Increased osteoprotegerin in Italian haemodialysis patients.
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Biomarkers↗
Biomedical subjects
G Valente
Publications and source records attributed to G Valente.
Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation index.
AIMS: To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. METHODS: Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. RESULTS: HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. CONCLUSIONS: To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index.
Aged↗
Muscular cramps: proposals for a new classification.
Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term "cramp" is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise "umbrella" term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.
Drug-Related Side Effects and Adverse Reactions↗
L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease.
OBJECTIVES: To estimate changes in motor inhibitory mechanisms at the spinal level in Parkinson's disease (PD) patients by measuring cutaneous silent responses to nociceptive stimuli in the course of L-Dopa therapy. MATERIALS AND METHODS: Fourteen patients with idiopathic PD (Group 1) and 13 patients with other forms of parkinsonism (Group 2) participated in the study. The cutaneous silent period (CSP) from the hand and clinical scores (UPDRS, part III) were measured "off" therapy (T0), after a single dose of L-Dopa (T1) and 3 months after the beginning of L-Dopa daily therapy (T2). RESULTS: At T0 the duration of the CSP was significantly prolonged in Group 1 and Group 2. At T1 and T2 the mean duration of the CSP significantly decreased in Group 1 (P < 0.05) and a significant correlation was found between the shortening of the CSP and the improvement of rigidity and bradikynesia in the upper limb. CONCLUSIONS: Our findings show that L-Dopa decreases the cutaneous nociceptive inhibition of motor activity in PD patients. CSP may be useful to assess L-Dopa responsiveness during the clinical course of PD.
Administration, Oral↗
Sinus floor augmentation with autogenous iliac bone block grafts: a histological and histomorphometrical report on the two-step surgical technique.
In thirteen patients, screw-type endosseous implants were inserted 6 months after sinus floor elevation and augmentation with autogenous iliac bone block grafts. Bone biopsies were harvested at graft positioning (baseline), at implant placement (6 month) and at abutment connection (1 year). Histological evaluation suggested a decrease in the volume of mineralized tissue and in the vitality of the grafts 6 months after graft insertion, followed by an increase at abutment connection. Histomorphometric analysis of the bone specimens showed that, at implant placement, bone content was reduced by 5.2% on average, while 12 months after grafting it had increased by 4.8% compared to the amount of mineralized tissue contained in the graft at baseline. The results suggest that in sinus floor augmentation procedures with autogenous iliac bone blocks, a two-step surgical technique allows implant insertion when graft healing is entering a phase of greater density and vitality.
Aged↗
Study of ethmoidal mucosa in a population at occupational high risk of sinonasal adenocarcinoma.
The occurrence of nasal adenocarcinomas was first described in 1965. Since 1988 these tumors have been accepted as an occupational disease for woodworkers in Italy. There are several underlying reasons why there is interest in studying the ways in which sinonasal adenocarcinomas occur. Often diagnosed at advanced stages of development because their symptoms are non-specific, these tumors are associated with a high mortality rate. A multidisciplinary study protocol was developed in this investigation. The aim was to identify the factors and conditions that promote sinonasal tumor growth in a population at risk due to occupational exposure to wood dust. Sixty-eight carpenters with a minimum of 10 years exposure to wood dust were studied. The control group comprised 81 volunteers. The patients underwent the following protocol: completion of a case report form, physical examination, evaluation of nasal cavity patency, clinical laboratory tests and histological study of the nasal mucosa. Our study provides significant evidence of the elevated incidence of pavimentous metaplasia in workers occupationally exposed to wood dust. In addition, it underscores a significant deficit of immunoglobulin A in such workers compared to the controls. However, we did not find, as reported elsewhere in the literature, a statistically significant difference between cases and controls as regards nasal symptoms and hyperemia of the nasal mucosa. Our study showed that, even in the absence of evident sinonasal lesions, it is still possible to determine an increased incidence of morphofunctional changes in subjects occupationally exposed to wood dust. Our findings may lead to the identification of occupational groups prone to elevated risk of the disease.
Adenocarcinoma↗
Sequential immunohistochemical p53 expression in biopsies of oral lichen planus undergoing malignant evolution.
Transformation in squamous cell carcinoma (SCC) may occur in a small percentage of patients affected by oral lichen planus (OLP), but the pathogenesis remains to be elucidated. Overexpression of p53 protein was investigated immunohistochemically in 28 cases of OLP, followed up by sequential biopsies for up to 96 months. In 15 cases (Group 1), no dysplastic changes or neoplastic transformation occurred during the follow-up period; in 7 cases, OLP and SCC were synchronously observed (Group 2), whereas in another 6 cases (Group 3) SCC developed several months or years after diagnosis of OLP. The percentage of p53-positive epithelial cells at first diagnosis was significantly higher in the cases of Groups 2 and 3 than in those of Group 1. In contrast, evaluation of growth fraction by MIB-1 monoclonal antibody did not show any statistical differences among the three groups. Although no conclusions can be drawn about the molecular pathway leading to neoplastic transformation of OLP, or about the role of p53, the results indicate that immunohistochemical evaluation of p53 expression may be a practical tool to select cases of OLP with a high risk of neoplastic transformation.
Aged↗
Detection of platelet-activating factor in gingival tissue surrounding failed dental implants.
BACKGROUND: Dental implant therapy has entered routine clinical practice. However, the failure rate of implants at 5 years, due to biological factors, is still around 7%. The pathogenesis of implant loss involves a complex network of cells and inflammatory mediators. This study evaluated platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, in soft tissue surrounding failed dental implants versus healthy implants. METHODS: PAF was estimated on extracted lipids by bioassay on washed rabbit platelets; inflammatory cell populations were assessed semiquantitatively after staining, and microvessel density was evaluated after immunohistochemical staining. RESULTS: Biologically active PAF was detected in the lipid extracts of samples excised from gingival tissue of patients with failed implants, but not in samples from patients with osseointegrated implants or from healthy edentulous subjects. The amount of PAF detected in failed implants was significantly higher than in healthy implants, suggesting a local production of this mediator. CONCLUSIONS: The presence of PAF was associated with histopathological findings of local inflammation and increased blood vessel density.
Adult↗
Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases.
In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical lymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatocyte growth factor/scatter factor, mediating epithelial cell motility and invasiveness. The MET gene is expressed in epithelia and over-expressed in carcinomas of specific histotypes, but not in lymphatic tissue. A total of 151 lymph nodes from 20 squamous cell carcinomas were studied with both in-depth histology and end-point and real-time quantitative RT-PCR. MET-encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in-depth histopathology. Parallel routine histopathologic analysis of 654 lymph nodes from the same cases identified 36 metastases (5%). Real-time quantitative RT-PCR was used to measure MET gene-specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2-8-fold increased expression in tumor cells which metastasize. RT-PCR for 3 cytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitive in detecting occult lymphatic metastases. Western blot analysis demonstrated the presence of the full-size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a valuable marker with which to detect occult tumor cells in lymph nodes, thanks to its high expression in metastatic cells. After RT-PCR analysis we were able to attribute a more advanced stage to 10 out of 20 HNSCC cases, including 5 cases classified as tumor-free after routine histopathology.
Biomarkers, Tumor↗
Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas.
A metastatic cancer develops by accumulation of mutations in genes that control growth, survival and spreading. The latter genes have not yet been identified. In lymph node metastases of head and neck squamous cell carcinomas (HNSCC), we found mutations in the MET oncogene, which encodes the tyrosine kinase receptor for Scatter Factor, a cytokine that stimulates epithelial cell motility and invasiveness during embryogenesis and tissue remodeling. We identified two somatic mutations: the Y1230C, known as a MET germline mutation which predisposes to hereditary renal cell carcinoma, and the Y1235D that is novel and changes a critical tyrosine, known to regulate MET kinase activity. The mutated MET receptors are constitutively active and confer an invasive phenotype to transfected cells. Interestingly, cells carrying the MET mutations are selected during metastatic spread: transcripts of the mutant alleles are highly represented in metastases, but barely detectable in primary tumors. These data indicate that cells expressing mutant MET undergo clonal expansion during HNSCC progression and suggest that MET might be one of the long sought oncogenes controlling progression of primary cancers to metastasis.
Alleles↗
Adaptive-optics corrections available for the whole sky
Adaptive-optics systems can in principle allow a telescope to achieve performance at its theoretical maximum (limited only by diffraction), by correcting in real time for the distortion of starlight by atmospheric turbulence. For such a system installed on an 8-m-class telescope, the spatial resolution and sensitivity could be up to 100 times better than conventional imaging. Adaptive-optics corrections have hitherto been achieved only for regions of the sky within a few arcseconds of a bright reference source. But it has been proposed theoretically that by using multiple guide stars, the tomography of atmospheric turbulence could be probed and used to extend adaptive-optics corrections to the whole sky. Here we report the experimental verification of such tomographic corrections, using three off-axis reference stars approximately 15 arcsec from the central star. We used the observations of the off-axis stars to calculate the deformations of the wavefront of the central star, and then compare them with the real measured values. This tomographic approach is found to reduce variations in the wavefront by approximately 92%. Our result demonstrates that a serious barrier to achieving diffraction-limited seeing over the whole sky has been removed.
Journal Article↗
Murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infection.
The course of mouse cytomegalovirus (MCMV) infection was compared between wild-type and mutant C57BL / 6 (B6) mice deficient in either RAG-2, perforin, granzyme A, granzyme B or combinations thereof at two time points post infection (p. i.). At day 15 p. i., virus titers were similarly elevated in salivary glands of all mutant, but not wild-type B6 mice and undetectable in lung and spleen tissues of any of the mouse strains. Significant pathological alterations were only seen in salivary glands and spleen from RAG2(- / -), but not in those from other mice whereas few inflammatory foci were observed in lung tissues of all mice except B6. At day 30 p. i., elevated virus titers were observed only in salivary glands, lung and spleen from RAG2(- / -), but in none of the other mice, and were accompanied by extended pathological alterations in all three organs. The data extend previous reports on the critical role of NK / CD8(+) T cells in the early control of MCMV infection by showing that both perforin and granzymes A / B contribute to viral elimination in salivary glands; however, neither of the three molecules alone seem to be indispensable for the final control of infection.
Animals↗
Afterdischarge activity in neuropathic patients with frequent muscle cramps.
OBJECTIVES: To evaluate the presence of the afterdischarge activity following M- and F-waves in patients with peripheral neuropathies with or without muscle cramps. MATERIAL AND METHODS: Ten patients with peripheral neuropathies complaining of frequent muscle leg cramps (Group 1) and 14 patients with peripheral neuropathies without muscle cramps (Group 2) participated in our study. The afterdischarge was evaluated through a repetitive stimulation of the peroneal and tibial nerves. RESULTS: An abnormal afterdischarge activity following F-wave was identified below 5 Hz only in Group 1. On high frequency of stimulation (> 5 Hz), this activity was present in every patient in Group 1. Moreover, it was particularly present in the muscle affected by cramps. CONCLUSION: Since the afterdischarges following F-waves have been considered to be the result of a hyperactive "bistable" state of alfa-motor neurons, our findings are indicative of an impairment of motor neuron excitability. Thus, it is hypothesizable that either peripheral and central mechanisms may together contribute in producing muscle cramps.
Aged↗
Expansion and molecular evolution of the interferon-induced 2'-5' oligoadenylate synthetase gene family.
The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze the polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block viral replication at the level of mRNA degradation. A molecular evolutionary analysis of available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The modern mammalian 2'-5'OAS genes underwent successive gene duplication events resulting in three size classes of enzymes, containing one, two, or three homologous domains. Expansion of the OAS gene family occurred by whole-gene duplications to increase gene content and by domain couplings to produce the multidomain genes. Evolutionary analyses show that the 2'-5'OAS genes in rodents underwent gene duplications as recently as 11 MYA and predict the existence of additional undiscovered OAS genes in mammals.
2',5'-Oligoadenylate Synthetase↗
Production and pro-apoptotic activity of soluble CD95 ligand in pancreatic carcinoma.
We report here that the progression of pancreatic carcinomas in tumor patients is associated with increased serum levels of both the soluble forms of CD95 ligand (CD95L/FasL) and its receptor, CD95 (Fas). Shedding of proteolytically processed soluble CD95L was also observed in pancreatic carcinoma cells in vitro, thus identifying one possible source of CD95L in patients' sera. Because the secreted forms of both CD95 and CD95L have been implicated previously in protection of cells from CD95-mediated cell death, we assessed the effect of soluble CD95L in supernatants of pancreatic carcinoma cells on viability of Jurkat T lymphocytes. We describe that (a) supernatants derived from cultured pancreatic carcinoma cells caused apoptosis of Jurkat cells; (b) soluble tumor-derived CD95L contributed significantly to this effect; and (c) in comparison to Jurkat cells, pancreatic carcinoma cells themselves revealed increased resistance to apoptosis induction by autocrine soluble CD95L. These results are consistent with the notion that in the microenvironment of pancreatic tumors, tumor-derived shed CD95L exerts paracrine pro-apoptotic effects. In addition, because it is released at high levels into the bloodstream, soluble CD95L may have systemic effects in tumor patients that reach beyond the microenvironment of the tumor site.
Adult↗
Stress echocardiography and exercise electrocardiography for risk stratification after non-Q-wave uncomplicated myocardial infarction.
The aim of our study was to compare the prognostic value of stress echocardiography and exercise electrocardiography after uncomplicated non-Q-wave acute myocardial infarction in a series of 68 consecutive patients. Our data show that stress echocardiography and exercise electrocardiography offer similar prognostic information after uncomplicated non-Q-wave AMI.
Adult↗
Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family.
Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC). PRCCs are often multiple and bilateral even in patients without a family history. We analyzed the germline of patients carrying multiple or single papillary tumors with and without family history. One patient had a familial cancer and carried a novel (V1110I) germline MET mutation, located in MET gene exon 16. This mis-sense mutation was found in affected members of this patient's family. Interestingly, the V1110I mutation is located in the ATP-binding site of the MET kinase and is homologous to the V157I mutation that triggers the sarcomagenic potential of the v-erbB oncogene. The V1110I mutated MET receptor is an active kinase and transforms NIH-3T3 fibroblasts in the in vitro assays. Patients without familiality did not show germline mutations in the MET kinase domain, showing that multiple and bilateral papillary kidney tumors develop in the absence of these mutations. In conclusion, we describe a new mutation in the MET oncogene kinase domain, associated to HPRCC, affecting an amino-acid residue critical for kinase activation in different oncogenes.
Adenosine Triphosphate↗
Sonographic appearance of aggressive angiomyxoma of the bladder.
Aggressive angiomyxoma is a rare, benign but locally aggressive mesenchymal neoplasm. We report the sonographic findings in a case of histologically proven aggressive angiomyxoma of the bladder. Sonography revealed a solid polypoid mass 2 cm in diameter with sharply demarcated borders, a heterogeneous echotexture, and a slightly hyperechoic rim.
Adult↗