Rolf Rohrbach

Expression profiling on chronically rejected transplant kidneys.

Background. Chronic transplant nephropathy remains a poorly defined inflammatory process that limits the survival rate of most renal transplants. We analyzed the gene profile of chronically rejected kidney transplants to identify candidate genes that characterize chronic transplant nephropathy. Methods. To distinguish genes present in normal renal tissue or specific for end-stage renal failure, we compared the gene profiles of 13 chronically rejected kidney transplants with 16 normal kidneys and 12 end-stage polycystic kidneys using a 7K human cDNA microarray. After elimination of genes with signals close to background, 2,190 genes were available for statistical analysis. Results. More than 20% of the examined genes were significantly regulated when compared with the expression level of normal renal tissue (P <0.0003). Hierarchic clustering based on 571 genes differentiated normal and transplant tissue, and transplant and polycystic kidney tissue. Most of these genes encoded proteins involved in cellular metabolism, transport, signaling, transcriptional activation, adhesion, and the immune response. Notably, comprehensive gene profiling of chronically rejected kidneys revealed two distinct subsets of chronically rejected transplants. Neither clinical data nor histology could explain this genetic heterogeneity. Conclusions. Microarray analysis of rejected kidneys may help to define different entities of transplant nephropathy, reflecting the multifactorial cause of chronic rejection.

Prolonged survival following palliative renal tumor embolization by capillary occlusion

Nine patients with renal cell carcinoma and severe hematuria were palliatively treated with a new type of angioocclusion: The concept of capillary embolization. The so-called occlusion gel Ethibloc was used as embolizing agent. Each patient was followed up until death or for at least 4 years. All patients had a stage T3 or T4 tumor, 3 patients had metastases to multiple organs, 3 had lung metastases, and 3 were free of metastatic disease. In all cases, very high volumes (14–40 ml) of the embolizing agent were necessary to achieve total occlusion of the entire arterial compartment. Patients without metastatic disease had a mean survival time of 6 years and 4 months, all of them without signs of malignant disease. Patients with metastases had a mean survival time of 3 years. Compared with the natural history of renal cell carcinoma treated otherwise, this represents a substantial prolongation of survival time. Contrary to other angioocclusive treatment modalities, the concept of capillary occlusion with Ethibloc seem to achieve total tumor destruction.

cDNA Microarray Analysis of Adaptive Changes after Renal Ablation in a Sclerosis-Resistant Mouse Strain

Background:5/6 nephrectomy (Nx) in susceptible animals causes glomerular sclerosis and interstitial fibrosis in the remnant kidney. Oxidative stress, transforming growth factor-β (TGF-β), and the de novo synthesis of collagen seem to contribute to this process. However, these factors might also be required for tissue repair without fibrosis. Methods:We examined dynamic changes after nephron loss in a mouse strain capable of complete recovery. C57BL/6 mice underwent single-session Nx and were followed for 40 weeks. Gene expression was monitored over 20 days using 22,000 cDNA microarrays. Results:The mice developed transient hypertension and glomerular hypertrophy after Nx but failed to progress to glomerular sclerosis or renal failure. Gene expression profiles revealed three stages of recovery, an early phase of injury response, an intermediate phase of extracellular matrix (ECM) production and a later phase of reconstitution. Surprisingly, oxidative stress responses and collagen production were strongly upregulated soon after Nx. Furthermore, TGF-β1 and connective tissue growth factor were rapidly upregulated and remained elevated. Conclusion:We suggest that oxidative stress, collagen production, profibrotic growth factors and ECM turnover are part of the comprehensive adaptation to nephron loss and not necessarily associated with progressive loss of renal function.

New Topics in Embolization Effects of Central, Peripheral, or Capillary Type of Occlusion in Animal Models Simulating Tumor Embolization

Embolization is one of the new therapeutic methods in radiology. It has found acceptance for special indications such as emergency treatment of intractable bleeding (Athanasoulis 1980; Kauffmann et al. 1979; Rosch et al. 1972). However, tumor embolization is still controversial, since long-term results are so disappointing that few indications for palliative treatment are left. Even in a case with hematuria caused by renal cell carcinoma, recurrent hemorrhage is reported following Gianturco-Anderson-Wallace coil occlusion (Flamm et al. 1981). Failure of tumor embolization is caused by collaterals and recanalization of occluded arteries. Therefore only temporary reduction of tumor size is achieved: collaterals provide continuing growth in the periphery of the tumor. Clearly the possibilities of tumor embolization are not exhausted so long as the tumor periphery is not primarily occluded. Up to now there has been no medium that reaches the periphery but avoids venous propagation. All media especially developed for embolization, like the Gianturco-Anderson-Wallace coil, detachable balloons, etc., allow occlusion only of the main renal arteries. Ethibloc is the first substance especially developed for peripheral transport (besides occlusion of the pancreatic duct). Its special properties for reducing efficiency of collateral supply were examined and compared with the effect of Gelfoam powder, Butyl cyanoacrylate/Lipiodol and ligation of the renal artery.

Die Stimulierung Dopaoxydase-positiver Melanocyten während der Carcinogenese der Haut

SummaryIn these investigations we endeavored to find out whether the dopaoxidasepositive melanocytes in the dorsal skin of hairless mice would react differently to treatment with carcinogenic, cocarcinogenic and hyperplasiogenic, non-carcinogenic substances. Furthermore, we explored the possible role of these active, melanin producing cells in the development of epithelial tumors.Carcinogenic substances, such as methylcholanthrene and dimethylbenzanthracene provoked an earlier and significantly greater stimulation of melanocytes than weak substances did. After administering one of these substances the number of melanocytes increased to about the same extent; after 2–3 months melanotic tumors developed in the skin.The cocarcinogenic croton-oil caused a much less pronounced reaction of the melanocytes, and the hyperplasiogenic, non-carcinogenic benzanthracene was almost inert. For each the reaction was confined to the dermis only. These two substances failed to produce melanotic tumors within 3–4 months after the beginning of application. Dopaoxidase-positive melanocytes were not involved in the development of epithelial tumors such as papillomas, keratoacanthomas and carcinomas.ZusammenfassungIn den vorliegenden Untersuchungen sollte geklärt werden, ob Unterschiede in der Aktivierung Dopaoxydase-positiver Melanocyten in der Rückenhaut haarloser Mäuse nach der Behandlung mit carcinogenen und hyperplasiogen-nichtcarcinogenen Substanzen bestehen. Ferner sollte eine Beteiligung dieser Melanocyten an der Neubildung epithelialer Tumoren geklärt werden.Die Haut stark reizende carcinogene Substanzen, wie Methylcholanthren und Dimethylbenzanthracen zeigen eine schnell und stark ausgeprägte Melanocyten-stimulierende Wirkung Diese ist bei beiden Substanzen annähernd gleich und führt nach 2–3 Monaten zur Entwicklung intradermaler Naevi.Das Cocarciogen Crotonöl ruft eine wesentlich schwächere und das hyperplasiogene Nichtcarcinogen Benzanthracen nur eine angedeutete Reaktion der Melanocyten hervor, die bei beiden nur auf das Corium beschränkt ist. Coriale Naevi werden von diesen beiden Substanzen in den ersten 3–4 Monaten nicht hervorgerufen. Dopaoxydase-positive Melanocyten beteiligen sich nicht an der Bildung von Papillomen, Keratoacanthomen und Carcinomen.