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Biomedical subjects

A Guarini

Publications and source records attributed to A Guarini.

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

Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors.

The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings.

Cells, Cultured↗
PubMed1990

Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease.

Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.

Antibodies↗
PubMed1990

Interleukin 2 does not promote the in vitro and in vivo proliferation and growth of human acute leukaemia cells of myeloid and lymphoid origin.

The effect of recombinant interleukin 2 (IL2) on the in vitro and in vivo proliferation and growth of human acute leukaemia cells of both myeloid and lymphoid origin was investigated. In none of the 25 primary samples tested could a continuously in vitro growing cell line be obtained by adding IL2 to the culture medium. Although IL2 induced a proliferative signal in three of the 31 acute leukaemias analysed, the overall 3H-thymidine uptake of the neoplastic cells was significantly reduced (P less than 0.05) in the presence of IL2. The unlikelihood of an important proliferative signal triggered by IL2 was confirmed in a semisolid clonogenic assay, which failed to document an increased colony growth in the 26 samples studied. Furthermore, using a colorimetric assay as a test for cell proliferation and survival, in seven of the 11 fresh acute leukaemia samples tested a 22-40% reduction in viability was observed in the presence of IL2, while in the remaining four, IL2 was ineffective. In order to investigate the effect of IL2 in an in vivo setting, an experimental model in heavily immunosuppressed nu/nu mice was established. In no case did IL2 promote the in vivo proliferation and growth of human myeloid and lymphoid acute leukaemia cells injected in the mice. On the contrary, with seven of the eight leukaemic cell lines which gave rise spontaneously to leukaemic masses, this could be prevented when the mice received locally 300 U of IL2 three times daily for 90 d. IL2 also blocked the growth in vivo of three fresh acute leukaemia samples (two myeloid and one lymphoid). Co-culture experiments using leukaemic cell lines and increasing numbers of normal lymphocytes suggest that the inhibitory effect of IL2 is probably exerted via an indirect mechanism. These findings, coupled to the well-documented ability of IL2 to generate lymphokine activated killer cells cytolytic against leukaemic blasts, further point to the potential role of immunotherapy with IL2 in the management of patients with haematological malignancies.

Animals↗
PubMed1989

In vivo and in vitro inhibitory effect of alpha-interferon on megakaryocyte colony growth in essential thrombocythaemia.

Megakaryocyte (MK) colony growth of bone marrow mononuclear non-adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK-colony forming units (CFU-MK per 3 x 10(5) plated cells) was similar in ET (68 +/- 33) and in controls (63 +/- 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P less than 0.01) greater in ET patients. Human recombinant alpha-interferon 2a (alpha-IFN), administered to 10 patients at a dose of 3 x 10(6) IU/d s.c. for 11 +/- 3 weeks, was capable of inducing a significant (P less than 0.01) decrease in the number (from 72 +/- 16 to 31 +/- 14) and size of bone marrow CFU-MK, together with a significant reduction of the platelet count (from 1031 +/- 325 to 378 +/- 75 x 10(9)/l). When added in vitro at time 0 to the culture dishes, alpha-IFN inhibited the CFU-MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that alpha-IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine.

Adolescent↗
PubMed1989

The inhibitory effect of serum from hairy-cell leukaemia patients on normal progenitor cells may disappear following prolonged treatment with alpha-interferon.

The possibility that serum from hairy-cell leukaemia (HCL) patients at diagnosis may show an inhibitory effect on the in vitro colony growth of normal haemopoietic progenitor cells has been suggested. Several studies have documented the efficacy of alpha-Interferon (alpha-IFN) in inducing a complete restoration of peripheral blood values and, in some cases, a complete clinical remission. In this study we have evaluated the regulatory effect of serum, collected before and after 3 and 12 months of alpha-IFN treatment, from 10 patients with untreated HCL, on the in vitro growth of normal bone marrow CFU-GM, BFU-E and CFU-MK. The effect of conditioned media, prepared from enriched hairy cells (HC) cultured in synthetic medium, on the growth of normal haemopoietic progenitors was also investigated. The results obtained confirm that sera from untreated HCL patients display a variable degree of inhibitory activity in the progenitor cell compartments analysed. Disappearance of the inhibitory activity, particularly evident for the erythroid compartment, was found only in patients who displayed a disappearance of circulating HC and a good haematological response after prolonged (12 months) treatment with alpha-IFN. The possibility that the serum of patients with HCL may contain a haemopoietic inhibitory factor, released by the neoplastic HC population, is suggested.

Adult↗
PubMed1988

Piperacillin plus amikacin versus cefotaxime plus amikacin in neutropenic and feverish patients with malignant hemopathies.

Seventy-one neutropenic patients under cytostatic treatment for malignant hemopathies (neutrophil granulocytes less than or equal to/mm3 with feverish episodes in progress (T greater than or equal to 38.5 degrees C) which were probably of an infectious nature were treated according to two antibiotic protocols (piperacillin + amikacin [P + A] or cefotaxime + amikacin [C + A] in a randomized, comparative, prospective study. Of the 71 patients enrolled, 65 could in the end be evaluated for the purposes of this study (36 treated according to the P + A protocol, 29 according to the C + A protocol). In 16 patients the infection was documented bacteriologically. In these cases the percentages of response were, respectively, 77.7% with the P + A and 71.4% with the C + A protocol. The positive clinical results of the two protocols being studied were, considering the entire survey (bacteriologically documented, clinically documented and FUO infections), respectively, 69.4% in the patients treated with P + A and 62.0% in those treated with C + A. The results of the study seem to indicate that the severity of the neutropenia (N.G. less than 500 or greater than 500) does not affect the response to the antibiotic therapy. Modest and transient side effects (hypokalemia and increase of the ClCr) were noted above all in the patients subjected to the therapy with C + A. The results of this study show, therefore, a superimposable effectiveness of the two therapeutic protocols (P + A and C + A) in the empirical treatment of infections in neutropenic patients with malignant hemopathies.

Adolescent↗
PubMed1987

Procoagulant cellular activity (PCA) in the classification of acute leukemia.

The procoagulant cellular activity (PCA) of leukemic cells was evaluated, before and after endotoxin stimulation, in 38 patients with acute leukemia at presentation subdivided according to the FAB classification. In the M4 and M5 subgroups the stimulated leukemic cells showed a significant increase in the production of PCA compared with freshly isolated cells. No evident PCA was documented in M1 and M2 AML as well as in the majority of acute lymphoid leukemias tested, both before and after endotoxin stimulation. The myeloid and lymphoid leukemic cells appear to behave similarly to normal leucocytes, within which only monocyte/macrophages are capable of producing PCA following endotoxin stimulation. These findings suggest that in human leukemic cells the endotoxin-induced production of PCA may be considered a indicator of monocyte/macrophage differentiation and thus represent a valuable diagnostic tool in the classification of acute leukemias.

Acute Disease↗
PubMed1987

Depressed fibrinolysis in patients with acute leukaemia.

The fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t-PA antigen and t-PA inhibitor activity. No correlation was found between the above-mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC, fever, liver failure. The decrease in immunological plasminogen and functional alpha 2-antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.

Adolescent↗
PubMed1987

Human T-lymphocyte-derived megakaryocyte colony-stimulating activity.

Conditioned medium from a T-lymphoblastic cell line (Mo) contains a number of well-characterized hemopoietins. In this paper we demonstrate that Mo cells also release a factor(s) able to stimulate the growth and the differentiation of megakaryocytic progenitors into large-size pure megakaryocytic colonies in plasma clot cultures. Comparison with other sources of human-active hemopoietins shows that Mo-conditioned medium performs better than others, especially for the megakaryocytic lineage. The factor(s) shows strong similarities with human Meg-CSF obtained from a thrombocytopenic patient's plasma, and is distinguishable from the other hemopoietins present in the medium.

Bone Marrow Cells↗
PubMed1986

Human myeloid precursor cells do not possess or produce procoagulant activity (PCA).

The procoagulant cellular activity (PCA) of human myeloid precursor cells was evaluated after fractionation of normal bone marrow cells over a discontinuous albumin density gradient. No PCA was documented in any of the six freshly isolated fractions (F1-F6); significant amounts of PCA were instead produced, after a 4-h endotoxin preincubation, in fractions F1 and F2, which, unlike the other fractions, contained up to 5% monocyte-macrophages. After removal of the latter by plastic adherence, the PCA was abolished. This study shows that PCA can be produced only by monocyte-macrophages upon endotoxin activation, while myeloid precursor cells, at all stages of differentiation, are incapable of PCA. The PCA demonstrated in some human acute myeloid leukemias, other than that of the monoblastic subgroup, appears therefore to be related to the neoplastic transformation rather than to a maturation arrest or to a toxemic stimulation.

Blood Coagulation Factors↗
PubMed1985

Procoagulant cellular activity and disseminated intravascular coagulation in acute non-lymphoid leukaemia.

The procoagulant cellular activity (PCA) of intact and lysed leukaemic cells was evaluated at diagnosis in 23 patients with acute non-lymphoid leukaemia (ANLL). The leukaemic cells of all 13 patients having DIC feature (excess of fibrin monomers, serum FDP and plasma fibrino-peptide A) showed a significant (P less than 0.0001) increase of PCA, while a pattern similar to that of normal granulocytes and lymphomonocytes was observed in the remaining 10 patients without evidence of DIC. When the patients were subdivided according to the FAB cytological classification, features of DIC and increased PCA were demonstrated in 3/3 M3 patients, 5/6 M5 patients and only in 5/14 remaining patients. These findings indicate that in ANLL patients: (1) the increased PCA of leukaemic cells is closely related to the occurrence of DIC; (2) the increased PCA seems related to the differentiation line and maturation level of the leukaemic cells.

Acute Disease↗
PubMed1985

Release of platelet-activating factor in human leukemia.

Cellular release of platelet-activating factor (PAF) was assessed in a series of human acute and chronic lymphoid and myeloid leukemias at presentation or in an active phase of the disease. PAF-like material, showing physicochemical properties similar to those of synthetic PAF and of PAF released from IgE-sensitized rabbit basophils, was found in cultures of cells from 5 of 6 acute lymphoblastic leukemias (ALL) (2 of 2 T-ALL and 3 of 4 common ALL) and from 13 of 24 B-cell chronic lymphocytic leukemias after stimulation with ionophore A23187 with or without phytohemagglutinin in the presence of acetyl coenzyme A. On the other hand, PAF was released only from 2 of 10 acute myeloblastic leukemias; both of them were of the more mature monoblastic subtype or M5 according to the French-American-British classification. Cells from all three cases of chronic myeloid leukemia studied were also capable of producing PAF. In eight cases of acute lymphoid and myeloid leukemia, the in vivo release of PAF was assessed by testing the plasma levels of this mediator. Only in two cases (one ALL and one acute myeloblastic leukemia) could detectable levels of circulating PAF be demonstrated; it is of interest that both of these cases showed clinical and hematological features of disseminated intravascular coagulation. No PAF was documented in the plasma of the five chronic leukemias tested (four B-cell chronic lymphocytic leukemias and one chronic myeloid leukemia). These findings indicate that lymphoid and myeloid leukemic cells have a different capacity of releasing PAF, possibly related to the level of cell differentiation rather than to an intrinsic property of the neoplastic cells. Furthermore, in some cases, an intravascular release of PAF may occur.

Animals↗
PubMed1984

High fibrinopeptide A (FPA) levels in acute non-lymphocytic leukemia are reduced by heparin administration.

Plasma levels of fibrinopeptide A (FPA) in 30 untreated patients with acute non-lymphocytic leukemia (ANLL) were significantly higher than in 30 healthy controls (p less than 0.001). Patients without laboratory signs of disseminated intravascular coagulation (DIC) had levels of FPA higher than controls (p less than 0.02) but markedly lower than patients with DIC (p less than 0.001). Five patients with M3 leukemia had a higher mean FPA level (p less than 0.02) and a lower peripheral blast cell count (p less than 0.05) than patients with other cytological subtypes of ANLL. When patients with M3 were excluded, a significant correlation was observed between the peripheral blast cell counts and the FPA levels (r = 0.66, p less than 0.001). FPA levels were similar with body temperature either above or below 38 degrees C. After intravenous bolus of heparin FPA dropped to normal levels in 14 out of 17 patients who had high baseline values. These findings indicate that intravascular thrombin formation, which probably result from the expression of procoagulant activities of blast cells, is the main cause of high FPA in the majority of patients with acute non-lymphocytic leukemia.

Acute Disease↗
PubMed1984

Procoagulant activity of macrophages associated with different murine neoplasms.

Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to tumor-associated fibrin deposition through the development of procoagulant activity (PCA). We have investigated PCA of tumor-associated macrophages (TAM) in 6 transplanted murine tumors in syngeneic hosts; peritoneal macrophages from tumor-bearing and control animals were studied also, as reference cell populations. PCA was evaluated by a one-stage clotting assay immediately after preparation and following incubation in the absence and in the presence of endotoxin. TAM from 5 poorly immunogenic tumors (mFS6, MN/MCA1, R 80/44, M109 and MS2) had basal PCA levels comparable to or somewhat lower than those of peritoneal macrophages from the same animals. Similar PCA was found in peritoneal macrophages from both control and tumor-bearing animals. Unlike peritoneal macrophages, TAM in all instances failed to respond with increased PCA when exposed to endotoxin in vitro. Failure to respond to endotoxin could not be ascribed to contaminating tumor cells or their products, to the presence of suppressive macrophage populations or to the lack of lymphocyte "help". TAM from a strongly immunogenic, regressing tumor (MSV sarcoma), in contrast to its non-immunogenic variant, MS2, and to the 4 other tumors mentioned above, expressed high levels of PCA immediately after isolation. The latter did not increase further following in vitro stimulation with endotoxin. When MSV sarcomas were induced in nude mice, TAM showed PCA levels similar to those of the euthymic hosts, suggesting that the procoagulant response was largely independent of T-cell-mediated immunity.

Animals↗
PubMed1983

A degradation product of circulating luteinizing hormone (beta-hCG subunit) in human semen.

Levels of beta-human chorionic gonadotropin (beta-hCG) were detected in semen under basal conditions. No significant correlation to levels of luteinizing hormone (LH) in blood was found. The beta-hCG level did not increase within 3-7 days after a 5000 IU dose of hCG was injected intramuscularly. Human chorionic gonadotropin was detected in semen only after injection. beta-Human chorionic gonadotropin in the semen represents a degradation product of circulating LH.

Chorionic Gonadotropin↗
PubMed1982

Biochemical and metabolic aspects of platelet dysfunction in chronic myeloproliferative disorders.

Fifty-two patients with chronic myeloproliferative disorders (13 with polycythemia vera; 23 with primary thrombocythemia; 6 with myelofibrosis and 10 with chronic granulocytic leukemia) had low platelet levels of adenine nucleotides and serotonin and abnormal uptake and storage of the amine. The storage pool deficiency was confined to the substances contained in the platelet dense bodies, because alpha-granule and lysosome markers were present in normal amounts. In chronic granulocytic leukemia the storage defect was usually less marked but was accompanied by a decreased formation of thromboxane B2 and normal platelet aggregation in response to arachidonic acid. There was no clearcut relationship of these biochemical abnormalities to prolongation of bleeding time or to thrombotic and hemorrhagic symptoms. The defect was still present in 15 patients after treatment had returned the cell counts to the normal range. Normal levels of 5HT and adenine nucleotides were observed in 8 patients whose platelet counts were high after splenectomy for non-hematological reasons. These findings suggest that biochemical abnormalities are related to the presence in the bone marrow of abnormal clones, resulting in the production of defective platelets.

Adenine Nucleotides↗