Serological identification and expression analysis of gastric cancer-associated genes

Serological identification of tumour antigens by recombinant expression cloning has proved to be an effective strategy for the identification of cancer-associated genes having a relevance to cancer aetiology and progression, and for defining possible targets for immunotherapeutic intervention. In the present study we applied this technique to identify immunogenic proteins for gastric cancer that resulted in isolation of 14 distinct serum-reactive antigens. In order to evaluate their role in tumourigenesis and assess the immunogenicity of the identified antigens, we characterised each cDNA clone by DNA sequence analysis, mRNA tissue distribution, comparison of mRNA levels in cancerous and adjacent non-cancerous tissues and the frequency of antibody responses in allogeneic patient and control sera. Previously unknown splice variants of TACC1 and an uncharacterised gene Ga50 were identified. The expression of a newly identified TACC1 isoform is restricted to brain and gastric cancer tissues. Comparison of mRNA levels by semi-quantitative RT–PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1 – an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development. An unusual DNA polymorphism – a three-nucleotide deletion was found in NUCB2 cDNA but its mRNA level was consistently decreased in gastric tumours compared with that in the adjacent non-cancerous tissues. This study has revealed several new gastric cancer candidate genes; additional studies are required to gain a deeper insight into their role in the tumorigenesis and their potential as therapeutic targets

Limited referral to nephrologists from a tertiary geriatric outpatient clinic despite a high prevalence of chronic kidney disease and anaemia

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is increasing in prevalence world-wide with the largest growth being in the elderly. The aim of this study was to examine the prevalence of CKD in a geriatric outpatient clinic within a tertiary hospital and its association with anaemia and mortality with a focus on the referral patterns towards nephrologists.</p> <p>Methods</p> <p>Retrospective study utilising administrative databases. The cohort was defined as all patients that attended the geriatric outpatient clinics of a single tertiary hospital within the first 3 months of 2006. Patients were followed for 18 months for mortality and referral to a nephrologist.</p> <p>Results</p> <p>The mean Glomerular filtration rate (eGFR) of the 439 patients was 67.4 ± 29.1 mL/min/1.73 m² (44% <60 mL/min/1.73 m²). 11.8% had a haemoglobin < 110 g/L, with anaemia being significantly associated with kidney function in those with a eGFR < 60 mL/min/1.73 m² (p = 0.0092). Kidney function and anaemia were significantly associated with mortality on multivariate analysis (p = 0.019 and p = 0.0074). After 18 months, 8.8% of patients with CKD were referred to a nephrologist.</p> <p>Conclusion</p> <p>Despite a high prevalence of CKD in patients attending a geriatric outpatient clinic and its association with anaemia and mortality, few of these patients were referred to a nephrologist. An examination of the reasons behind this bias is required.</p

Doença pulmonar intersticial relacionada a miosite e a síndrome antissintetase Myositis-related interstitial lung disease and antisynthetase syndrome

Em pacientes com miosite, é comum o comprometimento pulmonar, e a presença de anticorpos anti-aminoacil-RNAt sintetase (anti-ARS) é preditora da presença ou do desenvolvimento de doença pulmonar intersticial (DPI). Uma entidade clínica distinta - a síndrome antissintetase - é caracterizada pela presença de anticorpos anti-ARS, miosite, DPI, artrite, fenômeno de Raynaud e "mãos de mecânico". O mais comum anticorpo anti-ARS é o anti-Jo-1. Anticorpos anti-ARS mais recentemente descritos podem conferir um fenótipo que é distinto daquele de pacientes com positividade para anti-Jo-1, sendo caracterizado por uma menor incidência de miosite e uma maior incidência de DPI. Nos pacientes com DPI relacionada à síndrome antissintetase, a resposta a medicações imunossupressoras é em geral favorável.<br>In patients with myositis, the lung is commonly involved, and the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies marks the presence or predicts the development of interstitial lung disease (ILD). A distinct clinical entity-antisynthetase syndrome-is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud's phenomenon, and mechanic's hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable