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Biomedical subjects

A Antonelli

Publications and source records attributed to A Antonelli.

At least 19 recordsLinked to original sources
PubMed1996

Epidemiologic and clinical evaluation of thyroid cancer in children from the Gomel region (Belarus).

This study reviews the epidemiology of thyroid cancer during childhood from the environs of Gomel in Belarus and the clinical data of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma following the nuclear accident of Chernobyl. One case of thyroid cancer in children (aged < 15 years at diagnosis) was observed during the period 1981-1985 (rate = 0.5; expressed as annual averages per million children under age 15 years in the region of Gomel and period identified) before the Chernobyl accident. Twenty-one cases of thyroid cancer in children were observed during 1986-1990 (rate = 10.5) and 143 (rate 97) during 1991-1994 after the Chernobyl accident. During the first 7 months of 1995, there were 33 more cases of thyroid cancer observed in children. Three children with thyroid cancer were born since 1986 in the Gomel region. A total of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma had been reviewed by us during the period May to November 1994. The female/male ratio was 1.4:1.0. At the time of the first diagnosis the mean age of the children was 9.4 +/- 2.8 years, and at the time of the accident their mean age was 3.8 +/- 2.4 years. More than 90% of the patients were less than 6 years of age and 3 were still in utero at the time of the accident. The period of latency between the accident and the first diagnosis was 5.6 +/- 1.5 years. Their ages at the time of the first diagnosis and their ages at the time of the accident were significantly correlated (p = 0.001); there was no significant correlation between the age of each child at the time of the accident and the latent period before the onset of carcinoma. The aggressiveness of the tumor, evaluated on the basis of T stage, lymph node status, and lung metastases, did not correlate with age at the time of the first diagnosis or with the age at the time of the accident. The susceptibility of the thyroid to the carcinogenetic effects of radiation, particularly during the first years of life (< 5 years) has clearly been demonstrated. However, there appears to be no correlation between the aggressiveness of the tumor and the age of the patients.

Adolescent↗
PubMed1996

Effects of topoisomerase II inhibition in lymphoblasts from patients with progeroid and "chromosome instability" syndromes.

DNA topoisomerase II is involved in DNA topologic changes through the formation of a cleavable complex. This is stabilized by the antitumor drug VP16, which results in DNA breakage, aberrant recombination, and cell death. In this work, we compare the chromosomal damage induced by VP16 with that induced by bleomycin (BLM) in lymphoblasts from patients affected by the chromosome breakage syndromes ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Bloom syndrome (BS), and by the progeroid syndromes Werner (WS) and Cockayne (CS). Patients affected by AT, XP, BS, and WS have a greatly enhanced risk of developing cancer. The results show that AF and WS cells are hypersensitive to VP16, as revealed in the higher proportion of metaphases showing exchange figures and more than two breaks. All lines except AT and one CS line showed normal sensitivity to BLM. Our data on the sensitivity to VP16 of all these mutant cells underline the fact that VP16 damage is amplified only in cells that have abnormal illegitimate recombination (i.e., AT and WS).

Ataxia Telangiectasia↗
PubMed1996

VP16 hypersensitivity and increased faulty recombination in ataxia telangiectasia lymphocytes characterized by the tandem translocation t(14;14)(q11;q32).

Ataxia telangiectasia (AT) patients show variable degrees of immunodeficiency and a higher than normal predisposition to lymphoid malignancies. AT cells are characterized by spontaneous chromosome instability resulting in chromosome breakage and in non random chromosome rearrangements. Sequential cytogenetic studies on T-lymphocytes from an AT patient showed the progressive development of a clone bearing a tandem translocation t(14;14)(q11;q32). The abnormal clone had spontaneous chromosome rearrangements. Compared to non clonal cells, the abnormal clone displayed a higher frequency of spontaneous chromosome rearrangements. In only the clonal cells we observed two particular and predominant rearrangements: isodicentric chromosomes and telomeric associations which may derive from faulty recombination. Chromosome instability induced by the etoposide VP16, a DNA topoisomerase II inhibitor, was evaluated in terms of chromosome breakage and SCE frequency. T-lymphocytes from the AT patient showed hypersensitivity to VP16 significantly higher than normal T-lymphocytes. The chromosome instability induced by VP16 is significantly higher in clonal than in non clonal cells, whilst the chromosome instability induced by the radiomimetic drug bleomycin is not significantly different in the two AT lymphocyte subpopulations. The different spontaneous chromosome instability in clonal and non clonal cells together with their different behavior after treatment with only VP16, suggest that clonal cells bearing the tandem translocation could have increased faulty recombination. Given the presence of translocations t(14;14)(q11;q32) in T-prolymphocytic leukemias and T-cell tumors of non AT patients, our findings suggest that VP16 could be considered an antineoplastic treatment particularly indicated in these patients.

Adolescent↗
PubMed1996

Usefulness of MR signal intensity in distinguishing benign from malignant pleural disease.

OBJECTIVE: The aim of this study was to analyze the potential usefulness of MR signal intensity in differentiating malignant from benign pleural disease. SUBJECTS AND METHODS: Forty-five patients with pleural lesions identified on CT scans were subsequently examined by MR imaging at 0.5 T. T1-weighted, proton density-weighted, T2-weighted, and enhanced T1-weighted spin-echo images were obtained. For 34 patients, a diagnosis of malignant (n = 18) or benign (n = 16) disease was established. The morphologic features of the pleural lesions and MR signal intensity on T1-weighted, proton density-weighted, T2-weighted, and enhanced T1-weighted images were evaluated, and the ratio of lesion to muscle signal intensity was computed. RESULTS: Assessment of morphologic features by MR imaging and CT was not significantly different. High signal intensity on proton density-weighted and T2-weighted images was observed in all malignant lesions and in two benign lesions (sensitivity, 100%; specificity, 87%; negative predictive value, 100%). The ratio of lesion to muscle signal intensity on T1-weighted, proton density-weighted, T2-weighted, and enhanced T1-weighted images discriminated between malignant and benign lesions (p < .0001). For the subgroup of lesions misinterpreted by CT (n = 6), the evaluation of MR signal intensity on long-TR images made it possible to differentiate malignant from benign conditions. CONCLUSION: MR signal intensity is a valuable additional feature for differentiating malignant from benign pleural disease. Signal hypointensity with long-TR sequences is a reliable predictive sign of benign pleural disease.

Adult↗
PubMed1995

TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia.

The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL). It is also involved in T-acute and -chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11. Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation.

Adolescent↗
PubMed1995

Role of neck ultrasonography in the follow-up of patients operated on for thyroid cancer.

The aim of the study was to evaluate the role of neck ultrasonography in follow-up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level.

Adenocarcinoma, Follicular↗
PubMed1995

Risk of thyroid nodules in subjects occupationally exposed to radiation: a cross sectional study.

OBJECTIVES: To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex. METHODS: 50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2). RESULTS: Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects. CONCLUSION: The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules.

Adult↗
PubMed1995

Oral activated charcoal in patients with uremic pruritus.

Twenty-three chronic uremic patients on maintenance hemodialysis and suffering from severe pruritus were treated with activated powdered charcoal (6 g daily p.o.). In 10 patients pruritus disappeared completely, and in 10 other patients a partial effect was observed. The favorable results persisted for several weeks after discontinuation of the treatment. Only 3 cases were totally unresponsive. No relevant undesirable side effects were observed with the exception of 1 case who showed treatment intolerance. It is concluded that activated charcoal per os is a safe, effective, and low-cost therapy for patients with uremic pruritus, but its mechanism of action is unknown.

Administration, Oral↗
PubMed1994

Expression of genes carried by pR plasmid in damaged E. coli and mouse cells.

In LTA mouse cells pR plasmid constitutively expresses itself resulting in protection against typical SOS inducers (UV, 4NQO) and in sensitization to different DNA-damaging agents (MNNG, cisDDP, BLM and geneticin (G418). The pR sensitizing effect is specific to mammalian cells, since the plasmid can only protect prokaryotic cells against the damaging agents tested. The pR protecting effect requires the expression of both the uvp1 and uvp2 (mucAB) regions in bacteria as well as in mouse cells. The coordinated function of these regions could result in protection against typical SOS inducers through an SOS/SOS-like pathway. The sensitization conferred by pR plasmid depends mostly on the expression of the mucAB genes, as shown by the survival of mouse cells transfected with different pR::Tn5 mutants. In particular, BLM and G418 survival data demonstrate that, inserted into the pR plasmid, the ble and neo genes of the Tn5 transposon express themselves. This was confirmed by the presence of Tn5 transcripts in untreated mouse cells. The comparison between the pR effects in bacterial and mouse cells shows that during evolution the repair pathways against UV damage are better conserved than those against other kinds of damage.

4-Nitroquinoline-1-oxide↗
PubMed1994

The soluble but not mitochondrially bound hexokinase is a substrate for the ATP- and ubiquitin-dependent proteolytic system.

Intracellular protein degradation is highly selective, however, the mechanism(s) underlying this selectivity are not fully understood. We have previously shown that purified rabbit hexokinase type I, an enzyme present in mammalian brain both in soluble and mitochondrial bound form, is conjugate to ubiquitin and then degraded by a rabbit reticulocyte fraction II. In the present study we report that the mitochondrial bound hexokinase is stable for several hours in the same proteolytic system both in the presence or absence of ATP. E1, E2 and E3, the enzymes of the ubiquitin conjugating system, are able to incorporate 125I- or biotin-labelled ubiquitin in an ATP-dependent manner in soluble hexokinase as well as in a number of mitochondrial proteins. Furthermore, the mitochondria by themselves have a pronounced ATP-dependent ability to conjugate 125I-ubiquitin. However, Western blotting experiments, using a specific antibody against hexokinase, or against ubiquitin, showed that the mitochondrial bound enzyme is neither ubiquitinated nor degraded. This result has been confirmed by purification of bound hexokinase from the brain mitochondrial fraction or following the incubation of intact mitochondria with ATP, 125I-ubiquitin and E1, E2 and E3. Thus, mitochondrial bound hexokinase is not recognized by the ubiquitin conjugating system while the soluble enzyme is conjugate to ubiquitin and then degraded. Furthermore, the soluble hexokinase from rabbit brain was isolated by immunoaffinity chromatography and shown to be recognized by an anti-ubiquitin antibody. These results suggest that the intracellular distribution of protein is an important feature of a protein which determines its susceptibility to ubiquitin-dependent degradation.

Adenosine Triphosphate↗
PubMed1994

Red blood cell phagocytosis following hexokinase inactivation.

Hexokinase inactivating antibodies were loaded into human erythrocytes using an encapsulation procedure based on hypotonic haemolysis, isotonic resealing and reannealing. Red blood cells loaded with anti-hexokinase IgG showed 20 percent residual hexokinase activity and reduced glycolytic activity. Incubation of these cells in the presence of an oxidizing agent such as terbutyl hydroperoxide (TBH) and then in autologous plasma, promoted opsonization by autologous IgG and complement deposition, but not haemolysis. Furthermore, the antihexokinase IgG loaded cells treated with TBH were actively recognized and phagocytosed by macrophages. Thus, metabolic impairment of human erythrocytes promotes autologous IgG binding, C3 deposition and phagocytosis, a mechanism already reported for the removal of senescent erythrocytes.

Complement System Proteins↗
PubMed1994

PME of Unverricht-Lundborg type in the Mediterranean region: linkage and linkage disequilibrium confirm the assignment to the EPM1 locus.

Seven phenotypically homogeneous Mediterranean myoclonus families were studied using DNA markers from the genetically defined EPM1 region on chromosome 21. No recombinations between the disease phenotype and the markers studied were detected. Within the EPM1 region, the highest lod score value of 5.07 (at theta = 0.00) was reached at locus PFKL. Significant allelic association (P = 0.02) between the disease mutation and PFKL was detected suggesting a founder effect in Mediterranean myoclonus. However, haplotype data using four marker loci residing within 300 kb of each other and of EPM1 suggest the occurrence of more than one mutation. The data are compatible with Mediterranean myoclonus being caused by mutations in the EPM1 gene and strengthen the concept that a large subset of progressive myoclonus epilepsies conforms with Unverricht-Lundborg disease and that this subset is an etiologically homogeneous entity.

Adolescent↗
PubMed1994

Comparison between ethanol sclerotherapy and emptying with injection of saline in treatment of thyroid cysts.

We compared the results of ethanol sclerotherapy in thyroid cysts with emptying of cysts and instillation of saline. Twenty-six patients with recurrent thyroid cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A control group of 44 patients was submitted to cyst aspiration and subsequent injection with isotonic saline; among them 20 had previously been treated with repeated aspirations of the cyst fluid. The patients were followed up clinically and ultrasonically 1 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion or an ultrasonic cyst volume less than 50% of basal after 12 months from the start of treatment. Cytological study showed all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%) were cured, among whom 6 of 20 had previously been submitted to repeated aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%) were cured. Statistical analysis revealed a significantly higher effectiveness of treatment with ethanol than that with emptying and saline instillation (chi-square, P = 0.002) or with repeated aspiration and saline instillation (chi-square, P = 0.003). Slight pain was observed in two patients treated with saline and five treated with ethanol sclerotherapy. Three patients treated with ethanol sclerotherapy presented severe pain and one transitory hyperthyroidism. We conclude that ethanol sclerotherapy is effective and safe in the treatment of thyroid cysts.

Adult↗
PubMed1994

Pretibial myxedema and high-dose intravenous immunoglobulin treatment.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

Adult↗
PubMed1994

Findings from high resolution computed tomography of the lung and pleura of symptom free workers exposed to amosite who had normal chest radiographs and pulmonary function tests.

The lungs of 50 symptom free workers exposed to amosite and with normal pulmonary function tests were examined by high resolution computed tomography (HRCT). Twenty five had normal standard chest radiographs whereas the other 25 had radiographs interpreted as near normal (International Labour Office profusion score < 0/1 or suspected pleural plaques). In 13 of the workers the results of HRCT were negative; in 22 pleural plaques were found, in five there was only parenchymal involvement, and 10 had both pleural and parenchymal changes. The mean duration of exposure to amosite was significantly longer for the subjects with parenchymal signs than for those with normal parenchyma and for the workers with pleural plaques than for those with normal pleura and lung parenchyma. The prevalence of identified pleural and parenchymal abnormalities in the 50 workers was also significantly higher than in a reference group without exposure to asbestos. It is concluded that HRCT may detect initial lung and pleural involvement in symptom free workers exposed to amosite and the mean duration of exposure is longer for subjects with parenchymal or pleural involvement.

Adult↗
PubMed1994

Dipsogenic factors operating in chronic uremics on maintenance hemodialysis.

Thirst and hyperdipsia of anuric chronic uremics on maintenance hemodialysis and the possible dipsogenic factors were studied. Exaggerated thirst was present in 213 (86%) of the 247 studied patients. It usually started 4-6 h after the end of the dialysis session, persisted during the whole interdialytic period and often disappeared during the subsequent dialysis. Hyperdipsia, as indicated by the high body weight gain (> 4%) in the interdialytic periods, was present in 33.6% of patients. The highest rate of increase of body weight occurred in the first hours following the end of dialysis sessions. Hypernatremia, potassium depletion, increasing plasma urea levels and elevated plasma angiotensin II levels were considered as the possible dipsogenic factors of a nonpsychic nature. Sodium is certainly of paramount importance for its obliged extracellular position, and when sodium intake is elevated, hypernatremia is very likely the cause of exaggerated thirst and weight gain in patients on hemodialysis. Potassium depletion may cause thirst in animals, but this condition is extremely rare in patients on maintenance hemodialysis, who often accumulate it. In these patients it is, therefore, unlikely that potassium depletion is a dipsogenic factor. Increasing serum urea levels exert an evident dipsogenic effect in anephric rats and urea, when infused into normal volunteers, stimulates thirst. The extracellular urea levels in the interdialytic period are certainly higher than the intracellular ones, as a consequence of its continuous accumulation, and this creates an osmotic gradient with a dipsogenic effect. When this gradient is reversed, following hemodialysis (which removes first the extracellular urea), the dipsogenic effect disappears.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immunologic disturbances and levels of parathyroid hormone in uremic patients in replacement dialysis therapy.

We studied the changes in cellular immunity in patients in replacement dialysis therapy (RDT) and examined the relationship between T-lymphocyte function and plasma levels of parathyroid hormone (PTH). In a preliminary study we found that increased plasma levels of PTH were associated with a decrease of T-lymphocytes and CD4, an increase in CD8 and a reduction in the ratio of CD4 to CD8. In the present study we examined the relationship between plasma levels of PTH, interleukin 2 receptors (IL-2R) and soluble human CD8 (S-CD8). We studied 54 patients divided into two groups: 26 patients with normal levels of PTH and 28 patients with increased levels of PTH. We found a significant reduction in total T-lymphocytes in both groups as compared to controls, with an inverse correlation between total T-lymphocytes and plasma PTH in the second group (R = -0.52). There was an increase in IL-2R in the group II as compared to the controls and also in the total population of uremic patients with a linear correlation between levels of IL-2R and PTH (R = 0.6). The levels of S-CD8 showed a significant increase in both groups with a linear correlation between levels of SC-D8 and PTH (R = 0.63). No specific differences were seen between patients treated with and without 1,25-dihydroxyvitamin D3. The elevated levels of PTH affect the lymphocyte function and are associated with change in cellular immunity with reduction in total number of T cells, and increases in levels of CD8, S-CD8 and IL-2R.

Adult↗