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C Ferrari

Publications and source records attributed to C Ferrari.

At least 37 records · Page 2Linked to original sources
PubMed2001

Post-World War II uranium changes in dated Mont Blanc ice and snow.

Recent controversies concerning the possibility of environmental contamination due to the use of uranium in classical weaponry have led us to realize that there is a lack of time series for this metal from environmental archives. We have therefore performed analysis of a dated 140 m-long ice/snow core that was drilled in 1994 at a cold high altitude site (4250 m) near the summit of Mont Blanc in the French-Italian Alps. Ultraclean analytical procedures were employed in our analyses. Uranium concentrations were determined by inductively coupled plasma sector field mass spectrometry. In ice dating from before the 1940s, uranium concentrations are found to have remained fairly constant and can be explained simply by a crustal contribution. For the post-World War II layers, on the other hand, the data show large excesses above crustal contributions. These uranium excesses are attributed to tropospheric transport of dust emitted during extensive mining and milling operations which took place in the GDR and to a smaller extent in France at that time. There is no enhancement in uranium concentrations in the ice layer in which fallout from the 1986 Chernobyl accident was previously identified from a gross beta activity vs depth profile.

Altitude↗
PubMed2001

Greenland snow evidence of large scale atmospheric contamination for platinum, palladium, and rhodium.

Since 1976 in the United States, Canada, and Japan, and later in other countries, the exhaust system of gasoline powered cars has been equipped with catalytic converters containing Pt and/or Pd and/or Rh. This has resulted in a very significant decrease in urban air pollution for various chemical species such as NOx, CO, and hydrocarbons. There has however been concern that their ever increasing use might lead to Platinum Group Metals (PGMs) becoming widely dispersed in the environment. From the analysis of Pt, Pd, and Rh in central Greenland recent snow and ancient ice using the ultrasensitive inductively coupled plasma sector field mass spectrometry technique, we show here that the concentrations of these metals in snow dated from the mid 1990s are indeed approximately 40-120 times higher than in ice dated from 7000 years ago. The fact that such an increase is observed far away from populated areas at a high altitude location indicates there is now a large scale contamination of the troposphere of the Northern Hemisphere for PGMs. Pt/Rh mass ratio in the most recent snow samples is close to the same ratio documented for catalytic converter exhausts in a recent study, which suggests that a large fraction of the recent increase for Pt and Rh might originate from automobile catalytic converters.

Environmental Monitoring↗
PubMed2001

Transient hand paresthesias in Champagne vineyard workers.

BACKGROUND: The aim of the study was to assess the prevalence of hand paresthesias (HP) and their relationship with pruning activities. METHODS: A cross-sectional study was conducted among 537 workers pruning grapevines in the region of Champagne. All workers completed a questionnaire about nocturnal HP and musculoskeletal pain during the preceding 12-month period. RESULTS: The 12-month prevalence of nocturnal HP and hand-wrist pain were 37 and 12%, respectively. HP, predominantly affecting the dominant hand, only began during the pruning period and ended after the pruning season in 90% of cases. HP were transient in most cases, with a mean duration of symptoms of 3.3 +/- 3.2 months. Risk factors associated with HP were: female gender (OR = 2.3 [1.3-3.0]), being overweight (OR = 1.6 [1.1-2.5]), payment on a piecework basis (OR = 2.0 [1.2-2.3]) and traditional blade sharpening method (OR = 1.7 [1.1-2.7]). HP were less frequent in employees who used electric pruning shears (OR = 0.5 [0.2-1.6], P = 0.09). CONCLUSIONS: The development of HP, which affected a third of employees, was different from HP observed in industrial workers since most vineyard workers recovered without medical treatment after the pruning season.

Adult↗
PubMed2001

Computed tomography of pulmonary metastases from osteosarcoma: the less poor technique. A study of 51 patients with histological correlation.

BACKGROUND: The purpose is to evaluate the accuracy of computed tomography (CT) in the pulmonary staging of osteosarcoma. PATIENTS AND METHODS: Fifty-one patients presenting with osteosarcoma and at initial CT considered metastatic to the chest had lung surgery. Two teams of two senior radiologists independently reviewed all CT examinations. Their results were compared to the histological studies. RESULTS: One hundred nineteen CT's were reviewed. The 2 teams found 247 and 268 nodules on the initial. and 143 and 146 nodules on the preoperative CT. Histological studies confirmed metastatic nodules in 29 patients. Two hundred four nodules were excised and studied. One hundred nine were metastases. The 22 patients without metastases had 53 negative nodules removed. In the 29 patients with metastases, 151 nodules were removed, and 42 were non-metastatic. The positive predictive value was 53% with regard to 'nodules', and 57% with regard to 'patients'. Only 4 out of 13 patients with one nodule at surgery were metastatic, but all patients with more than 7 nodules were metastatic. The 46 cases with several available CT's, showed that no change in the number of nodules was more frequent in benign lesions. Other criteria revealed no significant difference. CONCLUSION: CT positive predictive value is limited, but as surgery is the only way to cure metastatic patients, CT will still be used as the reference technique until a more specific approach can be found.

Bone Neoplasms↗
PubMed2001

Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy.

The hepatitis B virus (HBV) cytotoxic T lymphocyte (CTL) response in patients with chronic HBV infection is generally weak or totally undetectable. This inability to mount protective CTL responses is believed to be a crucial determinant of viral persistence, and its correction represents an important objective of immune therapies for chronic hepatitis B. However, amplification of CTL responses in vivo may be ineffective if HBV-specific CD8 cells are either absent or nonresponsive to exogenous stimulation. In this study, we asked whether antiviral treatments able to inhibit viral replication and to reduce viral and antigen load can successfully reconstitute CTL responses creating the appropriate conditions for their therapeutic stimulation. For this purpose, the HBV-specific CTL response before and during lamivudine therapy was studied longitudinally in 6 HLA-A2-positive patients with HBeAg+ chronic hepatitis B. Both HBV-specific cytotoxic T cell activity measured by chromium release assay on peptide stimulation in vitro and CD8+ T cell frequency measured ex vivo by HLA-A2/peptide tetramer staining were significantly augmented by lamivudine therapy. This enhancement followed the reconstitution of CD4 reactivity and the decline of viral load induced by therapy. Our study shows that lamivudine treatment in chronic hepatitis B can restore CTL reactivity, making CTL susceptible to exogenous stimulation. This effect may enhance the probability that T cell-based immune therapies delivered after lamivudine treatment can successfully reconstitute a protective CTL response able to cure chronic HBV infection.

Adult↗
PubMed2001

Identification of immunodominant hepatitis C virus (HCV)-specific cytotoxic T-cell epitopes by stimulation with endogenously synthesized HCV antigens.

Hepatitis C virus (HCV)-specific CD8(+) cytotoxic T lymphocytes (CTL) are believed to play an important role in the pathogenesis of liver cell injury and viral clearance in HCV infection. Because HCV does not efficiently infect human cells in vitro and primary infected hepatocytes cannot be used as stimulator/target cells for CTL analysis, development of efficient systems to activate and expand CTL in vitro, reproducing antigen presentation to CTL occurring during natural infection, is mandatory to study CTL activity and to define the hierarchy of immunodominance of CTL epitopes. To achieve this goal, 5 different defective adenoviruses carrying structural and nonstructural HCV genes (core, core-E1-E2, E2, NS3-NS4A, NS3-NS5A) were used to induce the endogenous synthesis of HCV proteins in human adherent mononuclear cells in vitro and to allow their entry into the HLA class I cytosolic pathway of antigen processing. The cytolytic activity of peripheral blood lympho-mononuclear cells (PBMC) from HLA-A2(+) HCV-infected patients stimulated with recombinant adenovirus-infected cells was tested against target cells either pulsed with a panel of synthetic peptides containing the HLA-A2 binding motif or infected with recombinant vaccinia viruses carrying HCV genes. Our study defines a reproducible system to stimulate and expand HCV-specific CTL in vitro that mimics the conditions of antigen encounter in vivo. By this approach, we have identified several HLA-A2-restricted epitopes that should correspond to immunodominant HCV sequences recognized by CTL during natural infection. Therefore, these amino acid sequences represent ideal candidates for the design of therapeutic vaccines for chronic HCV infection.

Adenoviridae↗
PubMed2000

The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection.

Hepatitis B virus (HBV) is a noncytopathic virus, and the recognition of infected hepatocytes by HBV-specific CD8 cells has been assumed to be the central mechanism causing both liver damage and virus control. To understand the role of cytotoxic T cells in the pathogenesis of HBV infection, we used functional assays that require T cell expansion in vitro and human histocompatibility leukocyte antigen (HLA)-peptide tetramers that allow direct ex vivo quantification of circulating and liver-infiltrating HBV-specific CD8 cells. Two groups of patients with persistent HBV infection were studied: one without liver inflammation and HBV replication, the other with liver inflammation and a high level of HBV replication. Contrary to expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in the absence of hepatic immunopathology. In contrast, virus-specific T cells were more diluted among liver infiltrates in viremic patients, but their absolute number was similar because of the massive cellular infiltration. Furthermore, inhibition of HBV replication was associated with the presence of a circulating reservoir of CD8(+) cells able to expand after specific virus recognition that was not detectable in highly viremic patients with liver inflammation. These results show that in the presence of an effective HBV-specific CD8 response, inhibition of virus replication can be independent of liver damage. When the HBV-specific CD8 response is unable to control virus replication, it may contribute to liver pathology not only directly but by causing the recruitment of nonvirus-specific T cells.

CD8-Positive T-Lymphocytes↗
PubMed2000

Presence and expression of the simian virus-40 genome in human giant cell tumors of bone.

SV40 DNA sequences have been found in human tumors, such as mesotheliomas, ependymomas, and bone tumors, suggesting that SV40 may be involved in their etiology. The FOS oncogene could play an important role in bone development because SV40 is able to induce FOS in cell culture. In this study, the presence of SV40 sequences, large T antigen (Tag), and FOS protein expression were investigated in 120 giant cell tumors (GCTs), moderately benign bone tumors that in some cases can progress to a malignant phenotype. Polymerase chain reaction (PCR), using primers that amplify the RB1 pocket binding domain and the intron of Tag, was used to analyze GCT for the presence of SV40 DNA. Tag and FOS protein expression was evaluated by immunohistochemistry. SV40 sequences were found in 30/107 GCTs, and of these, 22/30 samples expressed Tag protein (73%) and 15/30 overexpressed the FOS oncogene (50%). FOS was undetectable in 77 SV40-negative GCTs. Sequence analysis of the amplified DNAs confirmed that the amplified sequences corresponded to SV40 DNA. The correlation between FOS overexpression and SV40-positive GCTs was highly statistically significant (P < 0.001). These results show that SV40 DNA sequences and SV40 Tag are present in GCTs and might induce FOS activity. These data suggest that SV40 might play a role in the development and progression of some GCTs.

Adult↗
PubMed2000

CD8+ T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained.

Cellular immune responses are likely to play a key role in determining the clinical outcome in acute infection with hepatitis C virus (HCV), but the dynamics of such responses and their relationship to viral clearance are poorly understood. In a previous study we have shown highly activated, multispecific cytotoxic T lymphocyte responses arising early and persisting in an individual who subsequently cleared the virus. In this study the HCV-specific CD8+ lymphocytes response has been similarly analyzed, using peptide-HLA class I tetramers, in a further nine individuals with documented acute HCV infection, six of whom failed to clear the virus. Significant populations of virus-specific CD8+ lymphocytes were detected at the peak of acute hepatic illness (maximally 3.5% of CD8+ lymphocytes). Frequencies were commonly lower than those seen previously and were generally not sustained. Early HCV-specific CD8+ lymphocytes showed an activated phenotype in all patients (CD38+ and HLA class II+), but this activation was short-lived. Failure to sustain sufficient numbers of activated virus-specific CD8+ lymphocytes may contribute to persistence of HCV.

Acute Disease↗
PubMed2000

Analysis of 12q13-15 genes in parosteal osteosarcoma.

The region q13-15 of chromosome 12 frequently is altered in human sarcomas, and several genes, such as SAS, CDK4, and MDM2, have been found to be amplified in bone and soft tissue sarcomas. These genes and their products were studied by quantitative polymerase chain reaction and immunohistochemical analysis in 25 parosteal osteosarcoma samples (22 Grades I or II, three dedifferentiated) to evaluate if the possible alterations detected of the genes on chromosome 12 could have a role in the development of this rare bone tumor. Immunohistochemical analysis was performed on formalin fixed, paraffin embedded tumor sections to evaluate CDK4 and MDM2 protein expression. To measure the degree of SAS and CDK4 gene amplification, quantitative polymerase chain reaction was done on deoxyribonucleic acid derived from the same samples. The results showed that CDK4 protein was expressed in 92% of the cases. Strong and uniform CDK4 and MDM2 immunoreactivity was found respectively in three of three and two of three dedifferentiated parosteal osteosarcomas. SAS and CDK4 genes were found to be amplified fourfold in two Grade II tumors and in one dedifferentiated tumor. These findings, which should be investigated further, might suggest a possible role of the chromosome 12 genes in the pathogenesis of parosteal osteosarcoma.

Bone Neoplasms↗
PubMed2000

Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301-302delAG) in the prophet of Pit-1 gene.

The Prophet of Pit-1 gene (PROP1) encodes a paired-like homeodomain protein, which is expressed early in pituitary gland development. When mutated, it is responsible for combined pituitary hormone deficiency (CPHD) in humans, as well as in Ames dwarf mice (df/df). Several independent mutations in the homeodomain of PROP1 have been identified as causative for the human CPHD phenotype, which has been characterized, thus far, as absence or low levels of GH, PRL, TSH, LH, and FSH. Here, we report 10 CPHD cases, 9 of which were born to consanguineous marriages occurring in a large family living in an isolated area in the Southeast of Brazil. All affected patients present complete absence of puberty and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland, as seen by MRI. All 3 exons of the PROP1 genes of these patients were sequenced. The 301-302delAG frameshift mutation was found in both alleles of each affected case. Surprisingly, we observed ACTH/cortisol insufficiency associated with the PROP1 phenotype. The patients' ages varied between 8 and 67 yr, and cortisol response impairment was identified in 5 of 6 of the older patients and in an 11-yr-old patient. Previous studies have not fully characterized patients at advanced ages, leading us to conclude that the phenotype of this PROP1 mutation includes late-onset adrenal insufficiency. We present an extensive clinical analysis of all of these patients. The presence of ACTH/cortisol deficiency in this family bearing the PROP1 301-302delAG mutation indicates the importance of a complete endocrine characterization and of life-long monitoring of PROP1 patients.

Adrenocorticotropic Hormone↗
PubMed2000

Familial growth hormone deficiency with mutated GHRH receptor gene: clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha.

OBJECTIVE: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. DESIGN: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. METHODS: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). RESULTS: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) +/- s.d.: -7.35+/-1.37 vs -1.84+/-1.44 respectively, P<0. 0001), and the wt/wt group (-1.85 +/- 0.81, P=0.0007). The height of the 13 wt/mt subjects did not differ from the 5wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. CONCLUSIONS: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

Adolescent↗
PubMed1999

Characterization of ligurian melanoma families and risk of occurrence of other neoplasia.

Germline mutations impairing the p16(INK4)-function have previously been demonstrated to be responsible for genetic predisposition in at least one half of melanoma-prone kindreds of North European origin. Familial melanoma kindreds have also been found to present an increased risk of pancreatic cancer and other cancers, but results relative to more common neoplasias incidence, in particular, are heterogeneous. We report here a clinical-epidemiological study, including the presence of additional neoplasias, in 14 apparently unrelated kindreds coming from a small geographic region of Northern Italy (Liguria), having therefore lived for generations in similar environmental conditions. We identified the common p16 missense mutation (Gly101Trp) reported in several previously studied kindreds, in 7 of 14 families, whereas the remaining 7 families had no detectable mutations in the coding region of p16 gene. Median age at diagnosis and other melanoma features were studied. When compared with the expected figures, based on regional incidence rates, a significant excess of pancreatic cancer, with 4 cases diagnosed, and of breast cancer, with 7 cases, was observed. The 7 families without apparent CDKN2A involvement were also negative for hot-spot exon 2 mutation of CDK4. Environmental factors do not appear to play a role in the excess of non-melanoma neoplasia in our families, as somewhat substantiated by the control group, composed of spouses and members of non-affected branches; they do not reveal any increased cancer incidence compared with the general population. Furthermore, given the proven significance of interaction between the melanoma susceptibility gene and the propensity to sunburns and other environmental risk factors, our results, obtained from a small but homogeneous sample, may have important implications for further risk assessment studies.

Adolescent↗
PubMed1999

Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vaccine development.

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.

Acute Disease↗
PubMed1999

Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection.

BACKGROUND & AIMS: Cytotoxic T cells have been suggested to be responsible for lysis of hepatitis B virus (HBV)-infected hepatocytes and control of virus infection. The frequency, kinetics, phenotype, and capacity for clonal expansion of circulating HBV-specific CD8 cells were analyzed directly in patients with acute HBV infection to clarify their pathogenetic role. METHODS: Three HLA-A2 peptide tetramers able to visualize HBV core, envelope, and polymerase epitope-specific cytotoxic T lymphocytes were synthesized and used for flow cytometric analysis of antigen-specific populations. RESULTS: Tetramer-positive cells specific for the core 18-27 epitope were found at a higher frequency than those specific for polymerase 575-583 and envelope 335-343 epitopes in most patients with acute HBV. The number of HBV-specific CD8 cells was highest during the clinically acute stage of infection and decreased after recovery. These cells expressed an activated phenotype and had an impaired capacity to expand in vitro and to display cytolytic activity in response to peptide stimulation. Recovery of these functions was observed when the frequency of specific CD8 cells decreased, coincident with a progressive decrease in their expression of activation markers. CONCLUSIONS: This study provides the first ex vivo evidence that the highest frequency of circulating HBV-specific CD8 cells coincides with the clinically acute phase of hepatitis B. These cells exhibit an activated phenotype with limited further proliferative capacity that is restored during recovery.

Adult↗
PubMed1999

T2 relaxation of the parotid gland of patients affected by pleomorphic adenoma.

The T2 behavior of parotid gland tissue was investigated in 11 patients affected by pleomorphic adenoma. A protocol that was previously set up to define acquisition and post-processing procedures, reaching an accuracy of 2.5% in phantoms and an in vivo long term reproducibility of 0.9-8.5%, was used for the evaluations. The measurements were carried out on a whole body, superconducting imager, using a neck coil as a receiver. Some reference gel samples were imaged together with the patient and used to correct T2 results. The sequence protocol was a multispin-echo, 16 echoes. Signals were fitted with mono and biexponential decay models and an automatic choice of the best model was performed using the two chisquared comparison. Two T2 maps (T2 monoexponential or short T2 component, and long T2 component) and chisquared maps were then produced. Pathologic and normal tissues showed a dominant monoexponential decay with a good level of biexponentiality (16%-27% of total fitted pixels) due to partial volume effects from the liquid content. Concerning the biexponentiality, no significant differences were found between the fitted pixel fraction of normal and pathologic tissue, because the T2 long component of the lesion was related both to the edema and saliva content, but probably the increase in the first compensated the decrease in the second. Chisquared maps showed that most of the lesions presented a monoexponential core surrounded by a biexponential border probably due to a solid component similar to normal tissue with partial volume effects from saliva content. Ninety-five percent confidence intervals for normal tissue were 69.40-87.80 ms (monoexponential relaxation), 38.19-44.67 ms and 285.84-691.28 ms (short and long components of biexponential relaxation). For pathologic tissue they resulted 172.17-275.83 ms, 53.86-89.98 ms and 442.10-814.58 ms. The monoexponential component, mostly present in the core of the lesion, was the parameter that better characterized pathologic tissue. A comparison was performed between normal tissue of patients and normal tissue of volunteers, whose statistics was collected in a previous study with the same evaluation protocol. Results showed no significant differences in the biexponential fitted fractions and the comparison of relaxation times. We conclude that, for tissue characterization, a multiexponential analysis should be carried out in order to improve accuracy and to obtain more reliable results. Moreover, other than relaxation calculations, a topographical analysis of relaxation distribution, using for instance the chisquared maps, might in the future give us more useful information on tissue structure.

Adenoma, Pleomorphic↗