Search PubMed⌕ Search

Biomedical subjects

P Corradini

Publications and source records attributed to P Corradini.

At least 73 records · Page 4Linked to original sources

B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50.

A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.

Amino Acid Sequence↗

Dual rearrangement of immunoglobulin and T-cell receptor gene in a case of T-cell hairy-cell leukemia.

We report a case of T-cell hairy-cell leukemia with a dual rearrangement of Ig- and T-cell receptor genes. The cytochemical, transmission electron microscopy, and surface antigens data (CD3+, CD8+, CD11+, HLA-DR+, CD19-, CD20-) were consistent with a T-cell hairy-cell leukemia. Molecular analysis according to Southern revealed a dual rearrangement of immunoglobulin heavy-chain (JH) and T-cell receptor beta (TcR beta) chain genes. Our findings suggest that the coexistence of JH and TcR gene rearrangements, frequently detected in acute leukemia, may also be observed in hematologic malignancies derived from more differentiated cells.

Aged↗

Human homologue of Moloney leukemia virus integration-4 locus (MLVI-4), located 20 kilobases 3' of the myc gene, is rearranged in multiple myelomas.

The structure of the c-myc locus and the flanking chromosomal region was investigated by Southern blot analysis of DNA from bone marrow aspirates from 42 patients with multiple myeloma. The main abnormality detected was the rearrangement of the MLVI-4 locus, 20 kilobases 3' of c-myc, which was observed in seven cases (16%). Two of these rearrangements were detected at the time of the initial diagnosis, four during treatment, and one at relapse, and their presence correlated with unresponsiveness to therapy. The MLVI-4 locus represents the human homologue of the Moloney leukemia virus integration-4 locus (Mlvi-4), a common region for provirus integration in Moloney murine leukemia virus-induced T-cell lymphomas in rodents. Provirus integration in this locus activates c-myc, and two additional genes, Mlvi-4 and Mlvi-1. The c-myc gene was rearranged in one patient; mutations involving the first exon of c-myc, frequently detected by altered restriction enzyme recognition sites in Burkitt's lymphomas, were not observed in these myelomas.

Chromosome Mapping↗

[Metadoxine in alcohol-related pathology].

Metadoxine is an active drug for treatment of acute and chronic alcohol intoxication, affecting both liver and brain function. The authors reviewed the international pharmacological and clinical literature on the drug which shows the potential usefulness of metadoxine in the treatment of alcohol-induced diseases. The case report concerns the results in 20 chronic alcoholics, admitted to the hospital for acute alcohol intake treated with metadoxine (one 500 mg tablet twice daily). Biohumoral hepatopathy parameters and clinical parameters of neuropsychic behaviour were examined simultaneously. Compared with a control group of patients undergoing traditional therapy (sedative and multi-vitamin drugs), metadoxine showed a significant improvement of the values of gamma-GT, GPT, blood ammonia, blood alcohol and of neuropsychic and behavioural parameters such as agitation, tremor, asterixis, sopor and depression. No side-effects or unfavourable reactions occurred during metadoxine treatment, which confirms the safety of this molecule.

Adult↗

Philadelphia-positive thrombocythemia with a complex translocation involving chromosomes 9, 15, and 22.

We report a case of Philadelphia chromosome (Ph) positive thrombocythemia with a complex translocation. G-banding analysis showed the predominant karyotype to be 46,XX,t(9;15;22). Southern blot analysis revealed a rearrangement within the breakpoint cluster region on chromosome 22 similar to findings in chronic myeloid leukemia. These data suggest the presence of a complex Ph translocation involving t(9;15;22)(q34.1 or q34.3;q26.1;q11 or q13).

Adult↗

Measurement by bioluminescence technique of erythrocyte membrane Na+,K+-ATPase activity in hypertensive patients.

Erythrocyte membrane Na+,K+-ATPase activity was measured using a bioluminescence technique in 28 hypertensive patients (24 with essential hypertension, 2 with renovascular hypertension and 2 with hypertension secondary to primary hyperaldosteronism) and in 28 normotensive control subjects matched for age and sex. Erythrocyte Na+,K+-ATPase activity was significantly reduced in the patients with essential hypertension (130.9 +/- 11.4 vs. 186.6 +/- 19.5 nmol ATP/mg prot per h; mean values +/- SEM; p less than 0.05) and in the patients with secondary hypertension. A significant negative correlation was found between erythrocyte Na+,K+-ATPase and systolic blood pressure (r = -0.603; p less than 0.01), but not between Na+,K+-ATPase and plasma renin activity or plasma aldosterone levels. These data confirm the findings of a number of previous studies reporting reduced activity of erythrocyte Na+,K+-ATPase possibly related to the presence of a circulatory inhibitor of sodium pump. The method, based on ATP assay by bioluminescence, presents a high degree of specificity as well as simple, rapid execution.

Adult↗

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Intracellular free calcium, [Ca2+]i, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca2+]i was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 +/- 5.0 vs 143.2 +/- 3.1 nmol/L; p less than 0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca2+]i in both the presence and absence of extracellular calcium. This [Ca2+]i increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p less than 0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca2+]i increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca2+]i but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.

Adult↗

Nizatidine in the short-term treatment of duodenal ulcer--an Italian Multicenter Study.

One hundred and seventy three patients suffering from duodenal ulcer, were selected for a double-blind, controlled and randomized parallel multicenter study, with interval endoscopic examinations. This study was undertaken to compare the efficacy and safety of nizatidine administered at a single dose (300 mg "nocte") versus ranitidine (300 mg "nocte") in the treatment of acute duodenal ulcer. One hundred and sixty five patients were found to meet every admission criterion and completed the study (86 on nizatidine and 79 on ranitidine). On admission to the study, both groups were seen to have been correctly selected and epidemiologically well-distributed as to history of duodenal ulcer, previous treatments and pre-study symptoms. The ulcer was considered healed when complete re-epithelialization had occurred in areas of ulcerated mucosa. Healing rates of duodenal ulcer proved to be globally similar in the two groups, both in the 4th week (nizatidine, 78%; ranitidine, 78%) and in the 8th week (nizatidine, 91%; ranitidine, 95%). After four weeks of treatment, 67% of the patients treated with nizatidine no longer had any symptoms, while 87% patients no longer suffered from day pain, and 91% had no nocturnal pain. As a result, intake of antacids quickly decreased during the first four weeks. A similar response was observed in the group receiving ranitidine. After administration at a single dose of 300 mg in the evening, nizatidine proved to be at least as effective and safe as 300 mg of ranitidine administered in the same way, with respect both to ulcer healing and symptom response.

Adult↗

Short-term treatment of reflux oesophagitis with ranitidine 300 mg nocte. Italian multicentre study.

A multicentre study involving 9 Italian institutions was carried out to compare the efficacy and safety of ranitidine 150 mg b.i.d. and ranitidine 300 mg nocte in the treatment of reflux oesophagitis. 117 patients with histologically proven oesophagitis were randomly allocated to two comparable treatment groups. Efficacy and reliability were evaluated by clinical and laboratory tests at the beginning of the study, and at 3 and 6 weeks; endoscopy and biopsies were performed at the beginning and at 6 weeks. Treatment with ranitidine for 6 weeks led to total disappearance of gastro-oesophageal reflux symptoms in 60% of patients, with percentages of partial improvement varying between 85% and 95% of cases. Improvement in the results of endoscopic examination was 85%, of which 55% were cured. Microscopic examination revealed an improvement of 36% and 44%, with a cure rate of 18% and 26% respectively. With regard neither to the regression of symptoms nor to the macroscopic and microscopic inflammation of the oesophageal mucosa did statistical examination show significant differences in the therapeutic efficacy of ranitidine 150 mg b.i.d. or 300 mg nocte for treatment of reflux oesophagitis.

Adult↗

Verapamil inhibits platelet aggregation by a calcium-independent mechanism.

We studied the inhibitory effects of the calcium channel blocker verapamil both on platelet aggregation and intracellular calcium [Ca2+]i in platelets loaded with a fluorescent indicator (quin 2). The inhibitory effects of verapamil on the platelet aggregation response to both thrombin and ionomycin were seen to be clearly dissociated from the verapamil-induced inhibition of the [Ca2+]i increase produced by these agonists. Verapamil-induced inhibition of platelet aggregation was also obtained when using the "calcium-independent" agonist phorbol-myristate acetate (PMA). It may be deduced that a calcium-independent mechanism plays a role in verapamil-induced inhibition of platelet aggregation. We postulate that this mechanism may operate via a protein-kinase C pathway.

Calcium↗

[H2 antagonists and the heart].

The large scale use of drugs that block tissue histamine receptors (H1 and H2) creates the problem of possible side effects due to the inhibition of the physiological role of histamine on certain systems and/or the direct action of histamine receptor blockers. In the case of H2 antagonists the effects on the heart so far reported are few but are considered important since they suggest the presence of physiological mechanisms that are as yet imperfectly understood. The literature on the cardiac effects of cimetidine and ranitidine is reviewed and the extent of the effect of the two drugs is outlined on the basis of an analysis of cases presented, experimental protocols and the various hypotheses put forward. Apart from the speculative interest of the study, a possible predisposition to the cardiac effects of cimetidine and ranitidine is identified in patients with major basal pathologies or in critical conditions. On the basis of the large numbers treated worldwide and the sporadic reports of cardiac effects it is concluded that the drugs are very easily handled even from the viewpoint of cardiac effects.

Animals↗

Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies.

Spectrin extractability was measured in the erythrocyte membranes from patients with Duchenne Muscular Dystrophy (DMD), from DMD definite carriers (in whom serum creatine kinase (CK) was also measured) and patients affected by other myopathies. After the extraction of spectrin from ghosts with EDTA, membrane proteins were examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Spectrin extractability was also investigated in the presence of an excess of calcium. Spectrin extraction from erythrocyte ghosts was significantly reduced with respect to controls in DMD patients, in DMD definite carriers and in patients affected by limb-girdle dystrophy, but not in patients suffering from other non-dystrophic myopathies. Fifty percent of DMD definite carriers showed a reduced extraction of spectrin and some of them had normal serum CK. Reduced extractability was also observed in red blood cells incubated in media containing excess calcium. Our results could suggest that reduced spectrin extractability is connected with a modification of intracellular calcium levels.

Adolescent↗

Increased leukocyte aggregation in patients with hypercholesterolaemia.

Leukocyte aggregation induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) has been measured in a group of patients with hypercholesterolaemia (n = 22) and in a group of control subjects (n = 26), age- and sex-matched. When hypercholesterolaemic patients were divided into two groups, with a discriminatory level of 7.7 mmol/l of plasma cholesterol, FMLP-induced leukocyte aggregation of patients with greater than 7.7 mmol/l of plasma cholesterol was significantly higher compared both with control subjects and patients with plasma cholesterol levels less than 7.7 mmol/l. A positive significant correlation was found between leukocyte aggregation and plasma cholesterol, whereas no correlation was observed between leukocyte aggregation and plasma triglycerides or APO-B levels. These findings provide further support for the hypothesis that elevated plasma cholesterol levels may induce a cellular membrane abnormality responsible for the increased leukocyte aggregation and, subsequently, endothelial damage.

Adolescent↗

[Incidence and prediction of coronary heart disease in the Italian cohorts of the Seven Countries Study. 10 year experience (author's transl)].

Three cohorts of man aged 40-59 at entry have been enrolled in Italy within the Seven Countries Study and followed-up for 10 years. They included demographic samples in the rural areas of Crevalcore, north Italy (n. 993) and of Montegiorgio, central Italy (n. 719) and a sample of Railroad men living in Rome and surroundings (n. 768) with an entry participating of about 92% and a 5 and 10 year follow-up participating of about the same level. Incidence of coronary heart disease in 10 years in men coronary-free at entry has been, for the pool of the three cohorts, of about 0.4% per year for hard criteria coronary heart disease (coronary deaths and hard infarcts) and of about 1% per year for all kinds of coronary heart disease including softer diagnoses. Differences between cohorts were small and altogether not significant except for coronary deaths which were higher in the Railroad group than in Montegiorgio. The prediction of coronary heart disease as function of the entry levels of some risk factors, estimated by the multiple logistic equation, suggested that also for these Italian samples, age, blood pressure, serum cholesterol, smoking habits and physical activity (the latter with a protective role) are the main risk factors although cholesterol seems to play a lesser role in the Railroad group than in the Rural cohorts. Proportions of 34 to 68% of the observed cases were located in the upper 20% of the distribution of the estimated risk and the ratio between cases in the upper and bottom quintile of risk ranged 4 to 14 folds. The degree of discrimination suggested by these and other indicators resulted to be directly related to the severity of the coronary heart disease manifestations considered as end-points (deaths, hard cases, all cases). Such varying discriminating role was mainly due to the varying predicting power of serum cholesterol.

Adult↗

[The prediction of coronary heart disease. A mathimatical model applied to Italian field studies (author's transl)].

The multiple logistic function (MLF) was applied for the estimation of coronary heart disease (CHD) - "hard criteria" in 5 years as a function of several risk factors in two rural Italian areas belonging to the "Seven Countries Study". CHD was estimated with solutions including 4, 5 and 11 factors respectively. Only serum cholesterol showed a statistically significant contribution; but other factors, like age and physical activity, very likely contributed to a better discrimination between "cases" and "non-cases". By increasing the number of factors the discrimination tends to improve anyway. In the solution with 11 factors, 46% of the observed cases was found in the upper 10% of the estimated risk probabilities; 57% in the upper 20%; while no cases were found in the lowest 20% of the same rank probability list. For practical purposes of selecting high risk individuals for preventive action, a simple 5 factor solution, including age, systolic blood pressure, serum cholesterol, consumption of cigarettes and physical activity is suggested.

Adult↗