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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 271 records · Page 15Linked to original sources
PubMed1991

Clonogenic leukemic progenitor cells in acute myelocytic leukemia are highly sensitive to cryopreservation: possible purging effect for autologous bone marrow transplantation.

The intrinsic AML-CFU sensitivity to cryopreservation was investigated. We compared the recovery of AML-CFU with six different freezing techniques in five myelocytic leukemic (AML) patients to the recovery of normal progenitors (CFU-GM and BFU-E) from control marrows. The recovery for AML-CFU (9.3% +/- 3.1, SE) was significantly lower (p less than 0.001) than for normal CFU-GM (48.4% +/- 4.6) and BFU-E (46.2% +/- 5.0). Moreover, the cloning efficiency of frozen AML-CFU was significantly reduced in 4/5 cases (p less than 0.001), as compared to fresh samples, while it was unaltered in 3/4 normal controls. There were no significant differences between the six freezing techniques, indicating that they are equally efficient for normal progenitors and inefficient for leukemic progenitors. These results indicate that human leukemic progenitors are more sensitive to cryopreservation than normal CFU-GM and BFU-E. These findings suggest that cryopreservation per se may have a purging effect in the context of autologous bone marrow transplantation for acute myelocytic leukemia in complete remission.

Bone Marrow Transplantation↗
PubMed1990

Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation.

T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL-2 after autologous BMT leading to a major immune activation 2.5 months after BMT.

Adolescent↗
PubMed1990

Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cell. I. Chemical modifications of ultraviolet-treated low-density lipoproteins.

A new experimental model system constituted by ultraviolet-treated low-density lipoproteins (LDL) has been designed in order to investigate the biological effects of lipid peroxides entering the cell through the endocytotic pathway. This paper reports the chemical modifications of the lipid components and apolipoproteins of the ultraviolet-treated LDL. Human LDL were submitted to short ultraviolet radiations (254 nm, 0.5 mW/cm2, for variable periods of time) and compared to LDL peroxidized by iron. The lipid peroxidation was monitored by following the formation of the peroxidation products (conjugated dienes, thiobarbituric acid-reactive substances (TBARS) and fluorescent lipid-soluble products) and the change of the composition in polyunsaturated fatty acids, carotenes and vitamin E. Several parameters of the apo B-100 structure were investigated: molecular size (by SDS-PAGE) and TNBS-reactive amino groups (chemical determination by trinitrobenzene sulfonic acid). The most important feature was the absence of major modification of apo B-100 in ultraviolet-treated LDL: the molecular weight and the content in TNBS-reactive amino groups of apo B-100 were not modified. In contrast, iron-treated LDL exhibited a loss of the apo B-100 band and a decrease in the number of TNBS-reactive amino group. Both ultraviolet radiations and iron ions induced a significant decrease in the content of polyunsaturated fatty acids, carotenes and vitamin E together with a large formation of lipid peroxidation products. However, the time-course of the formation of conjugated dienes, TBARS and fluorescent lipid-soluble products was quite different using the two oxidative systems. These results demonstrate that ultraviolet radiations induced a strong peroxidation of the lipid content of LDL and no (or only minor) changes in the apolipoprotein moiety whereas iron-catalyzed peroxidation resulted in the formation fo lipid peroxidation products as well as apo B alterations.

Amines↗
PubMed1990

Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. II. Uptake and cytotoxicity of ultraviolet-treated LDL on lymphoid cell lines.

The 'cytotoxicity' of ultraviolet-treated low-density lipoproteins (LDL) has been investigated using cultured lymphoid cell lines from normal subjects and from a patient with receptor-negative familial hypercholesterolemia. The ultraviolet-treated LDL were taken up by control lymphoblasts through the classical apo B/E-receptor pathway, while they were slowly taken up by receptor-negative lymphoblasts by non-specific endocytosis. These LDL were found highly 'cytotoxic' on normal lymphoblasts as demonstrated by Trypan blue dye uptake, [3H]thymidine incorporation, lactate dehydrogenase release and by electron microscopy. The 'cytotoxicity' increased progressively with the concentration of ultraviolet-treated LDL in the culture medium and with the incubation time. In contrast, lymphoblasts from familial hypercholesterolemia were not sensitive to low doses of ultraviolet-treated LDL (up to 150 micrograms apo-B/ml). The comparison of cells from normals and familial hypercholesterolemia showed that the 'cytotoxic' effect occurred subsequently to the LDL uptake, either receptor-mediated or receptor-independent. Experiments combining short-time (5 h) pulse with ultraviolet-treated LDL (labelled with [3H]cholesteryl oleyl ether) and a relatively long-chase period (72 h) showed: (1) a relationship between the delay for the appearance of the 'cytotoxicity' and the amount of ultraviolet-treated LDL taken up by the cells; and (2) the existence of a minimal dose (threshold dose) for triggering the 'cytotoxic' effect. The use of 'hybrid' LDL, prepared by partial delipidation of non-treated LDL and reconstitution by re-incorporating the neutral lipid fractions isolated from ultraviolet-treated LDL, demonstrated that the 'cytotoxic' effect is mainly mediated by triacylglycerols and cholesteryl esters. Scanning electron microscopy showed that the most prominent morphological change resulting from the uptake of ultraviolet-treated LDL was the early blebbing of plasma membranes.

Biological Transport↗
PubMed1990

[Fluorouracil and high-dose folinic acid in the treatment of advanced colorectal carcinoma].

Forty-five consecutive patients with advanced colorectal cancer were treated with 5-fluorouracil and high dose folinic acid. Among 43 evaluable patients there were 7 objective responses for an overall response rate of 16%. Toxicity was generally mild and rapidly reversible. Compared to those reported with 5-fluorouracil alone, these results failed to demonstrate an increase in response rate in the treatment of advanced colorectal cancer with the combination of 5-fluorouracil and folinic acid.

Adult↗
PubMed1990

On the interaction of gallamine with muscarinic receptor subtypes.

The interaction of gallamine with muscarinic receptor subtypes was examined using radioligand binding studies. In competition studies using [3H]N-methylscopolamine [( 3H]NMS), gallamine displayed high affinity for the rat cardiac and guinea-pig uterine M2 muscarinic receptors and for the atypical muscarinic receptor present in chicken heart. Gallamine displayed low affinity for rat glandular and human 1321 N1 astrocytoma cell M3 receptors and also for the M4 receptors of NG108-15 and PC12 cells. The compound displayed intermediate affinity for M1 receptors of rat cortex labeled using [3H]pirenzepine. The interaction of gallamine with the M1 and M2 receptors appeared to be competitive at the low concentrations required to determine affinity estimates. Thus, gallamine inhibited the binding of [3H]pirenzepine to M1 receptors and [3H]NMS to M2 receptors at concentrations that were 263- and 23-fold lower, respectively, than those required to decrease radioligand dissociation kinetics. Furthermore, gallamine, at a concentration that inhibited between 63 and 71% of specific radioligand binding, had no effect on the observed rate of association of the radioligand with either the M1 or the M2 receptor. At the M3 glandular receptor, there was little separation between the concentrations of gallamine that produced inhibition of binding and those that decreased the association and dissociation rates of [3H]NMS. It is therefore difficult to determine if the inhibition of binding seen in competition studies on the M3 receptor was produced through a competitive or an allosteric mechanism. Despite its possible allosteric properties at the M3 receptor, gallamine can be used to detect heterogeneity of muscarinic receptor subtypes in several tissues and therefore represents a useful tool for defining muscarinic receptor subtypes.

Animals↗
PubMed1990

"CD3low" human thymocyte populations can readily be triggered via the CD2 and/or CD28 activation pathways whereas the CD3 pathway remains nonfunctional.

We have investigated the role of the CD2 and the CD28 Ag-independent pathways of activation on CD3low thymocytes. We previously showed that anti-CD28 mAb synergized with anti-CD2 mAb directed against epitopes T11.1 and T11.2, in the activation of purified resting T cells or unseparated thymocytes. Proliferation induced via CD2 plus CD28 was mediated via an IL-2-dependent pathway and was not affected by prior modulation of the CD3-TCR complex. Here, we show that a subset of CD3low thymocytes, although unresponsive to CD3 activation, can be activated to proliferate through the CD2 or the CD28 pathways, in the presence of exogenous IL-2. The mitogenic combination of mAb to CD2 and CD28 induces a proliferation of thymocytes which, in absence of exogenous lymphokines, is restricted to the more mature intrathymic subpopulation, CD1a-. However, CD3low thymocytes can also be triggered through the CD2 plus CD28 activation pathways but require at least addition of exogenous IL-2 to proliferate. This study demonstrates that a fraction of immature CD3low thymocytes possesses functional CD2 and CD28 surface molecules at a time when CD3 is not yet functional.

Age Factors↗
PubMed1990

Activated but not resting T cells or thymocytes express colony-stimulating factor 1 mRNA without co-expressing c-fms mRNA.

Following the observation that, besides acute myeloid leukemia cells, acute lymphoid leukemia cells of either B or T phenotype could express the transcript for the colony-stimulating factor 1 (CSF-1), a growth factor known to be restricted to the monocytic-macrophage lineage, various sources of resting and/or activated T cells and thymocytes were screened for expression of this hemopoietic growth factor. We report here that the CSF-1 transcript was rapidly (7 h) induced in T cells by a variety of stimuli, but was not detectable in either resting T cells or thymocytes. In addition, secretion of CSF-1 was detectable in the supernatants of activated T cells by 72 h, with a peak around 92-120 h. In contrast to activated monocytes, the transcript of the c-fms proto-oncogene, the product of which is the receptor for CSF-1, was not detectable in either resting or activated T cells. This observation could be relevant to the intimate relationships between T cells and antigen-presenting cells during immune responses.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Acute morphine lowers brain stimulation reward thresholds in rats with depressed or elevated response rates.

The positively-reinforcing effect of acute morphine sulfate (MS) administration was assessed by concurrent rate-dependent and rate-independent measures of brain stimulation reward in male rats. An acute 4 mg/kg MS injection produced a rapid, statistically-significant decrease in reward threshold of 28.5%, when compared with saline control values, 45 min after injection. Response rates for brain stimulation delivery decreased by 60.6%, when compared with saline values during the period of maximum threshold change. Other animals, injected with an acute 1 mg/kg MS dose, exhibited significant threshold decreases (21.5%), relative to changes in saline values that occurred in a prior session, and response-rate increases of 23.1%, relative to saline-session changes, when the data were recorded 40 min after injection. The findings reported here demonstrate that the decreases in reward threshold produced by acute morphine administration are independent of the response-rate changes that occur and also support the idea that morphine's rewarding effect may be independent of the behavioral inhibition or activation that can result from the effects of different morphine doses.

Animals↗
PubMed1990

Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma.

We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.

Animals↗
PubMed1990

WGA binding to the surface of two autologous human melanoma cell lines: different expression of sialyl and N-acetylglucosaminyl residues.

Two autologous human melanoma cell lines were studied to determine their capacities to bind wheat germ agglutinin (WGA). Both cell lines were derived from the same patient, the first, IGR 39, originated from the primary tumor, the second, IGR 37, was established from a metastatic lymph node. WGA binding sites on the surface of these cell lines were compared before and after sialidase and/or tunicamycin treatments. IGR 39 cells exhibited two classes of WGA binding sites with high and low affinities, whereas IGR 37 cells had only one class of high affinity binding sites. After tunicamycin treatment, the capacity of IGR 39 cells to bind WGA was markedly altered, since only one class of WGA binding sites with high affinity was observed under these conditions, whereas tunicamycin did not induce significant changes in the lectin binding of IGR 37 cells. The low affinity WGA binding sites, which were only found on IGR 39 cells, corresponded to sialyl residues present in N-linked glycoproteins. The high affinity binding sites present on both cell lines probably involved sialyl and N-acetyl-glucosaminyl residues associated with O-linked glycoproteins and/or glycolipids. No direct correlation could be drawn between the number of WGA binding sites and the overall sialic acid levels exposed to sialidase treatment. The 3-fold increase in the amount of cell surface glycopeptides obtained after pronase digestion and specifically binding to WGA-Sepharose was in good agreement with the overall higher number of WGA binding sites on IGR 39 compared to IGR 37 cells. Thus, subtle carbohydrate changes of cell surface glycoconjugates might account for the differences between the biological properties of human melanoma cell lines of low and high tumorigenicity.

Acetylglucosamine↗
PubMed1990

[Perpropionic and peracetic acids destroy HIV in suspension, but do not inhibit the virus in contaminated units of blood].

The virucidal activity of peracetic and perpropionic acids was evaluated against HIV in an attempt to inactivate the virus which might contaminate blood units collected from donors. The results showed first that doses of peracids as weak as 50 ppm were able to kill the virus in free suspension, but that the doses that did not adversely affect blood components did not inactivate the virus in those components.

Acetates↗
PubMed1990

5-Fluorouracil, epirubicin, and BCNU (FEB) in advanced measurable gastric cancer.

Forty-eight patients with advanced measurable gastric cancer were treated with the three-drug combination of 5-fluorouracil, epirubicin, and BCNU (FEB). The response rate was 42% in 45 evaluable patients. There were five complete responders (11%). The median duration of response was 13 months, and the median survival of all patients was 9.2 months. Toxicity was generally mild to moderate. No instances of congestive heart failure were recorded. These results indicate that patients with metastatic gastric cancer can be effectively palliated with FEB chemotherapy.

Adenocarcinoma↗
PubMed1990

Expansion by folinic acid of the peripheral blood progenitor pool after chemotherapy: its use in autografting in acute leukaemia.

We have tested folinic acid (FA) for ability to increase peripheral blood stem cells (PBSC) after chemotherapeutic aplasia in acute leukaemia. Five adult patients (four AML, one ALL) entered the study, each patient underwent two series of three leukapheresis, the first following induction chemotherapy and the second following the first course of consolidation. The first leukapheresis of each series was done when the white blood cell count reached 10(9)/l with subsequent leukapheresis every other day. Folinic acid (Lederle Laboratories, France) was administered at a dose of 50 mg (i.v.) per day, 15 days from initiation of chemotherapy and continuing through the third leukapheresis of the series (days 25-30). PBSC were collected on a Haemonetics V50 cell separator. In these five cases we observed an increased yield of both colony-forming units, granulocyte macrophage (CFU-GM) and burst forming units-erythroid (BFU-E) expressed per ml of cytapheresis product: CFU-GM x 18, BFU-E x 3 and if expressed per 10(4)/kg of body weight: CFU-GM x 30, BFU-E x 3 (CFU-GM P less than 0.05, BFU-E less than 0.01). Long-term blood culture (LTSC) from FA stimulated leukapheresis, in an attempt to quantitate the most primitive stem cells, demonstrated that this expansion of the PBSC was sustained in time. We found by means of LTSC that FA did not stimulate CFU-L from patients with AML (two cases tested). Finally two AML patients were grafted with FA-PBSC after Cytotoxan and total body irradiation (TBI). Haematopoietic reconstitution was rapid complete and sustained in time in both patients. This indication for folinic acid should be further studied with or as an alternative to haematopoietic growth factors.

Adult↗
PubMed1990

Evaluation of Basidiomycete and Deuteromycete (Fungi Imperfecti) extracts for shared allergenic determinants.

Aqueous extracts of select members of the Basidiomycetes and Deuteromycetes (Fungi Imperfecti) were evaluated for the presence of shared allergenic determinants using skin prick and radio-allergosorbent test (RAST) inhibition. Twenty adults with perennial symptoms of rhinitis, with or without asthma, were skin-prick tested with six species of Deuteromycetes and seven species of Basidomycetes. Positive weal-and-flare reactivity to Pleurotus ostreatus was associated with Alternaria alternata, Fusarium solani and Epicoccum purpurescens. Positive skin reactivity to Calvatia cyathiformis was also associated with A. alternata and F. solani. Coprinus quadrifidus was associated only with F. solani, and Psilocybe cubensis was only associated with Aspergillus fumigatus. No other skin test associations were demonstrated. For every allergen tested by RAST inhibition, significant dose-dependent homologous inhibition was demonstrated. Although the ability of an individual heterologous extract to inhibit the direct RAST varied, inhibition was generally minimal. In the most extreme example, no heterologous allergen inhibited the A. alternata RAST. However, the Armillaria tabescens RAST was inhibited 52.6%, 38.1% and 25.1% by A. fumigatus, E. purpurescens, and Penicillium notatum, respectively, suggesting significant cross-reactivity. These results suggest that, although shared allergenic determinants exist between select species of Basidiomycetes and Deuteromycetes, crossreactivity is minimal and its clinical significance is not clear. These data confirm that for reliable diagnosis of fungal allergy, representatives of both major groups must be used.

Adult↗
PubMed1990

Immunological definition of acute promyelocytic leukemia (FAB M3): a study of 39 cases.

Acute promyelocytic leukemia (FAB-M3) is a distinct entity among acute non-lymphoid leukemias (ANLL) with peculiar morphological, biological, clinical and prognostic features. An atypical form of M3 (M3v) could be confused with other FAB ANLL and therefore the diagnosis of this variant requires ultrastructural analysis and/or cytogenetic study and/or selective gene rearrangement studies. The immunological phenotype of blast cells in 39 APL patients was studied at diagnosis. The diagnosis of M3 FAB type was ascertained in 32 and the diagnosis of M3v in 7 cases. Using a large series of monoclonal antibodies (mAb), the APL blast cells were B and T cell antigens-negative, HLA-DR constantly negative, CD13- and/or CD33-positive, CD9-positive. Among ANLL this phenotype seems to be closely related to APL both in M3 type and M3v subtype. Because the diagnosis of APL (M3 or M3v) is important in order to establish the specific therapeutic approach, the discriminant capacity of the immunological typing to identify M3 and mainly M3v (hypogranular) could be determinant for a "quick" diagnosis.

Adolescent↗