Immunohistologic demonstration of abnormal colonic crypt cell kinetics in ulcerative colitis

Franklin, Wilbur A.; McDonald, George B.; Stein, Harald; Gatter, Kevin C.; Jewell, D P; Clarke, Lisa; Mason, David Y.

doi:10.1016/s0046-8177(85)80181-7

Cited by 77 publications

(28 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kendall's test revealed a positive correlation of low statistical significance between Ki-67 positivity and this parameter (tau: 0.1566; p < 0.02). These results are summarized in table 6. 92 tumors were examined for axillary lymph node involvement.…”

Section: Resultsmentioning

confidence: 99%

K-67 Immunoreactivity in Breast Carcinomas in Relation to Transferrin Receptor Expression, Estrogen Receptor Status and Morphological Criteria

Wrba¹,

Chott²,

Reiner³

et al. 1989

Oncology

View full text Add to dashboard Cite

The number of proliferating cells was determined by Ki-67 antibody in 107 primary breast carcinomas. These results were compared with transferrin receptor (Trf R) expression, estrogen receptor (ER) status, histologic type, tumor grade, size and axillary lymph node status. The percentage of Ki-67-positive cells ranged from 0.9 to 26.4%. The proportion of Ki-67-positive cells was highest in medullary carcinomas. Immunoreactivity of Ki-67 in realtion to TrfR expression showed significant correlation (p = 0.0001). An inverse relationship between ER status and Ki-67 positivity existed (p = 0.0001). 88 cases were subjected to histologic grading. There was a significant relationship showing an increase of Ki-67 immunoreactivity with decrease of tumor differentiation (p = 0.0001). The distribution of Ki-67 reactivity in relation to tumor size and nodal status of the axilla revealed positive correlations (p = 0.02; p <0.05). In conclusion, the use of Ki-67 monoclonal antibody as a marker for cell proliferation represents a method to get kinetic data inhering prognostic value.

show abstract

Section: Resultsmentioning

confidence: 99%

K-67 Immunoreactivity in Breast Carcinomas in Relation to Transferrin Receptor Expression, Estrogen Receptor Status and Morphological Criteria

Wrba¹,

Chott²,

Reiner³

et al. 1989

Oncology

View full text Add to dashboard Cite

show abstract

“…During active inflammation, there is an accelerated migration and enhanced loss of ECs at the luminal surface, resulting in a greatly increased cell turnover (3,14). Thus there may be not enough time to induce the changes caused by physiological cell aging and oxidative damage, including the normal amount of mtDNA deletions.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis patients

Fukushima¹,

Fiocchi²

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Fukushima, Kouhei, and Claudio Fiocchi. Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis patients. Am J Physiol Gastrointest Liver Physiol 286: G804-G813, 2004; 10.1152/ajpgi.00398.2003.-Ulcerative colitis (UC) is a condition characterized by chronic inflammation targeted at the epithelial layer. In addition to being involved in immune phenomena, UC epithelial cells exhibit decreased oxidation of butyrate, downregulation of oxidative pathway regulatory genes, and overexpression of mitochondrial (mt) genes. We investigated whether these events, which translate an altered energy metabolism, are associated with an abnormal pattern of mtDNA deletions. Highly purified colonocytes were isolated from surgically resected control, involved and uninvolved inflammatory bowel disease mucosa. The frequency, type, and number of mtDNA deletions were assessed by PCR amplification, Southern blot analysis, and cloning and sequencing of amplified DNA fragments. The 4977 mtDNA deletion was less frequent in UC than control and Crohn's disease (CD) epithelium, regardless of patient age. Several other deletions were detected, but all were less common in UC than control and CD cells. The frequency, variety, and number of mtDNA deletions were invariably lower in colonocytes isolated from inflamed mucosa than in autologous cells from noninflamed mucosa. In conclusion, in the absence of inflammation, UC colonocytes exhibit an mtDNA deletion pattern similar to that of control cells, indicating a normal response to physiological levels of oxidative stress. In active inflammation, when oxidative stress increases, the frequency, variety, and number of mtDNA deletions decrease. Because comparable abnormalities are absent in active CD, the mtDNA deletion pattern of active UC suggests that colonocytes respond uniquely to inflammation-associated stress in this condition. epithelium; energy metabolism ALTHOUGH THE ETIOLOGY OF ULCERATIVE colitis (UC) is still uncertain, colonic epithelial cells (EC) have long been considered central to its pathophysiology. In addition to the restriction of the inflammatory process and associated dysplastic changes to the epithelial lining (43), there is abundant experimental evidence pointing to colonocytes as likely targets and mediators of key pathogenic events. Detection of circulating colon antibodies and cytotoxic mononuclear cells in UC patients initially suggested that colonocytes could be targets of autoimmune reactivity (6, 49). Subsequent studies demonstrated that in UC, EC express high levels of human leukocyte antigen D-related antigens (48), secrete abnormal mucin glycoconjugates (41), produce increased amounts of cytokines and chemokines (4,42,57), express costimulatory molecules (39), display autoantigens recognized exclusively by UC tissueeluted antibodies (53), and fail to mediate induction of suppressor T cells (36). Additional reports demonstrated cyclooxygenase 2 and NF-B activation (46, 51), as well as an increased rate of EC apoptosis in UC (...

show abstract

“…52,53 It is a possibility that increased proliferation rates in IBD promote increased plasticity at cell-cell contacts and change the regulation of tight junction claudin 2 expression. In 7-day confluent T84-cell monolayers, many proliferating cells were seen, dispersed among cells out of cycle, using the cell cycle marker Ki 67, whereas claudin 2 was expressed in small clusters of cells (Figures 8a and b).…”

Section: Expression Of Claudin 2 In An Intact Epithelial Barrier Doesmentioning

confidence: 99%

“…Increased rates of cell division and cell movement/shedding have been reported in IBD 52,53 prompting speculation that the increased expression of claudin 2 might be related to cell division or increased plasticity of tight junctions in disease. However, a recent study of fetal human colon, at 18-20 weeks gestation, revealed claudin 2 staining in the undifferentiated cells at the bases of developing colonic crypts with loss of staining as the cells differentiate, suggesting that the loss of expression of claudin 2 in normal tissue may relate to differentiation.…”

Section: Inflammatory Cytokines and Claudin Expressionmentioning

confidence: 99%

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

Prasad

Mingrino

Kaukinen

et al. 2005

Laboratory Investigation

427

384

View full text Add to dashboard Cite

Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along the inflamed crypt epithelium, whilst absent or barely detectable in normal colon. In contrast, CL 3 and 4 were present throughout normal colonic epithelium and were reduced or redistributed in the diseased surface epithelium. In a T84-cell culture model of the gut barrier, paracellular permeability decreased with time after plating and correlated with a marked decrease in the expression of CL 2. Addition of IFNc/TNFa led to further decreases in CL 2 and 3, the redistrbution of CL 4 and a marked increase in paracellular permeability. Conversely, IL-13 dramatically increased CL 2, with little effect on CL 3 or 4, but also resulted in increased paracellular permeability. Expression of CL 2 did not correlate with proliferation or junctional reorganisation after calcium ion depletion. Re-expression of CL 2 in response to IL-13 was inhibited by phophatidylinositol 3 kinase inhibitor, LY294002, which also restored the ion permeability to previous levels. CL 2 expression could be stimulated in the absence of IL-13 by activation of phospho-Akt in the phophatidylinositol 3 kinase pathway. These results suggest that INFc/TNFa and IL-13 have differential effects on CL 2, 3 and 4 in tight junctions, which may lead to increased permeability via different mechanisms.

show abstract

Immunohistologic demonstration of abnormal colonic crypt cell kinetics in ulcerative colitis

Cited by 77 publications

References 8 publications

K-67 Immunoreactivity in Breast Carcinomas in Relation to Transferrin Receptor Expression, Estrogen Receptor Status and Morphological Criteria

K-67 Immunoreactivity in Breast Carcinomas in Relation to Transferrin Receptor Expression, Estrogen Receptor Status and Morphological Criteria

Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis patients

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

Contact Info

Product

Resources

About