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51.
Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis 总被引:5,自引:0,他引:5
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Taranta A Migliaccio S Recchia I Caniglia M Luciani M De Rossi G Dionisi-Vici C Pinto RM Francalanci P Boldrini R Lanino E Dini G Morreale G Ralston SH Villa A Vezzoni P Del Principe D Cassiani F Palumbo G Teti A 《The American journal of pathology》2003,162(1):57-68
Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity. 相似文献
52.
Ferraris A Rappaport E Santacroce R Pollak E Krantz I Toth S Lysholm F Margaglione M Restagno G Dallapiccola B Surrey S Fortina P 《Human mutation》2002,20(4):312-320
Hereditary hearing loss (HHL) is one of the most common congenital disorders and is highly heterogeneous. Mutations in the connexin 26 (CX26) gene (GJB2) account for about 20% of all cases of childhood deafness, and approach 50% in documented recessive cases of non-syndromic hearing loss. In addition, a single mitochondrial DNA mutation, mt1555A>G, in the 12S rRNA gene (MTRNR1), is associated with familial cases of progressive deafness. Effective screening of populations for HHL necessitates rapid assessment of several of these potential mutation sites. Pyrosequencing links a DNA synthesis protocol for determining sequence to an enzyme cascade that generates light whenever pyrophosphate is released during primer strand elongation. We assessed the ability of Pyrosequencing to detect common mutations causing HHL. Detection of the most common CX26 mutations in individuals of Caucasian (35delG), Ashkenazi (167delT), and Asian (235delC, V37I) descent was confirmed by Pyrosequencing. A total of 41 different mutations in the CX26 gene and the mitochondrial mt1555A>G mutation were confirmed. Genotyping of up to six different adjacent mutations was achieved, including simultaneous detection of 35delG and 167delT. Accurate and reproducible results were achieved taking advantage of assay flexibility and experimental conditions easily optimized for a high degree of standardization and cost-effectiveness. The standardized sample preparation steps, including target amplification by PCR and preparation of single-stranded template combined with automated sequence reaction and automated genotype scoring, positions this approach as a potentially high throughput platform for SNP/mutation genotyping in a clinical laboratory setting. . 相似文献
53.
Sala G Galimberti G Canevari C Raggi ME Isella V Facheris M Appollonio I Ferrarese C 《Neurobiology of aging》2003,24(7):909-914
Various studies suggested that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). We investigated cytokine release from LPS-stimulated blood cells of 32 AD patients, with different disease severity, compared to 16 age-related controls. A significant decrease of IL-1beta and IL-6 secretion was observed in severely demented patients; TNF-alpha release was also decreased, but not significantly. By contrast, mild and moderate patients showed a cytokine release similar to controls. IL-1beta, IL-6 and TNF-alpha secretion was negatively correlated with the severity of dementia, quantified by the MMSE. Our data suggest that alterations of the immune profile are associated with AD progression. 相似文献
54.
Early detection of negative BACTEC MGIT 960 cultures by PCR-reverse cross-blot hybridization assay
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Romano L Sanguinetti M Posteraro B Ardito F Gesu G Schito AM Fadda G 《Journal of clinical microbiology》2002,40(9):3499-3501
We evaluated the efficacy of a PCR-reverse cross-blot hybridization assay, a test which permits identification of mycobacteria by means of species-specific probes and a Mycobacterium-specific probe, for early detection of negative BACTEC MGIT 960 mycobacterial cultures. Aliquots of 549 cultures were collected 7 days after the culture media were inoculated with various clinical specimens and tested with the molecular assay. PCR results were compared to those obtained at the end times with the BACTEC MGIT 960 system. Of the 549 specimens analyzed, 484 were found to be negative and 64 were found positive by both methods; one specimen, found to be positive by the BACTEC MGIT 960 system, was identified as negative by the molecular assay. In view of its high negative predictive value (99.8%), the PCR-reverse cross-blot hybridization assay appears to be a valid tool for early detection of negative BACTEC MGIT 960 cultures. 相似文献
55.
Paola Borgatti Giorgio Zauli Maria Luisa Colamussi Davide Gibellini Maurizio Previati Lewis L. Cantley Silvano Capitani 《European journal of immunology》1997,27(11):2805-2811
The biological basis for the pleiotropic activity of extracellular human immunodeficiency virus (HIV)-1 Tat protein on lymphoid T cell survival is not well understood. We have here demonstrated that the addition in culture of 0.1–10 nM Tat protein to 36-h serum-starved lymphoblastoid Jurkat T cells rapidly stimulates the catalytic activity of phosphatidylinositol 3-kinase (PI 3-K). The peak of activation was observed 30 min after Tat addition. Extracellular Tat also stimulated the catalytic activity of the Akt/PKB kinase, a major target of PI 3-K lipid products. Pretreatment of serum-starved Jurkat cells with 100 nM wortmannin (WT) or 10 μM LY294002, two unrelated pharmacological inhibitors of PI 3-K, markedly suppressed the catalytic activity of both PI 3-K and Akt/PKB in Jurkat cells. Moreover, at low concentrations (0.1–1 nM), extracellular Tat showed a small but reproducible protection of Jurkat cells from apoptosis induced by serum deprivation (p < 0.05), while the combination of Tat plus 100 nM WT significantly (p < 0.05) increased the percentage of apoptosis with respect to cells left untreated or treated with Tat alone. Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway. 相似文献
56.
Filaci G Contini P Fravega M Fenoglio D Azzarone B Julien-Giron M Fiocca R Boggio M Necchi V De Lerma Barbaro A Merlo A Rizzi M Ghio M Setti M Puppo F Zanetti M Indiveri F 《Human immunology》2003,64(1):9-20
Resident macrophages are mainly responsible for the clearance of apoptotic cells from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied by activation of inflammatory mechanisms, unlike what happens when necrotic phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on macrophage cell functions. After phagocytosis of apoptotic cells macrophages were unable to present an exogenous antigen to autologous antigen-specific T-cell lines. The inhibition was mediated by different mechanisms including binding of apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages, decreased expression of co-stimulatory molecules and increased secretion of tumor growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha) secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated by the binding of apoptotic DNA to macrophage HLA class II molecules as well as by the activation of biological mechanisms that induce an anti-inflammatory functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta secretion. These events are likely related to the preservation of healthy tissues from the onset of inflammation. 相似文献
57.
Aldo Scarpa Franco Bonetti Fabio Menestrina Marta Menegazzi Marco Chilosi Maurizio Lestani Chiara Bovolenta Giuseppe Zamboni L. Fiore-Donati 《Virchows Archiv : an international journal of pathology》1987,412(1):17-21
Summary The Southern blot hybridization technique has been applied to study the configuration of immunoglobulin and T-cell receptor genes in 6 cases of the so called mediastinal large cell lymphoma with sclerosis. This lymphoma has been recently recognized as a separate entity among non-Hodgkin lymphomas mainly affecting young adult patients. The B-cell origin of this neoplasm was suggested by means of immunohistochemical analysis. However, the immunophenotypical B-cell related markers used do not always exhibit lineage fidelity. The Southern blot analysis demonstrated the presence of unique heavy and k-light chain immunoglobulin gene rearrangements, establishing genotypically their B-cell origin.This work was supported by the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy, and Progetto finalizzato Oncologia (contratto no 86.00461.44), CNR, Rome, Italy. Aldo Scarpa and Maurizio Lestani are supported by a Scholarship from the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy 相似文献
58.
Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features 总被引:2,自引:0,他引:2
Rush AJ Zimmerman M Wisniewski SR Fava M Hollon SD Warden D Biggs MM Shores-Wilson K Shelton RC Luther JF Thomas B Trivedi MH 《Journal of affective disorders》2005,87(1):43-55
BACKGROUND: This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). METHODS: Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. RESULTS: Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. LIMITATIONS: Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. CONCLUSIONS: Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD. 相似文献
59.
Guido Martignoni Maurizio Pea Matteo Brunelli Marco Chilosi Alberto Zamó Manuela Bertaso Paolo Cossu-Rocca John N Eble Gregor Mikuz Giacomo Puppa Cecile Badoual Vincenzo Ficarra Giovanni Novella Franco Bonetti 《Modern pathology》2004,17(12):1455-1463
CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas. 相似文献
60.
Sergio Daga Chiara Fallerini Margherita Baldassarri Francesca Fava Floriana Valentino Gabriella Doddato Elisa Benetti Simone Furini Annarita Giliberti Rossella Tita Sara Amitrano Mirella Bruttini Ilaria Meloni Anna Maria Pinto Francesco Raimondi Alessandra Stella Filippo Biscarini Nicola Picchiotti Marco Gori Pietro Pinoli Stefano Ceri Maurizio Sanarico Francis P. Crawley Giovanni Birolo GEN-COVID Multicenter Study Alessandra Renieri Francesca Mari Elisa Frullanti 《European journal of human genetics : EJHG》2021,29(5):745
Within the GEN-COVID Multicenter Study, biospecimens from more than 1000 SARS-CoV-2 positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O2 supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical clustering analysis identified five main clinical categories: (1) severe multisystemic failure with either thromboembolic or pancreatic variant; (2) cytokine storm type, either severe with liver involvement or moderate; (3) moderate heart type, either with or without liver damage; (4) moderate multisystemic involvement, either with or without liver damage; (5) mild, either with or without hyposmia. GCB and GCPR are further linked to the GCGDR, which includes data from whole-exome sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population, and mapping genetically COVID-19 severity and clinical complexity among patients.Subject terms: Genetics research, Viral infection 相似文献