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At least 703 records · Page 39Linked to original sources
PubMed1999

Beta1-adrenergic receptors but not beta2-adrenergic or vasopressin receptors regulate K+ secretion in vestibular dark cells of the inner ear.

Receptors were identified pharmacologically in functional studies where K+ secretion was monitored as transepithelial current (Isc). Further, receptors were identified as transcripts by cloning and sequencing of reverse-transcriptase polymerase chain reaction (RT-PCR) products. Isc under control conditions was 796 +/- 15 microA/cm2 (n = 329) in gerbilline VDC and 900 +/- 75 microA/cm2 (n = 6) in murine VDC. Forskolin (10(-5) m) but not 1, 9-dideoxy-forskolin increased Isc by a factor of 1.42 +/- 0.05 (n = 7). 10(-9) m Arg8-vasopressin and 10(-9) m desmopressin had no significant effect in gerbilline and murine VDC. Isoproterenol, norepinephrine, epinephrine and prenalterol stimulated Isc maximally by a factor of 1.38 +/- 0.04 (n = 7), 1.59 +/- 0.06 (n = 6), 1.64 +/- 0.03 (n = 8) and 1.37 +/- 0.03 (n = 6), respectively. The EC50 values were (1.4 +/- 0.7) x 10(-8) m (n = 36), (2.5 +/- 1.0) x 10(-8) m (n = 31), (1.7 +/- 0.7) x 10(-7) m (n = 36) and (5 +/- 4) x 10(-7) m (n = 32), respectively. Propanolol inhibited isoproterenol-induced stimulation of Isc. Atenolol, ICI118551 and CGP20712A inhibited isoproterenol-induced stimulation of Isc with a pKDB of 5.0 x 10(-8) m (pKDB = 7.30 +/- 0.07, n = 38), 4.4 x 10(-8) m (pKDB = 7.36 +/- 0.14, n = 37) and 6.8 x 10(-12) m (pKDB = 11.17 +/- 0.12, n = 37), respectively. RT-PCR of total RNA isolated from microdissected vestibular labyrinth tissue using specific primers revealed products of the predicted sizes for beta1- and beta2-adrenergic receptors but not for beta3-adrenergic receptors. Sequence analysis of the amplified cDNA fragments from gerbilline tissues revealed a 96.4%, 91.5% and 89.6% identity compared to rat beta1-, beta2- and beta3-adrenergic receptors, respectively. These results demonstrate that K+ secretion in VDC is under the control of beta1- but not beta2- or beta3-adrenergic receptors or vasopressin-receptors.

Adrenergic beta-1 Receptor Agonists↗
PubMedDate not supplied

Interphase cytogenetics and comparative genomic hybridization of human epithelial cancers and precursor lesions.

The accuracy of cytogenetic analyses of human solid cancers has improved enormously over the past decade by the introduction and refinement of DNA in situ hybridization (ISH) techniques. This methodology can be applied to cells in the interphase state, thereby making it an excellent tool for the delineation of chromosomal aberrations in solid tumors. The use of non-isotopic ISH to intact and disaggregated cancer specimens will be discussed, as well as comparative genomic hybridization (CGH) with tumor-derived DNAs. In this review we will focus on hybridocytochemical interphase approaches for the detection of chromosomal changes in frequently occurring human epithelial malignancies, e.g., breast, lung, and prostate carcinomas. We will further discuss the use of ISH procedures for the genetic analysis of precursor conditions leading to invasive carcinomas. Knowledge concerning these precancerous conditions is increasing, and its importance in cancer prevention has been recognized. Interphase cytogenetics by ISH, as well as CGH, with DNAs derived from microdissected, precancerous, dysplastic tissue areas will increase our understanding of these lesions, both at the investigative and diagnostic levels.

Humans↗
PubMed2002

Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a destructive lung disease characterized by a diffuse hamartomatous proliferation of smooth muscle cells (LAM cells) in the lungs. Pulmonary LAM can occur as an isolated form (sporadic LAM) or in association with tuberous sclerosis complex (TSC) (TSC-LAM), a genetic disorder with autosomal dominant inheritance with various expressivity resulting from mutations of either the TSC1 or TSC2 gene. We examined mutations of both TSC genes in 6 Japanese patients with TSC-LAM and 22 patients with sporadic LAM and identified six unique and novel mutations. TSC2 germline mutations were detected in 2 (33.3%) of 6 patients with TSC-LAM and TSC1 germline mutation in 1 (4.5%) of 22 sporadic LAM patients. In accordance with the tumor-suppressor model, loss of heterozygosity (LOH) was detected in LAM cells from 3 of 4 patients with TSC-LAM and from 4 of 8 patients with sporadic LAM. Furthermore, an identical LOH or two identical somatic mutations were demonstrated in LAM cells microdissected from several tissues, suggesting LAM cells can spread from one lesion to another. Our results from Japanese patients with LAM confirmed the current concept of pathogenesis of LAM: TSC-LAM has a germline mutation but sporadic LAM does not; sporadic LAM is a TSC2 disease with two somatic mutations; and a variety of TSC mutations causes LAM. However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM.

Chromosomes, Human, Pair 16↗
PubMed2005

Frequent down-regulation of HIVEP2 in human breast cancer.

The HIVEP2 gene, located on 6q23-q24, belongs to a family of genes that encodes large zinc fingers containing transcription factor proteins. Although this gene has been implicated in the regulation of immune responses and cellular proliferation, its functions are largely unknown. In the present study, we investigated HIVEP2 gene abnormalities in microdissected breast cancer tissue. For real-time quantitational RT-PCR analysis of paired normal and tumor tissues, mRNA levels were down-regulated to a maximum of 96%. The overall median expression level in breast cancer (33 cases) was significantly lower than that in normal breast tissue (normalized median value of 4.49 versus 17.68; p < 0.0001). Through full-length 5'-RACE (rapid amplification of cDNA ends) analysis, we identified multiple exons in the 5'-untranslated regions with multiple transcriptional start sites, four of which were located in a large CpG island. No tissue- or cancer-specific usage patterns for the transcription start sites were identified by multiplex RT-PCR analysis. Only faint methylation was detected in the 5' region of the island in normal cells and breast cancer tissue, indicating physiological, aging and no tumor-specific methylation. Mutation screening showed only germline polymorphisms. Thus, down-regulation of the HIVEP2 genes frequently occurs and may be one of the genetic events responsible for breast cancer, and their transcription may be regulated by complex mechanisms involving interactions with other factors and/or by other genetic/epigenetic mechanisms.

5' Untranslated Regions↗
PubMed1981

Vascularity of gastrointestinal staple lines demonstrated with silicone rubber injection.

Gastrointestinal stapling devices were applied across canine small intestine, and then the blood supply of the stapled segments was immediately filled with silicone rubber. After tissue clearing and microdissection, the outstanding vascularity of the staple lines was clearly demonstrated. The B configuration of the closed staple allows blood vessels of substantial size to pass through it. This might make staple technique especially advantageous whenever vascularity is critical.

Animals↗
PubMed2005

Two-dimensional electrophoresis database of fluorescence-labeled proteins of colon cancer cells.

We constructed a novel database of the proteome of DLD-1 colon cancer cells by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of fluorescence-labeled proteins followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis. The database consists of 258 functionally categorized proteins corresponding to 314 protein spots. The majority of the proteins are oxidoreductases, cytoskeletal proteins and nucleic acid binding proteins. Phosphatase treatment showed that 28% of the protein spots on the gel are phosphorylated, and mass spectrometric analysis identified 21 of them. Proteins of DLD-1 cells and of laser-microdissected colon cancer tissues showed similar distribution on 2D gels, suggesting the utility of our database for clinical proteomics.

Amino Acid Sequence↗
PubMed2005

Array comparative genomic hybridization analysis of uterine leiomyosarcoma.

PURPOSE: Using a genome-wide array-based comparative genomic hybridization (array-CGH), DNA copy number changes in uterine leiomyosarcoma were analyzed. MATERIALS AND METHODS: We analyzed 4 cases of uterine leiomyoma and 7 cases of uterine leiomyosarcoma. The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted. Array-based CGH and fluorescence in situ hybridization (FISH) were carried out with Genome database (Gene Ontology). RESULTS: Uterine leiomyoma showed no genetic alterations, while all of 7 cases of uterine leiomyosarcoma showed specific gains and losses. The percentage of average gains and losses were 4.86% and 15.1%, respectively. The regions of high level of gain were 7q36.3, 7q33-q35, 12q13-12q15, and 12q23.3. And the regions of homozygous loss were 1p21.1, 2p22.2, 6p11.2, 9p21.1, 9p21.3, 9p22.1, 14q32.33, and 14q32.33 qter. There were no recurrent regions of gain, but recurrent regions of loss were 1p21.1-p21.2, 1p22.3-p31.1, 9p21.2-p22.2, 10q25-q25.2, 11q24.2-q25, 13q12-q12.13, 14q31.1-q31.3, 14q32.32-q32.33, 15q11-q12, 15q13-q14, 18q12.1-q12.2, 18q22.1-q22.3, 20p12.1, and 21q22.12-q22.13. In the high level of gain regions, BAC clones encoded HMGIC, SAS, MDM2, TIM1 genes. Frequently gained BAC clone-encoded genes were TIM1, PDGFR-beta, REC Q4, VAV2, FGF4, KLK2, PNUTL1, GDNF, FLG, EXT1, WISP1, HER-2, and SOX18. The genes encoded by frequently lost BAC clones were LEU1, ERCC5, THBS1, DCC, MBD2, SCCA1, FVT1, CYB5, and ETS2/E2. A subset of cellular processes from each gene was clustered by Gene Ontology database. CONCLUSION: Using array-CGH, chromosomal aberrations related to uterine leiomyosarcoma were identified. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.

Adult↗
PubMed1999

Association of K-ras mutations with p16 methylation in human colon cancer.

BACKGROUND & AIMS: K-ras mutations are early genetic changes in colon cancer. p16, a tumor-suppressor gene, is inactivated in neoplasms by mutation, deletion, or methylation. The aims of this study were to determine p16 methylation status and its possible association with K-ras mutations in human colon cancer. METHODS: DNA isolated from 8 colon cancer cell lines and 41 microdissected human colon tissue samples was analyzed. p16 methylation status was determined using two analytical methods. The level of p16 expression was determined by reverse-transcription polymerase chain reaction and Northern blot. K-ras mutations were determined by DNA sequence analysis. The DNA methyltransferase activity was determined by microassay. Parental and K-ras-transformed IEC-18 cells were used to determine the potential association between K-ras mutations and p16 methylation. RESULTS: Methylated p16 was found in 100% of colon cancer cell lines, 55% of colon cancers, 54% of adenomas, and 25% of transitional mucosa but not in normal colonic epithelium. Forty-five percent of cancers and 38% of adenomas showed both K-ras mutations and p16 methylation. Of 11 cancers and adenomas with K-ras mutation, 10 specimens showed methylated p16. In contrast, of 13 adenomas and cancers with wild-type K-ras, only 3 specimens showed methylated p16 (P = 0.001). Stable transformation of IEC-18 cells with K-ras increased the DNA methyltransferase activity, methylated the p16 gene, and suppressed the expression of p16. Treatment with a DNA methylation inhibitor (azadeoxycytidine) resulted in reexpression of p16 in K-ras-transformed IEC-18 cells, suggesting that the expression of p16 was suppressed by DNA methylation. CONCLUSIONS: p16 methylation occurs frequently in human colonic adenomas and cancers and is closely associated with K-ras mutations.

Azacitidine↗
PubMed1997

Increase in mRNAs encoding neonatal II and III sodium channel alpha-isoforms during kainate-induced seizures in adult rat hippocampus.

Subtypes I, II and III of sodium channel alpha-subunit mRNAs were analyzed in adult rat brain areas after kainate-induced seizures. Tissue samples were microdissected from occipital neocortex, CA1 and CA3 hippocampus areas and dentate gyrus. Three reverse transcriptase-polymerase chain reaction (RT-PCR) protocols were undertaken to amplify these mRNAs. Amplification products were then distinguished after digestion by restriction enzymes, electrophoresis separation and densitometric analysis of gel profiles. PCR 1 evidenced the relative percentage of mRNAs I, II and III as well as neonatal II and III subtype isoforms, which resulted from an alternative splicing. PCR 2 and 3 were performed to focus on the neonatal vs. adult ratio in II and III subtypes, respectively. Seizures were shown to induce an increase in both neonatal subtypes, which suggested an alteration at the splicing level. These changes exhibited a peculiar brain regional distribution, the maximal effect being observed in dentate gyrus and hippocampus CA1 area. In situ hybridization experiments, using a digoxigenin-labeled oligonucleotide probe-specific for neonatal II and III mRNAs, confirmed this increase in neonatal mRNA subtypes. These changes were transient, reaching a maximum 6 h after drug injection, then disappearing between 12 and 48 h. They were prevented by a pre-treatment of animals by MK-801, a non-competitive antagonist of NMDA receptors. This work, thus, suggested that KA-induced seizures can be accompanied by transient alteration in the splicing pattern of sodium channel alpha-subunit mRNAs which resulted in an increase in expression of their neonatal isoforms within localized areas of adult rat brain.

Animals↗
PubMed2001

Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women.

The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers. BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (< or = 40 years, Group 1) and 80 patients with age > 55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89.7% vs. 56.3% p < 0.001), node-positive (53.8% vs. 38.7%), larger size (p = 0.017), higher mitotic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.001, respectively). D17S855 LOH was 32.8% in group 1 vs. 21% in group 2; D17S786 LOH was 50.7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correlated with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in group 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p = 0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.

Adult↗
PubMed1996

Ki-ras point mutations and proliferation activity in biliary tract carcinomas.

The association between Ki-ras mutations and proliferation activity was investigated in a comprehensive series of biliary tract carcinomas (BTCs). We precisely microdissected samples of tissue from paraffin-embedded sections of 77 BTCs including 22 intrahepatic cholangiocarcinomas (ICCs), 36 extrahepatic cholangiocarcinomas (ECCs), and 19 gall bladder carcinomas (GBCs). Ki-ras mutations at exons 1 and 2 were determined by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method and confirmed by direct sequencing. Proliferation activity was immunohistochemically assessed to generate proliferating cell nuclear antigen labelling indices (PCNA LIs). Ki-ras mutations were detected in 10 of 22 ICCs (45%), 24 of 36 ECCs (67%), and in 16 of 19 GBCs (84%). The frequency of Ki-ras mutations in peripheral type ICCs was 33% (4 of 12) and that in the hilar type ICCs was 60% (6 of 10). In ECCs the highest value of 82% (9 of 11) was found for carcinomas located in the lower part of the biliary tree. Mean PCNA LI in mutation-positive BTCs was significantly elevated compared with the mutation-negative value. These results indicate frequent involvement of Ki-ras mutations in BTCs, especially in GBCs and in distal ECCs, and that carcinomas harbouring a mutation feature high cell proliferation activity.

Biliary Tract Neoplasms↗
PubMed1982

Polycystic kidney and liver disease in Springbok: I. Morphology of the lesions.

Spontaneous polycystic kidney and liver disease in an inbred herd of Springbok (Antidorcas marsupialis) was studied by light microscopy, transmission electron microscopy, and microdissection. Springbok are a small species of gazelle of the family Bovidae native to South Africa. Since 1976, 18% of all live calves born have had nephromegaly and died within 2 weeks of birth. Examination of kidney and liver from ten calves which had died or were sacrifices since 1978 revealed bilateral, symmetrical nephromegaly due to moderate to marked focal dilatation of tubules predominately in the outer zone of the medulla. Microdissection of renal tissue from three affected calves indicated polycystic kidneys had cysts in all of the bends of Henle's loops, over half of the ascending limbs, and about one fourth of the collecting ducts. All of these calves had proliferation and cystic dilatation of bile ducts in most hepatic portal areas. The bile ducts were irregularly dilated and confluent with only a slight increase in periductular connective tissue. Ultrastructural studies revealed no consistent changes in the basement membranes of either the renal or hepatic cysts. This disease has several features similar to the autosomal recessive form of polycystic kidney disease in man and may prove a useful animal model.

Animals↗
PubMed2001

Detection of Toxoplasma gondii DNA in primary intraocular B-cell lymphoma.

Primary intraocular lymphoma, a variant of primary central nervous system lymphoma with ocular involvement, is a large B-cell non-Hodgkin's lymphoma. Some cases of primary intraocular lymphoma have been reported to be associated with microorganisms including Epstein-Barr virus (EBV) and human herpes virus-8 (HHV-8), but not parasites. We analyzed 10 cases of primary intraocular lymphoma using microdissection and PCR. Tumor and normal cells were microdissected from ocular tissue on slides and subjected to PCR for genes from Toxoplasma gondii, EBV, and HHV-8. We detected Toxoplasma gondii, not HHV-8 or EBV, DNA in the lymphoma but not in normal cells of two cases that resembled ocular toxoplasmosis clinically. We speculate that Toxoplasma gondii may play a role in some forms of primary intraocular B-cell lymphoma.

Adult↗
PubMed2002

Expression of mRNA and functional alpha(1)-adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons.

1. Locus coeruleus neurons in adult rats express binding sites and mRNA for alpha(1)-adrenoceptors even though the depolarizing effect of alpha(1)-adrenoceptor agonists on neonatal neurons disappears during development. 2. In this study intracellular microelectrodes were used to record from locus coeruleus neurons in brain slices of adult rats and reverse transcription-polymerase chain reaction (RT - PCR) was used to investigate the mRNA expression of alpha(1)- and alpha(2)-adrenoceptors in juvenile and adult rats. 3. The alpha(1)-adrenoceptor agonist phenylephrine had no effect on the membrane conductance of locus coeruleus neurons (V(hold) -60 mV) but decreased the G protein coupled, inward rectifier potassium (GIRK) conductance induced by alpha(2)-adrenoceptor or mu-opioid agonists. The GIRK conductance induced by noradrenaline was increased in amplitude when alpha(1)-adrenoceptors were blocked with prazosin. 4. RT - PCR of total cellular RNA isolated from microdissected locus coeruleus tissue demonstrated strong mRNA expression of alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptors in both juvenile and adult rats. However, only mRNA transcripts for the alpha(1b)-adrenoceptors were consistently detected in cytoplasmic samples taken from single locus coeruleus neurons of juvenile rats, suggesting that this subtype may be responsible for the physiological effects seen in juvenile rats. 5. Juvenile and adult locus coeruleus tissue expressed mRNA for the alpha(2a)- and alpha(2c)-adrenoceptors while the alpha(2b)-adrenoceptor was only weakly expressed in juveniles and was not detected in adults. 6. The results of this study show that alpha(1)-adrenoceptors expressed in adult locus coeruleus neurons function to suppress the GIRK conductance that is activated by mu-opioid and alpha(2)-adrenoceptors.

Action Potentials↗
PubMed2001

Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer.

We have identified 14-3-3 sigma (sigma) as a gene whose expression is lost in breast carcinomas, primarily by methylation-mediated silencing. In this report, we investigated the timing of loss of sigma gene expression during breast tumorigenesis in vivo. We analysed the methylation status of sigma in breast cancer precursor lesions using microdissection for selective tissue sampling. We found hypermethylation of sigma in 24 of 25 carcinomas (96%), 15 of 18 (83%) of ductal carcinoma in situ, and three of eight (38%) of atypical hyperplasias. None of the five hyperplasias without atypia showed sigma-hypermethylation. Unexpectedly, patients with breast cancer showed sigma hypermethylation in adjacent histologically normal breast epithelium, while this was never observed in individuals without evidence of breast cancer. Also, samples of periductal stromal breast tissue were consistently hypermethylated, underscoring the importance of selective tissue sampling for accurate assessment of 14-3-3-sigma methylation in breast epithelium. These results suggest that hypermethylation of 14-3-3-sigma occurs at an early stage in the progression to invasive breast cancer, and may occur in apparently normal epithelium adjacent to breast cancer. These results provide evidence that loss of expression of sigma is an early event in neoplastic transformation.

14-3-3 Proteins↗
PubMed2000

F-actin fiber distribution in glomerular cells: structural and functional implications.

BACKGROUND: Glomerular distention is associated with cellular mechanical strain. In addition, glomerular distention/contraction is assumed to influence the filtration rate through changes in filtration surface area. A contractile cytoskeleton in podocytes and mesangial cells, formed by F-actin-containing stress fibers, maintains structural integrity and modulates glomerular expansion. In this study, the glomerular cell distribution of F-actin and vimentin filaments was studied in normal control and nine-month streptozotocin-diabetic rats. Results in situ were compared with observations in tissue culture. METHODS: Microdissected rat glomeruli were perfused to obtain a physiological 25% glomerular expansion over the basal value. Fixation was done without change in glomerular volume. Dual fluorescent labeling of F-actin and vimentin was carried out, and samples were examined by confocal laser scanning microscopy. RESULTS: The podocyte cell bodies and their cytoplasmic projections, including the foot processes, contained bundles of vimentin-containing fibers. Except for a thin layer at the base of foot processes, they did not demonstrate F-actin. While mesangial cells in culture had F-actin as long stress fibers resembling tense cables, mesangial cells stretched in situ contained a maze of short tortuous F-actin fibers organized in bundles that often encircled vascular spaces. This fibrillar organization was disrupted in diabetic glomeruli. CONCLUSION: Mesangial cells, but not podocytes, contain a cytoskeleton capable of contraction that is disorganized in long-term diabetes. Together with previous observations, the distribution of this cytoskeleton suggests that mesangial cell contraction may be involved in the redistribution of glomerular capillary blood flow, but not substantially in the modulation of glomerular distention. Disorganization of stress fibers may be a cause of hyperfiltration in diabetes.

Actins↗
PubMed2001

Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder.

Approximately 2/3 of patients diagnosed with superficial transitional cell carcinoma of the urinary bladder (TCC) will recur within 2 years. Loss of chromosome 9 and loss of heterozygosity (LOH) at 9q34 in index TCCs identify a subset of patients at high risk of recurrence. This study explores genetic alterations on chromosomes 4, 8, 11 and 17 as predictors of recurrence. A total of 109 carcinomas were investigated at 26 loci. DNA was extracted from microdissected archival normal/tumour tissue and was analysed for loss of heterozygosity (LOH). Fluorescent PCR was performed and genotyping carried out on a Perkin Elmer ABI377 sequencer. LOH of D11S490 or D17S928 was significantly more frequent in index carcinomas of patients who experienced recurrence compared to those with no recurrence (P = 0.004 and 0.019 respectively). These results suggest that loss of these regions is associated with recurrence of TCC. Further investigation is required to identify genes in these regions, which might be responsible for driving recurrence in TCC of the urinary bladder.

Carcinoma, Transitional Cell↗
PubMed2003

A panoramic view of gene expression in the human kidney.

To gain a molecular understanding of kidney functions, we established a high-resolution map of gene expression patterns in the human kidney. The glomerulus and seven different nephron segments were isolated by microdissection from fresh tissue specimens, and their transcriptome was characterized by using the serial analysis of gene expression (SAGE) method. More than 400,000 mRNA SAGE tags were sequenced, making it possible to detect in each structure transcripts present at 18 copies per cell with a 95% confidence level. Expression of genes responsible for nephron transport and permeability properties was evidenced through transcripts for 119 solute carriers, 84 channels, 43 ion-transport ATPases, and 12 claudins. Searching for differences between the transcriptomes, we found 998 transcripts greatly varying in abundance from one nephron portion to another. Clustering analysis of these transcripts evidenced different extents of similarity between the nephron portions. Approximately 75% of the differentially distributed transcripts corresponded to cDNAs of known or unknown function that are accurately mapped in the human genome. This systematic large-scale analysis of individual structures of a complex human tissue reveals sets of genes underlying the function of well-defined nephron portions. It also provides quantitative expression data for a variety of genes mutated in hereditary diseases and helps in sorting candidate genes for renal diseases that affect specific portions of the human nephron.

Cluster Analysis↗