing for use with V.A.C. therapy: morphological, mechanical, and antimicrobial properties.

The V.A.C.

Simultaneous above and below approach to giant pituitary adenomas: surgical strategies and long-term follow-up.

Introduction: Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach.

Method: A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.

High glucose and oxidative/nitrosative stress conditions induce apoptosis in retinal endothelial cells by a caspase-independent pathway.

Diabetic retinopathy (DR) is a leading cause of vision loss among working-age adults. Retinal endothelial cell apoptosis is an early event in DR, and oxidative stress is known to play an important role in this pathology. Recently, we found that high glucose induces apoptosis in retinal neural cells by a caspase-independent mechanism.

Modulation of human peripheral blood mononuclear cell proliferative response by diltiazem : in vitro comparison in younger versus older subjects.

Background: The gradual aging of population has increased the number of elderly patients receiving kidney transplants. In elderly transplant recipients, careful immunosuppression has to be maintained to avoid both rejection and adverse effects. Clinical protocols after kidney transplantation include use of the calcium channel antagonist diltiazem to ameliorate the hypertensive effect and nephrotoxicity of the immunosuppressant agent ciclosporin (cyclosporine).

Hemodynamic effects of PEEP in a porcine model of HCl-induced mild acute lung injury.

Background: Positive end-expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid.

Methods: Thirty-two pigs were randomly allocated into four groups (Control-PEEP, Control-SI, ALI-PEEP and ALI-SI).

Investigation of breast cancer using two-dimensional MRS.

Proton (1H) MRS enables non-invasive biochemical assay with the potential to characterize malignant, benign and healthy breast tissues. In vitro studies using perchloric acid extracts and ex vivo magic angle spinning spectroscopy of intact biopsy tissues have been used to identify detectable metabolic alterations in breast cancer. The challenges of 1H MRS in vivo include low sensitivity and significant overlap of resonances due to limited chemical shift dispersion and significant inhomogeneous broadening at most clinical magnetic field strengths.

High glucose changes extracellular adenosine triphosphate levels in rat retinal cultures.

Diabetic retinopathy (DR) is the leading cause of blindness in adults. In diabetes, there is activation of microglial cells and a concomitant release of inflammatory mediators. However, it remains unclear how diabetes triggers an inflammatory response in the retina.

The three-dimensional structure of bothropasin, the main hemorrhagic factor from Bothrops jararaca venom: insights for a new classification of snake venom metalloprotease subgroups.

Bothropasin is a 48kDa hemorrhagic PIII snake venom metalloprotease (SVMP) isolated from Bothrops jararaca, containing disintegrin/cysteine-rich adhesive domains. Here we present the crystal structure of bothropasin complexed with the inhibitor POL647. The catalytic domain consists of a scaffold of two subdomains organized similarly to those described for other SVMPs, including the zinc and calcium-binding sites.

Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study.

Objectives: The aim of this study was to evaluate the correlation of point-of-care measurement of platelet inhibition with clinical outcome in patients undergoing percutaneous coronary intervention (PCI).

Background: Individual variability of clopidogrel response might influence results of PCI.

Methods: A total of 160 patients receiving clopidogrel before PCI were prospectively enrolled.

Crystallographic structure of phosphofructokinase-2 from Escherichia coli in complex with two ATP molecules. Implications for substrate inhibition.

Phosphofructokinase-1 and -2 (Pfk-1 and Pfk-2, respectively) from Escherichia coli belong to different homologous superfamilies. However, in spite of the lack of a common ancestor, they share the ability to catalyze the same reaction and are inhibited by the substrate MgATP. Pfk-2, an ATP-dependent 6-phosphofructokinase member of the ribokinase-like superfamily, is a homodimer of 66 kDa subunits whose oligomerization state is necessary for catalysis and stability.

Müller cells do not influence leukocyte adhesion to retinal endothelial cells.

Purpose: Diabetic retinopathy is associated with inflammation. The authors investigated the influence of Müller cells on leukocyte adhesion to retinal endothelial cells.

Methods: ICAM-1 levels were assessed by Western blotting and immunocytochemistry.

Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning.

Vertebrate Crossveinless-2 (CV2) is a secreted protein that can potentiate or antagonize BMP signaling. Through embryological and biochemical experiments we find that: (1) CV2 functions as a BMP4 feedback inhibitor in ventral regions of the Xenopus embryo; (2) CV2 complexes with Twisted gastrulation and BMP4; (3) CV2 is not a substrate for tolloid proteinases; (4) CV2 binds to purified Chordin protein with high affinity (K(D) in the 1 nM range); (5) CV2 binds even more strongly to Chordin proteolytic fragments resulting from Tolloid digestion or to full-length Chordin/BMP complexes; (6) CV2 depletion causes the Xenopus embryo to become hypersensitive to the anti-BMP effects of Chordin overexpression or tolloid inhibition. We propose that the CV2/Chordin interaction may help coordinate BMP diffusion to the ventral side of the embryo, ensuring that BMPs liberated from Chordin inhibition by tolloid proteolysis cause peak signaling levels.

Asymmetry analysis in rodent cerebral ischemia models.

Rationale And Objectives: An automated method for identification and segmentation of acute/subacute ischemic stroke, using the inherent bi-fold symmetry in brain images, is presented. An accurate and automated method for localization of acute ischemic stroke could provide physicians with a mechanism for early detection and potentially faster delivery of effective stroke therapy.

Materials And Methods: Segmentation of ischemic stroke was performed on magnetic resonance (MR) images of subacute rodent cerebral ischemia.

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis.

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 +/- 6 days after the event. IRA was patent in 61 patients and occluded in 40.

Cholera toxin B subunit promotes the induction of regulatory T cells by preventing human dendritic cell maturation.

Cholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens. There is also good evidence that CTB acts as an immunosuppressant, as it is able to down-modulate human monocyte/macrophage cell line activation and to suppress Th1-type responses. In the present study, we examined the possibility that recombinant CTB (rCTB) may affect human dendritic cell (DC) functions in response to LPS stimulation and may induce the generation of DC with the capacity to generate CD4(+) regulatory T cells (Tregs).

Immunohistochemical profile of various neurotransmitters, neurotrophins and MIB-1 in cholesteatomas of the petrous bone.

Compared to the normal epidermal epithelium, cholesteatomas have altered growth properties characterized by the excessive growth of keratinocytes leading to mucosal destruction. Either congenital or acquired, these lesions, which grow in the middle ear space, the petrous apex or the mastoid of temporal bones, are mostly considered benign skin tumoral lesions. However, many questions remain concerning their pathophysiology.