RESUMEN
BACKGROUND: In 2013 palliative medicine (PM) will be integrated into the undergraduate curriculum as part of the mandatory education in German medical universities. The aim of this study is to determine the current state of implementation at German medical faculties (MF). METHODS: All German MFs were contacted using a written postal survey in June 2012. RESULTS: A total of 32 out of 36 MFs participated. Teaching staff consists of 15 or more lecturers in 8 MFs (30 %) and includes psychologists in 24 MFs (75 %) and also nurses in 18 MFs (56 %). Participating physicians are specialized in anesthesiology, internal medicine and general medicine. Teaching staff include palliative outpatient (20 MFs, 63 %) and consultation services (22 MFs, 69 %). Bedside teaching is provided in 15 MFs (47 %). Multiple choice tests are the major form of assessment (29 MFs, 84 %). The total number of teaching units in PM is between 12 and 43 and is usually provided at the end of medical school education. Nurses are employed in the education significantly more in MFs with a chair in PM. General practitioners were engaged only by faculties without a chair in PM. CONCLUSIONS: The implementation of the mandatory training in PM at MFs in Germany is inhomogeneous. Further steps include in particular the development of a competence-based curriculum and assessment.
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Educación de Pregrado en Medicina/legislación & jurisprudencia , Docentes Médicos , Programas Nacionales de Salud/legislación & jurisprudencia , Cuidados Paliativos , Competencia Clínica/legislación & jurisprudencia , Conducta Cooperativa , Curriculum , Evaluación Educacional , Docentes de Enfermería , Alemania , Humanos , Comunicación Interdisciplinaria , Medicina , Grupo de Atención al Paciente , Facultades de MedicinaRESUMEN
BACKGROUND: The fear-avoidance model implies that in situations with physical demands patients with back pain will overestimate the demand and underestimate their own capacities. PATIENTS AND METHODS: A total of 71 patients with back pain and 48 pain-free control subjects carried out a standardized lifting test with a preceding estimation of their lifting capacity. RESULTS: In both groups the self-estimation and real lifting capacity were in concordance for most group members with patients showing less disconcordance than controls. In the control group 35% of the subjects even underestimated their lifting capacity, which was the case in only 14% of the patients. Patients more frequently overestimated their capacity than pain-free controls (14% vs. 2%). Within the patients subgroups could be identified where patients in general either underestimated or overestimated their own capacity. A comparison between the groups demonstrated significant differences in pain intensity, fear avoidance beliefs and effort. CONCLUSION: As an explanation for these unexpected results it can be hypothesized that in cases of back pain, patients' attention is focused on pain-relevant issues which enables a more realistic estimation of their lifting capacity.
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Evaluación de la Discapacidad , Elevación , Dolor de la Región Lumbar/psicología , Dimensión del Dolor/psicología , Autoevaluación (Psicología) , Actividades Cotidianas/clasificación , Actividades Cotidianas/psicología , Adulto , Anciano , Atención , Cultura , Prueba de Esfuerzo , Miedo , Femenino , Humanos , Elevación/efectos adversos , Masculino , Persona de Mediana Edad , Prueba de Realidad , Valores de Referencia , Adulto JovenRESUMEN
Low back pain is still a big medical and social problem. During the last few decades a change of paradigm in treating non-specific low back pain has happened: physical activity and exercise therapy are now recommended as the first-line treatment in all relevant national and international guidelines. In chronic cases only biopsychosocial treatment concepts are successful, which have been introduced in Germany in 1990 in the form of the GRIP (Göttingen intensive low back program) for the first time. Meanwhile, this treatment has now been recommended by all evidence-based guidelines but we are still in the beginning of a full coverage care in Germany.
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Dolor de la Región Lumbar/terapia , Procedimientos Ortopédicos/normas , Grupo de Atención al Paciente , Modalidades de Fisioterapia/normas , Guías de Práctica Clínica como Asunto , Psicoterapia/normas , Enfermedad Crónica , Terapia Combinada , Alemania , HumanosRESUMEN
The energy level alignment at organic/inorganic (o/i) semiconductor interfaces is crucial for any light-emitting or -harvesting functionality. Essential is the access to both occupied and unoccupied electronic states directly at the interface, which is often deeply buried underneath thick organic films and challenging to characterize. We use several complementary experimental techniques to determine the electronic structure of pâ-quinquephenyl pyridine (5P-Py) adsorbed on ZnO(1 0 -1 0). The parent anchoring group, pyridine, significantly lowers the work function by up to 2.9 eV and causes an occupied in-gap state (IGS) directly below the Fermi level E F. Adsorption of upright-standing 5P-Py also leads to a strong work function reduction of up to 2.1 eV and to a similar IGS. The latter is then used as an initial state for the transient population of three normally unoccupied molecular levels through optical excitation and, due to its localization right at the o/i interface, provides interfacial sensitivity, even for thick 5P-Py films. We observe two final states above the vacuum level and one bound state at around 2 eV above E F, which we attribute to the 5P-Py LUMO. By the separate study of anchoring group and organic dye combined with the exploitation of the occupied IGS for selective interfacial photoexcitation, this work provides a new pathway for characterizing the electronic structure at buried o/i interfaces.
RESUMEN
The possibility that surface tension may affect the hydrostatic transmural pressure of pulmonary vessels and the development of pulmonary edema was studied in anesthetized, open-chested dogs. Isogravimetric pressure (the static intravascular pressure at which transmural osmotic and hydrostatic pressures are balanced such that net fluid flux is zero and lung weight is constant) was measured in nine animals under three conditions: (a) control, normal surface tension, at an alveolar pressure of 30 cm H2O with the apenic lung at room temperature; (b) after increasing surface tension by cooling and ventilating at a low functional residual capacity, at an alveolar pressure sufficient to produce the same lung volume present during control measurements; and (c) after restoring surface tension by rewarming while holding the lung at a high inflation volume, again at the control lung volume. Lung volumes were established from external dimensions and confirmed +/- 10% by deflation spirometry. The isogravimetric pressure (relative to alveolar pressure) was significantly less with increased surface tension than during either the initial control condition (P less than 0.01), or when the surface tension has been restored (P less than 0.01). Similar changes occurred in each of three additional studies performed with control alveolar pressures of 10 cm H2O. Thus, increased surface tension favors fluid leakage presumably because it increases the microvascular transmural pressure.
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Alveolos Pulmonares/fisiopatología , Edema Pulmonar/fisiopatología , Tensión Superficial , Anestesia , Animales , Perros , Femenino , Capacidad Residual Funcional , Presión Hidrostática , Mediciones del Volumen Pulmonar , Masculino , Presión Osmótica , Arteria Pulmonar/fisiopatologíaRESUMEN
The effect of dazoxiben, a selective thromboxane (Tx) synthetase inhibitor, on systemic and pulmonary hemodynamics, eicosanoids, and lung permeability was assessed in awake goats with lung lymph fistulae following infusion of Escherichia coli endotoxin (1 microgram/kg). Animals received endotoxin either with no treatment or pretreatment with a bolus (25 mg/kg) followed by a maintenance infusion (10 mg/kg per h) of dazoxiben. In untreated animals, the peak rise of 26.8 cm H2O in pulmonary artery (Ppa) and of 13.5 cm H2O in wedge (Pw) pressures occurred at the same time as the peak elevations in plasma thromboxane B2 (T X B2). Maximum reduction in cardiac output (Qt) also occurred at the same time. Lung lymph flow (QL) increased during this period and remained elevated for at least 6 h after endotoxin. T X B2 levels had returned from a peak of 13.1 to 0.7 ng/ml by 2 h. In dazoxiben-treated animals, plasma concentrations of T X B2 were never significantly elevated. Increases in Ppa and Pw were markedly reduced and decreased Qt was transient. QL in treated animals began to increase by 30 min after endotoxin and reached a peak by 2 h. Increased QL in treated animals was not as great as in the untreated animals. Moreover, lymph-plasma protein ratios increased significantly in treated animals. Plasma prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha concentrations were elevated in both groups after endotoxin with values significantly greater in treated animals. We conclude that selective inhibition of Tx ameliorates many adverse hemodynamic consequences of endotoxemia but does not prevent lung permeability changes.
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Permeabilidad Capilar/efectos de los fármacos , Pulmón/irrigación sanguínea , Tromboxano A2/fisiología , Tromboxanos/fisiología , Vasoconstricción/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Proteínas Sanguíneas/análisis , Endotoxinas/administración & dosificación , Cabras , Imidazoles/administración & dosificación , Leucopenia/etiología , Pulmón/fisiopatología , Linfa/análisis , Linfa/fisiopatología , Presión Esfenoidal Pulmonar/efectos de los fármacos , Tromboxano A2/sangre , Resistencia Vascular/efectos de los fármacosRESUMEN
The properties of a Gs alpha mutant with an Asn substituted for Ser at position 54, designated mutant 54Asn alpha s, were studied after expression in S49 alpha s-deficient (cyc-) cells. Ser-54 in alpha s is comparable to Ser-17 in Ras, which is involved in binding Mg2+ associated with bound nucleotide. 54Asn alpha s did not restore either hormone-induced cyclic AMP production in intact cyc- cells or hormone-induced adenylyl cyclase activation in membranes isolated from these cells. The defect was a failure of ligand-bound receptor to activate 54Asn alpha s, since the mutant protein retained the ability to activate adenylyl cyclase in isolated membranes in the presence of GTP or GTP gamma S. Guanine nucleotide regulation of mutant alpha s suggested that it has increased guanine nucleotide exchange rates and an increased preference for diphosphates over triphosphates. Hormone stimulation magnified the preference of 54Asn alpha s for diphosphates, which could account for its inability to be activated by receptor. The properties of this mutant are discussed in terms of similarities to and differences with the analogous RasH mutant, which has been shown to interfere with endogenous Ras function in cells.
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Proteínas de Unión al GTP/genética , Magnesio/metabolismo , Mutación/genética , Adenilil Ciclasas/metabolismo , Animales , Asparagina/genética , Sitios de Unión/genética , Northern Blotting , AMP Cíclico/metabolismo , Activación Enzimática , Proteínas de Unión al GTP/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Guanosina Trifosfato/metabolismo , Isoproterenol/farmacología , Cinética , Ratones , Proteína Oncogénica p21(ras)/genética , Serina/genética , Células Tumorales CultivadasRESUMEN
Previous studies have suggested that endotoxin tolerance induces macrophage desensitization to endotoxin through altered guanine nucleotide regulatory (G) protein function. In the present study the binding characteristics of the nonhydrolyzable GTP analogue GTP gamma [35S] to macrophage membranes from endotoxin tolerant and control rats were determined. Membranes were prepared from peritoneal macrophages harvested from rats 72 h after two sequential daily doses of vehicle or Salmonella enteritidis endotoxin (100 micrograms/kg on day 1 and 500 micrograms/kg on day 2). GTP gamma [35S] bound to a single class of sites that were saturable and displaceable in control and endotoxin tolerant macrophage membranes. The maximum specific binding of GTP gamma [35S] was significantly (P < 0.01) decreased in membranes from tolerant rats compared to control (Bmax = 39 +/- 7 pmol/mg protein in control vs. 11 +/- 2 pmol/mg protein in endotoxin tolerant; n = 5). There were no significant differences in the Kd values. To determine whether the reduced GTP gamma S binding was due to decreases in G proteins, macrophage membrane G protein content was determined by western blotting with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha, and the beta subunit of G. Scanning densitometric analysis demonstrated differential decreases in tolerant macrophage membrane G proteins. Gi3 alpha was reduced the most to 48 +/- 8% of controls (n = 3), and this reduction was significant compared to those of other G proteins. Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3) and 65 +/- 4% (n = 3) of control values, respectively. Gs alpha(L) and Gs alpha(H) were reduced to 61 +/- 5% (n = 3) and 68 +/- 3% (n = 3) of control, respectively. These results demonstrate that endotoxin tolerant macrophages exhibit decreased membrane GTP binding capacity and differential reductions in the content of specific G proteins. The cellular mechanisms leading to such alterations in G proteins and their functional significance in the acquisition of endotoxin tolerance merit further investigation.
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Endotoxinas/farmacología , Proteínas de Unión al GTP/metabolismo , Macrófagos Peritoneales/metabolismo , Animales , Western Blotting , Membrana Celular/metabolismo , GTP Fosfohidrolasas/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Proteínas de la Membrana/metabolismo , Unión Proteica , Ratas , Ratas Endogámicas , Transducción de SeñalRESUMEN
To investigate the relationship between the effects of a pertussis toxin-inhibitable class of G-proteins and the ras family of protooncogenes on cell growth, we isolated multiple cell lines transformed by oncogenic Hras or Nras genes and measured the ability of pertussis toxin to inhibit their growth rate. Although all of the cell lines were morphologically transformed and could grow in agar suspension, there was considerable variability in their resistance to pertussis toxin, ranging from cell lines completely resistant to pertussis toxin to cell lines as sensitive to pertussis toxin as the parental cells from which they derived. For those lines resistant to pertussis toxin, this resistance is not due to an inability of pertussis toxin to reach or react with its intracellular target; pertussis toxin could be shown to ADP-ribosylate the endogenous G-proteins of all lines tested regardless of whether it affected their growth rate. There was a strong correlation between the level of active ras protein expressed in the different lines and the degree of resistance to pertussis toxin (r = 0.80). Although the Hras-transformed cell lines were more resistant to pertussis toxin as a group than the Nras-transformed cell lines, we believe that this is not a primary difference between Nras and Hras, but, rather, is due to a higher average level of expression of ras in the cell lines receiving Hras. We suggest that the consequences of ras transformation vary with the concentration of oncogenic ras present in the cell, and that different assays or different properties of transformation show different sensitivities to the level of ras expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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División Celular , Transformación Celular Neoplásica/genética , Genes ras/genética , Toxina del Pertussis , Factores de Virulencia de Bordetella/farmacología , Adenosina Difosfato Ribosa/metabolismo , Animales , División Celular/genética , Línea Celular Transformada , Resistencia a Medicamentos , Técnicas de Inmunoadsorción , RatonesRESUMEN
The heterotrimeric GTP binding proteins, G proteins, consist of three distinct subunits: alpha, beta, and gamma. There are 12 known mammalian gamma subunit genes whose products are the smallest and most variable of the G protein subunits. Sequencing of the bovine brain gamma(10) protein by electrospray mass spectrometry revealed that it differs from the human protein by an Ala to Val substitution near the N-terminus. Comparison of gamma isoform subunit sequences indicated that they vary substantially more at the N-terminus than at other parts of the protein. Thus, species variation of this region might reflect the lack of conservation of a functionally unimportant part of the protein. Analysis of 38 gamma subunit sequences from four different species shows that the N-terminus of a given gamma subunit isoform is as conserved between different species as any other part of the protein, including highly conserved regions. These data suggest that the N-terminus of gamma is a functionally important part of the protein exhibiting substantial isoform-specific variation.
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Proteínas de Unión al GTP Heterotriméricas/química , Alanina/química , Animales , Bovinos , Cromatografía Líquida de Alta Presión , Clonación Molecular , Secuencia Conservada , Etiquetas de Secuencia Expresada , Proteínas de Unión al GTP Heterotriméricas/genética , Humanos , Filogenia , Unión Proteica , Isoformas de Proteínas , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Valina/químicaRESUMEN
Thyroid iodide labeled 72 h earlier with 131I was separated from organic iodine by polyacrylamide gel electrophoresis. The concentration of thyroid radioiodide was not significantly diminished 2 h after the administration of perchlorate (100 mg NaClO4) alone, but perchlorate reduced the rise in glandular radioiodide caused by simultaneously given TSH (1 IU). When propylthiouracil (PTU; 20 mg) was given along with it, perchlorate decreased thyroid radioiodide even in rats not treated with TSH. In rats given perchlorate, PTU caused a much slighter augmentation of the TSH-induced increase in the thyroid radioiodide concentration than in the absence of perchlorate. These results are interpreted as follows. Perchlorate-discharged iodide in rats not given TSH is largely transported iodide. Perchlorate can discharge intrathyroidally generated (internal) iodide too, but this is unequivocally reflected by a decrease in the thyroid iodide concentration only when the production of internal iodide is enhanced by TSH. Perchlorate in its own right interferes with organic binding of internal iodide, thereby partially preempting the effect whereby PTU causes accumulation of internal iodide in TSH-treated rats. We suggest that internal thyroid iodide is transported from its site of generation, the follicular cell, to its site of organic binding, the follicular lumen, by perchlorate-sensitive transport. It is also possible that internal iodide escaping from a follicle is conserved by perchlorate-inhibitable reuptake into follicular cells closer to the venous end of the capillary bed.
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Yoduros/metabolismo , Glándula Tiroides/metabolismo , Animales , Transporte Biológico , Masculino , Ratas , Tirotropina/sangreRESUMEN
Thyroid radioiodide to serum radioiodide concentration (*T/*S) ratios 1 h after 131I administration were 3 times higher in rats pretreated with propylthiouracil (PTU) than in rats with binding thyroids. Although indications of a preponderance of transported iodide in the thyroid early after 131I injection were found, a reduction of the 1-h *T/*S ratio in TSH-treated rats by the inhibitor of iodotyrosine dehalogenation, mononitrotyrosine, points to an early contribution of intrathyroidally generated (internal) iodide to total thyroid iodide. In rat thyroids labeled 72 h earlier, there was no rise in electrophoretically separated radioiodide 2 h after the administration of PTU alone, but the elevation of thyroid iodide due to TSH was augmented by concurrently given PTU. On the assumption that PTU affects transported components of thyroid iodide identically whether they are labeled 1 or 72 h earlier, we conclude that PTU must severely depress the generation of internal iodide. This effect is no longer evident if TSH is given simultaneously. Further, our results are consistent with the hypothesis that internal iodide passes through a stage in which it is not available for organic binding before it mixes with transported iodide. TSH appears to facilitate the transfer of internal iodide into the pool which it shares with external iodide.
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Yoduros/metabolismo , Propiltiouracilo/farmacología , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Tirotropina/farmacología , Animales , Radioisótopos de Yodo , Cinética , Masculino , Monoyodotirosina/farmacología , RatasRESUMEN
The involvement of a Gi- or G(o)-related G-protein as a regulator of the growth of guinea pig thoracic aorta smooth muscle (TASM) cells was studied by investigating the effects of pertussis toxin (PTX) on the growth of these cells. PTX treatment decreased the growth rate of TASM cells by 70-100%. This effect was apparent within 24 h after exposure to the toxin and persisted for at least 10 days after starting the treatment. The effect of the toxin appeared to be the result of the inactivation of a G-protein because 1) TASM cell membranes contained a 40-kilodalton substrate for the toxin in in vitro assays that was absent in membranes prepared from cells pretreated with toxin; and 2) the effect required both the enzymatic component (A-protomer) of the toxin that inactivates Gi/G(o)-related G-proteins and its B-oligomer necessary for binding and internalization of the A-protomer. The effect of the toxin was not due to an increased level of intracellular cAMP brought about by inactivation of a G-protein that normally inhibits adenylyl cyclase activity. Further, the toxin did not merely make some unknown mitogen rate limiting, because neither increasing concentrations of serum in the growth medium nor supplementation with platelet-derived growth factor could overcome its inhibition of TASM cell growth. Instead, some unknown process regulated by a PTX-sensitive G-protein appears to be required for the normal growth of these cells.
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Toxina de Adenilato Ciclasa , Fenómenos Fisiológicos Sanguíneos , Músculo Liso Vascular/efectos de los fármacos , Toxina del Pertussis , Factor de Crecimiento Derivado de Plaquetas/farmacología , Factores de Virulencia de Bordetella/farmacología , Adenosina Difosfato Ribosa/metabolismo , Animales , Aorta Torácica , División Celular/efectos de los fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas de Unión al GTP/fisiología , Cobayas , Proteínas de la Membrana/metabolismo , Músculo Liso Vascular/citologíaRESUMEN
We have examined porcine granulosa cells (pGCs) for the presence of immunodetectable mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinases, ERK) and have further studied the effects of epidermal growth factor (EGF) on the activation of these kinases. Cell lysates prepared from untreated monolayer cultures of pGCs were subjected to Western immunoblotting analysis using monoclonal antibodies to ERK1, ERK2 and pan-specific ERK. MAP kinases were detected having mol wts of 87K (ERK87), 54K (ERK54), 44K (ERK1), and 42K (ERK2). Treatment of pGCs with increasing concentrations (1-10 ng/ml) of EGF for 10 min resulted in electrophoretic mobility shifts of ERK1 and ERK2 suggesting hyperphosphorylation. Immunoprecipitation with an antiphosphotyrosine antibody (PY20), followed by Western analysis using pan-ERK, revealed a marked concentration-dependent increase in tyrosine phosphorylation of ERK2 in response to EGF treatment. The mobility shift and tyrosine phosphorylation of ERK2 was observed as early as 1 min after treatment with 10 ng/ml EGF. In-gel myelin basic protein (MBP) kinase assays revealed significant MBP kinase activity associated with ERK1 and ERK2 in total cell lysates and ERK2 in PY20 immunoprecipitates. Although ERK1 displayed a moderate mobility shift in response to EGF, tyrosine phosphorylation of this MAP kinase was not appreciably increased by EGF. Furthermore, PY20 immunoprecipitates demonstrated minimal MBP kinase associated with ERK1 in response to EGF treatment. Electrophoretic migration, tyrosine phosphorylation, and MBP kinase activity of the ERK54 and ERK87 was not effected regardless of EGF concentration or duration of treatment. These data demonstrate for the first time that pGCs contain immunodetectable MAP kinases. EGF, in a concentration- and time-dependent manner, increases tyrosine phosphorylation and MBP kinase activity (i.e. activation) of ERK2, and to a lesser degree ERK1, suggesting that the activation of MAP kinase may mediate the mitogenic action of EGF in pGCs.
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Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Células de la Granulosa/metabolismo , Tirosina/metabolismo , Animales , Células Cultivadas , Activación Enzimática , Femenino , Concentración Osmolar , Fosforilación , Porcinos , Factores de TiempoRESUMEN
Membrane-bound adenylyl cyclases from ram, dog, and human sperm are unresponsive to fluoride and guanylylimidodiphosphate [GMP-P(NH)P], two agents that stimulate the adenylyl cyclases of somatic cells by an action on the stimulatory guanine nucleotide-binding regulatory (Ns) component of adenylyl cyclase. We have investigated whether this is because the sperm cell catalytic unit is functionally uncoupled from Ns but, nevertheless, capable of interacting with it, or because the sperm cell adenylyl cyclase system is unique and regulated differently from that of somatic cells. Sperm cells were found to be deficient in Ns, as evidenced by the inability of detergent extracts from sperm cell membranes and fractions to reconstitute Ns-mediated regulation of the adenylyl cyclase of cyc- S49 cells. In addition, attempts to label Ns in sperm cell membranes by [32P]ADP ribosylation with cholera toxin revealed that, if present, Ns is less than 1% of that found in human erythrocyte membranes. This, however, was not the only reason for the unresponsiveness of sperm cell adenylyl cyclase, since fluoride stimulation of the sperm cell enzyme could not be induced by reconstituting it with Ns purified from human erythrocytes (hRBC). When intact hRBC membranes were added to sperm cell fractions in the presence of fluoride, the activities that resulted were greater than the sum of the individual activities. This apparent reconstitution of fluoride regulation of sperm cell adenylyl cyclase could be blocked by lima bean trypsin inhibitor and appears to have resulted from proteolytic activation of the hRBC adenylyl cyclase by sperm proteases. Sperm cell membranes also appear to lack a functional inhibitory regulatory protein of the adenylyl cyclase system (Ni), since they did not contain an ADP-ribosylatable substrate for pertussis toxin action. These results suggest that the sperm cell adenylyl cyclase system is unique and different from that of somatic cells. Sperm cells appear to neither contain Ns or Ni nor possess the ability of their adenylyl cyclase system to interact with Ns from an exogenous source.
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Adenilil Ciclasas/metabolismo , Membrana Celular/metabolismo , Espermatozoides/enzimología , Animales , Membrana Celular/enzimología , Células/metabolismo , Perros , Membrana Eritrocítica/fisiología , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/farmacología , Humanos , Membranas Intracelulares/metabolismo , Masculino , Ovinos , Espermatozoides/metabolismoRESUMEN
The membrane protein P-selectin tethers leukocytes to endothelial cells (EC) and on activated platelets, and may play a role in atherosclerosis. Lower plasma levels of a soluble (c) P-selectin have recently been observed in premenopausal women compared to those in men. Given the antiatherogenic-cardioprotective effect of 17 beta-estradiol (E2), we hypothesized that E2 may down-regulate the expression of P-selectin and subsequently decrease cP-selectin levels. The effects of E2 on levels of plasma cP-selectin were evaluated during the menstrual cycle in healthy women (n = 18) and by measuring the effect of a single im injection of 10 mg E2 valerate (n = 9) or placebo (n = 10) on cP-selectin levels in healthy male volunteers. In women, the cyclic increase in serum E2 concentrations was accompanied by a decrease in cP-selectin levels from 110 ng/mL [95% confidence interval (CI), 100-137 ng/mL] in the follicular phase. The decrease reached a maximum of 13% (95% CI, 2-19%, P = 0.014) in the luteal phase. In men, cP-selectin decreased from a median of 139 ng/mL (95% CI, 113-165) to 125 ng/mL (95% CI, 97-152; P = 0.038) 4 days after E2 injection. The median baseline value of cP-selectin in the 19 male volunteers was 133 ng/mL (95% CI, 115-143 ng/mL) and was approximately 30% higher than those in the female volunteers during the midcycle (P = 0.024) and luteal (P = 0.012) phases, but was not different from that during the follicular phase. In sum, our study suggests that E2 lowers cP-selectin levels. An E2-induced decrease in cP-selectin reflects either decreased activation or damage of platelets and/or endothelial cells in vivo. Thus, our study may point to an additional mechanism for the residual antiatherogenic-cardioprotective effect of E2 that cannot be explained by its lipid-lowering effects.
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Estradiol/farmacología , Selectina-P/sangre , Adulto , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Ciclo Menstrual/sangre , Selectina-P/metabolismo , Caracteres Sexuales , Solubilidad , Venas Umbilicales/citología , Venas Umbilicales/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
Pertussis toxin (islet-activating protein) treatment of intact Swiss 3T3 cells causes a time- and dose-dependent loss of availability of a 40 kDa membrane protein for toxin-catalyzed ADP-ribosylation in subsequent incubations with [32P]NAD. In parallel, [3H]thymidine uptake by quiescent cells stimulated with fresh serum, cell doubling time and cell saturation density are all decreased 30-50%. These results cannot be accounted for by the potential effect of the toxin on cell cAMP levels. They suggest that a pertussis toxin substrate, probably Gi, modulates some component of growth regulation in Swiss 3T3 cells.
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Ciclo Celular/efectos de los fármacos , Proteínas de Unión al GTP/fisiología , Toxina del Pertussis , Factores de Virulencia de Bordetella/farmacología , Adenosina Difosfato Ribosa/metabolismo , Animales , Línea Celular , Toxina del Cólera/farmacología , Ratones , NAD/metabolismoRESUMEN
The phenotype of a Ser to Asn mutation at position 54 of the alpha subunit of G(s)(N54-alpha(s)) was characterized in transient transfection experiments in COS and HEK293 cells. Expression of either wild type or N54-alpha(s) increased basal cAMP levels. In contrast, expression of wild type alpha(s), potentiated agonist-stimulated cAMP levels, while expression of N54-alpha(s)caused a decrease. Thus, the N54-alpha(s) mutant possesses a conditional dominant negative phenotype, suppressing preferentially hormone-stimulated effects.
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AMP Cíclico/metabolismo , Proteínas de Unión al GTP/metabolismo , Mutación , Tirotropina/metabolismo , Animales , Células COS , Bovinos , Línea Celular , Proteínas de Unión al GTP/genética , Humanos , Fenotipo , Ratas , Receptores de Tirotropina/metabolismoRESUMEN
Sixteen patients suffering from hemicranial attacks are reported. After many years of unsuccessful conservative treatment (mean = 12.4 years), the patients were treated surgically with good results. The radiological or electrophysiological examinations were non-specific or negative. Only vasoactive tests (provoking or relieving pain) or local anesthesia proved helpful in diagnosing and localizing the origin of pain. Intraoperatively, hemicranial attacks were found to be caused by vascular irritation or compression of the cervical nerve root C2. After decompression (n = 6) or dissection (n = 10) of the nerve root and the ganglion, 12 patients were relieved of their pain, 2 had improved relatively, 1 showed only a slight improvement, and in 1 patient no cause was found and no improvement was achieved. Two patients suffered recurrence of pain postoperatively; one had no further complaints after root extirpation following percutaneous thermorhizotomy. Electron microscopic examination of the nerve root and its ganglion revealed focal morphological changes, including proliferation of connective tissue in the endoneurium and the ganglion itself, the formation of onion-bulb-like structures around single axons, discrete signs of myelin damage and axonal degeneration. These morphological changes are possibly the result of a chronic vascular compression.
Asunto(s)
Lateralidad Funcional/fisiología , Cefalea/fisiopatología , Raíces Nerviosas Espinales/fisiopatología , Adulto , Femenino , Cefalea/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Raíces Nerviosas Espinales/irrigación sanguínea , Raíces Nerviosas Espinales/cirugíaRESUMEN
In recent years, multidisciplinary pain programs were seen to successfully treat patients by basing treatment on a combination of physical exercise and psychological interventions. However, in spite of their effectiveness, it still remains to be clarified exactly which features of these programs were responsible for patient improvement. Cognitive-behavioral models posit that improvement is due, in part, to changes in patient coping strategies. Nonetheless, as reflected by the conflicting opinions present in the literature, it is questionable whether a so-called 'cognitive shift' is an accurate indicator for return to work of disabled patients. Ninety patients with chronic low back pain took part in a multidisciplinary treatment program. Therapeutic environment reinforces wellness behavior and enhances the patients' sense of control over their pain and resulting disability. The main therapeutic target point was to facilitate return to work. Ways of coping were measured by a well studied coping inventory in the German language (FEKB). Factor analysis revealed three factors: 'catastrophizing', 'search for information' and 'cognitive control'. In addition, assessment included measurements of pain intensity, depression, disability, flexibility of the lumbar spine, and different performance parameters. All of them were measured prior to and at the end of treatment, and following intervals of 6 and 12 months after discharge from program. Measurements showed significant changes over time, but more importantly, nearly all results were seen to stabilize at the 6- and 12-month evaluation following treatment. The coping strategies demonstrated little or poor change. In addition, coping measures and change in coping behavior showed poor prognostic relevance. But other psycho-social parameters like self-evaluation of potential return-to-work, application for pension, the length of pre-absence from work, and a decrease in subjective disability following treatment were effective indicators for 'back-to-work'. Other objective parameters, such as medical history, physical impairment and general physical variables were seen to have little predictive value in determining a return to work. The results suggest that the primary target point for further investigation is the analysis of the patients' beliefs about their pain. Our results indicate that future research must be attentive to the complex interactions between environmental factors and the coping demands posed by the specific nature of pain problems.