RESUMEN
BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE), but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVES: We aimed to assess anti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: In total 124 patients with SSc were studied; 106 were female and the median age was 59·4 years (range 25-81·4). Overall 75 (60·5%) had limited cutaneous SSc and 49 (39·5%) had diffuse cutaneous SSc. Also included were 25 patients with Sjögren syndrome (SjS), 29 with rheumatoid arthritis (RA), 38 with SLE and 53 healthy controls. Enzyme-linked immunosorbent assays with high- and low-salt buffers were used to measure anti-C1q antibodies and CICs. The former allows only anti-C1q antibody binding to C1q and the latter also allows IgG Fc to bind to C1q. RESULTS: Anti-C1q antibodies were present in 20 of 124 (16·1%) patients with SSc: five had high levels (> 80 RU mL-1 ) and 10 (50%) had moderate levels (40-80 RU mL-1 ). Anti-C1q antibodies were also present in one of 25 (4%) patients with SjS, one of 29 (3%) with RA (P < 0·05 for both) and three of 53 (6%) healthy controls (P < 0·01). Anti-C1q antibodies were detected in 13 of 38 (34%) patients with SLEs. Anti-C1q antibodies were more frequent in male than female patients with SSc (P = 0·005); this association remained after multivariate regression analysis. Anti-C1q antibody level was the most important factor in predicting the presence of pulmonary fibrosis, and the second most important in predicting pulmonary arterial hypertension. Fourteen patients with SSc (11·3%) had CICs. CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc, and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension.
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Autoanticuerpos/sangre , Autoantígenos/inmunología , Complemento C1q/inmunología , Fibrosis Pulmonar/sangre , Esclerodermia Sistémica/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Estudios de Cohortes , Femenino , Voluntarios Sanos , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/inmunología , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunología , Factores Sexuales , Tomografía Computarizada por Rayos XRESUMEN
Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study ( n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Fosfatidilserinas/inmunología , Complicaciones del Embarazo/diagnóstico , Trombosis/diagnóstico , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/sangre , Estudios Transversales , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
INTRODUCTION: Antibodies to the domain 1 of beta 2 glycoprotein I (ß2GPI-D1) have been suggested as a risk marker for thrombosis in patients with the antiphospholipid syndrome (APS). This cross-sectional study aimed to analyze the clinical utility of a novel chemiluminescence assay for the detection of anti-ß2GPI-D1 antibodies. PATIENTS AND METHODS: Sera collected from patients with primary or secondary APS (n = 106; 72 with and 34 without history of thrombosis) and controls (n = 272) were tested for anti-ß2GPI-D1 IgG by chemiluminescence assay (QUANTA Flash) and by two anti-ß2GPI IgG assays (QUANTA Lite and QUANTA Flash ß2GPI IgG). RESULTS: Anti-ß2GPI-D1 IgG titers were significantly higher in patients with thrombosis (P = 0.0032) than those without. At the cut-off of 20 units, which yielded a 99.5% specificity, 24 of 72 (34.9%) patients with thrombosis and four of 34 (11.8%) without thrombosis were anti-ß2GPI-D1 IgG positive (odds ratio, OR = 4.0). By further optimizing the cut-off specifically for correlation with thrombosis, 20.8% of the patients with thrombosis and 2.9% of the patients without thrombosis were positive (OR = 8.7). The ORs were significantly lower for antibodies to the full-length ß2GPI by either the chemiluminescence assay or ELISA. Using the anti-ß2GPI chemiluminescence assay, the OR was 2.3 (recommended cut-off of 20 CU) or 4.1 (optimal cut-off 164.6 CU). Using the anti-ß2GPI ELISA, the OR was 2.7 (recommended cut-off of 20 units) or 3.7 (optimal cut-off 7.6 units). CONCLUSION: These data indicate that anti-ß2GPI-D1 IgG are present more frequently and in higher titers in APS patients with thrombotic complications than in those without.The novel ß2GPI-D1 chemiluminescence assay appears to be superior to full-length ß2GPI assays for the risk assessment of thrombotic events in APS patients.
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Anticuerpos Anticardiolipina/sangre , Síndrome Antifosfolípido/complicaciones , Inmunoglobulina G/sangre , Mediciones Luminiscentes/métodos , Trombosis/complicaciones , beta 2 Glicoproteína I/inmunología , Estudios Transversales , Humanos , Factores de RiesgoRESUMEN
Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-ß signalling in T cells (dnTGF-ßRII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-ßRII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-γ or tumour necrosis factor (TNF)-α. Sera from all the dnTGF-ßRII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-α had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-ßRII mice as well as to study the possible role of ANA in the pathophysiology of PBC.
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Anticuerpos Antinucleares/biosíntesis , Citocinas/metabolismo , Cirrosis Hepática Biliar/inmunología , Animales , Antígenos Nucleares , Autoantígenos , Células Cultivadas , Citocinas/genética , Citocinas/inmunología , Modelos Animales de Enfermedad , Epítopos/inmunología , Humanos , Ratones , Ratones Transgénicos , Proteínas de Complejo Poro Nuclear/inmunología , Eliminación de Secuencia/genéticaRESUMEN
OBJECTIVE: Anti-ß2 GPI are a formal laboratory criterion for the antiphospholipid syndrome (APS). They were demonstrated to be a risk factor for thrombosis and fetal losses but can also be detected in patients with systemic autoimmune disease (SAD), in healthy adults individuals and pre-school children. It has been suggested that different subpopulations of anti-ß2GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identified in patients with non-thrombotic conditions. METHODS: We studied 48 patients with SAD (32 systemic lupus erythematosus, 16 undifferentiated connettive tissue disease), 64 patients with APS, 57 one-year-old healthy children born to mother with SAD, 33 children with atopic dermatitis. All subjects were IgG anti-ß2 GPI positive. The specificity of anti-ß2 GPI was investigated using ELISA research products containing recombinant ß2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-ß2 GPI were tested at a validated home-made ELISA routinely performed in our laboratory. No thrombotic events were recordered in patients with SAD and in both groups of children. RESULTS: Patients with SAD and APS showed prevalent reactivity for D1 while children in both groups preferentially recognize D4/5. CONCLUSIONS: IgG anti-ß2 GPI against D1 seem to cluster in patients with systemic autoimmune conditions. Their pathogenic potential in determine APS manifestations may be mitigated by adequate prophylaxis.
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Autoanticuerpos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , beta 2 Glicoproteína I/inmunología , Adolescente , Adulto , Anciano , Especificidad de Anticuerpos , Autoanticuerpos/sangre , Autoantígenos/química , Enfermedades Autoinmunes/sangre , Enfermedades del Tejido Conjuntivo/sangre , Enfermedades del Tejido Conjuntivo/inmunología , Dermatitis Atópica/sangre , Dermatitis Atópica/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Materno-Adquirida/inmunología , Lactante , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Modelos Inmunológicos , Embarazo , Complicaciones del Embarazo/inmunología , Estructura Terciaria de Proteína , Adulto Joven , beta 2 Glicoproteína I/químicaRESUMEN
OBJECTIVE: Anti-ß2glycoprotein I antibodies (a-ß2GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-ß2GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a-ß2GPI in different clinical situations. METHODS: We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-ß2GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-ß2GPI positive. IgG a-ß2GPI were performed by homemade ELISA, while IgG a-ß2GPI D1 and D4/5 were tested on research ELISAs containing recombinant ß2GPI domains antigens. RESULTS: One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-ß2GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-ß2GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children. CONCLUSIONS: A-ß2GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the "innocent" profile of a-ß2GPI in children.
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Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Inmunoglobulina G/inmunología , Trombofilia/inmunología , beta 2 Glicoproteína I/inmunología , Adulto , Especificidad de Anticuerpos , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Dermatitis Atópica/sangre , Dermatitis Atópica/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Lactante , Recién Nacido , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Estructura Terciaria de Proteína , Proteínas Recombinantes/inmunología , Trombofilia/etiología , beta 2 Glicoproteína I/químicaRESUMEN
BACKGROUND: Clinically significant primary biliary cirrhosis occurs in 2.5% of patients with systemic sclerosis. Primary biliary cirrhosis-specific autoantibodies include anti-mitochondrial, anti-glycoprotein 210, and anti-sp100 antibodies. The majority of asymptomatic anti-mitochondrial-positive subjects express histological features of primary biliary cirrhosis. Early detection of primary biliary cirrhosis is important, as timely introduction of ursodeoxycholic acid may improve prognosis. The aim was to assess the prevalence of MIT3 IgG-anti-mitochondrial, gp210, sp100 and other autoantibodies in patients with systemic sclerosis and compare the clinical and biochemical parameters in those who are primary biliary cirrhosis-specific autoantibodies positive and negative. MATERIALS/METHODS: Fifty-two consecutive patients with systemic sclerosis were included. Thirty-three suffered from limited skin SS and 19 from diffuse SS. RESULTS: Eight (15%) patients with systemic sclerosis tested positive for primary biliary cirrhosis-specific autoantibodies. No significant differences were observed between primary biliary cirrhosis-specific autoantibodies positive and negative subjects in terms of various demographic, clinical or biochemical features. A trend towards increased prevalence of chronic fatigue in primary biliary cirrhosis-specific autoantibodies positive patients was observed. CONCLUSIONS: Primary biliary cirrhosis-specific autoantibodies were detected in 15% of the systemic sclerosis patients. Since patients with primary biliary cirrhosis-specific antibodies are at high-risk or do suffer from primary biliary cirrhosis, screening for primary biliary cirrhosis-specific autoantibodies may be considered during routine assessment of systemic sclerosis.
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Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/inmunología , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/inmunología , Antígenos Nucleares/sangre , Autoanticuerpos/sangre , Autoantígenos/sangre , Biomarcadores/sangre , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Inmunoglobulina G/sangre , Cirrosis Hepática Biliar/sangre , Masculino , Persona de Mediana Edad , Mitocondrias Hepáticas/inmunología , Proteínas de Complejo Poro Nuclear/sangre , Prevalencia , Esclerodermia Sistémica/sangreAsunto(s)
Enfermedades de las Arterias Carótidas/inmunología , Inmunoglobulina A/inmunología , beta 2 Glicoproteína I/inmunología , Anticuerpos Anticardiolipina/inmunología , Enfermedades de las Arterias Carótidas/epidemiología , Estenosis Carotídea/epidemiología , Estenosis Carotídea/inmunología , Humanos , Hipercolesterolemia/epidemiología , Modelos Logísticos , Oportunidad Relativa , Factores de RiesgoAsunto(s)
Arteriosclerosis/inmunología , Enfermedades de las Arterias Carótidas/inmunología , Inmunoglobulina A/inmunología , beta 2 Glicoproteína I/inmunología , Anciano , Arteriosclerosis/fisiopatología , Autoanticuerpos , Enfermedades de las Arterias Carótidas/fisiopatología , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Aterosclerosis/inmunología , Autoanticuerpos/inmunología , Inmunoglobulina A/inmunología , beta 2 Glicoproteína I/inmunología , Síndrome Antifosfolípido/complicaciones , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Autoanticuerpos/sangre , Femenino , Humanos , Inmunoglobulina A/sangre , MasculinoRESUMEN
BACKGROUND: It is ionized calcium that is physiologically active and under homeostatic control; however, total calcium is more conveniently measured. Formulae for correction of calcium to account for albumin binding have not been validated in a dialysis setting. METHODS: We measured ionized calcium simultaneously with total calcium (t[Ca]), albumin, total protein and pH before dialysis in 50 stable outpatients and convalescent inpatients. RESULTS: Although 92% of patients were taking calcium supplements and 70% taking alphacalcidol, 11 patients (22%) had ionized hypocalcaemia. To facilitate comparison of calculated ionized calcium, measured total calcium (t[Ca]), and 'corrected' calcium (c[Ca]), with the criterion measure of ionized calcium, all measurements were converted to z scores, standardized on the normal range for each variable. Results are expressed as intraclass correlation coefficients (ICC: 0, all differences are due to error; 1, all differences are due to between patient variation). CONCLUSIONS: None of the published formulae greatly improved the test characteristics beyond simply using the total calcium. A correction formula in widespread use (Payne), quoted in reference texts, agreed less well with ionized calcium than did the unadjusted measured calcium. Correction formulae should be abandoned in favour of the use of uncorrected calcium. In cases of doubt, ionized calcium should be directly measured.
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Proteínas Sanguíneas/análisis , Calcio/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Diálisis Renal , Albúmina Sérica/análisis , Calcifediol/administración & dosificación , Calcio de la Dieta , Convalecencia , Suplementos Dietéticos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Immunoglobulin A (IgA) deficiency occurs more frequently in patients with celiac disease (CD) than in the general population and can lead to false-negative results in the best serologic test for CD, endomysial IgA (EMA). To evaluate the impact of IgA deficiency on serologic detection of CD in a reference laboratory setting, IgA levels were measured in 510 consecutive serum specimens submitted for testing for EMA; 510 consecutive serum specimens submitted for Helicobacter pylori IgG testing served as a gastrointestinal symptom control group. The frequency of IgA deficiency was significantly higher among the specimens submitted for testing for EMA (5.1%) than among the specimens from the symptom control group (1.4%). Three subsets of sera from the group of specimens submitted for testing for EMA were then tested by additional serologic assays for CD; these subsets were EMA-positive sera (n = 25), EMA-negative, IgA-deficient sera (n = 26), and control sera (from EMA-negative, IgA-nondeficient patients age matched to IgA-deficient patients; n = 26). The proportions of EMA-positive sera positive by other assays for CD were 92% for transglutaminase IgA (TG-IgA), 80% for gliadin IgA, 84% for gliadin IgG, 60% for endomysial IgG (EMG), and 32% for transglutaminase IgG (TG-IgG). Very low proportions (0 to 8%) of IgA-deficient sera and control sera were positive for TG-IgA, gliadin IgA, EMG, and TG-IgG. Eight of 26 (31%) IgA-deficient serum samples were positive for gliadin IgG, whereas 3 of 26 (12%) control serum samples were positive for gliadin IgG, but this difference was not statistically significant. Physicians supplied clinical data for 18 of 26 patients with IgA deficiency; only 4 patients had undergone small-bowel biopsy, and 0 of 4 patients showed villous atrophy. These findings show that IgA deficiency is found more frequently among sera submitted for testing for EMA in a reference laboratory setting, but there was no clear-cut serologic or clinical evidence of CD in EMA-negative, IgA-deficient patients.
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Enfermedad Celíaca/diagnóstico , Deficiencia de IgA/inmunología , Inmunoglobulina A/inmunología , Músculo Liso/inmunología , Adolescente , Adulto , Anciano , Enfermedad Celíaca/sangre , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/fisiopatología , Niño , Preescolar , Humanos , Persona de Mediana Edad , Transglutaminasas/inmunologíaRESUMEN
Sera from patients with Lyme disease were evaluated for their ability to kill Borrelia burgdorferi in vivo and in vitro. Separate groups of C3H mice received sera from seropositive humans with early- or late-stage Lyme disease or from seronegative controls. Eighteen to 24 hours after passive transfer of sera, the mice were challenged with 100,000 low-passage B. burgdorferi strain B31 or CA287 organisms. Sera from subjects with late-stage Lyme disease protected the mice against infection after challenge with B. burgdorferi, but sera from subjects with early-stage Lyme disease were not protective. Late-stage sera also inhibited the growth of B. burgdorferi in microcultures on Barbour-Stoenner-Kelly media better than early-stage sera. Immunoblot analysis revealed that the protective properties of late-stage sera were associated with a response of antibodies to multiple proteins. This response included strong reactivity with the outer-surface proteins A and B, which was lacking in early-stage sera.
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Anticuerpos Antibacterianos/inmunología , Grupo Borrelia Burgdorferi/inmunología , Enfermedad de Lyme/inmunología , Animales , Humanos , Inmunización Pasiva , Enfermedad de Lyme/sangre , Enfermedad de Lyme/prevención & control , Ratones , Ratones Endogámicos C3HRESUMEN
The performance of Western blots (immunoblots) prepared with eight strains of Borrelia burgdorferi representing B. burgdorferi sensu stricto, B. garinii, and B. afzelii genospecies was tested with a panel of sera with various clinical presentations collected from eight geographic regions. European sera were generally more reactive to blots prepared with B. garinii or B. afzelii strain antigens, in particular B. garinii 20047 and B. afzelii VS461. North American sera were more reactive with B. burgdorferi sensu stricto strains. Our observation of significant differences in the levels of reactivity of some sera on Western blots of certain strains is potentially important for the development and implementation of generic interpretive criteria. Preferential reactivity of sera from patients with nerve and/or palsy symptoms to B. garinii strains and with cutaneous disease to B. afzelii strains was observed. On the basis of our results, we have concluded that strain 20047 is the best strain to use for the development of a generic Lyme borreliosis Western blot for Europe.
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Western Blotting/métodos , Grupo Borrelia Burgdorferi/inmunología , Borrelia burgdorferi , Borrelia/inmunología , Enfermedad de Lyme/diagnóstico , Pruebas Serológicas/métodos , Anticuerpos Antibacterianos/sangre , Anticuerpos Monoclonales , Antígenos Bacterianos , Grupo Borrelia Burgdorferi/clasificación , Reacciones Cruzadas , Europa (Continente) , Estudios de Evaluación como Asunto , Humanos , Enfermedad de Lyme/inmunología , Enfermedad de Lyme/microbiología , América del Norte , Especificidad de la EspecieRESUMEN
The mechanism of thrombosis following intravariceal injection of sodium tetradecyl sulphate (S.T.D.) was investigated with respect to effects on the vascular endothelium, the coagulation cascade, and platelet function. Using an umbilical cord model designed to simulate blood flow over the endothelium, it was found that S.T.D. is a potent toxin for endothelial cells in that brief exposure to even low concentrations of the agent were effective in stripping endothelium over a considerable distance, exposing highly thrombogenic endothelium in the process. Effects on coagulation and platelet function were found to be dependent on concentration. Diluted S.T.D. induced a hypercoagulable state, possibly in consequence of a selective inhibition of the physiological anticoagulant, protein C, and promoted platelet aggregation. Higher concentrations inactivated the coagulation cascade and lysed platelets completely. These results suggest that intravariceal infusion of S.T.D. at considerable dilution may be at least as effective in inducing thrombosis as standard dosage, and possibly more so.
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Várices Esofágicas y Gástricas/terapia , Soluciones Esclerosantes/uso terapéutico , Tetradecil Sulfato de Sodio/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Humanos , Microscopía Electrónica de Rastreo , Agregación Plaquetaria/efectos de los fármacos , Venas Umbilicales/efectos de los fármacosRESUMEN
Examination of serum for the presence of antibodies to the human immunodeficiency virus (HIV) by immunoblot analysis requires precise identification of reactivities with various HIV specific proteins. During a recent survey of approximately 2,000 sera, we identified 22 sera from non-HIV-reactive blood donors and 2 from individuals receiving blood products for congenital blood disorders, which consistently and exclusively reacted with a protein of a molecular weight slightly greater than 65,000 daltons (termed AT65). Since the HIV pol p65 protein reacts with specific antibodies at about the same position (i.e., 65,000 daltons), it was essential to determine the viral or nonviral origin of the AT65 reactivity. Our data indicate that the AT65 reaction is due to a protein present on normal or activated lymphocytes, which can co-purify with HIV preparations used for immunoblot analysis. Recognition of HIV-specific p65 and nonspecific AT65 reactions is important to those responsible for interpretation of HIV immunoblots and may aid in the evaluation of some "indeterminant" results.
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Western Blotting , Productos del Gen pol , Anticuerpos Anti-VIH/análisis , Seropositividad para VIH/diagnóstico , VIH/análisis , Proteínas de los Retroviridae/análisis , Donantes de Sangre , Línea Celular , Reacciones Cruzadas , Reacciones Falso Positivas , Humanos , Linfocitos T/análisis , Productos del Gen pol del Virus de la Inmunodeficiencia HumanaRESUMEN
Human retroviruses have been causally associated with the development of the acquired immune deficiency syndrome (AIDS) in groups of individuals at high risk including intravenous drug users, hemophiliacs, and homosexual men. Aside from classic AIDS, homosexual men also develop persistent generalized lymphadenopathy (PGL) which is considered a part of the AIDS-related complex (ARC). We have isolated 70 strains of retroviruses related to human T-lymphotropic viruses type III (HTLV-III) from patients with PGL, AIDS, or ARC. analyses of sera from these patients indicated a high degree of serologic heterogeneity in the antibody titers and their reactivities toward various HTLV-III viral proteins. In addition, we have detected virus-neutralizing antibodies in approximately 50% of the serum samples tested from patients with PGL or AIDS. This is the first comprehensive virologic and serologic report on more than 100 patients studied at one institution in Los Angeles.
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Síndrome de Inmunodeficiencia Adquirida/inmunología , Deltaretrovirus/inmunología , Enfermedades Linfáticas/inmunología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Anticuerpos Antivirales/inmunología , Antígenos de Diferenciación de Linfocitos T , Antígenos de Superficie/análisis , Médula Ósea/microbiología , California , Homosexualidad , Humanos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/patología , Enfermedades Linfáticas/microbiología , Masculino , Peso Molecular , Pruebas de Neutralización , Saliva/microbiología , Semen/inmunología , Proteínas Virales/análisisRESUMEN
The nucleotide sequence of the oncogene of the Rasheed strain of rat sarcoma virus was determined. The oncogene (Ra-v-ras) encodes a 29,000-dalton (p29) transforming protein. This protein is distinct from the immunologically related 21,000-dalton protein (p21) of the Harvey murine sarcoma virus in its amino terminus and in having additional mutations in its carboxyl terminus. Although the functional significance of these changes is unknown, they appear to occur only in rat sarcoma virus.
Asunto(s)
Oncogenes , Retroviridae/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Ratones , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas p21(ras) , RatasRESUMEN
A DNA fraction which is highly enriched in active gene sequences and tightly associated with a subset of nonhistone chromosomal proteins has been isolated from human placenta. After extraction with 2 M NaCl, placental chromatin was separated into two distinct components by centrifugation. Of the total DNA, approximately 96% (DNA-S) is protein free, while the remaining 4% (DNA-P) is tightly complexed with nonhistone chromosomal proteins. Reassociation studies revealed that the DNA-P fraction was enriched 22-fold in actively transcribed human placental lactogen gene sequences, while the DNA-S fraction was correspondingly depleted 22-fold in these sequences. Approximately 45% of the sequences present in DNA-P (equivalent to 1.8% of the genome) were not present in the DNA-S fraction. Reassociation of nick-translated DNA-P to DNA from a partial digest of DNase I treated nuclei indicated that 27% of the DNA-P sequences were DNAase I sensitive, suggesting they may represent actively transcribed gene sequences. Analysis of the overall sequence organization of DNA-P showed that relative to unfractionated DNA and DNA-S, DNA-P was enriched in single-copy sequences, slightly enriched in the class of middle repetitive sequences from C0t 0.01 to 100 M.s, devoid of the more highly repetitive sequences (C0t less than or equal to 0.01). The distribution of total active placental genes between DNA-P and DNA-S was measured by hybridization with a complementary DNA probe transcribed from total polysomal poly(A+) messenger RNA. We found that 57% of this cDNA probe reassociated to DNA-P and 58% to DNA-S, while 95% reassociated to DNA-P mixed with DNA-S at the observed ratio of 4 to 96, suggesting that the DNA-P fraction contained a different population of active gene sequences than DNA-S. From these results we estimate that approximately 85% of the transcribed sequences appear to be distinctly distributed and equally proportioned between DNA-P and DNA-S, while approximately 15% of the transcribed sequences are common to both fractions. We suggest that the strong affinity of the tightly bound nonhistone chromosomal proteins for the DNA-P fraction indicates a likely role for these proteins in the regulation of gene expression.