Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn's disease

Evidence is accumulating that colonic mucin glycoconjugates are altered in ulcerative colitis. In order to investigate this further, the lectin-binding properties of rectal glycoconjugates have been studied in ulcerative colitis, Crohn's disease, and controls using lectin-peroxidase histochemistry. Ten lectins were used including peanut agglutinin (PNA) which is known to bind to malignant and adenomatous but not normal colonic mucins. Eight of 21 ulcerative colitis rectal biopsies and 10 of 17 Crohn's disease rectal biopsies showed PNA positivity, particularly in the supranuclear region of surface epithelial cells. There was no correlation between PNA positivity and duration of disease or inflammation, and none of the biopsies showed evidence of dysplasia. This abnormality in epithelial cell glycoconjugates seems to be commonly present in nondysplastic mucosa and occurs in both ulcerative colitis and Crohn's disease. It may reflect a fundamental abnormality in mucus glycoprotein synthesis in inflammatory bowel disease.     

Muramidase (lysozyme) in Crohn's disease and in ulcerative colitis

Estimation of lysozyme (LZM) activity in the serum was suggested as a valuable test to distinguish between Crohn's disease and ulcerative colitis. Subsequently several reports either supported or denied the original observation. Selection of patients and methodological differences were suggested as an explanation for the controversy. We estimated serum LZM in a large group of patients using the lysoplate method and human LZM as a standard. The conditions of the assay were strictly standardized. In 90 patients with Crohn's disease the LZM level was 8.3±2.1 (sd) g/ml, in 57 patients with ulcerative colitis it was 7.4±2.0 (sd) g/ml, and in 40 healthy individuals it was 7.0±1.2 (sd) g/ml. Although the difference between the mean LZM levels in Crohn's disease and in ulcerative colitis was statistically significant, there was a definite overlapping of values between these two diseases. No significant correlation of LZM level to the duration or extent of the disease, activity, or treatment was found in Crohn's disease. In ulcerative colitis the LZM level was often a little higher in severe disease, especially when the whole colon was involved.Supported in part by grant-in-aid from the Medical Research Council of Canada.     

Serum concentration of 19 serum proteins in Crohn's disease and ulcerative colitis

The serum concentration of 19 serum proteins was determined by electrophoresis in 42 patients with Crohn's disease and 36 patients with ulcerative colitis. The results were compared with 78 healthy persons as matched controls. Distinctive, but similar, changes were present in the two diseases. An increased serum concentration of orosomucoid, alpha(1)-antitrypsin, easily precipitable glycoprotein, alpha(1)-antichymotrypsin, haptoglobin, and haemopexin was present. The serum concentration was decreased for prealbumin, albumin, alpha(2)-HS glycoprotein, caeruloplasmin, alpha(2)-macro-globulin, and transferrin. No significant difference between the two diseases existed as far as the serum protein pattern was concerned.Certain proteins, ;the acute phase reactants' (orosomucoid, alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, and haptoglobin) and the immunoglobulins were clinically useful, since their serum concentration reflected the grade of activity of the disease. A pronounced elevation of haptoglobin compared with that of the other ;acute phase reactants' was present in patients with Crohn's disease complicated by suppurative fistulas or abscesses. Patients with active Crohn's disease who responded favourably to medical treatment had significantly higher immunoglobulin levels than patients not responding. A similar observation, though not statistically significant, was made in patients with ulcerative colitis.     

Serum antibodies to cow's milk proteins in ulcerative colitis and Crohn's disease

Serum antibodies of immunoglobulin G, immunoglobulin M, and immunoglobulin A isotypes to five major proteins of cow's milk, casein, bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin A, and beta-lactoglobulin B, were measured using enzyme-linked immunosorbent assay in 51 patients with ulcerative colitis, 49 with Crohn's disease, and 20 age-matched controls. Immunoglobulin G and immunoglobulin M antibodies to cow's milk proteins were significantly elevated in patients with inflammatory bowel disease as compared to controls. In contrast, no significant increase in immunoglobulin A antibodies to 3 of 5 proteins was noted. The increased titers of antibodies to milk proteins seem to be specific and not due to a polyclonal immunoglobulin activation, as naturally occurring blood group antibodies were not elevated in patients with ulcerative colitis and Crohn's disease. A good correlation of disease activity, as measured by serum alpha 1-acid glycoprotein concentrations, and immunoglobulin G and immunoglobulin A antibody titers against certain cow's milk proteins could be demonstrated in Crohn's disease, but not ulcerative colitis. These findings suggest that production of antibodies to cow's milk proteins reflects specific immunization with these antigens. The study of antibody isotypes and correlation with disease activity may provide better insight into the immune response to dietary antigens and its possible role in the pathogenesis of inflammatory bowel diseases.     

Management of ulcerative colitis and Crohn's disease

The conventional medical treatment of IBD consists of aminosalicylates, corticosteroids, immunosuppressive drugs (azathioprine, 6-mercaptopurin, methotrexate, cyclosporin) and antibiotics. The only drugs able to modify the disease course are azathioprine, its metabolite 6-mercaptopurin and methotrexate. However, these drugs have a slow onset of action and are associated with important side-effects in some patients, necessitating the discontinuation of the drug. Moreover, up to 60% of patients do not respond to these drugs long-term. Fortunately, the management of IBD has entered a new era in the beginning of the 1990s with the development of new biological therapies, selectively blocking the inflammatory cascade. The novel molecules have arisen from the increasing knowledge about the disease pathogenesis and their production has been precipitated by the techniques of molecular biology. Infliximab, the first available biological for Crohn's disease has certainly revolutionised standard treatment. Because of its profound clinical, endoscopic and histological effects, the standard step up approach in the treatment of IBD has been challenged. A large array of new rationally designed biologicals, with a better safety profile and equally selectively acting is underway, and is likely to change our current practise even more dramatically in the next decade.     

2 The differential diagnosis of Crohn's disease and ulcerative colitis

Most cases of inflammatory bowel disease (IBD) can be correctly labelled as Crohn's disease (CD) or ulcerative colitis (UC) with careful initial gross and microscopic examination of biopsy and resection specimens together with close clinical and radiological correlation. Until we understand more of the aetiology and immunology of IBD we should admit that there are limitations imposed by current diagnostic criteria, consider the use of reporting proforma to improve diagnostic accuracy, and accept that in a small number of patients clinicopathological features will overlap, and CD may masquerade as UC.     

Esophageal lesions in Crohn's disease and ulcerative colitis

This article reviews the literature about esophageal involvement of Crohn's disease and ulcerative colitis. The review highlights the incidence of IBD, clinical features and difficulties of diagnosis and treatment of patients with esophageal involvement of IBD.     

实时定量PCR检测TRF1、TRF2和hRAP1基因在急性髓细胞性白血病中mRNA表达

目的：建立一种实时荧光RT—PCR方法,定量检测急性髓细胞性白血病（AML）患者外周血白细胞细胞TRF1、TRF2和hRAP1mRNA的表达水平及相互关系。方法：选取48例初治AML患者和21例健康志愿者,采用实时荧光RT—PCR与Lightcyeler荧光PCR仪定量检测TRFI、TRF2和hRAP1mRNA的表达水平;采用2^—△△Ct法处理实时荧光定量RT—PCR数据。结果：AML首治患者TRF1、TRF2和hRAP1mRNA表达水平较对照组健康志愿者分别下降了2．9倍,2．2倍和16．6倍,且差异有统计学意义;AML患者组TRF1和TRF2mR—NA的表达改变具有一定的相关性（r=0．57,P〈0．01）。结论：成功利用患者外周血检测出端粒结合蛋白TRF1,TRF2在白血病细胞中mRNA的表达水平下降,并首次检测发现hRAP1在AML患者细胞中存在表达下降,间接说明了hRAP1的表达下降也是白血病的发病原因之一。     

Endotoxin-induced microclots in ulcerative colitis and Crohn's disease

Radially oriented fibrin microclots were observed when blood from patients with active lesions of Crohn's disease and ulcerative colitis was kept in capillary tubes for 24 h. Addition of bacterial extract or endotoxins increased the fibrin formation. The phenomenon is not seen in healthy subjects or patients who have healed after colectomy. The data are consistent with our findings in patients with vasculitis and support the view that patients with Crohn's disease and ulcerative colitis have circulatory endotoxins.     

Clq metabolism in ulcerative colitis and Crohn's disease

The metabolism of pure radioiodine labelled Clq has been observed in five patients with ulcerative colitis, five patients with Crohn's disease, and in five control subjects. Both the fractional catabolic rate and the synthesis rate of Clq were increased in the five patients with Crohn's disease and in four of the five patients with ulcerative colitis. The fifth patient was in remission and had a normal synthesis rate. These results support the hypothesis that complement activation plays a role in the pathogenesis of these disease states and that the increased complement activation is primarily via the classical pathway.     

Macrophage turnover in Crohn's disease and ulcerative colitis

Monocytopoietic proliferation activity was determined in 8 patients during severe attacks of Crohn's disease and in 6 patients with ulcerative colitis. Similar results were obtained in both groups of patients. A moderate but significant hyperproliferation of monocytopoiesis was found to be present in about half of the patients, and with some of the remainder of cases, part of the criteria for hyperproliferation were also fulfilled. This indicates that Crohn's disease as well as ulcerative colitis are frequently associated with moderate overproduction of monocytes which may be assumed to be induced by macrophage demand of the affected tissues. In comparison with other diseases involving inflammations, the monocytopoietic hyperproliferation was moderate. Therefore, the inflammation in Crohn's disease and ulcerative colitis seems to be characterized by a relatively low macrophage turnover induced by pathogenetic mechanisms of moderate macrophage toxicity.     

溃疡性结肠炎及克罗恩病的内镜活检病理特点分析

目的 总结溃疡性结肠炎（UC）及克罗恩病（CD）的病理形态学特点,为其诊断提供借鉴.方法 收集临床首次诊断并经病理科证实的UC患者180例、CD患者106例,资料包括年龄、性别及病变累及肠道的部位,并选用病理组织学标准对病变的黏膜结构改变、黏膜慢性炎症细胞浸润、黏膜急性炎症改变、黏膜上皮改变进行评价,比较两类患者间的差异.结果 和CD病例比较,UC病例出现黏膜结构紊乱的比例较高（P＜0.05）,出现局灶间断性炎症的比例较低（P＜0.05）,隐窝炎、隐窝脓肿及固有膜内中性粒细胞浸润发生率较高（P＜0.05）,表面上皮变扁或糜烂、黏液细胞减少的发生率较高.肉芽肿样小结、假幽门腺化生及裂隙状溃疡改变仅出现在CD病例.180例UC病例中90%（162例）病例病变部位局限于结肠.106例CD病例中28%（30例）病变部位局限于回盲部,56%（59例）病变累及到2个及以上不同部位.结论 肠镜活检病理诊断UC及CD是一个综合分析的过程.若病变局限于回盲部或胃肠道多部位累及,黏膜出现肉芽肿样小结、局灶间断性炎细胞浸润、假幽门腺化生等改变则倾向于CD诊断;若病变局限于结肠,黏膜出现弥漫一致性炎或明显的黏膜结构改变、黏膜上皮改变则倾向于UC诊断.