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M Ciaccio

Publications and source records attributed to M Ciaccio.

At least 19 recordsLinked to original sources
PubMed2006

Differences in serum GH cut-off values for pharmacological tests of GH secretion depend on the serum GH method. Clinical validation from the growth velocity score during the first year of treatment.

BACKGROUND: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5-10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. METHODS: Fifty pre-pubertal patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). RESULTS: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. CONCLUSION: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.

Adolescent↗
PubMed2006

Maternal hyperphenylalaninemia syndrome: neuropsychological evaluation of four subjects during childhood and adolescence.

Maternal hyperphenylalanemia during pregnancy may induce a severe embryopathy characterized by microcephaly, mental retardation, facial dysmorphy and congenital heart defects. Four subjects, two pairs of sibs, with maternal hyperphenylalaninemia syndrome were included in this study and their neuropsychological performances were assessed. Maternal levels of hyperphenylalaninemia were similar in both mothers, one of them had not been diagnosed with the condition until her two children were examined at the ages of 10 and 6 years. A severe cognitive deficit was detected in all 4 subjects, with a typical profile of impaired perceptive abilities, behavioural disturbances, motor difficulties and poor familiar integration.

Adolescent↗
PubMed2002

High levels of exogenous C2-ceramide promote morphological and biochemical evidences of necrotic features in thyroid follicular cells.

CD95 and ceramide are known to be involved in the apoptotic mechanism. The triggering of CD95 induces a cascade of metabolic events that progressively and dramatically modifies the cell shape by intense membrane blebbing, leading to apoptotic bodies production. Although the CD95 pathway has been abundantly described in normal thyrocytes, the effects of cell permeable synthetic ceramide at morphological and biochemical levels are not fully known. In the present study, we show that thyroid follicular cells (TFC) exposed to 20 microM of C(2)-ceramide for 4 h are characterized by morphological features of necrosis, such as electron-lucent cytoplasm, mitochondrial swelling, and loss of plasma membrane integrity without drastic morphological changes in the nuclei. By contrast, TFC treated with 2 microM of C(2)-ceramide for 4 h are able to accumulate GD3, activate caspases cascade, and induce apoptosis. Furthermore, we provide evidence that 20 microM of C(2)-ceramide determine the destruction of mitochondria and are not able to induce PARP cleavage and internucleosomal DNA fragmentation, suggesting that the apoptotic program is not activated during the death process and nuclear DNA is randomly cleaved as the consequence of cellular degeneration. Pretreatment with 30 microM of zVAD-fmk rescued TFC from 2 microM of C(2)-ceramide-induced apoptosis, whereas, 20 microM of C(2)-ceramide exposure induced necrotic features. Deltapsi(m) was obviously altered in cells treated with 20 microM of C(2)-ceramide for 4 h (75% +/- 3.5%) compared with the low percentage (12.5% +/- 0.4%) of cells with altered Deltapsi(m) exposed to 2 microM of C(2)-ceramide. Whereas, only 20% +/- 1.1% of cells treated with anti-CD95 for 1 h showed altered Deltapsi(m). Additionally, Bax and Bak, two pro-apoptotic members, seem to be not oligomerized in the mitochondrial membrane following ceramide exposure. These results imply that high levels of exogenous ceramide contribute to the necrotic process in TFC, and may provide key molecular basis to the understanding of thyroid signaling pathways that might promote the apoptotic mechanism in thyroid tumoral cells.

Apoptosis↗
PubMed2001

Enzymatic activity, protein expression, and gene sequence of cruzipain in virulent and attenuated Trypanosoma cruzi strains.

Protein expression, characterized in Western blots and gelatinolytic activity, of cruzipain (Cr), the major Trypanosoma cruzi cysteine proteinase, was compared among 3 attenuated T. cruzi strains (TUL 0, TCC, and Y null) and their virulent counterparts (TUL 2, Tulahuen, and Y). All attenuated strains displayed a weaker gelatinolytic activity as compared with their virulent counterparts. The electrophoretic mobility and immunological reactivity revealed quantitative and qualitative differences, with the attenuated parasites showing bands of less density in all strains and lower mobility in 2 of them, as compared with the virulent strains. Sequence analysis of 1 Cr gene in the Tulahuen and TCC strains indicated 37/1404 base pair substitutions, corresponding to 20 amino acid changes in the attenuated strain. A similar comparative analysis of 1 Cr gene between Y and Y null strains showed 13/1404 base pair substitutions, corresponding to 8 amino acid changes in the attenuated strain. Although enough variability exists in the Cr gene to allow for less- or nonfunctional isoforms of the protein, further clones should be analyzed to establish whether attenuation is regularly associated with specific sequence changes of this enzyme.

Amino Acid Sequence↗
PubMed1999

Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25.

A 4.8-kb plasmid region carrying the four genes mcjABCD necessary for production of and immunity to the cyclic peptide antibiotic microcin J25 (MccJ25) has been sequenced. mcjA encodes the primary structure of MccJ25 as a precursor endowed with an N-terminal extension of 37 amino acids. The products of mcjB and mcjC are thought to be involved in microcin maturation, which implies cleavage of McjA and head-tail linkage of the 21-residue pro-MccJ25. The predicted McjD polypeptide, which is highly similar to several ABC exporters, was found to be required for MccJ25 secretion, thus explaining its ability to confer immunity to MccJ25.

ATP-Binding Cassette Transporters↗
PubMed1999

[Biologic effects of the static magnetic field generated by a 0.5 T magnetic resonance tomograph on the enzyme activity of catalase and creatine kinase in the rat].

PURPOSE: We investigated possible alterations in the enzyme activity of catalase and isozyme MB-creatine kinase induced by prolonged exposure of laboratory rodents to a static magnetic field generated by a .5 T Magnetic Resonance unit. MATERIAL AND METHODS: Thirty Wistar albino mice were divided into two groups of 15 mice, one to be exposed to the static magnetic field for 12 hours and the other to be kept in the same environmental conditions as a control group. Immediately after the exposure a peripheral venous blood sample was collected, the cardiac muscle was removed from the mice and the enzyme activity of catalase and MB-creatine kinase were assayed using the spectrophotometric analysis. RESULTS: No statistically significant variation was detected between the enzyme activity of catalase and MB-creatine kinase in the serum and cardiac muscle of the exposed versus the control mice. In the mice exposed to the static magnetic field the enzyme activity of serum and cardiac muscle catalase were respectively .2154 U/L and .0707 U/L after 10 minutes; they were; .2699 U/L and .0946 U/L after 160 minutes. In the control mice the enzyme activity of serum and cardiac muscle catalase were respectively .1941 U/L and .0707 U/L after 10 minutes; they were .2061 U/L and .1068 U/L after 160 minutes. The enzyme activity of MB-creatine kinase in mice was measured in the exposed (80.8 U/L) versus the control (79.6 U/L) group: the difference does not exceed standard deviation. DISCUSSION AND CONCLUSION: Our results seem to exclude any alteration in the activity of catalase and MB-CK after 12 hours' exposure to the static magnetic field. However some homeostatic mechanisms peculiar to pluricellular organisms might act in vivo to adapt to the effects of the static magnetic field during exposure.

Animals↗
PubMed1996

Functional adrenal cortical tumors in pediatric patients: a clinicopathologic and immunohistochemical study of a long term follow-up series.

BACKGROUND: Controversy exists as to which variable is a reliable predictor of clinical outcome of adrenal cortical tumors in children. METHODS: Twenty patients with adrenal cortical tumors were studied. Tumor weight, histologic features, and percentage of proliferating cell nuclear antigen (PCNA/cyclin) in tumor cells were analyzed to determine the best predictor of clinical outcome. RESULTS: Eleven patients had Cushing's syndrome with virilization and 9 had virilization without Cushing's syndrome. The mean age at diagnosis was 7.1 +/- 5.2 years (range, 0.4-15.6 years). Sixteen patients, with good outcomes have been followed for 10.7 +/- 7.8 years (range, 3-23 years). All but two patients had a tumor weight of less than 100 g (185 g and 800 g, respectively) (mean 47.7 g +/- 46.4 g). Two patients with large tumors (weighing 1000 g and 780 g, respectively) had poor outcomes; 1 died 3 months after surgery with metastasis and the other presented with lung metastasis 18 months after surgery. Histologic features did not correlate with clinical outcome. Overall, PCNA stained cells were 6.96 +/- 8.2% (range, 0-32.5%). PCNA values were significantly lower in tumors of patients with good outcomes (P < 0.002). Within all tumors, we found a weak correlation between tumor weight and PCNA (r = 0.51; P < 0.02), but a better correlation was found between tumor weight and PCNA in patients with Cushing's syndrome (r = 0.70; P < 0.01). Patients with Cushing's syndrome had higher PCNA values than those with virilization syndrome (10.3 +/- 9.6% vs. 2.8 +/- 3.3%; P < 0.03). CONCLUSIONS: Our data show that small tumors (less than 100 g) are associated with good outcome; the two patients with the poorest prognosis had Cushing's syndrome and large tumors (more than 100 g). Histologic features are not adequate predictors of outcome and PCNA may be useful in tumors of patients with Cushing's syndrome, but this parameter should not be used alone. Two patients had virilization syndrome, large tumors (185 g and 800 g, respectively), and good outcomes, which contradicts with the concept that these tumors are usually associated with poor prognosis.

Adolescent↗
PubMed1996

Genetic analysis of plasmid determinants for microcin J25 production and immunity.

Microcin J25 (MccJ25) is a small peptide antibiotic produced by an Escherichia coli strain isolated from human feces. The genetic determinants for MccJ25 synthesis and immunity have been cloned from the low-copy-number wild-type plasmid pTUC1OO into the compatible vectors pBR322 and pACYC184. Physical and phenotypical analysis of insertion mutations and complementation tests defined three contiguous genes involved in MccJ25 production which span a region of about 2.2 kb. Immunity to the antibiotic is provided by an additional gene adjacent to the production region.

Bacteriocins↗
PubMed1996

[A quantitative in-vitro analysis of the effects of magnetic fields and radiofrequencies on amino acid metabolism].

The extensive use of magnetic resonance imaging in medical diagnosis needs experimental confirmation of the real biological harmlessness of magnetic fields and radiofrequencies in the imaging process. To date, no unquestionable conclusions have been drawn and experimental results differ in various literature reports. We investigated the effects of radiofrequencies and magnetic fields on the amino acid content of plasma samples from 10 healthy volunteers aged 25 to 30 years; the samples were exposed for 60 minutes to MR fields at 0.5 T with the sequences commonly used in clinical practice. After exposure to magnetic fields, the samples were analyzed with chromatography and the results compared with those of plasma samples not exposed to MR fields. Thirty-four different amino acids were investigated and no significant changes were observed in the total concentration of any of them. Our results show that, at least in a cell-free system, exposure to a magnetic field at 0.5 T causes no significant quantitative changes in amino acid composition, at least no changes demonstrable at chromatography. On the other hand, our preliminary observation does not exclude that exposure to nonionizing radiation may modify in vivo enzyme kinetics with transient qualitative, but not quantitative, changes.

Adult↗
PubMed1995

Contribution of vitamin A to the oxidation resistance of human low density lipoproteins.

This study investigated the antioxidant contribution of vitamin A in protecting human low density lipoprotein (LDL) against copper-stimulated oxidation. The presence of small amounts of retinol (0.033 +/- 0.012 nmol/mol LDL) and retinyl palmitate (0.036 +/- 0.021 nmol/mol LDL) was routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase of retinol and retinyl palmitate in the LDL isolated 8 h after the supplementation. In comparison to autologous-control LDL, vitamin A-enriched LDL were more resistant to oxidation, as expressed both by a clear delay in the onset of lipid peroxidation and by a reduction of the rate of conjugated diene hydroperoxide production during the propagation phase. The calculated incremental increase in the lag phase produced by 1 mol retinol per mol LDL is about 1000 min, suggesting that retinol is more potent than alpha-tocopherol in LDL. Oxidation experiments carried out with LDL isolated from plasma incubated in vitro with either retinol or retinyl palmitate indicated that retinol does lengthen the lag phase, whereas retinyl palmitate can slow the rate of peroxyl chain propagation, without affecting the duration of the lag phase. Temporal disappearance of retinol and retinyl palmitate, followed in comparison with that of alpha-tocopherol and beta-carotene, indicated that the reactivity of the antioxidants with lipoperoxyl radicals was in the sequence alpha-tocopherol, retinol, beta-carotene, and retinyl esters. Although the detailed antioxidant mechanism remains to be elucidated, these results suggest that LDL-associated vitamin A can play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo.

Adult↗
PubMed1994

Self-healing localized cutaneous mucinosis.

A 54-year-old woman presented a lesion on the dorsum of the right hand. Routine laboratory tests were normal or negative. Histological examination revealed mucin deposits in the reticular dermis. The lesion cleared within 1 year without any treatment but biopsy. This case does not fit the diagnostic criteria of any known cutaneous mucinoses.

Female↗
PubMed1994

Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro.

Previous results from our laboratory gave evidence that safe doses of vitamin A were very effective in protecting rats from adriamycin-induced oxidative stress and lethal cardiotoxicity (Tesoriere, L. et al. (1994) J. Pharmacol. Experim. Ther. 269, 430-436). This was an incentive also to evaluate whether or not vitamin A affected the antitumor activity of adriamycin. K562 human erythroleukemia cells were exposed to adriamycin or to adriamycin plus vitamin A. Presence of 2.5 to 15 microM all-trans retinol in the cell culture did not impair the cytotoxicity of adriamycin. Rather, an enhanced cell death was observed when cell colony was exposed to both compounds. Additional assays showed that all-trans retinol counteracted the lipoperoxide formation, assayed as malondialdehyde, induced in cell cultures by the redox cycling activity of adriamycin. These data strongly encourage a new therapeuthical approach with safe doses of vitamin A as an adjuvant in cancer chemotherapy.

Cell Line↗
PubMed1994

Effect of vitamin A administration on resistance of rat heart against doxorubicin-induced cardiotoxicity and lethality.

The peroxyl radical-scavenging activity of vitamin A has been exploited to obtain protection against peroxidative damages induced in rat heart by administration of an acute dose of doxorubicin (10 mg/kg, in vein). Peroxidative lesions were evaluated by both biochemical and histological assays, 48 hr after the injection of doxorubicin. Heart tissue from rats receiving doxorubicin showed a marked increase of protein carbonyl levels, and of membrane conjugated dienes, as well as a decrease of membrane protein thiols. Abnormal chemistries, including a large increase of the activity of serum lactate dehydrogenase and creatine phosphokinase, an index of the myocardial damage caused by doxorubicin, were also observed. Pretreatment of rats with 25 I.U./kg b.wt. of vitamin A, once a day for 2 days, before injecting doxorubicin, substantially reduced the peroxidative damage to heart lipids and proteins, and markedly lowered the serum values of lactate dehydrogenase and creatine phosphokinase to values close to those of control rats. The significant prevention of doxorubicin-induced cardiomyopathy by vitamin A was evident from the histopathological pattern observed after light microscopy. The dosage of vitamin A useful to obtain the protective effect appears safe and does not injure the liver, as indicated by light microscopy of the tissue. A survival study, carried out by injecting rats with a single injection of 10 mg/kg of doxorubicin, showed that pretreatment with 25 I.U. of vitamin A per kg significantly increased survival rate of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Antioxidant activity of all-trans-retinol in homogeneous solution and in phosphatidylcholine liposomes.

A kinetic quantification of the lipoperoxyl radical-scavenging activity of all-trans-retinol has been carried out in homogeneous solution, when radicals were produced from the oxidation of methyl linoleate in methanol, initiated by the lipid-soluble 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) as well as in a soybean phosphatidylcholine membrane model, in which peroxidation was induced either by AMVN or the hydrophylic 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH). The physical microenvironment contributes to the determination of antioxidant efficiency of all-trans-retinol. In homogeneous solution the kinetic constant kinh is 3.5 x 10(5) M-1 s-1 and appears of the same order of magnitude as the inhibition constant measured for alpha-tocopherol under the same experimental conditions. Nevertheless, despite its very high chemical reactivity toward lipoperoxyl radicals, the overall antioxidant efficiency of all-trans-retinol in this system appears quite limited, since the evaluated stoichiometric factor is 0.21. When the polyenoic chain of all-trans-retinol is incorporated into a phosphatidylcholine lipid bilayer, the antioxidant efficiency depends on the site of peroxyl-radical production. The highest lipoperoxyl radical-scavenging activity is measured when radicals are generated by AHVN inside the bilayer multilamellar liposomes. Under these conditions, the relative antioxidant efficiency is similar to that of alpha-tocopherol, and the stoichiometric factor is 3.1. When radicals are generated by AAPH in the aqueous phase of an unilamellar liposomal system, the antioxidant effectiveness of all-trans-retinol appears reduced and lower than that measured with equivalent amounts of alpha-tocopherol. Synergistic antioxidant effects between all-trans-retinol and alpha-tocopherol are observed when both antioxidants are simultaneously incorporated into unilamellar liposomes in which peroxidation is induced by AAPH. This suggests that all-trans-retinol may interact with tocopheroxyl radicals, thereby regenerating alpha-tocopherol. This interaction, which may be related to molecular features and to the relative location of the antioxidants in the bilayer, could provide an effective antioxidant system that may be of great importance in vivo.

Amidines↗
PubMed1993

Sea urchin early histone H2A modulator binding factor 1 is a positive transcription factor also for the early histone H3 gene.

To shed some light on the mechanisms involved in the coordinate regulation of the early histone gene set during sea urchin development, we tested the hypothesis that the upstream sequence element USE1, previously identified in the early H2A modulator, could also participate in the transcription of the early histone H3 gene. We found by DNAse I protection analysis and by competition in electrophoretic mobility-shift experiments that two sequence elements of the H3 promoter closely resembled the USE1-H2A sequence in their binding activity for nuclear factors from 64-cell stage embryos. These modulator binding factor 1 (MBF-1)-related factors seem to recognize the ACAGA motif that is conserved between the USE1-like sequences of both H2A and H3 promoters. In fact, excess oligonucleotide containing a mutated USE1-H2A element in which the ACAGA sequence was mutated to AGTCA failed to compete with the USE1 sites of both H2A and H3 genes for interaction with MBF-1. Finally, in vivo transcriptional analysis in both Xenopus and sea urchin showed that an excess of USE1-H2A element efficiently competed for the activity of the H3 promoter. From these results we conclude that MBF-1 is a transcription factor conserved between sea urchin and frog and that MBF-1 or related transcription factors are involved in the coordinate expression of both H2A and H3 early histone genes.

Animals↗
PubMed1993

Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues in vivo.

The antioxidant activity of vitamin A against lipid peroxidation induced by doxorubicin in rat tissues in vivo was investigated. A single ip injection of doxorubicin (30 mg/kg body wt) markedly raised the level of peroxidated lipids measured as TBARS and conjugated dienes in heart and brain membrane preparations. Other tissues, such as retina and liver, did not show any increase of lipid peroxides over control values. Pretreatment of rats with two daily subcutaneous injections of retinol palmitate (0.25 g/kg body wt), for 2 days, before injecting doxorubicin, inhibited peroxidation of heart and brain membrane lipids. The antioxidant action of vitamin A does not appear to be mediated by enhancement of antioxidant enzyme activities committed to detoxify oxygen radicals. Superoxide dismutase and catalase, measured in heart and brain cytosol, were not affected by the vitamin A treatment. On the contrary, a slight increase of catalase activity was observed in heart and brain cytosol from rats that had been treated with doxorubicin. Excess vitamin A may be localized in membranes. Appreciable increase of retinyl esters and retinol was measured in membrane preparations from rats that had been treated with vitamin A, with respect to control animals. Brain and heart membrane preparations from rats receiving vitamin A, assayed in vitro in the presence of an Fe3+ ascorbate induction system, showed a delay at the beginning of the lipid peroxidation and generated lesser amounts of TBARS, with respect to membranes from control rats. Thus, the increase of vitamin A within cell membranes results in an increased resistance of membrane lipids to peroxidation, both endogenously produced and induced in vitro. These results may be consistent with the hypothesis that vitamin A may act as a physiological antioxidant in cell membranes where it is localized.

Animals↗
PubMed1993

Differences in serum insulin-like growth factor I and sex-hormone-binding globulin levels between late and early prepuberty in patients with idiopathic and organic growth hormone deficiency.

It has been reported that growth hormone modulates serum levels of insulin-like growth factor I (IGF-I) positively and serum levels of sex-hormone-binding globulin (SHBG) negatively. We have measured IGF-I and SHBG concentrations in 24 prepubertal patients with growth hormone deficiency. Twelve of these patients had had intracranial tumors removed (organic growth hormone deficiency) and 12 had growth hormone deficiency of unknown etiology (idiopathic). Fifty-two prepubertal control subjects, admitted for elective surgery, were also studied. All prepubertal patients were divided into two age groups: older and younger than 7 years of age. In both groups there were patients with multiple pituitary deficiencies on hydrocortisone and/or levothyroxine sodium replacement therapy. In the age group younger than 7 years, serum IGF-I was not significantly different between organic and idiopathic growth hormone deficiency (0.28 +/- 0.21 versus 0.062 +/- 0.071 mU/l) but serum SHBG levels were different (74.6 +/- 33.5 versus 173 +/- 59 nmol/l, p < 0.05). These values were not significantly different from controls (0.47 +/- 0.25 mU/l and 132 +/- 47 nmol/l, respectively). In the age group older than 7 years, there was no significant difference between organic and idiopathic growth hormone deficiency in serum IGF-I (0.33 +/- 0.17 versus 0.16 +/- 0.11 mU/l) or serum SHBG (113 +/- 72 versus 108 +/- 17 nmol/l). These values were significantly different from controls (1.04 +/- 0.36 mU/l and 68.7 +/- 31.7 nmol/l, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗