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Biomedical subjects

A Vozza

Publications and source records attributed to A Vozza.

At least 19 recordsLinked to original sources

New established melanoma cell lines: genetic and biochemical characterization of cell division cycle.

BACKGROUND: Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. OBJECTIVE: On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. RESULTS: The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. CONCLUSIONS: Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene.

Cell Division↗

Late onset Blueberry Muffin Syndrome following congenital rubella.

The authors report a case of congenital rubella in a 7-month-old female infant presenting a Blueberry Muffin Rash. Blueberry Muffin Syndrome is a cutaneous manifestation characterized by widespread maculo papular lesions of a reddish-blue or magenta colour, due to persistent dermal erythropoiesis in patients with congenital viral infections.

Erythropoiesis↗

Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate.

The genome of Saccharomyces cerevisiae contains 35 members of a family of transport proteins that, with a single exception, are found in the inner membranes of mitochondria. The transport functions of the 15 biochemically identified mitochondrial carriers are concerned with shuttling substrates, biosynthetic intermediates and cofactors across the inner membrane. Here the identification of the mitochondrial carrier for the essential cofactor thiamine pyrophosphate (ThPP) is described. The protein has been overexpressed in bacteria, reconstituted into phospholipid vesicles and identified by its transport properties. In confirmation of its identity, cells lacking the gene for this carrier had reduced levels of ThPP in their mitochondria, and decreased activity of acetolactate synthase, a ThPP-requiring enzyme found in the organellar matrix. They also required thiamine for growth on fermentative carbon sources.

Carbon↗

Prurigo gestationis.

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Administration, Oral↗

Dermatofibrosarcoma protuberans: experience with 14 cases.

Dermatofibrosarcoma is a rare, low-grade malignant skin tumour that can be considered the equivalent of malignant non-cutaneous soft tissue fibrohistiocytoma. The high rate of recurrence of this tumour is correlated with poor surgical management because lesions, often smaller than 2 cm in diameter, may be confused with dermatofibroma or keloid. Our findings confirm the importance of accurate diagnosis of primary lesions and the need for aggressive surgical treatment (excision of 5 cm of surrounding tissue) to lower the incidence of local relapse.

Adult↗

Contraception with the latest estroprogestagens in women suffering from systemic lupus erythematosus.

BACKGROUND: This study was performed to evaluate, in women suffering from Systemic Lupus Erythematosus (SLE), the relationship between the assumption of oral contraceptives and the evolution of the disease. METHODS: In the Institute of Obstetrics and Gynaecology in collaboration with the Institute of Dermosyphilopathical Clinic of Second University of Studies of Naples, 20 women in fertile age suffering from SLE with specific cutaneous manifestations were studied for the year 1999. All the patients requested to take, at contraceptive purpose, low-dosage estroprogestagens. The contraceptives we prescribed have, as active substance, the gestodene at the dose of 0.075 mg and the etinilestrdiol at the dose of 0.02 mg per day. Patients' group in object was compared for a year with a similar control group of women suffering from SLE not subjected to any pharmacological therapy. RESULTS: Only 5 patients out 20 have had to suspend therapy after 4 or 5 months, because a relapse of the illness was experienced while the others 15 patients did not lament a relapse of the illness. In the control group a more or less similar percentage of patients, during the months of the observation, spontaneously had episodes of relapse of the illness. CONCLUSIONS: The results of our brief study have shown that the administration of hormonal contraceptives in reality doesn't constantly produce immediate and remarkable exacerbations of the illness in women suffering from SLE. In our opinion the contraception with the latest estroprogestagens can comfortably be effected under strict medical control, probably because the medicines at low dosage are quickly metabolized and in the majority of the cases they don't have capacity to influence the course of such chronic connectivitis.

Adult↗

Identification and functions of new transporters in yeast mitochondria.

The genome of Saccharomyces cerevisiae encodes 35 putative members of the mitochondrial carrier family. Known members of this family transport substrates and products across the inner membranes of mitochondria. We are attempting to identify the functions of the yeast mitochondrial transporters via high-yield expression in Escherichia coli and/or S. cerevisiae, purification and reconstitution of their protein products into liposomes, where their transport properties are investigated. With this strategy, we have already identified the functions of seven S. cerevisiae gene products, whose structural and functional properties assigned them to the mitochondrial carrier family. The functional information obtained in the reconstituted system and the use of knock-out yeast strains can be usefully exploited for the investigation of the physiological role of individual transporters. Furthermore, the yeast carrier sequences can be used to identify the orthologous proteins in other organisms, including man.

Amino Acid Transport Systems, Basic↗

Identification of the yeast mitochondrial transporter for oxaloacetate and sulfate.

Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, including the OAC protein. The transport specificities of some family members are known, but most are not. The function of the OAC has been revealed by overproduction in Escherichia coli, reconstitution into liposomes, and demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate. Reconstituted OAC catalyzes both unidirectional transport and exchange of substrates. In S. cerevisiae, OAC is in inner mitochondrial membranes, and deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate. Mitochondria from wild-type cells swelled in isoosmotic solutions of ammonium salts of oxaloacetate, sulfate, thiosulfate, and malonate, indicating that these anions are cotransported with protons. Overexpression of OAC in the deletion strain increased greatly the [(35)S]sulfate/sulfate and [(35)S]sulfate/oxaloacetate exchanges in proteoliposomes reconstituted with digitonin extracts of mitochondria. The main physiological role of OAC appears to be to use the proton-motive force to take up into mitochondria oxaloacetate produced from pyruvate by cytoplasmic pyruvate carboxylase.

Anion Transport Proteins↗

The mitochondrial dicarboxylate carrier is essential for the growth of Saccharomyces cerevisiae on ethanol or acetate as the sole carbon source.

The dicarboxylate carrier (DIC) is an integral membrane protein that catalyses a dicarboxylate-phosphate exchange across the inner mitochondrial membrane. We generated a yeast mutant lacking the gene for the DIC. The deletion mutant failed to grow on acetate or ethanol as sole carbon source but was viable on glucose, galactose, pyruvate, lactate and glycerol. The growth on ethanol or acetate was largely restored by the addition of low concentrations of aspartate, glutamate, fumarate, citrate, oxoglutarate, oxaloacetate and glucose, but not of succinate, leucine and lysine. The expression of the DIC gene in wild-type yeast was repressed in media containing ethanol or acetate with or without glycerol. These results indicate that the primary function of DIC is to transport cytoplasmic dicarboxylates into the mitochondrial matrix rather than to direct carbon flux to gluconeogenesis by exporting malate from the mitochondria. The delta DIC mutant may serve as a convenient host for overexpression of DIC and for the demonstration of its correct targeting and assembly.

Acetates↗

Targeting and assembly of the oxoglutarate carrier: general principles for biogenesis of carrier proteins of the mitochondrial inner membrane.

We have studied the targeting and assembly of the 2-oxoglutarate carrier (OGC), an integral inner-membrane protein of mitochondria. The precursor of OGC, synthesized without a cleavable presequence, is transported into mitochondria in an ATP- and membrane potential-dependent manner. Import of the mammalian OGC occurs efficiently into both mammalian and yeast mitochondria. Targeting of OGC reveals a clear dependence on the mitochondrial surface receptor Tom70 (the 70 kDa subunit of the translocase of the outer mitochondrial membrane), whereas a cleavable preprotein depends on Tom20 (the 20 kDa subunit), supporting a model of specificity differences of the receptors and the existence of distinct targeting pathways to mitochondria. The assembly of minute amounts of OGC imported in vitro to the dimeric form can be monitored by blue native electrophoresis of digitonin-lysed mitochondria. The assembly of mammalian OGC and fungal ADP/ATP carrier occurs with high efficiency in both mammalian and yeast mitochondria. These findings indicate a dynamic behaviour of the carrier dimers in the mitochondrial inner membrane and suggest a high conservation of the assembly reactions from mammals to fungi.

Animals↗

Yeast mitochondria lacking the phosphate carrier/p32 are blocked in phosphate transport but can import preproteins after regeneration of a membrane potential.

Two different functions have been proposed for the phosphate carrier protein/p32 of Saccharomyces cerevisiae mitochondria: transport of phosphate and requirement for import of precursor proteins into mitochondria. We characterized a yeast mutant lacking the gene for the phosphate carrier/p32 and found both a block in the import of phosphate and a strong reduction in the import of preproteins transported to the mitochondrial inner membrane and matrix. Binding of preproteins to the surface of mutant mitochondria and import of outer membrane proteins were not inhibited, indicating that the inhibition of protein import occurred after the recognition step at the outer membrane. The membrane potential across the inner membrane of the mutant mitochondria was strongly reduced. Restoration of the membrane potential restored preprotein import but did not affect the block of phosphate transport of the mutant mitochondria. We conclude that the inhibition of protein import into mitochondria lacking the phosphate carrier/p32 is indirectly caused by a reduction of the mitochondrial membrane potential (delta(gamma)), and we propose a model that the reduction of delta(psi) is due to the defective phosphate import, suggesting that phosphate transport is the primary function of the phosphate carrier/p32.

Adenosine Triphosphate↗

[Ceftazidime in the therapy of chronic bronchitis relapses in elderly hospitalized patients].

We studied the clinical and bacteriological efficacy and the safety of ceftazidime in elderly patients suffering from recurrent chronic bronchitis. 33 hospitalized subjects (10 F. 23 M: mean age 78.5 +/- 6 yrs) were treated with ceftazidime (1 g b.i.d.) for a mean of 9 +/- 1.5 days. At the end of treatment all patients had positive clinical results, with bacteriological eradication equal to 95%. Only one case of relapse was observed at the follow up assessment. As to safety only one case of vomiting was observed (but did not require treatment withdrawal).

Aged↗

The efficacy, safety and tolerance of ceftazidime for the treatment of bacterial infections in the elderly.

An open multicentre trial to study the efficacy and safety of ceftazidime in elderly patients has been conducted in four geriatric units on 135 subjects suffering from urinary-tract or respiratory-tract infections. Sixty-two patients were cured (45.9%), and 60 improved (44.4%). Of the evaluable cases bacteriological eradication was achieved in 91.3%. No adverse events were recorded.

Age Factors↗

[Argon laser in dermatology: indications suggested by a 4-year experience].

The Argon laser has been used in the treatment of port wine stains, telangiectasias, spider ectasias, ruby spots, venous lakes, pyogenic granulomas, tattoos, keloids, verrucous naevus, angiokeratomas, verrucous hemangiomas. The outcome results have been compared with those achievable using other treatments in order to give right indications to the use of the Argon laser. The comparison point out that Argon laser is the treatment of choice only in port wine stains, while in all the other diseases it doesn't give any advantage with regard to conventional therapies, less sophisticated, easier and sometime more effective.

Adolescent↗