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Biomedical subjects

G Marchetti

Publications and source records attributed to G Marchetti.

At least 73 records · Page 4Linked to original sources

Plasmacytoma of the parotid gland. Report of a case and review of the world literature.

Extramedullary plasmacytoma (EP) is a relatively rare neoplasm; about 90% of cases are localized in the head and neck area. EP has been considered a precursor of multiple myeloma but cases showing long disease free intervals or cure by surgery alone have been reported. A research of the world literature pointed out the extremely rare localization of solitary plasmacytoma in the salivary glands. Only 9 cases have been reported until now, 6 in the parotid gland, 2 in the submandibular glands and 1 in both the parotid and submandibular gland.

Humans

RFLP analysis in families with sporadic hemophilia A. Estimate of the mutation ratio in male and female gametes.

To investigate the sporadic occurrence of hemophilia A and to estimate the sex ratio of mutation rates directly, 17 families with isolated cases of the disorder were studied by RFLP analysis and by clotting assays. Three RFLPs, one intragenic and two with close linkage to hemophilia A, were used. In eight families the RFLP study excluded the carrier status of the maternal grandmothers. Since hemostatic studies showed that the eight mothers of these propositi were hemophilia carriers, the origin of the newly mutated genes was inferred from the RFLP patterns: six hemophilic genes derived from the normal maternal grandfathers and two, from maternal grandmothers. The data indicate a higher mutation rate in males than in females, as previously suggested by segregation analysis and coagulation studies. However the sex ratio indicated by the RFLP analysis is lower than previously reported and could explain previous conflicting estimates.

Female

Effects of extracellular fluid volume changes on renal response to low-dose dopamine infusion in normal women.

Dopamine (DA) i.v. infused in a low dose (0.1 microgram/kg/min) in healthy women during sustained hypotonic polyuria, produced different renal functional effects as variations in extracellular fluid volume occurred. (1) In hydro-saline retention (n = 23), induced by desoxycorticosterone acetate treatment, DA produced typical vasodilator and hydro-natriuretic effects (Goldberg, 1972). (2) In hydro-saline depletion (n = 19), induced by diuretic treatment and low dietary sodium intake, DA lost its vasodilator and natriuretic efficacy, manifesting, on the other hand, renal sodium conserving effects mainly dependent on the increase in distal sodium reabsorption and a trend towards afferent arteriolar vasoconstriction. (3) Treatment with prazosin (n = 9) or propranolol (n = 9) in hydro-saline depletion, was efficacious in partly restoring the typical vasodilator and natriuretic effects of DA. Thus, in hydro-saline depletion, DA produced sympathomimetic effects which were sufficiently intense to outweigh those due to activation of specific DA renal receptors.

Adult

c-myc oncogene alterations in human thyroid carcinomas.

A possible role of the c-myc oncogene in the neoplastic transformation of the human thyroid has been investigated. The structure, the methylation status, and the copy number of this oncogene have been analyzed in normal and in tumor thyroid DNAs by Southern blotting technique and dot blot hybridization. Among six carcinomas, four presented abnormal c-myc DNA structure: Three cases showed a mutation in the 5' flanking region of the gene, originating a new EcoRI site; the other case showed a deletion of 5 kb involving the first exon of the gene. This deletion was also observed in the white blood cells of the same individual. In addition, in three carcinomas a double dose of the oncogene has been demonstrated. In all the carcinomas examined, undermethylation of the c-myc oncogene has been observed. These findings suggest that c-myc oncogene alterations might be involved in the malignant transformation of the human thyroids and can be considered as tumor markers.

Base Sequence

Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme.

A cDNA for coagulation factor XII has been used to investigate the presence of gene lesions and restriction fragment length polymorphisms in two brothers with Hageman trait and their family. A TaqI polymorphic fragment has been found in the two propositi and in 11 members of the paternal lineage. This polymorphism, absent in the normal population, is correlated with the reduction of factor XII activity and enables the identification of heterozygous factor XII deficiency. Factor XII gene deletion as the cause of Hageman trait in this family has been excluded. A restriction map has been constructed, and the TaqI polymorphic site has been localized within the 5' portion of the gene. The mutation in the polymorphic site is probably the cause of the factor XII deficiency. Data suggest the presence of one factor XII gene per haploid genome.

Collodion

Human leukemic K562 cells: suppression of hemoglobin accumulation by a monoclonal antibody to human transferrin receptor.

The receptor for transferrin plays an important role both in tumor cell growth and in hemoglobin synthesis. In this paper, we demonstrate that the monoclonal antibody 42/6 to human transferrin receptor inhibits iron uptake in the human leukemic K562 cell line and suppresses hemoglobin accumulation in K562 cells induced to erythroid differentiation by butyric acid. In contrast, only slight inhibitory effects were observed on cell proliferation of both uninduced and erythroid-induced K562 cells treated with the 42/6 monoclonal antibody. In addition, the 42/6 monoclonal antibody to human transferrin receptor does not inhibit butyric acid-induced accumulation of gamma-globin mRNA. The effect of the 42/6 monoclonal antibody on hemoglobin synthesis appears to be restricted to human cell lines, as murine Friend erythroleukemic cells undergo erythroid differentiation when cultured in the presence of hexamethylenebisacetamide plus the 42/6 monoclonal antibody. The findings reported in this paper suggest (a) a dissociation of iron transport and accumulation of heme molecules from the expression of globin genes and (b) a different requirement of iron uptake by different iron-dependent functions such as cell proliferation and hemoglobin expression.

Antibodies, Monoclonal

Identification of a c-myc oncogene lacking the exon 1 in the normal cells of a patient carrying a thyroid carcinoma.

In this paper we describe an alteration of the c-myc oncogene present in the white blood cells and normal as well as neoplastic thyroid cells of a subject carrying a thyroid carcinoma. Restriction enzyme mapping and hybridization to human c-myc probes specific for different regions of this gene demonstrate that this subject carries, in addition to the normal one, a c-myc oncogene lacking the first exon and part of the first intron. The levels of the c-myc mRNA in thyroid cells of this subject do not show differences with respect to thyroid cells from other subjects. Taken together, these findings indicate that the deletion of the first exon of the c-myc oncogene, in itself, does not produce overtranscription of this oncogene nor hematopoietic malignancies.

Base Sequence

Inhibition of prolactin and aldosterone secretion by the dopamine derivative ibopamine.

In 7 patients with congestive heart failure acute oral administration of ibopamine, a new dopamine derivative, induced a significant decrease in serum prolactin and aldosterone without affecting serum growth hormone or cortisol. The Metoclopramide-induced secretion of prolactin and aldosterone was blunted in 6 patients pretreated with 200 mg ibopamine. The data are consistent with a dopaminergic effect of ibopamine due to a peripheral action, probably on D-2 receptors.

Adult

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