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T Barbui

Publications and source records attributed to T Barbui.

At least 199 records · Page 11Linked to original sources
PubMed1990

Cancer procoagulant in acute lymphoblastic leukemia.

In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.

Adolescent↗
PubMed1990

Low incidence of bleeding from HIV-related thrombocytopenia in drug addicts and hemophiliacs: implications for therapeutic strategies.

The records of 608 intravenous drug addicts and 124 hemophiliacs diagnosed in 1985 to be seropositive for HIV were reviewed to identify patients with thrombocytopenia. The records of 54 drug addicts (8.9%) and 14 hemophiliacs (11.2%) who had chronic thrombocytopenia were then followed through June 1989 to estimate the incidence of bleeding episodes. The records of 55 HIV-seronegative patients with idiopathic thrombocytopenic purpura (ITP), comparable for age, platelet count at diagnosis and duration of follow-up, were used for comparison. Patients with ITP were significantly different from those with HIV-associated thrombocytopenia in having a higher proportion of females (M/F ratio 13/42 v 53/15, p less than 0.001) and more intensive treatment (treated: 62% v 21%, p less than 0.001; splenectomized 37% v 1.5%, p less than 0.001). The incidence of major bleeding was not significantly different in drug addicts, hemophiliacs and ITP patients (0.98, 1.82 and 1.17/100 patients/year). Among drug addicts, bleeding was significantly more frequent in women than in men (3.4 v 0/100 patients/year, p less than 0.05). Our results indicate that the incidence of major bleeding in patients with HIV-associated thrombocytopenia is low and similar to that observed in more intensively treated ITP patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Platelet-derived mitogenic activity and bone marrow fibrosis in myeloproliferative disorders.

Mitogenic activity, measured as 3H-thymidine incorporation by NIH 3T3 cells, following stimulation with platelet-rich-plasma-derived serum (PRS), platelet-poor-plasma-derived serum and platelet extract was studied in 14 patients with myeloproliferative disorders (MPD) and 7 normal subjects. Reduced mitogenic activity was found in PRS and platelet extract of patients with MPD, as compared to controls. The average levels of platelet-derived growth factor (PDGF) equivalents were as follows: 16.3 +/- 7.2 pg/10(6) platelets in controls, 6.2 +/- 2.2 pg/10(6) (p less than 0.05) platelets in patients with polycythaemia vera, 1.8 +/- 0.4 pg/10(6) (p less than 0.01) platelets in patients with idiopathic myelofibrosis and 4.0 +/- 0.8 pg/10(6) (p less than 0.05) platelets in patients with essential thrombocythaemia (Dunnett test). A reduction of intraplatelet levels of beta-thromboglobulin, although not statistically significant, was found in the same patients. No apparent relation was found between the amount of PDGF equivalents and the degree of bone marrow fibrosis.

Adult↗
PubMed1990

Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia.

The purpose of this study was to determine which factors were associated with an increased risk of thrombo-hemorrhagic complications in a historical cohort of 100 consecutive and unselected patients with essential thrombocythemia (ET) in whom busulfan treatment was given when platelets were more than 1,000 x 10(9)/L and/or a major thrombotic or hemorrhagic event occurred. The incidence of major hemorrhagic complications was very low (0.33%/person-time at risk [pt-yr]) in comparison with that of thrombotic episodes (6.6%/pt-yr). In an adequate and appropriate control historical group of 200 patients, no severe hemorrhages were recorded and the incidence of thrombotic events was 1.2% pt-yr. Thus, the analysis of risk factors was restricted to this latter group of events. Age, a previous thrombotic event, and long duration of thrombocytosis were identified as major risk factors for thrombosis, while smoking, diabetes mellitus, hyperlipidemia, and hypertension did not influence the rate of thrombotic episodes.

Adolescent↗
PubMed1989

Enhanced proteolysis of plasma von Willebrand factor in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome.

To examine whether enhanced in vivo proteolysis of von Willebrand factor (vWF) would account for the reported loss of larger multimers in acute thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), we studied eight patients with acute TTP/HUS whose blood samples were collected into an anticoagulant containing a cocktail of protease inhibitors to impede in vitro proteolysis. In all, enhanced proteolytic degradation of vWF was expressed as a relative decrease in the intact 225-Kd subunit of vWF and a relative increase in the 176-Kd fragment. However, instead of the loss of larger forms of normal multimers reported by other investigators, the plasma of all but one of our patients (whether they had TTP or HUS) contained a set of larger than normal (supranormal) multimers. Hence, although proteolytic fragmentation of vWF was enhanced during acute TTP/HUS, this phenomenon was not associated with the loss of larger multimers. In the five patients who survived the acute disease and underwent plasma exchange (three with HUS and two with chronic relapsing TTP), subunits and fragments returned to normal values, and supranormal multimers were no longer detected in plasma. In conclusion, even though vWF proteolysis is enhanced in acute TTP/HUS, it does not lead to loss of larger multimers.

Adolescent↗
PubMed1989

T cell receptor delta gene organization and expression in normal and leukemic natural killer cells.

In peripheral blood most NK activity is mediated by CD3- cells with large granular lymphocyte morphology which cannot be assigned to a specific hemopoietic lineage. In accordance with previous studies we have analyzed the organization of the TCR delta gene, which rearranges early in thymic ontogeny, in normal NK cells, and in granular lymphocytes proliferative disorders (GLPD), in an effort to further define their relationship to the T cell differentiation pathway and to identify a possible marker of clonality for CD3- GLPD. The alpha/delta locus was rearranged in five cases of CD3+ GLPD with a biallelic deletion of the C delta region, suggesting V-J alpha rearrangement, whereas CD3- GLPD and normal CD3- NK cells had the delta gene in germ-line configuration, but surprisingly expressed high levels of TCR delta-related mRNA. On the basis of this finding and of the presence of truncated TCR-beta and CD3-epsilon mRNA, we are led to speculate on a possible ontogenic relationship of NK cells to the T cell differentiation pathway at stages preceding TCR gene rearrangement.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Inhibition of cancer procoagulant by peptidyl diazomethyl ketones and peptidyl sulfonium salts.

Cancer procoagulant (CP) is a cysteine proteinase from cancer cells that initiates blood coagulation. Members of two classes of unique and highly specific cysteine proteinase inhibitors, peptidyl diazomethyl ketones (PDK) and peptidyl sulfonium salts (PSS), were studied to determine whether or not they inhibited CP. The inhibitors did not impair the activity of the coagulation system. There was a differential inhibitory effect of the 6 PDK and 2 PSS inhibitors, influenced by the amino acid composition or sequence of the peptide moiety, that suggests differences in structural features of the active site of CP and papain. CP was inhibited by both classes of inhibitors.

Animals↗
PubMed1989

Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells.

Clinical and laboratory findings of B-cell immune dysfunction were evaluated in ten patients with a large granular lymphocyte/natural killer cell proliferative disease (LGL/NK-PD). Increased immunoglobulin synthesis with autoantibody formation was documented: polyclonal hypergammaglobulinaemia (six patients), neutrophil autoantibody (one patient), antinuclear antibody (one patient), and rheumatoid factor (five patients). In addition, serum beta 2-microglobulin level was raised in seven patients, a benign monoclonal gammopathy was detected in one, and concurrent B-type hairy cell leukemia in another. Most patients experienced the complications of hemocytopenia, polyarthritis or rheumatoid arthritis, and immediate allergic reactions to drugs or environmental substances, rather than from symptoms of progressive LGL/NK-PD. A review of the literature confirms that an increased immunoglobulin production is common in LGL/NK-PD, and that patients are likely to develop multiple autoantibodies. The incapacity of proliferating, abnormal LGL/NK cells to suppress B-cell activation and immunoglobulin synthesis, documented by several in vitro studies, offers a pathogenetic explanation for these phenomena. This study shows that an anomalous B-cell function contributes greatly to the morbidity of disease in LGL/NK-PD, and points out the utility of investigating the LGL/NK cell system in patients with autoimmune pathologic characteristics of unclear origin.

Adult↗
PubMed1989

Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis.

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.

Actuarial Analysis↗
PubMed1989

Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis.

We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease.

Adolescent↗
PubMed1989

Hodgkin's disease in association with acquired immunodeficiency syndrome (AIDS). A report on 36 patients. Gruppo Italiano Cooperativo AIDS and Tumori.

In an Italian cooperative study on AIDS and cancer a diagnosis of Hodgkin's disease was established in 36 HIV-positive patients. The series was characterized by a high proportion of drug abusers, a high proportion of mixed cellularity and lymphocytic depletion subtypes and short survival. It is still unclear if HIV infection promotes the development of Hodgkin's disease or only modifies the course of the disease. According to the authors, however, patients who are HIV seropositive and have biopsy-proven Hodgkin's disease should be considered as fulfilling the criteria for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia.

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.

Animals↗
PubMed1989

Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes.

Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved.

Alkaline Phosphatase↗