Association of leupaxin with Src in osteoclasts.

Leupaxin (LPXN), which belongs to the paxillin extended family of adaptor proteins, was previously identified as a component of the sealing zone in osteoclasts. LPXN was found to associate with several podosomal proteins, such as the protein tyrosine kinase Pyk2, the protein-tyrosine phosphatase-PEST (PTP-PEST), actin-binding proteins, and regulators of actin cytoskeletal reorganization. It was previously demonstrated that inhibition of LPXN expression resulted in reduced osteoclast-mediated resorption.

A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation.

Cellular senescence is a stable state of proliferative arrest that provides a barrier to malignant transformation and contributes to the antitumor activity of certain chemotherapies. Senescent cells can accumulate senescence-associated heterochromatic foci (SAHFs), which may provide a chromatin buffer that prevents activation of proliferation-associated genes by mitogenic transcription factors. Surprisingly, we show that the High-Mobility Group A (HMGA) proteins, which can promote tumorigenesis, accumulate on the chromatin of senescent fibroblasts and are essential structural components of SAHFs.

An analysis of reaction pathways for proton tunnelling in methylamine dehydrogenase.

Computational methods have now become a valuable tool to understand the way in which enzymes catalyse chemical reactions and to aid the interpretation of a diverse set of experimental data. This study focuses on the influence of the condensed-phase environment structure on proton transfer mechanisms, with an aim to understand how C-H bond cleavage is mediated in enzymatic reactions. We shall use a combination of molecular simulation, ab initio or semi-empirical quantum chemistry and semi-classical multidimensional tunnelling methods to consider the primary kinetic isotope effects of the enzyme methylamine dehydrogenase (MADH), with reference to an analogous application to triosephosphate isomerase.

[Medical emergencies in the adult immigrant].

The need for medical care of the immigrant population is growing in proportion to the increase in the number of immigrants resident in Spain. This article reviews the socio-demographic characteristics of the immigrant population that come for consultations in the emergency services and discusses those particularities, both medical (neurocysticercosis, tuberculosis, infection by the AIDS virus, hepatitis, malaria, parasitosis, Ulysses syndrome) and paramedical (knowledge of the health card, concept of medicine, language barrier), that differentiate them from the native population. Nonetheless, since we are dealing with a young population that is in principle healthy, their reasons for consultation do not greatly differ from the general population.

Neospora caninum immunoblotting improves serodiagnosis of bovine neosporosis.

Neospora caninum ranges among the major causes of infectious abortion in cattle worldwide. The present study was designed to improve the serodiagnostic tools by complementing a conventional ELISA with a highly sensitive and species-specific N. caninum immunoblot.

Collagen birefringence in skin repair in response to red polarized-laser therapy.

We use the optical path difference (OPD) technique to quantify the organization of collagen fibers during skin repair of full-thickness burns following low-intensity polarized laser therapy with two different polarization incidence vectors. Three burns are cryogenerated on the back of rats. Lesion L(parallel) is irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction.

Unscheduled returns to the emergency department: an outcome of medical errors?

Background: The causes of unscheduled returns to the emergency department (ED) within 72 hours of discharge are unclear. A study was undertaken to identify factors associated with this quality care indicator.

Methods: 250 cases and 250 controls from the ED were prospectively studied.

Management of mouth opening in patients with temporomandibular disorders through low-level laser therapy and transcutaneous electrical neural stimulation.

Objective: The aim of this study was to evaluate the effectiveness of low-level laser therapy (LLLT) and transcutaneous electrical neural stimulation (TENS) on the improvement of mouth opening in patients with temporomandibular disorder (TMD).

Background Data: TMDs are conditions that affect the form and/or function of the temporomandibular joint (TMJ), masticatory muscles, and dental apparatus. Often TMD is associated with pain localized in the TMJ and/or in the muscles of the face and neck.

Insight into catalytically relevant correlated motions in human purine nucleoside phosphorylase.

The catalytic site of the homotrimeric enzyme human purine nucleoside phosphorylase enzyme (hPNP) features residue F200 and the 241-265 loop directly skirting the purine base and a residue belonging to the adjacent monomer, F159, immediately conterminous to the ribosyl moiety. Crystallographic B-factors of apo human purine nucleoside phosphorylase, and hPNP complexed with substrate/transition state (TS) analogues, show that residue E250 is the centroid of a highly mobile loop region. Furthermore, superimposition of apo hPNP and hPNP complexed with TS analogue Immucillin-H shows a tightening of the active site, caused by the ligand-dependent 241-265 loop rearrangement taking place upon substrate/inhibitor binding, suggesting a putative dynamic role of the loop in binding/catalysis.

N-acetyl-cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats.

Objective: Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]).

Study Design: Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS.

Growth hormone deficiency after chemotherapy for acute lymphoblastic leukemia in children who have not received cranial radiation.

Chemotherapy-related growth failure is a significant problem in children with acute lymphoblastic leukemia (ALL) and other childhood cancers. Growth impairment after cranial radiation (CR) can result in diminished adult height, but growth failure following chemotherapy without CR is usually followed by catch-up growth and normal adult height.1 A retrospective review of 347 ALL survivors registered in our Long Term Follow Up (LTFU) Clinic, since 1997 revealed that 109 had received CR; 3, total body irradiation (TBI); and 235, neither CR nor TBI.

Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro.

The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection.

Changes in the chemical and dynamic properties of cardiac troponin T cause discrete cardiomyopathies in transgenic mice.

Cardiac troponin T (cTnT) is a central component of the regulatory thin filament. Mutations in cTnT have been linked to severe forms of familial hypertrophic cardiomyopathy. A mutational "hotspot" that leads to distinct clinical phenotypes has been identified at codon 92.

Transition state structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli and its similarity to transition state analogues.

Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes reactions linked to polyamine metabolism, quorum sensing pathways, methylation reactions, and adenine salvage. It is a candidate target for antimicrobial drug design. Kinetic isotope effects (KIEs) were measured on the MTAN-catalyzed hydrolysis of 5'-methylthioadenosine (MTA) to determine the transition state structure.

He-Ne laser effects on blood microcirculation during wound healing: a method of in vivo study through laser Doppler flowmetry.

Background And Objectives: Low-intensity laser therapy (LILT) is widely used for wound healing promotion and its mechanism of action may be due to an enhancement of blood supply. The aim of this study was to evaluate blood flow alterations in a wound healing model, using laser Doppler flowmetry (LDF) associated with a normalized perfusion parameter.

Study Design/materials And Methods: An injury was provoked in 15 rats and blood flow was measured periodically over a period of 21 days.

Recommendation of an appropriate medium for in vitro drug susceptibility testing of the fish pathogen Tenacibaculum maritimum.

In the present study, Anacker and Ordal agar, marine agar (MA), and Flexibacter maritimus medium (FMM) were compared with the dilute versions of Mueller-Hinton agar (DMHA) medium recommended by the National Committee for Clinical Laboratory Standards (NCCLS) for their use in disk diffusion tests with Tenacibaculum maritimum strains and to calculate the MICs of five drugs by the Etest method. Preliminary growth tests performed with 32 strains of this pathogen on each medium revealed that all strains failed to grow on DMHA, while the remaining media supported good growth of all isolates. In the susceptibility tests, which were carried out with the other three media, all strains were resistant to oxolinic acid and were highly susceptible to amoxicillin and trimethoprim-sulfamethoxazole, showing a good correspondence with the Etest values, which ranged from 0.

Promoting vibrations in human purine nucleoside phosphorylase. A molecular dynamics and hybrid quantum mechanical/molecular mechanical study.

Crystallographic studies of human purine nucleoside phosphorylase (hPNP) with several transition-state (TS) analogues in the immucillin family showed an unusual geometric arrangement of the atoms O-5', O-4', and O(P), the nucleophilic phosphate oxygen, lying in a close three-oxygen stack. These observations were corroborated by extensive experimental kinetic isotope effect analysis. We propose that protein-facilitated dynamic modes in hPNP cause this stack, centered on the ribosyl O-4' oxygen, to squeeze together and push electrons toward the purine ring, stabilizing the oxacarbenium character of the TS.

[Prognostic factors for mortality related to nutritional status in the hospitalized elderly].

Background And Objective: The proportion of elderly patients hospitalized in acute care wards has progressively increased. Patients with a decreased functional status are prone to have malnutrition which negatively affects their prognosis and increases mortality. However, it is unclear whether functional and nutritional status are independent risk factors of mortality.

Follow-up study of adolescents exposed to di(2-ethylhexyl) phthalate (DEHP) as neonates on extracorporeal membrane oxygenation (ECMO) support.

Di(2-ethylhexyl) phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Animal data show that adverse effects of DEHP exposure may include reduced fertility, reduced sperm production in males, and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, extracorporeal membrane oxygenation (ECMO), and cardiovascular surgery.

Maternal LPS induces cytokines in the amniotic fluid and corticotropin releasing hormone in the fetal rat brain.

Perinatal infections are a risk factor for fetal neurological pathologies, including cerebral palsy and schizophrenia. Cytokines that are produced as part of the inflammatory response are proposed to partially mediate the neurological injury. This study investigated the effects of intraperitoneal injections of lipopolysaccharide (LPS) to pregnant rats on the production of cytokines and stress markers in the fetal environment.

Lack of efficacy of fadrozole in treating precocious puberty in girls with the McCune-Albright syndrome.

We administered the aromatase inhibitor fadrozole to 16 girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome. The girls' ages ranged from 3.2-9.

[Surveillance of Haemophilus influenzae serotypes and antimicrobial resistance in Colombia, 1994-2002].

Invasive disease caused by Haemophilus influenzae serotype b results in high rates of morbidity and mortality among children. In 1994, the Microbiology Group at the Instituto Nacional de Salud (Colombia) initiated a program to detect antimicrobial resistance in H. influenzae.