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Biomedical subjects

G Marchetti

Publications and source records attributed to G Marchetti.

At least 127 records · Page 7Linked to original sources

Methylation and expression of c-myc and c-abl oncogenes in human leukemic K562 cells before and after treatment with 5-azacytidine.

The correlation between expression and extent of DNA methylation of c-myc and c-abl oncogenes has been investigated in the human leukemic K-562 cell line before and after 5-azacytidine-mediated erythroid induction. RNA accumulation was analyzed by cytoplasmic dot hybridization and DNA methylation by using HpaII and MspI endonucleases, which differently cleave the CCGG sequence depending on cytosine methylation. Both the oncogenes are expressed in uninduced cells; however, whereas the c-myc expression does not change following 5-azacytidine treatment, the c-abl expression sharply decreases. The HpaII pattern shows that the c-myc DNA region is undermethylated and that the c-abl gene is hypermethylated both before and after the erythroid induction. Nevertheless, in both the genes 5-azacytidine produces variations in the MspI pattern compatible with mCmCGG to CmCGG demethylations.

Azacitidine↗

Effects of ibopamine on systemic, pulmonary and regional hemodynamics. Experimental investigations in anesthetized dogs.

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.

Anesthesia↗

Effects of ibopamine on acute cardiac failure following experimental coronary occlusion in dogs.

The activity of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on myocardial contractility and systemic and renal hemodynamics was investigated in the anesthetized dog with experimental infarction, instrumented with catheters and electromagnetic flowmeters. Ibopamine, given by the intraduodenal route at a dose of 24 mg/kg, was effective in improving the hemodynamic parameters depressed by myocardial infarction, in particular myocardial contractility and renal hemodynamics. In eliciting such activity which resembles that developed by dopamine in similar experimental conditions, ibopamine seems to meet the requirements of an orally active pharmacological agent useful in the therapy of acute heart failure.

Animals↗

A survey of 311 patients receiving ibopamine mainly during hospital treatment for severe congestive heart failure.

From a monitored release of ibopamine, the 3,4-diisobutyryl ester of N-methyldopamine, during the early Italian marketing of the drug a collection of 311 individual cases was formed. The cases were reported by 168 cardiologist-practitioners, self-selected for having a therapeutic interest in the inotropic properties of ibopamine and in trying it out in patients with mostly severe, refractory congestive heart failure (CHF). Most patients were monitored during a hospital admission for worsened CHF. After clinical reassessment and other drugs' adjustment, ibopamine was added and the patient followed-up for 20 days in hospital with regular recording of scored signs and symptoms, arterial pressure, heart rate, body weight, and any clinical event--adverse or beneficial. Concomitant drugs were also recorded. Global assessment of efficacy was mostly positive, with "ineffective" rates of only 15.9% (doctors) and 14.2% (patients). In the absence of a control group, it is impossible to determine to what extent the foregoing was really due to ibopamine or to the rest of the therapeutic policy. However, the fact that most of the severe cases had been refractory to prior treatment, and that they individually carried a grave prognosis on admission, do seem to point to real ibopamine-related benefit. The high rate of symptomatic benefit perceived by the patients would also seem likely to be drug-related. Heart rate after the ibopamine-including regimen was significantly lower than before. Systolic and diastolic arterial pressures also tended to decrease, especially in CHF of hypertensive etiology.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Hemodynamic profile of N-(2,5-dimethyl-1H-pyrrol-1-yl)6-(4-morpholinyl)-3-pyridazinamine hydrochloride in conscious dogs.

The effects of N-(2,5-dimethyl-1H-pyrrol-1-yl)6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899) on systemic, pulmonary, renal and coronary circulation and on myocardial contractility have been investigated in conscious dogs treated orally. The compound induced a decrease in systemic arterial blood pressure, slow in onset (peak effect at 4 h) and long-lasting (more than 7 h), by reducing total peripheral resistance, while the heart rate, cardiac output, cardiac work and myocardial contractility increased because of the reflex increase in sympathetic drive evoked by the blood pressure fall. Coronary and renal blood flows were increased for a long time. Pulmonary resistance was markedly decreased, but the pulmonary pressure was increased, probably due to the hyperkinetic activity triggered by the increases of cardiac output and heart rate. The hemodynamic changes induced by MDL-899 are qualitatively similar to those induced by hydralazine. The results suggest that the compound belongs to the class of vasodilators that act primarily on systemic arterioles to produce arteriolar dilation.

Animals↗

beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis.

Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I.

Autoradiography↗

Gene deletion in an Italian haemophilia B subject.

DNA from 20 Italian haemophilia B patients was analysed by the Southern blotting technique and hybridisation to a factor IX cDNA probe. A large deletion of factor IX gene was detected in one patient with antibodies to the infused factor; the EcoRI pattern of the other 19 subjects examined was normal.

Chromosome Deletion↗

Papillary carcinoma of thyroglossal duct cyst. A case report.

A case of papillary carcinoma of thyroglossal duct cyst in a 68 year old woman is here described. Histology showed a papillary carcinoma of thyroid type inside the cyst. The wall of this latter contained normal thyroid follicles. Psammoma bodies and ground glass nuclei were also observed. The origin, pathology and relationship of this neoplasia with a thyroid primary are discussed.

Aged↗

Human leukemia K562 cells: relationship between hemin-mediated erythroid induction, cell proliferation and expression of c-abl and c-myc oncogenes.

We have studied the expression of the c-myc and c-abl oncogenes in two human leukemic K562 cell lines which do express hemoglobin genes retaining a differential rate of cell proliferation. Our data indicate that in hemin-induced K562(S) cells the expression of c-abl oncogene decreases and appears to be related to a decrease in the proliferation capacity rather than to the activation of differentiated functions. The K562(hC) cell line, which produces large amounts of Hb Gower 1 retaining an efficient rate of cell proliferation, expresses indeed the c-abl oncogene at high level.

Cell Division↗

[Inhibition of heme biosynthesis in erythroid precursors (BFU-e) isolated from human peripheral blood: effects on globin synthesis].

We studied the relationship between heme accumulation and globin synthesis in human erythroid precursors which were stimulated by 2 I.U. of erythropoietin in semi-solid cultures (1% methyl-cellulose, 20% fetal calf serum) and treated with 6-9 micrograms/ml of desferrioxamina (DF), a potent inhibitor of heme synthesis (6). Heme accumulation was detected by specific reaction with benzidine (4), globin synthesis by CM-cellulose column chromatography. Our results demonstrate that globin gene expression occurs in DF-treated erythroid cells which do not accumulate heme molecules. As heme does affect translation and stability of globin mRNA (10) our system might be suitable for studies focused on pathological alterations of erythropoiesis associated with the presence of unstable globin mRNAs and/or unstable globins.

Chromatography, Ion Exchange↗

[Construction of a genome library from a beta-0-thalassemic individual from Ferrara: characterization of clones containing beta globin genes].

A library of genomic DNA was prepared from a patient with beta o Ferrara thalassaemia: random human DNA fragments (15 - 20 Kb) have been joined to phage lambda vectors and cloned has viable phage particles (4). 4x10(5) phages have been screened for their content in beta globin gene sequences, using a human beta cDNA plasmid (5) as hybridization probe. Five positive clones have been isolated and characterized by restriction endonuclease cleavage analysis and by the hybridization experiments. The results obtained allow the precise localization of the human fragments inside the beta like globin gene cluster (6). The comparison of the thalassaemic fragments with the normal DNA (6 - 7) shows two different restriction endonuclease sites, for Xba I and Eco RI respectively, downstream from the human beta globin gene.

Cloning, Molecular↗

Cardiac effects of clomipramine treatment. ECG and left ventricular systolic time intervals.

ECGs and left ventricular systolic time intervals were studied in 26 patients suffering from major depressive disorder treated with clomipramine. ECGs did not show, with one exception, drug-induced changes. The ratio of pre-ejection period to left ventricular ejection time, both corrected for heart rate (PEPc/LVETc), presented no significant changes, as compared with initial findings, in the group of patients considered as a whole. 27% of patients, however, showed individual percent changes greater than 8%, both increases and decreases having been observed. Cardiac findings were in no way related to clomipramine plasma levels.

Aged↗

[Phenotypic relations with regard to pyocin sensitivity, of 191 strains of Pseudomonas aeruginosa isolated in a hospital environment].

191 strains of Pseudomonas aeruginosa, isolated from clinical specimens, were tested by passive and active pyocin typing. The results of passive typing were computerized and a final dendrogram, with its peculiar similarity levels between the single strains, was obtains. This study will permit to build a system, to mark out the Pseudomonas strains, through active pyocin typing or through passive pyocin typing.

Air Microbiology↗

Positive inotropic effect of K-canrenoate: an investigation in anaesthetized dogs, untreated or treated with digitalis.

Potassium canrenoate (KCR) is widely used in cardiac patients as an aldosterone antagonist, antiarrhythmic and diuretic drug. According to experimental and clinical studies it can also elicit an inotropic action. It is not clear, however, whether this inotropic activity occurs in the absence of any treatment or after the myocardial contractility has already been improved with digitalis. In order to evaluate a possible interaction of this drug with digitalis we administered KCR intravenously to 41 anaesthetized dogs either untreated or treated with digitalis, in which aortic and left ventricular pressures were recorded and myocardial contractility was evaluated by calculating in real time the first derivative of ventricular pressure (Formula: see text) max and two other contractility indexes (Formula: see text) max and V.max. The results obtained showed that KCR given at doses of 10, 20 and 30 mg/kg i.v. did not elicit any inotropic effect in dogs not previously digitalized. 100 mg/kg i.v. first depressed cardiac contractility and then increased it. After cardiac performance had been improved by digitalis, KCR further increased all contractility indexes significantly. These results could explain previous observations that no inotropic effect was observed in human subjects not treated with digitalis after treatment with KCR.

Animals↗

Low-dose heparin in thoracic surgery: effect on blood coagulation and fibrinolysis system.

Plasma kallikrein, antithrombin III and antiplasmin were determined with chromogenic methods in 29 patients pre-, per- and post-operatively in a controlled, randomized study. 16 patients received calcium heparin, 5000 IU s. c. every 8 hr for 7 days, the first administration given 2 hr before surgical procedure. 13 control patients received saline. A significant reduction of kallikrein and antiplasmin in per- and post-operative periods was observed in the control patients compared with the heparin-treated patients, while there was a significant reduction of anti-thrombin III in the control patients compared with the treated patients only in the per-operative period. The results obtained suggest that activation of the coagulation and fibrinolysis system occurs in patients undergoing thoracic surgery, and that it is inhibited significantly by calcium heparin prophylaxis.

Adult↗

Quantitative structural changes of the rat thoracic aorta in early spontaneous hypertension. Tissue composition, and hypertrophy and hyperplasia of smooth muscle cells.

The thoracic aorta of 21-, 28-, 35-, and 45-day-old spontaneously hypertensive (SH) and Wistar Kyoto (WK) rats was analyzed morphometrically to evaluate the cellular hypertrophy and proliferation of medial smooth muscle cells during the development of genetically determined hypertension. The absolute increase in volume of collagen and ground substance, and elastic tissue was also measured. In SH animals, cellular hypertrophy was found to be the dominant mechanism of muscle growth in the 21- to 28-day and 35- to 45-day intervals, resulting in an overall 68% enlargement of the mean cell volume from 21 to 45 days. The total number of smooth muscle cells increased only 21% (not statistically significant) and the tendency toward hyperplasia was restricted to the 28- to 35-day period. Normotensive controls showed cell proliferation mainly from 21 to 28 days and cellular hypertrophy from 35 to 45 days with an absolute 33% increase in the number of cells and a 26% larger volume of the mean smooth muscle cell at 45 days of age. from 21 to 45 days, the above changes in cell size and number provoked an overall 104% and 67% growth of the muscle mass in SH and WK rats, respectively. The initial response phase of spontaneous hypertension was also characterized by an increase of collagen and ground substance, 184%, which was slightly greater than that of the elastic component, 168%. Changes in mural concentration of fibrous proteins that were similar to but of less magnitude than those of controls, were seen. These results demonstrate that short-term spontaneous hypertension determines a simultaneous growth adaptation in every component structure of the media of the thoracic aorta leading to a disproportionate accumulation of scleroproteins that markedly exceeds that of the contractile component of the vessel wall. At a cellular level, smooth muscle cell hypertrophy is the prevailing process that underlies the tissue response of the aorta in early hypertension.

Aging↗