Deletion of Cdh16 Ksp-cadherin leads to a developmental delay in the ability to maximally concentrate urine in mouse.

Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system of the mammalian kidney. The principal aim of the present study was to determine if Ksp-cadherin played a critical role in the development and maintenance of the adult mammalian kidney by generating and evaluating a mouse line deficient in Ksp-cadherin. Ksp-null mutant animals were viable and fertile, and kidneys from both neonates and adults showed no evidence of structural abnormalities. Immunolocalization and Western blot analyses of Na+-K+-ATPase and E-cadherin indicated that Ksp-cadherin is not essential for either the genesis or maintenance of the polarized tubular epithelial phenotype. Moreover, E-cadherin expression was not altered to compensate for Ksp-cadherin loss. Plasma electrolytes, total CO2, blood urea nitrogen, and creatinine levels were also unaffected by Ksp-cadherin deficiency. However, a subtle but significant developmental delay in the ability to maximally concentrate urine was detected in Ksp-null mice. Expression analysis of the principal proteins involved in the generation of the corticomedullary osmotic gradient and the resultant movement of water identified misexpression of aquaporin-2 in the inner medullary collecting duct as the possible cause for the inability of young adult Ksp-cadherin-deficient animals to maximally concentrate their urine. In conclusion, Ksp-cadherin is not required for normal kidney development, but its absence leads to a developmental delay in maximal urinary concentrating ability.NEW & NOTEWORTHY Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system. Using knockout mice, we found that Ksp-cadherin is in fact not required for kidney development despite its high and specific expression along the nephron. However, its absence leads to a developmental delay in maximal urinary concentrating ability.

Clinical efficacy of mesalamine in the treatment of the spondyloarthropathies.

OBJECTIVE: Sulfasalazine (SSZ) has been found to have beneficial effects in the treatment of patients with spondyloarthropathy (SpA) with active disease. The effectiveness of SSZ is limited by both idiosyncratic and dose related side effects when treating SpA. Mesalamine is a drug used to treat inflammatory bowel disease. Case reports have suggested potential efficacy in SpA. We investigated the efficacy and safety of the Pentasa formulation of mesalamine in treating SpA. METHODS: Thirty patients with SpA as defined by the European Spondylarthropathy Study Group were recruited from a rheumatology specialty clinic. All subjects began 16 week open label therapy with mesalamine 1500 mg/day. Dose escalation for lack of efficacy was permitted after 8 weeks of therapy. Clinical, physical, and laboratory data were collected at baseline, at 8 weeks, and at the conclusion of the study at 16 weeks. RESULTS: Twenty-nine of the 30 patients completed the study. There was clinically and statistically significant improvement in all clinical measures (morning stiffness, night awakenings, quality of sleep, severity of stiffness, severity of pain, Dougados functional index, patient and physician global indices). Joint counts and enthesitis counts improved, but measures of axial flexibility did not. Erythrocyte sedimentation rate and C-reactive protein also improved over the duration of the study. CONCLUSION: In this population of patients with SpA, mesalamine was well tolerated in the dose range 1500 to 4000 mg/day. Improvements in clinical, physical, and laboratory measures indicate the efficacy of mesalamine in treating SpA.

Serologic testing for reactive arthritis.

The objective of the study was to determine the sensitivity and specificity of quantitative serum antibody response to Salmonella enteritidis lipopolysaccharide (LPS) as a diagnostic test for post-Salmonella reactive arthritis (ReA). In a single food-source outbreak of Salmonella enteritidis, serum was collected from dysenteric individuals with and without ReA at 6, 12, and 24 months post infection. Serum was also collected from control patients with no prior exposure to Salmonella infection. Quantitative measurements of isotypic antibodies to Salmonella enteritidis LPS were performed by an ELISA. Sensitivity and specificity of quantitative isotypic antibody levels over time were plotted on receiver operator characteristic (ROC) curves. Serum IgG and IgA anti-LPS were found to be present in higher levels in the ReA patients than in controls. Using the optimal cutoff of 0.10 selected from an ROC curve, IgG anti-LPS is 88% sensitive and 94% specific, and IgA anti-LPS is 75% sensitive and 100% specific. We conclude that IgA anti-LPS is both sensitive and specific in distinguishing prior exposure to Salmonella LPS in ReA patients compared to unexposed controls.

Secretory immune response and clinical sequelae of Salmonella infection in a point source cohort.

OBJECTIVE: To determine the kinetic isotypic serum and secretory immune response to Salmonella enteritidis in a cohort of individuals exposed to the organism in a single food source outbreak of dysentery. To determine the clinical outcome and immunogenetics of the exposed cohort and to correlate these features with the immune response. METHODS: Following a single point source outbreak of Salmonella enteritidis, a cohort of dysenteric individuals were ascertained using a reactive arthritis screening questionnaire (QUEST). Serum and stimulated saliva samples were obtained at 6, 12, and 24 months following the outbreak of dysentery; examinations were conducted at the same time. Two unexposed control groups were ascertained: (1) general rheumatology clinic patients and (2) well nonarthritic family practice patients. An ELISA to determine quantitative IgA responses to Salmonella enteritidis lipopolysaccharide (LPS) was performed. RESULTS: Eleven of the 84 exposed individuals with dysentery developed reactive arthritis (ReA) of reactive enthesitis (ReE). There was a prolonged salivary IgA anti-LPS response in both the ReA/ReE and DYS (dysentery alone) patients compared with unexposed controls. A ratio of salivary IgA anti-LPS/serum IgA anti-LPS > 1 was associated with a good outcome (remission) of ReA, whereas a ratio < 1 was associated with chronic disease. CONCLUSIONS: There is a more prolonged humoral immune response to Salmonella LPS in exposed individuals than hitherto described. A risk factor in the prolongation of ReA is the inability to mount an appropriate specific salivary (secretory) immune response.

Nonelectrolyte permeability of canine tracheal epithelium.

We examined the nonelectrolyte permeability characteristics of canine tracheal epithelium in vitro and confirmed that the transepithelial potential difference was 26.3 +/- 2.2 mV, lumen negative. Exposure of the epithelium to a sucrose osmotic load resulted in a streaming potential (SP); a linear relationship was noted between osmotic load and SP. The presence of an osmotic load did not change the short-circuit current and the SP disappeared after removal of the osmotic load. The SP developed with urea, thiourea, D-xylose, and l-glycine were similar to the SP developed for equimolar concentrations of sucrose. The urea and insulin spaces were similar magnitude. When the bulk phase was stirred at 600 rpm, the effective thickness of the unstirred water layer (UWL) external to the epithelial surface was 144 +/- 12 micron. These results support the suggestion that the Staverman reflection coefficients (sigma) of these probe molecules are similar, the estimates of sigma are valid despite the presence of an UWL, and the tracheobronchial epithelium has a pore size smaller than the hydrodynamic radius of urea.