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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 343 records · Page 19Linked to original sources

T-helper phenotype chronic lymphocytic leukemia (Thp-CLL): characterization of an Italian case with particular biological findings.

A patient with Chronic Lymphocytic Leukemia (CLL) characterized by an expansion of helper phenotype mature T lymphocytes is here described. The phenotype of these cells was OKT3+, OKT4+, Leu 9+, 5/9+, OKT8-, Tac- and functional studies showed a strong helper activity on B cell differentiation; an "in vivo" presence of an IgG-lambda paraproteinaemia has been demonstrated. Cytogenetic studies showed multiple clonal, numerical and structural rearrangements which included a tandem t(14;14) (q11;32) translocation. Hybridization showed HTLV I related specific bands indicating the presence of exogenous sequences related to prototype virus but derived from a different Retrovirus (HTLV 1c). The clinical course was aggressive and unsuccessful treatments with various polichemotherapeutic protocols, associated with multiple leukaphereses, were performed. The authors underline that despite the morphological, immunological, biological and virological heterogeneity, the common feature of T-helper CLL is the inexorable clinical course which needs a new therapeutic approach.

Antibodies, Viral↗

Blood and spleen haematopoiesis in patients with myelofibrosis.

Blood nucleated cells collected by leukapheresis and spleen cell suspension from patients with myelofibrosis with myeloid metaplasia (MMM) were studied for their haematopoietic capacity. Using committed progenitor cell assays (CFU-GM, BFU-e) and a one-stage long-term liquid stem cell system, we have shown: (1) a preferential expansion of the circulating committed progenitor cell pool above the more primitive stem cell compartment; (2) the absence of any development of a stromal adherent layer in long-term cultures of peripheral blood nucleated cells suggesting the self-sustaining capacity of the circulating primitive stem cells; (3) that the spleen is only a production site of committed progenitor cells but does not generate primitive stem cells; (4) the presence, in the spleen, of stromal progenitor cells. We conclude that the peripheral blood primitive stem cells in patients with MMM are not of splenic origin.

Cells, Cultured↗

Basidiomycete allergy: measurement of spore-specific IgE antibodies.

RAST with 12 basidiospore extracts demonstrated that a significant percent of 42 individuals with symptoms of perennial rhinitis and/or asthma and skin reactivity to at least one spore extract had spore-specific IgE antibodies. These antibodies were not demonstrable in 14 atopic, symptomatic, skin test negative control subjects nor in five nonatopic, asymptomatic control subjects. There was a statistically significant association between RAST and skin test results for all but three of the spore extracts. A statistically significant association was also observed between RAST results obtained with most of the different spore extracts. A similar association was present for skin test results with different spore extracts. These results provide evidence that basidiospore extracts are suitable allergens for use in diagnostic studies of respiratory disease associated with exposure to basidiomycetes.

Adult↗

Bronchial asthma. Mechanisms and management of a complex obstructive airway disease.

Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy.

Adrenal Cortex Hormones↗

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro.

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord-blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.

Adolescent↗

Preferential differentiation of murine CFU-S toward granulopoiesis and megakaryocytopoiesis after in vitro incubation of bone marrow with ASTA-Z 7557.

We investigated the in vitro effect of ASTA-Z 7557 on the qualitative aspects of murine CFU-S differentiation, as assessed by the histological nature of day-9 colonies generated in the spleen of irradiated mice by bone marrow exposed to the drug at concentrations ranging from 0 to 150 micrograms/ml. The proportion of erythrocytic colonies declined linearly with the logarithm of the dose (a 22% decrease per log), whereas the granulocytic and megakaryocytic colony proportions increased linearly (a 10% increase per log for both cell lineages). This suggests a preferential channeling of CFU-S differentiation toward granulopoietic and megakaryocytic cell lineages as a consequence of the in vitro chemotherapy, and supports the hypothesis that some alteration of the qualitative potential of CFU-S to differentiate after in vitro purging of bone marrow with ASTA-Z 7557 takes place prior to autologous bone marrow transplantation.

Animals↗

CALLA-negative, TdT- and CD7-positive acute lymphoblastic leukemia: a phenotype associated with poor prognosis.

Eight ALL patients displaying a CD7+, Tdt+, CD10-, T MoAbs-, myeloid MoAbs-, AP+ phenotype are described. Some patients showed well-known risk factors such as cytogenetic abnormalities, high WBC count, mediastinal mass, and/or organomegalies. The clinical behaviour was very poor and only one patient is in CR and off therapy. Therefore such a pre-T phenotype, although sometimes associated with the other risk factors, could be considered a poor prognosis phenotype.

Adolescent↗

Difference in kinetics of hematopoietic reconstitution between ALL and ANLL after autologous bone marrow transplantation with marrow treated in vitro with mafosfamide (ASTA Z 7557).

The kinetics of hematopoietic recovery after autologous bone marrow transplantation (ABMT) reflect the hematopoietic capacity of the infused marrow. In vitro treatment of marrow with high doses of mafosfamide (ASTA Z 7557) alters the hematopoietic regenerative capacity of the graft. Thirty-two patients with acute leukemia (12 acute lymphoblastic leukemia (ALL) and 20 acute non-lymphoblastic leukemia (ANLL] with 27 in complete remission and five in partial remission were consolidated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (10 Gy), followed by reinfusion of autologous marrow treated in vitro with mafosfamide. The marrow of each patient had been incubated with the highest tolerable dose of mafosfamide, individually predetermined from a preincubation test. We report here that the kinetics of engraftment are strikingly different in ANLL and ALL patients. In the ANLL group recovery to 0.1% reticulocytes took a median of 20.5 days (range 14-32) versus 15 (11-28) in the ALL group; 33.5 days (18-45) versus 19 (15-30) for leukocytes to reach 1.0 x 10(9)/l; 35 (19-60) versus 20.5 (15-30) for neutrophils to reach 0.5 x 10(9)/l; 110+ (45-480+) versus 50 (23-90) for platelets to reach 50 x 10(9)/l (p less than 0.01 and p less than 0.05). Detection of granulocyte-macrophage progenitors (CFU-GM) regeneration in marrow aspirates post-ABMT was delayed in ANLL (p less than 0.05). Neither the nature of the previous induction therapy, nor the status of the blood or bone marrow at the time of collection (CFU-GM and erythroid burst-forming units/ml) nor the stem cell sensitivity to mafosfamide, nor the doses of progenitor cells infused could explain these differences. We interpreted these observations as suggesting that the engraftment potential has been more severely altered in ANLL than in ALL, which may reflect both the intensity of the in vitro treatment and the intrinsic fragility of the stem cell pool in ANLL.

Bone Marrow↗

Influence of single and double immunomagnetic depletion on the hemopoietic capacity of marrow in patients with advanced neuroblastoma submitted to autologous bone marrow transplantation.

Eighteen marrows from 16 patients with advanced neuroblastoma were submitted to a single or double immunomagnetic depletion procedure to purge them of tumor cells. Analysis of results showed that the CFU-GM recoveries were 59% +/- 16 (SE) and 33% +/- 16 after one or two cycles of incubation with microspheres. This led to yields of 7.8 x 10(4) and 4.1 x 10(4) CFU-GM available per kg body weight, respectively. Successful engraftment was demonstrated in all evaluable patients. However, some patients had delayed hematologic recoveries, particularly for platelets.

Antibodies, Monoclonal↗

Long-term human blood cultures: application to circulating progenitor cell autografting.

Peripheral blood cells collected by cytapheresis from patients with acute leukemia following induction therapy or with multiple myeloma off-therapy, were maintained in a one-stage long-term liquid culture system. The data indicate that: (1) blood-derived granulopoietic proliferation can be sustained for up to 8 weeks with generation of CFU-GM in a way similar to bone marrow cells; and (2) this normal hematopoiesis can be sustained in spite of the absence of any development of a substantial stromal adherent layer, which suggests that, unlike hematopoiesis from bone marrow, the blood-derived non-adherent cell population is a self-sustaining compartment. While autologous transplantation with peripheral progenitor cells is gaining importance as an alternative to autologous bone marrow transplantation, this study suggests that circulating progenitor cells may have a different behavior from marrow cells. This observation may be relevant to the understanding of cases of defective hematopoietic reconstitution.

Blood Cells↗

Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bone-marrow transplantation.

Seven patients with immunodeficiencies (Wiskott-Aldrich syndrome, combined immunodeficiency, and osteopetrosis) were given a mouse monoclonal antibody against the alpha subunit of human leucocyte functional antigen (HLFA-1; CD18) to facilitate the engraftment of mismatched haploidentical related-donor bone marrow. Other conditioning included busulphan, cyclophosphamide, and antilymphocyte globulin. To prevent graft-versus-host disease the bone-marrow T cells were depleted with sheep erythrocyte rosetting and cyclosporin therapy was given. HLFA-1 antibody injections were well tolerated without side-effects except slight, transient fever (38-40 degrees) after the first injection. Engraftment was rapid in all seven patients. The regenerating leucocytes were of donor origin in all cases, and two patients have a mixed chimera. Two patients died from infections. The others are alive and well 60-395 days after transplantation. In a historical control group given the same treatment without anti-HLFA-1 infusion, only one of seven transplants partially engrafted; only two patients remain alive with autologous reconstitution but with uncorrected immunodeficiency.

Antibodies, Monoclonal↗

Cardiac complications after bone marrow transplantation. A report on a series of 63 consecutive transplantations.

Cardiac complications related to bone marrow grafting were investigated in a group of 63 patients undergoing bone marrow transplantation (57 autologous, 6 allogeneic) in the transplant unit of Hôpital Saint-Antoine (Paris, France) between February 1977 and October 1983. The pregraft regimen was cyclophosphamide, 6-thioguanine, cytosine arabinoside, and CCNU (TACC) in 39 cases, cyclophosphamide (CY) associated with whole-body irradiation in 16 cases, and multiple chemotherapeutic agents in 8 cases. The study was retrospective in 49 patients, and prospective in 14. The morbidity was 43% and the mortality 9%. There were 6 fatal cases of cardiomyopathies and/or pericarditis, 14 nonfatal cases of heart failure, 7 nonfatal cases of pure pericarditis, and 32 arythmias including 14 bradycardias, diversely associated on a total of 27 patients. Cyclophosphamide and/or TACC/cyclophosphamide, 6-thioguanine, cytosine arabinoside, and BCNU (BACT) were the factors basically responsible for the cardiac toxicity. The best-defined entity was an acute fatal cardiomyopathy with associated pericarditis of which we report three additional cases. The best predictors of CY toxicity were the daily weight (a gain of more than 2 kg for more than 48 hours) and the electrocardiogram (a decrease of more than 14% in the sum of the QRS complexes in the standard leads on the fourth day of chemotherapy). Routine echocardiography confirmed the high incidence of subclinical cardiac abnormalities and their reversibility. It would seem that radiotherapy and anthracyclines play a secondary role. Currently, we consider that cardiac toxicity is one of the most important limiting factors for bone marrow transplantation. We suggest, therefore, that the transplantation should be done as early as possible and preference should be given whenever possible to whole-body irradiation over high-dose chemotherapy combinations such as TACC.

Adolescent↗