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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 253 records · Page 14Linked to original sources
PubMed1995

Retroviral infection (HTLV-I) induces cytokine-regulated immunomodulation and cytotoxicity of medulloblastoma cells.

Primitive neuroectodermal tumors are thought to result from disturbed differentiation of neuroepithelial stem cells. These tumor cells retain the capacity to differentiate toward the neuron or glia phenotype under extrinsic stimuli. Previously, we have developed a model for the differentiation of a medulloblastoma cell line (Dev cells) induced by infection with the human retrovirus HTLV-I. This virus delivers signals which trigger the Dev cells to differentiate toward an astrocytic lineage. The aim of this study was to characterize the time course of viral infection, to identify the soluble factors released and to analyze their effects on Dev cells. The early phase of viral replication is followed by latent infection. Viral infection induces glial differentiation in a subpopulation of cells and results in the death of others. The inflammatory cytokines TNF alpha, IL1 alpha and IL6 were detected in medium conditioned by infected Dev cells. TNF alpha was cytotoxic and cytostatic for subpopulations of Dev cells. Furthermore, TNF alpha treatment reproduced the modulation of expression of the major histocompatibility complex antigens (MHC class I) observed in infected Dev cells. These observations support the view that HTLV-I infection, which triggers glial differentiation of medulloblastoma Dev cells, also causes the release of soluble factors capable of downregulating proliferation of dividing tumor cells and of modifying their recognition by cellular immune effectors.

Cell Differentiation↗
PubMed1995

Diagnostic value of serum IL-6 level in monoclonal gammopathies.

The serum level of IL-6 was reported to reflect disease severity in patients with multiple myeloma. We used a specific radioimmunoassay to measure the level of IL-6 in 239 serum samples in which a monoclonal gammopathy was identified for the first time. The same sample was used for the measurement of serum C reactive protein and serum albumin. Then, an inventory of clinical and biological features allowed us to classify these patients into five groups: monoclonal gammopathy of undetermined significance (MGUS:128), multiple myeloma (MM:66), Waldenström's macroglobulinaemia (WM:27), non-Hodgkin's lymphoma (NHL:11) and chronic lymphocytic leukaemia (CLL:7). The number of patients with serum IL-6 (S-IL-6) level > 0.335 ng/ml (upper limit in normal sera) was significantly higher in the MM group (35%; Confidence Interval (CI) 23.5-46.5) compared with the MGUS group (15%; CI 8.8-21.2). The distribution of S-IL-6 levels was also significantly different between the groups (Mann-Whitney test: P < 0.01). High S-IL-6 levels were measured in 5/11 patients with NHL and 9/27 patients with WM. The distribution of S-IL-6 levels in these groups was the same as that in MGUS or MM groups. In patients with MM, elevated S-IL-6 levels were associated with haemoglobin level < 100 g/l (P < 0.005), bone marrow plasmocytosis > 50% (P < 0.005) and stages II and III in the Durie & Salmon staging system (P < 0.005). The S-IL-6 level was also related to light chain component excretion in urine (P < 0.01) and M component serum level for IgA (P < 0.01). In patients with MGUS, the S-IL-6 level correlated with serum CRP level (P < 0.05), serum lactate dehydrogenase (P < 0.05) and serum ferritin (P < 0.01). We conclude that the S-IL-6 level is a marker of high tumour burden in multiple myeloma. However, S-IL-6 level can be increased in patients with MGUS in relation to inflammatory parameters. Therefore the S-IL-6 level does not demonstrate high predictive value for the diagnosis of MM in patients with newly identified monoclonal gammopathy.

Adult↗
PubMed1995

Association between NAG-B and cadmium in urine with no evidence of a threshold.

OBJECTIVES: To explore the significance of the increase in urinary excretion of the lysosomal enzyme beta-N-acetylglucosaminidase (NAG) at low exposures to cadmium (Cd) that is frequently found in the absence of any other sign of renal dysfunction. METHODS: The activity was measured of the two main isoenzymes of NAG (NAG-A secreted by exocytosis and NAG-B released with cell membranes) in the urine of 49 male workers employed in a Cd smelter and of 20 age matched controls. RESULTS: An increased urinary excretion of low molecular weight proteins was noted only in subjects who excreted > 10 micrograms Cd/g creatinine. The urinary activity of NAG-B showed a dose related increase that was already significant in the group excreting 0.5-2 micrograms Cd/g creatinine. In multiple regression analysis the NAG-B activity correlated with the excretion of Cd but not with that of lead or mercury. The NAG-A activity was by contrast unaffected by exposure to Cd but correlated with the urinary excretion of lead and copper. CONCLUSIONS: As NAG-B is considered to be the lesional form of NAG, the existence of a specific association between this enzyme and urinary Cd excretion with no detectable threshold suggests that this metal produces cellular alterations at exposures commonly found in the general population.

Acetylglucosaminidase↗
PubMed1995

Subclinical signs of kidney dysfunction following short exposure to silica in the absence of silicosis.

Signs of kidney dysfunction detectable in urinary protein excretion were searched for in a group of 86 silica-exposed workers who were compared to 86 control subjects matched for age, smoking status and body mass index. No worker had any clinical, spirometric or radiographic sign of silicosis, and exposure duration averaged 15.2 months (range: 11-20). An increase in the urinary excretion of albumin, transferrin, retinol-binding protein and N-acetyl-beta-D-glucosaminidase was found in the exposed group, and the prevalences of pathological values were also elevated in this group. By contrast, both groups had similar serum levels of creatinine and beta 2-microglobulin. These results strongly suggest that occupational exposure to silica may lead to subclinical renal effects after less than 2 years and in the absence of silicosis.

Adult↗
PubMed1995

Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro.

Clara cell protein (CC-16, also designated CC-10) is synthesized by the bronchiolar epithelium and has been suggested as an inhibitor of phospholipase A2 (PLA2) activity. Therefore, CC-16 is a candidate for controlling inflammatory events in the lung. Because CC-16 amounts and function may be altered in fibrosing lung diseases in which bronchiolar injury has been reported, it was measured in alveolar fluids and sera. Secretory PLA2 activity in alveolar fluids and the influence of CC-16 on platelet-derived growth factor-induced human fibroblast chemotaxis and cytosolic PLA2 activity were also explored. CC-16 content was decreased in alveolar fluids from idiopathic pulmonary fibrosis (IPF: 1.3 +/- 0.1 mg/L) and bleomycin lung (1.1 +/- 0.2 versus 2.1 +/- 0.2 mg/L in controls, p < 0.05), whereas there was a three- to ninefold increase in secretory PLA2 activity (p < 0.05 versus controls). CC-16 inhibited fibroblast chemotaxis in a dose-dependent manner (90% inhibition at 30 micrograms/ml CC-16). This inhibition was reversed by reducing CC-16. CC-16 was also able to lower fibroblastic cytosolic PLA2 activity by 50% in vitro. In summary, CC-16 is able to inhibit fibroblast chemotaxis in vitro by mechanisms that may be related to a blockage of cytosolic PLA2 activity. It can be postulated that CC-16 deficiency may contribute to fibroblast burden activity in fibrosing lung diseases.

Adult↗
PubMed1995

Potent inhibition of both human interferon-gamma production and biologic activity by the Clara cell protein CC16.

The Clara cell 16 kD protein (CC16), the predominant product of the Clara cells lining the bronchiolar epithelium, is thought to protect the respiratory and urogenital tract from unwanted inflammatory reactions through its immunosuppressive action. In this report, we show evidence that CC16 establishes an anti-inflammatory activity by interfering with the interferon-gamma (IFN-gamma)-mediated actions of the cytokine network. The HuIFN-gamma production of stimulated single-donor peripheral blood mononuclear cells is inhibited by the presence of doses of CC16 in the range of 10(-12) M, with a maximal inhibition (up to 95%) when interleukin-2 is used as a stimulating agent. CC16 also diminishes the biologic activity of IFN-gamma: both the antiviral activity and the stimulation of phagocytosis by IFN-gamma, measured by means of chemiluminescence, are reduced in the presence of CC16. These observations indicate that CC16 acts as an anticytokine and could give new insight in the potential role of the Clara cells.

Bronchi↗
PubMed1995

Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury.

It is now recognized that epithelial cells lining airways and alveoli are capable of releasing various mediators, which have the potential to modulate local inflammatory reactions. The amount of the 16 kDa Clara cell protein (CC16), an inhibitor of phospholipase A2 activity produced by pulmonary epithelial cells, was measured by means of a sensitive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BALF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 after standard cardiopulmonary bypass surgery, a known risk factor for ARDS). The level of CC16 was compared with other markers of inflammation with a wide range of molecular weights: albumin (nephelometry); total protein (spectrophotometry); beta 2-microglobulin (latex immunoassay); cystatin C (latex immunoassay); alpha 1-antitrypsin (immunoradiometry), and lipocortin-1 (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and significantly higher levels of this protein were observed in BALF from patients with acute lung injury. Changes in BALF Clara cell protein levels differed from those of alpha 2-macroglobulin and the natural phospholipase inhibitor lipocortin-1. Alpha 2-macroglobulin levels were not significantly enhanced in patients at risk for ARDS, but were increased in patients with ARDS; whereas, lipocortin 1 levels were not elevated in either group. Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein recovered in BALF. The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived. The data presented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which might have a protective and immunosuppressive role.

Adult↗
PubMed1995

[Invasive pulmonary aspergillosis in neutropenic patients. Analysis of a series of 36 cases: contribution of thoracic scanners and itraconazole].

In neutropenic patients, one way of improving invasive pulmonary aspergillosis (IPA) prognosis is an earlier initiation of the antifungal treatment. We report our experience with 36 cases of IPA in 35 patients with haematological malignancies. When aspergillosis was diagnosed, all but 2 patients were neutropenic (PMN < 500; median duration = 20 days). The most frequent clinical signs were cough (100%), chest pain (78%) and haemoptysis (58%). Before the diagnosis of IPA, Aspergillus antibody test was positive in 60% of cases. A thoracic CT-scan was performed in 23 patients and demonstrated highly suggestive images in 22 cases (96%) with presence of CT halo sign (n = 13) or CT air-crescent sign (n = 9). Moreover, Aspergillus antigen test was positive in 13 of 28 tested patients. IPA diagnosis was determined to be definite in 23 cases and probable or possible in 13 cases. Thirty-five patients were treated: in 3 cases with amphotericin B (2 failures) and in 32 cases with itraconazole (7 failures and 25 successes or improvements). In 7 cases (including 5 emergencies) surgical resection was successfully combined with the medical treatment. In neutropenic patients with fever, we consider that thoracic CT-scan and repeated biological tests (Aspergillus antibody and antigen tests) can be used to establish the diagnosis of aspergillosis. Early treatment with itraconazole and surgical resection appears to improve prognosis.

Adult↗
PubMed1995

[Intraoperative radiotherapy. Preliminary results].

We report a series of 40 patients treated by intraoperative radiotherapy between 1988 and 1992 (18 primary tumors, 13 local recurrences and 9 nodal extensions). The doses delivered were 15 Gy to 25 Gy, completed by external radiotherapy (15 to 45 Gy) in 13 cases. The local tumor control rate was 61% for initial therapy in primary tumors (70% for adenocarcinoma of the stomach) and 80.9% after complete en bloc surgery. The local control rate after palliative surgery for local recurrences is 38% and 33% for nodal extension. Two patients died (5%) during the postoperative period. We observed 2 hemorrhages and 3 cases of stone-free cholecystitis. The value of this approach must be confirmed in rigorous indications in comparison with surgery alone in controlled and randomised clinical trials.

Adult↗
PubMed1995

[Intestinal infarctions. A re-evaluation of prognostic factors of postoperative mortality].

The aim of this study, based on a series of 67 patients, was to assess the prognostic factors of postoperative mortality of intestinal infarctions (small and large bowel). Known risk factors were studied (age, sex, shock, Concomitant disease, use of arteriography and vasodilators), together with less studied factors, such as recent vascular or cardiac surgery less than 4 months before the infarction and length of bowel infarction. Postoperative mortality was defined as any death occurring within 45 days after surgery. The risk factors were assessed by univariate and multivariate analysis with logistic regression. The postoperative mortality was 63%. Age, shock, other medical diseases, recent cardiovascular surgery, and length of bowel infarction were significant predictive factors of postoperative mortality on univariate analysis. Shock, age greater than 70 years and recent cardiovascular surgery were three independent risk factors selected on multivariate analysis with equivalent weights.

Adult↗
PubMed1995

[Emergency lung resections for invasive aspergillosis in neutropenic patients].

Mortality due to Invasive Pulmonary Aspergillosis (IPA) remains high in neutropenic patients due to pulmonary haemorrhage. The aim of this study was to evaluate the emergency surgical management of IPA. Seven neutropenic patients, with a mean age of 47 years (range: 30-64) (4 women and 3 men) were treated for (6 cases) acute leukaemia one Myeloma (1 case). Presumptive diagnosis of IPA was based on: Halo sign (n = 6) or air-crescent sign (n = 1) on CT scan, positive serology (n = 4), positive antigenemia (n = 3) and positive broncho-alveolar lavage (n = 1). In 2 cases, IPA diagnosis was only based on CT scan. In all cases, aspergillosis lesions were located near the left (n = 5) or right (n = 2) pulmonary artery. The type of pulmonary resection was: left superior lobectomy in 3 cases, left superior lobectomy and Fowler's segmentectomy in 1 case, Left inferior lobectomy in 1 case, right superior lobectomy in 1 case and middle lobectomy and paracardiac segmentectomy. Sleeve resection of the pulmonary artery was performed in two patients. There were no deaths or major postoperative complications. Mean hospital stay after surgery was 12 days (rang: 8-19). Histological examination confirmed the diagnosis of IPA. CT is essential to determine the optimal timing for surgery.

Adult↗
PubMed1995

Effect of 1-28 alpha-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation.

The efficacy and safety of (1-28) alpha-human ANP in preventing acute tubular necrosis (ATN) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration (MH) regimen which we previously reported as effective in lowering the incidence of ATN (1, 2). Since the production of endogenous ANP increases with volume overloading (3), we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients. We thus conducted an open randomized study comparing the effect on early renal allograft function of MH (control group) versus moderate hydration plus ANP infusion (ANP group). Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time (mean +/- 2 h). The demographic characteristics of donors and recipients were similar. Using a Swan-Ganz catheter, hemodynamic parameters were monitored for 4 h after transplantation. The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure (PAP) of < or = 20 mmHg. The PAP in patients receiving MH was driven to > or = 25 mmHg. In the ANP group, a bolus of 100 micrograms of ANP was infused into the graft's renal artery at the time of unclamping, followed by 24 h of continuous intravenous infusion at 0.03 microgram/kg/min. Thereafter, the patients received ANP at a rate of 0.01 microgram/kg/min until the serum creatinine reached < 2 mg/dl. As a consequence of the hydration regimen, the PAP at unclamping was lower in the ANP group than in the control group; 20 +/- 3 and 26 +/- 4 mmHg, respectively (p < 0.05). The ANP plasma levels were significantly higher during the first 3 d in the ANP group (p < 0.001). The median recovery rate of renal function was similar in both groups. No patients in the ANP group experienced ATN while 4 patients (20%) in the control group did (p = 0.125). The need for hemodialysis was markedly reduced in the ANP group compared to the control group (1 ANP-treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times; p = 0.068). ANP administration was well-tolerated and no hypotensive episodes were reported. This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a standard regimen in managing kidney allograft recipients.

Acute Kidney Injury↗
PubMed1994

Involvement of microsomal vesicles in part of the sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition in mitochondrial fractions of rat liver.

Liver mitochondrial fractions as normally isolated contain only 10-20% of total mitochondria and may not be representative of the whole mitochondrial population. This study was designed to evaluate the dependence of the sensitivity of carnitine palmitoyl-transferase I (CPT I) to malonyl-CoA inhibition in mitochondrial fractions that are not normally studied. Four fractions prepared from rat liver were found to be contaminated to different extents by microsome vesicles, on the basis of marker-enzyme activities and micrographic data. Purification of mitochondrial fractions on a Percoll gradient decreased to some extent the microsomal contamination, which was due in part to the existence of close bonds between microsomes and the outer membranes of mitochondria. A greater degree of contamination of mitochondrial fractions by microsomes was correlated with a greater sensitivity of CPT I to malonyl-CoA inhibition. Attempts were made to enhance the sensitivity of CPT I to malonyl-CoA with the use of microsomes. Measurements performed by adding mitochondria and microsomes in the same CPT I assay failed to demonstrate any significant enhancement of malonyl-CoA inhibition. However, addition of ATP to a mixture of mitochondria and microsomes was shown to trigger the binding of both particles, as assessed by enzymic and micrographic data, and to increase the sensitivity of CPT I to malonyl-CoA inhibition. These results demonstrated that the binding of microsomes to mitochondria, unlike the simple mixing of both particles, was capable of altering the sensitivity of CPT I to malonyl-CoA. The data also suggest that this process could be of physiological importance, owing to the frequency of contiguous zones between mitochondria and endoplasmic reticulum observed in sections of intact liver cells.

Adenosine Triphosphate↗
PubMed1994

Contribution of tyrosine kinases to the selective orientation of human CD4+ bifunctional cloned T cells toward proliferation or cytolytic function.

We show that T cell activation of human CD4+ cloned T cells through the CD2 molecule can induce either autocrine proliferation or cytolysis, depending on the pair of anti-CD2 mAbs used for stimulation, that is, D66/T11(1) or GT2/T11(1), respectively. As the earliest biochemical event after CD2 stimulation is likely the induction of tyrosine phosphorylation of various proteins, we investigated whether differential activation of protein tyrosine kinases (PTKs) could contribute to the selective induction of each function. Results show that herbimycin A, a potent PTK inhibitor, markedly decreased the induction of both proliferation and cytolysis. This implies a regulatory role for tyrosine phosphorylation in the induction of each function by CD2. However, that PTKs are differentially activated upon induction of proliferation by D66/T11(1) or cytotoxic function by GT2/T11(1) emanated from two different approaches. First, immunoblotting total cellular extracts with an anti-phosphotyrosine mAb showed different patterns of tyrosine phosphorylation depending on the pair of CD2 mAbs used for stimulation. Second, a differential activation of p56lck, a src-related PTK, was observed after stimulation with D66/T11, and GT2/T11(1). Although induction of proliferation by D66/T11(1) was correlated with increased Lck activity, this was not observed when cells were triggered to lyse by GT2/T11(1). Thus, by providing striking correlative evidences linking differences in PTK activation with induction of different functions in bifunctional cloned T cells, our results strongly suggest that PTKs may contribute to the selective orientation of T cell functions at a single-cell level.

Antibodies, Monoclonal↗
PubMed1994

Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA87). French Group on Therapy for Adult Acute Lymphoblastic Leukemia.

The aim of the multicentric trial LALA87 was to test the efficacy of different postremission therapies in adults (15 to 60 year olds) with acute lymphoblastic leukemia (ALL). An immunologic subclassification based on surface marker expression was proposed. Among the 562 tested patients, 511 were assigned either to the B lineage (361 cases, 63%) or to the T lineage (150 cases, 26%). T-ALL were significantly associated with male sex, age less than 35 years, mediastinal mass, central nervous system involvement, high white blood cell count, and low anemia. In a univariate and multivariate analysis, T-cell leukemia had a more favorable outcome than B-cell leukemia with respective median disease-free survivals (DFSs) of 28 and 14 months (P < .005). However, the type of postremission therapy modifies the value of the immunophenotype prognostic factor. In the chemotherapy arm, T-ALL patients (26 patients) had a more favorable outcome than B-ALL patients (57 patients) (P < .003). In the autologous bone marrow transplantation (ABMT) arm, the apparent better outcome of T-ALL patients (35 T/50 B) did not reach statistical significance (P = .2) and there was no difference in the allogeneic bone marrow transplantation (alloBMT) arm (37 T/71 B: P = .9). In the B-cell-lineage leukemias, subclassification by stages and myeloid antigen coexpression (10%) were not associated with different prognosis. CD10+ T-ALL (31 patients) were associated with a better DFS compared with the CD10- T-ALL (73 patients) with respective median DFS, not reached and 18.5 months (P = .04).

Adult↗
PubMed1994

Engagement of the CD45 molecule induces homotypic adhesion of human thymocytes through a LFA-1/ICAM-3-dependent pathway.

Cell-cell interactions play a central role during differentiation and development of the immune system. T or B lymphocyte homotypic adhesions can be induced via several surface molecules which, in some cases, are known to trigger the LFA-1/ICAM-1 adhesion pathway. We show here that mAbs reacting with the CD45 common epitopes or restricted RO epitope lead to a strong and rapid aggregation of all human thymocytes, and of T cell lines with an immature phenotype, but not of peripheral T lymphocytes. Aggregation requires energy, a physiologic temperature, Mg2+ divalent cations, and an intact cytoskeleton. It is LFA-1 dependent because CD11a and CD18 mAbs inhibit homotypic aggregation, whereas CD11b and CD11c mAbs do not. Homotypic thymocyte adhesion, however, is not decreased by CD54 mAb (anti-ICAM-1) but is inhibited by CDw50 mAb (anti-ICAM-3). Soluble CD22 fails to induce thymocyte adhesion, suggesting that CD45-induced aggregation is triggered by another ligand. Finally, because inhibitions observed with mAbs against LFA-1 and ICAM-3 are only partial, it can be assumed that another adhesion pathway is involved in thymocyte adhesion. The adhesion event specific for thymocytes we describe here is likely to play an important role in T cell differentiation.

Antibodies, Monoclonal↗