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Biomedical subjects

G Dini

Publications and source records attributed to G Dini.

At least 145 records · Page 8Linked to original sources

Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

Antineoplastic Combined Chemotherapy Protocols↗

Allogeneic bone marrow transplantation versus chemotherapy for childhood acute lymphoblastic leukaemia in second remission.

Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.

Antineoplastic Combined Chemotherapy Protocols↗

[Treatment of neuroblastoma: role of total body irradiation].

Advanced neuroblastoma, scarcely responsive to conventional therapies, can take advantage of high dose chemio-radiotherapic treatment followed by bone marrow transplant. Nineteen young patients underwent an ablative chemotherapy with high dose Vincristine and Melphalan plus Total Body Irradiation in Genoa, Italy; all of them underwent autologous bone marrow transplantation. Fourteen children were in complete remission (CR), 5 had residual disease. Thirteen are alive after a median of 7 months following transplant; 9 are in CR; 4 have disease; 1 died for toxicity; 5 for relapse. The results seem to suggest that ablative therapy should be given to patients in CR. Toxicity was not remarkable mainly as far as TBI is concerned.

Antineoplastic Combined Chemotherapy Protocols↗

Intracellular collagen in fibroblasts of Peyronie's disease.

Ultrastructural study of fibrotic plaques from six patients with Peyronie's disease disclosed collagen fibrils located within smooth membrane bound cytoplasmic structures in most of the fibroblasts. These cells also contained prominent rough endoplasmic reticulum, which was dilated and filled with electron dense material, and hypertrophic Golgi structures in which occasional collagen fibrils were seen. Vacuoles containing collagen fibrils and amorphous substance or cellular detritus were also observed. Data from the present study support the hypothesis that intracytoplasmic collagen fibril formation is caused by excessive collagen synthesis by fibroblasts of Peyronie's fibromatosis.

Cells, Cultured↗

Clonal development from a progenitor with restricted differentiative expression in acute lymphoblastic leukemia.

Three patients with acute lymphoblastic leukemia (ALL) and heterozygous for the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) have been investigated with the 2-deoxyglucose-6-phosphate (2dG6P) method to determine the number and type of progenitor cells in which the disease arose. A monoclonal origin was established for the lymphoblasts, while the other hemopoietic cell lines were not involved in the leukemic process.

Child↗

Plasminogen activator: morphological evidence of binding, internalization and delivery to lysosomes in 3T3 mouse fibroblasts.

Using a direct conjugate of urokinase and ferritin, the binding has been followed at the plasma membrane and the internalization of urokinase into BALB/C-3T3 fibroblasts, cultured in plasminogen-free conditions. At 0 degree C, the conjugate was observed bound on both coated and uncoated cell surface regions as singlets, and small and large clusters. No binding was observed in the presence of excess native urokinase. The binding was impaired by preincubation of the conjugate with a competitive inhibitor of the catalytic site, suggesting an interaction between the receptor and the catalytic site of the enzyme. Within 1 min at 37 degrees C, urokinase clustered on coated regions of the plasma membrane. At 5 min after warming, ferritin was found on deeply indented coated pits and in both coated and uncoated vesicles close to the cell surface. By 10 min at 37 degrees C, ferritin particles were present in uncoated endosomes and in multivesicular bodies in the Golgi area. Within 10 min, the receptors on the surface strongly decreased. New receptors were observed on the membrane after 20 min at 37 degrees C. At this time, ferritin was observed both in endosomes or multivesicular bodies and in vesicles close to the plasma membrane.

Animals↗

Effects of leucine methylester on guinea-pig atria.

Superfusion of guinea-pig atria with 10 mM l-leucine methylester leads to a mechanical arrest and to an increase in protein outflow. Homogenate of atria exhibits a decrease in the sedimentability of phosphatase acid activity as compared to control. Morphological studies reveal that leucine methylester causes not only a lysosomal swelling but also a disruption of myofibrils and slight mitochondrial damage.

Acid Phosphatase↗

Metastatic tumors in the breast: sonographic findings.

The sonographic findings observed in eight patients with metastatic tumors in the breast were reviewed. Solitary breast nodules were present in four patients; multiple metastases were seen in the other four patients, with bilateral lesions in two of them. A total number of 20 breast masses was appreciated. All lesions had a round or oval shape and hypoechoic, solid echopattern, when compared with the surrounding breast parenchyma. In three patients, they presented with many small medium-level internal echoes while, in the other five patients they were almost anechoic, with only a few low-level echoes within. Regular and well-defined margins were seen in four patients; in the remaining four patients, irregular walls were seen. The posterior walls of the lesions were well defined, and great acoustic attenuation was never seen. In one case, slight acoustic enhancement was present posterior to the lesions from non-Hodgkin's lymphoma. Multiple masses in the same patient always had the same sonographic features. While evaluating a breast mass in a patient with a known malignancy elsewhere in the body, the absence of an acoustic shadow posterior to the lesion may allow the metastatic nature of the disease to be considered as a diagnostic possibility.

Adolescent↗

Receptors for plasminogen activator, urokinase, in normal and Rous sarcoma virus-transformed mouse fibroblasts.

We have prepared a conjugate of the plasminogen activator urokinase (UK) and ferritin, which maintains fibrinolytic activity. Monolayers of BALB/c-3T3 cells and of Rous sarcoma virus-transformed highly malignant line AA12-3T3, subcultured in plasminogen-free serum, were incubated with UK-ferritin at 0 degree and processed for transmission electron microscopy. Under these conditions, both of the lines showed specific receptors on the cell surface that were distributed in singlets, in small or large clusters. In the presence of excess native UK, the binding of ferritin was reduced by 99%, indicating the interaction of UK:ferritin with a specific receptor. The ligand-receptor interaction involves the catalytic site of UK, since the binding was completely impaired by preincubation of UK:ferritin with p-aminobenzamidine, a competitive inhibitor of the catalytic site of UK. The number and density of receptors decreased about one order of magnitude on the membrane of AA12 cells when compared with normal 3T3 cells. Saturation kinetics, using 125I-labeled UK, indicate the presence of 4 X 10(4) and 2.5 X 10(3) receptors on the membrane of 3T3 and AA12 cells, respectively. At 37 degrees, UK:ferritin redistributed on the plane of the membrane, in a process which was faster in malignant than in normal cells. Ferritin particles clustered in large groups on coated areas of the surface and were internalized by adsorptive pinocytosis. After 10 min at 37 degrees, the vesicles showed a progressively deeper internalization and a fusion with lysosomes, and some were observed in the Golgi complex area. Since the experiments were planned in order to exclude the presence of protease-nexin in the incubation medium, these data suggest the existence of a plasminogen-independent novel receptor for the catalytic site of plasminogen activators, the number on the cell surface of which decreases in Rous sarcoma virus-transformed mouse fibroblasts.

Animals↗

Early deaths in acute lymphoblastic leukemia (ALL): results of the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).

In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL- AIEOP . Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify "high-risk" groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.

Adolescent↗

Ultracytochemical localization of guanylate cyclase activity in guinea-pig peritoneal macrophages under different physiological conditions.

Guanylate cyclase activity was investigated in guinea-pig peritoneal macrophages under different physiological conditions (such as adhesion and phagocytosis) with an ultracytochemical method using guanylyl-imidodiphosphate as a substrate. The enzyme was detected on the perinuclear envelope, endoplasmic reticulum, Golgi complex and mitochondria of adherent and phagocytozing macrophages. No reaction product was present around phagocytozed polystyrene particles. The amount of final reaction product was increased by the addition of sodium azide to the incubation medium and no staining was observed when the substrate was omitted from the medium.

Animals↗

[Analysis of variations in cardiac performance induced by tilt and hand-grip in athletes and in untrained subjects].

The aim of the present study is to analyze variations of external cardiac work and of indices of myocardial oxygen consumption induced by upright tilting and hand-grip in volley-ball athletes (group A) in comparison with a group of normal subjects (group N). For this purpose we have used impedance cardiography, a simple, reproducible and non invasive technique, which is very reliable in evaluating both systolic time intervals and hemodynamic parameters such as stroke volume and cardiac output. No significant differences, of external cardiac work, double and triple product were observed between group A and N upon upright tilting. Hand-grip test, on the other hand, can differentiate the myocardial behaviour of trained people from that of the control group. The double product was significantly reduced in group A in comparison with group N (P less than 0.001 and the end of the test, P less than 0.05 after 30", P less than 0.001 after 1' and 3"). The triple product was significantly reduced in group A in comparison with group N at the end of the test (P less than 0.005). External cardiac work was always higher in group A in comparison with group N (P less than 0.02, at the stop P less than 0.05 after 30", P less than 0.01 after 1', P less than 0.0001 after 3'). Therefore in volleyball athletes the myocardium exhibits better mechanical performance than in normal subjects.

Blood Pressure↗

Differences of adenylate cyclase localization in guinea-pig peritoneal macrophages under different physiological conditions: an ultracytochemical study.

The ultrastructural localization of adenylate cyclase activity has been investigated in unfixed guinea-pig peritoneal macrophages in different physiological states (such as suspension, adhesion and phagocytosis) using a medium containing 5'-adenylyl-imidodiphosphate (AMP-PNP) as the substrate. Adenylate cyclase activity was observed in cytoplasmic vacuoles of macrophages in suspension; in the perinuclear space, endoplasmic reticulum, Golgi complex and pseudopods of adherent macrophages; and surrounding phagocytosed polystyrene particles. The activity was inhibited by Alloxan added to the incubation medium and no staining was observed when AMP-PNP was omitted from the medium. The segregation of this enzyme to phagocytic vacuoles and pseudopods may have significant implications in understanding cyclic nucleotide function in adhesion and phagocytosis.

Adenylyl Cyclases↗

[Skeletal changes in acute lymphoblastic leukemia in children. Incidence and prognostic significance].

119 children with acute lymphoblastic leukemia at onset underwent radiography of the whole body in order to determine whether initial radiological bone lesions were correlated with subsequent clinical course. Radiological findings were divided into three groups: 101 children (84.8%) had no bone involvement (group 0); 10 had bone changes compatible with acute lymphoblastic leukemia, such as slight metaphyseal transverse lucent bands with or without diffuse demineralization (group 1); 8 had bone changes, such as periosteal reaction with or without intramedullary osteolytic mottling. Bone involvement was not correlated with prognostic factors. Furthermore there was no significant correlation between bone changes and complete remission or survival.

Adolescent↗

Involvement of glycosaminoglycans in detachment of early myeloid precursors from bone-marrow stromal cells.

Fibroblast-like cells were obtained by in vitro cultivation of needle aspirations of human bone-marrow. These cells show a unique composition of coat-associated glycosaminoglycans: 10% chondroitin 4-sulfate, 30% hyaluronic acid and 60% heparan sulfate which were resolved and characterized by electrophoresis, nitrous acid treatment and enzymatic degradation. Chondroitin 4-sulfate is the only glycosaminoglycan detectable on the surface of mature granulocytes, whereas the immature cells do not seem to possess surface glycosaminoglycans. Immature hemopoietic cells can adhere on to marrow-derived fibroblast cells, whereas mature granulocytes cannot. Treatment with mucopolysaccharidases of both mature leukocytes and marrow stromal cells can interfere in these adhesive relationships, suggesting a role of glycosaminoglycans in regulating short-range interactions during hematopoiesis.

Bone Marrow Cells↗