The intrarenal distribution of renin changes markedly during maturation. To determine whether renin gene expression changes along the developing renal vasculature, renin mRNA distribution was assessed using in situ hybridization histochemistry. Fetal, newborn, and adult kidney tissue sections from Wistar-Kyoto rats were hybridized with an oligonucleotide complementary to rat renin mRNA. In fetal kidneys, renin mRNA was found in the vascular pole of juxtamedullary glomeruli and along afferent, interlobular, and arcuate arteries. In kidneys from newborn rats, renin mRNA localized throughout the whole length of afferent arterioles, but was not detected in interlobular or arcuate arteries. In adult kidneys, hybridization signals were less intense and confined to the juxtaglomerular apparatus. Immunolocalization of renin with a polyclonal anti-rat renin antibody paralleled closely the mRNA distribution. Northern blot analyses demonstrated that renin mRNA levels were higher in fetal and newborn (20- and 10-fold, respectively) than in adult kidneys. We conclude the following. 1) The fetal kidney expresses the renin gene. 2) Expression of the renin gene is subjected to developmental changes. 3) As maturation progresses, localization of renin synthesis and storage shifts from large intrarenal arteries to a restricted, classical juxtaglomerular site in the afferent arteriole.

Astract. The present study examined the role of cell-mediated immunity (CMI)

We phenotyped with monoclonal antibodies (MAb) the cellular infiltrates in kidneys of patients with rapidly progressive glomerulonephritis (RPGN) responsive (R) or nonresponsive (NR) to pulse methylprednisolone therapy (PM)-eight anti-GBM, six no immune deposits, three immune complex, two vasculitis, and one proliferative GN. There were glomerular, periglomerular, crescentic, and interstitial T and T-cell subsets. Few interstitial and no glomerular B and NK cells were observed. TH cells were much more common than TS. Phenotypes were quantitatively evaluated in 221 nephritic and 32 control glomeruli. T and/or TH cells were positively correlated with M phi, r = 0.30 to 0.74, P less than 0.05 to 0.0005. Although differences in phenotypes were observed, these differences were insufficient to distinguish between subtypes. Analysis of R and NR revealed no relationship to percent crescents, entry serum creatinine, oliguria, or need for dialysis. NR was related to presence of anti-GBM disease, P = 0.001, as was ability to stop dialysis, 0 of 7 GBM versus 9 of 10 other, P less than 0.001. Mild infiltrates of lymphocytes and M phi correlated with R, P less than or equal to 0.02. R had fewer numbers of TH and M phi in glomeruli, P = 0.0001, in crescents, P less than 0.02, and total TH and M phi compared to NR, P less than 0.001. Crescentic and total TH/S ratios were lower in NR than R, P less than 0.05. These findings demonstrate that components of the cell-mediated immune (CMI) system are present by MAb analysis, that subtypes cannot be differentiated by CMI constitution, and R to PM is related to intensity and composition of CMI involvement. Independence of the CMI system relative to anti-GBM disease remains to be clarified.

In osteoarthritis the articular cartilage becomes roughened, fibrillar, softened, thinned, and finally eroded, with secondary changes occurring in the underlying bone. Histologically, early cartilage lesions in osteoarthritis are characterized by loss of metachromasia in the matrix, and it has been postulated that the initial disturbance involves the intercellular substance (1, 2). The decrease in metachromatic material in the matrix apparently is not due to degenerative changes in the cartilage cells; on the contrary, areas of osteoarthritis usually show proliferation of chondrocytes and increased radiosulfate uptake (2). The loss of metachromasia has been attributed to a diminution in chondroitin sulfate content. Hirsch has shown a decreased sulfate concentration in chondromalacia of the patella, associated with loss of metachromatic staining and loss of elasticity of the cartilage (3). Matthews (4) reported a fall in hexosamine-hydroxyproline ratio in fibrillar osteoarthritic cartilage, and Kuhn and Leppelmann (5) showed a fall in galactosamine and glucosamine concentration of femoral articular cartilage in individuals with "arthrosis deformans." Such observations suggest that metabolic changes occur in the cartilage lesions of osteoarthritis.In the studies to be reported, chondroitin sulfate concentration was determined as glucuronic acid, a more specific assay for this polysaccharide than hexosamine, since the latter is also present in the keratosulfate in cartilage; for example, the hexosamine concentration of adult rib cartilage is four times greater than can be accounted for as chondroitin sulfate (6). A decrease in chondroitin sulfate concentration was found in osteoarthritic cartilage, most marked in the more advanced lesions. In addition, qualitative changes in the polysaccharide-protein complex of osteoarthritic cartilage * Supported by U. S. Public Health Service research grant AM-03421 and training grant 2A-5233. were found, suggesting that polysaccharide breakdown was responsible for the decreased concentration of chondroitin sulfate. METHODSArticular cartilage was obtained from the knee and shoulder of 20 subjects 6 to 18 hours post-mortem. Knee cartilage was excised from the condylar surfaces of the femur or the posterior surface of the patella; in a few instances, samples were taken from the tibial plateau. Shoulder cartilage was taken from the anterior portion of the humeral head. Each sample was graded and processed separately. The degree of cartilage erosion in each area was quantitated on the basis of the smoothness of the surface, thickness, and consistency by the following criteria. Normal: Cartilage was smooth, white, glistening, and firm; pale yellow discoloration was occasionally present. Grade 1 osteoarthritis: Earliest lesions; minimal pitting and fraying of the surface, sometimes visible only in strong light; normal consistency and thickness. Grade 2 osteoarthritis: Obvious irregularity of cartilage surface with pitting and fraying; some softening, but normal thickness. Grade 3 o...

Of 46 patients with acute crescentic glomerulonephritis involving 20 to 90% of glomeruli, 16 had no definable systemic disease and no significant glomerular immune deposits by immunofluorescent or electron microscopy. Anti-GBM antibody and circulating immune complexes were further excluded by radioimmunoassay and Raji cell assay in all patients tested. Clinical features included a 10:6 male:female ratio, mean age of 58 years (range, 13-77), disease duration of less than 3 months, rapidly deteriorating renal function, and frequent pulmonary manifestations. Nine patients had oliguria, serum creatinine concentrations over 6 mg/100 ml, and required dialysis, but three of these patients subsequently recovered renal function. These three patients and seven patients with creatinine concentrations of less than 6 mg/100 ml have not progressed to chronic renal failure. In this series, idiopathic acute crescentic glomerulonephritis without immune deposits was more common than was immune complex or anti-GBM nephritis. The clinical, laboratory, and pathologic characteristics of these patients were similar to those reported in anti-GBM and immune-complex-induced glomerulonephritis. These observations expand the spectrum of rapidly progressive crescentic glomerulonephritis. They suggest that glomerular immune deposits may be less important than other factors in determining the extent of renal injury and subsequent clinical course in crescentic glomerulonephritis.