Effect of dietary protein on the renin-angiotensin system in subtotally nephrectomized rats

Dietary protein restriction improves the course of renal disease in the remnant kidney model. Dietary protein restriction can also reduce plasma renin activity in several circumstances. We examined the interaction between dietary protein and the renin-angiotensin system in subtotally nephrectomized rats (1-2/3 nephrectomy). No difference was seen in tissue renin activity in rats ingesting a high (30%) versus a low (6%) protein diet. To determine the pathophysiological role of angiotensin II in subtotally nephrectomized rats, we examined the acute renal response to an intrarenal infusion of the angiotensin II antagonist Sar1 Gly8-angiotensin II (10 micrograms/kg/min). Only those subtotally nephrectomized animals ingesting a high protein diet exhibited a consistent improvement in glomerular permselectivity, as manifested by a 24% fall in the fractional clearance of albumin (basal 16.19 +/- 3.65 x 10(-4) vs. Sar1 Gly8-AII 12.26 +/- 3.21 x 10(-4); P less than 0.02) and a 19% fall in the fractional clearance of IgG (basal 3.75 +/- 0.67 x 10(-4) vs. Sar1 Gly8-AII 3.03 +/- 0.48 x 10(-4); P less than 0.02). No consistent change occurred in glomerular permselectivity in the rats on the low protein diet or rats infused with vehicle only. No change in mean arterial pressure or whole-kidney hemodynamics were seen with angiotensin II blockade. Decrements in SNGFR and glomerular capillary pressure occurred with angiotensin blockade in the animals ingesting the high protein diet, suggesting hemodynamic factors as a mechanism for the improvement in permselective defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deletion mapping in Alport syndrome and Alport syndrome-diffuse leiomyomatosis reveals potential mechanisms of visceral smooth muscle overgrowth

Diffuse leiomyomatosis is associated with the inherited kidney disease Alport syndrome, and characterized by visceral smooth muscle overgrowth within the respiratory, gastrointestinal and female reproductive tracts. Although partial deletions of the type IV collagen genes COL4A5 and COL4A6, paired head-to-head on chromosome Xq22, are known to cause diffuse leiomyomatosis, loss of function for type IV collagen does not explain smooth muscle overgrowth. To further clarify pathogenic mechanisms, we have characterized novel deletions in patients with Alport syndrome-diffuse leiomyomatosis or Alport syndrome alone. A 27.6-kb deletion, in a female with Alport syndrome-diffuse leiomyomatosis, is marked by the most proximal, i.e. most 5', COL4A5 breakpoint described to date. By comparing this deletion to others described here and previously, we have defined a minimal overlap region, only 4.2 kb in length and containing the COL4A5-COL4A6 proximal promoters, loss of which contributes to smooth muscle overgrowth. A novel deletion in a male with Alport syndrome alone is>1.4 Mb in length, encompassing COL4A5 and COL4A6 entirely, as well as neighboring genes. We postulate that loss of the 4.2-kb region in diffuse leiomyomatosis causes misregulation of neighboring genes, contributing to smooth muscle overgrowth. Deletion of the neighboring genes themselves may afford protection from this condition.     

Botryoid-type of embryonal rhabdomyosarcoma of renal pelvis in an adult. A case report and review of the literature

A case of botryoid-type embryonal rhabdomyosarcoma of the renal pelvis in a 49-year-old woman is reported. The tumor led to hydronephrosis. The surgical resection specimen disclosed a translucent, polypoid mass attached to the wall of the renal pelvis by thin stalk. Light-microscopic examination revealed a large exophytic polypoid tumor with intact surface epithelium, which was negative for dysplasia or carcinoma in situ. There was a condensation of epithelioid to spindle cells underneath the basement membrane, forming a cambium layer. The core of the lesion contained interspersed epithelioid to spindle cells with myxoid change and edema. Cells of the cambium layer as well as interspersed cells in the core exhibited marked cytologic atypia with mitotic figures. Immunohistochemical stains for cytokeratin, S-100 and myoglobin were negative, stains for desmin and actin were positive. Although botryoid-type embryonal rhabdomyosarcomas have been reported to occur at various sites in the genital tract and lower urinary tract, to our knowledge, this is the first reported case of the tumor within the renal pelvis. Also, the occurrence of these tumors in adults is quite rare.     

Downregulation of plasma membrane expression/cytoplasmic accumulation of beta-catenin predicts shortened survival in non-small cell lung cancer. A clinicopathologic study of 100 cases

The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported to be dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associates with tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role in the Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenin causes a loss of intercellular adhesions resulting in increased tumor cell motility and invasiveness. Tissue sections from 100 cases of non-small cell lung cancer (NSCLC) were immunostained with a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53 adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivity was scored for intensity and distribution and correlated with tumor stage, grade and survival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observed in 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. On univariate analysis, loss of beta catenin expression correlated with high tumor stage (p = 0.025), large tumor size (p = 0.02) and decreased patient survival (p = 0.04). The loss of beta catenin expression associated with high grade NSCLC reached near significance (p = 0.07). On multivariate analysis, the loss of beta catenin expression independently predicted shortened overall patient survival in NSCLC (p = 0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independent predictor of shortened patient survival in NSCLC.     

Spontaneous acute lymphoblastic leukemia in Sprague-Dawley rats. II. Cytogenetic analysis of nine individual leukemias

Nine spontaneous acute lymphoblastic leukemias (SD1-SD9) in Sprague-Dawley rats were investigated cytogenetically by G-banding. The chromosome numbers of metaphase cells in all studied SD leukemias were near diploid and in all leukemias numerical or structural abnormalities were found. Affected were chromosomes No. 11, 2, 13 and 1. A common finding in most leukemias was trisomy 11 observed either as simple trisomy (SD1, SD4 and 2 clones of SD6), or the translocation form of trisomy (SD3), or the tandem translocation t(11;13) in SD7, or the Robertsonian fusion -rob(2;11) in SD5. In SD9 and one cell clone of SD8 no apparent trisomy was found, but the cells contained an 11q+ marker. Among the rearranged chromosomes, chromosome 2 was most frequently involved. Der No. 2 with terminal deletion was found in some of SD3 metaphases and a probable partial duplication of chromosome 2 was found in SD6. The finding of trisomy 2 in SD5 and SD6 occurred rarely. Further structural rearrangements concerned No. 13, the involvement of which was evident in the 13q+ marker typical of SD2, one cell clone of SD6, SD7 and SD8 leukemias. 1q+ aberration was the common finding in SD3 and SD5, while 1q-was observed in all SD6 metaphases. According to the cytogenetic examination of SD leukemias, we considered that the changes of chromosomes 11, 2, 13 and 1 were nonrandom. Based on the similarity of chromosomal rearrangements in individual leukemias, probable breakpoints on the affected chromosomes could be determined. 11cen, 11q12, 2q32-33, 2q16, 13q22, 1q43 and 1q54 were found to be the most frequently afflicted regions in SD leukemias.     

Study of relationship between allogeneic transplantability of tumors and their effects on drug-metabolizing system in rats

Effects of three different fibrosarcomas on the hepatic mixed-function oxidase system were studied in males of the Lewis inbred strain of rats. No association between graded potentiality of these tumors to grow across histocompatibility barriers and their suppressive effects upon the microsomal drug-metabolizing system was found.