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Biomedical subjects

A Pileri

Publications and source records attributed to A Pileri.

At least 127 records · Page 7Linked to original sources
PubMed1990

Defective interleukin-2 induction of lymphokine-activated killer (LAK) activity in peripheral blood T lymphocytes of patients with monoclonal gammopathies.

The recombinant interleukin-2 (rIL-2) generation of lymphokine-activated killer (LAK) cells was investigated in peripheral blood T lymphocytes (PBT) of 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 32 patients with multiple myeloma (MM). LAK activity was significantly decreased in MM, but not in MGUS patients, and was partially recovered in MM in the remission phase. This finding was unexpected, because CD8+ CD11b+ cells, which contain LAK precursors, are significantly increased in MM. LAK activity was investigated in purified CD8+ CD11b+ lymphocytes to discriminate between an intrinsic defect or a defective regulation by other T cell subsets. These cells were intrinsically unable to generate LAK activity fully following rIL-2 stimulation. MM showed the more pronounced LAK deficiency, while MGUS patients showed intermediate values. Phenotyping revealed significantly increased proportions of Leu7+ and HLA-DR+ cells in MM patients. These data reveal another dysregulation of T cell effector functions in patients with monoclonal gammopathies and offer further evidence of the impairment of their cell-mediated immunity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Durable and complete hematopoietic reconstitution after autografting of rhGM-CSF exposed peripheral blood progenitor cells.

Two patients with poor prognosis stage III multiple myeloma have been treated with myeloablative chemoradiotherapy, i.e. 10 Gy fractionated total body irradiation plus 120 mg/m2 intravenous melphalan, and then transplanted with autologous peripheral blood cells harvested by four leukaphereses during the phase of rapid hematopoietic recovery following induction therapy with high-dose (2 g/m2) etoposide and recombinant human glycosylated granulocyte macrophage-colony stimulating factor (rhGM-CSF). Following myeloablative therapy and autologous peripheral blood cell transplantation, both patients experienced brief pancytopenia followed by rapid hematopoietic recovery of leukocytes (time to greater than 500 x 10(6)/l = 12 days) and platelets (time to greater than 100 x 10(9)/l = 14 days). In particular, single donor platelet transfusion requirements were limited to one and two transfusions per patient, respectively. Reconstitution has so far been maintained throughout the follow-up period for the two patients (9 and 6 months, respectively). These two cases show that rhGM-CSF-exposed peripheral blood cells are capable of producing prompt and sustained hematopoietic reconstitution in patients treated with myeloablative chemoradiotherapy.

Adult↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), given to accelerate recovery from cytopenia induced by high-dose (7 g/m2) cyclophosphamide, reproducibly brought about a dramatic increase (up to 1000-fold) in the number of peripheral blood granulocyte-macrophage colony-forming units (CFU-GM). These circulating progenitors were harvested by leucapheresis and reinfused, together with autologous bone marrow cells, in seven patients with cancer after total body irradiation and melphalan. Complete haemopoietic recovery occurred in all seven transplanted patients in a very short time: mean (SD) 9.1 (0.9) days (range 8-11) to achieve more than 0.5 x 10(9)/l neutrophils, 9.9 (1.7) days (range 8-13) to over 1 x 10(9)/l neutrophils, 10.7 (2.6) days (range 9-16) to over 0.5 x 10(11)/l platelets, and 13.6 (4.2) days (range 13-21) to over 1.0 x 10(11)/l platelets. A reduction in the severity of mucositis was also observed. The rapid haematological recovery made possible by this approach promises to increase the therapeutic index of high-dose chemoradiotherapy regimens and to widen their role as treatment for chemoradiosensitive tumours.

Adult↗
PubMed1989

Altered expression of growth-regulated protooncogenes in human malignant plasma cells.

The expression of three growth-regulated protooncogenes, c-myc, c-myb, and p53, and the S-phase-specific histone H3 gene, was compared in bone marrow cells from multiple myeloma patients and normal controls by measuring the amount of specific RNA by Northern blot analysis. Four samples contained at least 72% of myeloma cells, one sample 43%, and one 11%. Expression of the protooncogenes was similar in normal and myeloma bone marrow cells, whereas that of histone H3 gene was significantly reduced (between 10 and 15 times) in samples containing at least 43% of malignant plasma cells and not detectable in those containing more than 72% of neoplastic cells. Protooncogene levels of expression were compared to those of the H3 gene to distinguish the increased expression of a growth-regulated gene due to a true deregulation from overexpression reflecting solely an increase in the fraction of cycling cells. The ratios of expression of protooncogenes to histone H3 were markedly increased in multiple myeloma cells; the highest ratios were found in the patients with the highest number of malignant plasma cells. These results suggest that the expression of three growth-regulated oncogenes (c-myc, c-myb, p53) is altered in myelomatous plasma cells.

Actins↗
PubMed1989

Paraproteinaemias and platelet aggregation: role of whole blood aggregometry.

Whole blood and optical platelet aggregation were measured in normals and in patients with paraproteinaemias; extent of aggregation was correlated with paraprotein concentrations in patients and in normals after addition of different doses of paraproteins; threshold aggregating concentrations of several agonists were also determined in whole blood and in PRP from both groups of subjects. The results indicate that patients with macromolecular monoclonal component bear a "hyperaggregable" state which can be probably ascribed also to plasma hyperviscosity and which is better detected with the impedance aggregometer.

Adenosine Diphosphate↗
PubMed1989

Monoclonal immunoglobulin gene rearrangement in peripheral lymphocytes of a patient with multiple myeloma.

We analyzed the immunoglobulin (Ig) heavy chain gene rearrangement in the peripheral blood lymphocytes of a patient with multiple myeloma (MM). Although the morphological and immunological examination did not reveal the presence of circulating plasma cells, a monoclonal Ig gene rearrangement was detected. This observation indicates that a monoclonal expansion of circulating B cells was present in the peripheral lymphocytes of this patient.

DNA↗
PubMed1989

CD8+CD11b+ peripheral blood T lymphocytes contain lymphokine-activated killer cell precursors.

CD3+CD8+ cells, purified from peripheral blood T cells by depletion of CD4+ lymphocytes, were tested for their cytotoxic activity against K-562 or HL-60 cells. Freshly prepared cells had no cytotoxic function, but upon exposure to recombinant interleukin 2 (rIL2) in vitro they acquired a lymphokine-activated killer (LAK) activity. Fractionation of CD3+CD8+ cells into CD11b+ and CD11b- cells demonstrated that all the cells with the potential of developing LAK cell functions were within the CD8+CD11b+ subset. These cells lacked natural killer cell markers such as CD16 or NKH1, but a proportion of them stained for Leu-7. Furthermore, they expressed the alpha/beta chains, but not the gamma/delta chains, of the T cell receptor, as could be determined by staining with the appropriate monoclonal antibodies. CD8+CD11b+ cells had a large granular lymphocyte morphology, as shown by both cytochemical and electron microscopy analyses. They proliferated in response to IL2 in vitro and developed cytotoxic functions against a number of natural killer resistant targets. Their response to phytohemagglutinin or pokeweed mitogen was very weak or absent. By contrast, CD8+CD11b- cells failed to generate LAK cells in response to rIL2, did not show a large granular lymphocyte morphology, but responded vigorously to phytohemagglutinin or pokeweed mitogen. Purified CD8+CD11b+ cells were cloned by limiting dilution in the presence of rIL2. The observed cloning efficiency of 19 +/- 0.3% indicates that a fraction of the cells only could respond to IL2. Furthermore, only 50% of the clones obtained had a LAK cell function. These data show that CD8+CD11b+ cells represent a heterogeneous cell population. Nevertheless this cell subset probably represents the major source of LAK cell progenitors within the circulating T cells.

Acid Phosphatase↗
PubMed1989

Effect of two aliphatic aldehydes, methylglyoxal and 4-hydroxypentenal, on the growth of Yoshida ascites hepatoma AH-130.

The influence of a ketoaldehyde, methylglyoxal (MG), and a hydroxyalkenal, 4-hydroxypentenal (HPE), on the growth of a highly-deviated tumour has been investigated. MG and HPE, administered intraperitoneally, strongly depressed in rats the proliferative activity of the Yoshida ascites hepatoma AH-130, reducing its mitotic and labelling indices as well as the proportion of cycling cells (growth fraction). Monitoring the effects on the cell cycle by the labelled mitoses method showed that the percentage of labelled mitoses was markedly lowered after either aldehyde, which is indicative for a blocking effect in the S phase. In addition, the mean cell cycle time was slightly prolonged by MG, probably due to accumulation of cells in G1, whereas HPE delayed the first mitotic peak and increased the mean DNA synthetic period without modifying the overall cycle time. The effects of HPE on the cell cycle were prevented by pretreatment with polyamines. Repeated doses of MG significantly increased the fraction of tumour-bearing rats surviving at 90 days ('indefinite' survivors) as well as the survival time of those which succumbed, implying that the carcinostatic effect of MG persisted over several cell cycles. By contrast, HPE did not significantly modify the survival of AH-130-bearing rats, suggesting that its influence on tumour growth was rapidly reversible.

Aldehydes↗
PubMed1989

Advances in biology of multiple myeloma: cell kinetics, molecular biology and immunology.

Bone marrow plasma cell proliferative activity has been evaluated in a large series of multiple myeloma (MM) patients. This kinetic parameter has been shown to be a useful tool for patient management, and contributes to a correct diagnosis and a selection of high-risk patients who can be offered high-dose chemotherapy. The role of ras oncogenes has been evaluated in the pathogenesis of MM. A point-mutated and activated H-ras oncogene, introduced in a human lymphoblastoid cell line, was able to induce neoplastic transformation and differentiation to plasma cell. Indeed, mutated alleles of ras genes have been detected in a high percentage of myeloma patients in relapse phase. Phenotypical and functional studies have been carried out in T-lymphocyte subsets and an impaired cellular immunity has been detected. Such an impairment was related to the disease status: marked alterations were detected in relapse phase, whereas a partial recovery was observed during remission phase.

Cell Cycle↗
PubMed1989

Multiple myeloma: beta-2-microglobulin is not a useful follow-up parameter.

Serum beta-2-microglobulin (beta 2M) has been suggested as the most powerful prognostic factor in multiple myeloma (MM). This paper investigates its ability to detect remission and relapse in individual patients. A correlation analysis was carried out between beta 2M and M component determinations, at diagnosis and monthly during follow-up in 21 consecutive MM patients with normal renal function. A statistically significant correlation was observed in 52.4% only. The lack of correlation in the remaining cases was due to low beta 2M production at diagnosis, or independent fluctuation of these 2 parameters. Serum beta 2M proved a much less reliable parameter for the detection of tumour variations than simpler M-component determination.

Blood Proteins↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor requires interaction with accessory cells or granulocyte-colony stimulating factor for full stimulation of human myeloid progenitors.

Human recombinant GM-CSF (rGM-CSF) was tested on highly purified and fractionated CFU-GM subsets. The fractionation was performed with the DS1-1 monoclonal antibody (MoAb), which distinguishes early and late CFU-GM. On whole bone marrow cells, rGM-CSF had a colony-stimulating activity comparable to that of known sources of CSFs, ie, the supernatant (SN) of TPA 30-1 or 5637 cell lines, used as control. A greatly reduced activity was observed when CFU-GM were depleted of phagocytizing and E rosetting cells (colony growth of 27% as compared with control). On fractionated CFU-GM, the rGM-CSF activity was even more reduced on both early and late progenitors (18% and 6% of colony growth, respectively). However, when rGM-CSF was used together with rG-CSF at suboptimal concentrations, the colony growth reached values analogous to that of control cultures. A synergistic interaction between rGM-CSF and rG-CSF in stimulating either early or late myeloid progenitors was observed. The results suggest that the activity of rGM-CSF on CFU-GM is mainly exerted through cooperation with accessory cells. r-G-CSF is one of the factors that can synergistically cooperate with r-GM-CSF in the myelopoietic stimulation.

Bone Marrow↗
PubMed1989

No evidence of platelet activation during atrial pacing in subjects with stable angina.

Platelet behaviour (activation) in ischemic heart disease (stable angina) during pacing-induced tachycardia was studied. ECG was recorded during the trial. Ischemic heart disease (IHD) subjects had 75% or more narrowing of the luminal diameter of a coronary artery, demonstrated by coronary angiography. Eight subjects needing cardiac catheterism because of supraventricular rhythm disturbances with no evidence of IHD were studied as controls. Beta-thromboglobulin (beta-tg) and platelet factor 4 (PF4) were studied as platelet activation markers; beta-tg and PF4 were evaluated before atrial pacing in peripheral venous blood and, by catheterism, before and at maximum pacing rate in coronary venous sinus (CVS) and in ascending aorta (AA). Catheterism and blood withdrawals were performed in order to reduce platelet activation in vivo. No significant difference in platelet activation between IHD patients and control group in peripheral venous blood were found. No trans-myocardial gradient neither in IHD subjects nor in controls were observed. In conclusion, no platelet activation in IHD patients during pacing-induced tachycardia could be observed.

Adult↗
PubMed1988

The generation of alloreactive cytotoxic T lymphocytes requires the expression of ecto-5'nucleotidase activity.

Ecto-5'-nucleotidase (ecto-5'NT) activity is highly expressed by CTL precursor cells. The aim of this work was to investigate whether ecto-5'NT is involved in their functional activation. The inhibition of ecto-5'NT activity by biochemical (alpha,beta-methyleneadenosine 5-diphosphate; AOPCP) or immunologic inhibitors (polyclonal anti-ecto-5'NT serum) suppressed the proliferative and cytotoxic activation of CTL against a lymphoblastic B cell line in primary one-way MLC. The kinetic analysis of suppression showed that AOPCP and anti-5'NT serum had different effects: AOPCP suppressed only the activation of the cytotoxic program whereas anti-5'NT serum suppressed also recognition and binding to the stimulatory/target cell. Inhibition of CTL generation was not a metabolic consequence of the purine salvage blockade. Incubation of AOPCP-treated MLC with hypoxanthine restored proliferation but not cytotoxicity. The ecto-5'NT inhibitors used had no general toxic effect on cell numbers or viability. AOPCP selectively affected CTL generation and displayed no activity against mitogen-induced proliferation, activation of Ts cells, and generation of IL-2-activated killer cells. These data indicate that ecto-5'NT has a critical role in the functional activation of alloreactive CTL.

5'-Nucleotidase↗