Biomedical subjects
Publications and source records attributed to J L Binet.
The present nosography of lymphoproliferative disorders is continuously in progression. Until now, a number of data regarding cytomorphological, cytochemical, immunological and molecular biological findings demonstrated importance in diagnostic and prognostic evaluation.
Most CLL cases correspond to proliferation of a B-cell clone characterized by (1) low amounts of SmIg, (2) the presence of receptors for mouse red blood cells, (3) the presence of a 67-kd antigenic determinant recognized by CD5 monoclonal antibodies, also present in normal T cells, (4) the ability of these cells to differentiate in vitro, and (5) the ability at least for some clones to differentiate and secrete immunoglobulins in vivo. The normal counterpart to this B-cell clone corresponds to a small subpopulation of lymphocytes, present at the edge of the germinal center in human lymph nodes. Interestingly, this subpopulation appears to constitute a substantial part of the B-cell population in 20-week-old fetal lymph nodes and spleen. These results have induced most authors to assume that the CLL B lymphocyte corresponds to proliferation of an immature B-cell clone, arrested at an intermediate stage between pre-B cells and mature B cells. However, this hypothesis does not explain the high frequency with which hypogammaglobulinemia and autoimmune hemolytic anemia are found in B CLL. In this work, we discuss the possibility that the CLL B lymphocyte corresponds to proliferation of a B-cell line, whose counterpart in the mouse is the Ly1 B, Lyb5+ subpopulation.
We review here results obtained from the various treatment modalities that have been used in CLL patients: chemotherapy; radiotherapy; splenectomy; leukapheresis; monoclonal antibodies and other immunomodulating agents. We conclude that it is still unclear whether patients in stage A (good prognosis) should be treated; intermediate forms of the disease (stage B) should, in most cases, be treated, but a better treatment than chlorambucil has not emerged; results from the Cooperative Group on CLL of Société Française d'Hématologie indicate that significant progress in the therapy of the advanced stage (stage C) has been achieved with the introduction of the CHOP regimen, using low doses of adriamycin; radiotherapy, splenectomy and immunomodulators such as levamizol, interleukins or interferons, and possibly monoclonal antibodies, are now being actively tested; the results are not yet conclusive.
The efficacy of bone marrow transplant (BMT) T-cell depletion for the prevention of acute graft-versus-host disease (GVHD) has been demonstrated in animal models and in clinical studies. The importance of T-cell depletion has to be evaluated with standardized methods suitable for routine purposes. We report herein an in vitro mature T-cell depletion using a cocktail of three monoclonal antibodies (CD2, CD5, and CD7) and baby rabbit complement in 38 histocompatibility leucocyte antigen (HLA)-identical BMT with no more than grade II acute GVHD. The T-cell depletion was quantified using three prestandardized immunological methods: immunofluorescence (IF) analysis, SRBC-rosetting assay, and PHA proliferation assay. A mean of 97.5% IF-assessed T-cell depletion was achieved in the 38 BMT. The immediate IF analysis using three distinct sets of anti-T-cell monoclonal antibodies allowed us to detect a mean of 1.2% residual T cells. The SRBC-rosetting assay was not useful to quantify T-cell depletion because no residual SRBC-rosette-forming cells could be detected in every case. The results of a prestandardized PHA-induced proliferation assay gave a mean 96.7% inhibition of proliferation, and they were correlated with the IF results although the IF threshold of detection was higher. From these data we conclude that our in vitro T-cell-depletion procedure is reproducible and that standardized simple immunological methods such as immediate immunofluorescence analysis and PHA proliferation assay provide good tools to assess a T-cell depletion effective in the prevention of acute GVHD.
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Three new cases of systemic mycosis due to Trichosporon cutaneum are reported and compared with the 23 previous reports. Two patients had acute leukemia and one patient had a lymphoblastic lymphoma. Blood cultures in two patients and cerebrospinal fluid in the third patient were positive for T. cutaneum. Only one patient recovered after antimycotic therapy and concomitant remission of his leukemia. At autopsy, the two other patients showed widespread infection with T. cutaneum. The authors conclude that diagnosis and management of such infection in the immunosuppressed host are difficult and the prognosis is poor.
Using principles from the theory of mathematical morphology, a semiautomatic analysis of the size and shape of cell nuclei on tissue sections was carried out on a Leitz Texture Analysis System (Leitz-TAS). The four parameters proposed here are more discriminatory than conventional shape evaluation by the form factor (FF), which is based on the ratio of perimeter squared to area. The parameters quantified, respectively, nuclear elongation (ND), narrow (R1) and wide (R2) irregularities, and the distribution of R1 and R2 along the nuclear contour (ID). The properties of these parameters were tested nucleus-by-nucleus on 24 nuclear models. The methodology was then illustrated by a study of lymph node nuclei in non-Hodgkin's lymphoma (NHL). Prior to analysis, 45 lymphomas were classified into five categories of nuclear size and shape according to the International Working Formulation (IWF). Two hundred nuclei were measured on each lymph node section. Statistical interpretation was based upon an analysis of the nuclear surface area on sections and upon the mean values of R1, R2, and ND, the standard deviations of R1 and R2, and the percentage of cleaved nuclei detected by ID. The mean value of R2 discriminated best between the two sets of populations with regular and irregular nuclear contours, respectively. Parameters R1, ND, and ID permitted the distinction of certain NHL cases among populations with irregular nuclei. Nuclear invaginations decreased in depth as the nuclear area became greater. The median surface area was well correlated to the IWF, and the skewness coefficient (third statistical moment of the nuclear surface area distribution) was related to the number of nuclear size or shape subpopulations.
A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. In the light of these results, alfuzosin was selected for clinical evaluation.
In 18 chronic lymphocytic leukaemia (CLL) and 2 diffuse, well-differentiated lymphoma (DWDL) lymph node biopsies, morphometric results analysing nuclear area distribution curves by the skewness coefficient were compared to histological findings, clinical stage and survival. Lymphocytic proliferation was subclassified according to the number and the distribution of large lymphoid cells. All cases with a component of large lymphoid cells had a right deviation of the nuclear area distribution curve and a positive value of the skewness coefficient in contrast to those where lymphocytic proliferation was monomorphous. Good correlation was observed between histological findings, morphometric analysis and survival: most patients with a right deviation of nuclear area distribution curve and positive skewness coefficient are clinically stage C, or died within 2-44 months, in contrast to patients with a symmetric distribution of nuclear area curve who are clinically stage A or B and still alive. The results indicate that in CCL and DWDL the lymph node biopsy with quantitative analysis has prognostic significance.
The present study is concerned with clinical prognostic classifications of chronic lymphocytic leukemia derived from numerous statistics and multivariate survival analysis. We analyse the prognostic significance of some biological patterns: bone marrow histological studies, lymph node biopsies, size, structure and doubling time of blood lymphocytes, tumoral markers and karyotype analysis. The problem of the monoclonal clone origin is discussed: differentiation abnormality or proliferation of a physiological clone.
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In addition to the nuclear area and a form factor, four morphometric parameters of nuclear shape (ID, R1, R2 and ND), obtained by the application of the principles of mathematical morphology, were used to characterize the nuclear contours in non-Hodgkin's malignant lymphomas. The values for each parameter were determined in 58 cases of non-Hodgkin's lymphoma categorized according to the Kiel and National Cancer Institute classifications. Small-cell, mixed and large-cell lymphomas could be distinguished on the basis of the mean nuclear area. The shape parameters R1, R2 and ID were efficient discriminators of the large centrocytic (cleaved-cell) lymphomas. Neither size nor shape factors could distinguish between centroblastic and immunoblastic tumors. The good correlation between the morphometric findings and the histopathologic categories suggest that morphometry may provide a quantitative and objective method for grading lymphomas.
Therapeutic leukapheresis was performed in a patient with hairy cell leukaemia (100,000 WBC/mm3; 98 p. 100 hairy cells) without signs of hypersplenism. Twenty-five sessions were carried out in 12 weeks. A rapid and significant improvement was observed with the WBC falling to 25,000 WBC/mm3 with 70 p. 100 of hairy cells and the normalisation of the bone marrow biopsy. When these sessions were finished, splenectomy was performed in optimal conditions. This treatment would seem to be valuable in hairy cell leukaemia without severe hypersplenism. Long-term improvement may be hoped because hairy cells have a very short turnover rate.
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Using affinity-purified 125I-F(ab')2 anti-human C3, we have investigated the ability of various leukemic cells to activate complement. Lymphocytes from patients with chronic lymphocytic leukemia (CLL) activated the alternative pathway, but cells from patients with other forms of leukemia or normal lymphocytes did not do so. The amount of C3 deposited on the CLL cells was significantly higher in patients with organomegaly (i.e., splenomegaly and/or hepatomegaly). Activation of complement by CLL cells as assessed by C3 deposition on the membrane occurred both in vivo and in vitro and was not related to the N-acetylneuraminic acid content of the membrane.
The technical performances of the Coulter S+II counter was evaluated for lymphocyte counts and the data obtained were compared to those supplied by the ELT 800 analyzer to the results for manual and Hemalog D counting methods. We assessed accuracy of three types of information supplied by the S+II model in the following conditions: erythrocyte indices in anemia, white cell histograms in chronic myeloid leukemia, chronic lymphoid leukemia, acute leukemia and eosinophilia, and the reliability of the analyzer in showing the degree of thrombopenia and hyperthrombocytosis.
To illustrate some features of Jean Bernard's last book le sang et l'histoire we publish extracts from the work by Lucien Lévy-Bruhl entitled le surnaturel et la nature de la mentalité primitive, a page of drawings by Wifredo Lam, and a brief commentary on the place of Lucien Lévy-Bruhl in the French School of Sociology and on the significance of blood in the art of Wifredo Lam.
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