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2.
J Immunol ; 142(3): 913-8, 1989 Feb 01.
Article in English | MEDLINE | ID: mdl-2536415

ABSTRACT

In various mammalian cell types the stimulation of the plasma membrane amiloride-sensitive Na+/H+ exchange and the resulting increase of intracellular pH (pHi) play a key role in the initiation of cell proliferation. In the present work we have investigated whether Na+/H+ exchange is involved in normal human B cell proliferation and whether it is also operating in malignant B-chronic lymphocytic leukemia (B-CLL) lymphocytes. Our results show that: 1) normal human B cells contain an operating Na+/H+ exchanger, as inferred by their ability to recover pHi after acid-loading in a HCO3- -free medium and by evidences that LPS and phorbol ester PMA elicit a pHi rise inhibitable by either 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or a Na+-free medium; 2) LPS-induced proliferation of normal human B cells is strongly inhibited when the amiloride analog EIPA (5 microM) is present in the culture medium (after 72 h the proportion of B cells incorporation bromodeoxyuridine falls from 13.9 +/- 3.9% to 2.8 +/- 1.1%); 3) EIPA does not affect BdR incorporation when B cells proliferation is induced by the co-mitogenic activity of IL-4 and low m.w. B cell growth factor (BCGF); 4) B-CLL cells, which proliferate in response to IL-4/BCGF but not to LPS, fail to increase pHi above their pHi resting levels when challenged with LPS or PMA and pHi recovery after acid-loading is highly impaired. These results lead to conclude that Na+/H+ exchange operation is necessary for LPS-(but not for IL-4/BCGF)-induced proliferation of human normal B lymphocytes and that Na+/H+ exchange activation is impaired in malignant B-CLL lymphocytes.


Subject(s)
B-Lymphocytes/metabolism , Carrier Proteins/physiology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Lipopolysaccharides , Lymphocyte Activation , Aged , Amiloride/analogs & derivatives , Amiloride/pharmacology , B-Lymphocytes/classification , B-Lymphocytes/immunology , Child , Female , Humans , Hydrogen-Ion Concentration , Interleukin-4 , Interleukins , Leukemia, Lymphocytic, Chronic, B-Cell/classification , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Lymphocyte Activation/drug effects , Male , Middle Aged , Sodium-Hydrogen Exchangers
3.
Scand J Haematol ; 27(5): 311-22, 1981 Nov.
Article in English | MEDLINE | ID: mdl-7051264

ABSTRACT

The presence of immune-complexes (IC) and antipolymorphonuclear neutrophil (PMN) autoantibodies was investigated in 28 patients with chronic idiopathic neutropenia and normal or hypercellular bone marrow, 19 with a metamyelocyte arrest and 9 with more dysplastic features. The in vivo interaction between IC and PMN membrane receptors was evaluated by means of the PMN immunohistological technique. Circulating IC was evaluated with the C1q and rheumatoid factor agglutination inhibition techniques. An anti-PM autoantibody activity was investigated by challenging Fab obtained from the sera of 22 patients with PMN from normal donors. IC were detected in a high percentage of patients; in no case could an anti-PM autoantibody activity be seen. Most patients with a metamyelocyte arrest, but only 1 with more dysplastic features, were IC+. During a follow-up period of l2-52 months, none of the patients with a metamyelocyte arrest (IC+) developed anaemia, thrombocytopenia or leukaemia, while anaemia and thrombocytopenia were almost the rule in the clinical course of dysplastic bone marrow IC- patients: 2 of them developed acute myeloblastic leukaemia.


Subject(s)
Agranulocytosis/immunology , Antigen-Antibody Complex/analysis , Neutropenia/immunology , Neutrophils/immunology , Adult , Aged , Agglutination Tests , Autoantibodies/analysis , Blood Cell Count , Bone Marrow/pathology , Complement C1 , Female , Humans , Immunologic Techniques , Male , Middle Aged , Neutropenia/blood
4.
Br J Haematol ; 49(1): 17-21, 1981 Sep.
Article in English | MEDLINE | ID: mdl-7272228

ABSTRACT

Sixteen patients with idiopathic myelofibrosis (IM) have been investigated with respect to the possibility that immune mechanisms may be of importance in the pathogenesis of bone marrow fibrosis. The following points appear relevant: (1) immune-complexes (IC) are detectable with different techniques in a high percentage of patients with IM. Their presence is associated with evidence of bone-marrow histological markers of immune activity. (2) IgG is the main Ig class in the composition of IM IC. The results obtained favour the hypothesis that autoimmune mechanisms are involved in IM patients.


Subject(s)
Antigen-Antibody Complex/analysis , Primary Myelofibrosis/immunology , Aged , Autoimmune Diseases , Bone Marrow/immunology , Female , Humans , Immunoglobulin G/metabolism , Immunoglobulins/metabolism , Male , Middle Aged , Primary Myelofibrosis/etiology
5.
Clin Nephrol ; 14(6): 280-7, 1980 Dec.
Article in English | MEDLINE | ID: mdl-7008994

ABSTRACT

Twenty-nine patients with Systemic Lupus Erythematosus (SLE) and 6 patients with Acute Poststreptococcal Glomerulonephritis (APGN) have been studied with the polymorphonuclear neutrophil (PMN) immunohistological technique to detect in vivo interaction between circulating immune complexes (IC) and PMN membrane receptors. Patients have been studied both at diagnosis and during follow-up and the results compared to those yielded by the C1qSP test. Our data provide evidence that the PMN immunohistological technique may prove a useful tool in monitoring IC disease. Moreover, elution studies may allow the detection and characterization of the antigens in the PMN-bound IC.


Subject(s)
Antigen-Antibody Complex/isolation & purification , Glomerulonephritis/immunology , Lupus Erythematosus, Systemic/immunology , Neutrophils/immunology , Cell Membrane/immunology , Follow-Up Studies , Humans , Immunologic Techniques
7.
Int Arch Allergy Appl Immunol ; 62(1): 1-15, 1980.
Article in English | MEDLINE | ID: mdl-7372359

ABSTRACT

This study reports the results of in vitro investigations on the aggregation of polymorphonuclear neutrophils (PMN) induced by the C5a anaphylatoxin complement component as well as the cationic proteins (CP), which are released by challenging PMN with immune complexes (IC). The carboxy-peptidase-derived des-Arg fragments of CP and C5a; CPi and C5ai, inactive in terms of anaphylactic and chemotactic activity, nevertheless showed a more potent ability to aggregate PMN than CP and C5a. The process of PMN aggregation required metabolic energy and divalent cations, Ca++ and Mg++. The microtubular system and the subplasmalemmal microfilaments appeared to be of critical importance. Electron microscopic studies on aggregates of PMN obtained on stimulation with CP, C5a, CPi and C5ai showed parallel tracts of variable length of cell membranes at the points where cells were in contact with each other.


Subject(s)
Anaphylatoxins/pharmacology , Antigen-Antibody Complex , Complement C5/analogs & derivatives , Neutrophils/immunology , Peptides/pharmacology , Anaphylatoxins/isolation & purification , Animals , Blood Proteins/metabolism , Cell Aggregation , Chromatography, Gel , Chromatography, Ion Exchange , Complement C5/isolation & purification , Complement C5a, des-Arginine , Cytoplasmic Granules/analysis , Electrophoresis, Cellulose Acetate , Glucuronidase/metabolism , Humans , Molecular Weight , Neutrophils/ultrastructure , Rabbits
8.
Arch Sci Med (Torino) ; 136(2): 295-302, 1979.
Article in Italian | MEDLINE | ID: mdl-518282

ABSTRACT

90 patients suffering from Hodgkin's disease, 32 in stages I and II, 42 in stage III and 16 in stage IV have been studied retrospectively. The first were treated with supra and subdiaphragmatic extensive radiotherapy, the second with total nodal or polychemotherapy (MOPP), the third with polychemotherapy. Results were highly satisfactory in stages I and II with a complete remission rate of 100% (duration: 4/100 months) and with survival of 91.8% at 7 years. At the 3rd stage, total nodal therapy led to complete remission in 73.3% of patients (9--46 months) with 5-year survival of 76.1%; at this stage, polychemotherapy induced complete remission in 65.2% of cases (6--34 months) with 4-year survival of 64%. Much worse were the results of polychemotherapy in the IVth stage. The same series has been reconsidered with allowance for explorative laparotomy by splenectomy carried out in 15 patients in I-II stage and treated with extensive radiotherapy, in 7 IIIrd stage patients subjected to total nodal therapy and in 10 in IIIrd stage treated with MOPP. In IIIrd stage splenectomized patients, the incidence of recurrences is lower than in the controls and independent of treatment. The lower incidence of recurrences also observed in I-II stage cannot be evaluated for the moment.


Subject(s)
Antineoplastic Agents/therapeutic use , Hodgkin Disease/therapy , Adult , Antineoplastic Agents/administration & dosage , Drug Therapy, Combination , Evaluation Studies as Topic , Female , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Humans , Male , Neoplasm Staging , Remission, Spontaneous , Retrospective Studies , Splenectomy , Time Factors
9.
Int Arch Allergy Appl Immunol ; 58(2): 135-9, 1979.
Article in English | MEDLINE | ID: mdl-154476

ABSTRACT

A simple immunohistological test has been developed to detect and to quantitate the presence of immune complexes (IC) on the surface of human polymorphonuclear neutrophils (PMN). The interaction between IC and PMN has been evaluated in several human IC diseases. High amounts of immunoglobulins (Ig) and C3 were detected on the PMN surface from these patients. The deposits of Ig and C3 were inversely related to the percentage of membrane-free receptors for Fc and C3.


Subject(s)
Immune Complex Diseases/immunology , Neutrophils/immunology , Acid Phosphatase/blood , Alkaline Phosphatase/blood , Humans , Immune Complex Diseases/diagnosis , L-Lactate Dehydrogenase/blood , Lupus Erythematosus, Systemic/immunology , Phagocytosis , Polyethylene Glycols/blood , Receptors, Antigen, B-Cell
10.
Br J Haematol ; 33(1): 91-9, 1976 May.
Article in English | MEDLINE | ID: mdl-1268093

ABSTRACT

The haematological and clinical data in 254 Italian subjects with beta-thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4-15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5% to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers.


Subject(s)
Thalassemia/blood , Adolescent , Blood Cell Count , Child , Child, Preschool , Erythrocytes , Female , Hemoglobins/analysis , Humans , Italy , Male , Osmotic Fragility , Reticulocytes , Thalassemia/epidemiology
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