Biomedical subjects
Publications and source records attributed to A Zanetti.
Three clusters of measles cases occurred between June and September 2006, in the Roma/Sinti populations in three different Italian regions: the Bolzano-South Tyrol in northern Italy; Lazio in central Italy; and the island of Sardinia in the southwest.
A pretransplant positive cross-match is a contraindication for kidney transplantation, unlike in liver transplantation (OLT). In combined liver kidney transplantation (LKT) it is hypothesized that liver can protect kidney from rejection. We report the case of a 35-year-old woman on renal replacement therapy with gastrointestinal tract compression due to a hematoma following spontaneous liver rupture (May 2004). She was affected by amyloidosis, treated with a bone marrow autotransplantation (2001). The liver rupture was surgically untreatable, so an LKT was proposed. Panel-reactive antibody was 80% to 100% (complement dependent cytotoxicity) with specific anti-HLA antibodies (enzyme-linked immunosorbent assay). A compatible donor was found (July 2004). The cross-match before LKT was positive for B and T cells (score 8): an emergency OLT was performed. Immediately after liver reperfusion the cross-match result was less positive (6) for T cells. After 6 hours it was negative for T and slightly positive for B cells (4): the kidney was transplanted. The immunosuppressive therapy was: alemtuzumab, steroids, and tacrolimus. Renal function immediately recovered. On day 7 a rejection episode was successfully treated by increasing steroids (intravenous bolus). At discharge hepatic and renal function were normal (creatinine 1 mg/dL). They are stable after 1 year. This case showed LKT efficacy even in complex immunological situations. Many immunological mechanisms, still not defined, are hypothesized about the protective role of the liver. This case confirmed experimental data that highlighted that in vivo in humans a cross-match can change from positive to negative after OLT giving highly sensitized patients the possibility for LKT.
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OBJECTIVE: Varicella is a potential occupational hazard for susceptible individuals working in pediatric institutions because infected adults run a greater risk of severe or even fatal varicella and because the disease is so common in children and so contagious. The seroprevalence of varicella-zoster virus (VZV) was examined in a sample of day-care workers in Lyon (France) to determine whether a targeted vaccination policy was needed. METHODS: Two hundred forty-one sera were sampled and analysed with an Elisa test between March and May 2001. Histories of past VZV infection were collected via questionnaires documented either before or after consultation of medical records or other sources of information. RESULTS: The overall VZV seroprevalence was 99.6%. The positive predictive values of past varicella histories (documented or not) were>99% showing that a history of previous varicella in day-care workers was reliable. However, only 68 to 71% of these with serologically confirmed varicella reported a prior history of varicella. All subjects reporting a non-positive history of varicella were seropositive. CONCLUSIONS: Virtually all day-care workers enrolled in this study presented serological evidence of VZV so that sub-populations at risk for varicella infection for which VZV vaccination may be effective could not be identified. However, the VZV seroprevalence of the workers in pediatric institutions being presumably higher than that of the general adult population (94-96.3%), vaccination of susceptible young recruits before any exposure to the VZV, or even vaccination of students willing to work in a pediatric institution, may be positive.
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The use of NAT technology to screen blood donations in Italy became mandatory on 28 June 2002, but had been available experimentally since 2001. During the transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had also been permitted. Considering the large number of blood transfusion centres in Italy, an initial reorganisation of the biological validation of blood units was necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the Study of Transfusion-Transmissible Diseases) conducted a national survey evaluating NAT testing, based on an annual collection of data through a questionnaire sent to all centres. In the first three years of the investigation, 219 blood transfusion centres returned the questionnaires. In the period between January 2001 and December 2003, 3,894,894 blood donations were investigated for HCV RNA and 2,186,468 for HIV RNA. Of these, 12 were found to be HCV RNA positive and four HIV RNA positive, with an observed NAT versus antibody-based assay yield of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and their donations would have been discarded even in absence of NAT testing. Thus the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV transmission by blood transfusion after NAT implementation is currently estimated to be extremely low in Italy.
AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.
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Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.
Live virus vaccines for human use, 29 monovalent vaccines against measles, mumps, rubella or polio, eight polyvalent vaccines against measles-mumps-rubella and one bacterial polyvalent vaccine against Streptococcus pneumoniae, were tested by reverse transcriptase-nested PCR for the presence of petivirus or pestivirus RNA. Twenty-four samples were selected from European manufacturers, ten were from U.S.A. and four from Japan. Five (13.1%) out of 38 tested samples were positive for pestivirus RNA. Three vaccines (rubella and two measles) were from Europe and two (mumps and rubella) from Japan. The 5'-untranslated genomic region of the contaminant pestivirus RNA were amplified by reverse transcription-PCR and sequenced. Analyses based on primary nucleotide sequence homology and on secondary structures, characteristic to genotypes, revealed that the cDNA sequences belonged to bovine viral diarrhea virus (BVDV). A cDNA sequence, detected from one measles sample, belonged to BVDV-1b genotype. Pestiviral cDNA detected from the Japanese mumps and rubella vaccine samples, belonged to the BVDV genotypes 1a and 1c, respectively. Analysis on two cDNA sequences detected from measles and rubella vaccine samples from Europe showed their appurtenance to a new genotype, BVDV-1d. These findings indicate that contamination by animal pestivirus may occur in biological products for human use.
Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (P<0.0001). There was no correlation between IL-8 levels and hematological data or hemoglobin patterns. High serum IL-8 levels were observed in VOC patients independently of the crisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear.
In areas with low hepatitis B virus (HBV) endemicity such as most parts of Europe and the United States "anti-HBc alone" is found in 10-20% of all individuals with HBV markers, i.e., 1-4% of the population. In about 10% of these individuals HBV DNA is detected by PCR, the proportions varying greatly depending on the population studied, being highest in individuals coinfected with hepatitis C virus (HCV) (above 35%) and HIV (above 85%). A small proportion of individuals with "anti-HBc alone" are in the window phase of an HBV infection or in a stage of late HBV immunity. For the large proportion of these individuals this is not the case and they are thought to have an unresolved HBV-infection or a chronic infection in a late or "low grade" productive state. Currently, limited studies have been performed concerning the clinical aspects of individuals with "anti-HBc alone" and suspected chronic HBV infection. The majority of these individuals seem to be healthy. Some chronic carriers with "anti-HBc alone," however, do present signs of chronic hepatitis. Individuals with "anti-HBc alone" are potentially infectious. This is exemplified by a few case reports of HBV transmission to sexual contacts, perinatal transmission between mother and newborns and in blood recipients. Recommendations are given in relation to both the diagnostic and therapeutic procedures in the individuals with "anti-HBc alone" and in the blood banking and transplantation services.
BACKGROUND/AIMS: Recently, the presence of a novel nonenveloped single-stranded DNA virus (TTV) has been associated with either acute or chronic hepatitis of unknown aetiology, suggesting a possible aetiological role. The aim of this study was to evaluate the prevalence, the significance and the clinical impact of TTV infection in patients with acute viral hepatitis of defined aetiology and in patients with non-A-E acute hepatitis. METHODS: TTV-DNA was tested by hemi-nested PCR in serum samples collected from 121 patients during and after acute hepatitis (103 with acute viral hepatitis of defined aetiology and 18 with acute non-A-E hepatitis) and in 30 healthy controls. RESULTS: Overall, the rate of TTV infection was 12.6% (13/103) in patients with acute hepatitis of defined aetiology, 16.6% (3/18) in patients with non-A-E acute hepatitis and 6.6% (2/30) in the healthy control group, (p=n.s). TTV-DNA was detected in the following proportions: hepatitis B, 13.2% (7/53); hepatitis C, 16.6% (4/24); hepatitis A, 4.7% (1/21); hepatitis E 20% (1/5). Moreover, acute hepatitis with and without TTV infection/coinfection were comparable in terms of both liver biochemistry and chronicity rate. The results of TTV re-testing after serial dilutions of six TTV-DNA positive serum samples during and after the peak of liver transaminases failed to demonstrate a correlation between liver damage and viral titre. CONCLUSIONS: The prevalence of TTV infection appeared to be comparable in patients with non-A-E hepatitis, in acute hepatitis of defined aetiology and in the control group. Hence, an aetiological role of TTV for acute hepatitis of unknown aetiology seems questionable. Moreover, TTV infection does not modify the natural history of acute hepatitis of defined aetiology.
Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown. Here, targeted inactivation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdeltaC/deltaC) of the VE-cadherin gene was found not to affect assembly of endothelial cells in vascular plexi, but to impair their subsequent remodeling and maturation, causing lethality at 9.5 days of gestation. Deficiency or truncation of VE-cadherin induced endothelial apoptosis and abolished transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bcl2 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival.
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Endothelial adherens junctions (AJ) promote intercellular adhesion and may contribute to the control of vascular permeability. These structures are formed by a transmembrane and cell-specific adhesive protein, vascular endothelial (VE)-cadherin, which is linked by its cytoplasmic tail to intracellular proteins called catenins (alpha-catenin, beta-catenin, and plakoglobin) and to the actin cytoskeleton. Little is known about the functional regulation of AJ in endothelial cells. In this study, we analyzed the effect of histamine on AJ organization in cultured endothelial cells. We first observed that histamine induced detectable intercellular gaps only in loosely-confluent cells, whereas this effect was strongly reduced or absent in long-confluent cultures. Despite this difference, in vitro permeability was augmented by histamine in both conditions. In resting conditions, tyrosine phosphorylation of AJ components and permeability values were higher in recently-confluent cells as compared with long-confluent cells. Histamine did not affect the phosphorylation state of AJ in recently-confluent cells but strongly increased this parameter in long-confluent cultures. In addition, in long-confluent cells, histamine caused dissociation of VE-cadherin from the actin cytoskeleton measured by a decrease of the amount of the molecule in the detergent-insoluble fraction of the cell extracts. Dibutyryl cAMP was able to prevent the effect of histamine on both tyrosine phosphorylation of AJ components and on endothelial permeability. The effect of histamine was specific for VE-cadherin because the phosphorylation state of neural (N)-cadherin, the other major endothelial cadherin, was unchanged by this agent. Hence AJ components are a target of histamine activation cascade; we suggest that induction of tyrosine phosphorylation of VE-cadherin and catenins contributes to the histamine effect on permeability, even in absence of frank intercellular gaps and cell retraction.
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Met protein encoded by MET oncogene is the high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF). HGF/SF has to be cleaved in its heterodimeric form by the urokinase-type plasminogen activator (uPA) to become active as a ligand for Met receptor. The expression of Met protein and of the high affinity receptor for uPA (uPA-R) was investigated in 39 samples of papillary carcinoma using immunohistochemistry. Reactivity for Met protein was present in 33 of 34 tumours, mostly with a diffuse pattern of staining. Reactivity for uPA-R was present in 78 per cent of papillary tumours and exhibited a pattern of staining similar to that of Met protein. Staining for uPA-R was present in 23 of 25 cases (92 per cent) of papillary carcinoma with prominent sclerosis, and in only 1 of 7 cases (14 per cent) without sclerosis. Peritumoural normal thyroid, follicular adenomas, and follicular carcinomas were negative for Met protein and for uPA-R. Hyperfunctioning tall thyroid cells showed weak membrane reactivity for uPA-R and for Met protein. The findings of immunohistochemistry were confirmed at the mRNA level using in situ hybridization, since the signal for uPA-R and Met RNAs was detected in most tumour cells of five cases of papillary carcinoma.