Use of simple noninvasive biomarkers to predict liver fibrosis in HIV/HCV coinfection in routine clinical practice.

BACKGROUND: Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions. PATIENTS AND METHODS: HIV/HCV-coinfected patients who had participated in a multicentre cross-sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver-operating-characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values. RESULTS: A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66-0.71) and that of the FI was 0.67 (0.62-0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was > or =15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB. CONCLUSIONS: In HIV/HCV-coinfected patients, the diagnostic accuracy of the APRI in real-life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti-HCV therapy may prevent a significant proportion of patients from having to undergo LB.

[Medical and surgical management of noniatrogenic traumatic tracheobronchial injuries]. / Manejo médico-quirúrgico de las lesiones traqueobronquiales traumáticas no iatrogénicas.

OBJECTIVE: To describe the medical and surgical management of noniatrogenic traumatic tracheobronchial injuries. PATIENTS AND METHOD: From January 1993 to July 2004, 15 cases of traumatic tracheobronchial injury were treated in our department. The diagnosis was established by bronchoscopy and a computed tomography chest scan was performed on all patients. Surgical treatment was selected for patients with unstable vital signs, an open tracheal wound, associated esophageal lesions, progression of subcutaneous or mediastinal emphysema, mediastinitis or suspicious mediastinal secretions on imaging tests, or difficulties with mechanical ventilation due to the traumatic tracheobronchial injury. RESULTS: The mean (SD) age of the patients was 35.5 (18.9) years and 12 (80%) were male. Of the 15 cases, 13 (86.7%) had penetrating trauma and 2 (13.3%) blunt trauma. The most common location of the injury was in the bronchi (9 cases; 60%), followed by the cervical trachea (4 cases; 26.6%), followed by both the thoracic trachea and bronchi (2 cases; 13.4%). The most common initial symptom was subcutaneous emphysema, which presented in 11 (73.3%) patients. Chest (12 cases; 86.7%) and orthopedic injuries (9 cases; 60%) were the most common associated injuries. Surgery was the treatment of choice in 11 (73.3%) cases and conservative medical treatment in 4 (26.7%). An irreversible brain injury caused the death of 1 patient receiving conservative treatment. CONCLUSIONS: Tracheobronchial injuries may be treated conservatively if they meet strict selection criteria. Size and location should not be used as selection criteria for surgical treatment.

Manejo médico-quirúrgico de las lesiones traqueobronquiales traumáticas no iatrogénicas / Medical and surgical management of noniatrogenic traumatic tracheobronchial injuries

Objetivo: Describir el manejo médico-quirúrgico de las lesiones traqueobronquiales traumáticas no iatrogénicas. Pacientes y método: De enero de 1993 a julio de 2004 se registraron en nuestro servicio 15 casos de lesiones traqueobronquiales traumáticas. En todos los pacientes el diagnóstico se estableció por broncoscopia y a todos se le realizó una tomografía computarizada de tórax. Se eligió tratamiento quirúrgico cuando había inestabilidad vital del paciente, herida traqueal abierta, lesiones esofágicas asociadas, progresión de enfisema subcutáneo o mediastínico, mediastinitis o colecciones mediastínicas sospechosas en pruebas de imagen o dificultades en la ventilación mecánica por la lesión traqueobronquial traumática. Resultados: La edad media (± desviación estándar) de los pacientes fue de 35,5 ± 18,9 años y 12 (80%) eran varones. Se registraron 13 traumatismos cerrados (86,7%) y 2 abiertos (13,3%). La localización más frecuente de la lesión fue bronquial (9 casos; 60%), seguida de tráquea cervical (4 casos; 26,6%) y tráquea toracicobronquial (2 casos; 13,4%). El síntoma inicial más frecuente fue el enfisema subcutáneo, que presentaron 11 pacientes (73,3%). Las lesiones asociadas más frecuentes fueron torácicas, con 12 casos (86,7%), seguidas de ortopédicas, con 9 (60%). El tratamiento de elección fue quirúrgico en 11 casos (73,3%) y médico conservador en 4 (26,7%). Falleció una paciente tratada de forma conservadora por lesión cerebral irreversible. Conclusiones: Las lesiones traqueobronquiales pueden tratarse de forma conservadora si cumplen criterios estrictos de selección. El tamaño o la localización no debe ser un criterio para la elección del tratamiento quirúrgico

Objective: To describe the medical and surgical management of noniatrogenic traumatic tracheobronchial injuries. Patients and method: From January 1993 to July 2004, 15 cases of traumatic tracheobronchial injury were treated in our department. The diagnosis was established by bronchoscopy and a computed tomography chest scan was performed on all patients. Surgical treatment was selected for patients with unstable vital signs, an open tracheal wound, associated esophageal lesions, progression of subcutaneous or mediastinal emphysema, mediastinitis or suspicious mediastinal secretions on imaging tests, or difficulties with mechanical ventilation due to the traumatic tracheobronchial injury. Results: The mean (SD) age of the patients was 35.5 (18.9) years and 12 (80%) were male. Of the 15 cases, 13 (86.7%) had penetrating trauma and 2 (13.3%) blunt trauma. The most common location of the injury was in the bronchi (9 cases; 60%), followed by the cervical trachea (4 cases; 26.6%), followed by both the thoracic trachea and bronchi (2 cases; 13.4%). The most common initial symptom was subcutaneous emphysema, which presented in 11 (73.3%) patients. Chest (12 cases; 86.7%) and orthopedic injuries (9 cases; 60%) were the most common associated injuries. Surgery was the treatment of choice in 11 (73.3%) cases and conservative medical treatment in 4 (26.7%). An irreversible brain injury caused the death of 1 patient receiving conservative treatment. Conclusions: Tracheobronchial injuries may be treated conservatively if they meet strict selection criteria. Size and location should not be used as selection criteria for surgical treatment

[Importance of routine mediastinal staging in women with non-small cell lung cancer]. / Importancia de la estadificación mediastínica, sistemática en mujeres con carcinoma broncogénico, no microcítico.

OBJECTIVE: To study the specific importance of mediastinal staging in women with nonsmall cell lung cancer. PATIENTS AND METHODS: Between July 1981 and September 2003 we surgically staged 2172 patients with nonsmall cell lung cancer who met the inclusion criteria for resectability and operability. A subgroup of 108 women was studied. Cervical mediastinoscopy was performed in all cases, with the addition of anterior mediastinotomy in cases with left upper lobe involvement. All patients underwent a preoperative computed tomography chest scan. RESULTS: Cervical mediastinoscopy was performed on all 108 patients, 26 of whom also underwent anterior mediastinotomy. Positive findings were recorded in 44 (40.7%) of the 108 cases: 39 of the 108 mediastinoscopies (36.1%), 9 of the 26 mediastinotomies (34.6%), and in 5 cases (19.2%) both mediastinoscopy and mediastinotomy. Nodal involvement was found in 13% of cases in clinical stage IA and 30.8% of cases in clinical stage IB. The percentage of positive findings was significantly higher for cases with adenocarcinoma or large cell carcinoma (P<.05). We performed 67 thoracotomies: 46 patients underwent lobectomy (42.6% of the 108), 7 bilobectomy (6.5%), 9 pneumonectomy (8.3%), and 5 exploratory thoracotomy (4.6%). The agreement between clinical staging after mediastinoscopy and pathological staging after thoracotomy was 47% (stage IA) and 57% (stage IB). CONCLUSIONS: Routine mediastinoscopy is indicated for all women with nonsmall cell lung cancer, regardless of clinical stage.

Importancia de la estadificación mediastínica, sistemática en mujeres con carcinoma broncogénico, no microcítico / Importance of routine mediastinal staging in women with nonsmall cell lung cancer

OBJETIVO: Investigar la importancia específica de la estadificación mediastínica de mujeres con carcinoma broncogénico, no microcítico. PACIENTES Y MÉTODOS: Entre julio de 1981 y septiembre de 2003 estadificamos quirúrgicamente a 2.172 pacientes con carcinoma broncogénico no microcítico que cumplían criterios de resecabilidad y operabilidad. Se realizó mediastinoscopia cervical de forma habitual, y mediastinotomía anterior en caso de afectación del lóbulo superior izquierdo. Todos los pacientes tenían una tomografía axial computarizada de tórax preoperatoria. Se estudió al subgrupo de 108 mujeres. RESULTADOS: Realizamos mediastinoscopia cervical en 108 casos y mediastinotomía anterior en 26. Fueron positivas 44 (40,7%) —39 (36,1%) mediastinoscopias, 9 (34,6%) mediastinotomías y en 5 (19,2%) casos ambas—. Se objetivó afectación ganglionar en un 13% de los casos en estadio IA y en un 30,8% en estadio IB. El porcentaje de positividad fue significativamente mayor en caso de adenocarcinoma o carcinoma de células grandes (p < 0,05). Realizamos 67 toracotomías: 46 (42,6%) lobectomías, 7 (6,5%) bilobectomías, 9 (8,3%) neumonectomías y 5 (4,6%) toracotomías exploradoras. La concordancia entre estadificación clínica posmediastinoscopia y patológica postoracotomía fue del 47% (IA) y del 57% (IB). CONCLUSIONES: La mediastinoscopia sistemática está indicada en todas las mujeres con carcinoma broncogénico no microcítico independientemente del estadio clínico

OBJECTIVE: To study the specific importance of mediastinal staging in women with nonsmall cell lung cancer. PATIENTS AND METHODS: Between July 1981 and September 2003 we surgically staged 2172 patients with nonsmall cell lung cancer who met the inclusion criteria for resectability and operability. A subgroup of 108 women was studied. Cervical mediastinoscopy was performed in all cases, with the addition of anterior mediastinotomy in cases with left upper lobe involvement. All patients underwent a preoperative computed tomography chest scan. RESULTS: Cervical mediastinoscopy was performed on all 108 patients, 26 of whom also underwent anterior mediastinotomy. Positive findings were recorded in 44 (40.7%) of the 108 cases: 39 of the 108 mediastinoscopies (36.1%), 9 of the 26 mediastinotomies (34.6%), and in 5 cases (19.2%) both mediastinoscopy and mediastinotomy. Nodal involvement was found in 13% of cases in clinical stage IA and 30.8% of cases in clinical stage IB. The percentage of positive findings was significantly higher for cases with adenocarcinoma or large cell carcinoma (P<.05). We performed 67 thoracotomies: 46 patients underwent lobectomy (42.6% of the 108), 7 bilobectomy (6.5%), 9 pneumonectomy (8.3%), and 5 exploratory thoracotomy (4.6%). The agreement between clinical staging after mediastinoscopy and pathological staging after thoracotomy was 47% (stage IA) and 57% (stage IB). CONCLUSIONS: Routine mediastinoscopy is indicated for all women with nonsmall cell lung cancer, regardless of clinical stage

Detection methods of the drug-addiction and alcoholism treatment programme of the Spanish National Railway Company (RENFE).

BACKGROUND: Social problems in enterprises need to be approached by all groups involved in order to achieve a satisfactory result. With regard to Occupational Health and, specifically, drug-addiction, the groups concerned are Occupational Health Services, Trade Unionists and Managers. OBJECTIVES: To analyse the involvement of the social groups (Occupational Health Service, Management and Trade Unions) in relation to the detection of workers suffering from drug-addiction and/or alcoholism. METHODS: During the first eight years of implementation (1990-1997) of the Drug-Addiction and Alcoholism Treatment Programme of the Spanish National Railway Company (RENFE), a total of 477 workers consuming alcohol and drugs were detected and treated under the Programme (1.1% prevalence), 465 men (97.5%) and 12 women (2.5%), with an average age of 39.8 years. RESULTS: The subjects were detected by occupational physicians (55.4%), occupational psychologists (2.9%), managers (11.3%), trade unionists (19.5%), via self-referral (9.4%) and by other means (1.5%). CONCLUSIONS: The results demonstrate the efficiency and the profitability to the company of prevention and treatment interventions and the need for the coordination of managers, trade unions and occupational health services.

El abordaje de las drogodependencias en el mundo laboral. Experiencia en el sector del transporte / Approaching drug-addiction in the workplace. Experiences in the Transport Sector

Las principales actuaciones sobre drogodependencias acontecidas en el medio laboral durante los últimos 30 años han sido revisadas, mostrando la prevalencia de los diferentes consumos de sustancias tóxicas, en el ámbito español y en diferentes sectores de la producción. Igualmente, se describen los principales programas implantados por la Dirección de los Servicios Médicos de la Red Nacional de los Ferrocarriles Españoles y sus principales logros. También se exponen los diversos programas contra las drogodependencias y el alcoholismo existentes en las empresas (de asesoramiento y referencia, preventivos, disuasorios y asistenciales), así como diversas actuaciones desafortunadas realizadas por algunas empresas en relación con este problema. Por último, se anima a corresponsabilizarse a empresarios, representantes sindicales y responsables de los servicios de prevención (Unidad Básica de Salud) en el enfoque, diseño de programas contra el alcoholismo y las otras drogodependencias en la empresa, además de en la detección y seguimiento de la reinserción laboral de los pacientes afectados por estas enfermedades. También se recomienda la inclusión con fines preventivos de preguntas relacionadas con el consumo de alcohol, tabaco y otras drogas en los protocolos de los exámenes de salud de riesgos laborales de los trabajadores (AU)

A review of the main interventions on drug-dependencies which took place in the workplace for the last 30 years was carried out. It showed the prevalence of the different consumptions as a general level in Spain as well as particular studies carried out in several other economic sectors. The main programmes against drug-dependencies implemented by Occupational Service Management of the National Railway Network of Spain and their main achievement are related. Also, several company programmes against drug-dependencies are exposed (advice and reference, prevention, dissuasion and treatment), as well as, some inadvisable actions realised by some companies in relation to this problem. Employers, trade unionists and personnel of prevention services (occupational health units) must encourage co-responsibility in the approach, implementation, detection and surveillance of the occupational reinstatement of these patients (sick workers). The inclusion of the answers related to the consumption of alcohol, tobacco and other drugs with the only preventive aim in all healthy questionnaires of the workers’ check-ups about industrial risks is recommended (AU)

Alcohol y drogas en las empresas de la Unión Europea / Alcohol and drugs in the European entreprises

La empresa es considerada por la Unión Europea como una de las instituciones más importantes para afrontar los problemas derivados del consumo de alcohol.Las Leyes y normativas de los diferentes Estados miembros están adaptadas a las peculiaridades propias de cada uno de ellos, pero carecen de leyes específicas frente a este problema, basándose en leyes generales penales, de salud y seguridad y de empleo. Igualmente, poseen unas obligaciones limitadas en relación al tratamiento, la educación y el asesoramiento de los trabajadores, evidenciándose también posturas de castigo que afortunadamente son cada vez menos usadas. Sin embargo, las disposiciones que protegen la intimidad dificultan el control de los problemas relativos al consumo de alcohol y drogas que afectan a los trabajadores, si bien todos los Estados miembros parecen estar de acuerdo en la necesidad de tratar dichos problemas en los sectores de alto riesgo y de responsabilidad.Los sindicatos y la mayoría de las empresas tampoco poseen políticas que afronten este problema, con excepción de las grandes empresas donde los sindicatos también tienen una mayor implantación.Las Administraciones de los Estados miembros y las empresas y los sindicatos realizan actividades preventivas, en general, y de identificación de los trabajadores de riesgo, en particular, para que aquellos trabajadores con problemas derivados del consumo de alcohol y drogas sean tratados, recuperados y reinsertados social y laboralmente (AU)

[Technical complications in the surgical inspection of the mediastinum in the staging of cancer of the lung]. / Complicaciones técnicas de la exploración quirúrgica del mediastino en la estadificación del cáncer de pulmón.

Between January 1974 and December 1996 we performed exploratory surgery (mediastinoscopies/mediastinotomies) on 1,618 patients diagnosed of bronchogenic carcinoma who were considered functionally operable and whose cancer was believed to be resectable. Findings were positive in 26%. Thirty-four (2.1%) complications were encountered, with a significantly higher incidence of complication among those for whom the results of exploratory surgery were positive (p = 0.004) as follows: only 13 cases (0.8%) of significant bleeding; 12 cases (0.74%) of recurrent left nerve palsy (0.74%), 4 (0.25%) subcutaneous wound infections; 3 cases (0.18%) of pneumothorax; 1 (0.06%) perforated esophagus; and 1 case (0.06%) of chylomediastinum. The rate of morbidity associated with exploratory surgery was within the range reported in the literature. No deaths occurred. Mediastinoscopy, in our experience, is the most effective way of staging mediastinal ganglia. Provided the procedure is performed carefully by experienced surgeons, the risk of complication is minimal.

[Pulmonary lymphangioleiomyomatosis (LAM). Diagnostic usefulness of immunohistochemical markers]. / Linfangioleiomiomatosis pulmonar (LAM). Utilidad diagnóstica de los marcadores inmunohistoquímicos.

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown cause affecting the lungs of female patients. Although clinical and radiological findings may suggest LAM, a firm diagnosis is usually made after lung biopsy. Cases of LAM (histochemical diagnosis) or "suggestive of LAM" at the "12 of October" Hospital are reviewed. We applied a battery of immunohistochemical tests not used to date--involving estrogen, progesterone, desmin and HMB45 receptors--that allowed us to classify specimens as having either LAM lesions or lesions with non-LAM muscle proliferation. Smooth muscle proliferation in LAM is a distinct phenotype, such that diagnosis is facilitated by analyzing for immunohistochemical markers such as HMB45. This marker can be detected on formalin-fixed paraffin-embedded sheets in specimens obtained by either open lung or transbronchial biopsy.

Differential capacity of various anti-Ig reagents to synergize with interleukin-4 to induce clonal expansion in resting and activated B cells.

The regulation of B cell growth responses by cross-linking of surface Ig receptors by monoclonal or polyclonal antibodies and its interaction with interleukin-4 (IL-4) has been evaluated. High-density B cells from autoimmune NZB/W mice were proliferated in the presence of low concentrations of a polyclonal goat anti-mu antibody and IL-4. Similarly, slight but significant positive responses were obtained with anti-K monoclonal antibodies and IL-4. In contrast, the same concentration of other surface Ig binding agents such as monoclonal antibodies against mu and delta immunoglobulin heavy chains did not synergize with IL-4 in order to induce clonal expansion of resting B cells. Polyclonal and monoclonal anti-Ig reagents inhibited the spontaneous cell growth of low-density B cells (in vivo activated B cells), although the negative effect was less noticeable with anti-delta monoclonal antibodies. Upon addition of IL-4 to activated B cell cultures in the presence of goat anti-mu antibody, a significant proliferative response was obtained. However, this lymphokine was unable to induce clonal expansion of B cell blasts in the presence of the various monoclonal anti-Ig antibodies employed in this study. Similar results were obtained with splenic B cells from normal animals, suggesting that the results shown in this report are not due to putative functional peculiarities of autoimmune B cells.

The requirements for growth of in vivo activated autoimmune B cells are similar to those of in vitro generated lipopolysaccharide B cell blasts and dissimilar to anti-IgM plus IL-4 induced B lymphoblasts.

The requirements for growth of in vivo activated B cells (natural blasts) from autoimmune NZB/W mice and of B cells from the same animals activated in vitro with either LPS or anti-IgM plus IL4 (mimicking 'in vitro' antigen induced TH cell-B cell interaction) were studied comparatively. The proliferation of natural and LPS blasts was inhibited by anti-IgM antibodies and augmented by recombinant IL-5. In contrast, anti-IgM stimulated the growth of anti-IgM plus IL-4 primed B cells but was without effect on the proliferative responses in the presence of IL-5. The growth inhibition induced by anti-IgM signalling on natural and LPS blasts seemed to be due to cross-linking of sIg rather than to binding of anti-IgM antibodies to the Fc receptors since a similar effect was observed with the F(ab)'2 fragment of this molecule. Maximum proliferation was obtained by a combination of IL-4 and IL-5 in natural and LPS blasts, whereas peak responses in anti-IgM plus IL-4 blasts were achieved by a combination of anti-IgM and IL-4. Lymphoblasts recovered after preculturing natural blasts in medium alone (more differentiated in vivo activated B cells) displayed high spontaneous proliferation which was strongly inhibited by anti-IgM. This inhibition was reversed partially by IL-4 and totally by IL-5. To define better the role of BLy+ cells in the spleen of NZB/W mice, purified Ly1+ and Ly1- cells, obtained by separation using magnetic beads, were analysed. The growth of both cell subpopulations was inhibited by anti-IgM and enhanced by IL-5. Cytotoxic elimination of Ly1+ cells from the primed B blast populations did not modify the proliferative pattern of these cells. Our results show that the growth requirements of in vivo activated autoimmune B cells resemble those of LPS blasts and differ from those following stimulation with anti-IgM plus IL-4, suggesting that B cells in systemic autoimmune diseases may have been activated by polyclonal stimulation. Nevertheless, other mechanisms for autoimmune B cell activation cannot be ruled out by the present experimental approach.

Protein kinase C-independent expression of stromelysin by platelet-derived growth factor, ras oncogene, and phosphatidylcholine-hydrolyzing phospholipase C.

Changes in the expression of several genes play critical roles in cell growth and tumor transformation. A number of proteases are increased in some tumors, and the level of these enzymes correlates with the metastatic potential of several cancer cell lines. Stromelysin, with the widest substrate specificity, can degrade the extracellular matrix conferring metastatic potential to tumor cells. The mechanisms whereby growth factors and oncogenes control the expression of stromelysin are beginning to be characterized. In the study shown here we also identify a region in the stromelysin promoter which is involved in the induction of stromelysin in response to platelet-derived growth factor, phosphatidylcholine-hydrolyzing phospholipase C, and ras oncogene. Our results are consistent with the notion that platelet-derived growth factor/phosphatidylcholine-hydrolyzing phospholipase C induces stromelysin gene expression through a phorbol myristate acetate/protein kinase C-independent mechanism by acting through elements in the stromelysin promoter distinct from the 12-O-tetradecanoylphorbol-13-acetate-responsive element.

Interleukin 2 production in a family with systemic lupus erythematosus and a C4Q0 heterozygous inheritance.

Interleukin 2 production was studied in a family with systemic lupus erythematosus (SLE) and a C4Q0 heterozygous inheritance. Autoimmune manifestations seemed to be associated with the HLA haplotype containing the C4Q0 allele, which was shared by all four ill family members. Concentrations of interleukin 2, however, did not associate either with the haplotype or with the clinical or serological manifestations, as diminished concentrations of interleukin 2 were found in only two subjects with SLE. Thus the defect in this family seemed to be acquired rather than genetically conditioned.

Lack of correlation between in vitro immunological alterations and the development of scleroderma-like skin lesions in toxic oil syndrome patients.

We examined whether immunological disturbances could influence the development of scleroderma-like skin lesions in patients affected by the Spanish toxic oil syndrome (TOS). To this end, peripheral blood mononuclear cells (PBMC) were collected from 13 chronic patients and 8 control subjects. All patients had suffered a toxic-induced severe neuromyopathy, and 6, in addition, had developed sclerodermoid skin manifestations. The phenotypic profile and the concentrations of interleukin-2 (IL-2) and of molecules with B cell differentiation factor IgG activity (BCDF-IgG) in supernatants of phytohemagglutinin-stimulated lymphocytes were analyzed both in patients and in normal controls. Molecules with BCDF-IgG activity were found increased in supernatants of mitogen-stimulated lymphocytes from TOS patients. Concentrations of IgG secreted by staphylococcus aureus-SAC-B blasts in the presence of TOS PBMC supernatant was 88 +/- 32.62 ng/ml (mean +/- 1 SD) versus 53 +/- 5.34 ng/ml in the presence of control supernatant (p less than 0.01). Levels of BCDF-IgG activity in TOS PBMC supernatants positively correlated with IgG serum levels (r = 0.69, p less than 0.01). The phenotypic profile of lymphocyte populations and the production of IL-2 were not altered in TOS subjects. No statistically significant differences were observed in the lymphocyte distribution nor in the IL-2 and BCDF-IgG production when comparing patients with or without scleroderma-like skin lesions. The results indicate that there was a dysfunction of the immune response in TOS subjects, which, however, was not sufficient for the development of the sclerodermoid lesions.

A role for T3+4-6-8- transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes.

In vivo, immunocompetent T lymphocytes are only detected late in ontogeny, among mature thymocytes expressing either T4 (L3T4 in mouse) or T8 (Lyt-2) surface glycoproteins. We have previously shown, however, that there are functional precursors among T3+4-6-8- human thymocytes in vivo. Here we report on the in vitro differentiation of prothymocytes into T3+4-6-8- and mature T cells. T11+3-4-6-8- prothymocytes (0.5% of total thymocytes, greater than 98% pure) were obtained after treatment of thymocytes with OKT3 (T3), OKT4A (T4), Na1/34 (T6), and B9.4 (T8) monoclonal antibodies plus complement. During culture, the prothymocyte precursors acquire first T3 and then either T4 or T8, but not T6. The largest subpopulation in the thymus, T4+6+8+ cells, are not detected among the in vitro T-cell precursors. During culture, the precursors acquire cytolytic activity as soon as they express either the T3+4-6-8- or the mature (T3+4+8- or T3+4-8+) phenotypes. We suggest that T3+4-6-8- cells are a productive, transitional stage in T-lymphocyte development.

Differentiation of human mature thymocytes: existence of a T3+4-8- intermediate stage.

A T3 complex-bearing subpopulation was characterized within an in vivo cycling T4-8- early thymocyte compartment which contains cells constitutively expressing interleukin 2 and transferrin receptors. We show differentiation in vitro of both mature subsets of thymocytes (T3+4+8- and T3+4-8+) from the above T4-8- compartment, their appearance being preceded by cells in a T3+4-8- intermediate stage. Furthermore, those mature thymocytes generated in vitro contain functionally competent cells which use T3, T4 and T8 structures for their cytolytic activity. The finding of T3+4-8- thymocytes in vivo, together with the observation that T3 antigen expression precedes that of T4 or T8 molecules in vitro, shows that T3 (and presumably Ti) is present early in ontogeny, and suggests that T3+4-8- cells constitute an "intermediate" stage relevant to the connection between early precursors and mature thymocytes during T lymphocyte ontogeny.