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P Soler

Publications and source records attributed to P Soler.

At least 37 records · Page 2Linked to original sources
PubMed1998

Langerhans cells in Langerhans cell granulomatosis are not actively proliferating cells.

Pulmonary Langerhans cell granulomatosis (LCG), also called histiocytosis X, is a disorder of unknown etiology characterized by the presence of destructive granulomas containing numerous Langerhans cells (LCs). The process may be localized or multifocal, and it remains unclear whether the same pathogenic mechanism is involved in all forms of the disease. It is often assumed that the massive accumulation of LCs at the sites of the lesions results from the abnormal proliferation of these cells, although it has been suggested that LCG in adults, at least in the lung, could be a reactive disorder initiated by activated LCs. Little is known, however, concerning the mechanisms responsible for the accumulation of large numbers of LCs in the course of the disease, and the relative contribution of recruitment and local proliferation of these cells remains to be established. To investigate this question, the proportion of replicating LCs was evaluated in biopsied granulomas from patients with localized or diffuse form of LCG by means of several histopathological techniques currently used in assessment of cell proliferation. The findings demonstrate that, except for proliferating cell nuclear antigen (PCNA), all parameters measured are low in all forms of the disease. They are similar to those of renewing epithelial cells and clearly less than those of neoplastic cells. These data strongly suggest that LCs in LCG granulomas are not a rapidly dividing cell population and that local LC replication makes only a minimal contribution to granuloma maintenance. Caution appears to be necessary in the use of PCNA as a marker of growth fraction.

Adenocarcinoma↗
PubMed1997

Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response.

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.

Adult↗
PubMed1997

Different size limitations for increased transepithelial paracellular solute flux across phorbol ester and tumor necrosis factor-treated epithelial cell sheets.

By observing increases in the transepithelial paracellular permeability of a range of radiolabeled solutes and electron dense dyes, changes in molecular sieving caused by the cytokine, TNF (tumor necrosis factor), and the phorbol ester, TPA (12-0-tetra-decanoylphorbol-13-acetate), were characterized. Using 14C-labeled mannitol (mw 182), raffinose (mw 504), PEG (polyethylene glycol; mw 4000), and dextran (mw 10,000, 70,000 and 2,000,000), the transepithelial flux rates of these compounds were determined at the peak of the transepithelial electrical resistance (TER) changes caused by these two agents. TNF treatment resulted in increased permeability across LLC-PK1 epithelial cell sheets only to relatively small solutes, with an upper limit of approximately 4,000 mw. The low molecular weight "ceiling" for the TNF-treated epithelium is further evidence against TNF increasing transepithelial permeability by means of inducing nonspecific, microscopic "holes" in the epithelium, for which a "ceiling" would not exist. TPA treatment increases transepithelial paracellular permeability to a much broader range of solutes, extending well beyond 2 million mw. Transmission electron micrographs provide evidence that even the electron-dense dye complex, ruthenium red, can cross tight junctions of TPA-treated cell sheets. However, cationic ferritin cannot cross tight junctions of TPA-treated cell sheets. This shows that there is an upper limit to solutes able to cross TPA-treated cell sheets, but that this upper limit will include most proteins, which would then be able to cross tumor promoter-exposed (protein kinase C-activated) epithelial layers at accelerated rates. The biomedical implications for a high molecular weight cutoff in tumor promoter action in epithelial carcinogenesis, and for a low molecular weight cutoff in cytokine-induced epithelial apoptosis in inflammation, are discussed.

Animals↗
PubMed1997

Activation of T-cells through an antigen-independent alternative pathway induces precocious sensitivity to Fas-induced apoptosis.

Autoreactive T-cells can be activated inadvertently during immune responses through antigen-independent pathways. It has been suggested that Fas/Fas ligand interactions may play a role in eliminating these cells, but the extent that cells activated through such alternative pathways are sensitive to Fas-induced apoptosis has not been extensively evaluated. Proliferation of peripheral blood T-cells from normal individuals activated for 4 days with PHA or PMA + ionophore was not influenced by the presence of anti-Fas antibody. When the same cells were activated with soluble factors produced by previously activated T-cells (lymphostimulatory activity), anti-Fas antibodies inhibited thymidine incorporation by 74+/-4%. The presence of typical morphological changes and oligonucleosomal fragmentation of DNA indicated that the reduced proliferation resulted from apoptotic death of the lymphoblasts. Fas-sensitivity of T-cells activated by lymphostimulatory activity was first detectable 4 days after activation, and at 5 days the majority of lymphoblasts had become sensitive to Fas, whereas no evidence of sensitivity to Fas was observed for lymphoblasts generated by PHA or PMA + ionophore during the first 5 days of culture. Incubation of cells activated with PHA or PMA+ ionophore in the presence of IL-2 at concentrations 10-fold higher than that present in lymphostimulatory activity did not induce early sensitivity to Fas, indicating that exposure to IL-2 could not explain the precocious development of sensitivity to Fas seen following activation by lymphostimulatory activity. These studies demonstrate that T-cells activated through an antigen-independent 'alternative' pathway develop precocious sensitivity to Fas-induced apoptosis, which may be important in permitting the elimination of autoreactive bystander cells activated in the course of immune responses.

Adult↗
PubMed1997

Characterization of proliferative responses and cytokine mRNA profiles induced by Vespula venom in patients with severe reactions to wasp stings.

The reasons why severe allergic reactions to bee and wasp stings develop in only a small portion of exposed individuals are incompletely understood, but differences in T cell responses to venom antigens comparing allergic and non-allergic individuals are likely to be important. To identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula venom-allergic patients and non-allergic individuals were compared. Mononuclear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n = 19), and the extent of proliferation was greater for patients with a history of multiple prior stings and those with high levels of venom-specific IgE. Although mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 +/- 711 ct/min, n = 8), production of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula venom by cells from non-allergic subjects was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that these individuals had been previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients released a more restricted profile of cytokines following stimulation with venom. Only IFN-gamma mRNA expression was detected in all individuals evaluated, whereas IL-2 mRNA was not detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells from these individuals, because polyclonal stimulation with phorbol myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the two groups. These studies demonstrate clear differences in the T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.

Adult↗
PubMed1997

Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone.

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim-Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim-Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester disease, are discussed.

Biomarkers↗
PubMed1996

The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer.

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Reliability and validity of an HIV-specific health-related quality-of-life measure for use with injecting drug users.

OBJECTIVE: To assess the reliability and validity of an HIV-specific quality of life (QoL) questionnaire for use with injecting drug users (IDU). METHOD: One hundred IDU with HIV infection (27 asymptomatic, 48 symptomatic, 25 with AIDS) completed the HIV adaptation of the Medical Outcomes Study questionnaire (MOS-HIV). Validity of the scale was assessed by comparing the scores on the MOS-HIV with measures of health and psychological status. Measures of health status used included Centers for Disease Control and Prevention (CDC) stage, CD4 cell count and number of HIV-related illnesses. Psychological status was assessed using the Hospital Anxiety and Depression Scale. Sociodemographic data and information on illegal drug consumption were also collected. RESULTS: The MOS-HIV showed a good internal reliability on all scales and the factor structure was comparable with that reported from previous studies. The psychological scales from the MOS-HIV showed good concurrent validity. For the physical aspects of QoL, however, some scales were poor at discriminating between different HIV disease stages. One reason for this may have been that factors associated with a history of injecting drug use had a significant negative impact on QoL, particularly for asymptomatic patients. It was notable that QoL in asymptomatic infection was found to be substantially lower than has been reported for gay/bisexual men using the same instruments and was more strongly associated with factors related to drug use rather than to HIV disease status. CONCLUSION: The MOS-HIV is a reliable and valid measure, but in patients with a history of injecting drug use some of the scales measuring the physical aspects of QoL may be relatively insensitive to changes in health.

Adult↗
PubMed1996

Role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of adult pulmonary histiocytosis X.

BACKGROUND: Pulmonary histiocytosis X is a disorder characterised by the presence of destructive granulomas preferentially involving distal bronchioles, that contain numerous activated Langerhans' cells. Recent studies have shown that granulocyte-macrophage colony stimulating factor (GM-CSF), which is produced by normal bronchiolar epithelium, may play an important part in the distribution and differentiation of Langerhans' cells. The aim of this study was to evaluate the role of this factor in the pathogenesis of pulmonary histiocytosis X. METHODS: Four patients with pulmonary histiocytosis X were examined by immunohistochemical techniques for GM-CSF and CD1a surface molecules. RESULTS: In early lesions the epithelium of bronchioles affected by the disease was strongly positive for GM-CSF and infiltrated by numerous CD1a+ Langerhans' cells organised into granulomas. In contrast, the expression of GM-CSF was substantially lower in bronchioles not affected by the disease, and these bronchioles contained few Langerhans' cells. When destruction by histiocytosis X lesions was more advanced, only remnants of bronchiolar epithelium could occasionally be identified; these remained strongly reactive for GM-CSF. Langerhans' cells within granulomas also moderately expressed this cytokine. CONCLUSIONS: These results support the hypothesis that GM-CSF could be one of the factors responsible for the local accumulation of lymphostimulatory Langerhans' cells in early lesions of pulmonary histiocytosis X.

Adult↗
PubMed1995

Effect of polycations on barrier and transport properties of alveolar epithelium in situ.

We examined the effect of polycations, classes of which are released by activated leukocytes, on the transport properties of the alveolar epithelium in isolated-perfused rat lungs. Protamine, polylysines, and ruthenium red produced rapid, dose-dependent increases in mannitol permeability (PAmann) when instilled into airspaces. The coupling between active transepithelial Na+ transport and alveolar fluid absorption was not altered, despite > 10-fold increases in PAmann. The increase in albumin permeability compared with that in mannitol suggested preservation of alveolar barrier-size selectivity. Tracheal instillation of protamine produced no cellular abnormality, whereas its addition to the perfusate resulted in damage to endothelial and type I cells. Protamine produced an even larger (P < 0.05) increase in PAmann in the presence of isoproterenol or dibutyryl adenosine 3',5'-cyclic monophosphate + 3-isobutyl-1-methyl-xanthine. The stimulation of Na+ and fluid transport by these agents was unaffected by protamine. Mastoparan, a peptide that activates G proteins, produced effects comparable to those of the polycations. The protamine- and mastoparan-induced increase in PAmann was abolished by barium, a K+ channel blocker, but not by zinc, a membrane-protective cation. Other K+ channel blockers, tetraethylammonium and quinine, had no effect. Thus short-term apical application of polycations and mastoparan alter alveolar epithelium paracellular permeability by a noncytotoxic mechanism that is inhibited by barium. The resulting increase in paracellular permeability does not alter fluid absorption driven by active Na+ transport. Polycations have very different effects, depending on whether they are present on one side or the other side of the alveolar capillary barrier.

Absorption↗
PubMed1995

Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations.

The risk of lung injury due to alveolar overdistension during mechanical ventilation has been clearly delineated in healthy animals with intact lungs. In contrast, the effect of high-volume ventilation (HV) on previously injured lungs is less well documented: whether HV would simply add its own deleterious effects or act synergistically with previous injury has not been addressed. We compared the effect of 7 ml/kg body weight tidal volume mechanical ventilation for 2 min with that of 25 (HV25), 33(HV33), and 45(HV45) ml/kg body weight HV in anesthetized rats previously exposed or not exposed to alpha-naphthylthiourea (ANTU). ANTU alone produced moderate permeability edema with significant increases in extravascular lung water (Qwl), dry lung weight (DLW), and albumin distribution space in lungs (ASp). HV alone resulted in a permeability edema in which severity was dependent on the magnitude of the tidal volume. The effects of HV25 and HV33 and those of ANTU were only additive, as indicated by the absence of any significant two-factor (ANTU-HV) interaction by analysis of variance (ANOVA). In contrast, HV45 after ANTU produced significantly greater increases in Qwl, DLW, and ASp than expected from the sum of the effects of either insult alone. Two-way ANOVA disclosed two-factor interactions with p values < 0.001, < 0.02, and < 0.01 for Qwl, DLW, and ASp, respectively, indicating synergistic adverse effects on pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1995

Migratory bronchiolitis obliterans organizing pneumonia after unilateral radiation therapy for breast carcinoma.

We report the case of a 59 year old woman who developed cough, dyspnoea and fever with patchy migratory airspace infiltrates, 2 months after right breast radiation therapy for breast carcinoma. Lung infiltrates were initially localized in the irradiated area and spread to the contralateral lung. Lung biopsy, performed in an unirradiated area of the contralateral lung 9 months after completion of radiotherapy, revealed a typical histological pattern of bronchiolitis obliterans organizing pneumonia. No cause of bronchiolitis obliterans organizing pneumonia other than radiation was found. Treatment with corticosteroids resulted in rapid clinical improvement and complete resolution of airspace opacities. This case suggests that localized lung irradiation might trigger the development of a bilateral lung disease, with a histological pattern of bronchiolitis obliterans organizing pneumonia.

Biopsy↗
PubMed1995

[Immunohistochemistry. What place should freeze drying of tissues be accorded?].

Immunohistochemical labeling of frozen tissue sections is a valuable technique that allows the detection of most antigens usually destroyed by fixation in conventional tissue processing. This technique, however, has a number of limitations: difficulty in storage of tissue samples, loss of morphologic details, presence of staining artifacts, diffusion of soluble proteins. The use of freeze-dried paraffin-embedded tissues is helpful in overcoming these problems: tissue morphology is better preserved than in frozen sections; a wide range of antigens can be labeled with the same staining intensity as in frozen sections; background or diffusion artifacts are uncommon; tissue blocks may be handled as conventional paraffin blocks. The technique is based on the rapid freezing of tissue samples and their subsequent freeze-drying, followed by embedding in paraffin. Because of the expense of the necessary equipment (tissue dryer) and the limited number of samples that can be processed at one time, this technique has not been widely used by routine pathological services.

Artifacts↗
PubMed1995

Pulmonary Langerhans cell granulomatosis.

Pulmonary Langerhans cell granulomatosis (LCG), also called histiocytosis X, is characterized by the presence of destructive granulomas containing large numbers of Langerhans cells. The lesions are almost exclusively centered on distal bronchioles, and it may be more accurate to consider the disease as a bronchiolitis. Isolated pulmonary LCG is an uncommon disease that usually affects young adult smokers. Multifocal or diffuse involvement can also occur, though more often in infants or children. High-resolution computed tomography has proved to be useful in the diagnosis of the disease by allowing the identification of characteristic cystic lesions associated with nodules. Bronchoalveolar lavage strongly supports the diagnosis in only the occasional patient. The pathogenesis of pulmonary LCG remains unknown, although several arguments suggest that, at least in adults, it may result from an uncontrolled immune response initiated by Langerhans cells. Granulocyte macrophage colony-stimulating factor could be one of the factors responsible for the local accumulation of Langerhans cells in early lesions. Recently, evidence that lesional Langerhans cells are of clonal origin has been reported in patients who have various forms of the disease, but this finding has not yet been shown for pulmonary LCG. Further studies are needed to determine whether the pathogenetic mechanisms are different in patients who have localized or diffuse forms of the disease.

Adult↗
PubMed1994

[Pathogeny of sarcoidosis].

Sarcoidosis is a multisystemic granulomatous disorder due to an immune response of unknown etiology. The interactions between monocytes/macrophages and T lymphocytes through direct contact between the cells play a major role in the occurrence of these responses. Factors depending on the host, such as the polymorphism of the major histocompatibility complex molecules could be implicated in sarcoidosis pathogenesis. The factors that regulate the degree of granulomatous reaction, or those that determine the degree of fibrous response observed in some patients with sarcoidosis are poorly understood. Two recent studies, using the high sensitivity of the polymerase chain reaction, have shown the presence of M. tuberculosis DNA in 13 to 50% of biopsy samples from sarcoid patients, suggesting a role of this agent in the disease, at least in certain cases.

Antigens↗
PubMed1994

Pulmonary sarcoidosis with a diffuse ground glass pattern on the chest radiograph.

BACKGROUND: Several chest radiographic abnormalities have been described in pulmonary sarcoidosis, but a diffuse ground glass pattern is extremely rare. METHODS: The chest radiographs of more than 1600 patients with sarcoidosis evaluated in our service between 1976 and 1991 were reviewed to determine the prevalence of this pattern on chest radiography at presentation, and to assess the clinical characteristics of these patients. RESULTS: Ten patients (0.6%) were identified with diffuse ground glass abnormalities on the chest radiography (eight men); all had associated hilar or mediastinal adenopathy. All patients were white and nine were smokers or former smokers. Nine patients were symptomatic and six had inspiratory crackles on physical examination. As a group these patients were remarkable for the frequency and severity of physiological abnormalities and the presence of various findings typically associated with "active" disease. Nine patients were followed for more than three years. All were treated with oral corticosteroids because of significant symptoms or physiological abnormalities, or both. Symptoms and radiological abnormalities disappeared or improved in all patients, but recurred in a high proportion when steroids were tapered or discontinued. By December 1992 only three patients had been withdrawn from treatment. CONCLUSIONS: A diffuse ground glass pattern on the chest radiograph is unusual in patients with sarcoidosis and may occur more commonly in white subjects and cigarette smokers. Its presence suggests the existence of active disease of recent onset likely to require long term treatment with corticosteroids.

Acute Disease↗