Recognition of Tumor-Specific Proteins in Human Cancer

Cancer is a disease of all ages and even though cancer is not a common disease in younger people, cancer is recognized as one of the most imp0l1ant causes of death at any age. In fact, when considering the main death causes in people younger than thirty years, cancer is second only to accidents. Beyond the age of thirty years, the number of deaths from cancer increases upon aging, gradually at first, rising simply later on. Apm1 from cancer causing death, the disease is fem'ed because patients who suffer from cancer are often condemned to a long and painful terminal illness. Based on their frequency of occurrence, cancers are traditionally categorized as either epithelial cancers (approximately 85% of all human cancers) or non-epithelial cancers (approximately 15% of all human cancers). Cancers arising from epithelial cells (i.e. cells lining the body cavities and skin) are called cm'Cinomas (Latin: km'kinos - crab or lobster; oma - swelling), while those arising from non-epithelial cells are further subdivided according to the tissue and cell type from which they originate. Thus, sarcomas are derived from connective tissue or muscle cells (Greek: sarx - meat), while leukemias are derived from hematopoietic cells (Greek: leucos - white; haimablood). Other non-epithelial cancers include the ones deJived fi'Om cells ofthe nervous system and germinal or embryonal cells

Subtractive isolation of phage-displayed single-chain antibodies to thymic stromal cells by using intact thymic fragments

In the murine thymus, the stroma forms microenvironments that control different steps in T cell development. To study the architecture of such microenvironments and more particularly the nature of communicative signals in lympho–stromal interaction during T cell development, we have employed the phage antibody display technology, with the specific aim of isolating thymic stromal cellspecific single-chain antibodies from a semisynthetic phage library. A subtractive approach using intact, mildly fixed thymic fragments as target tissue and lymphocytes as absorber cells generated monoclonal phages (MoPhabs) detecting subsets of murine thymic stromal cells. In the present paper we report on the reactivity of single-chain antibodies derived from three MoPhabs, TB4–4, TB4–20, and TB4–28. While TB4–4 and TB4–20 are both epithelium specific, TB4–28 detects an epitope expressed on both epithelial- and mesenchymal-derived stromal cells. TB4–4 reacts with all cortical epithelial cells and with other endoderm-derived epithelia, but this reagent leaves the majority of medullary epithelial cells unstained. In contrast, MoPhab TB4–20 detects both cortical and medullary thymic epithelial cells, as well as other endoderm- and ectoderm-derived epithelial cells. Cross-reaction of single-chain antibodies to human thymic stromal cells shows that our semisynthetic phage antibody display library, in combination with the present subtractive approach, permits detection of evolutionary conserved epitopes expressed on subsets of thymic stromal cells

Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice

Background: Macrocytic anaemia (MCV \xe2\x89\xa5 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. Methods: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. Results: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. Conclusion: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice