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J R Turner

Publications and source records attributed to J R Turner.

At least 19 recordsLinked to original sources
PubMed2001

Clostridium difficile toxins disrupt epithelial barrier function by altering membrane microdomain localization of tight junction proteins.

The anaerobic bacterium Clostridium difficile is the etiologic agent of pseudomembranous colitis. C. difficile toxins TcdA and TcdB are UDP-glucosyltransferases that monoglucosylate and thereby inactivate the Rho family of GTPases (W. P. Ciesla, Jr., and D. A. Bobak, J. Biol. Chem. 273:16021-16026, 1998). We utilized purified reference toxins of C. difficile, TcdA-10463 (TcdA) and TcdB-10463 (TcdB), and a model intestinal epithelial cell line to characterize their influence on tight-junction (TJ) organization and hence to analyze the mechanisms by which they contribute to the enhanced paracellular permeability and disease pathophysiology of pseudomembranous colitis. The increase in paracellular permeability induced by TcdA and TcdB was associated with disorganization of apical and basal F-actin. F-actin restructuring was paralleled by dissociation of occludin, ZO-1, and ZO-2 from the lateral TJ membrane without influencing the subjacent adherens junction protein, E-cadherin. In addition, we observed decreased association of actin with the TJ cytoplasmic plaque protein ZO-1. Differential detergent extraction and fractionation in sucrose density gradients revealed TcdB-induced redistribution of occludin and ZO-1 from detergent-insoluble fractions constituting "raft-like" membrane microdomains, suggesting an important role of Rho proteins in maintaining the association of TJ proteins with such microdomains. These toxin-mediated effects on actin and TJ structure provide a mechanism for early events in the pathophysiology of pseudomembranous colitis.

Actins↗
PubMed2000

Show me the pathway! Regulation of paracellular permeability by Na(+)-glucose cotransport.

The physiological impact of Na(+)-nutrient cotransport-dependent regulation of intestinal tight junction permeability has been controversial. Nonetheless, increased permeability of small intestinal mucosae and enterocyte tight junctions as a consequence of Na(+)-nutrient cotransport has been documented by a significant number of in vivo and in vitro studies. Some details of the intracellular signaling events that regulate this process have been described recently. The aims of this article are to: (i) review studies of tight junction regulation and paracellular nutrient absorption in mammalian intestine, (ii) identify potential applications of tight junction regulation, and (iii) summarize recent progress in defining molecular mechanisms that lead to altered tight junction permeability.

Absorption↗
PubMed2000

Pericolonic tumor deposits in patients with T3N+MO colon adenocarcinomas: markers of reduced disease free survival and intra-abdominal metastases and their implications for TNM classification.

BACKGROUND: A pericolonic tumor deposit (PTD) is a grossly palpated adenocarcinomas within pericolonic adipose tissue not within a lymph node. The source and prognostic significance of PTDs has not been well defined. METHODS: The authors studied 418 T3N+M0 colon adenocarcinomas to determine the frequency and significance of PTDs. They also step-sectioned 30 PTDs to determine their origin and assist in their optimum TNM classification. RESULTS: Seventy-one (18%) of 400 consecutively examined cases had PTDs. The actuarial 1-, 2-, and 5-year disease free survival rates were significantly lower among patients with a PTD. PTDs, regardless of size, significantly impacted disease free survival. Increasing numbers of PTDs was associated with shorter disease free survival. Adenocarcinoma grade, a PTD, increasing numbers of PTDs, and number of lymph node metastases were independently associated with shorter disease free survival. The likelihood of extrahepatic abdominal failure was proportionally greater with increasing numbers of PTDs. Adenocarcinoma was observed in perineural, peri-large vessel, or intravascular locations in step-sectioned PTDs. CONCLUSIONS: A PTD is a perineural, perivascular, or intravascular tumor extension beyond the muscularis propria. They are distinct from lymph node metastases and should not be considered their prognostic equivalent. The disease free survival impact of even small PTDs was significant, suggesting that PTDs of all sizes should be considered a single entity. TNM classification of PTDs as lymph node metastases or discontinuous tumor extension is probably not accurate. The number and greatest dimension of PTDs should be reported separately from lymph node metastases.

Adenocarcinoma↗
PubMed2000

'Putting the squeeze' on the tight junction: understanding cytoskeletal regulation.

The apical perijunctional actomyosin ring of epithelia is structurally associated with the tight junction. The functional association between the tight junction and the perijunctional actomyosin ring was initially described in studies using pharmacological agents that disrupt microfilaments. More recently, this interaction has been studied in physiological, pathophysiological, and molecular models of tight junction regulation. These studies have demonstrated the central role of actomyosin contraction in tight junction regulation. With the identification of novel tight junction proteins and characterization of their protein:protein interactions comes the promise of detailed understanding of the molecular interactions that mediate tight junction regulation.

Actomyosin↗
PubMed2000

Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma.

A variety of prognostic markers have been related to decreased patient survival in patients with epithelial malignancies. These include expression of the homotypic adhesion molecule E-cadherin (ECAD) and the hyaluronic acid receptor CD44. Expression of ECAD and CD44 was evaluated in Barrett's-associated adenocarcinoma (BAd) from 67 patients. Expression was determined by immunoperoxidase staining and graded semiquantitatively based on the proportion of positively stained cells. These data were then correlated with clinical and pathological parameters, including the presence or absence of chemoradiotherapy (chemrad) and patient survival. There were 56 men and 11 women (mean age, 62 years). Thirty-nine (58%) patients received preoperative chemrad. ECAD expression was detected in all (100%) tumors. The ECAD staining grade did not correlate with other pathological features of the tumors. However, ECAD staining was significantly increased in BAd of patients who received chemrad (P = .003), in comparison with those who did not, and in individual patients when prechemrad biopsies and postchemrad resection specimens were compared (P = .04). In terms of prognosis, increased ECAD expression was associated with shortened patient survival only in BAd patients who had received chemrad (univariate analysis of chemrad patients with stage I and II BAd, P = .02). ECAD expression was not significantly associated with survival in BAd patients who did not receive chemrad. CD44 expression was detected in 88% of cases. CD44 expression did not correlate with any of the pathological features of the tumors or with chemrad status. Increased expression of CD44 was significantly associated with shortened patient survival in chemrad patients only (univariate analysis P = .03, multivariate analysis P = .04), although a strong trend was observed when all patients were analyzed regardless of chemrad status (P = .07). The results of this study indicate that chemrad alters the expression of ECAD in BAd. Thus, the prognostic utility of ECAD expression must be evaluated in the context of chemrad status. CD44 also may be a valuable prognostic marker in BAd.

Adenocarcinoma↗
PubMed2000

Mink cell focus-forming murine leukemia virus infection induces apoptosis of thymic lymphocytes.

In a previous study we identified the subpopulations of thymus cells that were infected by the lymphomagenic MCF13 murine leukemia virus (MLV) (F. K. Yoshimura, T. Wang, and M. Cankovic, J. Virol. 73:4890-4898, 1999) and observed an effect on thymus size by virus infection. In this report we describe our results which demonstrate that MCF13 MLV infection of thymuses reduced the number of T lymphocytes in this organ. Histological examination showed diffuse lymphocyte depletion, which was most striking in the CD4(+) CD8(+) lymphocyte-enriched cortical zone. Consistent with this, flow cytometric analysis showed that the lymphocytes which were depleted were predominantly the immature CD3(-) CD4(+) CD8(+) and CD3(+) CD4(+) CD8(+) cells. A comparison of the percentages of live, apoptotic, and dead cells of the gp70(+) and gp70(-) thymic lymphocytes suggested that this effect on thymus cellularity is a result of virus infection. Studies of the survival of thymic T lymphocytes in culture showed that cells from MCF13 MLV-inoculated mice underwent greater apoptosis and death than cells from control animals. Assays for apoptosis included 7-amino-actinomycin D staining, DNA fragmentation, and cleavage of caspase-3 and poly(ADP-ribose) polymerase proenzymes. Our results suggest that apoptosis of thymic lymphocytes by virus infection is an important step in the early stages of MCF13 MLV tumorigenesis.

Animals↗
PubMed2000

Transepithelial resistance can be regulated by the intestinal brush-border Na(+)/H(+) exchanger NHE3.

Initiation of intestinal Na(+)-glucose cotransport results in transient cell swelling and sustained increases in tight junction permeability. Since Na(+)/H(+) exchange has been implicated in volume regulation after physiological cell swelling, we hypothesized that Na(+)/H(+) exchange might also be required for Na(+)-glucose cotransport-dependent tight junction regulation. In Caco-2 monolayers with active Na(+)-glucose cotransport, inhibition of Na(+)/H(+) exchange with 200 microM 5-(N,N-dimethyl)- amiloride induced 36 +/- 2% increases in transepithelial resistance (TER). Evaluation using multiple Na(+)/H(+) exchange inhibitors showed that inhibition of the Na(+)/H(+) exchanger 3 (NHE3) isoform was most closely related to TER increases. TER increases due to NHE3 inhibition were related to cytoplasmic acidification because cytoplasmic alkalinization with 5 mM NH(4)Cl prevented both cytoplasmic acidification and TER increases. However, NHE3 inhibition did not affect TER when Na(+)-glucose cotransport was inhibited. Myosin II regulatory light chain (MLC) phosphorylation decreased up to 43 +/- 5% after inhibition of Na(+)/H(+) exchange, similar to previous studies that associate decreased MLC phosphorylation with increased TER after inhibition of Na(+)-glucose cotransport. However, NHE3 inhibitors did not diminish Na(+)-glucose cotransport. These data demonstrate that inhibition of NHE3 results in decreased MLC phosphorylation and increased TER and suggest that NHE3 may participate in the signaling pathway of Na(+)-glucose cotransport-dependent tight junction regulation.

Acids↗
PubMed2000

Aging alters gastric mucosal responses to epidermal growth factor and transforming growth factor-alpha.

Administration of pharmacological doses of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) in young rats stimulates gastric mucosal proliferation, but, in aged rats, the same treatment inhibits proliferation. This may be due to enhanced ligand-induced internalization of EGF receptor (EGFR). In support of this, we demonstrated that although a single injection of EGF (10 microg/kg) or TGF-alpha (5 microg/kg) in young (4-6 mo old) rats greatly increased membrane-associated EGFR tyrosine kinase activity, the same treatment slightly inhibited the enzyme activity in aged (24 mo old) rats. This treatment also produced a greater abundance of punctate cytoplasmic EGFR staining in gastric epithelium of aged rats, consistent with EGFR internalization. In vitro analyses demonstrated that exposure of isolated gastric mucosal cells from aged but not young rats to 100 pM TGF-alpha resulted in marked increases in intracellular EGFR tyrosine kinase activity and that induction of EGFR tyrosine kinase activity in mucosal membranes from aged rats occurred at doses 1,000-fold less than those required in young rats. Our data suggest that aging enhances sensitivity of the gastric mucosa to EGFR ligands. This may partly explain EGFR-mediated inhibition of gastric mucosal proliferation in aged rats.

Aging↗
PubMed2000

Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells.

The epithelial lining of the gastrointestinal tract forms a regulated, selectively permeable barrier between luminal contents and the underlying tissue compartments. Permeability across the epithelium is, in part, determined by the rate-limiting barrier of the paracellular pathway-the most apical intercellular junction referred to as the tight junction (TJ). The TJ is composed of a multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ structure and function, and therefore epithelial permeability, are influenced by diverse physiological and pathological stimuli; here we review examples of such stimuli that are detected at the cell surface. For example, luminal glucose induces an increase in paracellular permeability to small molecules. Similarly, but by other means, cytokines and leukocytes in the vicinity of the epithelium also regulate TJ structure and paracellular permeability by influencing the TJ protein complex and/or its association with the underlying actin cytoskeleton.

Cytokines↗
PubMed2000

Ethnicity and socioeconomic status: impact on cardiovascular activity at rest and during stress in youth with a family history of hypertension.

OBJECTIVE: The purpose of the present study was to examine the potential interaction of ethnicity and SES on hemodynamic functioning at rest and during acute stress in normotensive adolescents with a family history of essential hypertension (EH). DESIGN: The influences of ethnicity and socioeconomic status (SES) on cardiovascular function were evaluated at rest and in response to five different laboratory stressors. METHODS: 110 (50 female) Caucasian and 162 (85 female) African-American normotensive youth (initial age 11.2+/-2.4 years) with a family history of essential hypertension (EH) were tested on two occasions, an average of 2.5 years apart. Based on previous findings, it was predicted that African Americans, particularly those of low SES, would exhibit higher resting blood pressure (BP) and greater cardiovascular reactivity to acute laboratory stressors than would Caucasians. RESULTS: As predicted, African-American youth exhibited higher resting diastolic blood pressure (DBP) and total peripheral resistance (TPR) than Caucasians on both visits (both Ps<.04). African Americans exhibited greater systolic blood pressure (SBP) reactivity than did Caucasians to the video game stressor during both lab visits (both Ps<.02) and greater heart rate reactivity during the first lab visit (P<.01). African Americans exhibited greater SBP and/or DBP, and TPR reactivity to the cold pressor during the first lab visit and the parent-child discussion during the second visit (all Ps<.03). CONCLUSION: As predicted, African Americans exhibited higher resting BP and TPR, and greater cardiovascular reactivity than Caucasians. Although not in the predicted direction, a pattern of interactions began to emerge on the second evaluation. For example, upper SES youth exhibited greater heart rate reactivity compared to all other groups on the social competence interview and parent-child discussion stressors. Further study is needed to clarify the role cardiovascular reactivity may play in the link between ethnicity, SES, and cardiovascular disease risk.

Adolescent↗
PubMed1999

The prognostic significance of lymph node micrometastasis in patients with esophageal carcinoma.

BACKGROUND: Lymph node metastasis is a well known feature of poor prognosis in patients with esophageal adenocarcinoma and squamous cell carcinoma. However, a significant proportion of apparently lymph node negative patients die early of metastatic disease. The aim of this study was to determine the prevalence and prognostic significance of occult lymph node metastasis in patients with esophageal adenocarcinoma and squamous cell carcinoma. METHODS: Lymph node sections from esophagectomy specimens of 78 patients with lymph node negative esophageal carcinoma (49 patients with adenocarcinoma and 29 with squamous cell carcinoma) were cut serially, it toto, and immunostained with the cytokeratin antibody AE1/AE3 and evaluated for occult lymph node metastasis. The results were correlated with the clinical and pathologic features and with patient survival. RESULTS: Fifteen of 49 patients (31%) with adenocarcinoma and 5 of 29 patients (17%) with squamous cell carcinoma had occult lymph node metastasis detected by cytokeratin staining. In the adenocarcinoma patients, the presence of occult lymph node metastasis showed a significant correlation with increasing depth of invasion, but was not associated significantly with any other clinical or pathologic feature. In the squamous cell carcinoma patients, the presence of occult lymph node metastasis did not correlate significantly with any clinical or pathologic parameter, except that patients with occult lymph node metastasis were more likely to have received preoperative chemotherapy or radiation therapy. Occult lymph node metastasis did not correlate with poorer survival rates in patients with either adenocarcinoma (Cox proportional hazards ratio: 1.42; P - 0.46) or squamous cell carcinoma (Cox proportional hazards ratio: 0.86; P = 0.90). CONCLUSIONS: Occult lymph node metastasis is not an independent poor prognostic feature in esophageal adenocarcinoma or squamous cell carcinoma. Therefore, the authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostication of patients with these malignancies.

Adenocarcinoma↗
PubMed1999

Pathologic prognostic factors in Barrett's associated adenocarcinoma: a follow-up study of 96 patients.

BACKGROUND: The objective of this study was to evaluate a variety of histologic features, some of which to our knowledge have never been evaluated in Barrett's-associated adenocarcinoma (BAd) (such as Crohn's-like lymphoid reaction and peritumoral lymphoid response) in patients with and without preoperative neoadjuvant chemotherapy combined with radiotherapy (chemrad) to determine their prognostic significance in these two groups of patients. METHODS: Tumor sections from 96 patients (83 males and 13 females; mean age, 62 years) with resected BAd (61 with chemrad and 35 without chemrad) were evaluated for numerous histologic features such as pathologic stage according to the American Joint Committee on Cancer TNM staging system, peritumoral lymphoid infiltrate, Crohn's-like lymphoid reaction, and degree of post chemrad residual tumor and correlated with the preoperative chemrad status and with survival (mean follow-up, 23 months). RESULTS: By univariate analysis, older patient age (P = 0.02), higher pathologic stage (P = 0.02) (including depth of invasion and lymph node status), infiltrative growth pattern (P = 0.05), perineural invasion (P = 0.05), vascular invasion (P = 0.04), and the absence of a peritumoral lymphoid infiltrate (P = 0.04) were associated with shortened survival in the entire cohort and in patients without chemrad, with the exception of infiltrative growth pattern (P = 0.1 in the nonchemrad group only). Higher stage was the only feature associated with decreased survival in the chemrad group. Subcategorization of lymph nodes according to the number involved with metastases (fewer than four, four to seven, and greater than seven) had no further effect on prognosis. However, subcategorization of T1 tumors into Tla and T1b did influence prognosis in a negative manner. Using multivariate analysis, only older patient age (P = 0.005) and the absence of a peritumoral lymphoid infiltrate (P = 0.05) were statistically associated with poor survival independent of stage. In addition, perineural invasion (P = 0.07) showed a trend toward shortened survival in patients with this feature. Preoperative chemrad had no effect on survival in this retrospective nonrandomized cohort of patients. CONCLUSIONS: This study confirms the strong prognostic usefulness of the TNM staging system in patients with resected BAd, even in those patients who received preoperative chemrad. In addition, older patient age, the absence of a peritumoral lymphoid infiltrate, and possibly perineural invasion correlate with poor survival independent of pathologic stage in patients with these tumors.

Adenocarcinoma↗
PubMed1999

Effects of race, sex, and socioeconomic status upon cardiovascular stress responsivity and recovery in youth.

Cardiovascular (CV) responsivity to and recovery from acute laboratory stressors, as derived from aggregate scores of CV functioning during and after postural change, video game challenge, social competence interview, and parent-child conflict discussion, were evaluated in 272 youths [mean age 13.5 +/- 2.6 years; 162 Blacks (77 males, 85 females), 110 Whites (60 males, 50 females)], all with a positive family history of essential hypertension. Blacks demonstrated greater systolic and diastolic blood pressure (SBP, DBP) and lower heart rate responsivity compared to Whites (all P values < 0.05). A race by neighborhood socioeconomic status (SES) interaction for SBP responsivity was also observed where low SES Whites and high SES Blacks had the greatest responsivity compared to their same race cohorts. Additionally, upper SES Whites had the lowest total peripheral resistance responsivity. For recovery, Blacks and males exhibited higher SBP during recovery compared to Whites and females, respectively. These findings extend previous studies and provide further support for the hypothesis that recovery from stress is a potentially informative component of the contribution of stress responsivity to cardiovascular disease.

Adolescent↗
PubMed1999

PKC-dependent regulation of transepithelial resistance: roles of MLC and MLC kinase.

The mechanisms by which protein kinase C (PKC) activation results in increased transepithelial resistance (TER) are unknown [G. Hecht, B. Robinson, and A. Koutsouris. Am. J. Physiol. 266 (Gastrointest. Liver Physiol. 29): G214-G221, 1994]. We have previously shown that phosphorylation of the regulatory light chain of myosin II (MLC) is associated with decreases in TER and have suggested that contraction of the perijunctional actomyosin ring (PAMR) increases tight junction (TJ) permeability [J. R. Turner, B. K. Rill, S. L. Carlson, D. Carnes, R. Kerner, R. J. Mrsny, and J. L. Madara. Am. J. Physiol. 273 (Cell Physiol. 42): C1378-C1385, 1997]. We therefore hypothesized that PKC activation alters TER via relaxation of the PAMR. Activation of PKC by the phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in a progressive dose-dependent increase in TER that was apparent within 15 min (111% of controls) and maximal within 2 h (142% of controls). Similar increases were induced by a diacylglycerol analog, and the effects of both PMA and the diacylglycerol analog were prevented by the PKC inhibitor bisindolylmaleimide I. PMA treatment caused progressive decreases in MLC phosphorylation, by 12% at 15 min and 41% at 2 h. Phosphorylation of MLC kinase (MLCK) increased by 64% within 15 min of PMA treatment and was stable over 2 h (51% greater than that of controls). Thus increases in MLCK phosphorylation preceded decreases in MLC phosphorylation. These data suggest that PKC regulates TER via decreased phosphorylation of MLC, possibly due to inhibitory phosphorylation of MLCK. The decreased phosphorylation of MLC likely reduces PAMR tension, leading to decreased TJ permeability.

Biological Transport↗
PubMed1999

Evidence of T cell receptor beta-chain patterns in inflammatory and noninflammatory bowel disease states.

T cell activation, as defined by expression of relevant cell surface molecules, such as the interleukin-2 receptor (CD25), is increased in many chronic relapsing diseases, including inflammatory bowel disease (IBD). These T cells are generally activated through contact of their clonotypic T cell receptor (TCR) with a peptide antigen presented by a major histocompatibility complex molecule. One of the putative antigenic contact sites for the TCR is the third complementarity determining region (CDR3) of the TCR beta-chain variable region (TCRBV). Therefore, analysis of the TCRBV CDR3 provides insight into the diversity of antigens encountered by a given T cell population. This study evaluated the TCRBV CDR3 usage of the activated intestinal lymphocytes from human subjects with IBD, diverticulitis (inflammatory control), and a normal tissue control. Public patterns, as demonstrated by shared TCRBV CDR3 amino acid sequences of activated intestinal T cell subpopulations, were observed. In particular, a public pattern of TCRBV22, a conserved valine in the fifth position, and use of TCRBJ2S1 or TCRBJ2S5 was present in three of four Crohn's disease subjects while not present in the ulcerative colitis subjects. However, the private patterns of TCRBV CDR3 region amino acid sequences were far more striking and easily demonstrated in all individuals studied, including a normal noninflammatory control. Thus we conclude that selective antigenic pressures are prevalent among an individual's activated intestinal lymphocytes.

Amino Acid Sequence↗
PubMed1999

Pathologic prognostic factors in esophageal squamous cell carcinoma: a follow-up study of 74 patients with or without preoperative chemoradiation therapy.

One of the primary goals of pathologic examination of esophageal squamous cell carcinoma resection specimens is to provide information regarding morphologic features which can help prognosticate and guide management of affected patients. The purpose of this study was to determine the prognostic utility of a variety of histopathologic prognostic factors in patients with esophageal squamous cell carcinoma with and without preoperative chemotherapy and radiotherapy (chemrad). Multiple clinical and histologic features such as peri-tumoral lymphocytic infiltrate, Crohn's-like lymphoid reaction, degree of residual tumor, mitosis per 1000 cells, tumor differentiation, lymphatic/vascular invasion, perineural invasion, desmoplastic reaction, and tumor growth pattern were evaluated in patients with (53) and without (21) preoperative chemrad and correlated with survival (mean follow-up, 25 mo). Data were analyzed for the entire cohort and for each separate treatment group by univariate and multivariate analysis. Patients who received chemrad showed no significant survival benefit (hazard ratio = 2.5, P = .10). In the whole cohort of patients, higher pathologic stage (P = .04), poor tumor differentiation (P = .003), increased mitotic count (P = .005), perineural invasion (P = .01), lymphatic/vascular invasion (P = .002), tumor size (P = .05), and absence of a Crohn's-like lymphoid reaction (P = .05) were significantly associated with poor survival by univariate analysis. In multivariate analysis, poor tumor differentiation (P = .005), high mitotic count (P = .01), and vascular invasion (P = .03) were important prognostic features, independent of pathologic stage, for the entire cohort. In the chemrad group only, tumor size (in patients with macroscopic residual tumor) (P = .05), lymph node metastasis (P = .03), mitotic count (P = .01), and lymphatic/vascular invasion (P = .02) were significant prognostic indicators by univariate analysis. Upon multivariate analysis, only lymphatic/vascular invasion (P = .02) and mitotic rate (P = .01) were independent predictors of survival. In the nonchemrad group, only tumor differentiation was significant by both univariate (P = .008) and multivariate analysis (P = .03). The differences in pathologic prognostic factors between chemrad and nonchemrad treated cases suggests that chemrad has a significant effect on the biologic properties of these tumors.

Adult↗
PubMed1998

Development of gastrointestinal beta2-microglobulin amyloidosis correlates with time on dialysis.

Dialysis-associated beta2-microglobulin (beta2m) amyloidosis affects predominantly musculoskeletal tissue, but visceral involvement also occurs. To evaluate the clinical significance and prevalence of gastrointestinal beta2m amyloidosis, we studied hemodialysis patients admitted for gastrointestinal-related complaints. Hemodialysis patients (excluding those with non-beta2m amyloidosis) who were admitted with gastrointestinal complaints from 1984 to 1994 were identified. Gastrointestinal tissues from patients with available autopsy or surgical specimens were examined using hematoxylin and eosin stain, Congo red stain, and beta2m immunostain. Each case was evaluated independently by two pathologists and scored for quantity and location of beta2m amyloid and associated pathology. Of 24 patients, eight (four men and 4 women) had beta2m amyloid deposits within the gastrointestinal tract. Acute clinical presentation ranged from abdominal pain to gastrointestinal bleeding and was not significantly different for patients with or without gastrointestinal beta2m amyloid deposits. However, the mean time on dialysis of 15.3 +/- 5.7 years (range 6-24 years) for patients with gastrointestinal beta2m amyloidosis was significantly greater than that of patients without gastrointestinal beta2m amyloidosis (10.5 +/- 7.0 years, range <1 to 22 years, p < 0.05). Vascular histopathology ranged from mild focal thickening of vessel walls to massive vascular beta2m amyloid deposition with thrombosis. Extravascular beta2m amyloid ranged from mild to severe with marked expansion of the submucosa. Mucosal pathology ranged from none to severe ulceration. The degree of beta2m amyloid and the associated pathology tended to increase in severity with time on dialysis. Gastrointestinal beta2m amyloid deposition is an underappreciated complication of chronic hemodialysis that is significantly associated with increased time on dialysis. Gastrointestinal beta2m amyloidosis should be considered in any patient on hemodialysis 10 years or more who has gastrointestinal symptoms and can be identified in resection specimens as well as some biopsy specimens. Congo red stain and beta2m immunostains may be necessary for sensitive histopathologic evaluation of gastrointestinal beta2m amyloidosis.

Adult↗