We conclude that islet macrophages are major contributors to islet IL-1β secretion in response to TLR2/6 and TLR4 ligands. BMDMs stimulated with TLR2/6 and TLR4 ligands reduce insulin secretion from pancreatic beta cells, partly via IL-1β- and IL-6-mediated decreased insulin gene expression.

The gene for dihydrofolate reductase of Mycobacterium tuberculosis was amplified by polymerase chain reaction (PCR) from M. tuberculosis H37Rv strain genomic DNA. The protein was expressed in inclusion bodies in high yield in Escherichia coli under the control of the T7 promoter. Active enzyme was obtained by refolding from guanidine HCl and after a single chromatography step the sample was s 99% homogeneous with a specific activity of V15.5 Wmol min 31 mg 31 . Mass spectrometry analysis confirmed the expected mass of 17.6 kDa. Gel filtration of the enzyme indicated that it was a monomer. Steady-state kinetic parameters were determined and the effect of pH and KCl on the enzyme examined. Methotrexate and trimethoprim inhibited the enzyme.

Background:Kidney biopsy is considered the gold standard for diagnosis of renal disease. It is increasingly performed in cases of diagnostic uncertainty, including in patients with coexistent diabetes and hypertension, for which a presumptive clinical diagnosis can be made. Little is known about the incidence and distribution of biopsy-proven kidney diseases. Changes in the distribution of biopsy diagnoses over time may have significant implications for resource allocation and future research.Objective:We studied the relative frequency of kidney diseases in Southern Alberta over the past 30 years, to determine whether the population-standardized annual biopsy rate and incidence of selected diagnostic categories have changed. We hypothesized an increasing incidence of renal biopsies and a growing proportion of nonglomerular diseases (eg, tubulointerstitial disorders) likely due to evolving indications for biopsy. Given the rise in obesity, diabetes, and aging population with chronic kidney disease (CKD), we anticipated a rise in nephroangiosclerosis and diabetic nephropathy over time.Design:Retrospective population-based cohort study using the Biobank for the Molecular Classification of Kidney Disease (BMCKD).Setting:Southern Alberta, Canada.Patients:All patients who underwent renal biopsy between 1985 and 2015 in our database.Measurements:We used descriptive and quantitative analysis to characterize demographics and biopsy-based diagnoses.Methods:We conducted a retrospective population-based cohort study to analyze all consecutive patients who underwent at least one kidney biopsy over a 30-year period in Southern Alberta (1985-2015). We considered the first adequate biopsy. We described the annual standardized incidence of biopsy-proven kidney diseases over time and summarized associated patient characteristics. We assumed a Poisson distribution for biopsy counts and used provincial demographic information to standardize rates.Results:During the study period, 6434 people (58% male; mean age: 47.9 years) underwent a kidney biopsy. The population-standardized annual biopsy rate increased from 10.8 biopsies per 100 000 person-years in the first 5 years of the study (1985-1989) to 18.2 biopsies per 100 000 person-years in the last 5 years (2010-2014). The mean age at the time of biopsy increased from 42.5 years (1985-1989) to 51.4 years (2010-2014). Glomerular diseases remained the most prevalent histopathological group, with a growing representation of diabetic kidney disease from 3.69% to 16.18%, and a relative decrease in the proportion of other glomerular diseases from 72.32% to 62.92% of glomerular diagnoses. Tubulointerstitial diseases increased from 5.87% to 7.36% of total diagnoses.Limitations:Classification schemes have changed over time, so recently recognized conditions may have been misclassified in earlier data. There was a changing group of pathologists and nephrologists over this period. Variations in interpretation and application of biopsy indications by physician may influence recorded prevalence of...