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Biomedical subjects
G Perona
Publications and source records attributed to G Perona.
Selenium and glutathione peroxidase variations induced by polyunsaturated fatty acids oral supplementation in humans.
Serum and erythrocyte selenium, erythrocyte and platelet glutathione-peroxidase (GSH-Px) activities, and erythrocyte reduced glutathione (GSH) content were measured in 25 healthy adult individuals before and after daily supplementation with 20 ml of fish oil for 10 weeks. Serum-Se decreased from 0.83 +/- 0.01 mumol/l to 0.75 +/- 0.02 mumol/l (mean +/- S.E.M.) (P less than 0.01); erythrocyte-Se decreased from 4.39 +/- 0.17 nmol/g hemoglobin (Hb) to 2.83 +/- 0.15 nmol/g (P less than 0.001). GSH-Px activities increased both in erythrocytes (6.93 +/- 0.24 iu/g vs 8.18 +/- 0.27 iu/g Hb, P less than 0.01) and in platelets (69.2 +/- 2.8 iu/g vs 90.9 +/- 3.6 iu/g protein, P less than 0.001). The concentration of GSH in erythrocytes fell from 9.56 +/- 0.29 mumol/g Hb to 5.90 +/- 0.30 mumol/g Hb (P less than 0.001). The effects on plasma lipids were evident only for triglycerides (before 1.96 +/- 0.16 mmol/l, after 1.75 +/- 0.14 mmol/l, P less than 0.001). We hypothesise the enrichment of erythrocyte and platelet membranes with polyunsaturated fatty acids (PUFAs), following fish oil intake, can generate increased amounts of lipid peroxides and thus allosterically activate GSH-Px: with time this is harmful for the integrity of the enzyme molecule and Se release may result. We suggest that the Se status of individuals given PUFAs is assessed before and during intake; Se supplements should only be given when serum and/or erythrocyte Se are reduced.
Administration, Oral↗
[Teaching hematology to medical students].
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Curriculum↗
Selenium dependent glutathione peroxidase: a physiological regulatory system for platelet function.
In human platelets the selenoenzyme glutathione peroxidase (GSH-Px) acts as a scavenger of the peroxides generated during the burst of arachidonic acid (AA) metabolism. Such a mechanism inhibits the biosynthesis of both thromboxane A2 (TXA2) and lipoxygenase products. The same mechanism is not effective on the prostacyclin (PGI2) biosynthesis from cultured endothelial cells. In order to evaluate this effect in vivo, besides in vitro, we activated the enzyme in eight normal volunteers by increasing their daily Se intake for 8 weeks, monitoring: platelet GSH-Px activity, platelet aggregation induced by AA and U 44069, and concurrent malondialdehyde (MDA) and thromboxane B2 (TXB2) production, urinary excretion of renal and systemic TXA2 and PGI2 metabolites, platelet enzyme activities of the hexose monophosphate pathway and glutathione content, platelet adenine nucleotides, bleeding time, plasma Se concentration. We found: a) progressive platelet GSH-Px activation by Se paralleling an enhancement of platelet aggregation threshold values for AA, but not for U 44069; b) concurrent inhibition of platelet biosynthesis of TXA2 both in vitro and in vivo while the biosynthesis of systemic prostacyclin was unaffected; c) a progressive increase in the bleeding time, unmodified by aspirin. In conclusion, we believe that Se-dependent GSH-Px represents a physiological mechanism regulating the biosynthesis of prostanoids with implications in platelet function and that a Se dietary supplement might be considered in the prevention of arterial thrombosis.
Adult↗
Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.
We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.
Adolescent↗
Determination of neutral haemoglobin variants by immobilized pH gradient, reversed-phase high-performance liquid chromatography and fast-atom bombardment mass spectrometry: the case of a Hb Torino alpha 43 (CE1) Phe----Val.
A neutral haemoglobin variant was identified by the combined use of different analytical methods. Isoelectric focusing on immobilized pH gradients (under denaturing conditions) allowed to detect and alpha chain variant. HPLC of tryptic digest showed that its amino-acid variation resided on T alpha 6 peptide (position 41-56). In the fast-atom bombardment (FAB) positive mass spectrum of the tryptic digest, the protonated molecular ion of the T alpha 6 peptide occurred 48 mass units lower than the normal T alpha 6 fragment, corresponding to a Phe----Val substitution. To a partial sequence determination (aminopeptidase digestion of the T alpha 6 peptide, followed by amino acid determination and FAB-MS analysis of the digestion-generated mixture) the substitution appeared to be on Phe43 (CE1). This variant is already known as Hb Torino. The procedure here described proved to be fast and simple, and feasible whenever neutral variants are supposed to occur.
Child, Preschool↗
Soluble interleukin-2 receptors in the serum of patients with Hodgkin's disease.
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Adolescent↗
A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia.
In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor. The haematological findings of the five patients were uniform, producing a benign form of thalassaemia intermedia, transfusion independent, with a long life expectancy. The pattern of inheritance of the two genetic determinants and the more pronounced beta/alpha globin chain imbalance, demonstrates that the genetic combination is indeed the cause of the phenotype. The pattern of restriction enzyme site polymorphisms suggests the presence of the beta IVS I 110 G----A mutation at least in three of these cases.
Adolescent↗
Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity.
In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.
Antibodies, Monoclonal↗
Platelet glutathione peroxidase activity is impaired in patients with coronary heart disease.
Platelet glutathione peroxidase (GSH-Px) activity was measured in 25 healthy individuals and in 25 patients affected with well-documented coronary artery stenosis. In parallel, malondialdehyde (MDA) production was assayed on platelets following stimulation with sodium arachidonate. Mean platelet GSH-Px activity was significantly reduced and mean platelet MDA production was significantly increased in the patient group. The difference observed in the GSH-Px activity might be a consequence of different nutritional habits, suggesting an impaired intake of selenium, the inorganic moiety of GSH-Px. As low GSH-Px activities in human platelets may be associated with increased MDA and thromboxane production, we hypothesize that a low enzyme activity may be a risk factor for the development of coronary artery disease.
Adult↗
Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement.
Selenium added to the culture medium of confluent pig aortic endothelial cells caused a time-related elevation in the activity of the hydroperoxide scavenging enzyme: glutathione peroxidase. This increased activity was associated with an enhanced ability to produce prostacyclin irregardless of whether the agonist was arachidonic acid or thrombin. Since prostacyclin synthetase is believed to be irreversibly inhibited by alkyl hydroperoxides, we feel that the greater production of prostacyclin by selenium-treated cells as compared with control cells may reflect a protective effect of GSH.Px towards the synthetase enzyme. The results from this study may explain the observations made on a group of human volunteers ingesting selenium as a dietary supplement. After six weeks treatment with selenium, bleeding time in this group was prolonged suggesting an improved ability to synthesize prostacyclin as a result of selenium-dependent glutathione peroxidase activation in the vessel wall.
6-Ketoprostaglandin F1 alpha↗
Assessment of liver and spleen involvement in Hodgkin's disease.
Prognosis and proper treatment in Hodgkin's disease (HD) are strictly related to staging accuracy: liver and spleen involvement is of particular importance in this regard. We have evaluated, in 113 consecutive patients, the accuracy of clinical parameters to detect histologically documented HD involvement by comparing hepatosplenomegaly, liver function tests, liver and spleen scan, inspection of liver and spleen surface at laparoscopy with histologic findings. Our data suggest that of all the parameters studied, laparoscopy has the highest sensitivity and specificity values (about 100%). Laparoscopy may precede laparotomy as a staging procedure in HD and may give, in patients not submitted to laparotomy whatever the reasons, very reliable information.
Adolescent↗
B cells in chronic lymphocytic leukaemia. Comparative analysis of blood and bone marrow.
A study was performed on cell suspension from peripheral blood and bone marrow aspirates and on cryostat sections from bone marrow biopsies in order to investigate the membrane phenotype of neoplastic B cells in chronic lymphocytic leukaemia (B-CLL). The immunological analyses, performed on 43 patients, included rosetting ability with sheep and mouse erythrocytes, evaluation of surface immunoglobulins and reactivity with anti-HLA-DR, UCHT 1 (OKT-3 like) and RFA-1 (OKT-1 like) monoclonal antibodies. The results demonstrate that neoplastic B lymphocytes in B-CLL display an identical phenotype in peripheral blood and bone marrow. Possible interpretations on the origin of proliferating cells in B-CLL are discussed.
Adult↗
Immunohistological analysis of Tac antigen expression in tissues involved by Hodgkin's disease.
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Antigens, Neoplasm↗
The enzyme glutathione peroxidase in arachidonic acid metabolism of human platelets.
We investigated the possible regulatory role of glutathione peroxidase on thromboxane formation by reducing peroxides in platelets. Experiments carried out in platelet lysates demonstrated that the burst of the arachidonate metabolism was accompanied by a simultaneous burst of hydrogen transfer from glutathione to peroxides, catalyzed by endogenous glutathione peroxidase. The burst of hydrogen transfer was partially inhibited by acetylsalicylate concurrently with the complete inhibition of malondialdehyde formation, thus suggesting that the hydrogen acceptor peroxides were derived in part from the cyclooxygenase pathway. Moreover, increasing glutathione peroxidase activity by adding purified enzyme to the incubation media decreases thromboxane formation. Intact platelets, stimulated with arachidonic acid or thrombin, produced malondialdehyde and thromboxane in amounts roughly inversely related to the endogenous glutathione peroxidase activity. In contrast, no correlation was observed between glutathione peroxidase activity and agonist-induced platelet aggregation. Our experiments suggest that in normal platelets, glutathione peroxidase controls thromboxane formation.
Adult↗
Empiric therapy of infections in hematologic malignancies: a prospective, randomized trial.
Patients with hematologic malignancies were randomly assigned to receive cefuroxime (group A) or tobramycin plus ampicillin (Group B) during 86 febrile episodes. In both regimens carbenicillin was added during neutropenia (71% of all episodes: groups C and D). The most common type of infection was pneumonia (48% alone; 72% with other sites involved), which accounted for a high fatality rate (15%); the highest rate occurred during septicemia with pneumonia (50%). The overall response rate to initial therapy was 63% without significant differences among the four regimens. The worst prognosis was observed in neutropenic patients without granulocyte recovery. When initial and cross-over trials were combined, there were favorable outcomes in 90% of all cases. Cefuroxime alone seems to be as effective as tobramycin plus ampicillin in the treatment of infections in hematologic malignancies. No side effects could be attributed to the cefuroxime-containing regimens.
Adolescent↗
A new glucose 6-phosphate dehydrogenase variant (G-6-PD Verona) in a patient with myelodysplastic syndrome.
A 67-year-old woman investigated because of 'myelodysplastic syndrome' was found to have a 4-fold increase in G-6-PD activity in her erythrocytes. The enzyme was partially purified and characterized. On grounds of: (a) reduced electrophoretic mobility, (b) abnormal cathodic band(s) in isoelectrofocusing, (c) increased Michaelis constant for glucose 6-phosphate, (d) abnormal thermostability, and (e) abnormal interaction with the ligand NADPH, we conclude that this is a new structural variant which we designate G-6-PD Verona. G-6-PD Verona was the sole apparent source of G-6-PD activity in the patient's erythrocytes; by contrast, the patient's fibroblasts had only normal G-6-PH (type B). The patient's haematological course terminated into acute myeloid leukaemia. We believe G-6-PD Verona was the result of a somatic mutation in an X-chromosome which took place in a haemopoietic cell clone which subsequently underwent neoplastic transformation.
Aged↗
Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia.
Bone marrow trephine biopsies from 17 patients with B-chronic lymphocytic leukemia (B-CLL) were studied by immunohistologic techniques in order to investigate the cellular phenotypes of both neoplastic (B-lymphoid) and reactive (T-lymphoid) infiltrates. For this purpose, several heteroantisera and monoclonal antibodies against human Ig isotypes, HLA-DR antigens, and T-cell subpopulations were used in immunofluorescence. The findings were analyzed in relationship to the histologic pattern of involvement, as well as to the immunologic data of cell suspensions from peripheral blood. In all cases, the dominant lymphoid population within the bone marrow infiltrates showed identical phenotypic characteristics of B-CLL cells from the blood (HLA-DR+, mu +, most frequently delta +, kappa +, or lambda +, and weakly RFA-1+). The infiltration by these malignant B cells was diffuse in 5 cases and nodular plus interstitial in 12. The number of T cells (UCHT1+, RFA-1+, mu) was variable (5%-25%) in the different samples, but the values were high when compared to the proportion of T cells in normal bone marrow and in the blood of most patients studied. Furthermore, a clear predominance of T cells exhibiting the inducer phenotype (Leu-3+) was observed in all bone marrow samples, which is in contrast with the findings from peripheral blood, where T cells with the suppressor/cytotoxic phenotype (Leu-2+) were dominant. These data suggest a different blood and tissue distribution of inducer and suppressor/cytotoxic cells in B-CLL, which may have important pathophysiologic significance.
Adult↗