Investigative urology最新文献

Nonobstructive pyelonephritis was produced in the rhesus monkey (Macaca mulatta) by means of retrograde inoculation of Escherichia coli to the point of pyelotubular backflow. The effects of treatment with cyclophosphamide or azathioprine were determined. Commensal renal viruses were not activated by the immunosuppression, and thus did not complicate our results. Both cyclophosphamide and azathioprine prolonged the bacteriuria and produced more severe pathology. Cyclophosphamide decreased the leukocytic response and partically suppressed the antibody response. The increased amount of acute pyelonecytic response and partially suppressed the antibody response. The increased amount of acute pyelonephritic lesions after treatment with this drug suggest that the antibody and inflammatory responses may be important protective mechanisms, particularly regarding prevention of abscesses. In contrast, azathioprine did not decrease the leukocytosis nor the antibody responses, but resulted in decreased in vitro responsiveness of lymphocytes to mitogens. The increased severity of chronic pyelonephritic lesions after azathioprine treatment suggests that the cellular immune response also may be an important protective mechanism during late stages of the disease. The results thus indicate that the immune response is protective and is not directly responsible for the chronic scarring of pyelonephritis.

In histochemical studies it was shown that sulfated acid glycosaminoglycans (AGAGS) were produced and secreted into the tubular lumen in renal papilla, but not in the renal cortex of muddy stone forming kidney. There was no secretion of sulfated AGAGS in renal papilla histochemically during hydronephrosis before stone formation. On autoradiographic study with the use of 45Ca and 35S for labeling of sulfated AGAGS, we found that 45Ca accumulated in renal papilla of muddy stone forming kidney, but not in the other. 35S apparently accumulated into muddy stones. Measurement of calcium content of the renal papilla and cortex proved the results of autoradiographic studies, and measurement of uronic acid in the urine showed increased secretion of AGAGS in the urine from muddy stone forming kidney. From these results it was proposed that the sulfate AGAGS secreted in the urine could bind calcium crystals to each other amd make crystals aggregate massively.

Dispersed tumor cells from primary human renal adenocarcinomas showed typical clonogenic growth in soft agar in seven of 31 instances. In vitro chemotherapy sensitivity testing was performed successfully for five of the seven clonogenic tumors. Extensive inherent resistance to the cytotoxic effects of many standard and experimental chemotherapeutic agents were observed. Occasionally, a single drug showed marked cytotoxicity. Similar results were obtained with soft agar clonogenic chemotherapeutic drug sensitivity assays performed on cells from human renal carcinoma xenografts. These in vitro results agree with clinical experience in the chemotherapy of advanced renal carcinoma. It remains to be determined if the sensitivity or resistance to chemotherapeutic drugs of human renal carcinomas noted in vitro reflects the characteristics of the tumors in vivo. Our results show that it is feasible to evaluate the soft agar assay as a method for selecting drugs for individual patients with renal carcinoma, a disease for which no chemotherapeutic treatment can be recommended at present.

In vitro cultivated cells derived from normal human renal cortex were characterized morphologically and biochemically. Although the epithelial monolayer was composed of heterogeneous cells, it included cells with a surface structure similar to microvilli as well as some resembling the desmosome between neighboring cells. Enzymatic studies revealed a marked decrease in alkaline phosphatase activity, and the activity of gamma-glutamyl transpeptidase was also reduced to about one-fifth of that in the original tissue. The electrophoretic mobility of the enzyme was not identical with that of normal kidney or of the novel enzyme in renal neoplastic tissue. Lactate dehydrogenase activity was similar to that of normal kidney tissue but the isozyme pattern was completely inverted. These cells responded to the addition of 10 ng per ml of parathyroid hormone in culture medium and there was a 33 fold increase in intracellular cyclic adenosine monophosphate. Estrogen specific binding protein was not detectable in the monolayer cells. These results clearly indicated that the biologic transformation observed in the cultivated normal cells was not attributable to simple fetalism or dedifferentiation, but was a more complicated process.

We graded obstructed kidneys of infants on the hypodysplasia scale to assess the influence of complete and partial obstruction on the pathogenesis of hypodysplasia. Kidneys with complete obstruction exhibited severe grades; those with partial ureteral obstruction had near normal grades. Those kidneys subjected to partial urethral obstruction ranged from mild to severe grades which correlated with degrees of lateral ectopy of the urethral office. Renal parenchymal development was impaired by complete obstruction but was tolerant to incomplete obstruction. Abnormal orifice positions associated with urethral obstructions were considered to be manifestations of ectopic ureteric buds and the hypodysplasia to be evidence of abnormal induction of abnormal renal blastema.

An age related increased cellularity in the lamina propria of the mouse bladder is described. The identified cell types involved are plasma cells, lymphocytes, and eosinophilic leukocytes, and probably represent an inflammatory plasma cell infiltration. Two rare unidentified cell types were also seen. The cause of the inflammatory reaction is unknown, but the failure to detect a causative microorganism suggests that it might be an autoimmune response, possibly related to the clinical condition of interstitial cystitis. From foci of increased cellularity, located in the close proximity of blood vessels, lymphocytes migrate to the urothelium which otherwise shows no ultrastructural changes with age.