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Biomedical subjects

L Sacchetti

Publications and source records attributed to L Sacchetti.

70 records · Page 4Linked to original sources

Serum immunoglobulins in homozygous beta-thalassemia.

IgG, IgA and IgM levels were studied in 187 homozygous beta-thalassemic patients and compared with age-matched normal control subjects. The not yet transfused and the polytransfused nonsplenectomized patients showed a significant increase of all Ig classes. The polytransfused splenectomized patients showed a significant increase only of IgG and IgA. The splenectomized patients, when compared to the nonsplenectomized ones, showed a significant increase of IgG, of IgA in the elder ones and a significant reduction of IgM. High ASLO and ASFLO titers were found especially in the splenectomized patients. The high Ig levels in younger not yet transfused patients, with little iron storage and normal hepatic enzyme values, demonstrate that transfusion therapy and liver damage do not play a main role in hypergammaglobulinemia. The absence of antimitochondrial, anticonnective tissue and homogeneous antinuclear antibodies seems to exclude a deficient suppressor mechanism. The hemocatheteric "overworking' of RES may reduce the antigen clearance with a consequent increase of antibody response. Splenectomy, by removing a consistent part of RES, enhances the phenomenon.

Adolescent↗

Behaviour of myeloid precursors in homozygous beta thalassaemia.

Maintaining a high haemoglobin level, through a high transfusion regime, is the best method for treating thalassaemia. Not much is known about the effect of this treatment on medullary or extramedullary haemopoiesis, particularly on the extent of erythropoietic inhibition and on the behaviour of myelopoiesis. In order to analyse some aspects of the problem, we studied the myeloid stem cells (CFU-c) in the bone marrow and in the peripheral blood of children with homozygous thalassaemia, using the agar culture technique. The number of circulating CFU-c observed in 68 patients was higher than in normal subjects. This number was significantly increased after splenectomy. A positive correlation was demonstrated between the number of circulating CFU-c and the time elapsed since the last transfusion. Patients with a high Hb level displayed a marked reduction in the number of CFU-c in their peripheral blood. In 10 patients, before the beginning of transfusions, bone marrow CFU-c were lower than in normal subjects; their number increased after therapy. Most circulating CFU-c were proliferating as shown by the thymidine suicide technique.

Adolescent↗

Electrophoretic behavior and partial characterization of disease-associated serum forms of gamma-glutamyltransferase.

We have recently devised an improved procedure for the rapid electrophoretic separation of multiple forms of serum gamma-glutamyltransferase (GGT). This procedure is based on the separation on cellulose acetate strips, usually employed for lipoprotein electrophoresis, followed by visualization with a fluorescent reagent. The method is highly sensitive and the fractions are more clearly resolved than with other procedures. Reference intervals have been evaluated in the sera from 142 healthy subjects and the patterns (two GGT forms comigrating with alpha 1 and alpha 2-globulin) are reproducible. In 150 sera from patients with various hepatobiliary diseases (including neoplasias), acute pancreatitis and non liver-involving neoplasias, we observed some disease-specific GGT forms: an albumin comigrating enzyme (Alb-GGT) specific of liver neoplasia; a gamma-globulin comigrating GGT (gamma-GGT) and a nonmigrating isoform (dep-GGT) both specifically associated to extrahepatic jaundice. Multiple lipoprotein fraction precipitation showed that beta-, gamma- and dep-GGT are complexes between GGT and low density lipoprotein and very low density lipoproteins (LDL + VLDL), and that some of the alpha 1-GGT from cirrhotic patients is a complex between GGT and high density lipoprotein (HDL). GGT fractions from normal subjects and Alb-GGT from patients with liver neoplasia do not appear to be complexed with lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Genetic typing of Corallium rubrum.

Corallium rubrum taxonomy is based on morphologic criteria; little is known about its genome. We set up a rapid, easy method based on amplified fragment length polymorphism to characterize the genetic patterns of C. rubrum in an attempt to understand better the evolutionary relations between species from diverse geographic areas and to help define migration patterns. Applying this procedure to C. rubrum specimens from Spain and Italy, we identified 6 AFLP amplification fragments common to the 4 coral populations studied and 4 fragments that differentiated between these populations. Using this characterization we were able to plot a "genetic identity card" of this commercially harvested species, which is also a marker of pollution.

Animals↗

Pyrimidine 5'-nucleotidase and oxidative damage in red blood cells transfused to beta-thalassemic children.

Pyrimidine 5' nucleotidase (P5'N) acquired deficiency has been found in several hematologic disorders including beta-thalassemia. Our previous studies suggested that the aldehydes produced during membrane lipid peroxidation could play a role in P5'N inactivation in thalassemia. To evaluate the effects of the thalassemic "environment" on transfused red blood cells, we tested P5'N, pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G-6PD) activity, creatine content, reduced glutathione (GSH) levels and the hexose monophosphate shunt (HMS) in the red cells of homozygous transfusion-dependent thalassemic children, immediately following and again one month after transfusion. In red cells aged in thalassemic plasma, P5'N activity, creatine level, GSH stability and stimulated HMS flux were significantly decreased. These results fit in with the presence in thalassemic plasma of molecules interfering with antioxidant red cell defenses. Normal red cells incubated in thalassemic plasma display a significant stimulation of the basal HMS (p less than 0.01). Transfused red cell metabolic alterations could be explained by the plasma pro-oxidant activity and may contribute to reducing red cell survival in the host plasma.

5'-Nucleotidase↗

Analysis of the carbonyl compounds produced in beta thalassaemic erythrocytes by oxidative stress.

Several carbonyls more toxic than malonaldehyde (MDA) are also generated during the propagation of lipid peroxidation stimulated "in vitro" in human erythrocytes. As regards thalassaemia, after "in vitro" treatment with tert-butyl hydroperoxide (TBHP), the total amount of aldehydes formed (MDA plus the other carbonyls) is significantly increased in the red cells from homozygous as compared to heterozygous and normal subjects. These findings lead to the conclusion that the extent of lipid peroxidation in erythrocytes is actually wider than that measurable in terms of malonaldehyde only, and that aldehydes of the hydroxyalkenal class in particular may play a role in the pathogenesis of reduced red cell survival in haemolytic anaemias.

Aldehydes↗

Gamma-glutamyltranspeptidase isoenzyme forms and lipoproteins in normal and pathological sera.

The molecular nature of serum (from normal subjects and from patients affected by various hepatobiliary diseases) gamma-glutamyltranspeptidase (GGT) isoenzymes has been studied by selective lipoprotein precipitation. Some fractions co-precipitate with LDL + VLDL (pre-beta-, beta-, beta/gamma-, gamma-, and dep-GGT fractions) or with HDL (partial precipitation of alpha 1-GGT in cirrhosis). Alpha 1-GGT + alpha 2-GGT in normal subjects, and Alb-GGT did not precipitate with either of the precipitation treatments. Total GGT and its isoenzymes were stable at 4 degrees C and at -20 degrees C for at least 20 days, with the exception of Alb-GGT which at -20 degrees C decreased by 20%. The percentage of GGT associated with LDL + VLDL appeared to be a possible marker to discriminate liver tumors from cirrhosis. A cut-off value of 20 U/L of this marker yielded a diagnostic sensitivity of 87% and a diagnostic specificity of 85%.

Cholestasis↗

The use of receiver operating characteristic (ROC) curves analysis in the evaluation of the diagnostic efficiency of serum pseudouridine as a tumor marker.

The biochemical parameters used in this study were: (1) serum pseudouridine, expressed as nmols/mL; (2) pseudouridine index, expressed as mol to mol ratio of serum pseudouridine versus serum creatinine concentration. The receiver operating characteristic (ROC) analysis has been used to exemplify the selection of discriminant values or "cut-off points" to maximize the diagnostic utility of a biochemical tumor marker, serum pseudouridine. This marker has been used in a variety of group population samples, i.e., normal subjects, subjects affected by several nonneoplastic diseases, subjects with neoplastic disorders in less advanced or more advanced stages, and finally in a sample population of patients affected by lymphomas and leukemias of different types. An analysis of the relative ROC curves allowed the selection of cut-off values that maximize the diagnostic efficiency or, alternatively, the diagnostic sensitivity or the diagnostic specificity for pseudouridine parameters, and has allowed the comparison of the two tests to answer the same clinical question.

Biomarkers, Tumor↗

A specifically induced bronchoconstriction by distilled water in children and adults.

Respiratory function (FVC, FEV1, FMF and FEF200-1200) was measured before and after nebulized distilled water in 68 subjects divided in the five following groups: a) 21 healthy children (age range 7 to 15 years); b) 10 children with asthma (age range 6 to 11 years); c) 10 children with cystic fibrosis (age from 5 to 15 years); d) 7 children with different diseases of the respiratory system (age range from 6 to 11 years); e) 20 healthy adults (aged from 18 to 33 years). The only statistically significant changes were noted in the asthmatic children group. We conclude that a specifically induced bronchoconstriction by nebulized distilled water is a good mean of assessing bronchial lability.

Adolescent↗