Altered oligosaccharide expression in ulcerative colitis with increasing grades of inflammation

Ulcerative colitis is an idiopathic chronic inflammatory condition of the large bowel associated with åbnormalities of mucin synthesis and secretion. In the present study, glycans were identified in 45 formalin-fixed, paraffin-embedded tissue samples from patients with ulcerative colitis. The tissue samples represented a spectrum of inflammation from chronic quiescent disease to severe inflammation. Thirteen biotinylated lectins, directed against a range of sialyl, fucosyl andN-acetylgalactosaminyl sequences, were applied using an avidin-peroxidase revealing system. The results were assessed semiquantitatively for a number of cellular sites. The expression of all sialyl sequences was increased in absorptive cells and in goblet cells and the expression of 2–6-linked sialyl sequences was enhanced in proportion to the degree of inflammation, while 2–3-linked sialyl sequences were diminished in more severe inflammation. The binding ofN-acetylgalactosaminyl-directed lectins was increased in the Golgi apparatus, while there was a reduction in the expression of -fucosyl sequences in severe degrees of inflammation. This suggests that there is an increased biosynthetic rate for sialyl residues in all stages of disease with a reduction in 2–3-linked sialyl and fucosyl sequences in severe inflammation, and a shift from storedN-acetylgalactosaminyl sequences in goblet cells to an earlier form in the Golgi apparatus. The changes in sialyl sequences are a feature of ulcerative colitis even in quiescent disease and may be related to its aetiology and early pathogenesis, while most of the other changes reflect the severity of the disease and are probably part of its later pathogenesis or of induced reactive changes.     

Glycosylation of α1-acid glycoprotein in inflammatory disease: analysis by high-pH anion-exchange chromatography and concanavalin A crossed affinity immunoelectrophoresis

High-pH anion-exchange chromatography with pulsed amperometric detection is a highly sensitive technique that can be used for detecting changes in sialylation and fucosylation, as well as different branching patterns of N-linked oligosaccharides in glycoproteins. We examined the N-glycans of α1-acid glycoprotein obtained from twelve patients with various inflammatory conditions with this technique, as well as traditional concanavalin A crossed affinity immunoelectrophoresis. We found the chromatographic profiles of N-glycans in all patients with rheumatoid arthritis to be very similar, but significantly different from normal controls. N-glycans from patients with ulcerative colitis also showed specific alterations in their chromatographic profiles. However, some heterogeneity was found between these patients, perhaps reflecting changes in glycosylation secondary to certain states of the disease, or to medical treatment. We conclude that this technique is useful for detailed mapping of glycosylation changes in α1-acid glycoprotein in clinical samples, and that it may be used to further increase our knowledge about glycosylation changes in response to inflammatory disease. Abbreviations: AC, acute cholangitis; AGP, α1-acid glycoprotein; CAIE, crossed affinity immunoelectrophoresis; Con A, concanavalin A; HPAEC-PAD, high-pH anion-exchange chromatography with pulsed amperometric detection; IEC, ion exchange chromatography; RA, rheumatoid arthritis; SLex, sialyl Lex; UC, ulcerative colitis This revised version was published online in November 2006 with corrections to the Cover Date.     

Microcirculatory Rarefaction in South Asians — A Potential Mechanism for Increased Cardiovascular Risk and Diabetes

People of South Asian descent have an increased risk of cardiovascular disease (CVD) and diabetes, but little is known about the microcirculation in South Asian people despite evidence that this plays an important role in the aetiology of CVD. We compared the retinal microcirculation in a population-based sample of 287 middle-aged adults (144 European 143 South Asian) matched for age and sex. Retinal photographs were taken and analysed using a validated semi-automated program and microvascular measures were compared. Blood pressure, anthropometry and fasting bloods were also measured. South Asians had significantly fewer arteriolar and venular vessels and bifurcations. Arterioles and venules were longer and venules were also more tortuous in South Asians. These differences were not explained by adjustment for traditional risk factors including blood pressure, body mass index, diabetes or measures of insulin resistance. People of South Asian descent have rarefaction of the retinal microcirculation compared to age-sex matched individuals of European descent. Reduced microvascular density could contribute to the elevated risk of CVD and impaired glucose tolerance in South Asian people.     

Quiescent stem cells in intestinal homeostasis and cancer

Adult stem cell niches are characterized by a dichotomy of cycling and quiescent stem cells: while the former are responsible for tissue turnover, their quiescent counterparts are thought to become active upon tissue injury thus underlying the regenerative response. Moreover, quiescence prevents adult stem cells from accumulating mutations thus ensuring a reservoir of unaltered stem cells. In the intestine, while cycling stem cells were shown to give rise to the main differentiated lineages, the identity of their quiescent equivalents remains to date elusive. This is of relevance for conditions such as Crohn's disease and ulcerative colitis where quiescent stem cells may underlie metaplasia and the increased cancer risk associated with chronic inflammation. Tumours are thought to share a comparable hierarchical structure of adult tissues with pluripotent and self-renewing cancer stem cells (CSCs) giving rise to more differentiated cellular types. As such, neoplastic lesions may encompass both cycling and quiescent CSCs. Because of their infrequent cycling, quiescent CSCs are refractory to chemo- and radiotherapy and are likely to play a role in tumour dissemination, dormancy and recurrence.     

Quiescent stem cells in intestinal homeostasis and cancer

Abstract

Adult stem cell niches are characterized by a dichotomy of cycling and quiescent stem cells: while the former are responsible for tissue turnover, their quiescent counterparts are thought to become active upon tissue injury thus underlying the regenerative response. Moreover, quiescence prevents adult stem cells from accumulating mutations thus ensuring a reservoir of unaltered stem cells. In the intestine, while cycling stem cells were shown to give rise to the main differentiated lineages, the identity of their quiescent equivalents remains to date elusive. This is of relevance for conditions such as Crohn's disease and ulcerative colitis where quiescent stem cells may underlie metaplasia and the increased cancer risk associated with chronic inflammation. Tumours are thought to share a comparable hierarchical structure of adult tissues with pluripotent and self-renewing cancer stem cells (CSCs) giving rise to more differentiated cellular types. As such, neoplastic lesions may encompass both cycling and quiescent CSCs. Because of their infrequent cycling, quiescent CSCs are refractory to chemo- and radiotherapy and are likely to play a role in tumour dissemination, dormancy and recurrence.     

Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling.     

Intermarriage among new immigrants in the USA

Using the 2003 New Immigrant Survey data, we explore marital behaviour among new immigrants in the USA. Marital assimilation with mainstream US natives was highest among European immigrants, followed by Latin Americans, Southeast Asians, East Asians, and finally South Asians. There is no single ‘Asian’ pattern of marital assimilation. While South Asians and East Asians defy the classical assimilation theory with their strong resistance to intermarriage within the mainstream despite their high degree of structural assimilation, Southeast Asians display high rates of such marital assimilation. Europeans, as predicted by classical theory, evince high rate of marital assimilation. Latin Americans and Southeast Asians lie in between the two extremes of Europeans and other Asian subgroups. While they seem to follow a path of segmented assimilation by demonstrating within-region endogamy, compared to Europeans they have only a slightly higher propensity to marry within their nationality, suggesting ongoing assimilation along classical lines.     

An Investigation of Two-Dimensional Ultrasound Carotid Plaque Presence and Intima Media Thickness in Middle-Aged South Asian and European Men Living in the United Kingdom

Objectives

Ultrasound studies of carotid intima media thickness (cIMT) and plaques are limited in South Asians, a group at elevated cardiovascular disease (CVD) risk. We determined whether South Asians have a difference in these ultrasound markers compared to Europeans living in the United Kingdom and whether measured risk factor(s) could account for any such differences.

Methods

One hundred South Asian men, aged 40 to 70 years and 100 European men of similar age and BMI, without diagnosed CVD or diabetes, underwent carotid ultrasound for measurement of cIMT and carotid plaque presence. Physical activity, cardiorespiratory fitness, anthropometry and blood pressure were assessed, fasted blood taken for measurement of cardiometabolic risk factors and demographic and lifestyle factors recorded.

Results

Age-adjusted mean (SD) cIMT was similar in South Asians and Europeans (0.64 (0.16) mm v 0.65 (0.12) mm, p = 0.64). Plaque was present in 48 South Asians and 37 Europeans and overall, there was no age-adjusted difference between South Asian and Europeans for plaque score(odds ratio 1.49, 95% CI, 0.86-2.80, p = 0.16), however, South Asians appeared to have more plaques at a younger age than Europeans; at age 40-50 years the odds of South Asians having plaques was 2.63 (95% CI, 1.16-5.93) times that for Europeans.

Conclusions

cIMT is similar between healthy South Asian and European men. Whilst there was no overall difference in plaque presence in South Asians, there is an indication of greater plaque prevalence at younger ages - an observation requiring further investigation. Prospective studies linking plaques to CVD outcomes in South Asians are needed to investigate whether these measures help improve CVD risk prediction.     

Ultrastructural study of inflammatory bowel disease.

Ultrastructural changes that occurred in chronic active ulcerative colitis and Crohn's disease were investigated and compared to normal as well as to higher grades of dysplasia in adenomas and carcinomas. A greater number of immature absorptive cells, undifferentiated and intermediate cells were seen as compared to normal. One case of Crohn's and two cases of chronic ulcerative colitis including one with coexisting carcinoma showed increased number of vesicles and electron-dense bodies (EDB) in the absorptive cells and increased heterogeneity of mucin droplets in goblet cells and presence of atypical secretory cells (ASC). Higher grades of dysplasia characterised by large numbers of atypical secretory cells were not seen in the present series and provide no relationship between the atypical ultrastructural features and increased risk of malignancy. However, the number of cases investigated is too small and a large series is required to clarify the significance of observations such as increased number of electron-dense bodies and vesicles in the apical cytoplasm and presence of atypical secretory cells.     

亚洲地区人类群体亲缘关系：活体测量数据统计分析

本文采用多元统计方法分析了亚洲地区２５个人群的活体测量资料以探讨亚洲地区各人类群体之间的相互关系,数据分析结果显示这一地区的人类按活体特征的差异可以划分为两大类型。包括中国、朝鲜、日本等东北亚的人类构成一个组群;东南亚的人类形成另一个组群。南亚地区的人类在分类上与东南亚的人类接近但仍呈现一些特殊性。日本列岛的人类具有两种体质特征类型。本岛居民与东北亚人类接近;而包括阿伊努、硫球群岛岛民及台湾土著在     

Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (colitis ulcerosa)

Ulcerative colitis (colitis ulcerosa) is a non-specific inflammatory bowel disease of unknown etiology. The symptoms which are observed in the course of ulcerative colitis are: an increase in the number of leukocytes and blood platelets, an increase in the concentration of IL-6 and anemia. Blood platelets are the key element, linking the processes of hemostasis, inflammation and the repair of damaged tissues. Activation of blood platelets is connected with changes in their shape and the occurrence of the reaction of release. P-selectin appears on the surfaces of activated blood platelets and the concentration level of soluble P-selectin increases in the blood plasma. The aim of this study was to define whether the increased number of blood platelets in patients with ulcerative colitis accompanies changes in their activation and morphology. A total of 16 subjects with ulcerative colitis and 32 healthy subjects were studied. Mean platelet count, morphological parameters of platelets and MPC were measured using an ADVIA 120 hematology analyzer. Concentrations of sP-selectin and IL-6 in serum were marked by immunoassay (ELISA). MPC, concentration of sP-selectin and IL-6 were significantly higher in subjects with ulcerative colitis compared to those in the healthy group. There was a decrease of MPV in patients with ulcerative colitis, which is statistically significant. Chronic inflammation in patients with ulcerative colitis causes an increase in the number of blood platelets, a change in their morphology and activation. Decreased MPV value reflects activation and the role blood platelets play in the inflammatory process of the mucous membrane of the colon. A high concentration of sP-selectin, which is a marker of blood platelet activation, demonstrates their part in the inflammatory process. The increase in the concentration of sP-selectin correlated positively with the increase in concentration of IL-6. This is why it may be a useful marker of the activity of colitis ulcerosa.     

Colonic mucins in ulcerative colitis: evidence for loss of sulfation

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [³⁵S] sulfate and [³H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by -elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed >90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.Abbreviations WGA wheat germ agglutinin - UC ulcerative colitis - HRP horseradish peroxidase     

Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis

Increased sialylation of cell surface glycoconjugates is among the key molecular changes associated with malignant transformation and cancer progression. We investigated significance of linkage-specific sialylation changes in oral carcinogenesis. Tissue and serum levels of total sialic acid (TSA), linkage-specific sialyltransferases (ST) and sialoproteins were analyzed from patients with oral precancerous conditions (OPC) and oral cancer as well as the post-treatment follow-up blood samples of oral cancer patients. TSA levels were measured using a spectrophotometric method. The linkage-specific lectins, Sambusus nigra (SNA) and Maackia amurensis (MAM) detects α2-6- and α2-3-linked sialic acid, respectively, were used to analyze ST activity and sialoproteins. Malignant tissues showed significantly higher levels of TSA, reactivity of SNA and MAM, and α2,3-ST activity compared to the adjacent normal tissues. α2,6-ST was also higher in malignant tissues. Similarly, the marker levels were higher in precancerous tissues than their adjacent normal tissues. Serum levels of TSA, TSA/ total proteins, α2-6-sialoproteins and α2,6-ST were markedly increased in untreated oral cancer patients compared to the controls and OPC as well as responder (CR) patients. Serum levels of the markers were higher or comparable between untreated oral cancer patients and non-responders (NR). Serum levels of α2-3-sialylation were elevated in non-responders compared with the responders. Further, the observed sialylation changes in tissue and serum were found to be associated with various clinicopathological features and disease progression. Thus, the data suggest potential utility of sialylation markers in early detection, prognostication and treatment monitoring of oral cancer.     

Should Physical Activity Recommendations Be Ethnicity-Specific? Evidence from a Cross-Sectional Study of South Asian and European Men

Background

Expert bodies and health organisations recommend that adults undertake at least 150 min.week⁻¹ of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week⁻¹.

Methods

Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week⁻¹ MPA.

Findings

For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week⁻¹; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week⁻¹.

Conclusions

South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.     

Ethnic‐Specific Differences in Abdominal Subcutaneous Adipose Tissue Compartments

South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat‐free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X‐ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm² vs. 145.15 cm², P < 0.001), SSAT (median 92.0 cm² vs. 76.1 cm², P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.     

The use of BMI and waist circumference as surrogates of body fat differs by ethnicity

Objective: To compare the prediction of percentage body fat using BMI and visceral adipose tissue (VAT) using waist circumference (WC) in individuals of Chinese, European, and South Asian origin. Research Methods and Procedures: Healthy men and women of Chinese, European, and South Asian origin (n = 627) between the ages of 30 and 65 years were recruited to ensure equal distribution of gender and representation across BMI ranges (18.5 to 24.9, 25 to 29.9, and ≥30 kg/m²). Participants were assessed for demographics, anthropometry, lifestyle, and regional adiposity. Percentage body fat and VAT were measured by DXA and computer tomography scan, respectively. Results: BMI and WC were highly correlated with total and regional measures of adiposity in each ethnic group. At any BMI, the percentage body fat of Chinese participants was similar to that of Europeans, but that of South Asians was greater by 3.9% (p < 0.001). Above a WC of 71.0 cm, the Chinese participants had an increasingly greater amount of VAT than the Europeans (p = 0.017 for interaction). South Asians had significantly more VAT than the Europeans at all but the most extreme WC (above 105 cm) (p < 0.05). Discussion: Compared with Europeans, percentage body fat was higher for a given BMI in South Asians, whereas VAT was higher for a given WC in both Chinese and South Asian men and women. These findings support the use of ethnic‐specific anthropometric targets.     

Risk Factors for Acute Stroke among South Asians Compared to Other Racial/Ethnic Groups

Background

Studies of racial/ethnic variations in stroke rarely consider the South Asian population, one of the fastest growing sub-groups in the United States. This study compared risk factors for stroke among South Asians with those for whites, African-Americans, and Hispanics.

Methods

Data on 3290 stroke patients were analyzed to examine risk differences among the four racial/ethnic groups. Data on 3290 patients admitted to a regional stroke center were analyzed to examine risk differences for ischemic stroke (including subtypes of small and large vessel disease) among South Asians, whites, African Americans and Hispanics.

Results

South Asians were younger and had higher rates of diabetes mellitus, blood pressure, and fasting blood glucose levels than other race/ethnicities. Prevalence of diabetic and antiplatelet medication use, as well as the incidence of small-artery occlusion ischemic stroke was also higher among South Asians. South Asians were almost a decade younger and had comparable socioeconomic levels as whites; however, their stroke risk factors were comparable to that of African Americans and Hispanics.

Discussion

Observed differences in stroke may be explained by dietary and life style choices of South Asian-Americans, risk factors that are potentially modifiable. Future population and epidemiologic studies should consider growing ethnic minority groups in the examination of the nature, outcome, and medical care profiles of stroke.     

Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes

BackgroundThe Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.Conclusions/SignificanceAlthough only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.     

Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn's disease

Summary. Nitric oxide synthase (NOS) activities are responsible for the enzymatic conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO are produced in intestinal epithelial cells or are released from nerve endings. The effects of NO production are related to the maintenance of epithelial integrity and permeability. A pathological role of an increased NO production has been suggested to play a role in models of experimental colitis. In humans, NOS activity in colon mucosa from patients with ulcerative colitis is clearly increased when compared with the activity of the control group. In contrast, an increase of NOS activity in the colon mucosa from patients with Crohn's disease remains controversial. In the present work, we have measured NOS activity in colon biopsies originating from the control group (n = 16), from patients with ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical method of the conversion of L-[guanido-¹⁴C] arginine into radioactive L-citrulline. In the control group, NOS activity was mainly of the inducible type (88% of total NOS activity) since it was characterised by its insensibility to the absence of calcium in the assay medium. In colon biopsies originating from patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p < 0.005) and in patients with Crohn's disease, inducible NOS activity was increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies and the intensity parameters of the disease i.e. Truelove index, endoscopic score and histo-logical parameters were evidenced in patients with ulcerative colitis. In contrast, in patients with Crohn's disease, the high inducible NOS activity was not correlated with any intensity parameters of the disease. From these data, we concluded that although inducible NOS activity was increased several fold in colon biopsies originating from patients with both ulcerative colitis and Crohn's disease, a correlation between this activity and the severity of bowel inflammation was not found in either cases. Received August 7, 1999