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Biomedical subjects

B Chatelain

Publications and source records attributed to B Chatelain.

At least 37 records · Page 2Linked to original sources
PubMed1994

Tolerance of sequential or simultaneous administration of IL-3 and G-CSF in improving peripheral blood stem cells harvesting following multi-agent chemotherapy: a pilot study.

A pilot study was devised to assess tolerance of combined administration of interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) given after chemotherapy to mobilize peripheral blood progenitors cells (PBPC). Eight patients with advanced malignancies received 1 week courses of both IL-3 and G-CSF in one of three schedules: simultaneous 7 days administration (3 patients), sequential administration (3 patients) or partial (3 days) overlap of the two growth factors (2 patients). IL-3 (7.5 micrograms/kg/day) and G-CSF (5 micrograms/kg/day for the simultaneous schedule and 12 micrograms/kg/day for the partial overlapping and sequential schedules) were administered subcutaneously. Side-effects during cytokine administration included WHO grade I-II fever in 6 of 8 patients, flu-like symptoms (including myalgias and arthralgias) in 4 of 8, WHO grade I-II headache in 2 of 8 and WHO grade II nausea and vomiting in 1 of 8. Overall, side-effects appeared similar during combined administration of IL-3 and G-CSF to those observed during administration of IL-3 alone. No fever was observed when G-CSF was administered alone. Two leukaphereses were performed following the treatment with cytokines. Only the seven patients who received cytokines following chemotherapy were analyzed for PBPC mobilization. The median collection of CFU-GM/kg per patient in the seven analyzed patients was 1.3 x 10(5) (range 5.7 x 10(2)-3.6 x 10(5)). In two patients, a second cycle of mobilization with either granulocyte macrophage-colony stimulating factor (GM-CSF) or G-CSF was administered to allow safe engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Fc alpha-receptor expression on the myelomonocytic cell line THP-1: comparison with human alveolar macrophages.

Immunoglobulin A (IgA) and alveolar macrophages are two important components of the immune system in the respiratory tract. Fc alpha-receptors (Fc alpha R) are present on neutrophils, eosinophils and a series of human mononuclear phagocytes, including monocytes, alveolar macrophages and leukaemia cell lines (U-937). In the present study, using idiotypes and anti-idiotypic antibodies, we report that THP-1 cells, a myelomonocytic cell line, constitutively express Fc alpha R and that all IgA preparations used bind the receptor. Of the stimuli used (phorbol myristate acetate, retinoic acid, calcitriol), only calcitriol can induce differentiation of THP-1 cells, as assessed by CD14 expression. The expression of Fc alpha R appears to be independent of cell differentiation, since calcitriol pretreatment has no effect on IgA-binding. Finally, My43, a monoclonal antibody recognizing the Fc alpha R on U-937 cells, does not bind to THP-1 cells or to human alveolar macrophages. In addition, preincubation of THP-1 cells or human alveolar macrophages with My43 does not diminish IgA-binding to these cells. Ribonucleic acid (RNA) encoding the Fc alpha R isolated from U-937 is expressed, although possibly at a lower level, in alveolar macrophages and THP-1 cells. In conclusion, Fc alpha R are constitutively expressed on THP-1 cells and share some characteristics with the Fc alpha R described in human alveolar macrophages. THP-1 cells, therefore, may represent a reasonable model for further investigation of the interaction of immunoglobulin A and tissue macrophages.

Base Sequence↗
PubMed1993

Blunted rise in intracellular calcium in CD4+ T cells in response to mitogen following autologous bone marrow transplantation.

Following autologous bone marrow transplantation (ABMT), both impaired T cell activation and defective production of the principal T cell growth factor, interleukin-2 (IL-2), has been observed. These processes are dependent on a rise of intracellular calcium ([Ca2+]i), a step which follows binding of T cell receptor (TCR) and transduction of signal via the generation of cytoplasmic second messengers. In order to better understand the nature of defective cellular immunity in ABMT, in the present study we investigated the rise of [Ca2+]i in T cells of recipients of ABMT. By concomitant labelling lymphocytes with anti-CD4 antibody and addition of fluo-3 as fluorescent calcium indicator, we have selected for the T cell subset which is the principal source of IL-2. Short-term (less than 1 year post-transplantation) recipients of ABMT show a statistically significant blunted rise in [Ca2+]i in response to concanavalin A as compared to normal controls not accounted for solely by a decreased percentage of CD4+ cells in these patients. The [Ca2+]i response of CD4+ cells from long-term (greater than 1 year post-transplant) recipients was lower than that of the normal group although not to a statistically significant level. These findings suggest that following ABMT is a defect in the early stages of T cell activation involving either T cell receptor binding or early signal transduction ultimately resulting in depressed transcription of IL-2 mRNA. These defects are analogous to findings in both allogeneic transplantation where factors of histoincompatibility and graft-versus-host disease (GVHD) come into play, as well as in the defective T cell activation of the normal ageing process.

Adolescent↗
PubMed1993

Hemostasis variables in type I diabetic patients without demonstrable vascular complications.

OBJECTIVE: To determine hemostasis variables in type I diabetic patients without clinically demonstrable micro- and macroangiopathy and to relate them to glycemic control. RESEARCH DESIGN AND METHODS: Fifty patients and 50 comparable control subjects were enrolled in this study. The patients were subdivided in two groups, according to their level of HbA1c (group 1, n = 30, HbA1c < or = 8%; group 2, n = 20, HbA1c > 8%). We determined the platelet count, the platelet aggregation in the spontaneous state and in the presence of ADP or collagen, beta-thromboglobulin, platelet factor 4, fibrinogen, von Willebrand factor (factors VIII:C, VIIIR:Ag, and VIIIR:VW), plasma and urinary fibrinopeptide A, euglobulin lysis time, anticoagulant proteins C and S, and plasma viscosity. RESULTS: All coagulation variables were significantly higher in diabetic patients compared with control subjects. Moreover, when the patients were subdivided according to their levels of HbA1c, the hemostatic disturbances appeared significantly more pronounced in the poorly controlled than in the well-controlled subjects. CONCLUSIONS: This study confirms the existence of a state of hypercoagulability in type I diabetes. This hypercoagulability may be related to poor glycemic control. Our study suggests that the hemostasis disturbances precede demonstrable vascular complications.

Adenosine Diphosphate↗
PubMed1992

Quality control in haemostasis.

Laboratory investigation of the haemostatic system deserves particular procedures in the quality control of analytical variables as well as preanalytical variables. This paper reviews the precautions that have to be taken in the blood prelevement, the transport of the tubes and the performance of the laboratory tests aimed to investigate the haemostatic system in order to obtain reliable results.

Blood Coagulation Tests↗
PubMed1992

Effects of escalating doses of recombinant human interleukin-2 in correcting functional T-cell defects following autologous bone marrow transplantation for lymphomas and solid tumors.

High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-unrestricted cytotoxicity in vitro, can be applied in vivo as immunotherapy to reduce these potential complications. Recombinant human IL-2 (rIL-2) was administered by continuous i.v. infusion for four courses in 19 patients following ABMT for lymphomas and solid tumors. The patients were assigned to five groups of escalating doses of rIL-2 ranging from 3 to 30 x 10(6) IU/m2/day. The immunological effects and toxicity were monitored. After a transient reduction of lymphocytes in the peripheral blood, a significant lymphocytosis was observed during the rIL-2 infusion with an augmentation of CD2+, CD25+, and CD8(+)-Ia+ T cells and a dose-related increase of CD56+ lymphocytes. Natural killer (NK) activity appeared enhanced in patients treated with as little as 6 x 10(6) IU/m2/day. No statistically significant increase in lymphokine-activated killer (LAK) activity was seen after rIL-2, when compared to LAK activity following ABMT prior to rIL-2 administration. Administration of exogenous rIL-2 to patients who have undergone ablative chemotherapy and ABMT has a role in restoring defective T-cell function. Further trials defining those patients most likely to benefit from rIL-2 integrated with ablative chemotherapy and ABMT are now warranted.

Adult↗
PubMed1992

[The value of flow cytometry in the prognosis and treatment of head-and-neck cancers. Preliminary studies].

There is no reliable method to determine the malignancy degree of a tumour. Histology is not accurate. TNM classification is very interesting for planning surgical technique but gives little information about cancer aggressiveness. Flow-cytometry is a new technique to measure nuclear DNA quantity with great reproducibility and sensitivity. A normal cell is diploid (2N chromosome) and a tumoral one aneuploid. DNA quantitation is possible on fresh as well as on histological samples stored in formaldehyde or paraffin. Aneuploidy reflects the cancer aggressiveness. Aneuploidy is also correlated with TNM classification. Aneuploid tumors could require a more "aggressive" treatment regardless their size.

DNA, Neoplasm↗
PubMed1991

Immune response after collagen injection for laryngeal rehabilitation: development of an enzyme-linked immunosorbent assay.

The appearance of circulating antibodies directed against bovine collagen has been observed in dermatology after collagen injections with or without clinical reactions. Knowing the serologically positive patients among the clinically negatives ones is important if a second collagen injection should be planned. In these cases, skin and blood tests have to be carefully checked to confirm reactivity. In connection with this, we have developed an enzyme-linked immunosorbent assay (ELISA) for determining the response to GAX collagen injections. Such injections induce a very low rate of anti-collagen antibodies. However, without having recourse to a positive control permitting statistical analysis of data, no conclusions can be made about significant positivity. In the present investigation of 12 patients following GAX collagen injections into the larynx, 1 was found to be borderline and 1 positive (17%). The positive control was made up with 20 ng/ml anti-type III collagen antibodies, which was purified and tested against type III bovine and human collagen. The present study showed that the systematic detection of antinuclear or anti-DNA antibodies after GAX collagen injection is not useful. However, the anti-collagen positivity of two control samples from 3 patients already positive for antinuclear antibodies demonstrates that bovine collagen injections are contraindicated in auto-immune disease.

Adolescent↗
PubMed1990

Interleukin-2 after autologous bone marrow transplantation as consolidative immunotherapy against minimal residual disease.

Recipients of autologous BMT demonstrate clinically significant immune deficiency, particularly involving the T lymphocytes. While quantitatively the immune system generally returns to normal during the first 3 months, there is a prolonged delay in the recovery of qualitative immune functions. T cell proliferation is impaired immediately after transplantation and slowly recovers over a period of more than 1 year. In addition, a defect has been documented in IL-2 producing cells and may be of major importance in the pathophysiology of this immunodeficiency. However, post-ABMT, PHA-stimulated T cells are TAC+ and are able to respond to exogenous IL-2 in vitro. Very early after ABMT, NK and LAK activities of PBMC normalize but are significantly increased in vitro by IL-2. On this basis, a clinical assessment of rIL-2 administration on the immunological reconstitution of ABMT patients and as consolidation immunotherapy against minimal disease has been initiated in a phase I/II study.

Bone Marrow Transplantation↗
PubMed1989

Surface IgA and Fc-alpha receptors on human alveolar macrophages from normal subjects and from patients with sarcoidosis.

Human alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) were found to bear cytophilic IgA and Fc alpha-receptors (Fc alpha R) on their surface. The cytophilic IgA belongs to the IgA1 subclass, but unoccupied receptors can be saturated with either IgA1 or IgA2 molecules. Although both polymeric and monomeric forms could attach, binding was about 5-fold greater for the polymers. Both cytophilic IgA and Fc alpha R are sensitive to trypsin and disappear after 18 h of AM culture. An increase in cytophilic IgA was observed on AM from untreated patients with pulmonary sarcoidosis, but not on AM from steroid-treated patients. A significant correlation was found between IgA levels in BAL and the percentage of AM with cytophilic IgA in normal subjects and in steroid-treated sarcoid patients. However, no such relationship was seen among untreated patients. These data suggest that multiple factors may modulate AM surface receptors for IgA. Inflammatory events occurring in the lungs could alter receptor expression and perhaps be of significance in the immunophysiopathology of certain pulmonary diseases.

Binding, Competitive↗
PubMed1988

Antiproteases are increased in bronchoalveolar lavage in interstitial lung disease.

The present study evaluates different cellular and soluble components in the bronchoalveolar lavage (BAL) from patients with interstitial lung disease. We observed an increased T4/T8 lymphocyte ratio in BAL but not in blood from 24 patients with active pulmonary sarcoidosis compared to sixteen normal individuals and to eleven patients with inactive pulmonary sarcoidosis. Seven patients with hypersensitivity pneumonitis had a normal T4/T8 ratio. In the active sarcoidosis and hypersensitivity pneumonitis groups, alpha 1-Protease Inhibitor (alpha 1 PI) in BAL is significantly higher than in the normal group and a significant correlation between the two antiproteases (alpha 2-macroglobulin and alpha 1 PI) is observed. These data demonstrate that antiprotease levels (alpha 1 PI and alpha 2 M) are increased in the lower respiratory tract of patients with interstitial lung disease and that among cellular and soluble components of BAL, alpha 2 M represents a sensitive marker of the alveolitis.

Alveolitis, Extrinsic Allergic↗
PubMed1987

IgA-induced chemokinesis of human polymorphonuclear neutrophils: requirement of their Fc-alpha receptor.

The influence of purified human immunoglobulins on the migration of human neutrophils (PMN) was measured in a 48-well micro chemotaxis chamber, with results expressed as percentages of maximal formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated chemotaxis. Both monomeric and polymeric IgA, of both subclasses, in monoclonal and polyclonal form, as well as secretory IgA and Fc-alpha, but not Fab-alpha fragments, enhanced PMN migration when present either in the lower or in both compartments of the chamber (chemokinesis) at concns as low as 0.1 mg/ml. IgM and IgE had no such effect. In contrast, IgG was chemotactic at low concn (0.1 mg/ml). Both monomeric and polymeric IgA decreased the maximally induced FMLP-chemotaxis, but IgA increased chemotaxis induced by suboptimal levels of FMLP. Binding of 3[H]-FMLP to PMN was not affected. Cytofluorographic analysis revealed that, under the conditions of the assay, IgA did bind to 93% of PMN. Thus, the various forms of IgA have a dual effect on human PMN mobility: (1) increase PMN random migration (chemokinesis); and (2) decrease the maximal FMLP-induced chemotaxis. Our data support the requirement of binding of IgA to the Fc-alpha receptor of PMN for expression of these activities. This effect of IgA on PMN mobility may be relevant in IgA deficiency states.

Antibodies, Monoclonal↗
PubMed1984

[Indications and results of coronary surgery in patients aged 70 or more].

Among 400 consecutive patients who underwent coronary bypass performed by the same surgical team, 20 (5%) were aged 70 or more (mean: 71.52 years). This group represented one-third of coronary arteriographies carried out at that age. Most patients had stage III or IV coronary disease. All were seriously invalidated but in good general condition without systemic disease or dangerous arterial lesions. Coronary arteriography showed highly surgical lesions in all 20 cases, with 3-vessel lesions in 45% and tight stenosis of the main vessel in 25%. Ventricular function was generally normal. The average number of bypasses per patient (1.65) was distinctly lower than in younger subjects. The results obtained were most encouraging, with no death and no myocardial infarction either postoperatively or during a mean follow-up period of 2.5 years. Only 2 patients had residual angina. Compared with operated patients under 70, this group was characterized by a longer duration of the disease prior to surgery and by a higher percentage of severe clinical stages and life-threatening and highly surgical lesions. Post-operative and medium-term results were also distinctly better, probably because of stricter selection for surgery. All this has been confirmed in several North American publications which also report excellent results in patients over 70 years of age. To conclude, there are excellent reasons for performing coronary bypass in these elderly patients and age should not preclude pre-surgical arteriography, especially when the patient is seriously invalidated and when his general condition is sufficiently good to tolerate cardiopulmonary bypass.

Aged↗