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Biomedical subjects

E Ascari

Publications and source records attributed to E Ascari.

At least 109 records · Page 6Linked to original sources
PubMed1988

Tetrahydrofolate dehydrogenase cytochemistry in acute lymphoblastic leukemia.

We studied the cytochemical distribution of tetrahydrofolate dehydrogenase (FH4D), an enzyme involved in nucleic acid metabolism and thus in cell proliferation and differentiation processes, in bone marrow blasts from 37 cases of acute lymphoblastic leukemia (ALL), of whom 23 were pediatric patients. 26 cases were analyzed at onset, 11 in relapse. The ALL cases were immunologically classified as T (10), common (20), B (3) and null (4). In each subgroup the majority of lymphoblasts were positive, with heterogeneous positivity patterns and variable degrees of enzyme activity. Most T lymphoblasts were characterized by focal localization of FH4D, whereas in common blasts reactivity - usually less strong - was either focally localized or scattered with several fine granules. Finally, many B and null blasts showed diffuse positivity. A quantitative evaluation of FH4D activity using cytophotometric technique (Vickers M86) demonstrated higher degrees of reactivity in leukemic blasts than in normal lymphocytes. Moreover, slightly different levels of reactivity were observed in relation to immunological phenotype, age and stage of the disease. Therefore we think that FH4D is a useful additional marker for ALL characterization.

Bone Marrow↗
PubMed1988

Platelet aggregation in platelet rich plasma and whole blood in 18 patients affected by idiopathic myelofibrosis.

Platelet aggregation in whole blood (WB) and in platelet rich plasma (PRP) was studied in 18 consecutive patients affected by idiopathic myelofibrosis (IM). On the basis of WB studies, 22% of patients were classified as normo-aggregating and 22% as hypo-aggregating, while 55% had spontaneous platelet aggregation (SPA). SPA was observed also when platelets from patients were stirred in the presence of normal erythrocytes, while it never occurred when normal platelets were stirred in the presence of red cells from patients. PRP studies revealed that 33% and 66% of patients were, respectively, hypo- and normo-aggregating. The most frequent abnormality in PRP was represented by defective or absent aggregation response to epinephrine.

Adenosine Diphosphate↗
PubMed1988

The effect of red cells on platelet aggregation: a study with the electronic whole blood aggregometer.

Platelet aggregation was studied in the same platelet rich plasma (PRP) by the simultaneous use of Born's optical method and Cardinal's electronic method. The maximum rate of impedance change (electronic method) correlated well with both the rate and the extent of aggregation as measured by the optical method. The rate of impedance change was therefore the parameter chosen for the study of the effect of red cells on platelet aggregation. Erythrocytes, both at 40 and 60% haematocrit (Hct.), greatly inhibited platelet aggregation induced by ADP and adrenalin, but only minimally affected platelet aggregation induced by collagen.

Electronics↗
PubMed1988

Recombinant gamma-interferon induces in vitro monocytic differentiation of blast cells from patients with acute nonlymphocytic leukemia and myelodysplastic syndromes.

gamma-Interferon (IFN-gamma) has previously been found to induce monocytic differentiation in established leukemic cell lines, such as HL-60 and U937. The aim of the present study was to evaluate the differentiative effect of highly purified recombinant (r)IFN-gamma on fresh bone marrow cells from patients with acute nonlymphocytic leukemia (n = 11) or myelodysplastic syndromes (n = 3). Blast cells were cultured in suspension in the presence or absence of rIFN-gamma (10-10(3) U/ml). While 6 out of 14 cases were unresponsive to rIFN-gamma in vitro, the remaining 8 patients showed a significant increase (0.05 greater than p greater than 0.001) in the percentage of cells expressing C3bi receptors, detected by OKM1 (median value in control cell, 9.5; median value in rIFN-gamma-treated cells, 31) and Mo1 (8.5 vs. 36), and in the percentage of cells expressing the monocytic antigens detected by Mo2 (8 vs. 28) and MY4 (6.5 vs. 32.5). In the responsive patients morphologic changes consistent with monocytic maturation, as well as a strong increase of alpha-naphthyl acetate esterase activity and of nitroblue tetrazolium reducing capability were observed upon culture with rIFN-gamma. We conclude that (a) rIFN-gamma may induce in vitro monocytic differentiation of blasts from acute nonlymphocytic leukemia and myelodysplastic syndrome patients, and that (b) this agent should be investigated for its capacity to be active in vivo.

Acute Disease↗
PubMed1988

Synergistic antiproliferative effect of recombinant interferon-gamma with recombinant interferon-alpha on chronic myelogenous leukemia hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM).

Recombinant interferons, alpha (rIFN-alpha) and gamma (rIFN-gamma), have been demonstrated to have significant antitumor activity as single agents in the treatment of chronic myelogenous leukemia (CML). Due to their possible synergistic efficacy, a combination rIFN therapy in CML has been proposed. To establish a biologic basis for this, we have studied the suppressive effects of rIFN-alpha and rIFN-gamma on the in vitro growth of CML-derived progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, CFU-GM), the optimal conditions for rIFN synergism, and the possible role of hematopoietic accessory cells (T-lymphocytes and monocytes-macrophages) in mediating rIFN-induced growth inhibition. When added to unseparated bone marrow cells, rIFN-alpha and rIFN-gamma significantly reduced colony formation, with 50% inhibition occurring at 71 and 186 U/mL for CFU-GEMM, 40 and 152 U/mL for CFU-Mk, 222 and 1,458 U/mL for BFU-E, and 119 and 442 U/mL for CFU-GM, respectively. A small amount of rIFN-gamma (5 U/mL) acted synergistically with increasing doses of rIFN-alpha, and the values of 50% inhibitory concentrations fell outside the lower limit (10 U/mL) used in our experiments. This synergy was evident even when rIFN-gamma was added 72 hours after the initiation of cultures; however, it was completely lost when the target cells were depleted of accessory cells. When a low dose of rIFN-alpha (5 U/mL) was added to rIFN-gamma, the 50% inhibitory concentration values were decreased up to tenfold. These studies (1) confirm that CML-derived hematopoietic progenitors are responsive to the suppressive activity of both rIFN-alpha and rIFN-gamma in vitro, (2) demonstrate that different mechanisms are responsible for the suppressive activity of the two rIFNs, and (3) characterize their synergistic interaction, providing a basis for future clinical trials aimed at investigating combination rIFN therapy in CML.

Bone Marrow↗
PubMed1988

Natural history of idiopathic refractory sideroblastic anemia.

We analyzed the natural history of idiopathic refractory sideroblastic anemia (IRSA) in 37 patients studied between 1969 and 1986. Although erythroid abnormalities were prominent in all, 12 patients also showed involvement of the granulocytic and/or megakaryocytic cell lines, and nonrandom chromosomal aberrations were observed in five of 23 patients studied for such defects. Measurements of erythroid marrow function showed in most cases erythroid expansion with ineffective erythropoiesis. In seven patients, however, the erythroid activity was found to be inappropriately low for the degree of anemia. Transfusion dependence occurred in 26 of 37 cases. Iron overload was a common feature at presentation but produced clinical manifestations of hemochromatosis only in those patients who subsequently had a regular need for blood transfusions. Five patients progressed to bone marrow failure, and another five patients (two of whom had monosomy 7) evolved into acute nonlymphocytic leukemia (ANLL). The median survival was 72 months, with a high transfusion requirement, multilineage defects, and inappropriately low erythroid proliferation being associated with a poor prognosis. The most common causes of death were complications of iron overload and evolution into ANLL. We conclude that (a) the natural history of IRSA is characterized by an initial phase of erythroid hyperplasia and ineffective erythropoiesis, which is usually stable for many years but in a subset of patients may be followed by a phase of marrow failure with or without the later emergence of leukemic blasts; (b) peripheral blood counts, measurement of erythroid marrow function, and chromosomal analysis are useful for identifying subjects at risk of evolution into marrow failure or ANLL; and (c) IRSA patients with no need for blood transfusions are very likely to be long survivors, whereas those who become transfusion dependent are at risk of death from the complications of secondary hemochromatosis.

Adult↗
PubMed1988

Flow cytometric analysis of paraffin-embedded material in human gastric cancer.

Flow cytometric DNa analysis was performed on formalin-fixed, paraffin-embedded samples obtained by gastroscopic biopsy from 9 patients with histologically normal gastric mucosa (36 specimens) and by radical gastrectomy from 42 cases of human gastric cancer (120 specimens). Ploidy patterns and the distribution of cells in the different cell cycle phases were estimated, and the results were correlated with the histologic and clinical features. All samples of normal mucosa showed a diploid modal DNA content whereas DNA aneuploidy was encountered in 71.4% of the gastric tumors. The correlation between aneuploidy and histologic malignancy grading was statistically significant: aneuploidy was found in 36.4% of highly differentiated (grade 1 and grade 2) tumors and in 75.0% of poorly differentiated (grade 3) tumors (P less than .05). The percentage of cells in S-phase in normal gastric mucosa (median: 5.0%) was lower than that in the tumors (median: 11.3%) (P less than .05). There was a trend for grade 3 tumors to have higher median values (median: 13.4%) than grade 1 and 2 tumors (median: 9.3%); however, this was not statistically significant. An aneuploid DNA pattern was associated with a poorer prognosis, both in early and in advanced stages of gastric tumors, while proliferative activity did not correlate with postoperative survival.

Adult↗
PubMed1987

Serum thymidine kinase and beta-2 microglobulin in monoclonal gammopathies.

We evaluated the serum thymidine kinase (TK) and beta-2 microglobulin (beta-2) levels of 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and of 29 patients with multiple myeloma (MM). Both parameters were significantly lower in MGUS than in MM patients and in early (stage I + II) than in advanced (stage III) MM. TK was also lower in MGUS than in stage I MM (p less than 0.025). A seven-fold increase of TK level was documented in one patient who developed a full blown picture of MM 6 years after a diagnosis of MGUS. In 3 patients with stage III MM, a sharp decrease in TK (40-77%) and in beta-2 (29-53%) levels at remission was evident with respect to the levels measured at diagnosis. Patients with high levels of TK or beta-2 had a shorter survival than those with low levels; however, this was statistically significant only for beta-2 levels (p less than 0.02). Serum TK as well as beta-2 levels appear to be of clinical value in monoclonal gammopathies and related to the course of the disease.

Adult↗
PubMed1987

Selective bone marrow involvement of lymphoplasmacytic cells secreting monoclonal IgA rheumatoid factor in a patient with Sjögren's syndrome and serum hyperviscosity.

The clinical features and results of serological studies of a patient with Sjögren's syndrome, IgA kappa monoclonal gammopathy, and hyperviscosity syndrome are reported. The novel aspect of this case is the selective localisation to the bone marrow of lymphoplasmacytoid cells secreting IgA kappa morphologically identical to the cells infiltrating the salivary glands. The serum of the patient contained large amounts of immunoglobulin-anti-immunoglobulin immune complexes. By gel filtration chromatography it was shown that the immune complexes formed a peak of molecular weight 680 kilodaltons. The immune complexes were dissociable under acidic conditions. The immunoglobulin with rheumatoid activity was characterised as monoclonal IgA kappa protein. Treatment with plasmapheresis combined with immunosuppressive treatment with cyclophosphamide reduced the serum viscosity with concomitant clinical improvement.

Blood Viscosity↗
PubMed1987

Prognostic factors in malignant lymphomas (Hodgkin and non-Hodgkin).

The prognosis of malignant lymphomas, Hodgkin (HL) and non-Hodgkin (NHL), varies in a very wide range, from a 60-70% survival at 10 years in HL to a median survival of 2-3 years in high-grade NHL. Tumor characteristics, host characteristics, factors related to the impact of the tumor on the host and treatment effectiveness are the main components of prognosis, the last factor being complementary to the first three. An extremely large number of parameters have been considered important for prognosis inasmuch as related to differences in survival at univariate analysis: hematologic variables at onset, humoral markers, cytologic, cytochemical and cytogenetic data. It is well known, however, that multivariate analysis dramatically reduces the number of factors, singly evaluated as important, to only those retaining a true, independent prognostic role.

Hodgkin Disease↗
PubMed1987

Severe platelet dysfunction in a patient with autoantibodies against membrane glycoproteins IIb-IIIa.

A young women affected by Hodgkin's disease developed chronic autoimmune thrombocytopenic purpura. Splenectomy induced normalization of her platelet count, but hemorrhagic symptoms did not disappear. The patient's platelets did not aggregate in response to collagen and ADP and the IgG fraction of the patient's plasma induced the same defect in normal platelets. The women's IgG recognized glycoproteins IIb and IIIa of normal platelet membranes. Prednisone therapy induced the disappearance of bleeding symptoms and the normalization of platelet aggregation.

Adult↗
PubMed1987

Ploidy and proliferative activity of human brain tumors. A flow cytofluorometric study.

Ploidy and proliferative characteristics were estimated by flow cytometry of the nuclear DNA content of 92 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and single cell suspensions were obtained with a mechanical dissociation technique. Propidium iodide was employed for nuclear DNA staining. Human normal brain tissue was used as internal diploid reference standard. 86% of benign tumors had unimodal DNA distribution with a DNA index (DNA I = modal channel of the G0/1 peak of the studied population/modal channel of the G0/1 peak of the normal brain) usually within the diploid or near-diploid range. 14.0% had aneuploidy, with an additional cell peak having a median DNA I of 1.60. Among malignant tumors, these figures were 61.2 and 38.8% (p less than 0.001). The percentage of S phase cells was higher in malignant (median = 3.6) than in benign tumors (median = 2.0, p less than 0.01), without correlation to histological tumor subtype. Flow cytometry appears to be a useful method for evaluating differences in DNA distribution in tumors of the central nervous system.

Adolescent↗
PubMed1987

Effects of a new aminodiphosphonate (aminohydroxybutylidene diphosphonate) in patients with osteolytic lesions from metastases and myelomatosis. Comparison with dichloromethylene diphosphonate.

We have compared in an open trial the clinical and biochemical effects of a new aminodiphosphonate, aminohydroxybutylidene diphosphonate, with those of dichloromethylene diphosphonate, which has been proved effective. The patients presented extensive and symptomatic bone involvement from multiple myeloma, breast cancer, and other metastatic tumors. The treatment consisted of aminohydroxybutylidene diphosphonate, 2.5 mg/d intravenously for five days, or dichloromethylene diphosphonate, 300 mg/d intravenously for seven days, followed by 100 mg/d intramuscularly for ten days. Twelve patients treated with aminohydroxybutylidene diphosphonate and 16 patients treated with dichloromethylene diphosphonate were assessable and were followed up for one to six months. Therapy with aminohydroxybutylidene diphosphonate showed a quicker action in reducing bone pain and reduced significantly more the serum calcium level than did therapy with dichloromethylene diphosphonate. Aminohydroxybutylidene diphosphonate therapy also affected urinary calcium levels and hydroxyproline excretion more markedly than did dichloromethylene diphosphonate, although the differences are not statistically significant. However, the biochemical indexes rebounded more quickly in patients treated with aminohydroxybutylidene diphosphonate, indicating that the loading amount (only 12.5 mg) used in this preliminary study is insufficient to sustain a prolonged effect. The effectiveness and lack of side effects render aminohydroxybutylidene diphosphonate an attractive treatment for malignant bone resorption.

Adult↗
PubMed1987

Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU-GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100-fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.

Antibodies, Monoclonal↗
PubMed1986

Characterization of the platelet-aggregating activity of cancer cells with different metastatic potential.

We studied the mechanisms of platelet activation by sublines exhibiting different metastatic potential of two murine experimental tumors: sublines M4 and M9 of the benzopyrene-induced mFS6 sarcoma and sublines B77-AA6 and B77-3T3 of RSV-transformed BALB/c 3T3 fibroblasts. The neoplastic cells of both models induced platelet aggregation, secretion and prostaglandin biosynthesis. In the first model but not in the second, all these processes correlated with the in vivo malignancy of cells. Pretreatment of B77-AA6 and B77-3T3 cells with apyrase significantly decreased platelet aggregation, while pretreatment of M4 cells was ineffective. However, pretreatment with trypsin or neuraminidase was effective in reducing platelet aggregation induced by M4 cells, but not that induced by any of the others; furthermore, phospholipase A2 reduced the platelet response by all sublines. Finally, platelet-activating activity was also found in the pellets obtained following centrifugation of culture media. These results suggest that platelets are stimulated by cancer cells through different mechanisms; platelet activation by a sialo-lipo-protein complex of the cellular membrane was found to be characteristic of the model in which the platelet-aggregating activity of neoplastic cells correlated with their in vivo metastatic behavior.

Adenosine Diphosphate↗
PubMed1986

Multisystemic disease with intracranial hypertension and autoimmune cytopenia in chronic active hepatitis.

A 14-year-old girl with postinfectious chronic hepatitis developed a life threatening autoimmune multisystemic illness with arthralgias, intracranial hypertension, Coomb's positive hemolytic anemia and hemorrhagic diathesis (due to antiplatelet and antifactor X antibodies). Mannitol and immunosuppressive therapy abolished acute symptoms. During the first year of follow-up, two attempts of decreasing prednisone below 15 mg/day caused recurrence of the hemolytic anemia and appearance of low titer antinuclear antibodies, while doses above 15 mg/day caused an increase in transaminase levels. Daily prednisone dose was therefore fixed at 15 mg. The patient was well and, although signs of mild hemolysis persisted, there was no anemia. Transaminases were found greatly elevated on two occasions. An autoimmune multisystemic steroid sensitive disease was seemingly initiated by a postinfectious steroid irresponsive chronic hepatitis.

Adolescent↗
PubMed1986

Peptichemio, vincristine and prednisone versus melphalan and prednisone as induction therapy in multiple myeloma.

Seventy-five patients with previously untreated multiple myeloma were randomly treated with the association of Peptichemio, Vincristine and prednisone (PTC-VCR-P) or of melphalan and P (MPH-P) for first induction therapy. After induction, all responsive patients received MPH and P until relapse, while unresponsive patients received it until unequivocal evidence of disease progression was observed. A second induction therapy with PTC-VCR-P was then administered, except to patients resistant to this association at first induction (who received combination chemotherapy which included cyclophosphamide and adriamycin). The response rate was 58% in the PTC-VCR-P and 41% in the MPH-P group (P greater than 0.05). The PTC-VCR-P responsive patients experienced a median duration of response shorter than MPH-P responsive patients (20.3 vs 39.7, P = 0.041). Median survival from the start of treatment was 26.2 months in the PTC-VCR-P and 54.1 months in the MPH-P group of patients (P = 0.039). Stage I and II myelomas had the same response rate to PTC-VCR-P and to MPH-P, but their survival was shorter on PTC-VCR-P than on MPH-P (P = 0.014). Stage III myelomas responded more frequently to PTC-VCR-P than to MPH-P (P less than 0.02) and there was a trend to survive longer on PTC-VCR-P than on MPH-P (22.0 vs 12.5 months, P greater than 0.05).

Antineoplastic Combined Chemotherapy Protocols↗