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We have performed extensive calculations to investigate thermal energy, rotationally inelastic collisions of NaK (A(1)Σ(+)) with He. We determined a potential energy surface using a multi-reference configuration interaction wave function as implemented by the GAMESS electronic structure code, and we have performed coupled channel scattering calculations using the Arthurs and Dalgarno formalism. We also calculate the Grawert coefficients B(λ)(j, j') for each j â j' transition. These coefficients are used to determine the probability that orientation and alignment are preserved in collisions taking place in a cell environment. The calculations include all rotational levels with j or j' between 0 and 50, and total (translational and rotational) energies in the range 0.0002-0.0025 a.u. (â¼44-550 cm(-1)). The calculated cross sections for transitions with even values of Δj tend to be larger than those for transitions with odd Δj, in agreement with the recent experiments of Wolfe et al. (J. Chem. Phys. 134, 174301 (2011)). The calculations of the energy dependence of the cross sections and the calculations of the fraction of orientation and alignment preserved in collisions also exhibit distinctly different behaviors for odd and even values of Δj. The calculations also indicate that the average fraction of orientation or alignment preserved in a transition becomes larger as j increases. We interpret this behavior using the semiclassical model of Derouard, which also leads to a simple way of visualizing the distribution of the angles between the initial and final angular momentum vectors j and j'. Finally, we compare the exact quantum results for j â j' transitions with results based on the simpler, energy sudden approximation. That approximation is shown to be quite accurate.
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OBJECTIVE: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. METHOD: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. RESULTS: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. CONCLUSION: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.
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Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Polifarmacia , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto , Quimioterapia Combinada , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
INTRODUCTION: Psychotropic drug combinations (PDC) are common in the treatment of patients with schizophrenia but there is little research regarding the effects of PDC on cognition. OBJECTIVE: The aim of this study was to analyse the effects of antipsychotic monotherapy and various types of PDC on cognitive processing speed (CPS). METHODS: ELAN is a 24-month multi-site prospective observational controlled trial following up 374 patients with schizophrenia under routine treatment conditions following discharge from inpatient treatment. The propensity score method, multinomial logistic regression analyses and mixed effects regression models were used. RESULTS: CPS correlated significantly with PANSS and GAF scores and improved over time in the monotherapy group. Negative effects of some PDC (antipsychotics + tranquilizers/antipsychotics+at least 2 other psychopharmacological subclasses, sedative/anticholinergic drugs/high adjusted antipsychotic dose) lost significance after controlling for clinical characteristics. DISCUSSION: Indications for PDC should be examined with care although, in the present study, effects on cognition were small.
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Trastornos del Conocimiento/tratamiento farmacológico , Trastornos Psicóticos/complicaciones , Psicotrópicos/uso terapéutico , Esquizofrenia/complicaciones , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Trastornos del Conocimiento/etiología , Quimioterapia Combinada , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/tratamiento farmacológico , Análisis de Regresión , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológico , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: The present investigation was undertaken to elucidate the differences in the progression of metabolic responses during incremental exercise between men and women of similar maximal aerobic capacity. METHODS: Twenty males and 20 females served as subjects for the study. Each subject was randomly assigned to perform a graded exercise test on either a cycle ergometer or a treadmill. Of the 20 subjects within each gender, 10 were tested on the cycle ergometer, whereas the other half was tested on the treadmill. During each test, absolute VO2, relative VO2, and HR were recorded during the last 15 seconds of every minute throughout the test. These variables were then plotted separately as a function of work rate so that a best-fit linear regression equation was generated for each of the three plots. RESULTS: Under the cycle condition, we found no difference in slope of increment in absolute VO2 between genders. However, the slope of increment in relative VO2 and HR was greater (P<0.05) in women than men. A negative correlation (r=-0.858, P<0.05) was found between body mass and slope of increment in relative VO2 in men and women combined. Under the treadmill condition, the slope for absolute VO2 were greater (P<0.05) in men than women. However, in terms of relative VO2 and HR, no between-gender differences were observed in the slope of increment. A positive correlation (r=0.769, P<0.05) was found between body mass and slope of increment in absolute VO2 in men and women combined. CONCLUSIONS: These results indicate that the progression of metabolic responses during incremental exercise differs between men and women despite a similar fitness. These gender differences may be further attributed to body mass that seems to play a distinctive role when the incremental exercise is conducted on a cycle ergometer and treadmill.
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Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Consumo de Oxígeno/fisiología , Adulto , Índice de Masa Corporal , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
Applications in robot-aided surgery are currently based on modifications of manipulators used in industrial manufacturing processes. In this paper we describe novel rotatory kinematics for a manipulator, specially developed for deployment in robot-aided surgery. The construction of the gearing mechanism used for the positioning and orientation of a linkage point is described. Forward and inverse kinematics were calculated, and a constructive solution proposed. The gearing mechanism is based on two disk systems, each of which consists of two opposing rotatable discs. The construction was designed in such a way that the linkage point can be positioned freely anywhere within the mechanism's range of motion. The kinematics thus permits an x-y-positioning via rotating movements only. The spatial arrangement of two of such disc systems permits movements in four degrees of freedom (DOF). The construction is compact, but can be further miniaturized, is flexible and manufacturing costs are low. On the basis of this mechanical concept a new, small automated manipulator for surgical application will be developed.
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Microcirugia/instrumentación , Robótica/instrumentación , Cirugía Asistida por Computador/instrumentación , Telemedicina/instrumentación , Diseño Asistido por Computadora , Diseño de Equipo , Falla de Equipo , Microcirugia/métodos , Movimiento (Física) , Robótica/métodos , Cirugía Asistida por Computador/métodos , Telemedicina/métodosRESUMEN
Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic: polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of gamma-interferon or interleukin-4, either in cultures or in cells recovered from adoptive recipients. We conclude that islet antigens involved in the initiation of autoimmune diabetes in BB rats may be absent or deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to deletion or anergy of diabetogenic T-cells or to the positive selection of regulatory T-cells.
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Diabetes Mellitus Tipo 1/inmunología , Islotes Pancreáticos/inmunología , Linfocitos T/inmunología , Timo/inmunología , Traslado Adoptivo , Animales , Células Cultivadas , Técnicas de Cocultivo , Diabetes Mellitus Tipo 1/patología , Inmunidad Innata/inmunología , Inmunofenotipificación , Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Islotes Pancreáticos/citología , Islotes Pancreáticos/patología , Ganglios Linfáticos/inmunología , Transfusión de Linfocitos , Ratas , Ratas Endogámicas BB , Ratas Desnudas , Receptores de Transferrina , Bazo/inmunología , Linfocitos T/citología , Timo/citología , Factores de Tiempo , Trasplante HomólogoRESUMEN
Congenitally lymphopenic diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous T cell-dependent autoimmunity. Coisogenic diabetes-resistant (DR) BB rats are not lymphopenic and are free of spontaneous autoimmune disease, but become diabetic in response to depletion of RT6+ T cells. The basis for the predisposition to autoimmunity in BB rats is unknown. Abnormal T cell development in DP-BB rats can be detected intrathymically, and thymocytes from DR-BB rats adoptively transfer diabetes. The mechanisms underlying these T cell developmental abnormalities are not known. To study these processes, we established adult thymus organ cultures (ATOC). We report that cultured DR- and DP-BB rat thymi generate mature CD4 and CD8 single-positive cells with up-regulated TCRs. DR-BB rat cultures also generate T cells that express RT6. In contrast, DP-BB rat cultures generate fewer CD4+, CD8+, and RT6+ T cells. Analysis of the cells obtained from ATOC suggested that the failure of cultured DP-BB rat thymi to generate T cells with a mature phenotype is due in part to an increased rate of apoptosis. Consistent with this inference, we observed that addition of the general caspase inhibitor Z-VAD-FMK substantially increases the number of both mature and immature T cells produced by DP-BB rat ATOC. We conclude that cultured DR-BB and DP-BB rat thymi, respectively, recapitulate the normal and abnormal T cell developmental kinetics and phenotypes observed in these animals in vivo. Such cultures should facilitate identification of the underlying pathological processes that lead to immune dysfunction and autoimmunity in BB rats.
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ADP Ribosa Transferasas , Diabetes Mellitus Tipo 1/inmunología , Glicoproteínas de Membrana , Linfocitos T/citología , Timo/citología , Clorometilcetonas de Aminoácidos/farmacología , Animales , Antígenos de Diferenciación de Linfocitos T , Apoptosis/efectos de los fármacos , Diferenciación Celular/inmunología , División Celular/inmunología , Senescencia Celular/inmunología , Diabetes Mellitus Tipo 1/etiología , Femenino , Antígenos de Histocompatibilidad/metabolismo , Inmunidad Innata , Recuento de Linfocitos/efectos de los fármacos , Masculino , Técnicas de Cultivo de Órganos , Ratas , Ratas Endogámicas BB , Linfocitos T/inmunología , Antígenos Thy-1/análisis , Timo/inmunologíaRESUMEN
Stimulation of CD4(+) helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-alpha/Ig-beta heterodimers which, second, target antigens to MHC class II-containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-alpha-associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-alpha cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide- MHC class II complexes through antigen targeting by BCR subunits.
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Presentación de Antígeno , Antígenos CD/fisiología , Proteínas de Unión al ADN , Precursores Enzimáticos/fisiología , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Proteínas Tirosina Quinasas/fisiología , Receptores de Antígenos de Linfocitos B/fisiología , Animales , Antígenos CD/química , Antígenos Virales/metabolismo , Linfocitos B/enzimología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Bacteriófago lambda/inmunología , Antígenos CD79 , Citoplasma/inmunología , Precursores Enzimáticos/metabolismo , Epítopos de Linfocito T/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Activación de Linfocitos , Linfoma de Células B , Ratones , Proteínas Tirosina Quinasas/metabolismo , Ratas , Receptores de Antígenos de Linfocitos B/química , Proteínas Represoras/inmunología , Quinasa Syk , Células Tumorales Cultivadas , Tirosina/fisiología , Proteínas Virales , Proteínas Reguladoras y Accesorias ViralesRESUMEN
The mammalian urinary bladder exhibits transepithelial Na+ absorption that contributes to Na+ gradients established by the kidney. Electrophysiological studies have demonstrated that electrogenic Na+ absorption across the urinary bladder is mediated in part by amiloride-sensitive Na+ channels situated within the apical membrane of the bladder epithelium. We have used a combination of in situ hybridization, Northern blot analysis, and immunocytochemistry to examine whether the recently cloned epithelial Na+ channel (ENaC) is expressed in the rat urinary bladder. In situ hybridization and Northern blot analyses indicate that alpha-, beta-, and gamma-rat ENaC (rENaC) are expressed in rat urinary bladder epithelial cells. Quantitation of the levels of alpha-, beta-, and gamma-rENaC mRNA expression in rat urinary bladder, relative to beta-actin mRNA expression, indicates that, although comparable levels of alpha- and beta-rENaC subunits are expressed in the urinary bladder of rats maintained on standard chow, the level of gamma-rENaC mRNA expression is 5- to 10-fold lower than alpha- or beta-rENaC mRNA. Immunocytochemistry, using an antibody directed against alpha-rENaC, revealed that ENaCs are predominantly localized to the luminal membrane of the bladder epithelium. Together, these data demonstrate that ENaC is expressed in the mammalian urinary bladder and suggest that amiloride-sensitive Na+ transport across the apical membrane of the mammalian urinary bladder epithelium is mediated primarily by ENaC.
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Canales de Sodio/biosíntesis , Transcripción Genética , Vejiga Urinaria/metabolismo , Animales , Células Epiteliales/citología , Células Epiteliales/metabolismo , Canales Epiteliales de Sodio , Técnica del Anticuerpo Fluorescente Indirecta , Mamíferos , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Sodio/metabolismo , Canales de Sodio/análisis , Vejiga Urinaria/citologíaRESUMEN
Membrane-bound immunoglobulin (mIg) of the IgG, IgA, and IgE classes have conserved cytoplasmic tails. To investigate the function of these tails, a B cell line was transfected with truncated or mutated gamma2a heavy chains. Transport to the endosomal compartment of antigen bound by the B cell antigen receptor did not occur in the absence of the cytoplasmic tail; and one or two mutations, respectively, in the Tyr-X-X-Met motif of the tail partially or completely interrupted the process. Experiments with chimeric antigen receptors confirmed these findings. Thus, a role for the cytoplasmic tail of mIg heavy chains in endosomal targeting of antigen is revealed.
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Presentación de Antígeno , Linfocitos B/inmunología , Endosomas/inmunología , Cadenas gamma de Inmunoglobulina/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Transporte Biológico , Citoplasma , Dimerización , Cadenas gamma de Inmunoglobulina/química , Cadenas gamma de Inmunoglobulina/genética , Memoria Inmunológica , Ratones , Mutación , Receptores de Antígenos de Linfocitos B/química , Receptores de Antígenos de Linfocitos B/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Transfección , Células Tumorales CultivadasRESUMEN
PURPOSE: This report analyzes the delivery of exercise conditioning services in the 1991 Pennsylvania, New Jersey, and Delaware regional survey of pulmonary rehabilitation programs. METHODS: Data from a questionnaire was analyzed with special consideration given to whether the program provided services for patients with only pulmonary diseases (n = 41) or with cardiac and pulmonary diseases (n = 18). RESULTS: All 59 programs included exercise conditioning. Most programs (67%) used oxygen saturation and/or expired gas analysis for writing exercise prescriptions. Only pulmonary programs used 6- or 12-minute walk data. The exercise prescription was written by nonphysicians in 51% of the programs. Most pulmonary-only programs used respiratory therapists by themselves or in combination with other professionals as exercise supervisors (71%). Cardiopulmonary programs used exercise physiologists by themselves (22%) or nurses by themselves or in combination with other professionals (50%). For all programs, the standard for ratio of patients to exercise staff averaged 3.0:1. Pulmonary-only programs did slightly but significantly more continuous arterial oxygen percent saturation (SaO2) monitoring rather than spot checking. A standard determining the use of supplemental oxygen during exercise was reported by 78% of all programs. Most used supplemental oxygen after observing the SaO2 level falling to < 90%. Electrocardiograph monitoring was done in 66% of pulmonary-only programs, but in 94% of the cardiopulmonary programs. Maintenance sessions were offered by 64% of the pulmonary-only programs and also by 78% of the cardiopulmonary programs. CONCLUSION: The type of rehabilitation program, either pulmonary-only or cardiopulmonary, appears to influence the exercise conditioning services used by the pulmonary patient.
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Atención a la Salud/organización & administración , Terapia por Ejercicio/organización & administración , Cardiopatías/rehabilitación , Enfermedades Pulmonares Obstructivas/rehabilitación , Delaware , Prueba de Esfuerzo , Investigación sobre Servicios de Salud , Humanos , Monitoreo Fisiológico , New Jersey , Pennsylvania , Prescripciones , Programas Médicos Regionales , Encuestas y CuestionariosRESUMEN
PURPOSE: This report summarizes the pulmonary rehabilitation characteristics found in the 1991 survey of programs in the Pennsylvania, New Jersey, and Delaware region. METHODS: A listing of 111 potential Tri-state regional programs with pulmonary rehabilitation was compiled. A 34-item questionnaire was developed. Using multiple mailings and phone-call follow-up, 59 programs of 100 the active programs in the region returned the questionnaires. Programs that were providing services to patients with pulmonary disease were compared to those focusing on patients with cardiac and/or pulmonary disease. RESULTS: A third of all programs (31%) used combined cardiopulmonary services. Pulmonary-only programs averaged 1.7 hours per day, and cardiopulmonary programs averaged 1.1 hours per day (P < .01). Both types of programs averaged 2.4 days per week. Average duration of pulmonary-only programs was 8.7 weeks, and duration of cardiopulmonary programs was 10.6 weeks (P < .05). Most programs (85%) required referral from the patients' primary physician. Many programs (64%) reported that local physicians other than the program's medical director referred a majority of the patients. Almost all programs (92%) performed exercise testing before initiating pulmonary rehabilitation. Post-rehabilitation discharge planning seemed to be based in many programs on performance measures taken during the final rehabilitation sessions or from a final 6- or 12-minute walk. Educational sessions were provided by 95% of the programs. Maintenance sessions were not offered by 39% of the programs. Seventy-three percent of the pulmonary-only programs and 44% of the cardiopulmonary programs offered support groups (P < .05). The pulmonary-only program coordinator's specialty was mostly respiratory therapy (70%), whereas in cardiopulmonary programs, coordinators tended to be nurses (39%) or from other nonrespiratory specialties (28%). No respiratory staff were used by 38% of the cardiopulmonary programs. CONCLUSIONS: The type of rehabilitation program, either pulmonary-only or cardiopulmonary, appears to influence many program characteristics (e.g., hours per day, weeks in duration, coordinator's specialty, and staffing).
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Rehabilitación Cardiaca , Enfermedades Pulmonares/rehabilitación , Evaluación de Programas y Proyectos de Salud , Análisis de Varianza , Delaware , Humanos , New Jersey , Pennsylvania , Evaluación de Programas y Proyectos de Salud/normas , Evaluación de Programas y Proyectos de Salud/tendenciasRESUMEN
The B cell antigen receptor of class IgM is a multimeric protein complex containing the membrane-bound immunoglobulin molecule and a heterodimer of the two B cell-specific transmembrane proteins Ig-alpha and Ig-beta. The B cell antigen receptor fulfills a dual role on the surface of B cells. First, it is a signal transduction complex which can activate protein tyrosine kinases and induce the release of Ca2+ ions from intracellular stores. Second, its internalization mediates the specific uptake of bound antigens, which are processed intracellularly and presented as major histocompatibility complex-bound peptides on the cell surface. In case of the IgM antigen receptor, the association with the heterodimer is necessary for expression of large amounts of IgM on the surface. We show here that the IgG2a antigen receptor can be expressed on the surface of myeloma cells in two structurally different forms: either with or without the Ig-alpha/Ig-beta heterodimer. A functional comparison of the two forms of antigen receptors demonstrates that the Ig-alpha and Ig-beta molecules are required for the activation of protein tyrosine kinases after cross-linking of the B cell antigen receptor. In contrast, both forms of IgG2a are equally well internalized. This suggests that Ig-alpha and Ig-beta are essential for signal transduction through the IgG2a antigen receptor, whereas internalization can occur independently of the heterodimer.
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Antígenos CD , Inmunoglobulina G/metabolismo , Glicoproteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Antígenos CD79 , Células Cultivadas , Endocitosis , Activación Enzimática , Técnicas In Vitro , Sustancias Macromoleculares , Ratones , Proteínas Recombinantes , Transducción de Señal , TransfecciónAsunto(s)
Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal , Secuencia de Aminoácidos , Animales , Línea Celular Transformada , Secuencia Conservada , Ratones , Datos de Secuencia Molecular , Fosforilación , Mutación Puntual , Receptores de Antígenos de Linfocitos B/química , Receptores de Antígenos de Linfocitos B/genéticaRESUMEN
BACKGROUND: Many transmembrane proteins of eukaryotic cells have only a short cytoplasmic tail of 10 - 100 amino acids, which has no obvious catalytic function. These tails are thought to be involved either in signal transduction or in the association of transmembrane proteins with the cytoskeleton. We have previously identified, in the cytoplasmic tails of components of B and T lymphocyte antigen receptors, an amino-acid motif that is required for signalling. The same motif is also found in the cytoplasmic tails of two viral proteins: the latent membrane protein, LMP2A, of Epstein Barr virus and the envelope protein, gp30, of bovine leukaemia virus. Interestingly, both viruses can activate infected B lymphocytes to proliferate, as does signalling by the B-cell receptor. RESULTS: In this study, we show that the cytoplasmic tails of the two viral proteins, and the cytoplasmic tail of the B-cell receptor immunoglobulin-alpha chain, when linked to CD8 in chimeric transmembrane proteins, can transduce signals in B cells. Cross-linking of these chimeric receptors activates B-cell protein tyrosine kinases and results in calcium mobilization. Furthermore, these cytoplasmic sequences are also protein tyrosine kinase substrates and may interact with cytosolic proteins carrying SH2 protein-protein interaction domains. CONCLUSION: Our findings suggest that viral transmembrane proteins can mimic the antigen-induced stimulation of the B-cell antigen receptor and thus can influence the activation and/or survival of infected B lymphocytes.
RESUMEN
The B cell antigen receptor is a complex containing the antigen-binding immunoglobulin molecules and the Ig-alpha/Ig-beta heterodimer which presumably connects the B cell antigen receptor to intracellular signaling components. To analyze the functional properties of the cytoplasmic parts of the B cell antigen receptor, we used the K46 B lymphoma line (IgG2a, kappa) to express chimeric molecules composed of the extracellular and transmembrane part of the CD8 alpha molecule and the cytoplasmic sequence of either the Ig-alpha (CD8 alpha/Ig-alpha), the Ig-beta (CD8 alpha/Ig-beta) protein or the membrane-bound gamma 2a heavy chain (CD8 alpha/gamma 2a). From these three types of chimeric molecules only (CD8 alpha/Ig-alpha and CD8 alpha/Ig-beta, but not CD8 alpha/gamma 2a, could transduce signals, thus providing the first evidence that the cytoplasmic tail of Ig-alpha and Ig-beta have a signaling capacity. After cross-linking with anti-CD8 alpha antibodies, both molecules induced a similar increase in intracellular free calcium ion and in MAP kinase phosphorylation. Protein tyrosine kinases, however, were strongly activated via the CD8 alpha/Ig-alpha and only marginally via the CD8 alpha/Ig-beta molecule. This suggests that the Ig-alpha and Ig-beta proteins have distinct roles during signal transduction through the B cell antigen receptor.
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Antígenos CD , Glicoproteínas de Membrana/fisiología , Fosfoproteínas/fisiología , Receptores de Antígenos de Linfocitos B/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Antígenos CD79 , Antígenos CD8/fisiología , Calcio/fisiología , Citoplasma/fisiología , Ratones , Datos de Secuencia Molecular , Fosfoproteínas/metabolismo , Fosforilación , Fosfotirosina , Proteínas Recombinantes de Fusión , Transducción de Señal , Transfección , Tirosina/análogos & derivados , Tirosina/metabolismoAsunto(s)
Receptores de Antígenos de Linfocitos B/fisiología , Transducción de Señal , Animales , Linfocitos B/fisiología , Proteínas Quinasas Dependientes de Calcio-Calmodulina , Diferenciación Celular , Inmunoglobulina G/fisiología , Fosforilación , Proteínas Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Células Tumorales CultivadasRESUMEN
Up to now, mandibular nerve blocks have been carried out without knowing the exact blood concentrations resulting from the use of the local anesthetics. Due to the high vascularity a rapid increase in serum local anesthetic levels is to be expected. Due to analytical problems, the literature provides controversial statements about the pharmacokinetics of articaine which is generally used for this block. The given half-life periods following intramuscular application range from 39 min [8] to 31 h [6]. For this reason, mandibular nerve blocks with 2 ml 4% articaine with 1:200,000 epinephrine were carried out in 10 awake patients and 10 patients during intubation anesthesia. RESULTS. Blood samples from peripheral veins showed an average maximum concentration of 2.1 +/- 1.3 mg/l after 12.5 +/- 2.5 min. After 8 h the value had fallen below the minimum detection limit of 0.05 mg/l. In the present study, a half-life of approximately 20 min was determined for articaine after conduction anesthesia. This local anesthetic holds an exceptional position because as an amide-type local anesthetic it contains an additional ester group that is hydrolytically metabolized in the blood. The concentration of the resulting metabolite reaches a maximum value of 2.6 +/- 1.6 mg/l after 40 to 50 min. CONCLUSIONS. Compared to other amide-type local anesthetics, whose terminal plasma half-life varies between 1 and 3.6 h [5], the value of 20 min found for articaine is very low. This is in part due to its structure, as the ester group is rapidly metabolized by plasma esterases. Because of its rapid breakdown articaine is very suitable for use in oral surgery. The HPLC method represents an uncomplicated analytical technique for the determination of local anesthetics levels in blood and other body fluids.
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Carticaína/farmacocinética , Nervio Mandibular , Bloqueo Nervioso , Carticaína/sangre , Humanos , MasculinoRESUMEN
This report presents five adolescent girls and adult women with small cell carcinoma of the ovary (SCCO) who were treated with a polychemotherapy regimen consisting of vinblastine, cisplatin, cyclophosphamide, bleomycin, Adriamycin (doxorubicin), and etoposide (VPCBAE). Two patients had Stage IA, one Stage IIC, and two Stage IIIA disease. Initial therapy consisted of unilateral salpingo-oophorectomy in two cases and total abdominal hysterectomy and bilateral salpingo-oophorectomy in three cases. Three patients remained clinically free of disease after six courses of VPCBAE and the two patients who had measurable pelvic disease before the administration of chemotherapy had objective responses. Four patients died of disease from 11 to 18 months after initial laparotomy. One patient is alive and disease-free at 29 months. The VPCBAE combination appears to be effective in select cases of SCCO. A study of the efficacy of VPCBAE in a larger group of patients with SCCO seems to be indicated.