Contribution of proteomics to the molecular analysis of renal cell carcinoma with an emphasis on manganese superoxide dismutase.

Renal cell carcinoma (RCC) originates in the renal cortex. It accounts for 2-3 percent of all cancers occurring in adults and it is characterised by lack of early clinical manifestations, unpredictable outcome, and absence of effective treatment modalities except early surgery. RCC comprises a heterogeneous group of tumours with various molecular and cytogenetic abnormalities and different histological features as cell types and tumour architecture. Molecular genetic and proteomic tools led to the discovery of potential diagnostic prognostic and therapeutic biomarkers of RCC. In this review we discuss recent developments in understanding genotype-phenotype relationships, with attention to manganese superoxide dismutase, a mitochondrial enzyme related to the redox cycle which affects various regulatory functions of cells. The expression of this protein has been evaluated in numerous human tumour types including RCC, and post-translational modifications are being investigated.

Modified expression of plasma glutathione peroxidase and manganese superoxide dismutase in human renal cell carcinoma.

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool to separate thousands of polypeptides and to highlight the modification of protein expression in malignant diseases. By applying 2-D PAGE to ten normal human kidney and ten homologous renal cell carcinoma (RCC) tissues, we found two peptides in all ten normal tissues but not in RCCs and, conversely, two peptides were detected in all RCCs but not in normal tissues. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and internal sequence analysis, the two first peptides were identified as two isoforms of plasma glutathione peroxidase (GPxP). The two other peptides isolated in all RCCs but not in normal tissues were identified by N-terminal sequence analysis as multimeric forms of manganese superoxide dismutase (Mn-SOD). No multimeric Mn-SODs and only two monomeric forms were detected in normal tissues. GPxP and Mn-SOD are metallo-enzymes encoded on chromosome 5q32 and on chromosome 6p25, respectively. Their regions are within the locus 5q21-->qter and 6q21-6q27 on which deletions and translocations are described in some cytogenetic studies of RCC transformation. Therefore, our results might suggest a correlation between the modified expression of GPxP and Mn-SOD in tumor tissues and chromosomal modifications, and that the two proteins may be putative markers for diagnosis of RCC.

Renal cell carcinoma and normal kidney protein expression.

Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular and cytogenetic analysis have highlighted deletions, translocations, or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC have not yet provided a marker for early renal cell carcinoma diagnosis. Current diagnostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxido-reductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution.

Cost/benefit analysis of hospital operations: reducing length of stay.

Today's healthcare environment continues to become more competitive. Mergers and affiliations occur at breakneck speed, and anxiety regarding managed care contracts increases. In this fast paced environment integrated hospital systems need to become more in tune with the ¿business¿ side of healthcare, which includes the cost of providing and receiving payment for health care services. Too often providers do not realize the total cost of providing care, nor do they understand the nature of payment/reimbursement for services provided. This article looks at how to analyze the cost of hospital operations from a provider's point of view.

Is memory impairment greater than cognitive impairment in moderate chronic alcoholics?

The aims of the research were to test (i) whether moderate chronic alcoholics (A/pts) perform worse than non teetotaler controls (C/pts) either on memory or on intelligence tasks or on both, and (ii) whether there was a significant difference between verbal and spatial memory scores pointing to the claimed prevailing right hemisphere sensitivity to alcohol abuse. Great care was taken in selecting C/pts not to exaggerate by sample biasing the psychological effects of alcoholism. Intelligence was tested by means of verbal and performance Wechsler-Bellevue IQ and Raven PM47; memory was tested by means of serial immediate memory span and learning by means of verbal and spatial devices. The results support the conclusion that chronic wine alcoholism in a band of drinkers with lowish educational background and very set drinking habits impairs memory and intelligence without any significant difference. Moreover there is no evidence of a prevalent right hemisphere sensitivity to chronic alcohol addiction.