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Infant ventilation and oxygenation by basic life support providers: comparison of methods.

INTRODUCTION: Little information is available in the performance of infant ventilation by basic life support (BLS) personnel. HYPOTHESIS: There are no significant differences between mouth-to-mouth (M-M), mouth-to-mask (M-Ma), pediatric bag-mask (PBM), and adult bag-mask (ABM) devices in the percent of acceptable breaths delivered by BLS providers. METHODS: Fifty certified BLS providers performed five ventilation methods in random sequences for 60 seconds each on a 5kg infant mannequin following standardized instructions. Supplemental oxygen, 10 l/min, was supplied with one M-Ma trial and PBM methods. Airway patency, peak airway pressure (PAP), ventilatory rate (VR), tidal volume, and delivered oxygen concentration (FiO 2) were recorded. The percent of breaths with excessive PAP (i.e., greater than 30 mmHg), percent of acceptable breaths using loose (i.e., 25-125ml) and strict (i.e., 50-100ml) criteria, and FiO 2 at 15, 30, 45, and 60 seconds were compared between ventilation methods using ANOVA. RESULTS: For all subjects and those with a patent airway (n=36), there were no significant differences in the percentage of acceptable breaths produced by PBM (56+/-6) (mean+/-SEM; all subjects) and ABM (41+/-6.2) was significantly greater than M-Ma, with and without a patent airway. Although RR and the percentage of excessive breaths were not significantly different, the percentage of acceptable breaths and FiO 2 delivered with each ventilation method was significantly better in the patent airway group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression.

Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the development and maintenance of tol erance. It is thus not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease (the bare lymphocyte syndrome (BLS)). The genetic defects responsible for BLS do not lie within the MHCII locus, but in genes encoding transcription factors required for MHCII expression. A great deal of our current knowledge about the mechanisms regulating expression of MHCII genes has been derived from the study of BLS. Four different MHCII regulatory genes have been identified. These genes encode RFXANK, RFXS, RFXAP and CIITA. The first three are subunits of RFX, a ubiquitously expressed factor that binds to the promoters of all MHCII genes. RFX binds co-operatively with other factors to form a highly stable multiprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the co-activator CIITA, which is recruited via protein-protein interactions CIITA is the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression.

Animals↗

Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas.

We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role.

Alleles↗

Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome.

Bare lymphocyte syndrome (BLS) is an autosomal recessive severe-combined immunodeficiency that can result from mutations in four different transcription factors that regulate the expression of major histocompatibility complex (MHC) class II genes. We have identified here the defective gene that is responsible for the phenotype of the putative fifth BLS complementation group. The mutation was found in the regulatory factor that binds X-box 5 (RFX5) and was mapped to one of the arginines in a DNA-binding surface of this protein. Its wild-type counterpart restored binding of the RFX complex to DNA, transcription of all MHC class II genes and the appearance of these determinants on the surface of BLS cells.

Amino Acid Motifs↗

High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase.

The penultimate step in the pathway of riboflavin biosynthesis is catalyzed by the enzyme lumazine synthase (LS). One of the most distinctive characteristics of this enzyme is the structural quaternary divergence found in different species. The protein exists as pentameric and icosahedral forms, built from practically the same structural monomeric unit. The pentameric structure is formed by five 18-kDa monomers, each extensively contacting neighboring monomers. The icosahedrical structure consists of 60 LS monomers arranged as 12 pentamers giving rise to a capsid exhibiting icosahedral 532 symmetry. In all lumazine synthases studied, the topologically equivalent active sites are located at the interfaces between adjacent subunits in the pentameric modules. The Brucella sp. lumazine synthase (BLS) sequence clearly diverges from pentameric and icosahedric enzymes. This unusual divergence prompted us to further investigate its quaternary arrangement. In the present work, we demonstrate by means of solution light scattering and x-ray structural analyses that BLS assembles as a very stable dimer of pentamers, representing a third category of quaternary assembly for lumazine synthases. We also describe by spectroscopic studies the thermodynamic stability of this oligomeric protein and postulate a mechanism for dissociation/unfolding of this macromolecular assembly. The higher molecular order of BLS increases its stability 20 degrees C compared with pentameric lumazine synthases. The decameric arrangement described in this work highlights the importance of quaternary interactions in the stabilization of proteins.

Binding Sites↗

Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice.

Laminins, heterotrimers of alpha, beta, and gamma chains, are prominent constituents of basal laminae (BLs) throughout the body. Previous studies have shown that laminins affect both myogenesis and synaptogenesis in skeletal muscle. Here we have studied the distribution of the 10 known laminin chains in muscle and peripheral nerve, and assayed the ability of several heterotrimers to affect the outgrowth of motor axons. We show that cultured muscle cells express four different alpha chains (alpha1, alpha2, alpha4, and alpha5), and that developing muscles incorporate all four into BLs. The portion of the muscle's BL that occupies the synaptic cleft contains at least three alpha chains and two beta chains, but each is regulated differently. Initially, the alpha2, alpha4, alpha5, and beta1 chains are present both extrasynaptically and synaptically, whereas beta2 is restricted to synaptic BL from its first appearance. As development proceeds, alpha2 remains broadly distributed, whereas alpha4 and alpha5 are lost from extrasynaptic BL and beta1 from synaptic BL. In adults, alpha4 is restricted to primary synaptic clefts whereas alpha5 is present in both primary and secondary clefts. Thus, adult extrasynaptic BL is rich in laminin 2 (alpha2beta1gamma1), and synaptic BL contains laminins 4 (alpha2beta2gamma1), 9 (alpha4beta2gamma1), and 11 (alpha5beta2gamma1). Likewise, in cultured muscle cells, alpha2 and beta1 are broadly distributed but alpha5 and beta2 are concentrated at acetylcholine receptor-rich "hot spots," even in the absence of nerves. The endoneurial and perineurial BLs of peripheral nerve also contain distinct laminin chains: alpha2, beta1, gamma1, and alpha4, alpha5, beta2, gamma1, respectively. Mutation of the laminin alpha2 or beta2 genes in mice not only leads to loss of the respective chains in both nerve and muscle, but also to coordinate loss and compensatory upregulation of other chains. Notably, loss of beta2 from synaptic BL in beta2(-/-) "knockout" mice is accompanied by loss of alpha5, and decreased levels of alpha2 in dystrophic alpha2(dy/dy) mice are accompanied by compensatory retention of alpha4. Finally, we show that motor axons respond in distinct ways to different laminin heterotrimers: they grow freely between laminin 1 (alpha1beta1gamma1) and laminin 2, fail to cross from laminin 4 to laminin 1, and stop upon contacting laminin 11. The ability of laminin 11 to serve as a stop signal for growing axons explains, in part, axonal behaviors observed at developing and regenerating synapses in vivo.

Aging↗

Coordinate control of axon defasciculation and myelination by laminin-2 and -8.

Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer alpha2beta1gamma1) and Ln-8 (alpha4beta1gamma1). Loss of Ln-2 in humans and mice carrying alpha2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (alpha5beta1gamma1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.

Animals↗

The study of a swept electron beam in order to apply Boag's theory for calculation of the collection efficiency: I. Beam and swept area characteristics.

The characteristics of swept electron beams produced by Sagittaire or Saturne type accelerators were investigated by film dosimetry. Beam sections perpendicular to the beam limiting system (BLS) axis are fully described by Gaussian curves close to the centre of the field defined by the BLS, but they become more and more distorted as the elementary beam approaches the BLS. The swept area was also evaluated and was related to the magnitude of the current applied to the two orthogonal magnets of the sweeping system.

Evaluation Studies as Topic↗

Determination of an antibody-antigen binding constant by enzyme immunoassay and a theory for analysis of competitive binding of two ligands to heterogeneous receptor.

A method for determining antigen-antibody binding constants by using enzyme-labeled antigens has been developed. In the measurement, enzyme-labeled and unlabeled antigens (Ag* and Ag) were allowed to compete in binding to the antibody (Ab) under conditions where Ag* much less than Ab much less than Ag. The data were analyzed according to a new theory developed for the analysis of competitive binding of two ligands to a heterogeneous receptor. The theory indicates that the binding degree of a labeled ligand measured at various concentrations of the receptor can be used to prepare a standard curve relating the binding degree of the labeled ligand and the average of the concentrations of the free receptor components which are in binding equilibrium with another unlabeled ligand. For homogeneous receptors, the method gives usual binding constants for the unlabeled ligand, but for heterogeneous receptors, it gives a new type of average binding constant for the unlabeled ligand in which the contribution of each receptor component is amplified in proportion to its affinity against the labeled ligand. This average binding constant was named the "affinity-average binding constant." A rabbit anti-blasticidin S (BLS) antiserum analyzed by the present method using beta-galactosidase-labeled BLS as the labeled ligand was found to be fairly homogeneous with respect to the affinity and to have a binding constant of 1.48 +/- 0.24 (S.D.) X 10(8) M-1 for unlabeled BLS.

Animals↗

Public health workforce enumeration: beware the "quick fix".

The most common source of information on workforce in the United States is the Bureau of Labor Statistics (BLS), a branch of the Department of Labor. In 1998, 14 public health workforce titles were added to the BLS Standard Occupational Classification (SOC) system. While this was a constructive step, it is not a "quick fix," because these additional titles do not solve the longstanding problems inherent in capturing accurate PH workforce data. As is true for all currently available sources, BLS statistics capture a limited segment of public health's broadly defined and multidisciplinary workforce. A standard system of data collection is needed to guide planning to sustain the present and future workforce. Revision of the 1998 SOC in preparation for the 2010 Census is now underway. This presents an opportunity for the public health community to act on prior recommendations regarding workforce data and advocate for more inclusive enumeration of public health occupations that can inform policies and planning for the current and future workforce.

Employment↗

Problems in pharmacokinetic analysis of alcohol disposition: a trial of the Bayesian least-squares method.

The technical problems of the pharmacokinetic analysis of alcohol disposition were studied using the Michaelis-Menten elimination kinetic model. This model was defined by two forms of equations: differential and integrated, with the latter being derived by integration of the differential equation. We compared the parameter values, estimated by one-line curve-fitting, using these two equation forms. We concluded that, for the kinetic analysis of alcohol disposition, curve-fitting with the differential equation was superior to that with the integrated equation. We also studied the methodological problems involved in one-line fitting. The ordinary least-squares (OLS) method was compared with the Bayesian least-squares (BLS) method. Correlation between the Vmax and beta (ethanol elimination rate) values, and between the Vmax and K(m) values was seen when the parameter values were estimated by the OLS method. These results suggested that one-line fitting by the OLS method was not adequate for Michaelis-Menten-type elimination kinetic analysis. BLS analysis resulted in no correlation between the estimated parameter values that did not change with the level of the dose. The BLS method seemed to be more useful than the OLS method for the estimation of individual pharmacokinetic parameter values.

Animals↗

Epstein-Barr virus nuclear antigen 2 (EBNA2) gene deletion is consistently linked with EBNA3A, -3B, and -3C expression in Burkitt's lymphoma cells and with increased resistance to apoptosis.

Most Epstein-Barr virus (EBV)-positive Burkitt's lymphomas (BLs) carry a wild-type EBV genome and express EBV nuclear antigen 1 (EBNA1) selectively from the BamHI Q promoter (latency I). Recently we identified a distinct subset of BLs carrying both wild-type and EBNA2 gene-deleted (transformation-defective) viral genomes. The cells displayed an atypical "BamHI W promoter (Wp)-restricted" form of latency where Wp (rather than Qp) was active and EBNA1, -3A, -3B, -3C, and -LP were expressed in the absence of EBNA2 or latent membrane proteins 1 and 2. Here we present data strongly supporting the view that the EBNA2-deleted genome is transcriptionally active in these cells and the wild-type genome is silent. Single-cell cloning of three parental Wp-restricted BL lines generated clones carrying either both viral genomes or the EBNA2-deleted genome only, never clones with the wild-type genome only. All rescued clones displayed the Wp-restricted form of latency characteristic of the parent line and retained the original parent cell phenotype. Interestingly, Wp-restricted parent lines and derived clones were markedly more resistant to inducers of apoptosis than standard latency I BL lines. Furthermore, in vitro infection of EBV-negative BL lines with an EBNA2 gene-deleted virus generated EBV-positive converts with Wp-restricted latency and a similarly marked apoptosis resistance. We postulate that, in the subset of BLs displaying Wp-restricted latency, infection of a tumor progenitor cell with an EBNA2 gene-deleted virus has provided that cell with a survival advantage through broadening antigen expression to include the EBNA3 proteins.

Antigens, Viral↗

A subject with a novel type I bare lymphocyte syndrome has tapasin deficiency due to deletion of 4 exons by Alu-mediated recombination.

HLA class I expression depends on the formation of a peptide-loading complex composed of class I heavy chain; beta(2)-microglobulin; the transporter associated with antigen processing (TAP); and tapasin, which links TAP to the heavy chain. Defects in TAP result in a class I deficiency called the type I bare lymphocyte syndrome (BLS). In the present study, we examined a subject with a novel type I BLS who does not exhibit apparent TAP abnormalities but who has a tapasin defect. The subject's TAPASIN gene has a 7.4-kilobase deletion between introns 3 and 7; an Alu repeat-mediated unequal homologous recombination may be the cause of the deletion. No tapasin polypeptide was detected in the subject's cells. The cell surface class I expression level in tapasin-deficient cells was markedly reduced but the reduction was not as profound as in TAP-deficient cells. These results suggest that tapasin deficiency is another cause of type I BLS.

Alu Elements↗

Blunt trauma to large vessels: a mathematical study.

BACKGROUND: Blunt trauma causes short-term compression of some or all parts of the chest, abdomen or pelvis and changes hemodynamics of the blood. Short-term compression caused by trauma also results in a short-term decrease in the diameter of blood vessels. It has been shown that with a sudden change in the diameter of a tube or in the direction of the flow, the slower-moving fluid near the wall stops or reverses direction, which is known as boundary layer separation (BLS). We hypothesized that a sudden change in the diameter of elastic vessel that results from compression may lead not only to BLS but also to other hemodynamic changes that can damage endothelium. METHODS: We applied Navier-Stokes, multiphase and boundary layer equations to examine such stress. The method of approximation to solve the BL equations was used. Experiments were conducted in an aerodynamic tube, where incident flow velocity and weight of carriage with particles before and after blowing were measured. RESULTS: We found that sudden compression resulting from trauma leads to (1) BLS on the curved surface of the vessel wall; (2) transfer of laminar boundary layer into turbulent boundary layer. Damage to the endothelium can occur if compression is at least 25% and velocity is greater than 2.4 m/s or if compression is at least 10% and velocity is greater than 2.9 m/s. CONCLUSION: Our research may point up new ways of reducing the damage from blunt trauma to large vessels. It has the potential for improvement of safety features of motor vehicles. This work will better our understanding of the precise mechanics and critical variables involved in diagnosis and prevention of blunt trauma to large vessels.

Aorta↗

Over-the-head cardiopulmonary resuscitation improves efficacy in basic life support performed by professional medical personnel with a single rescuer: a simulation study.

Two-rescuer cardiopulmonary resuscitation (CPR) is considered the best method for professional basic life support (BLS). However, in many prehospital cardiac arrest situations, one rescuer has to begin CPR alone while the other performs additional tasks. In theory, over-the-head CPR is a suitable alternative in this situation, with the added benefit of allowing the single rescuer to use a self-inflating bag for ventilation. In this trial, we compared standard single-rescuer CPR with over-the-head CPR in manikins. We planned this study using a crossover study design where each participant administered both CPR techniques in a randomized order. Ventilation and chest compression data were collected with analysis software during a 2-min CPR test for each technique. Sixty-seven emergency medical technician students participated in this trial. Over-the-head CPR allowed for superior ventilation compared to standard CPR (number of correct ventilations: 330 of 760 versus 279 of 779; P = 0.002). The quality of delivered chest compressions did not differ between the two groups (correct chest compressions: 4293 of 6304 versus 4313 of 6395; P = 0.44). In conclusion, our study has shown that over-the-head CPR may be an effective alternative BLS technique when a single professional rescuer has to perform CPR, likely offering superior ventilation and comparable chest compression quality compared with standard BLS.

Adolescent↗

Research of blastocyte-like structure in chicken.

The chicken embryo is a classic model used to investigate embryonic development, gene expression, and tissue differentiation, and is also an important research tool in studying the animal functional genomics. The whole blastoderms of fresh unincubated eggs from White Leghorn chickens were collected with a paper ring, mechanically broken into small pieces and cultured in medium. Then the small pieces would develop into blastocyte-like structures (BLS), which could be facilitated by an addition of fetal bovine serum (FBS) to the primary culture and their diameter was nearly doubled from 12 to 24 h. The additional yolk had no positive effect on the development in the first 12 h but encouraged the BLSs attaching and inner cells differentiating instead in 24 h. The inner cells of the BLS showing a high alkaline-phosphatase activity similar to those in mouse embryonic stem (ES) cells and also expressing a large amount of the specific stage embryonic antigen-1 (SSEA-1) on the surface, which was known to be the characteristic of non-differentiated mouse and avian ES cells, could finally differentiate into nerve-like cells, fibroblast cells and so on in the medium. Leukemia inhibitory factor (LIF) facilitated the cells' proliferation and prevented differentiation in the suspended culture of the BLSs. So we drew the conclusion that the BLS obtained from broken blastoderm can be used to amplify avian ES cells so as to initiate a new method of producing transgenic chickens.

Animals↗

Beta 57-Asp plays an essential role in the unique SDS stability of HLA-DQA1*0102/DQB1*0602 alpha beta protein dimer, the class II MHC allele associated with protection from insulin-dependent diabetes mellitus.

Studies of the stability of HLA-DQ have revealed a correlation between SDS stability of MHC class II alphabeta dimers and insulin-dependent diabetes mellitus (IDDM) susceptibility. The MHC class II alphabeta dimer encoded by HLA-DQA1*0102/DQB1*0602 (DQ0602), which is a dominant protective allele in IDDM, exhibits the greatest SDS stability among HLA-DQ molecules in EBV-transformed B-lymphoblastoid cells and PBLs. DQ0602 is also uniquely SDS stable in the HLA-DM-deficient cell line, BLS-1. We addressed the molecular mechanism of the stability of DQ0602 in BLS-1. A panel of mutants based on the polymorphic differences between HLA-DQA1*0102/DQB1*0602 and HLA-DQA1*0102/DQB1*0604 were generated and expressed in BLS-1. An Asp at beta57 was found to be critical for SDS stability, whereas Tyr at beta30, Gly at beta70, and Ala at beta86 played secondary roles. Furthermore, the level of class II-associated invariant chain peptide bound to HLA-DQ did not correlate with SDS stability, suggesting that class II-associated invariant chain peptide does not play a direct role in the unique SDS stability of DQ0602. These results support a role for DQB1 codon 57 in HLA-DQ alphabeta dimer stability and IDDM susceptibility.

Alleles↗

[Guidelines for revised cardiopulmonary resuscitation--basic life support].

Basic life support(BLS) does not require any special instruments or drugs, and its skills can be understood and performed easily by the lay person. The main goal of cardiopulmonary resuscitation(CPR) for the victims of cardiac pulmonary arrest(CPA) is not only restoration of cardiopulmonary function but also return to their previous life. An early bystander CPR plays a pivotal role to achieve this target. When encountering an unconscious person, emergency medical systems(EMS) such as calling 119 must be activated immediately. As the next step, cardiopulmonary condition status has to be determined after assurance of airway patency. When there are no signs of breathing or pulse, BLS consisting of artificial respiration and/or chest compression must be started immediately and continued until EMS staffs arrive. In this article, the details of the revised guidelines for BLS by the American Heart Association are described. Current CPR education for pre- or early post-graduate medical students in our institution is reported.

American Heart Association↗