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Biomedical subjects

S Cosentino

Publications and source records attributed to S Cosentino.

At least 37 records · Page 2Linked to original sources
PubMed1994

Loss of thrombospondin transcriptional activity in nickel-transformed cells.

mRNA from normal Chinese hamster embryo (CHE) cells was transcribed to cDNA and subtracted with an excess of mRNA from Chinese hamster embryo cells transformed by nickel compounds. Here we report the recovery of a sequence found to be highly homologous to the mouse thrombospondin 1 gene that was obtained by this subtraction procedure. Since thrombospondin is antiangiogenic, cancer cells expressing high levels of thrombospondin cannot grow in vivo because capillaries will not proliferate to cells secreting thrombospondin. To examine expression of thrombospondin, normal CHE cells were stained with monoclonal antibodies to human thrombospondin. The protein was present abundantly in the cytoplasm of normal cells but at greatly reduced levels in Ni-transformed cells. Analysis of mRNA by Northern (RNA) blot revealed transcripts in normal cells but little thrombospondin mRNA in Ni-transformed cells. Loss of thrombospondin mRNA expression was related to Ni treatment rather than transformation, since Ni-resistant cells also exhibited fewer thrombospondin transcripts than did wild-type cells. Digestion of genomic DNA with various combinations of restriction enzymes revealed thrombospondin gene patterns that were identical in both cell types, suggesting that there were no major deletions or rearrangements of the gene in the nickel-transformed cells. The inactivation of the thrombospondin gene was further investigated by analyzing the promoter activity of this gene linked to a chloramphenicol acetyltransferase (CAT) reporter plasmid that was transfected into normal and Ni-transformed cells. The CAT activity in normal cells was significantly higher than in Ni-transformed cells, suggesting that the promoter region of thrombospondin was less efficiently transcribed in Ni-transformed cells. We studied the consequences of enhanced expression of the retinoblastoma (Rb) gene, a known tumor suppressor gene, on CAT transcription driven by the human thrombospondin promoter. Cotransfection of an expression vector containing the mouse Rb gene greatly enhanced the transcription from the thrombospondin promoter such that the expression was higher in normal cells than in transformed cells.

Amino Acid Sequence↗
PubMed1994

Molecular mechanisms of nickel carcinogenesis.

Carcinogenic, water-insoluble Ni compounds are phagocytized by cells; and the particles undergo dissolution inside the cell, releasing Ni ions that interact with chromatin. Ni produces highly selective damage to heterochromatin. The longest contiguous region of heterochromatin in the Chinese hamster genome is found on the q arm of the X chromosome, and this region is selectively damaged by Ni. More than half of the male mice in which there were Ni-induced transformations of Chinese hamster cells exhibited complete deletion of the long arm of the X chromosome. The introduction of a normal X chromosome into these cells resulted in cellular senescence, suggesting that the Ni interacted with Chinese hamster genome to inactivate a senescence gene. Investigations were conducted into the mechanisms by which Ni produced damage to chromatin. Ni ions have a much higher affinity for proteins and amino acids than for DNA (by five to seven orders of magnitude). Therefore, Ni interacted with chromatin because of the protein present, not because of its reactivity for DNA. Studies have shown that Ni produced an increase in oxidative products in cells as indicated by oxidation of the fluorescent dye dichlorofluorescein; Ni has also been shown to produce oxidation of proteins in cells, as measured by carbonyl formation. Ni cross-linked certain amino acids and proteins to DNA. These covalent cross-links were not dissociated by EDTA and are inconsistent with direct Ni involvement, but they are consistent with Ni acting catalytically. Using subtractive hybridization, we have isolated a number of clones that are expressed in normal but not in Ni-transformed cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Metal mutagenesis in transgenic Chinese hamster cell lines.

Metals are toxic agents for which genotoxic effects are often difficult to demonstrate. To study metal mutagenesis, we have used two stable hprt/gpt+ transgenic cell lines that were derived from Chinese hamster V79 cells. Both the G12 and G10 cell lines are known to be very sensitive to clastogens such as X-rays and bleomycin, with the mutagenic response of the integrated xanthine guanine phosphoribosyl transferase (gpt) gene in G10 usually exceeding that of the same gene in the transgenic G12 cells. In studies with carcinogenic insoluble nickel compounds, a high level of mutagenesis was found at the gpt locus of G12 cells but not at the endogenous hypoxanthine phosphoribosyl transferase (hprt) locus of V79 cells. We have since demonstrated the similar recovery of a high frequency of viable G12 mutants with other insoluble nickel salts including nickel oxides (black and green). The relative mutant yield for the insoluble nickel compounds (G12 > G10) is the opposite of that obtained with nonmetal clastogens (G10 > G12). In the G12 cells, nickel mutagenesis may be related to the integration of the gpt sequence into a heterochromatic region of the genome. For some of the insoluble nickel compounds, significant inhibition of both cytotoxicity and mutant yield resulted when the G12 cells were pretreated with vitamin E. In comparison with the nickel studies, the mutagenic responses to chromium compounds in these cell lines were not as dramatic. Mutagenesis of the gpt target could not be demonstrated with other metals such as mercury or vanadium.

Animals↗
PubMed1994

Histologic patterns of omeprazole and nizatidine-healed duodenal ulcers:accuracy of endoscopic diagnosis.

The mechanisms underlying duodenal ulcer (DU) recurrence after endoscopically confirmed healing are unclear. We sought to examine histologic differences in healing induced by omeprazole and nizatidine. This also entailed assessing interobserver variation in endoscopic diagnosis and the correlation between endoscopic and histomorphologic healing. We treated 31 DU patients for 4 weeks with either omeprazole (20 mg daily a.m.) or nizatidine (300 mg twice daily). The healing rates of both groups showed no significant differences (86.7% versus 81.2%; p = 0.5). Good mucosal repair rates did not differ significantly (38.5% versus 69.2% respectively; p = 0.5). Endoscopists' agreement over scar type was 0.80, with the chance of agreement 0.70 (k = 0.34 +/- -0.08). The correlation between macroscopic and histologic appearance of scars was fair, but fully significant (r = 0.48; p < 0.05). We conclude that the study was too small to detect significant differences in healing patterns between the two drugs. The wide variation in endoscopic diagnosis suggests that mucosal repair is best assessed by histologic examination of biopsy samples.

Adult↗
PubMed1993

Dialysis treatment using an ethylene vinyl alcohol membrane and no anticoagulation for chronic uremic patients.

Anticoagulation used in hemodialysis treatment brings with it the risk of hemorrhagic complications and the possible consequences associated with chronic heparin administration. These problems have not been satisfactorily addressed to date. This study examined a new dialysis method that does not require the administration of anticoagulants. Dialysis is performed for 3 h with a continuous infusion of 750 ml of physiological saline solution in predilution mode and using filters made of ethylene vinyl alcohol copolymer membranes. Eleven patients with chronic uremia underwent more than 2,000 dialysis treatments performed with 9 episodes of coagulation of the dialyzer or blood tubings (0.43%). An evaluation of individual treatments revealed a high degree of biocompatibility and only a scanty activation of coagulation. Blood depuration efficacy was very good as evaluated from pretreatment and posttreatment routine blood chemistries. The technique described here represents a simple and effective method for performing regular dialysis treatment and does not require anticoagulant therapy.

Adult↗
PubMed1992

HCV and HIV infection among intravenous drug abusers in eastern Sicily.

In a study of 175 intravenous drug addicts from Eastern Sicily, 58.3% were found to be anti-HCV positive. In this population, the presence of anti-HCV was independent of HIV infection, age, duration of drug use and the practice of needle sharing. This may indicate that HCV is more readily transmitted (or spread earlier in this population) among drug addicts than is HIV.

Female↗
PubMed1992

Preliminary investigation on intrafamilial spread of hepatitis C virus (HCV).

To determine the risk of cohabitant HCV infection, we investigated the sera of 101 family members of 53 anti-HCV antibody positive chronic liver disease patients. Altogether 14.8% of the cohabitants were also anti-HCV antibody positive, compared to a prevalence of 1.4% in the general population. These results suggest that hepatitis-C-virus may spread by person-to-person infection.

Chronic Disease↗
PubMed1990

Pollen and mold allergy: aerobiologic survey in the atmosphere of Cagliari, Italy (1986-1988).

The occurrence of pollens and molds in the atmosphere of Cagliari, Italy over a 3-year period (1986-88) is reported. Pollen grains are present in the air from February to July, with a maximum in May. Urticaceae and Cupressaceae were the major contributors to the total pollen airspora, followed by Graminaceae, Oleaceae, Pinaceae, Cheno-Amaranthaceae, and Fagaceae. Fungal spores showed two periods of high sporulation, from April to June and in September-October, and two marked decreases, during winter and August. Cladosporium was by far the most abundant spore identified, followed by Basidiomycetes, Alternaria, and Fusarium.

Air Microbiology↗
PubMed1989

Fungal air-borne spores as health risk factors among workers in alimentary industries.

A survey to evaluate the occurrence of air-borne fungal spores in two different food industries, dairies and bakeries, was conducted. Our data revealed considerable fungal pollution in the environments of both industries, as well as some differences in the distribution of the genera of fungi recovered. Noteworthy was the frequent finding of numerous fungi frequently responsible for allergic rhinitis, asthma and other diseases, or well-known for their production of mycotoxins in foods or characterized by their degradative activity against various substances. Aspergillus, Candida, Fusarium, Geotrichum, Mucor and Penicillium were the most common genera identified in dairies while Alternaria, Aspergillus, Botrytis, Candida, Cladosporium, Penicillium and Saccharomyces occurred more frequently in bakeries. The survey showed that fungi can play a significant role in allergic and non-allergic diseases in modern working environments.

Air Microbiology↗
PubMed1984

[Monoclonal antibodies in the pathology of infective agents].

Reports in the literature on recent significant research into the production of monoclonal antibodies opposing schizomycetes protozoa and viruses are presented. Such research has provided valuable new information about the epidemiology, aetiopathogenesis and prophylaxis of several infectious diseases. Monoclonal antibodies have in fact been used to identify new antigenic determinants in various microorganisms, to show antigenic differences between species, strains, types and development cycles and to reveal the existence of natural antigenic variants. Finally it is reported that only human monoclonal antibodies can be used in human immunoprophylaxis and therapy.

Antibodies, Monoclonal↗