Is renal preservation with pulsatile perfusion a model for reperfusion?
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Adenosine↗
Biomedical subjects
V Paradis
Publications and source records attributed to V Paradis.
What is the value of procurement biopsy lipid peroxidation lesions in the assessment of kidney graft function?
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Aldehydes↗
Clonal analysis of micronodules in virus C-induced liver cirrhosis using laser capture microdissection (LCM) and HUMARA assay.
Most hepatocellular carcinomas (HCC) arise from malignant transformation of regenerative cirrhotic nodules. Because HCC has a very poor prognosis, detection of these premalignant lesions may improve the management of patients with cirrhosis. In this regard, clonal analysis of liver micronodules should be of particular interest in order to differentiate polyclonal regenerative micronodules from monoclonal neoplastic potentially malignant micronodules. To address this issue, 112 micronodules from 15 cases of explanted liver cirrhosis were carefully microdissected from paraffin-embedded tissue using a laser capture microscopy system. Clonal analysis was performed by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each microdissected micronodule, a large set of pathological features was evaluated and correlated with their clonal status. Clonal analysis showed that 57 micronodules (51%) were monoclonal and 55 (49%) were polyclonal. Prevalence of monoclonal nodules ranged from 25% to 71% according to cases. In all cases, mono- and polyclonal nodules were randomly distributed in the cirrhotic liver. Although the clonal status was not significantly affected by the presence or absence of macronodules in the adjacent liver, size of monoclonal micronodules was significantly larger than size of polyclonal micronodules (mean size of the monoclonal nodules: 3 + 0.1 mm vs mean size of the polyclonal nodules: 2.5 +/- 0.1 mm, p = 0.007). Among the elementary pathological features evaluated, only the presence of iron overload was correlated with a monoclonal status (p = 0.04). In conclusion, clonal analysis of liver cirrhosis shows that 51% of micronodules are monoclonal lesions, supporting the notion that liver cirrhosis is a multineoplastic lesion. Because monoclonality is a marker of neoplasia, cirrhosis with accumulation of monoclonal nodules may be carefully followed, and monoclonal nodules should be screened for additional markers to assess their biological behavior.
Adult↗
Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay.
Recent observations support the notion that telomerase expression is essential for the formation of human tumor cells [W-C. Hahn et al., Nature (Lond.), 400: 464-468, 1999]. The expression pattern of hTERT, the human telomerase catalytic subunit gene, is a rate-limiting determinant of the enzymatic activity of human telomerase. We have developed a real-time quantitative RT-PCR assay based on Taq-Man fluorescence methodology to quantify the full range of hTERT mRNA copy numbers. We validated the method on a series of 134 unilateral invasive primary breast cancer patients with known long-term outcome. Three-quarters of the breast tumors (75.4%; 101 of 134) were hTERT positive, i.e., contained detectable and quantifiable hTERT mRNA. hTERT-positive patients had significantly shorter relapse-free survival (P = 0.017) after surgery compared with hTERT-negative patients. The prognostic significance of hTERT status persisted in Cox multivariate regression analysis. When we subdivided hTERT-positive patients (n = 101) into three equal groups (tumors showing small, intermediate, or high increase in hTERT mRNA content), we observed statistical (or a trend toward) links between high hTERT mRNA levels and Scarff-Bloom-Richardson histopathological grade III (P = 0.066), and negative estrogen (P = 0.002) and progesterone (P = 0.048) receptor status, and therefore with higher aggressiveness of breast tumors. High hTERT mRNA levels were also linked to MYC gene overexpression (P = 0.007). These findings show that the quantitative evaluation of hTERT mRNA can have important prognostic significance in human breast cancer. In addition, our simple, rapid, and semiautomated assay method is suitable for routine hTERT mRNA detection and quantification and will be a powerful tool in large, randomized, prospective, cooperative group trials and in the hTERT-based therapy project.
Adult↗
Molecular expression of PSMA mRNA and protein in primary renal tumors.
Human prostate-specific membrane antigen (PSMA), a 100-kDa integral transmembrane glycoprotein, is considered to be a highly specific marker of the prostate gland, and has successfully been used as a marker of circulating prostatic epithelial cells. Extended PSMA homology has been demonstrated with a cDNA found in rat cerebral and renal tissues. In this study, we aimed to evaluate the expression of PSMA mRNA in a variety of human renal cancer tissues (n = 20) and cell lines (n = 12). Using reverse transcriptase-polymerase chain reaction, DNA sequencing, blottings, and specific anti-PSMA labelling with CYT 351 antibody, we identified PSMA mRNA and protein in normal and in neoplastic renal tissue. The sequence of the polymerase-chain-reaction products is identical to that of PSMA cDNA derived from prostate tissue. Immunological staining with the CYT 351 reveals that PSMA is expressed mainly in tubular cells. Since PSMA does not appear to be restricted to prostatic tissue, this novel biomarker may prove useful in the staging of renal cancer and in the search for the hematogenous spread of renal cells.
Adenocarcinoma↗
Expression of the RNA component of human telomerase (hTR) in prostate cancer, prostatic intraepithelial neoplasia, and normal prostate tissue.
Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected by a polymerase chain reaction (PCR)-based assay (TRAP) in many immortal cell lines and various cancers, including prostate cancers. To investigate the role of telomerase in prostate cancer at the cellular level, the expression of one of the ribonucleoprotein complexes, the RNA component of human telomerase (hTR), was studied in normal, preneoplastic, and cancerous prostate tissues using a non-radioactive in situ hybridization procedure. Nine human prostates resected at the time of radical prostatectomy were studied. In each case, archival paraffin-embedded samples from normal tissue, prostatic intraepithelial neoplasia (PIN) lesions, the putative precancerous lesion, and prostate carcinomas were selected for in situ hybridization. hTR mRNA expression was detected in carcinomatous glands of seven out of the nine cancers (75 per cent). Furthermore, in seven out of the eight cases showing PIN lesions, the epithelial cells of PIN foci also expressed hTR mRNA. By contrast, in normal tissue, epithelial cells were negative, whereas hTR mRNA expression was detected in the basal cells. The detection of hTR mRNA in PIN lesions clearly strengthens the link between PIN and carcinomatous glands and suggests that telomerase expression occurs early in prostate carcinogenesis. Furthermore, this study confirms previous experimental data suggesting that the basal cell layer is the stem cell compartment in prostate.
Aged↗
Expression of connective tissue growth factor in experimental rat and human liver fibrosis.
Connective tissue growth factor (CTGF) stimulates in vitro fibroblast proliferation and extracellular matrix synthesis. The aim of this study was to assess the role of CTGF in liver fibrogenesis. CTGF expression was investigated both at the protein and mRNA level in biopsies of chronic liver diseases, in experimental models of liver fibrosis, and in hepatic stellate cells in culture. CTGF immunostaining was observed in most human liver biopsies with significant fibrosis. An increase of CTGF immunostaining was associated with a higher score of fibrosis both in the group of chronic hepatitis C (chi(2) = 9.3; P <.01) and in the non-hepatitis C group (chi(2) = 7.2; P <.02). In situ hybridization showed CTGF mRNA expression in spindle cells in both the fibrous septa and sinusoidal lining. In experimental models of liver fibrosis, CTGF accumulated in parallel with the development of septal fibrosis and cirrhosis. Quantification of CTGF mRNA by a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay showed a significant increase of CTGF mRNA in both CCl(4)-induced and bile duct-ligated rat models of liver fibrosis. Expression of CTGF protein and mRNA was definitively assigned to hepatic stellate cells, because CTGF was detected by Western blot both in lysate and supernatant of a hepatic stellate cell line derived from rats. These cells also displayed CTGF protein and mRNA as shown by immunohistochemistry and in situ hybridization. In conclusion, this study shows that CTGF is strongly expressed during liver fibrogenesis, and hepatic stellate cells seem to be the major cellular sources of CTGF in the liver.
Adolescent↗
Caverno-pudendal nervous communicating branches in the penile hilum.
Classically, the peripheral neural pathways for erection are proerectile, issuing from the parasympathetic sacral fibres, and antierectile from the thoracolumbar sympathetic trunk. The cavernous nerves as terminal branches of the pelvic plexus convey the parasympathetic fibres to the penis. The pudendal nerve conveys sensory fibres from the penis and somatic fibres to the bulbos-pongiosus and ischiocavernosus striated mm. In animals, it has been demonstrated that the dorsal nerve of the penis contains sympathetic fibres. These findings suggest that communicating branches exist between the cavernous nerves and the dorsal nerve. Our aim in this study was to demonstrate the presence of such connections in man. We dissected 20 fresh male cadavers. The pelvic plexus and pudendal nerves were dissected to identify their terminal branches and connections. Histologic study was performed. Our results showed evidence of communicating nervous branches between the cavernous nerves and the dorsal nerve of the penis. Several variants existed concerning the number and type of connections. The presence of such communicating branches proves that the supralevator and infralevator neural pathways communicate and suggest the possibility of a kind of plasticity of the nervous supply of penile erection. Further studies are needed to identify the nature of these communicating branches.
Adult↗
Chester-Erdheim disease: a neoplastic disorder.
Chester-Erdheim disease is a rare non-langerhans cell histiocytosis characterized by a xanthomatous infiltration of foamy macrophages. The cause and pathogenesis remain unclear. The aim of the present study was to determine whether Chester-Erdheim disease is a polyclonal reactive disease or a clonal neoplastic disorder. The clonal status of samples obtained from five patients with Chester-Erdheim disease was studied. DNA was extracted from fixed and paraffin-embedded sections after microdissection and clonal status was studied using the Xchromosome inactivation pattern of the human androgen receptor gene (HUMARA assay). One patient was homozygous for the HUMARA gene and noninformative. Three other cases were monoclonal. One was polyclonal, and this case showed a dense reactive infiltrate in association with spumous macrophages. This study suggests strongly that Chester-Erdheim disease is a monoclonal lesion consistent with neoplastic disorder. Thus, Chester-Erdheim disease may be considered as the "macrophage" counterpart of Langerhan's cell histiocytosis in the histiocytosis spectrum. Further studies are needed to establish the origin of this clonal proliferation.
Adult↗
Supra and infralevator neurovascular pathways to the penile corpora cavernosa.
The aim of this study was to provide a comprehensive description of both penile innervation and vascularisation. Eighty-five male cadavers were examined through gross and microscopic anatomical analysis. The pelvic nerve plexus had both parasympathetic and sympathetic roots. It was distributed to the external urethral sphincter giving rise to cavernous nerves which anastomosed in 70% of the cases with the pudendal nerve in the penile root. Accessory pudendal arteries were present in the pelvis in 70% of the cases, anastomosing in 70% of the cases with the cavernous arteries that originated from the pudendal arteries. Transalbugineal anastomoses were always seen between the cavernous artery and the spongiosal arterial network. There were 2 venous pathways, 1 in the pelvis and 1 in the perineum with a common origin from the deep dorsal penile vein. It is concluded that there are 2 neurovascular pathways destined for the penis that are topographically distinct. One is located in the pelvis and the other in the perineum. We were unable to determine the functional balance between these 2 anastomosing pathways but experimental data have shown that they are both involved in penile erection. These 2 neurovascular pathways, above and below the levator ani, together with their anastomoses, form a neurovascular loop around the levator ani.
Aged↗
Abnormal restriction pattern of PIP gene associated with human primary prostate cancers.
The PIP gene, localized in the 7q34 region that contains a number of fragile sites such as FRA 7H and FRA TI, codes for gp17/PIP, a protein secreted by breast apocrine tumors. We analyzed the integrity of this gene in 20 tumors of the urogenital tract. We found rearranged EcoRI fragments in 5 of 15 primary prostate carcinomas. No rearrangement was found in normal prostates derived from five patients undergoing prostatocystectomy during treatment of bladder cancers. By Southern blot hybridization with PIP gene exon-specific probes, the rearrangements were mapped at or near the 3' end of the gene. These abnormalities were found, not only in the neoplastic cells invading the prostatic tissues, but also in seminal vesicles without histologic tumoral features. These data suggest a critical role of the PIP gene or neighboring genes in prostate cancer.
Apolipoproteins↗
Detection of telomerase in hepatocellular carcinomas using a PCR ELISA assay: comparison with hTR expression.
BACKGROUND: While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected in many immortal cell lines and various cancers. AIM: To investigate telomerase expression in hepatocellular carcinoma, and to assess the expression of the RNA component of telomerase, hTR. METHODS: 39 hepatocellular carcinomas were studied using a telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay, which does not require radioactive PCR amplification and yields a semiquantitative measurement. Expression of hTR was also assessed by a non-radioactive in situ hybridisation procedure. The correlations between these two markers and the clinicopathological data were analysed. RESULTS: Telomerase activity was detected in 23 of 39 hepatocellular carcinoma specimens (59%). Comparison of hepatocellular carcinoma with and without telomerase expression, or with high and low telomerase (10 cases v 13 cases), showed no differences in the principal clinicopathological data. Although median survival was lower in the group with detectable telomerase activity than in that with undetectable activity (510 v 720 days) the difference was not significant (log-rank test, p = 0.08). hTR expression was detected in 11 of 14 cases of hepatocellular carcinoma tested (78%) and in four of 12 samples of adjacent non-cancerous tissue (33%). Five tumours and four non-cancerous tissues were positive for hTR, whereas no telomerase activity was detected in these. CONCLUSIONS: The presence of telomerase activity in hepatocellular carcinomas is confirmed. No correlation was observed between clinicopathological data and telomerase expression in hepatocellular carcinoma, but survival seemed better in the absence of telomerase expression. hTR seems to be more widely expressed than telomerase.
Adult↗
CD44 is an independent prognostic factor in conventional renal cell carcinomas.
PURPOSE: CD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions. De novo expression of CD44 and its variant isoforms has been associated with aggressive behavior in various tumors. Since few data are available concerning the role of CD44 in the biological behavior of locally confined renal tumors, we analyzed the expression of CD44 in a large set of conventional renal cell carcinomas to determine its prognostic value in association with other clinicopathologic variables. MATERIALS AND METHODS: Ninety-one patients with locally confined conventional renal cell carcinomas were studied. CD44 standard form (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. The prognostic value of the usual clinicopathological variables and CD44 expression was tested using Kaplan-Meier plots by the log rank test and Cox multiple hazard regression analysis. RESULTS: No immunostaining was observed in normal renal tissue. Thirty-two of the 66 conventional renal cell carcinomas (48%) showed CD44H membranous staining of the tumor cells. Only 2 cancers displayed CD44v6 immunostaining. Among the different clinicopathological variables analyzed, tumor stage (p = 0.001), nuclear grade (p = 0.01), size (p = 0.02), vascular (p = 0.05) and perirenal adipose tissue invasion (p = 0.005), and CD44H expression (p = 0.01) were found to be significant prognostic parameters for survival using univariate analysis. Moreover, multivariate analysis indicated stage, nuclear grade and CD44 expression as independent prognostic factors both for overall and disease-free survival. CONCLUSION: CD44 can be considered as a useful prognostic parameter in conventional renal cell carcinoma and may be used in evaluation of the outcome of these tumors.
Adult↗
In situ detection of lipid peroxidation by-products as markers of renal ischemia injuries in rat kidneys.
PURPOSE: Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. In renal transplantation, this mechanism is triggered by ischemia/reperfusion and may be of relevance in graft failure. MATERIALS AND METHODS: Using specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, we investigated, in situ, by means of an immunohistochemical procedure, the occurrence of lipid peroxidation during different warm ischemic periods of 0, 15, 30, 45 and 60 minutes in rat kidneys prior to reperfusion. The same experiments included followup of the rats after nephrectomy and reperfusion for 10 days. RESULTS: We observed superficial and deep cortex immunostaining with both antibodies against MDA and HNE after 30 minutes of warm ischemia. This immunostaining was observed in the absence of any histological lesions, as assessed by routine staining. After 45 and 60 minutes of warm ischemia, lipid peroxidation byproducts were detected both in the cortex and in the medulla, which is associated with 33% and 66% of rat deaths respectively. CONCLUSIONS: This study confirms the involvement of the lipid peroxidation process in kidney damage during anoxia before reperfusion, and its extension to the whole organ. Lipid peroxidation byproducts were detectable in warm ischemic kidney, and the presence of medulla immunostaining was associated with the animals' death. Lipid peroxidation immunostaining might thus be useful as a sensitive tool to detect ischemic damage after warm ischemia prior to reperfusion, as well as in the decision to carry out kidney transplantation in humans.
Aldehydes↗
Successful treatment of encrusted pyelitis in a renal transplant with local acidification and surgical ileocaliceal anastomosis.
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Adult↗
Clonal analysis of macronodules in cirrhosis.
Several arguments suggest that most hepatocellular carcinomas (HCCs) occurring in human cirrhotic livers arise from large hepatocellular nodules or macronodules. Except for nodules with obvious features of HCC, there exist no consistent criteria enabling the differentiation between benign regenerative and neoplastic, potentially malignant macronodules. Surrogate markers able to accurately discriminate those lesions that will evolve toward a HCC are required. In this study, we investigated the clonality of 26 macronodules isolated from eight cases of explanted cirrhotic livers in women by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each macronodule, a large set of pathological features was evaluated and used to classify the macronodules into four groups: entirely benign-looking nodule (type 1), low-grade dysplastic nodule (type 2), high-grade dysplastic nodule (type 3), and HCC (type 4). Clonal analysis showed that 14 macronodules (54%) were monoclonal and 12 (46%) were polyclonal. Monoclonality was detected in 5 of 11 (45%) nodules from groups of entirely benign-looking and low-grade dysplastic nodules (types 1 and 2) and in 9 of 15 (60%) nodules from the group of high-grade dysplastic nodule and HCC (types 3 and 4). Neither the etiology of cirrhosis nor the size or histological classification of macronodules was correlated with the clonal status. In conclusion, clonal analysis of macronodules enables the differentiation between mono- and polyclonal macronodules in cirrhosis. Because monoclonal macronodules are prone to evolve to HCC, the determination of the clonal status of a macronodule could provide additional information for evaluating the prognosis of these lesions.
Adult↗
Bcl-2 and Bax expression on rat ischemic kidney.
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Animals↗
Clonal analysis of renal sporadic angiomyolipomas.
Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.
Adult↗