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Biomedical subjects

B David

Publications and source records attributed to B David.

At least 145 records · Page 8Linked to original sources

The Epstein-Barr virus-induced production of IgE by human B cells.

B cells, isolated from the blood of healthy individuals and patients allergic to pollen, produced IgE when exposed to the human B-cell polyclonal activator, Epstein-Barr virus (EBV) in vitro and placed in culture. Secreted IgM and IgE were measured using immunoenzymatic assays. No difference was seen between healthy donors and allergic patients in the amount of IgE (or IgM) secreted. Cells were placed in limiting dilution cultures in order to determine the frequency of cells producing IgE or IgM (total and pollen specific) on exposure to EBV. Again, no significant differences in EBV-driven, B-cell precursor frequencies (PF) were seen between normal and allergic individuals. EBV-driven B-cell PF for total IgM and IgE, and pollen-specific IgM and IgE secretion, were 1/450, 1/6500, 1/83,000, and less than 1 per 2,500,000, respectively, for cells from healthy donors, and 1/140, 1/4000, 1/56,000 and less than or equal to 1 per 2,000,000, respectively, for cells from allergic patients. We propose that the increased IgE levels seen in atopic individuals result solely from regulatory defects, rather than an increase in the frequency of B cells committed to the secretion of IgE.

Allergens↗

[Collection and freezing of blood stem cells in acute nonlymphoblastic leukemia].

Blood-derived hemopoietic stem cells were collected using a continuous (10 patients) or a semi-continuous flow separator (2 patients) in some patients with acute non-lymphocytic leukemia. For ten out of those patients, five to seven leukaphereses were performed during a short period (median = 11 days) of marrow recovery following severe aplasia induced by an intensive chemotherapy. The mean number of CFU-GM cells collected per leukapheresis and per patient respectively was 6.7 X 10(4)/kg and 38.5 X 10(4)/kg. This latter number was similar to that obtained during a marrow harvest performed for a bone marrow transplantation, suggesting that high numbers of hemopoietic stem cells can be collected from the peripheral blood in leukemic patients and used for autologous transplantation.

Acute Disease↗

Thermoinactivation of human IgE: antigenic and functional modifications.

The thermoinactivation kinetics of IgE were studied in experimental models revealing the antigenic properties and the basophil-sensitizing capacity of these immunoglobulins. A pool of human sera containing anti-Dactylis glomerata (Dg) IgE was heated from 5 min up to 4 hr at 56 degrees. The IgE antigenicity was tested by two polyclonal 125I-labelled anti-IgE antibodies; one anti-IgE was specific of the whole Fc epsilon region, while the other had a specificity restricted to the D epsilon 2 domain. Radioimmunoassays showed that the D epsilon 2 epitopes were more rapidly altered than the D epsilon 1 epitopes. The capacity of IgE to bind to basophil Fc epsilon receptors was assayed by passive sensitization experiments. Basophil sensitivity towards the Dg pollen extract was tested by histamine release experiments in the presence of this allergen. A progressive decrease in cell sensitivity was observed when IgE samples used for cell sensitization were heated for longer than 5 min. Thermoinactivation kinetics of IgE revealed an unexpected increase in the apparent quantity and biological activity of IgE heated for 5 min at 56 degrees. This fact could be due to auto-anti-IgE antibodies linked to the unheated IgE and which interfere with the biological activities of IgE and their quantification.

Basophils↗

Successful autologous transplantation with peripheral blood hemopoietic cells in a patient with acute leukemia.

One patient with acute nonlymphocytic leukemia (ANLL) in remission was given intensive chemotherapy (DAT regimen) as late intensification treatment. Seven leukaphereses were performed during the period of marrow recovery following aplasia induced by the DAT regimen. High numbers of nucleated cells (7.8 X 10(8)/kg) and granulocyte-macrophage precursors (9.5 X 10(4)/kg) were collected and then cryopreserved and stored in liquid nitrogen. When he relapsed, the patient was treated with etoposide (600 mg/m2), cyclophosphamide (120 mg/kg), and total body irradiation (1000 rad), followed by the transfusion of thawed autologous leukocytes. The time to reach 0.5 X 10(9) granulocytes/liter and 50 X 10(9) platelets/liter was 16 and 35 days, respectively. This observation demonstrates that circulating hemopoietic stem cells are capable of complete hemopoietic reconstitution after marrow-ablative therapy with supralethal doses of chemoradiotherapy.

Adolescent↗

[Intestinal decontamination in the neutropenic patient. Apropos of a prospective randomized study].

Sixty-five patients undergoing remission-induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to selective antimicrobial modulation of the intestinal flora (SAM) with trimethoprim-sulfamethoxazole, or total antibiotic decontamination (TAD) with gentamicin, vancomycin and colimycin. Digestive tract colonization with Streptococcus D was more prevalent in the SAM group (p less than 0.01); colonization with yeasts was more prevalent in the TAD group (p less than 0.001). However, there was no difference between the two groups as regards to clinically and microbiologically documented infections, septicemias and survival. Selective antimicrobial modulation with trimethoprim-sulfamethoxazole is as effective and cheaper than total antibiotic decontamination with gentamicin, vancomycin and colimycin.

Acute Disease↗

[Desensitization for 4 successive years using calcium phosphate-adsorbed pollen extracts: study of sera with RAST and PRIST immunoimprints].

The clinical study for four years running of desensitization treatment to adsorbed pollen calcium phosphate, prepared "at request" by Institut Pasteur, shows that these preparations produced particularly good results. The population of allergic subjects is divided into two categories as from first year of treatment: good responders and non responders. A study on the serums of these patients, in view of a different "immuno-imprint" in these two groups, has not yet been conclusive, whereas we were expecting much from this prognosis test, which would have given us better treatment information.

Adolescent↗

Relationship between patients' age, bone marrow karyotype, and outcome of induction therapy in acute myelogenous leukemia.

Bone marrow karyotypes were performed in 88 cases of adult acute myelogenous leukemia (AML) at diagnosis and classified NN (normal), AA (abnormal), and AN (mixture of normal and abnormal metaphases). A clear relationship was found between karyotype and complete remission (CR) rate: 58% CR in (NN + AN) cases; 14% CR in AA cases (P less than .009). This relationship was even stronger when only patients under 60 years of age were studied. Considering failures of induction treatment, no relationship was found between the NN/AN/AA classification and a drug resistance. In patients over 60, the worse prognosis could be explained by an inferior ability to tolerate intensive treatment.

Adolescent↗

Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features.

This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.

Acute Disease↗

Megakaryoblastic transformation of primary thrombocythemia.

The progression of primary thrombocythemia (PT) into acute leukemia was diagnosed in a 64-year-old man who was previously treated by hydroxyurea without alkylating agents or radioactive phosphorus. Such an event has only been reported in very rare cases. The blast cells had a lymphocytic morphology but were identified as promegakaryoblasts by the ultrastructural demonstration of platelet peroxidase. These data suggest that a megakaryoblastic transformation could occur in PT as had previously been reported in chronic granulocytic leukemia.

Aged↗

Relationship between specific circulating IgE, basophil cell-bound IgE and histamine release induced by purified allergens of Dermatophagoides farinae.

In this study we analysed the presence and proportions of IgE specific for Df 6 and Df 11, two purified allergens of Dermatophagoides farinae. The characterisation of serum IgE and cell-bound IgE for 3 D. farinae-sensitive patients were performed by CRIE, RAST and PRIST assays. Furthermore the basophils from these same patients were studied by histamine release assays in the presence of Df 6 and Df 11. All the individual patient's cell and serum IgE samples displayed the presence of IgE antibodies specific for Df 6 and Df 11, but the relative quantities of the IgE for these two specificities were characteristic of each patient. The ratios (Specific IgE for Df 11) : (Specific IgE for Df 6) (ratio 11 : 6) were similar in the serum and on the cells for an individual patient. As judged by histamine release assays, the basophil sensitivities towards Df 6 and Df 11 were very different from one atopic patient to another. Moreover cell sensitivities reflected the proportion of Df 6- and Df 11-specific IgE antibodies found in the serum and in the cell eluate.

Animals↗

Histamine and mast cell distribution in the gastrointestinal wall of the rat: comparison between germ-free and conventional rats.

The distributions of histamine and mast cells in the intestinal mucosa have been studied in conventional (CV) and germ-free (GF) rats. Both distributions do not appear to be uniform throughout the gastrointestinal tract. The presence of digestive microflora influences these distributions: more histamine and mucosal mast cells are present in the small intestine of CV than in GF rats. Paradoxically the opposite is observed in the large intestine. Differences in mast cell counts in the crypt area of the small intestine (higher in CV than in GF rats) confirm the role of microflora on crypt cell proliferation due to a mild chronic inflammation. In the large intestine, however, the microflora appears to have a more complex influence and could act indirectly on histamine turnover.

Animals↗

Purification and characterization of a major allergen from Dactylis glomerata pollen: the Ag Dg1.

We have isolated an allergen (Ag Dg1) from Dactylis glomerata pollen which is recognized by the serum of 95% of human patients sensitive to D. glomerata pollen, as has been shown by the nitrocellulose immunoprint technique. After two successive purifications by preparative isoelectric focusing (IEF), Dg1 was characterized as a single band in analytical agarose IEF with a pI of 5.9 and was found to display 3 bands by sodium dodecyl sulfate polyacrylamide gel with the respective molecular weights: 21,000, 31,000 and 33,000 daltons. The high recognition frequency by IgE antibodies of Dg1 in the sera of allergic patients and its ability to trigger histamine release from sensitized human basophils allow to consider that Ag Dg1 is the main major allergen extracted from D. glomerata pollen.

Allergens↗

Induction of a passive cutaneous anaphylaxis inhibitory factor in mice.

The administration of a purified protein from Dactylis glomerata pollen, named Dactylis inhibitory protein (DIP), to Balb/C mice results in the production of a heat-resistant seric factor that blocks the passive cutaneous anaphylaxis (PCA) reaction in rat skin. This PCA inhibitory factor (PCA-IF) was purified following different purification procedures and analyzed in sodium dodecyl sulfate polyacrylamide gel. Amongst the array of bands detected it was possible to ascribe the inhibitory activity to a protein band of 76,000 daltons but only when it was associated either with another protein band of 69,000 daltons (obtained after a one-step purification procedure) or two other protein bands of 55,000 and 26,000 daltons (obtained after a three-step purification procedure). The inhibitory activity of the PCA-IF is present at a low level in normal Balb/C mice sera and is enhanced after DIP treatment of the mice.

Animals↗

Waldenström's macroglobulinemia and peripheral neuropathy: deposition of M-component and kappa light chain in the endoneurium.

Some cases of peripheral neuropathy associated with benign IgM monoclonal gammopathy, or Waldenström's macroglobulinemia, are probably of autoimmune origin; in some cases, anti-IgM serum reacts with the myelin sheaths of peripheral nerves. However, mechanisms may differ in other cases. In one case of neuropathy with macroglobulinemia, we found deposits of IgM immunoglobulin in the endoneurium. On ultrastructural examination, the deposits had erased the basement membrane of some nerve fibers that showed damage of both myelin and axon.

Humans↗

[Hypermyelination in a case of peripheral neuropathy with benign IgM monoclonal gammopathy].

A 65 year-old man presented with a 8 months history of ataxia and weakness of the lower limbs. Acroparesthesias had been present for ten years in all four limbs. Serum protein electrophoresis showed a monoclonal IgM kappa spike. Bone marrow showed no increase in plasma cells. Motor conduction velocities were reduced. A biopsy from the right superficial peroneal nerve revealed several enlarged myelin sheaths in each fascicle on semi-thin sections. Under electron microscopy these large myelin sheaths were either regularly arrayed around the axon or formed several large additional loops. The outer lamellae of these abnormal myelin sheaths and of the additional loops were frequently widened. Other fibers showed a widening of some myelin lamellae (W.M.L.) with a myelin sheath of varying thickness, and these widened lamellae were frequently joined together. A direct immunopathological study could not be made. The widening of some myelin lamellae is present in most cases of peripheral neuropathy with IgM monoclonal gammopathy and a fixation of anti IgM serum on some myelin sheaths may be demonstrated by direct immunopathology. Hypermyelination has been reported in a few cases. In this patient hypermyelination was as developed as in typical cases of tomaculous neuropathy. An association in some myelin sheaths of hypermyelination and W.M.L. has been noted in serum induced myelin aberrations in peripheral nervous system cultures.

Aged↗