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A Vitelli

Publications and source records attributed to A Vitelli.

At least 19 recordsLinked to original sources
PubMed1996

Elevated levels of interleukin-6 in unstable angina.

BACKGROUND: Elevated plasma levels of C-reactive protein have been found in the majority of patients with unstable angina. The evidence of elevated levels of acute-phase proteins in unstable angina is in line with a growing body of evidence that suggests that inflammation plays a role in this syndrome and is an indirect sign of increased production of interleukin-6, which is the major determinant of acute-phase-protein production by the liver. However, in unstable angina, there is no direct proof of the role played by interleukin-6. METHODS AND RESULTS: We measured levels of interleukin-6 in 38 patients with unstable angina at the time of their admission to the coronary care unit and in 29 patients with stable angina. In the same groups of patients, we also measured C-reactive protein. Interleukin-6 (undetectable, ie, < 3 pg/mL, in healthy volunteers) was detectable in 23 (61%) of 38 patients with unstable angina but in only 6 (21%) of 29 with stable angina (P < .01). Median interleukin-6 levels were 5.25 pg/mL (range, 0 to 90 pg/mL) in patients with unstable angina but were below the detection limit of the assay in patients with stable angina (range, 0 to 7 pg/mL). A significant correlation was observed between interleukin-6 and C-reactive protein levels (r = .4, P = .013). CONCLUSIONS: Our study demonstrates that raised levels of interleukin-6 are common in unstable angina, correlate with C-reactive protein, and are associated with prognosis, thus confirming the importance of the cytokine pathway for the production by the liver of acute-phase proteins and strengthening the importance of inflammation in this syndrome. Further studies are required to elucidate better the role of interleukins in unstable angina.

Aged↗
PubMed1993

The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms.

The promoter regions of three IL-6 inducible genes, hemopexin (Hpx), haptoglobin (Hp) and C-reactive protein (CRP) contain cis-acting IL-6 responsive elements (IL-6REs) which are necessary and sufficient to induce IL-6 transcription activation. Transcription factors of the C/EBP family interact with IL-6REs. Among these, IL-6DBP/NF-IL6 plays a key role in IL-6 signal transduction because its trans-activation potential is induced by IL-6 in the human hepatoma cell line Hep3B. We show here that a different C/EBP-related factor, C/EBP delta/NF-IL6 beta, is the major IL-6 induced protein interacting with IL-6REs in the nuclei of Hep3B cells. In contrast to IL-6DBP/NF-IL6, whose activity in Hep3B cells is modulated by IL-6 via a post-translational mechanism, C/EBP delta/NF-IL6 beta is transcriptionally induced by IL-6. Another contrasting feature is that the C/EBP delta cDNA transfected in Hep3B cells activates transcription from an IL-6RE synthetic promoter in a constitutive manner which is not further enhanced by IL-6. Therefore, in Hep3B cells, two distinct members of the C/EBP family are recruited in the IL-6 signal transduction pathway via different mechanisms.

Acute-Phase Proteins↗
PubMed1991

Identification of regulatory residues of the yeast adenylyl cyclase.

We have attempted to identify amino acid residues of the yeast adenylyl cyclase that are involved in the regulation of its activity, by isolating adenylyl cyclase-linked spontaneous mutations capable of suppressing the temperature-sensitive phenotype of ras1- ras2-ts1 strains. We previously identified a mutated adenylyl cyclase in which a single point mutation, called CR14, led to the replacement of threonine 1651 with isoleucine. We have now investigated the biological effects of CR14, and of other mutations that cause the replacement of threonine 1651 by distinct amino acids. We have observed that the response of adenylyl cyclase to Ras can be either enhanced or attenuated, without significant effects on the steady-state level of the former enzyme in vivo, depending on the amino acid side chain at position 1651. Therefore, this residue identifies a regulatory region on the adenylyl cyclase molecule. We have also taken advantage of the attenuation of adenylyl cyclase function caused by the replacement of threonine 1651 with aspartic acid to isolate intragenic suppressor mutations. We have identified several point mutations, leading to single amino acid substitutions, individually capable of reactivating the attenuated adenylyl cyclase. The corresponding amino acid changes are located within a relatively small region, including residues 1331, 1345, 1348 and 1374. This region could be physiologically involved in the negative control of the carboxy-terminal catalytic domain.

Adenylyl Cyclases↗
PubMed1989

The origin of DNA single strand breaks induced by ethylating agents in mammalian cells.

Chinese hamster ovary (CHO) cells were treated with two ethylating agents, N-ethyl-N-nitrosourea (ENU) and diethylsulfate (DES), and the kinetics of DNA single strand break (ssb) induction and rejoining were determined in parallel with DNA adduct formation and removal. In the case of DES, DNA ssb as determined by alkaline elution (AE) were repaired very slowly with more than 50% of the lesions still present on DNA 3 h after treatment. In contrast, 45% of ENU-induced ssb were repaired within 10 min. From the relative concentration of the different ethylated products and their repair rates as measured by high performance liquid chromatography (HPLC) analysis of the ethylated DNA, a theoretical function was constructed that describes the number of ssb expected at each time point after exposure to the mutagen. DES-induced ssb are explained by excision repair processes active on the ethylated purines, mainly 3-ethyladenine (3-EtAde) and 7-ethylguanine (7-EtGua). On the same basis, the rapidly repaired ENU-induced ssb remain unexplained. These results are also discussed in relation to the sensitivity of the two techniques, AE and HPLC, for detecting DNA damage.

Alkylating Agents↗
PubMed1988

Yeast mutants temperature-sensitive for growth after random mutagenesis of the chromosomal RAS2 gene and deletion of the RAS1 gene.

Saccharomyces cerevisiae strains with a disrupted RAS1 gene and with an intact RAS2 gene (ras1- RAS2 strains) grew well on both fermentable and nonfermentable carbon sources. By constructing isogenic mutants having a disrupted RAS1 locus and a randomly mutagenized chromosomal RAS2 gene, we obtained yeast strains with specific growth defects. The strain TS1 was unable to grow on nonfermentable carbon sources and galactose at 37 degrees C, while it could grow on glucose at the same temperature. The mutated RAS2 gene in TS1 cells encoded a protein with the glycines at positions 82 and 84 replaced by serine and arginine respectively. Both mutations were necessary for temperature sensitivity. We also isolated a mutant yeast that was unable to grow on nonfermentable carbon sources both at 30 and 37 degrees C, while growing on glucose at both temperatures. This phenotype was caused by a single chromosomal mutation, leading to the replacement of aspartic acid 40 of the RAS2 protein by asparagine. A ras1- yeast strain with a chromosomal RAS2 gene harbouring the three mutations together did not grow at any temperature using non-fermentable carbon sources, but it was able to grow on glucose at 30 degrees C, and not at 37 degrees C. The mutated proteins were much less effective than the wild-type RAS2 protein in the stimulation of adenylate cyclase, but were efficiently expressed in vivo. The possible roles of residues 40, 82 and 84 of the RAS2 protein in the regulation of adenylate cyclase are discussed.

Adenylyl Cyclases↗
PubMed1988

Relationship between specific alkylated bases and mutations at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells.

DNA adduct formation and induction of mutations at 2 gene loci, hypoxanthine-guanine-phosphoribosyltransferase (HPRT) and Na,K-ATPase, were determined simultaneously in Chinese hamster ovary (CHO) cells after treatment with 2 ethylating agents, ethylnitrosourea (ENU) or diethyl sulfate (DES). Doses of DES and ENU, which resulted in equal levels of O6-ethylguanine (O6-EtGua) and O4-ethylthymine (O4-EtThy) in the DNA, were found to induce very similar frequencies of 6-thioguanine-resistant (6-TGr) mutants. Formation of these DNA adducts might therefore be correlated with mutations induced at the HPRT locus. When, however, the same analysis was applied to ouabain-resistant (ouar) mutants, it was found that, at similar levels of O6-EtGua and O4-EtThy, DES induced many more ouar mutants than ENU. This result supports the notion that primary DNA lesions other than O6-EtGua and O4-EtThy are involved in the fixation of ENU- and DES-induced mutations at the Na,K-ATPase gene locus.

Alkylating Agents↗
PubMed1987

Induction kinetics of mutations at two genetic loci, DNA damage and repair in CHO cells after different exposure times to N-ethyl-N-nitrosourea.

Ouabain resistance (ouar) and 6-thioguanine resistance (6-TGr) mutation frequencies were measured in Chinese hamster ovary cells after treatment with N-ethyl-N-nitrosourea (ENU) for varying periods of time. Maximal mutation frequency at the Na+/K+ ATPase gene locus (ouar mutations) was attained within 5 min of exposure, whereas the mutation frequency at the hypoxanthine guanine phosphoribosyltransferase locus (6-TGr mutations) continued to increase up to 60 min, following the theoretical curve for exponential decay of ENU with time. Detection of DNA single strand breaks (ssb) by alkaline elution showed that maximal levels were attained within 5 min of treatment with ENU. Fast repair of DNA ssb occurred early after exposure (greater than 50% repair within 10 min). Analysis of DNA ethylation products by h.p.l.c. showed initially rapid removal of O2-ethylcytosine (25% in the first hour), slow removal of 7-ethylguanine, 3-ethyladenine and 3-ethylguanine and no removal at all of O6-ethylguanine, O4-ethylthymine and ethylphosphotriesters. These time-course studies reveal different target gene responses in the fixation of DNA damage into mutations.

Animals↗
PubMed1986

Suppression of defective RAS1 and RAS2 functions in yeast by an adenylate cyclase activated by a single amino acid change.

We have constructed the yeast strain TS1, with the RAS2 gene replaced by mutant allele encoding a partially defective gene product, and with an inactive RAS1 gene. TS1 cells accumulate as unbudded cells upon temperature shift from 30 to 37 degrees C, thus showing that the RAS1 and RAS2 gene functions are important for progression through the G1 phase of the cell cycle. After the isolation of revertants able to grow at the nonpermissive temperature, we have found that a chromosomal point mutation can bypass the G1 arrest of TS1 and cdc25 cells, and the lethality of ras1 ras2 mutants. The mutation predicts the replacement of threonine by isoleucine at position 1651 of yeast adenylate cyclase. The RAS-independent, as well as the RAS-dependent adenylate cyclase activity, is increased by the mutation. Like the wild-type enzyme, the RAS-dependent activity of the mutant adenylate cyclase is turned on by the GTP-bound form of the RAS2 protein. The amino acid sequence surrounding the threonine 1651 shows similarity with protein kinase substrates. Possible implications for the function of adenylate cyclase are discussed.

Adenylyl Cyclases↗
PubMed1986

Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.

Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.

Adolescent↗
PubMed1984

IV-S neuroblastoma: a cooperative study of 30 children.

The clinical features of 30 children with IV-S neuroblastoma have been reviewed. They were treated at 11 Italian pediatric institutions in the period 1970-1981. Patients with IV-S neuroblastoma comprise 6.1% of all the neuroblastoma cases observed during that period. The age at diagnosis ranged from birth to 11 months (mean, 3 months). The distribution of "primary" lesions was of interest. The adrenal gland was affected most often (57% of patients), but tumors of the chest and neck were also encountered. No specific "primary" lesion was identified in ten children. The most frequent site of widespread disease was the liver (87%). Neither the size of the "primary" tumor, nor the number or size of subcutaneous nodules was of prognostic significance. Unfavorable features were age less than 2 months and clinical signs of pulmonary, renal, or hepatic embarrassment. These data confirm the need for prompt intervention in the infant who is suffering from compression of these vital structures by the enlarged liver. Radiation therapy is to be preferred for this purpose, because of the often severe toxicity that is associated with chemotherapy in infants. One, and possibly two babies in this series died of chemotherapy-related complications.

Adrenal Gland Neoplasms↗