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81.
Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT- 9K/129G 总被引:14,自引:0,他引:14
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A Podda L Nencioni M T De Magistris A Di Tommaso P Bossù S Nuti P Pileri S Peppoloni M Bugnoli P Ruggiero 《The Journal of experimental medicine》1990,172(3):861-868
PT-9K/129G, a nontoxic mutant of pertussis toxin (PT) obtained by genetic manipulation, has been shown in animal models to be a promising candidate for new vaccines against whooping cough. To assess the safety and the immunogenicity of PT-9K/129G in humans, a pilot study has been performed in adult volunteers. The protein was found to be safe, capable of inducing high titers of toxin-neutralizing antibodies, and capable of generating immunological memory. In fact, vaccination caused an increase of cell-mediated response to PT, PT-9K/129G, S1 subunit, and B oligomer, indicating that memory T cells are induced by the vaccine. Since PT-9K/129G is mitogenic for T lymphocytes in vitro, it was investigated whether this activity is also present in vivo. No variation was observed in the proportion of T cells (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+), as well as in that of other lymphoid populations, by FACS analysis. Interestingly, no thorough correlation was found between humoral and cellular responses. In one case, a very high cellular response was present in absence of detectable antibodies, suggesting that the antibody response, which is the only parameter measured in most clinical trials, may not give a complete picture of the response induced by a vaccine. 相似文献
82.
83.
Giorgia Querin Elisa DaRe Ilaria Martinelli Luca Bello Cinzia Bertolin Davide Pareyson Caterina Mariotti Elena Pegoraro Gianni Sorarù 《Neurological sciences》2016,37(11):1815-1821
The Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) is an established rating instrument used to assess the functional status of patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to validate an Italian version of the scale. We administered the SBMAFRS to sixty SBMA patients during routine follow-up of clinical evaluations. To estimate the test stability, the scale was re-administered to a subset of 39 randomly selected patients after 8 weeks. The patients underwent clinical evaluation including 6-min walk. Psychometric analysis included reliability assessment and factorial analysis. To evaluate convergent validity, correlations between SBMAFRS items and muscular force assessed by manual testing, ALSFRS total score and subscales scores, and forced vital capacity, were performed. Internal consistency as measured by Cronbach’s alpha (total scale 0.85) was high. Test–retest reliability assessed by Spearman’s rho was also high. Principal component analysis with varimax rotation yielded a four-factor solution accounting for approximately 79 % of the variance. The scale total score and subscales score were strongly correlated with respective items and subscores of the ALSFRS, with respiratory function and with the 6-min walk test. In conclusion, we performed an Italian validation of the only existing disease-specific Functional Rating Scale for SBMA patients. This scale will be a useful tool not only in the clinical practice but also as an outcome measure in upcoming clinical trials. 相似文献
84.
U. Maggi M. Iavarone M. Fabbi D. Yiu G. Fornoni E. Melada D. Dondossola P. Cantù G. Rossi 《Transplantation proceedings》2018,50(10):3105-3110
Background and aim
Liver grafts from donors with chronic and active history of alcohol abuse are usually immediately ruled out for use in liver transplantation (LT). The aim of our study is to evaluate the use of those grafts.Methods
From 2011 to 2016, a study group (Group 1) composed of 5 adult LT patients transplanted with livers from donors with alcohol abuse, was compared with a control group (Group 2) of 10 randomly matched patients who received liver transplants. Preoperative, intraoperative, and postoperative data were compared.Results
Among donors, serum gamma-glutamyl transferase values were significantly higher in Group 1. In recipients, post-LT laboratory exams showed significantly higher peak values of aspartate transaminase and alanine transaminase in Group 1; higher values of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in Group 1 were also recorded on day 0. Early allograft dysfunction occurred at higher rates in Group 1 (80% vs 20%, P = .025), with no differences in early rejection episodes or early surgical repeat interventions. All patients from both groups were alive after 20 ± 10 (range 6–35) months from LT.Conclusion
Despite higher rates of early allograft dysfunction, selected liver grafts from donors with alcohol abuse can be accepted for LT with good clinical results. 相似文献85.
Marco Bortolato Roberto Frau Marco Orrù Mauro Fà Christian Dessì Monica Puligheddu Luigi Barberini Giuliano Pillolla Lorenzo Polizzi Federico Santoni Giampaolo Mereu Francesco Marrosu 《Seizure》2010,19(4):226-231
Rich evidence has highlighted that stimulation of γ-amino-butyric acid (GABA)B receptors increases the occurrence of spike-and-wave discharges (SWDs), the electroencephalographic (EEG) landmark of absence epilepsy (AE). Recent findings suggest that the outcomes of GABAB activation in vivo are contingent on the chemical characteristics of the agonist. In particular, the endogenous ligand γ-hydroxybutyrate (GHB) and its precursor γ-butyro-lactone (GBL) have been shown to elicit different effects than the prototypical GABAB agonist baclofen. In view of these premises, the present study was aimed at the characterization of the effects of baclofen (0.5–10 mg/kg, i.p.) and GBL (5–100 mg/kg, i.p.) on the spontaneous SWDs and locomotor activity of DBA/2J mice.While both baclofen and GBL dose-dependently increased SWDs episodes, high doses of the latter (100 mg/kg, i.p.) reduced the occurrence of these phenomena and increased the number of isolated spikes. Interestingly, both compounds elicited a dose-dependent reduction of locomotor activity, in comparison with their vehicle-treated controls. The GABAB selective antagonist, SCH50911 (50 mg/kg, i.p.), reversed the changes in SWD occurrence and locomotion induced by baclofen and GBL, but failed to elicit intrinsic effects on either paradigm. These results indicate that GABAB receptor signaling might exert differential effects on SWDs in DBA/2J mice. 相似文献
86.
Maurizio Iacobone Giulia Masi Luisa Barzon Andrea Porzionato Veronica Macchi Francesco Antonio Ciarleglio Giorgio Palù Raffaele De Caro Giovanni Viel Gennaro Favia 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2009,394(5):817-825
Background Hyperparathyroidism–jaw tumor syndrome (HPT–JT) is a rare autosomal disease caused by inactivating germ-line mutations of
HRPT2 gene, with subsequent loss of Parafibromin expression. It is characterized by familial HPT, ossifying jaw tumors, and other
associated neoplasms.
Methods Clinical, histopathological, and genetic features of three large Italian unrelated HPT–JT kindred were assessed.
Results Three different germ-line HRPT2 inactivating mutations were identified. Seventeen affected members and six healthy mutation carriers were found. HPT was
diagnosed in virtually all affected patients, at a median age of 36.3 years (range 11–71). In all cases, a single parathyroid
involvement was found at surgery, although a metachronous multiglandular involvement causing recurrence after selective parathyroidectomy
occurred in 17.6% of cases, after a mean disease-free interval of 13.7 years (range 5–27). Parathyroid carcinoma, atypical
parathyroid adenoma, and jaw tumor occurred in one case; uterine involvement in 61.5% of women; other associated neoplasms
were thyroid carcinoma (two cases) and renal and colon carcinoma (one case). Immunohistochemistry confirmed the loss of Parafibromin
as the distinctive feature of the disease both in parathyroid and uterine tumors.
Conclusions HPT–JT has a frequent single-gland parathyroid involvement and a relatively increased risk of parathyroid carcinoma. The penetrance
of the disease is high but incomplete. Regardless of the denomination of the syndrome, jaw tumors occur rarely, while uterine
involvement is frequently present. Selective parathyroidectomy may be an effective strategy, but a prolonged follow-up is
required because of the risk of recurrences and malignancies. A systematic investigation is also required because of associated
malignancies.
Best of Endocrine Surgery in Europe 2009 相似文献
87.
Maccioni P Pes D Orrù A Froestl W Gessa GL Carai MA Colombo G 《Psychopharmacology》2007,193(2):171-178
Rationale and objectives The positive allosteric modulator of the GABAB receptor, GS39783, has recently been found to suppress acquisition and maintenance of alcohol drinking behavior in selectively
bred Sardinian alcohol-preferring (sP) rats exposed to the standard, homecage two-bottle “alcohol vs water” choice regimen.
The present study was designed to extend the characterization of the “anti-alcohol” effects of GS39783 to oral self-administration
of alcohol under an operant procedure.
Materials and methods Two separate groups of male sP rats were trained to lever-press (on an FR4 schedule) to orally self-administer alcohol (15%,
v/v) or sucrose (0.3%, w/v) in daily 30-min sessions. Once lever-pressing behavior reached stable levels, the effect of GS39783 (0, 25, 50, and 100 mg/kg,
i.g.) on responding for alcohol and sucrose was determined.
Results Pretreatment with GS39783 resulted in a significant, dose-dependent reduction in responding for alcohol; at the dose of 100 mg/kg
GS39783, the number of lever responses for alcohol was reduced by approximately 50% in comparison to vehicle-treated rats.
The effect of GS39783 on alcohol self-administration was specific, as responding for sucrose was completely unaffected by
pretreatment with GS39783.
Conclusions These data demonstrate the capability of GS39783 to attenuate the reinforcing properties of alcohol in alcohol-preferring
rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the GABAB receptor in the control of alcohol drinking and reinforcement. 相似文献
88.
Patterns of hepatocellular carcinoma development in hepatitis B virus and hepatitis C virus related cirrhosis. 总被引:6,自引:0,他引:6
To compare incidence, risk factors and morphologic pattern of hepatocellular carcinoma (HCC) development in hepatitis B virus (HBV) and hepatitis C virus (HCV) related cirrhosis, 401 patients were followed prospectively by periodic ultrasound examination for 14-189 months (mean: 84.8+/-36.7). During follow-up, 77 (19.2%) patients developed HCC, with 5 and 10 year cumulative incidence of 10 and 27.5%, respectively. The risk of HCC was significantly higher in HBV and HCV co-infected patients (P=0.014) compared to those with single HBsAg or anti-HCV (antibodies to hepatitis C virus) positivity. In anti-HCV positive cases the annual risk of HCC increased from 2% in the first 5 year period to 4% in the third 5 year period, while it decreased from 2 to 0% in the same time periods in the HBsAg positive group. By Cox's regression, age above 59 years (P=0.001), male sex (P=0.09), longer duration (P=0.04) and more advanced stage (P=0.01) of cirrhosis, lower platelets count (P=0.001) and higher ALT levels were significant risk factors for HCC in anti-HCV positive patients, while only high alpha-fetoprotein (AFP) levels during follow-up (P=0.04) was a significant risk factor for HCC in HBsAg positive cases. The pattern of HCC was nodular in 63 (81.8%) patients and infiltrating in 14 (18.2%), and the former type was associated with older age (P=0.0001), longer duration (P=0.002) and more advanced stage (P=0.0001) of cirrhosis but not with the viral etiology of disease. In contrast, development of infiltrating HCC was unrelated to age and disease duration and stage, and was associated with male sex (P=0.01), HBV infection (P=0.06) and HBV and HCV co-infection (P=0.0001). Our results indicate different incidence profile, risk factors and patterns of morphogenesis of HCC development in HBV and HCV associated cirrhosis, suggesting different mechanisms of carcinogenesis. 相似文献
89.
90.
Gianpaolo Guzzi Giovanni Battista Fogazzi Mariadele Cantù Claudio Minoia Anna Ronchi Paolo D Pigatto Gianluca Severi 《Journal of environmental pathology, toxicology and oncology》2008,27(2):147-155
Chronic exposure to elemental metallic mercury may induce an immunological glomerular disease. Since humans are exposed to mercury vapor (Hg0) from dental amalgam restorations and kidney is an important target organ of mercury vapor and mercury deposition in kidney increases proportionally with the dose, our aim was to test the occurrence of specific antibodies to antiglomerular basement membrane (anti-GBM-IgG) among individuals with adverse effects to mercury from dental amalgam fillings. We selected a group of patients (n=24) with a history of long-term exposure to mercury vapor from mercury-containing amalgam fillings and showing adverse effects that were laboratory confirmed. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate serum levels of antibodies to anti-GBM-IgG. None of the patients showed evidence of anti-GBM autoimmunity, either in subgroups with strong allergy to mercury or its compounds (i.e., organic mercury) or in those patients who had past thimerosal-containing vaccines coverage (7 of 24). There was no evidence of the presence of circulating anti-GBM antibodies in subjects suffering from adverse events due to long-term exposure to mercury from dental amalgams, even in individuals who presented allergy to mercury. 相似文献