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Biomedical subjects

M Salem

Publications and source records attributed to M Salem.

At least 55 records · Page 3Linked to original sources
PubMed1990

Phlebotomy via the pulmonary artery catheter introducer for intraoperative autotransfusion.

Fear of the acquired immune deficiency syndrome and other blood-transmitted diseases has created a revival of autologous transfusion during cardiac surgery. The present report is of 200 patients undergoing cardiopulmonary bypass during cardiac surgery in whom phlebotomy was performed via the sideport of the introducer for the pulmonary artery catheter for later reinfusion. Each unit of phlebotomized blood was replaced with 500 mL of normal saline. Cardiac output and mean arterial blood pressure decreased significantly after phlebotomy (P less than 0.05) and returned toward control values after administration of the sodium chloride. The autologous blood was replaced after cardiopulmonary bypass. Fresh frozen plasma and platelets were not administered to the patients in the operating room. Eleven patients undergoing coronary artery bypass grafting received fresh frozen plasma in the recovery room because they were receiving aspirin and dipyridamole up to the day of surgery. Prolonged duration of cardiopulmonary bypass in two double-valve replacements, and one coronary artery bypass graft patient who required insertion of an intra-aortic balloon, accounted for the administration of fresh frozen plasma and platelets in three patients. The average volume of phlebotomized blood was 875 mL, which resulted in a decrease of the hematocrit from 40.5% +/- 0.5% (P less than 0.05) to 29.75% +/- 0.5% and 30.5% +/- 0.5% at the end of surgery and at discharge from the hospital, respectively. Phlebotomy via the Y port of the introducer of the pulmonary artery catheter is an easy, simple, and cost-effective way to remove autologous blood in patients undergoing cardiac surgery.

Adult↗
PubMed1990

Histamine blockade and cardiovascular changes following heparin administration during cardiac surgery.

Large doses of heparin given as a bolus may produce hypotension; however, conflicting reports exist about the mechanisms involved. This study was undertaken to determine the role of histamine in beef lung heparin-induced hypotension and the efficacy of histamine-receptor blockade in attenuating this undesirable side effect in patients undergoing cardiac surgery. Two hundred patients with good ventricular function were studied after they were randomized into four equal groups. Group I (control) received no histamine-receptor blockade, group II received 1 mg/kg of diphenhydramine 30 minutes prior to heparin administration, group III received 5 mg/kg of cimetidine 4 hours and again 30 minutes before heparin administration, and group IV received 1 mg/kg of diphenhydramine 30 minutes prior to heparin administration and 5 mg/kg of cimetidine 4 hours and 30 minutes before heparin administration. Hemodynamic variables, plasma histamine, and ionized calcium levels were measured before and after heparin administration. Significant hypotension occurred in group I patients after heparin administration. Mean arterial pressure decreased from 95 +/- 5 to 67 +/- 1.5 mm Hg (P less than 0.005) after 1 minute and to 85 +/- 2 mm Hg (P less than 0.05) at 4 minutes. Those changes were significantly greater than in group II (P less than 0.025) and Group IV (P less than 0.005) patients, in whom no significant hypotension was found. In group III, mean arterial pressure decreased from 92 +/- 3 to 75 +/- 1 mm Hg (P less than 0.05) after 1 minute and returned toward baseline values after 4 minutes. Histamine levels increased significantly in all groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor.

In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.

Adult↗
PubMed1990

Characterization of avian retroviruses carrying activated transforming human c-src genes and of steps involved in expression of activated src-PKases in vitro.

We have isolated four activated transforming human c-src mutants derived spontaneously from viruses carrying the normal human c-src (SRC) genes in the form of Rous sarcoma virus. These mutants induced transformed cell morphology distinguishable from each other in vitro as well as tumors in chicks, whereas normal SRC-carrying viruses did not. Analyses of the transforming SRC proteins together with the normal SRC protein showed that levels of the carboxy-terminal Tyr-phosphorylation were negatively correlated with both transforming ability and protein kinase (PKase) activity as determined by in vitro autophosphorylation. It was observed that two cell lysis methods, that is, NP-40 and RIPA, yielded two different phosphorylated forms of transforming SRC proteins: one possessed low levels of phosphorylation at the autophosphorylation site and the other possessed high levels of phosphorylation at this site. Using the two types of transforming SRC preparations, we have studied in vitro SRC-PKase reactions in relation to in vivo and in vitro autophosphorylation and in vitro phosphorylation of an exogenous substrate. A possible functional relationship between autophosphorylation and SRC-PKase expression is discussed.

Animals↗
PubMed1990

Hemopoietin-1 activity of interleukin-1 (IL-1) on acute myeloid leukemia colony-forming cells (AML-CFU) in vitro: IL-1 induces production of tumor necrosis factor-alpha which synergizes with IL-3 or granulocyte-macrophage colony-stimulating factor.

Interleukin-1 (IL-1) has hemopoietin-1 (H-1) activity, i.e., it synergizes with macrophage-colony stimulating factor (M-CSF), granulocyte-macrophage-CSF (GM-CSF) and interleukin-3 (IL-3) in stimulating in vitro colony formation of hematopoietic progenitor cells. In this study the synergistic activity of IL-1 was investigated on IL-3 and GM-CSF induced growth of acute myeloid leukemia colony forming cells (AML-CFU) in vitro. Among 12 cases of human AML, IL-1 significantly elevated IL-3 stimulated colony numbers in eight instances and enhanced GM-CSF induced colony growth in five cases. As IL-1 is an inducer of cytokine production and since tumor necrosis factor (TNF) elevates IL-3 or GM-CSF induced proliferation of AML-CFU, we examined whether IL-1 enhanced AML-CFU growth via the induction of TNF production. Neutralizing anti-TNF-alpha antibodies significantly decreased IL-1/IL-3 or IL-1/GM-CSF stimulated colony numbers in six of seven cases studied, whereas anti-TNF-beta had no effect, indicating that endogenously produced TNF-alpha costimulated the growth of AML-CFU. Furthermore, AML blast cells stimulated by IL-1 released increased amounts of TNF-alpha (between 25 and 533 pg/ml; median 255 pg/ml) into the culture medium (TNF-alpha specific radioimmunoassay) as compared with noninduced AML cells (less than 1 to 149 pg TNF-alpha/ml; median 31 pg/ml). Thus, the effect of IL-1 on AML-CFU proliferation is not the result of direct activation of AML progenitors, but IL-1 stimulates the release of TNF-alpha by AML cells and endogenous TNF subsequently synergizes with IL-3 or GM-CSF.

Antibodies↗
PubMed1990

Hyponatremia and hypouricemia: differentiation from SIADH.

Hypouricemia in coexistence with hyponatremia often differentiates the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from most other causes of hyponatremia. We report clearance studies in 5 cases of hyponatremia and hypouricemia that were not due to SIADH. One had metastatic pancreatic carcinoma with ascites, edema, hypoalbuminemia and hypophosphatemia. Two had adenocarcinoma of the lung with metastasis to the brain in 1, 1 had disseminated cryptococcus and 1 had Hodgkin's disease. None received radiation or known nephrotoxins at least 4 months prior to study. None had serum creatinine greater than 106.1 mumol/l (1.2 mg/dl). Two had postural hypotension and hyponatremia that responded to saline therapy. Fluid restriction corrected the hyponatremia in all patients, but the hypouricemia, high fractional excretion (FE) of urate, and high urine sodium concentration persisted. In 2 patients studied, ADH was appropriately suppressed after volume repletion but there was a defect in free water clearance due to high renal solute excretion. In contrast to patients with SIADH who correct their defect in renal urate transport with correction of hyponatremia by water restriction, our patients appear to have a persistent renal urate transport defect and abnormality in sodium conservation. Elevated FE urate of greater than 10% after correction of hyponatremia can thus differentiate these patients from SIADH. The diametrically opposing goals of fluid therapy emphasize the importance of differentiating one group from the other.

Adult↗
PubMed1989

Interleukin-1 stimulates proliferation of acute myeloblastic leukemia cells by induction of granulocyte-macrophage colony-stimulating factor release.

In this study, we further established the role of interleukin-1 (IL-1) alpha and IL-1 beta as regulators of proliferation of acute myeloid leukemia (AML) cells. IL-1 stimulated tritiated thymidine (3H-TdR) uptake of AML cells in 13 of 28 cases. Cytogenetic analysis confirmed the leukemic clonality of the IL-1-stimulated cells. Most likely, IL-1 exerted these stimulative effects directly on AML blast cells because IL-1 effectively induced 3H-TdR uptake of CD34-positive AML blasts (separated following cell sorting). Furthermore, adherent cell-depleted AML samples of three patients were more effectively stimulated than nondepleted AML fractions. Cluster and colony formation from adherent cell depleted AML samples could also be stimulated with IL-1, ie, in seven of ten cases analyzed. Subsequent experiments indicated that IL-1 stimulation depended on the release of GM-CSF because (1) induction of DNA synthesis of AML cells by IL-1 could be abrogated with antigranulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, (2) conditioned media (CM) prepared from IL-1 stimulated AML blasts (adherent cell depleted) could stimulate the proliferation of purified normal bone marrow progenitors whereas supernatants from nonstimulated AML blasts did not, and (3) GM-CSF was demonstrated in IL-1/AML-CM with a specific radioimmunoassay, while GM-CSF was not detectable in nonstimulated supernatants. In one case of AML showing significant 3H-TdR uptake in the absence of CSFs, this spontaneous DNA synthesis was found to depend on autocrine IL-1 beta release as it could be suppressed with anti-IL-1 beta antibody or anti-GM-CSF. The blockade by anti-IL-1 beta could be overcome by the addition of high concentrations of IL-1 beta as well as GM-CSF. Thus, in this particular case, endogenously produced IL-1 beta had stimulated the release of GM-CSF which resulted in GM-CSF-dependent proliferation. The results indicate that GM-CSF production by AML blasts is often regulated by IL-1 rather than being constitutive.

Cell Division↗
PubMed1989

Cell to cell contact enhances the proliferation of acute myeloid leukemia (AML) cells in vitro without an apparent role of adhesion glycoproteins LFA1, MAC1 and P150-95.

Acute myeloblastic leukemia (AML) cells were cultured under conditions facilitating or preventing cell to cell contact. Proliferation of AML blasts of 24 patients was assessed in semisolid (containing 0.9% methylcellulose) and in liquid cultures, in which identical concentrations of colony stimulating factors (CSFs) had been provided. In all but one of the cases, significant DNA synthesis (evaluated by 3H-thymidine uptake) was observed when the cells were incubated in the liquid system, whereas in only 14 cases (58%), the cells were able to form clusters or colonies in the semisolid system. These findings suggest that AML cells from a large proportion of patients can proliferate only after stimulation with CSFs in a liquid system, i.e. when cultured under conditions permitting reciprocal contact between the cells. To establish further the importance of cell to cell contact for AML cell proliferation, cells from 19 patients were cultured in liquid medium concurrently in flat bottom microwells (in which a majority of the cells lie separate) and in round bottom microwells (in which cells show a tendency to aggregate). A significantly higher 3H-thymidine (TdR) incorporation in the round bottom cultures was observed in 15 out of 19 cases. The role of the leukocyte function antigens (LFA) LFA1, Mac1, P150-95 in this phenomenon was then analyzed, as these structurally related glycoproteins are involved in reactions requiring contact between hematopoietic cells. Membrane expression of the three antigens was first examined in 16 patients. LFA1, Mac1 and P150-95 were expressed on the AML cells of 15, 6 and 8 patients, respectively. Expression of these antigens did not change following short term incubation of the AML cells in the presence of CSFs. AML cells cultured in presence of saturating concentrations of monoclonal antibodies reacting with structures of these 3 antigens in order to abrogate their function did not suppress 3H-TdR uptake. Thus, no direct role for LFA1 and/or Mac1 and/or P150-95 antigens in mediating contact-induced AML proliferation could be demonstrated. It remains to be established which components are involved in the cell-cell contact-mediated upregulation of AML cell proliferation.

Antigens, CD↗
PubMed1989

Maturation of human acute myeloid leukaemia in vitro: the response to five recombinant haematopoietic factors in a serum-free system.

The abilities of human recombinant IL-3, GM-CSF, G-CSF, M-CSF and Epo to induce maturation in human AML cells in vitro were investigated using cell specimens from 25 AML patients. The experiments were carried out under exactly defined serum-free culture conditions. In the absence of CSFs, monocytic and/or granulocytic maturation was detected in 14/25 cases. IL-3, GM-CSF, G-CSF and M-CSF elevated the proportions of monocyte/macrophages in 3/25, 2/25, 1/25 and 6/25 cases respectively, and increased the percentages of mature granulocytes in 2/25, 1/25, 1/25 and 0/25 cases, and if so only to a limited extent (values below 50%). The 3H-thymidine (3H-TdR) uptake studies revealed that IL-3, GM-CSF, G-CSF and M-CSF were efficient stimulators of DNA synthesis of AML cells in 19, 15, 13 and four of those cases, respectively. Thus, although the cells in most cases responded to CSFs by activation of DNA synthesis, they were unable to give rise to terminally differentiated stages. Provision of CSFs in combination was more frequently effective in enhancing maturation and also increased the magnitude of maturation response. Monocytic versus granulocytic maturation of AML cells after culture did not correlate with the FAB cytology nor with the type of CSF presented; but generally granulocytic maturation was an infrequent phenomenon. Epo stimulated erythroid differentiation and DNA synthesis only in the case of erythroleukaemia, but it had no effect on the cells of 10 other AML cases. Extrapolation of these in vitro findings would suggest that CSFs would have a limited therapeutic utility to induce AML cell maturation in vivo and that hazards of stimulating blast cell proliferation with these factors may be anticipated.

Cell Transformation, Neoplastic↗
PubMed1988

Human AML colony growth in serum-free culture.

Here we report experiments dealing with the development of a fully serum-free culture system for AML cell proliferation. A number of compounds were tested for the requirements of AML colony formation and DNA synthesis in vitro in an attempt to replace serum with an artificial mixture. The results indicate that bovine serum albumin (BSA, 15 mg/ml), cholesterol (7.8 micrograms/ml), transferrin (7.7 X 10(-6) M) and insulin (1 microgram/ml) were essential for AML cell proliferation. Linoleic acid, 2-mercaptoethanol and selenite contributed only moderately beneficial effects. This mixture obviated the need for adding exogenous fetal calf or horse serum to the cultures and permitted equivalent and frequently superior AML colony formation and DNA synthesis. This is the first serum-free culture method for human AML that may allow for in-vitro studies of the growth regulation by recombinant growth factors under exactly defined and standardized conditions.

Cell Division↗
PubMed1988

Effects of recombinant multi-CSF, GM-CSF, G-CSF and M-CSF on the proliferation and maturation of human AML in vitro.

To investigate the relative role of the individual hematopoietic growth factors in stimulating AML cell growth we compared the effects of recombinant (r) Multi-CSF (IL-3), rGM-CSF, rG-CSF and rM-CSF on DNA synthesis of AML blasts in culture. In order to establish the interrelationship between the proliferative effects exerted by these CSFs on AML cells, the ability of these factors to induce progressive monocytic or granulocytic maturation in AML blasts was also assessed. The studies were conducted in 25 cases of AML. They show that AML blasts often are responsive to at least one of the physiologic regulators but the patterns of response reveal a considerable heterogeneity among patients with AML. Although the cells react to these factors, they are usually inert in their capacity to mature, which indicates their intrinsic maturation defect.

Cell Division↗
PubMed1988

Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system.

The response of human acute myeloid leukemia (AML) cells to the distinct hematopoietic growth factors (HGFs), ie, recombinant interleukin-3 (IL-3), granulocyte-macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), and erythropoietin (Epo) was investigated under well-defined serum-free conditions. Proliferative responses to these factors, when added separately as well as in combinations, were analyzed in 25 cases of human AML using 3H-thymidine incorporation and colony assays. The 3H-thymidine uptake data revealed that IL-3, GM-CSF, G-CSF, and M-CSF were stimulators of AML proliferation in 19, 15, 13, and 4 cases, respectively. Epo only stimulated DNA synthesis in the cells of the single erythroleukemia case. GM-CSF stimulation was seen only in IL-3 reactive cases and GM-CSF, when combined with IL-3, could not further elevate the DNA synthesis evoked by IL-3 alone. On the other hand, in six cases, G-CSF enhanced the IL-3- or GM-CSF-stimulated thymidine uptake. These results suggest that subpopulations of AML cells that are activated by distinct CSFs (eg, IL-3/GM-CSF-responsive cells and G-CSF-responsive cells) coexist. The 3H-thymidine incorporation assay was more sensitive for measuring CSF responses than methylcellulose colony cultures, since activation of DNA synthesis was more frequently seen than induction of colony formation. DNA synthesis experiments revealed eight different CSF response patterns among these 25 cases. CSF phenotyping may be a useful addition to the morphologic classification of AML, since these patterns directly reflect the ability of the proliferating subsets of AML cells to respond to the CSFs.

Cell Division↗