Biomedical subjects
Publications and source records attributed to B David.
A large phytochemical survey of the flora of the Malaysian Peninsula and Sabah is described, covering the systematic search for alkaloids, and partly, for saponins and flavonoids. Details of some chemical studies are reported. This emphasizes the great interest of such a study.
The aim of the study was to determine the effect of cetirizine, a new potent H1 antihistamine, on acute cutaneous inflammatory response and eosinophil accumulation induced in vivo by platelet-activating-factor (PAF-acether) and allergen. In a double-blind, crossover study, seven subjects allergic to grass pollen and three nonallergic control subjects received orally either cetirizine, 20 mg/day, or placebo for 4 days. On day 4, the subjects were skin tested with grass pollen and PAF-acether (400 and 40 ng per site). After the challenge, an evaluation of time-course cutaneous eosinophil infiltrations by a skin window technique was performed. Cetirizine pretreatment reduced skin wheal and erythema elicited by allergen and PAF, 400 and 40 ng, by 74.6% (p less than 0.001), 53.9% (p less than 0.001), and 47% (p less than 0.01), respectively. Skin reactivity induced by PAF-acether was also significantly reduced by cetirizine in nonallergic subjects. Cetirizine reduced at hour 24 eosinophil infiltrations induced by allergen and PAF, 400 and 40 ng, by 63% (p less than 0.001), 58.5% (p less than 0.001), and 57.8% (p less than 0.01), respectively. This inhibitory effect of cetirizine on allergen and PAF-induced eosinophil infiltration was already effective 2 hours after the challenge. PAF induced a nonsignificant eosinophil influx in all nonallergic subjects. In conclusion, cetirizine inhibited both the immediate cutaneous response and the eosinophil influx induced by allergen and by a potent eosinophil chemotactic factor, such as PAF-acether. Therefore, cetirizine, besides its anti-H1 effect, has the potential to modulate the allergic inflammatory response.
Alternaria allergens, separated by SDS polyacrylamide gel electrophoresis and transferred onto a nitrocellulose membrane, were identified using sera from Alternaria-allergic patients. 30 Alternaria components of spore and mycelium, ranging in molecular weight from more than 150 to 12 kD, bound IgE antibodies. 15 were detected by more than 25% of the sera and only 4 (85, 56, 42, 31 kD) by more than 50% of the sera. Among these four major allergens, the 56-kD component was present mostly in the spore extract, the 85- and 42-kD fractions in the mycelium extract and the 31-kD in both extracts. The 31-kD component showed the highest IgE binding and the highest frequency of binding (95% with mycelium extract and 79% with spore extract). It was composed of two subunits.
Between April and December, 1982, a multicentre pilot study was conducted in 45 patients aged from 16 to 73 years suffering from acute lymphoblastic leukaemia to test the feasibility of an intensive and short induction phase followed by an early consolidation phase. All patients received a 5-day course of induction chemotherapy with prednisone, vincristine, AraC and rubidazone, then a "triple A regimen" for consolidation, consisting of adriamycin, AraC and asparaginase. The complete remission rate was 73 per cent. Toxicity during induction was characterized by frequent infections, but the consolidation treatment was well tolerated. Thus, the sequence intensive induction-early consolidation proved feasible and acceptable. In terms of survival, 8 out of the 33 patients in remission are still alive and well after more than 4 1/2 years.
FPLC purification of mouse monoclonal anti-human IgE antibody xb6-16 showed 2 major peaks of different molecular weight, peak 1 (greater than 10(6) d) and peak 3 (1.6 x 10(5) d). Peak 1 consisted of IgG1 and IgM, peak 3 of IgG1 only. On a protein weight basis, peak 1 was 100 times more potent than peak 3 in inducing histamine release from human basophils. Preincubation of peak 3 with anti-IgG1 enhanced the mediator release triggered by this fraction. On this basis, the potentiating effect of aggregated IgG1 or IgG1-IgM complexes on mediator release from basophils is discussed.
The study of the relationship between the guanine content and Dermatophagoides pteronyssinus (Dp) allergens in house dust samples is reported. Mattress and carpet dust of bedrooms from 22 different homes constituted the house dust samples. The guanine content was determined by quantitative measurements and the mite allergenicity by two immunochemical assays with a partially purified extract of Dp as internal reference: RAST inhibition and crossed and rocket line immunoelectrophoresis. A large scale range of guanine content was obtained among the 22 house dust samples studied (0.01 to 1.78 mg/0.1 gm of dust). Data of RAST inhibition, analyzed according to parallel line bioassay, demonstrated no significant difference between the slopes of the reference and the house dust sample lines, but a 100-fold variation in the relative Dp potencies was observed. By crossed and rocket line immunoelectrophoresis technique, the presence and the amounts of major Dp allergens (Der p I and Dp 4) were established in most house dust extracts. A significant correlation was found between the guanine content of the house dust samples and their relative Dp potencies (r = 0.86) on the one hand, and with their relative content of Der p I and Dp 4, two major Dp allergens (r = 0.75 and r = 0.74, respectively) on the other hand; in each case, a quantitative relationship was established. These results suggest that the guanine determination could assess mite allergens in house dust and may be a useful tool in large-scale investigations of house dust.
Eighty-five adult patients under the age of 50 years with acute myeloid leukaemia (AML) were entered into a prospective controlled study conducted to compare the effectiveness of allogeneic or autologous bone marrow transplantation and intensive chemotherapy for patients in first complete remission. Sixty-one patients (72%) achieved complete remission then received a consolidation treatment. After consolidation, 58 patients who were still in remission were assigned to three different therapeutic modalities. Fifty-two patients were evaluable: 20 patients who had an HLA-identical sibling donor underwent allogeneic bone marrow transplantation within 3 months after achievement of complete remission; the other 32 patients were randomized to receive autologous bone marrow transplantation or intensive sequential chemotherapy. The actuarial risk of relapse at 3 years was 18% for the allogeneic patients, 50% for the autologous patients and 83% in the chemotherapy group. The difference was highly significant (P less than 0.0002). The disease-free survival was respectively 66% (95% confidence interval 41-85%), 41% (95% confidence interval 16-66%) and 16% (95% confidence interval 0-31%) (P less than 0.004). We conclude that allogeneic bone marrow transplantation is presently the best therapeutic approach for patients with AML in first complete remission.
In this preliminary report, we describe our inability to induce IgE antibody to a well-characterized bacterial component, the membrane proteoglycan of Klebsiella pneumoniae and its major protein fraction FIII-B in BALB/c mice. In contrast, an immunomodulatory effect of membrane proteoglycan of K. pneumoniae on the IgE and IgG antibody responses to ovalbumin could be demonstrated.
Water-soluble grass pollen extracts (Dactylis glomerata) were separated by isoelectric focusing in a wide pH range (2-11) in agarose gel. After focusing, two successive gel prints were taken. The first one, on an ordinary nitrocellulose filter during 10 s, enabled the visualization of separated components of the pollen, after india ink staining. The second one, on a cyanogen bromide-activated nitrocellulose filter obtained after a 10-min transfer and saturation step, was incubated overnight with patient sera, and the specific antibodies bound to antigens or allergens were detected. The screening of different patient sera showed great variability in the antigen spectra. There was no obvious relationships between IgM and IgA antigen spectra as compared to IgE. Some association between IgE and IgG4 subclass was observed.
Transient thrombocytopenia may occur in infants born to mothers with idiopathic thrombocytopenic purpura, suggesting transplacental passage of the antiplatelet factor. Labor in women with idiopathic thrombocytopenic purpura calls for a special management. Irrespective of the maternal platelet count, we believe that labor should be conducted vaginally but reassessed after a thrombocyte count of fetal scalp blood. Maternal thrombocytopenia, which may indicate a possible risk of coagulopathy, should be treated aggressively and followed up with replacement therapy. Percutaneous umbilical sampling is to be avoided because it carries an immediate risk of fetal and maternal complications. A count of 50,000/mm3, obtained early during the course of labor, may be taken as a threshold indicator for abdominal delivery via cesarean section.
This article reports 18 cases of acute nonlymphocytic leukemia (ANLL) and abnormal chromosome 16. Thirteen had the same hematological pattern at diagnosis, i.e., peripheral blood hyperleukocytosis with high percentage of monocytes and blast cells, and bone marrow showing three different cell populations: (a) myeloblasts, (b) monocytes and promonocytes, and (c) abnormal eosinophils. In these cases the diagnosis was acute myelomonocytic leukemia with bone marrow eosinophilia, as described. However three other cases were of the M5 type and two others of the M2 type, all showing an abnormal eosinophilia in their bone marrow. All cases showed an abnormal chromosome 16 in the bone marrow cells: inv (16) in 13 cases, t (16;16) in two, del (16) in one of poor quality, and in two other translocations involving band 16q22. In one case the inv (16) was found in a subclone, indicating that it could be a secondary cytogenetic defect. Five patients died soon after diagnosis; the other 13 had a median complete remission duration of 8 months. The central nervous system was frequently involved upon relapse. We do not support the hypothesis that patients with M4-Eo ANLL and chromosome 16 abnormality have a favorable prognosis.
The use of mAb allowed us to further analyze the cross-reactivity between purified Dac g I and Lol p I, the major allergens of Dactylis glomerata (cocksfoot) and Lolium perenne (Rye grass), respectively. It was first shown, using IEF, followed by immunoprinting, that serum IgE antibodies from most grass-sensitive patients recognize both Dac g I and Lol p I. Second, three different anti-Lol p I mAb, 290A-167, 348A-6, and 539A-6, and one anti-Dac g I mAb, P3B2 were all shown to react with Dac g I and Lol p I, indicating that the two molecules share common epitopes. Epitope specificity of the mAb was determined by competitive binding inhibition of a given labeled mAb to solid phase fixed Dac g I or Lol p I by the mAb. The results indicated that the four mAb are directed against four different and non-overlapping epitopes present on both allergens. Using double-binding RIA, our data strongly suggest that the common epitopes are not repetitive on both molecules. In addition to their similar physicochemical characteristics, such as isolectric points and m.w., Dac g I and Lol p I share four identical epitopes. Binding inhibition of human IgE to Lol p I and Dac g I by the mAb was also assessed. The results indicated that each mAb was able to inhibit such reactions to variable degree but no additive inhibition was observed when two mAb of different specificities were used in combination, suggesting that the human IgE binding site is partially shared by each epitope recognized by the four mAb.
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Six patients with acute non-lymphocytic leukemia underwent autologous transplantation of circulating stem cells collected during remission. They were given cyclophosphamide (120 mg/kg) and total body irradiation (1,000-1,200 rads) (five patients) or busulfan (16 mg/kg) and melphalan (140 mg/m2) before the transfusion of 6.7 X 10(8) nucleated cells/kg corresponding to 19.7 X 10(4) CFU-GM/kg. Granulopoietic engraftment was observed in every case and was influenced by the number of CFU-GM injected. Megakaryocytic recovery was obtained in four cases.
A synthetic dipeptide, magnesium salt of N-acetyl-L-aspartyl-glutamic acid (NAAGA) identical to a natural dipeptide found as traces in cerebral tissues of mammalian brains, was shown to inhibit, in vitro, the hemolytic activity of both classical and alternate pathways complement; the required concentration of NAAGA was 2 to 10 mM. Cross immuno electrophoretic analysis demonstrated an inhibition of C3 cleavage by both classical and alternate pathway C3 convertases with 24 mM NAAGA. As expected, if C3 convertases were really the target of inhibition, the release of highly inflammatory C3a, C5a fragments scored by R.I.A. was impaired when complement was incubated with activators of classical and alternate pathways. Such a low molecular weight dipeptide, quite atoxic and inhibiting the complement dependent cytotoxicity and release of phlogistic by-products could be interesting for pharmacological manipulation of complement activation in inflammatory processes.
We investigated the proliferative response of lymphocytes from mite-sensitive patients (RAST D.far greater than 3.5 PRU/ml) in the presence of the major allergen Der.f.I purified from Dermatophagoides farinae. Comparative studies were carried out with peripheral blood mononuclear cells from non-atopic donors (RAST = 0), and from patients undergoing hyposensitization treatment (5 to 24 months). According to Student's t-test, there was no significant difference in the Der.f.I-induced proliferation of peripheral blood mononuclear cells from normal donors, untreated atopic patients and hyposensitized patients. In conclusion, it was impossible to discriminate between normal donors, atopic patients and hyposensitized patients with regard to their circulating lymphocyte responses to the purified major allergen Der.f.I.
This study was designed to analyse further the idiotypic cross-reactivity between anti-Lol p I murine monoclonal antibodies of IgG isotype and basophil-bound human IgE antibodies from grass pollen-sensitive patients. It was also designed to determine the expression frequency of the idiotypes present on cell-bound IgE. Rabbit anti-idiotypic antisera were produced against idiotypes of three anti-Lol p I monoclonal antibodies (290A-167, 539A-6 and 348A-6) of different specificities. Basophils from 19 patients reacting to Lol p I allergen, as shown by positive skin test reactions and by the presence of serum-specific IgE antibodies (measured by RAST), were challenged with these rabbit anti-idiotypic antibodies and the histamine released was measured. Our data indicate that IgE-borne idiotypes were expressed as follows: (i) co-expression of the three idiotypes in 15% of patients; (ii) co-expression of two idiotypes in 21% of patients; and (iii) expression of a unique idiotype (290A-167) in 42% of patients. Among the three idiotypes, 290A-167 was shown to be a public idiotype since it was expressed in 80% of patients. Fab fragments of anti-idiotypic antibodies could inhibit anti-idiotype-induced histamine release, but optimal conditions varied from one patient to another.
A new regimen of chemotherapy was used to reduce toxicity of EBVP I: the number of injections and the doses of bleomycin and vinblastine were reduced by half, the duration of treatment by third. Fifty patients with Hodgkin's disease stage I to IIIA, previously untreated, received three courses of this regimen before radiotherapy. Gastro-intestinal toxicity was similar and alopecia was more marked than with EBVP I. Immediate efficacy is similar, with 90% of complete remission and only one failure. This regimen is shorter and more intensive than EBVP I. It deserves larger comparison with previously used chemotherapy in a more extensive controlled trial.