We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process.

Alterations in the balance between synthesis and degradation of extracellular matrix may result in glomerulosclerosis. The interaction between metalloproteinases and their inhibitors presumably modulates the rate of glomerular matrix degradation. We examined the gene expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in human glomeruli and TIMP-2 protein in tissue sections. Kidney tissue was obtained from adults undergoing nephrectomy for renal tumor (n = 9) or biopsy for nephrosis and renal failure (n = 1). Glomeruli were microdissected and subjected to reverse transcription. TIMP cDNAs were quantitated by competitive polymerase chain reaction assays. Five nephrectomy specimens had normal glomeruli and four had diffuse glomerulosclerosis. TIMP-1 and TIMP-2 cDNA levels, detected in glomeruli from all patients, were increased fourfold and threefold, respectively, in patients with glomerulosclerosis. The elevated TIMP cDNA levels could not be attributed to an increased number of glomerular cells. TIMP-2 protein was detected within normal and sclerotic glomeruli. In conclusion, both TIMP genes were expressed in normal glomeruli, and their level of expression was increased in glomerulosclerosis associated with renal carcinoma, suggesting that expression of these inhibitors may correlate with the development of sclerosis.

BackgroundLittle information exists on U.S. physicians who have been disciplined with licensure or restriction-of-clinical-privileges actions or have had malpractice payments because of sexual misconduct. Our objectives were to: (1) determine the number of these physicians and compare their age groups’ distribution with that of the general U.S. physician population; (2) compare the type of disciplinary actions taken against these physicians with actions taken against physicians disciplined for other offenses; (3) compare the characteristics and type of injury among victims of these physicians with those of victims in reports for physicians with other offenses in malpractice-payment reports; and (4) determine the percentages of physicians with clinical-privileges or malpractice-payment reports due to sexual misconduct who were not disciplined by medical boards.Methods and ResultsWe conducted a cross-sectional analysis of physician reports submitted to the National Practitioner Data Bank (NPDB) from January 1, 2003, through September 30, 2013. A total of 1039 physicians had ≥ 1 sexual-misconduct–related reports. The majority (75.6%) had only licensure reports, and 90.1% were 40 or older. For victims in malpractice-payment reports, 87.4% were female, and “emotional injury only” was the predominant type of injury. We found a higher percentage of serious licensure actions and clinical-privileges revocations in sexual-misconduct–related reports than in reports for other offenses (89.0% vs 68.1%, P = < .001, and 29.3% vs 18.8%, P = .002, respectively). Seventy percent of the physicians with a clinical-privileges or malpractice-payment report due to sexual misconduct were not disciplined by medical boards for this problem.ConclusionsA small number of physicians were reported to the NPDB because of sexual misconduct. It is concerning that a majority of the physicians with a clinical-privileges action or malpractice-payment report due to sexual misconduct were not disciplined by medical boards for this unethical behavior.