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Biomedical subjects

R Santoro

Publications and source records attributed to R Santoro.

At least 19 recordsLinked to original sources
PubMed1995

Does hypomethylation of linker DNA play a role in chromatin condensation.

The inhibitory effect that H1 histone exerts on the in vitro DNA methylation process, catalysed by mammalian DNA methyltransferase, together with the relative hypomethylation of linker DNA in eukaryotic cells chromatin, suggest that this hypomethylated state of linker DNA can be of importance in allowing or regulating H1-dependent chromatin condensation. In native oligonucleosomes (olnu), i.e., in chromatin fragments consisting of 5-20 nucleosomes each, there was a correlation between the effects of H1 on the DNA ellipticity at 280 nm and the in vitro assayed methyl-accepting ability. The same was true in H1-depleted or in H1-reconstituted preparations. Artificial methylation caused olnu DNA to lose its ability to allow cooperative H1-H1 interactions under ionic strength conditions similar to those known to affect the transition of the 10-nm filament to the 30-nm chromatin fiber. These results suggest that hypomethylation of linker DNA plays a role in the H1-H1 interactions that are needed for solenoid condensation.

Animals↗
PubMed1995

Specific variants of H1 histone regulate CpG methylation in eukaryotic DNA.

Upon HPLC fractionation of human placenta or calf thymus H1 histone preparations, only some fractions enriched in the H1e-c variants were able to exert a severe inhibition on in vitro enzymatic DNA methylation. These fractions, though similar to the other variants in interacting with genomic DNA, were also the only ones which could bind CpG-rich ds-oligodeoxyribonucleotides (oligos). Both the 6-CpG ds-oligo and the DNA purified from chromatin fractions enriched in 'CpG islands' were good competitors for the binding of H1e-c to the 6meCpG ds-oligo. This ability to bind any DNA sequence and to suppress the enzymatic methylation in any sequence containing CpG dinucleotides suggests, for these particular H1 variants, a possible role in maintaining CpG island DNA and linker DNA at low methylation levels.

Animals↗
PubMed1995

Binding of histone H1e-c variants to CpG-rich DNA correlates with the inhibitory effect on enzymic DNA methylation.

Within the H1 histone family, only some fractions enriched in the H1e-c variants are effective in causing a marked inhibition, in vitro, of enzymic DNA methylation and, in gel retardation and Southwestern blot experiments, in binding double-stranded (ds) CpG-rich oligonucleotides. Both the 6-CpG ds-oligonucleotide and the DNA purified from chromatin fractions enriched in 'CpG islands' are good competitors for the binding of H1e-c to 6-meCpG ds-oligonucleotide. Because of their ability to bind any DNA sequence and to suppress the enzymic methylation in any sequence containing CpG dinucleotides, these particular H1 variants could play some role in maintaining linker DNA at low methylation levels and even in preserving the unmethylated state of the CpG-rich islands which characterize the promoter regions of housekeeping genes.

Animals↗
PubMed1995

p53 oncoprotein overexpression correlates with mutagen-induced chromosome fragility in head and neck cancer patients with multiple malignancies.

In this study, we analysed immunocytochemically p53 expression in first primary and second primary cancers from 25 head and neck cancer patients (HNCPs) with multiple malignancies in comparison with oncoprotein expression in tumour tissues from 25 historical HNCP controls with single cancer in a match-paired analysis. Moreover, we investigated bleomycin-induced chromosome fragility in both groups of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25 (44%) from single cancer patients and 28 out of 50 (56%) tumours from HNCPs with multiple malignancies were p53 positive. In the group of multiple primary cancers, nine patients (36%) showed positive staining of both first and second primaries, whereas six (24%) had positive labelling of first primary cancer but not of the subsequent second primary, four (16%) patient showed p53 expression only in the second primary cancer and six (24%) patients showed no p53 immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher sensitivity to clastogens of HNCPs with multiple tumours than of HNCPs with a single cancer (P < 0.01), and a significant correlation between chromosome fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple malignancies more than in those with single head and neck cancer (P = 0.11). Moreover, we found that patients with p53-positive staining of both first and second primaries showed a statistically significant higher mutagen sensitivity than those with a single p53 immunoreactive tumour or those in whom both cancers were p53 negative (P < 0.01). Our data suggest that subjects with increased susceptibility to carcingogens after exposure to tobacco or alcohol are at higher risk for multiple cancers in which one of the most common genetic events is aberrant p53 expression.

Aged↗
PubMed1994

Immunolocalization of alpha 2, alpha 5, and alpha 6 integrin subunits in salivary tissue and adenomas of the parotid gland.

The localization of the integrin subunits alpha 2, alpha 5, alpha 6 was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed alpha 2 and alpha 6 chains at the basal cell pole facing the basement membrane. alpha 2 also localized at sites of cell-cell contact. No staining of the epithelial component was seen with alpha 5. The polarized expression of alpha 2 and alpha 6 subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The alpha 5 subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells.

Adenolymphoma↗
PubMed1994

[The efficacy of creatine phosphate in the treatment of patients with heart failure. Its echographic evaluation after acute and protracted treatment].

The hemodynamic effects of acute and long-term administration of creatine phosphate were studied in 23 patients with heart failure (NYHA classes II and III) under stabilized treatment. Acute creatine phosphate (5 g i.v.) induced a significant increase of the ejection fraction (FE) and of other parameters of cardiac contractility. Once these improvements of cardiac contractility were obtained by acute treatment, further significant increases in cardiac function were observed if treatment was continued for six days, i.e. telesystolic diameter and volume, as well as parietal stress were significantly reduced, and ejection fraction and shortening fraction were significantly increased. Creatine phosphate treatment has a favourable influence on the hemodynamics of patients with an obvious contractility deficit and chronic ischemia of the myocardium.

Acute Disease↗
PubMed1993

[Predictive value of various echocardiographic parameters of systolic and diastolic function in the development of congestive heart failure after infarction].

To evaluate the predictive value of systolic and diastolic left ventricular (LV) function parameters, in the development of congestive heart failure (CHF) after acute myocardial infarction (AMI), 48 patients (mean age 56.2 +/- 10.4 years) were studied with two-dimensional and Doppler echocardiography (2D echo) in the acute phase (36 +/- 12 hours) and after 6 months of follow-up. The following parameters have been evaluated: LV wall motion score-index; peak velocity of early diastolic filling (E); peak velocity of filling during atrial systole (A); the ratio A/E; percent of LV filling contributed by atrial systole (A%). During follow-up 10 patients (Group B; 21%) developed symptoms and/or signs of CHF, while 38 patients (Group A; 79%) did not. In the patients who developed CHF 2D echo showed a depressed contractile function (mean value of wall motion score-index 3.08 +/- 0.45 versus 3.53 +/- 0.32 of Group A; p < 0.001) and a marked impairment of filling during atrial systole: A/E = 1.89 +/- 0.80 versus 1.07 +/- 0.35 (p < 0.001); A% = 52.2 +/- 9.9 versus 39.1 +/- 8.4 (p < 0.001). The multivariate analysis showed that the ratio A/E, A% and the wall motion score-index are the only variables that may predict the development of CHF. This capacity has been confirmed also considering the cut-point as conditional variables (A/E > 1.4; A% > 45%; score-index < 3.1). Our results demonstrate that a combined evaluation by 2D echo of systolic and diastolic LV function parameters allowed a better stratification of patients at risk of developing CHF after an AMI.

Adult↗
PubMed1991

Histones and DNA methylation in mammalian chromatin. II. Presence of non-inhibitory tightly-bound histones.

After removal, by high-salt extraction, of the loosely-bound components present in human placenta chromatin, tightly-bound cationic proteins could be solubilized, by acid extraction, from the 'stripped' chromatin, as well as from the 'stripped' loops or from the 'digested matrix'. These acid-soluble tightly-bound proteins are, in terms of apparent molecular mass and immunoreactivity, quite similar to the 'typical', loosely-bound histones, and, similarly to their 'loosely-bound' counterparts, they can be subdivided in distinct H1-, H2A-, H2B-, H3- and H4-like components, the 'digested matrix' being however characterized by the absence of tightly-bound H1. These tightly-bound histones, at variance from the 'typical' ones, readily find a right-handed helical conformation upon renaturation by progressive dialyses. The H1 components strongly differ also in their effects on enzymic DNA methylation: while 'typical' H1 has a strong inhibitory effect, its tightly-bound counterpart exerts a slight but definite stimulation.

Chromatin↗
PubMed1991

Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2.

Complete nucleotide sequencing of the RNAs of two unrelated neurovirulent isolates of Sabin-related poliovirus type 2 revealed that two nucleotides and one amino acid (amino acid 143 in the major capsid protein VP1) consistently departed from the sequences of the nonneurovirulent poliovirus type 2 712 and Sabin vaccine strains. This pattern of mutation appeared to be a feature common to all neurovirulent variants of poliovirus type 2.

Amino Acid Sequence↗
PubMed1990

Activities and mechanisms of action of halogen-substituted flavanoids against poliovirus type 2 infection in vitro.

The effects of some halogen-substituted flavanoids (dichloroflavan, halogenated isoflavans, and isoflavenes) on poliovirus type 2 infection was examined. Only two isoflavenes exhibited a significant inhibitory activity on the virus-induced cytopathic effect and plaque formation. In a single cycle of viral replication, both compounds reduced the viral yield by approximately 90%. The presence of the isoflavenes from the beginning of infection or during the adsorption period only prevented the shutoff of host translation and viral RNA and protein synthesis, suggesting that the drugs blocked an early step of viral replication. Indeed, both isoflavenes were not virucidal, did not protect virus infectivity from heat inactivation, and had no measurable effect on the binding of virus to cells, viral penetration, and uncoating of the viral RNA. In contrast, both compounds significantly reduced the infectivity of free viral RNA. The possibility that compounds interfere with poliovirus replication at a very early stage of translation of the input RNA is discussed.

Flavonoids↗
PubMed1989

Alterations of coagulase-negative staphylococcal flora in cardiac surgery patients: comparative study between cefamandole and pefloxacin perioperative prophylaxis.

The changes in coagulase-negative staphylococcal flora induced by cefamandole prophylaxis were compared with those induced by pefloxacin prophylaxis among patients undergoing heart valve surgery. Twenty-five patients (15 receiving cefamandole prophylaxis and 10 receiving pefloxacin prophylaxis) were included in the study. In the pefloxacin group, colonization rates in anterior nares and in chest skin or wound that were 60% and 50% respectively before surgery, became 50% and 20% respectively after surgery. In the cefamandole group, colonization rates in anterior nares and chest skin or wound were 53.3% and 60% respectively before surgery and became 53.3% and 40% respectively after surgery. Cefamandole did not appear to induce the emergence of oxacillin or pefloxacin resistant coagulase-negative staphylococcal colonization in any cultured site. On the other hand pefloxacin appeared somewhat more efficacious than cefamandole in eradicating staphylococcal flora of anterior nares and chest skin or wound. Pefloxacin and oxacillin resistant strains were found in the perianal area in 0% of patients before pefloxacin prophylaxis and in 70% of patients after pefloxacin prophylaxis. However, further studies are necessary to confirm the emergence of antibiotic resistant coagulase-negative staphylococci in the intestinal microflora after quinolone administration. The clinical implications of such apparently disturbing phenomenon remain to be evaluated.

Cefamandole↗
PubMed1987

Paralytic poliomyelitis in Italy (1981-85).

Fifteen cases of presumptive poliomyelitis occurring in Italy between 1981-85 were studied in order to differentiate between paralysis caused by poliovirus and that of different etiology. Out of seven confirmed cases three were "temporally associated with vaccination". Three aspects are discussed: the need for a careful differential diagnosis of paralytic cases; the over concern about the problem of vaccine-associated cases: the risk connected with re-importation of wild poliovirus strains.

Child, Preschool↗
PubMed1987

Antigenic and biochemical characterization of poliovirus type 2 isolated from two cases of paralytic disease.

Three isolates of poliovirus type 2 were obtained from rectal and pharyngeal swabs of two patients with paralytic poliomyelitis from Southern Italy (1981/1983). Neither one of the patients had received oral poliovirus vaccine, although a systematic vaccination campaign is conducted in the area. Neutralization tests with strain-specific antisera and analysis of the structural proteins by SDS-PAGE indicated that the three isolates were typical Sabin-like poliovirus type 2. Moreover, neutralization assays by means of a panel of well-characterized monoclonal antibodies indicated that the three isolates carried an antigenic mosaic where both wild-type and Sabin-specific epitopes were represented. The T1 fingerprints of the RNA of the three isolates diverged slightly from the standard Sabin reference map. A comparison of the oligonucleotide fingerprints of the viruses isolated from the pharynx and the feces of one patient indicated that mutations appeared as early as during replication in the intestinal tract.

Antibodies, Monoclonal↗