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Biomedical subjects

M Grasso

Publications and source records attributed to M Grasso.

At least 181 records · Page 10Linked to original sources

Morphodynamic and biochemical assessment of seminal plasma in patients who underwent local prostatic hyperthermia.

Fourteen young and sexually active patients with chronic abacterial prostatitis who failed to respond to conventional medical therapy underwent four 60 minute sessions of local prostatic hyperthermia. Calculated prostatic temperature was 42 +/- 0.5 degrees C. Analysis of seminal plasma was performed pre- and postoperatively and included: number, motility, and morphology of spermatozoa; zinc, citric acid, D-fructose, and free testosterone content. Preoperative semen analysis was normal in five patients and abnormal in nine. Morphodynamic and biochemical patterns of seminal plasma were not significantly altered by thermotherapy. Local prostatic hyperthermia can be safely used in patients with chronic abacterial prostatis not responding to conventional medical therapy and desiring to preserve their reproductive potential.

Adult↗

The morphologic spectrum of dilated cardiomyopathy and its relation to immune-response genes.

Endomyocardial biopsies from 174 patients with dilated cardiomyopathy (DC) were examined. Eight patients with histologically proven myocarditis were excluded from the study. A peculiar pattern of oversized and bizarre nuclei was observed in only some of the remaining patients. Two groups were identified: those with and without this feature (groups A and B, respectively). Myocyte width, nuclear diameter and nuclear/sarcoplasmic ratio were significantly higher in group A. The mean respective values were 36 +/- 5 mu, 14 +/- 3 mu and 0.41 +/- 0.08 for group A versus 20 +/- 8 mu, 7 +/- 2 mu and 0.37 +/- 0.08 for group B. Interstitial fibrosis was similarly present in groups A and B. Endocardial thickness was significantly increased in all patients, with group A showing the highest mean value. The morphologic features showed no correlation with the clinical condition of the patients at time of presentation. HLA typing was performed in 50 consecutive patients, 38 from group A and 12 from group B. DR4 and DR5 antigens were significantly more frequent in DC patients than in a normal population control (400 blood donors), while DR3 was less frequent. Group A was more strongly associated with the DR5 antigen than group B (55.3 vs 25.0%, respectively). It was less strongly associated with the DR4 antigen compared with group B (21.5 vs 41.7%, respectively). No difference was observed between the 2 groups concerning negative association with the DR3 antigen. Endomyocardial biopsies from DC patients reveal marked morphologic changes from patient to patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Isochromosome not translocation in trisomy 21q21q.

After primary trisomy, "de novo" 21q21q trisomy is the most frequent chromosomal aberration responsible for Down syndrome. This rearrangement is more commonly referred to as a Robertsonian translocation or centric fusion product than as an isochromosome, e.g., t(21q;21q) instead of i(21q); however, in practice, it has not so far proved possible to distinguish between these alternatives. The aim of this work was to establish which of the two alternatives is acceptable.

Adult↗

Myocardial iron grading by endomyocardial biopsy. A clinico-pathologic study on iron overloaded patients.

Endomyocardial biopsy was performed in 13 patients with primary or secondary iron overload. Prussian blue staining showed visible iron in the biopsy fragments of 8 out of 13 patients. Because of the inhomogeneity of iron deposition in the biopsy fragments, a semi-quantitative myocardial iron grading system was used in which the percentage of Perls' positive cells on 4 to 6 biopsy fragments was averaged from each case. The presence of stainable iron in the myofibrils was not predictable from serum iron, transferrin saturation, serum ferritin or liver iron grading, nor from evidence of endocrine dysfunction. In patients with Perls' positive material in the myocardium, there was a significant correlation between the endomyocardial iron grade and serum iron and transferrin saturation. These results suggest that other factors besides the body iron load determine cardiac iron deposition. The fact that myocardial siderosis was documented only in patients with hepatic cirrhosis, irrespective of the hepatic iron load, suggests that severe liver damage may be a prerequisite for the accumulation of iron in the heart.

Adult↗

[Progressive changes in the lymphocyte subpopulations and the clinical picture in 2 brothers with familial dilated cardiomyopathy].

We report two brothers, aged 22 and 34, affected by dilated cardiomyopathy. At the first examination both patients were in NYHA functional class I. Their echocardiograms showed dilated and hypokinetic ventricles. Their clinical condition remained stable for three years, during which the peripheral immunophenotyping of T-lymphocyte subsets showed T-helper/T-suppressor ratio values lower than normal (normal value for our laboratory = 1.64 +/- 0.53) due both to low T-helper and to high T-suppressor subsets. Subsequently, the clinical condition of both patients deteriorated, exercise tolerance decreased and echocardiographic ventricular diameters increased. T-helper/T-suppressor ratio progressively increased from the initial values of 0.8 and 0.42 to 2.5 and 2.24, respectively. A few months later, both patients died, one because of refractory heart failure and the other one suddenly. Histologic examination of myocardial tissue in one patient showed a diffuse necrotizing disease involving myocytes with focal lymphocyte infiltrates, granulation tissue and endocardial thrombosis. The reported data underline the importance of genetic and familial factors in the pathogenesis and evolution of dilated cardiomyopathies. The increasing T-helper/T-suppressor ratio value which matched the deterioration of the clinical status, is proposed as a useful evolutive and prognostic marker.

Adult↗

Myocardial involvement due to a disseminated human cytomegalovirus infection in a heart transplant recipient. A case report.

A cytomegalovirus seronegative 9 year-old child, affected by terminal dilated cardiomyopathy, underwent cardiac transplantation and received the heart of a cytomegalovirus seropositive donor. After the positive outcome of an acute moderate rejection episode which was treated with steroids, the patient developed an infectious clinical syndrome with cytomegalovirus seroconversion and virus isolation from peripheral blood leukocytes. The 5th endomyocardial biopsy showed a typical cytomegalovirus-like nuclear inclusion in a single cell. In spite of specific treatment with (9-(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl-guanine) (BW B759U) (Wellcome), the patient died 45 days after the operation from cytomegalovirus-induced interstitial pneumonia and virus-associated hemophagocytic syndrome.

Cardiomyopathies↗

High efficiency in the attribution of parental origin of non-disjunction in trisomy 21 by both cytogenetic and molecular polymorphisms.

The precise origin of the supernumerary chromosome can be defined in the majority of trisomy 21 cases. This is achieved by evaluating the chromosome 21 short arm polymorphism and analysing restriction fragment length polymorphisms (RFLPs) of multiple chromosome 21 loci. We report a study on 37 Italian families with Down's syndrome. In 35 cases (94.6%) both the parental and the meiotic stage of non-disjunction could be established. Knowledge of the origin of the extra chromosome 21 is a pre-requisite for investigations of genetic or environmental factors that may affect the meiotic process.

Down Syndrome↗

Antigenic similarities among rodent urinary tract glycoproteins.

Urinary glycoconjugates (glycosaminoglycans, glycoproteins, mucopolysaccharides) have been postulated as the natural defense mechanisms which prevent urinary tract infections. As a direct approach to establish the validity of this hypothesis, we have prepared a glycoprotein fraction (GP1) from rabbit bladder mucosal tissue and shown that it may be involved in the prevention of bacterial adherence. Immunohistochemical studies using fluorescence have demonstrated that murine antibodies raised to rabbit GP1 can be used as a semiquantitative index of glycoprotein production. The present investigation addresses the question of the species restriction of the glycoprotein--whether it is confined to the rabbit or whether a similar or identical substance occurs in other species. Using an immunoperoxidase staining technique, we have examined the genitourinary tracts of Sprague Dawley rats, Golden hamsters, and Hartley guinea pigs. Mouse anti-rabbit GP1 was used as the primary antibody with an avidin-biotin complexing system. All three species reacted well with the murine antiserum but were negative with normal sera. Semiquantitative estimates of the relative amounts of this material in different areas of the genitourinary tract showed that the distal renal tubules, renal pelvic mucosa, ureters and bladders were rich in this glycoprotein while urethra and vagina were not.

Animals↗

Favism: impairment of proteolytic systems in red blood cells.

Red blood cells (RBC) from favic patients are characterized by (a) severe oxidative damage (contributed by autoxidation of divicine and isouramil, two pyrimidine aglycones present in fava beans) and (b) greatly increased calcium levels. In vitro, both autoxidation of divicine and calcium loading produced marked alterations of proteolytic systems in intact RBC. Specifically, autoxidizing divicine inactivated procalpain, the proenzyme species of calcium-activated cytosolic neutral proteinase, or calpain. Inactivation was much greater with glucose-6-phosphate dehydrogenase (G6PD)-deficient RBC than with normal RBC. On the other hand, loading of normal and G6PD-deficient RBC with calcium resulted in conversion of procalpain to calpain and eventual autoproteolytic inactivation of calpain itself, and extensive release of acid endopeptidase activity from the membranes into the cytosol. Damaged RBC from favic patients had significantly lowered procalpain activity and an abnormal subcellular distribution of acid proteinase activity that was found mostly in the cytosol. When purified calpain was incubated with membranes from acetylphenylhydrazine (APH)-treated RBC, significant proteolysis was observed affecting mostly band 3 and hemoglobin chains, ie, the two proteins involved in the onset of aggregation of Heinz bodies. Moreover, exposure of intact RBC to 20 mmol/L APH induced depletion of procalpain activity for which the time course was inversely related to formation of Heinz bodies. These findings support the role of procalpain in protecting G6PD-deficient RBC from oxidant-induced Heinz body formation and imply that exhaustion of the procalpain-calpain system is an important step in the mechanisms of RBC damage and destruction in favism.

Calcium↗

Alterations of red blood cell proteolysis in favism.

Damaged RBC drawn from favic patients during acute hemolysis showed marked alterations in their two major proteolytic systems. Cytosolic procalpain (i.e., the proenzyme species of Ca2+-activated neutral proteinase, or calpain) had considerably lower activity than in matched RBC from asymptomatic G6PD-deficient subjects. The total RBC activity of the three acid endopeptidases that are normally membrane-bound was not reduced in favism, but its subcellular distribution was mostly cytosolic, suggesting quantitative release from membranes. Changes in procalpain activity are the result of both autoxidation of divicine and of the intracellular elevation of Ca2+ that is found in favism. Changes in acid endopeptidase activity are the consequence of perturbed Ca2+ homeostasis. Overall, the picture shows a marked impairment of the RBC proteolytic machinery that in turn may worsen cellular damage.

Calcium↗

Myocarditis and cardiomyopathy: diagnosis by endomyocardial biopsy.

UNLABELLED: To investigate the incidence of myocarditis, 30 patients, with unexplained congestive heart failure, underwent endomyocardial biopsy. For each case three to five samples were examined on light and electron microscopy. Inflammatory infiltrates and injury to adjacent myocytes consistent with myocarditis were detected in 3 of the 30 cases (10%). Changes attributable to cardiomyopathy were found in the remaining 27 cases. Two of the three patients with biopsy-proven myocarditis were treated with prednisone and azathioprine. Their control biopsies six months later showed interstitial fibrosis and absence of inflammatory infiltrates. They clinically improved but hemodynamic and angiocardiographic patterns failed to show the expected improvement. The third patient affected by myocarditis died two weeks later. IN CONCLUSION: in our series of patients with unexplained congestive heart failure, the incidence of biopsy-proven myocarditis resulted low (10%). The results of the immunosuppressive treatment in two patients with myocarditis were unconclusive. Therefore the effectiveness of such therapy should be confirmed in a larger number of patients.

Biopsy↗

Oxidative inactivation of the calcium-stimulated neutral proteinase from human red blood cells by divicine and intracellular protection by reduced glutathione.

Calpain, the micromolar Ca2+-requiring form of Ca2+-stimulated neutral proteinase purified from human red cells, is remarkably inactivated during autoxidation of divicine (2,6-diamino-4,5-dihydroxypyrimidine), an aglycone implicated in the pathogenesis of favism. Inactivation of purified calpain is produced, in decreasing order of efficiency, by transient, probably semiquinonic species arising from autoxidation of divicine, by the H2O2 that is formed upon autoxidation itself, and by quinonic divicine, respectively. Purified procalpain, the millimolar Ca2+-requiring form that can be converted to the fully active calpain form by a variety of mechanisms, is less susceptible than calpain itself to inactivation by the same by-products of divicine autoxidation. When intact red cells are exposed to autoxidizing divicine, procalpain undergoes a significant loss of activity. At 1 mM divicine, intracellular inactivation is observed with procalpain only, while the activity of a number of red cell enzymes is unaffected. Inactivation of procalpain is consistently greater in red cells from glucose-6-phosphate dehydrogenase-deficient subjects than in normal cells. Restoration of normal levels of glucose-6-phosphate dehydrogenase activity by means of entrapment of homogeneous human glucose-6-phosphate dehydrogenase in the deficient red cells results in normal stability of intracellular reduced glutathione; decreased susceptibility of procalpain to inactivation by autoxidizing divicine. These findings suggest that in the glucose-6-phosphate dehydrogenase-deficient red cells the procalpain-calpain system is a major target of divicine cytotoxicity.

Calpain↗

Calcium-induced alterations in the levels and subcellular distribution of proteolytic enzymes in human red blood cells.

Human red cells were treated with 100 microM Ca2+ and ionophore A 23187. This treatment induces remarkable changes in the activities of the two major proteolytic systems of red cells, i.e. Ca2+-dependent neutral proteinase and acid endopeptidases. Ca2+-dependent neutral proteinase undergoes intracellularly preliminary activation of the inactive proenzyme species, followed by eventual inactivation through self-proteolysis. Transient activation is shown by selective degradation of cytoskeletal proteins known to be targets of this enzyme system. Concomitantly, acid endopeptidase activity is substantially released from the membrane into the cytosol. Preliminary inactivation of the Ca2+-dependent neutral proteinase by exposure of Glucose 6-phosphate dehydrogenase-deficient red cells to auto-oxidizing divicine prevents alterations induced by Ca2+ loading on cytoskeletal membrane proteins, while leaving solubilization of acid endopeptidase activity unaffected. The two events, although dependent on Ca2+ loading, are therefore unrelated to each other.

Calcimycin↗

Effect of nerve growth factor on glucose utilization and nucleotide content of pheochromocytoma cells (clone PC12).

The effect of nerve growth factor (NGF) on the utilization and fate of uniformly labeled 14C glucose and on the content of several pyridine and purine nucleotides has been tested in the clonal cell line PC12. After incubation for 72 h with NGF, PC12 cells exhibit a 2.7-fold increase in glucose utilization and a 4.7-fold increase in CO2 release. During the same incubation period, all the nucleotides tested (NAD+, AMP, GMP, UDP-glucose, UDP-galactose, UDP, ADP, GDP, UTP, CTP, ATP, and GTP) underwent significant increments, varying from a minimum of 27% for ADP to a maximum of 90-120% for AMP, GMP, UDP-glucose, and UDP-galactose. These findings are discussed in connection with the trophic and differentiative effects of NGF in PC12 cells, which, in the presence of this factor, shifted from a neoplastic to a neuronal-like cell population.

Adenosine Monophosphate↗