RESUMEN
The aim of this prospective study was to observe immunophenotypic patterns in the ejaculate of patients with noninflammatory chronic pelvic pain syndrome (Cat IIIB CPPS) and to test for a possible autoimmune aetiology. Thirty-five patients of a total of 88 patients with chronic prostatitis Cat IIIB were consecutively selected. Monthly ejaculate testing was carried out for IgG, IgA, IgM, IL-1alpha, sIL-2R and IL-6. The control group for ejaculate analysis was composed of 96 normal ejaculates (according to the WHO criteria). Immunohistochemical detection of CD3 cells (T lymphocytes) and CD20 cells (B lymphocytes) was performed in 71 biopsy cylinders of Cat IIIB CPPS patients and in 25 prostate biopsy cylinders of subjects without symptoms or obstruction. Intra-acinar T-lymphocytic infiltrates were dominated by T-cytotoxic cells (P = 0.05). Ejaculate IL-6 and ejaculate IgA increased significantly and dropped again, correlating with a release of clinical symptoms. Inflammatory ejaculate interleukin concentrations correlated with the immunohistochemical findings with presence of large numbers of T cells (all P-values < or = 0.01). Immunomodulation was performed in a pilot series of three patients by five monthly cycles of IgG (Sandoglobulin), 1 g kg-1 body weight. Immunomodulation with IgG decreased pain moderately and did not change ejaculate interleukin and immunoglobulin concentrations. In summary, interleukin and immunoglobulin determinations in the ejaculate revealed an inflammatory process even in Cat IIIB CPPS. The findings of intra-acinar T-cell rich infiltrates and the associated inflammatory reaction may indicate a possible autoimmune component in the aetiology of CPPS. Exact origin and role of interleukin changes in the ejaculate of CPPS patients need to be further evaluated. Unfortunately, pilot series with immunomodulation with IgG do not seem to provide clear clinical benefit.
Asunto(s)
Autoinmunidad , Prostatitis/inmunología , Semen/inmunología , Adulto , Antígenos CD20/análisis , Linfocitos B/inmunología , Linfocitos B/patología , Complejo CD3/análisis , Linfocitos T CD8-positivos/patología , Enfermedad Crónica , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunohistoquímica , Interleucina-6/análisis , Masculino , Persona de Mediana Edad , Próstata/patología , Prostatitis/clasificación , Prostatitis/patología , Receptores de Interleucina-2/análisis , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
BACKGROUND: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T-cell chemokine expression. METHODS: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12-myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP-1alpha and MIP-1beta, RANTES (regulated on activation, T-cell expressed and secreted), monocytic chemotactic protein-1 (MCP)-1, and interleukin (IL)-8, or the cytokines interferon (IFN)-gamma and IL-4. Serum levels of MIP-1alpha, MIP-1beta, RANTES, MCP-1, IL-8, IFN-gamma and IL-4 were also assessed by quantitative ELISA. RESULTS: Intracellular expression of MIP-1beta by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75-3.50) vs 4.57% (3.38-6.64), P = 0.05; 14.20% (13.18-17.88) vs 44.10% (30.38-48.70), P = 0.01). Similarly, intracellular expression of MIP-1alpha by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17-5.42) vs 17.10% (4.97-20.43), P = 0.05). Conversely, IL-8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77-11.28) vs 4.14% (3.61-7.11), P = 0.05; 8.40% (6.97-10.04) vs 4.98% (3.37-6.08), P = 0.05). Examination of intracellular IFN-gamma and IL-4 revealed no significant difference in the expression of either cytokine by CD4+ T-cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN-gamma was significantly reduced in CD8+ T-cells from allergic asthmatics (24.60% (21.08-32.50) vs 48.40% (41.50-55.28), P = 0.01). CONCLUSIONS: The occurrence in mild allergic asthma of peripheral T-cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.
Asunto(s)
Asma/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Interleucina-8/biosíntesis , Proteínas Inflamatorias de Macrófagos/biosíntesis , Adulto , Asma/sangre , Quimiocina CCL3 , Quimiocina CCL4 , Femenino , Humanos , Interleucina-8/sangre , Proteínas Inflamatorias de Macrófagos/sangre , MasculinoRESUMEN
The brain is believed to be an immunologically privileged organ, sheltered from the systemic immunological defense by the blood-brain barrier (BBB). However, there is increasing evidence for a marked inflammatory response in the brain after traumatic brain injury (TBI). Markers for cellular immune activation, neopterin, beta2-microglobulin (beta2M), and soluble interleukin-2 receptor (sIL-2R), were measured for up to 3 weeks in cerebrospinal fluid (CSF) and serum of 41 patients with severe TBI in order to elucidate the time course and the origin of the cellular immune response following TBI. Neopterin gradually increased during the first posttraumatic week in both CSF and serum. Concentrations in CSF were generally higher than in serum, suggesting intrathecal release of this marker. beta2M showed similar kinetics but with higher serum than CSF concentrations. Nonetheless, intrathecal release as assessed by the beta2M index could be postulated for most of the patients. The mean levels of sIL-2R in both CSF and serum were elevated during the whole study period, serum concentrations being up to 2 x 10(4) times higher than in CSF. No significant intrathecal production of sIL-2R could be detected. The present data shows that severe TBI leads to a marked cell-mediated immune response within the brain and in the systemic circulation. In the intrathecal compartment the activated cells appear to be predominantly of the macrophage/microglia lineage, while the immune activation in the systemic circulation seems to involve mainly T-lymphocytes.
Asunto(s)
Lesiones Encefálicas/inmunología , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Lesiones Encefálicas/sangre , Lesiones Encefálicas/líquido cefalorraquídeo , Femenino , Humanos , Inmunidad Celular/inmunología , Masculino , Persona de Mediana Edad , Neopterin/biosíntesis , Neopterin/sangre , Neopterin/líquido cefalorraquídeo , Receptores de Interleucina-2/biosíntesis , Receptores de Interleucina-2/sangre , Receptores de Interleucina-2/metabolismo , Microglobulina beta-2/biosíntesis , Microglobulina beta-2/sangre , Microglobulina beta-2/líquido cefalorraquídeoRESUMEN
Few human monoblastic cell lines have been characterized to date. We have established the SigM5 cell line from a patient with acute monoblastic leukaemia (FAB M5a). Original leukaemic cells had a karyotype of 47,XY,+8, whereas the cell line showed a stemline clone of 81,XX,Y,Y,1,4,6,7,+8,+8,9,10,10,11,13,16,19[cp], with a minor sideline also present. Cytochemical staining was strongly positive with alpha-naphthylbutyrate acetate esterase, particulate positive with Sudan black and weakly positive for myeloperoxidase. Cells were positive for CD13, CD15, CD18, CD23, CD33, CD38, CD45, CD68 and myeloperoxidase. CD14 expression was 3-15%. SigM5 constitutively secreted interleukin (IL)-2, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, ferritin, lysozyme, N-elastase and neopterin upon stimulation with interferon (IFN)-gamma. Cells expressed the proinflammatory mediator macrophage migration inhibitory factor (MIF). All NADPH oxidase subunits were constitutively present, but nitroblue tetrazolium reduction was only detectable upon activation with IFN-gamma. SigM5 monoblasts were sensitive to arsenic trioxide (As2O3) previously not described to induce apoptosis in monoblastic cells. Differing considerably in morphology, immunophenotype and sensitivity to arsenics from the widely used cell lines U937, HL-60 and THP-1, SigM5 is a new monoblastic cell line useful for studying leukaemogenesis, monocyte differentiation and tumour cell susceptibility to arsenic compounds.
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Antineoplásicos/farmacología , Arsenicales/farmacología , Técnicas de Cultivo de Célula/métodos , Leucemia Monocítica Aguda/patología , Leucocitos Mononucleares/patología , Óxidos/farmacología , Apoptosis/efectos de los fármacos , Trióxido de Arsénico , Diferenciación Celular , Línea Celular/inmunología , Línea Celular/patología , Cromosomas Humanos Par 8 , Humanos , Cariotipificación , Leucemia Monocítica Aguda/genética , Microscopía Electrónica , PoliploidíaRESUMEN
The pathophysiology of postparturient paresis is still not completely understood. Knowledge recently acquired in immunology, endocrinology and cell physiology has still to be integrated in order to elucidate the aetiopathogenesis of the disease. For that purpose, the effect of the EDTA infusion model on the plasma concentrations of selected cytokines and growth factors, and of a calcium binding protein was examined in dairy cows. Six 6- to 11-year-old Brown Swiss cows in mid lactation were infused with a 5% solution of Na2EDTA in one jugular vein over a period of 5 h. Blood samples were collected from the contralateral side daily two days before, and then hourly for five hours during the infusion, hourly for five hours after the end of the infusion, and once daily for 10 days thereafter. The plasma concentrations of cortisol, tumour necrosis factor-alpha, interleukin-1 receptor antagonist, granulocyte colony-stimulating factor, granulocyte and macrophage colony-stimulating factor, and the calcium binding protein S-100 were determined. Before the EDTA infusion, during the infusion and for two days thereafter, the mean plasma concentrations of cortisol were significantly higher than those from days 4 to 10 after the infusion. The plasma concentrations of tumour necrosis factor-alpha and interleukin-1 receptor antagonist followed a similar profile. At the end of EDTA infusion, low concentrations of granulocyte colony-stimulating factor were detected in one cow only. On days 3 and 4, the mean plasma concentrations of granulocyte colony-stimulating factor were significantly higher than the pre-infusion values, but this was followed by a significant decrease on post-infusion day 5. From day 4 to 7, the plasma concentrations of S-100 were significantly lower than the pre-infusion values. The importance of these findings in the pathophysiology of postparturient paresis remains to be established.
Asunto(s)
Enfermedades de los Bovinos/fisiopatología , Citocinas/sangre , Hipocalcemia/veterinaria , Estrés Fisiológico/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/inducido químicamente , Ácido Edético/efectos adversos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Hidrocortisona/sangre , Hipocalcemia/inducido químicamente , Hipocalcemia/fisiopatología , Técnicas para Inmunoenzimas/veterinaria , Radioinmunoensayo/veterinaria , Receptores de Interleucina-1/antagonistas & inhibidores , Receptores de Interleucina-1/sangre , Proteínas S100/sangre , Estrés Fisiológico/inducido químicamente , Estrés Fisiológico/fisiopatología , Factor de Necrosis Tumoral alfa/análisisAsunto(s)
Herpesvirus Humano 8/aislamiento & purificación , Mieloma Múltiple/virología , Paraproteinemias/virología , Sarcoma de Kaposi/virología , Médula Ósea/virología , Ensayo de Inmunoadsorción Enzimática , Humanos , Mieloma Múltiple/complicaciones , Paraproteinemias/complicaciones , Reacción en Cadena de la Polimerasa , Sarcoma de Kaposi/complicacionesRESUMEN
Persons with immune deficiency may present with atypical results in serological tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially obtained over time from a cohort of 57 HIV-infected patients, all of whom tested positive only for antibody to hepatitis B core antigen (anti-HBcAg), were therefore retested for HBV markers, including HBV DNA. The results were assessed for their time course and correlated with clinical data and alanine aminotransferase (ALT) values. Forty-eight patients were male; intravenous drug users constituted the principal risk group (n = 30), followed by homosexual men (n = 22). Thirty-three persons tested positive for antibody to hepatitis C virus (anti-HCV). During a median of 31 months from the first to the last serum, anti-HBcAg remained the sole marker of HBV infection in 98.2% of the patients. Polymerase chain reaction (PCR) to detect DNA for HBV core and HBV surface gene was positive in 126 (62.4%) and 121 (59.9%) of all 202 serum samples, respectively. Over time, HBV DNA was detected at least once in 51 (89.5%) patients. In contrast, decomplexed hepatitis B surface antigen (HBsAg) was detected at least once in 14 (24.6%) patients. Among patients positive for HBV DNA and negative for anti-HCV, eight (36.4%) of 22 had chronic hepatitis (ALT elevation > or = 6 months) that was attributable only to persisting HBV infection. Similarly, 12 (41.4%) of 29 patients positive for both HBV DNA and anti-HCV had chronic viral hepatitis, but their ALT values were significantly higher. In HIV-infected patients, anti-HBcAg as the sole serological HBV marker detected must be considered indicative of chronic HBV infection and is in part associated with chronic hepatitis and ALT elevation.
Asunto(s)
Infecciones por VIH/complicaciones , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Adulto , Alanina Transaminasa/sangre , Biomarcadores , Estudios de Cohortes , ADN Viral/análisis , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de TiempoRESUMEN
To study the virological, immunological and clinical effects of the protease inhibitor indinavir in human immunodeficiency virus (HIV)-infected patients with CD4 counts < 50 cells/mm3, indinavir was added to prior treatment with nucleoside analogues in a prospective open-label study in 23 HIV-infected patients with median CD4 count of 10 cells/mm3 and median serum HIV-1 RNA load of 27,508 copies/ml. Addition of indinavir induced a decrease in HIV-1 RNA levels to < 400 copies/ml in 15 patients that was maintained until week 36 of the study in 8 (35%) patients. The median increase in CD4 cell counts was 92 cells/mm3 (range 55-258 cells/mm3) and in CD8 counts was 245 cells/mm3 (range 51-1552 cells/mm3) at week 30. The treatment induced a significant CD8 T cell expansion, consisting in the first 6 weeks of predominantly memory CD45RO+ cells and followed by expansion of naive cells from week 12 on, and a significant decrease in the proportion of activated CD8/CD38 cells. In addition, significant increases in T cell proliferation following stimulation with phytohaemagglutinin and significant decreases in the rates of spontaneous apoptosis of CD4+ and CD8+ T cells were observed. In conclusion, the addition of indinavir induced restoration of both memory and naive CD8 T cells. Corresponding evidence of improving T cell function, as assessed by enhanced lymphoproliferative capacity and diminished propensity to undergo apoptosis, provides evidence for treatment-induced regeneration of immune function even in patients with severe immunodeficiency.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Indinavir/uso terapéutico , Adulto , Anciano , Apoptosis , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Subgrupos de Linfocitos TRESUMEN
To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.
Asunto(s)
Infecciones por VIH/complicaciones , Hipertensión Pulmonar/complicaciones , Adulto , Fármacos Anti-VIH/uso terapéutico , Anticuerpos Anticardiolipina/análisis , Estudios de Casos y Controles , Didanosina/uso terapéutico , Ecocardiografía Doppler , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/inmunología , Hipertensión Pulmonar/mortalidad , Inmunoglobulina M/análisis , Masculino , Estudios Prospectivos , Tasa de Supervivencia , Zidovudina/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the in vivo relationship between HIV replication and circulating levels of the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES (acronym for Regulated upon Activation, Normal T-cell Expressed and presumably Secreted), interleukin (IL)-16 and monocyte chemotactic protein (MCP)-1, which have recently been characterized as factors capable of regulating in vitro HIV replication. DESIGN AND METHODS: We have compared changes in plasma HIV-RNA levels and circulating levels of MIP-1 alpha, MIP-1 beta, RANTES, IL-16 and MCP-1 in 20 severely immunodeficient HIV-infected individuals (CD4+ T cells = 14 +/- 3 cells x 10(6)/l; plasma HIV RNA = 4.45 +/- 0.27 log 10 copies/ml) undergoing treatment with the HIV protease inhibitor indinavir that added to pre-existing nucleoside-based therapy. At weeks 0, 2, 6 and 12, viral load was quantified using a commercial reverse-transcription polymerase chain reaction assay, peripheral blood T-cell subpopulations assessed by flow cytometry, and chemokine levels quantified using commercial sandwich enzyme-linked immunosorbent assay kits. RESULTS: Following initiation of indinavir-based therapy, significant decreases in plasma HIV-RNA levels (change = 2.0 +/- 0.75 log 10 copies/ml) were observed in conjunction with significant increases in absolute CD4+ (change = 83 +/- 19 cells x 10(6)/l) and CD8+ (change = 293 +/- 96 cells x 10(6)/l) T-cell numbers. Concomitantly, significant increases in MIP-1 alpha (19% increase), MIP-1 beta (14% increase), RANTES (15% increase) and IL-16 (1213% increase) levels occurred. In contrast, MCP-1 levels decreased significantly (47% decrease). CONCLUSION: The in vivo demonstration of an association between diminishing plasma HIV-RNA levels and the emergence of a circulating chemokine profile capable of inhibiting HIV replication corroborates recent in vitro observations and provides evidence for the restoration of chemokine capacity by HIV protease inhibitor-based therapy.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/sangre , Fármacos Anti-VIH/uso terapéutico , Quimiocina CCL2/sangre , Quimiocina CCL5/sangre , Indinavir/uso terapéutico , Interleucina-16/sangre , Proteínas Inflamatorias de Macrófagos/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/virología , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocinas/sangre , Femenino , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , ARN Viral/sangre , Estudios Retrospectivos , Linfocitos T/clasificación , Linfocitos T/citología , Carga ViralRESUMEN
BACKGROUND: S100 proteins are low-molecular-weight calcium-binding proteins and appear to play an important role in various cellular processes such as cell division and differentiation. In histopathology, S100 is widely accepted as the marker of choice for immunohistochemical identification of malignant melanoma. When S100 was detected in the serum of patients with malignant melanoma, it was suggested that serum S100 may be a useful marker for the stage of disease. OBJECTIVE: The aim of this study was to examine serum S100 concentrations of patients with different stages of malignant melanoma and to determine the value of serum S100 in the follow-up of melanoma patients during treatment. METHODS: Sera were obtained from 73 melanoma patients in different stages of the disease. The control group consisted of 130 healthy subjects. In 4 patients with metastatic melanoma, serum S100 was measured serially. Serum levels were measured by a commercially available immunoradiometric assay. RESULTS: While only 1 out of 25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage III, 21.4%) showed detectable serum S100 levels, 27 of 34 patients with disseminated disease (stage IV, 79.4%) had elevated serum S100. Interestingly, rising levels of serum S100 in the serial measurement indicated progression of the disease, and a complete decline reflected 2 patient remissions. CONCLUSION: The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.
Asunto(s)
Biomarcadores de Tumor/sangre , Melanoma/secundario , Proteínas S100/sangre , Neoplasias Cutáneas/sangre , Adulto , Diferenciación Celular , División Celular , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Peca Melanótica de Hutchinson/sangre , Peca Melanótica de Hutchinson/secundario , Peca Melanótica de Hutchinson/terapia , Inmunohistoquímica , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Metástasis Linfática/patología , Masculino , Melanoma/sangre , Melanoma/patología , Melanoma/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Inducción de Remisión , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
Interferon-alpha combined with retinoid or PUVA is used for the treatment of cutaneous T-cell lymphoma. Anti-IFN-alpha antibodies (IFN ab) occur regularly during IFN-alpha treatment. We investigated the incidence of neutralizing and binding IFN ab and analysed their relationship with clinical and immunological parameters. A group of 17 CTCL patients were treated with IFN alpha-2a three times weekly subcutaneously at a dose of 3 Mill. I.U. combined either with retinoid (acitretin, Neotigason; 0.5 mg/kg bodyweight) daily or with 5-methoxypsoralen (1.2 mg/kg bodyweight) plus UVA radiation three times weekly. Prior to and during treatment we monitored stage, skin involvement by a tumour burden index, serum levels of beta 2-microglobulin, neopterin, binding and neutralizing IFN ab, Interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2r) and the CD4/CD8 ratio of peripheral blood mononuclear cells. We observed two complete, two partial and six minor responses, four patients with stable disease and three patients with progressive disease. Of the 17 patients, 7 developed binding IFN ab, but only 2 had neutralizing IFN ab which were associated with high titres of binding IFN ab. IFN ab formation was more frequent in patients with normal CD4/CD8 ratios and a high tumour burden index and showed a trend to be more frequent in PUVA-cotreated patients than in retinoid-cotreated patients. Responses were more frequently seen in IFN ab-negative patients. IFN ab developed in patients treated with PUVA or retinoid combined with IFN. Binding as well as neutralizing IFN ab may have an impact on the treatment success in CTCL patients.
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Acitretina/administración & dosificación , Anticuerpos/sangre , Interferón-alfa/administración & dosificación , Interferón-alfa/inmunología , Linfoma Cutáneo de Células T/terapia , Terapia PUVA , Anciano , Femenino , Humanos , Interferón alfa-2 , Linfoma Cutáneo de Células T/inmunología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Estudios RetrospectivosRESUMEN
The professional activity of air traffic controllers (ATC) is often considered to be rather stressful. Certain characteristics of this job are likely to produce stress; for example an ATC can not predict when a situation becomes critical and he is not able to regulate the workload. In order to assess psychophysiological stress reactions in this working situation, saliva samples were taken from 158 male air traffic controllers before and after each of two working sessions. In contrast to the expected immunosuppressive effects, the working sessions caused a marked increase in the concentration and secretion rate of salivary immunoglobulin A (sIgA), as well as in the concentration of salivary cortisol. The increase in sIgA, however, was not correlated with the salivary cortisol response or with the amount of actual or perceived workload, whereas the cortisol response was correlated with both workload measures. It is suggested that positive emotional engagement is responsible for the observed sIgA increase and that measuring this physiological response may be a valuable tool for differentiating between positive and negative stress effects or between successful and unsuccessful adaptation or coping with situational demands.
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Aeronaves , Nivel de Alerta/fisiología , Hidrocortisona/sangre , Inmunoglobulina A/sangre , Estrés Psicológico/complicaciones , Carga de Trabajo/psicología , Adaptación Psicológica/fisiología , Adulto , Humanos , Masculino , Persona de Mediana Edad , Psiconeuroinmunología , Psicofisiología , Saliva/inmunologíaRESUMEN
We determine the correlation between viremia in serum specimens, transaminase activity (ALT and AST) and histological grading in 37 patients with chronic hepatitis C. In addition we compared two PCR methods for hepatitis C virus (HCV)-RNA in serum specimens. For the histological grading we used a modified Knodell score. For detection and quantification we measured the viremia (HCV-RNA titer) with a standardized "nested primer" PCR (end-point dilution method) and the commercially available Amplicor HCV Monitor. The mean HCV-RNA and AST level was significantly higher in patients with a histologically active inflammation. In the individual patient we could not conclude from the titer of HCV-RNA on the histologic grading because of the wide range of the results. We did not find a significant difference in ALT in patients having varying histological gradings. HCV-RNA titer and transaminases (ALT and AST) did not correlate significantly. The HCV-RNA titer was significantly marked in older patients (above 40 years) and patients having sporadic hepatitis than in younger patients and patients with chronic hepatitis after drug abuse. The "nested primer" PCR (end-point dilution method) was more sensitive for detection of HCV-RNA in serum specimens than Amplicor HCV Monitor. The lack of HCV-RNA with Amplicor HCV Monitor in 12 of 37 patients (32%) did not rule out viremia. We conclude that in patients with a chronic hepatitis C marked viremia points to a histologically active inflammation. In the individual patient we could not conclude from the titer of HCV-RNA on the histological grading. Because of the lower sensitivity of Amplicor HCV Monitor it is necessary to confirm negative results with a "nested primer" PCR.
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Hepatitis C/patología , Hepatitis C/virología , Hepatitis Crónica/virología , Adulto , Biopsia , Femenino , Hepacivirus , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/aislamiento & purificación , Transaminasas/aislamiento & purificación , Viremia/virologíaRESUMEN
Between 1990 and 1992 (2 years), 102 patients with clinical liver pathology underwent standardized clinical, pathological, sonographic and serologic investigations (HAV, HBV, HCV, HDV autoantibodies and tumor markers). During the same period seroepidemiological studies with the same parameters as above were performed on the following control groups: healthy pregnant women (n = 383), blood donors (n = 85), HIV-positive individuals (n = 93), and hospitalized patients in all age groups with minor ailments unrelated to liver pathology (n = 108). The results are discussed in detail. Virtually all adults had HAV infection. HBV and HCV infection appears to play a major role in chronic liver pathology in southern Cameroon. The two infections frequently occur together (over 40% of liver cases) and correlate significantly with liver cirrhosis. The marked prevalence of HBV and HCV markers in healthy pregnant women is of epidemiological concern due to the potential for vertical transmission of the infection (immunization). Endemic infections such as falciparum malaria are probably responsible for unspecific stimulation of the immune system, which is reflected in a generally marked prevalence of autoimmune markers in liver patients and controls, since histologically there was no evidence of autoimmune liver disease.
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Virus de Hepatitis/inmunología , Hepatopatías/virología , Abdomen/diagnóstico por imagen , Adolescente , Adulto , Anticuerpos Antivirales/aislamiento & purificación , Autoanticuerpos/aislamiento & purificación , Biopsia con Aguja , Donantes de Sangre , Western Blotting , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Seropositividad para VIH/inmunología , Humanos , Hígado/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Embarazo , Estudios Prospectivos , Estudios Seroepidemiológicos , UltrasonografíaRESUMEN
BACKGROUND: A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood. EXPERIMENTAL DESIGN: The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8. RESULTS: In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed. CONCLUSIONS: Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine production within the feto-maternal unit.
Asunto(s)
Líquido Amniótico/química , Corioamnionitis/metabolismo , Citocinas/efectos adversos , Citocinas/análisis , Desarrollo Embrionario y Fetal/fisiología , Líquido Amniótico/inmunología , Corioamnionitis/mortalidad , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Retardo del Crecimiento Fetal , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Inmunohistoquímica , Interleucina-6/sangre , Interleucina-8/sangre , Placenta/química , Preeclampsia/metabolismo , Preeclampsia/mortalidad , Embarazo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
In a prospective study, 102 hospital patients with liver disease were evaluated in West Cameroon, Africa. Blood donors, pregnant women and patients without liver disease served as controls. A total of 757 individuals were tested for markers of hepatitis A, B, C and D and for immunological markers (autoantibodies, procollagen III, alpha-foetoprotein, CA50 antigen, alpha-1-antitrypsin and antibodies to human immunodeficiency virus types 1 and 2). One-third of the liver disease patients had focal lesions on ultrasound examination. Histologically, 20 cases of cirrhosis, 14 cases of chronic hepatitis, 15 hepatocellular carcinomas and 17 cases of acute hepatitis were detected. All hepatic patients and virtually all controls had had a previous hepatitis A virus infection. Over 85% of adult patients and controls had at least one marker of hepatitis B virus infection. Over 30% of patients with liver disease had markers of possible hepatitis B virus replication. Antihepatitis C virus antibody was present in 18% of hepatic patients and in 6% of controls. Hepatitis C virus infection seems to play an important role in the development of chronic liver pathology; 40% of cirrhotic patients had a combined hepatitis B and C virus infection. Serum autoantibodies were frequently found and were not correlated with the presence of autoimmune liver disease.
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Hepatopatías/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biomarcadores , Camerún/epidemiología , Niño , Preescolar , Femenino , Estado de Salud , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/virología , Humanos , Lactante , Hepatopatías/etiología , Hepatopatías/inmunología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Until today only five pathogens of viral hepatitis have been discovered: hepatitis virus A (HAV), B (HBV), C (HCV), D (HDV) and E (HEV). An update on the state of the art of actually established diagnostic procedures is briefly summarized. Some recent topics and problems are covered more extensively; in the case of HBV the value of HBsAG concentration as a prognostic marker, the finding 'anti-HBc only' the role of HBV mutants, the determination of circulating HBV genomic material, and modalities for HBV vaccination control; in the case of HCV the indications for study of its viral genomic material and the role of HCV subspecies are explained. Finally, first results on HEV prevalence in Switzerland are introduced.
Asunto(s)
Hepatitis Viral Humana/diagnóstico , Hepacivirus/inmunología , Virus de la Hepatitis A Humana/inmunología , Anticuerpos contra la Hepatitis B/aislamiento & purificación , Antígenos de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis E/inmunología , Hepatitis Viral Humana/prevención & control , Hepatitis Viral Humana/virología , Humanos , Técnicas Inmunológicas , Suiza/epidemiología , Vacunas contra Hepatitis ViralRESUMEN
The aim of the study was to determine the frequency and course of hepatitis C viremia in clinically healthy, anti-HCV positive test subjects, and to ascertain whether the HCV antibodies of the IgM type differed between viremia and immunity. In 21 anti-HCV positive blood donors (test subjects) with normal transaminase activity, two serum samples, taken at an interval of 25 +/- 10 months, have been investigated for HCV-RNA and HCV-IgM antibodies. In a total of 16 test subjects (76%) HCV-RNA was found during the first test and/or the follow-up: 14 of them were positive on both occasions, and one test subject each was HCV-RNA positive exclusively at the first test and the follow-up respectively. At the time of the follow-up the serum transaminase level was elevated in 4 test subjects. 3 of these 4 were HCV-RNA positive also. On the other hand, the results of the HCV-PCR were nonuniform in HCV-IgM antibody negative test subjects. The above results demonstrate that in the majority of clinically healthy, anti-HCV positive test subjects with normal transaminase activity, a viremia exists which persists and the course of which may include inflammatory phases. The proof of HCV-IgM antibodies correlates with a viremia. On the other hand, the lack of HCV-IgM antibodies does not exclude viremia.