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Clinical Association (clinical + association)
Selected AbstractsLoss of the actin regulator HSPC300 results in clear cell renal cell carcinoma protection in Von Hippel-Lindau patients,,HUMAN MUTATION, Issue 6 2007Alberto Cascón Abstract Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney. The majority of hereditary and sporadic ccRCC cases are associated with germline and somatic mutations in the Von Hippel-Lindau gene (VHL), respectively. Gross deletions at the VHL locus can result either in ccRCC or in a mild clinical phenotype, with the absence of ccRCC development. Our goal in this study was to identify the molecular basis responsible for these differences in the clinical behavior in order to predict patients' phenotype. Using multiplex ligation-dependent amplification (MLPA), we identified and characterized gross VHL deletions in Spanish VHL families. A candidate gene related to this clinical association, HSPC300, was identified and depleted by RNA interference. It was possible to narrow the susceptibility region related to the mild clinical phenotype down to ,14,kb that included HSPC300 (C3orf10), a regulator of actin dynamics and cytoskeleton organization. Whereas 9 out of 10 families with ccRCC retained HSPC300 in the germline, loss of the HSPC300 locus was associated with mild clinical presentation of the disease in 6 out of 8 families. In fact, genetic depletion of HSPC300 resulted in cytoskeleton abnormalities and cytokinesis arrest in several tumor cell lines including ccRCC cells, suggesting that tumor cell proliferation was compromised in the absence of HSPC300. These clinical and functional data indicate a relevant function of HSPC300 in tumor cell progression, and suggest future therapeutic strategies based upon the inhibition of HSPC300 in renal cell carcinoma and possibly on other cancers. Hum Mutat 28(6), 613,621, 2007. © 2007 Wiley-Liss, Inc. [source] MYC gene amplification reveals clinical association with head and neck squamous cell carcinoma in Indian patientsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2009N. Bhattacharya Background:, Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). This study is focused to analyze the correlation between MYC gene amplification and various clinicopathological features and outcome in a cohort of 49 dysplastic and 187 primary head and neck lesions. Methods:,MYC gene amplification was assessed by differential polymerase chain reaction using primer sets from the MYC gene as target locus and DRD2 gene as the control locus. Result:, The MYC gene amplification was detected in a total of 23.7% (56/236) head and neck lesions comprising 14.2% (7/49) dysplastic lesions and 26% (49/187) HNSCC samples. The clinicopathological association study between MYC gene amplification with the different clinical parameters like sex, tumor stage, tumor differentiation, lymph node status, tobacco habit and HPV 16/18 status determined significant association of MYC amplification with tumor progression (P = 0.009). Kaplan Meier analysis revealed MYC gene has no prognostic significance on survival in HNSCC. Conclusion: , In conclusion, our results suggest that MYC gene amplification is associated with tumor progression in HNSCC. [source] Chronic urticaria and associated coeliac disease in children: A case,control studyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2005L. Caminiti Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case,control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5,10 wk, whereas the disappearance of serological markers occurred in longer times (5,9 months). Conclusions. The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU. [source] Serum chemokine profile in patients with bullous pemphigoidBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007H. Nakashima Summary Background, Bullous pemphigoid (BP) is an autoimmune inflammatory disease causing blister formation at the dermoepidermal junction. Cutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during the disease process, suggesting that the trafficking of circulating leucocytes through the sites of inflammation is crucial in the pathogenesis of the disease. While the accumulated evidence suggests that some cytokines are involved in the pathogenesis, there have been few reports about serum chemokine profiles in patients with BP. Objectives, To determine serum profiles of various chemokines and their clinical association in patients with BP. Methods, Concentrations of 10 chemokines , interferon (IFN)- , -inducible protein-10 (IP-10), monokine induced by IFN- , (MIG), macrophage inflammatory protein (MIP)-1,, MIP-1,, RANTES, eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3 and growth-regulated oncogene- ,, were measured in serum samples from 38 patients with BP, 16 with pemphigus vulgaris (PV) and 17 normal controls using a sandwich immunoassay-based multiplex protein array system. Results, While there was no significant increase in any serum chemokine levels in patients with PV, serum levels of IP-10 and MCP-1 were significantly increased in patients with BP compared with healthy controls. Furthermore, serum levels of IP-10, MIG, MCP-1 and eotaxin in patients with BP increased significantly with disease severity as determined by the area affected. Conclusions, These observations suggest that an elaborately orchestrated network of chemokines, especially MCP-1 and IP-10, contributes to the pathomechanism of BP. [source] Prevalence and clinical aspects of human bocavirus infection in childrenCLINICAL MICROBIOLOGY AND INFECTION, Issue 6 2010L. Karalar Clin Microbiol Infect 2010; 16: 633,639 Abstract Human bocavirus (HBoV) was recently described as a new member of the Parvoviridae. In order to investigate the suggested association of HBoV with respiratory and gastric disease in infants and young children, sera of 357 paediatric patients hospitalized with infectious and non-infectious diseases were retrospectively analyzed for the presence of HBoV DNA and virus-specific antibodies using quantitative PCR and ELISA, respectively. HBoV seroprevalence was determined to range from 25% in infants younger than 1 year of age to 93% in children aged more than 3 years. Viral loads between 1 × 102 and 1.2 × 106 geq/mL were observed in 6.7% (20/297) of sera obtained preferentially from young children suffering from infectious diseases. HBoV genomes were furthermore detected in 5% (3/60) of sera collected from individuals with non-infectious illnesses. HBoV DNA was present most frequently in patients with respiratory disease (9.6%). Whereas only 5.2% of patients with upper respiratory tract disease were viraemic, HBoV DNA was found in 14.6% and 10.0% of patients with lower respiratory tract illness and pneumonia, respectively. Acute HBoV infections were also observed in 7.5% of patients with gastroenteritis and in one child with inflammatory bowel disease. None of 77 patients hospitalized for various other infectious diseases (e.g. rash, urinary tract infection, meningitis) displayed viraemia. In 60.9% and 47.8% of DNA-positive children, HBoV-specific IgM and IgG was observed, respectively. The present prospective study provides comprehensive data on the clinical association of acute HBoV infection with respiratory illness and on the seroprevalence of virus-specific antibodies in children. [source] Activated eosinophils in nasal polyps: a comparison of asthmatic and non-asthmatic patientsCLINICAL OTOLARYNGOLOGY, Issue 3 2005N.D. Bateman Objectives:, There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. Design:, Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). Setting:, Teaching hospital otolaryngology unit. Participants:, Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty-four asthmatic and 35 non-asthmatic patients were studied. Main outcome measures:, Eosinophil density was measured using a standardized counting technique. Results:, Asthmatic patients were significantly more likely to have had previous polyp surgery (chi-square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t -test: P < 0.05). Conclusions:, We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non-asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps. [source] Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patientsCLINICAL OTOLARYNGOLOGY, Issue 6 2004N.D. Bateman The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process. [source] Allergic contact dermatitis from hair dye and development of lichen simplex chronicusCONTACT DERMATITIS, Issue 1 2004Won Young Chey Those who dye their hair frequently manifest allergic contact dermatitis (ACD) from p -phenylenediamine (PPD)-containing hair dye. PPD is known to be the most frequent sensitizer in hair dye, but there has been no documentation of this sensitizer having a role in chronic dermatologic conditions. Our department experienced a case of a 62-year-old woman with lichen simplex chronicus (LSC), who complained of aggravation after hair dyeing and made such an association. We conducted a prospective and retrospective study to further evaluate the clinical associations between the two. In our prospective study, patch testing was performed in selected patients who regularly carried out hair dyeing and also had clinical manifestations of LSC. Also a retrospective examination was conducted in cases where patch testing had been performed with PPD in the past for suspected ACD and further selected cases with concurrent LSC and/or other neurodermatitis. 11 and 14 patients in our prospective and retrospective study, respectively, presented with both LSC and positive findings to PPD. 5 (45.5%) and 4 (28.6%) patients in our prospective and retrospective study showed clinical relevance from clinical improvement after stopping use and rechallenge. We report several cases of patients diagnosed as having LSC and/or prurigo nodularis who showed clinical improvement after discontinuing the use of hair dye. The suggestion can therefore be made that hair dye could be a possible aetiologic agent causing LSC in those using hair dyes. [source] Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospitalJOURNAL OF MEDICAL VIROLOGY, Issue 8 2010Katherine E. Arden Abstract There are few data describing the comprehensive identification in and influence of newly identified respiratory viruses on asthma exacerbations. Most studies focus on inpatients. In this preliminary study, the point prevalence and the associations of picornavirus species described recently and human bocavirus (HBoV) with the recovery from exacerbations in non-hospitalized asthmatic children (median age 5.1 years) were examined. Human rhinoviruses (HRVs) were present in 52.6% of specimens, HBoV-1 was in 7.7%. Viral co-detections occurred in 25.6% of children and were associated (P,=,0.04) with lower asthma quality of life scores upon presentation than were single viral detections. The undifferentiated presence or absence of virus did not influence the severity of asthma or recovery however when virus species were examined individually, specific clinical associations emerged. HRV species C (HRV-Cs) were the viruses most frequently detected as single virus detections. Among 41 genotyped HRVs, more HRV-Cs (n,=,23) were identified than HRV-As (n,=,16) however HRV-A detection was associated (P,=,0.01) with worse asthma symptoms and cough for longer than was HRV-C detection. Larger, PCR-based studies are required to elucidate further the true impact of HRV species in childhood asthma exacerbations of both hospitalized and non-hospitalized cohorts. J. Med. Virol. 82:1458,1461, 2010. © 2010 Wiley-Liss, Inc. [source] Prevalence and clinical associations of posttransplant fatty liver diseaseLIVER INTERNATIONAL, Issue 1 2007Lee Guan Lim Abstract Background and Aims: Nonalcoholic fatty liver disease (NAFLD) could recur after liver transplant in patients with preexisting NAFLD, and has recently been reported to occur after transplant in patients transplanted without preexisting NAFLD. The literature on posttransplant NAFLD is limited. We aimed to study the prevalence of posttransplant NAFLD in patients transplanted for non-NAFLD-related liver diseases. Methods: Thirty liver transplant recipients: 18 with chronic hepatitis B (CHB), seven with chronic hepatitis C (CHC), five others, were recruited. Liver biopsies were performed in all CHB and CHC patients annually as per protocol, or when clinically indicated. All biopsies were reviewed by one hepato-histopathologist blindly to assess and stage for steatosis and steatohepatitis. Results: After a mean follow-up of 44±4 months, 12 (40%) and four (13%) developed posttransplant steatosis and steatohepatitis, respectively. None developed steatosis-related fibrosis or cirrhosis. Posttransplant steatohepatitis was associated with higher pretransplant body mass index (BMI) (32.3±3.9 vs 23.1±0.8, P=0.02) and higher BMI at last biopsy (32.5±4.3 vs 22.9±0.7, P=0.01). Conclusion: Posttransplant steatosis is common after liver transplant even in patients transplanted for non-NAFLD-related liver diseases. However, it is mostly benign during our follow-up, with only 13% developing steatohepatitis and none with fibrosis or cirrhosis. [source] Independent association of anti,,2 -glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patientsARTHRITIS & RHEUMATISM, Issue 8 2009Francesco Boin Objective Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti,,2-glycoprotein I (anti-,2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-,2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-,2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results Positivity for anti-,2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti-,2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-,2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion Anti-,2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-,2GPI as a biomarker of vascular disease in SSc should be further explored. [source] Adverse effects of corticosteroid therapy in neuromuscular diseased patients are common and receive insufficient prophylaxisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009D. McDougall Background ,, Corticosteroid therapy is known to have long-term adverse effects and complications, but our knowledge of the adverse effects of corticosteroids within a neuromuscular patient population is limited. Aims of the study ,, We sought to determine the prevalence and impact of corticosteroid use in a population of patients with neuromuscular diseases, as well as possible clinical associations for presence of adverse effects. Methods ,, A retrospective chart review from a comprehensive database from a tertiary care neuromuscular clinic spanning 1988,2007 was performed. Results ,, Corticosteroids led to adverse effects in 74% of exposed patients, without proper prophylaxis considered in about 50% of cases. There were no associations determined to have impact upon adverse effect occurrence, including the exposure to cumulative corticosteroid dosing or diagnosis. Conclusion ,, Corticosteroid therapy is frequently associated with adverse effects, although prediction of their occurrence is not clear. Prophylaxis of their occurrence is underperformed in our tertiary care clinic patient population. [source] Distal limb malformations: underlying mechanisms and clinical associationsCLINICAL GENETICS, Issue 3 2001S Sifakis Congenital malformations of the extremities are conspicuous and have been described through the ages. Over the past decade, a wealth of knowledge has been generated regarding the genetic regulation of limb development and the underlying molecular mechanisms. Recent studies have identified several of the signaling molecules, growth factors, and transcriptional regulators involved in the initiation and maintenance of the apical ectodermal ridge (AER) as well as the molecular markers defining the three axes of the developing limb. Studies of abnormal murine phenotypes have uncovered the role played by genes such as p63 and Dactylin in the maintenance of AER activity. These phenotypes resemble human malformations and in this review we describe the underlying mechanisms and clinical associations of split hand/foot malformation and ectrodactyly,ectodermal dysplasia,cleft lip/palate syndrome, which have both been associated with mutations in the p63 gene. [source] | |||||||||||||