Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-α and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.
We present 56 patients with urethral calculi. In males the commonest location was the posterior urethra; 46 patients complained of dysuria but urinary retention was present in only 7. In 9 patients with penile urethral calculi, 6 had associated urethral disease (urethral stricture in 5 and urethral diverticula in 1). Transurethral litholapaxy or lithotripsy after retrograde manipulation was performed in 33 patients. Endoscopic manipulation was found to be the safest procedure.
We have treated 167 patients with staghorn calculi. Conservative therapy was used in 61 patients who have been followed up for 1 to 18 years (average 7.8). Chronic renal failure occurred in 22 of these patients and 7 died from uraemia. The causes of chronic renal failure were bilateral staghorn calculi, staghorn calculi and contralateral urinary calculi, and chronic pyelonephritis of the contralateral kidney. The morbidity and mortality rates following conservative treatment were higher than those following surgical management. The pathological findings in 47 kidneys after nephrectomy showed severe hydronephrosis, renal abscess and xanthogranulomatous pyelonephritis. These results indicated that staghorn calculi destroyed the kidney and early complete removal of these stones is advisable.
Spontaneous peripelvic extravasation of urine is relatively uncommon. We experienced 11 cases of spontaneous peripelvic extravasation. Urinary obstruction was caused by calculi in 9 cases, invasion by sigmoid carcinoma in 1 case and ureteral tumour (transitional cell carcinoma) in 1. Six patients presented with signs of peritonitis and 4 out of 9 with calculus did not develop microhaematuria. It is important to differentiate peripelvic extravasation from other acute abdominal conditions. We must pay special attention to patients with signs of peritonitis and normal urinalysis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.