Biomedical subjects

R Buttyan

Publications and source records attributed to R Buttyan.

At least 91 records · Page 5Linked to original sources

PubMed1995

Clusterin expression and apoptosis in tissue remodeling associated with renal regeneration.

To analyze the role of clusterin in renal diseases involving a regenerative process, we have used a novel rodent model to compare temporal and spatial expression of clusterin mRNA. Thus, renal artery stenosis was used to induce unilateral non-infarctive renal atrophy. After several weeks, when cellular pathology of atrophic kidneys involved minimal apoptosis or inflammatory response and mitosis was at normal levels, regeneration of atrophic kidneys was stimulated by removal of the contralateral healthy kidneys. The regrowth response was very rapid and involved renal hyperplasia rather than hypertrophy. Regenerating kidneys were studied 0, 4, 8, 24 hours and 2, 3, 5, 7, and 14 days after contralateral nephrectomy. Several parameters were compared: level and localization of clusterin mRNA; cell proliferation; cell dedifferentiation and redifferentiation and apoptosis. During the acute regenerative phase (first 24 hr) clusterin expression was markedly increased, decreasing to untraceable levels by five days of regeneration. Clusterin mRNA was localized in dilated or collapsed atrophic tubules that had lost identifying surface structures of normal tubular epithelium (termed dedifferentiated). Clusterin was also localized in the periphery of some blood vessel walls. Cell proliferation peaked at three to five days of regeneration, and was also localized in dedifferentiated tubules. Despite the regenerative stimulus, an unexpected result was a transient but marked increase in apoptotic cell death in atrophic tubules in the first 24 hours of regeneration. Our results provide evidence of a temporal association between increased clusterin expression and apoptosis, but in situ localization showed clusterin mRNA over apparently viable, as well as apoptotic, cells in the epithelium of tubules showing clusterin expression. Clusterin mRNA was rarely identified over epithelial cells in foci of non-atrophic (non-dedifferentiated) nephrons that responded to the regenerative stimulus by cellular hypertrophy. The dramatic response after initiation of regeneration, especially the initiation of apoptosis in the tubular epithelium, may have applications for the study of genetic changes leading to renal oncogenesis.

Animals↗

PubMed1995

Molecular staging of prostate cancer. II. A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for prostate specific antigen versus prostate specific membrane antigen.

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80%) had positive polymerase chain reactions for PSA, while only 10 (50%) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cN0M0), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67% versus 34% sensitivity for detecting capsular penetration, 87% versus 46% sensitivity for detecting disease to the surgical margin and 83% versus 16% sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Adenocarcinoma↗

PubMed1995

Genetic and cellular characteristics of bladder outlet obstruction.

Urinary bladder outlet obstruction is a common medical problem. In order to understand the effects of outlet obstruction on bladder morphology, physiology, and pharmacology, several animal models of obstruction have been developed using a variety of species. Although there are marked differences in bladder size, capacity, compliance, physiology, and pharmacology among these species, responses to outlet obstruction have many common characteristics. This article will be separated into six areas: introduction, genetic factors mediating the response during the initial period of partial outlet obstruction and overdistension, cytostructural alterations that accompany compensated bladder function, alterations in innervation accompanying bladder hypertrophy secondary to partial outlet obstruction, alterations in calcium translocation during bladder hypertrophy, and metabolic factors involved in the response to partial outlet obstruction.

Animals↗

PubMed1994

An early molecular response induced by acute overdistension of the rabbit urinary bladder.

In the rabbit, partial urinary bladder outlet obstruction rapidly increases bladder mass and alters several parameters of normal bladder function. Previous experiments on this animal model (Buttyan et al. Neurourol. Urodyn. 11:225-238, 1992) had identified an early molecular response to partial outlet obstruction that involved the profound induction of mRNA encoding a heat-shock gene, hsp-70, as well as induced expression of mRNA for basic fibroblast growth factor and certain protooncogenes. Numerous physiological studies of the hypertrophied rabbit bladder indicate that the primary stimulus for bladder growth may be the initial overdistension that occurs as the bladder fills following partial outlet obstruction. The present study was undertaken to determine if the sequence and characteristics of gene activation during the recovery following a brief period of overdistension of the rabbit bladder are comparable with the gene activity previously described in association with partial outlet obstruction. Rabbit bladders were overdistended to 20% above capacity for 1 hr and then relieved. Bladders were recovered from control (untreated) rabbits and from rabbits at 1 hr or at 1, 3 or 5 days following relief of overdistension. RNAs extracted from these tissues were examined by Northern blot assays for a number of different mRNA transcripts previously shown to be altered by partial outlet obstruction. By 1 hr following the relief from acute overdistension, there was already a greater than 10-fold increase in the expression of hsp-70 related transcripts as well as a marked increase in the expression of mRNA encoding bFGF and decreased expression of TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Enhanced expression of p53 mRNA and protein in the regressing rat ventral prostate gland.

Previously, increased expression of mRNA encoding the p53 tumor suppressor protein was described during castration-induced regression of the rat ventral prostate gland with Northern blot techniques. This activity was confirmed with a ribonuclease protection assay that demonstrated a 16-fold induction of p53 transcripts in ventral prostate RNA within 72 hrs after castration. The induced expression of p53 mRNA correlated with increased detection of p53 protein in nuclei of regressing prostate epithelial cells. Immunohistochemical staining with anti-p53 antibody was strongly reactive for epithelial nuclei in castrated glands but unreactive for nuclei of control adult glands. In contrast to the upregulation of p53 in regressing prostate glands with a large proportion of apoptotic cells, expression of p53 mRNA was decreased in rat prostate glands that were stimulated to regrow by testosterone replacement.

Animals↗

PubMed1994

Apoptosis: molecular control point in toxicity.

Apoptosis is a controlled form of cell death that serves as a molecular point of regulation for biological processes. Cell selection by apoptosis occurs during normal physiological functions as well as toxicities and diseases. Apoptosis is the counterpart and counterbalance to mitosis in cell population determination. Complex patterns of cell signaling and specific gene expression are clearly involved in the control of cell fate. Exposure to an apogen, a trigger of apoptosis, can significantly increase apoptotic cell loss during homeostatic processes as well as acute or chronic toxicities. Alternately, suppression of apoptosis through, for example, interference in cell signaling can result in pathological accumulation of aberrant cells and diseases such as tumors. Investigations into the mechanisms underlying apoptosis have extended into many areas, driven by increasingly sophisticated instrumental and molecular biology techniques. This symposium summary explores related aspects of apoptosis, including control of cell population size and function, specific gene activity and regulation, chromatin condensation and scaffold detachment, oxidative stress-induced cell proliferation versus death by apoptosis or necrosis, and hepatotoxicant-induced apoptosis versus necrosis. Insights into the mechanisms governing apoptosis and increasing appreciation of the relevance of apoptotic cell death are redirecting research in toxicology and carcinogenesis and are yielding novel therapeutic approaches for the control of toxicity, disease, and ultimately perhaps senescence.

Alkylation↗

PubMed1994

Update on bladder smooth-muscle physiology.

The urinary bladder responds to distension induced by a number of different stresses with rapid and substantial increases in bladder mass and concomitant alterations in the contractile responses to neuronal stimulation, pharmacological simulation by autonomic agonists, and membrane depolarization. Furosemide, sucrose, or diabetes-induced diuresis, as well as outlet obstruction and overdistension all produce similar effects on the bladder. Accompanying the increases in bladder mass and contractile changes are increases in DNA synthesis and [3H]-thymidine uptake. Autoradiographic studies have localized the increased DNA synthesis following bladder distension initially to the urothelium, followed by slower increases in labelling of the lamina propria and extramural connective tissue. The net result of these compartmental differences in DNA synthesis is a reorganization of the structural relationships between smooth-muscle cells, the connective-tissue matrix, and the extrinsic connective-tissue lamina. This may contribute to the functional changes which occur after severe overdistension. Increases in the expression of heat-shock protein-70, basic fibroblast growth factor, N-ras, and c-myc, and decreases in transforming growth factor-beta occurred acutely after obstruction, suggesting that these changes may play a role in obstruction-induced bladder hypertrophy. Removal of the obstruction induces apoptosis of urothelial and connective tissue elements in the bladder, accompanied by increases in transforming growth factor-beta and decreases in basic fibroblast growth factor genes, and a reversal of the bladder dysfunction. Therefore the bladder hyperplasia after outlet obstruction and the regression following removal of the obstruction seem to be directly opposing processes governed by gene expression.

Animals↗

PubMed1994

Molecular staging of prostate cancer with the use of an enhanced reverse transcriptase-PCR assay.

OBJECTIVE: Because up to 40 percent of surgically treated patients with prostate cancer are subsequently found to be clinically understaged, a more sensitive staging modality to identify extraprostatic disease prior to surgery is required. METHODS: We describe an enhanced reverse transcriptase [RT] polymerase chain reaction (PCR) assay utilizing oligonucleotide primers specific for the human prostate-specific antigen (PSA). This assay identifies PSA-synthesizing cells from reverse transcribed mRNA. This assay was applied to RNAs extracted from the peripheral blood lymphocytes of 65 patients with clinically localized prostate cancer. In addition, blood from 20 women, 20 young men, 25 age-matched control men under treatment for benign prostatic hyperplasia (BPH), and 18 men with established, untreated metastatic prostate cancer was tested. RESULTS: An RT-PCR assay for PSA can recognize one PSA-expressing cell diluted into one hundred thousand lymphocytes. The sensitivity of this assay can be enhanced by the addition of digoxigenin-modified nucleotides to the PCR reaction and this assay was applied to RNAs extracted from the peripheral lymphocyte fraction of 148 prostate cancer patients and controls at this institution. Although no specimen from women or men without cancer was positive in this assay, 14 of 18 metastatic prostate cancer patients were positive (77.8%). Additionally, 25 of 65 (38.5%) patients with clinically localized disease (T1-2b) were positive from blood specimens obtained prior to surgery. Final pathologic results from this group of patients identified a correlation between positivity on this assay and the presence of capsular tumor penetration (sensitivity, 68%; specificity, 84%) as well as strong correlation with the finding of carcinoma at the surgical margin (sensitivity, 87%; specificity, 76%). Logarithmic regression analysis of the results of the RT-PCR assay indicates its remarkable superiority to digital rectal examination, computed tomography scan, endorectal coil magnetic resonance imaging, PSA, prostate-specific antigen density, or Gleason score for predicting the true pathologic stage of prostate cancer in these surgically treated patients. CONCLUSIONS: An RT-PCR assay using PSA primers to detect prostate cells in the peripheral circulation of surgical-candidate patients is significantly correlated with capsular penetration and tumor-positive surgical margins. This molecular assay provides a sensitive and specific means to stage correctly apparent localized prostate cancer prior to radical prostatectomy.

Adult↗

PubMed1994

Neurotrophic factors in the rat penis.

An intact nerve supply is essential for normal erectile function. We have undertaken a study to examine the presence and synthesis of growth factors of the penis that support neural function. Extracts were obtained from deskinned penises of Sprague-Dawley rats, aged 3, 6 and 10 weeks, representing prepubertal, pubertal and postpubertal states. Penile extracts were subjected to Northern blot analysis to evaluate expression of nerve growth factor-beta (beta-NGF)-mRNA, PC-12 bioassay to quantitate the nerve growth promoting activity and immunoassay to detect the amount of beta-NGF protein. These initial experiments showed a disproportionately abundant level of nerve growth promoting activity as compared with the levels detected with the immunoassay. The PC-12 bioassay is sensitive to both beta-NGF and fibroblast growth factors (FGFs). To further investigate these findings, the bioassay was conducted again after heparin chromatography, with beta-NGF receptor blockade, or with the addition of anti-beta-NGF, anti-basic-FGF, or anti-acidic-FGF. These studies confirmed that the abundant nerve growth promoting activity in the rat penis is due largely to basic FGF. In conclusion, the neurotrophin NGF is expressed in the rat penis at levels consistent with its expression in other peripheral tissues. Basic-FGF, on the other hand, has been detected at levels far in excess of NGF. Since erectile function is dependent on the integrity of the vascular structure and its intact innervation and since basic FGF presents as an abundant penile growth factor with both angiogenic and neurotrophic activities, basic FGF might play a significant role in erectile physiology.

Animals↗

PubMed1994

Hyperplasia and apoptosis. Opposing cellular processes that regulate the response of the rabbit bladder to transient outlet obstruction.

BACKGROUND: Partial obstruction of the rabbit urethra induces rapid bladder growth. This growth is characterized by hypertrophy of smooth muscle cells in addition to hyperplasia of cells in the urothelium and serosa. The local synthesis of growth factors has been proposed to be influential in this growth since partial outlet obstruction rapidly increases the bladder's expression of basic fibroblast growth factor, while suppressing the expression of transforming growth factor-beta. Upon release of the outlet obstruction, the hypertrophied bladder regresses to its normal weight. Here, we examined whether regression of the hypertrophied rabbit bladder involves apoptosis (programmed cell death) of specific cellular elements and whether the expression of growth factors is altered concomitant with apoptotic cell deletion. EXPERIMENTAL DESIGN: Regressing rabbit bladders were analyzed for markers of apoptosis, including DNA fragmentation and histology. An in situ enzymatic immuno-histochemical procedure was utilized to localize apoptotic cells in these tissues. Finally, Northern blot analysis was used to identify changes in the expression of basic fibroblast growth factor and transforming growth factor-beta during bladder regression. RESULTS: Regressing rabbit bladders demonstrated the characteristic electrophoretic "ladder" pattern of DNA fragmentation associated with apoptosis. An in situ technique to distinguish cells with degraded nuclear DNA identified apoptosis only within the urothelium and serosal lamina of the regressing bladders. RNAs extracted from regressing bladders exhibited decreased expression of basic fibroblast growth factor mRNA as well as increased expression of transforming growth factor-beta 1 mRNA when compared with RNAs from hypertrophied bladders. CONCLUSIONS: We conclude that hyperplasia and apoptosis are opposing cellular processes that mediate the bladder's response to short-term obstructive stimuli and that local synthesis of growth-promoting and growth-inhibitory factors may be responsible for initiating both of these responses.

Animals↗

PubMed1993

Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat.

We describe early alterations in rat bladder gene expression which may relate to the development of diabetic bladder dysfunction in a streptozotocin model of inducible diabetes. Utilizing cDNA probes, the gene products sulfated glycoprotein-2 (SGP-2), transforming growth factor-beta (TGF-beta), beta-actin (beta-actin), N-ras and beta nerve growth factor (beta-NGF), were quantitated in bladders of male Sprague-Dawley rats at 1, 2, 4 and 6 weeks after induction of diabetes with streptozotocin (STZ). beta-actin and SGP-2 expression were transiently increased at 1 and 4 weeks after induction, respectively. TGF-beta was not altered over the period of the study. N-ras was reduced at all times compared with control rat bladders. Transcripts encoding beta-NGF were dramatically increased in STZ-treated rats at 4 weeks. None of these changes were seen in diuresis control group fed 5% sucrose. Our results suggest that during the early stages of diabetes, cellular hypertrophy, growth and remodeling are occurring concomitantly with cellular injury and programmed cell death. Furthermore, the transient increase in expression of beta-NGF mRNA may represent a compensatory response to the diabetic condition in an attempt to attract further innervation and revascularization.

Actins↗

PubMed1993

Rodent models for targeted oncogenesis of the prostate gland.

Currently, prostate cancer ranks as the most frequent non-skin malignancy detected in males. Yet, of the major human cancers, it remains one of the least understood in terms of its molecular and genetic basis. Research on prostate cancer has been limited by the paucity of tissues available for study. Much of the tissue obtained through surgery for localized prostate cancer will be required for pathological staging and grading. The more aggressive forms of prostate cancer are usually detected subsequent to metastatic involvement at which point there is little reason to surgically remove the prostate tumor(s). A final complication is the propensity of prostate cancer to metastasize to the bone, a site extremely difficult to obtain suitable biopsies for study. Further hindering research efforts on prostate cancer is the lack of suitable animal models for study. In contrast to its frequent occurrence in humans, prostate cancer is a rare event in most other mammalian species, particularly laboratory rodents. Therefore, in order to make this disease more amenable for study, there is a growing effort to identify or develop a means to target oncogenesis to the prostate gland of rodents. As will be reviewed here, this goal is being approached with the use of 3 different methods; one that takes advantage of the unique androgenic hormone requirement for prostate growth to exaggerate the effects of carcinogens at that site and two methods (recombinant retrovirus transduction prior to organ reconstitution and transgenic targeting) that allow direct genetic manipulation of cells in the prostate gland leading to the development of prostatic malignancy.

Animals↗

PubMed1993

Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.

Antibodies, Monoclonal↗

PubMed1992

Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle.

Castration initiates extensive apoptosis of the secretory epithelial cells lining the ducts of the rat ventral prostate, resulting in the striking regression of this male sexual accessory tissue. We had previously described the paradox of finding similar cascades of gene activity (c-fos greater than c-myc greater than hsp-70) induced during the early period of ventral prostate regression and during the regrowth of the ventral prostate gland initiated by testosterone replenishment. This common pattern of protooncogene expression during periods of predominant cellular apoptosis or proliferation caused us to examine further the possibility that the two cellular events occur through identical early molecular pathways. In the present study we demonstrate that apoptotic prostate epithelial cells incorporate bromodeoxyuridine into nuclear high-molecular-weight DNA prior to nuclear DNA fragmentation. The DNA synthetic activity occurs in coordination with a massive induction of proliferative cell nuclear antigen, a proliferation marker, in the nuclei of androgen-deprived prostatic epithelial cells. Moreover, this activity is also associated with the increased expression of mRNA encoding p53, a suppressor gene well known as a cell cycle-blocking agent. Our data indicate that quiescent (G0) prostate epithelial cells undergo apoptosis due to two sequential events initiated by testosterone depletion. The first event is the active reentry of these cells into the cell cycle. The second event is the apoptotic destruction resulting from the inability of the differentiated cells to successfully complete this cycle.

Animals↗

PubMed1992

Renal growth factor expression during the early phase of experimental hydronephrosis.

Unilateral ureteral obstruction in the rat leads to hydronephrosis of the affected kidney and renal cell deletion through the process of apoptosis. We studied this experimental model to determine whether acute alterations in renal growth factor expression might be involved in the initiation of the apoptotic response. Northern blot analysis of hydronephrotic, contralateral and sham operated kidney polyadenylated messenger ribonucleic acid (mRNA) was performed to quantitate the expression of mRNA encoding the growth factors epidermal growth factor, transforming growth factor-beta and insulin-like growth factor II during the first 48 hours following ureteral obstruction. Although the expression of the insulin-like growth factor II mRNA was unchanged by ureteral obstruction, the expression of epidermal growth factor mRNA rapidly declined in the obstructed kidney during this period. The loss of epidermal growth factor expression was further confirmed by an immunocytochemical staining procedure that demonstrated high concentrations of epidermal growth factor in control renal tubules and a drastic loss of this staining in obstructed renal tubules. In contrast, expression of transforming growth factor-beta mRNA increased in the obstructed kidney. We believe that the altered growth factor environment of the hydronephrotic kidney might be an initiating factor in the onset of renal apoptosis associated with this condition.

Animals↗

PubMed1992

Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia.

A multiparametric analysis to demonstrate that even brief periods of arterial clamping can initiate extensive cell loss in a rat kidney through the process of apoptosis during the 48-hour period after reperfusion was performed. Microscopic examination of rat renal tissues subject to a 5-, 30-, or 45-minute period of complete ischemia showed the presence of apoptotic bodies both within and occasionally between renal tubules, appearing as early 12 hours after reperfusion, and increasing in numbers at 24 hours. Furthermore, DNA extracted from such reperfused renal tissue demonstrated the appearance of a distinct "ladder" pattern of DNA fragments after electrophoresis in agarose gels, a phenomenon commonly associated with cells undergoing apoptosis and in contrast to the predominant smear pattern obtained after electrophoresis of DNA extracted from necrotic renal tissue. Finally, messenger RNA (mRNA) encoding sulfated glycoprotein-2, a gene product previously identified to apoptotic renal cells, was found to be highly expressed in the 30-minute arterial clamped rat kidney after 24 hours of reperfusion, but was not detectable in mRNA extracted from renal tissue after 24 hours chronic infarction. This study demonstrates that a combination of morphologic, biochemical, and molecular markers can be used to distinguish predominant modes of cell death in varying forms of tissue injury. Application of these analytical techniques to renal vascular injury has distinguished that brief periods of complete ischemia initiates a form of cell death (apoptosis) during a subsequent reperfusion phase that is drastically different from cellular necrosis induced by prolonged severe ischemia.

Animals↗

PubMed1991

Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications.

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis.

The onset of hydronephrosis following unilateral ureteral obstruction is associated with the induced expression of RNA and proteins encoded by the SGP-2 gene. SGP-2 expression has been shown to demarcate mammalian cells undergoing apoptosis. Using in situ hybridization, the cellular localization of SGP-2 expression in the obstructed kidney was determined as a means to study the various phases involved in the progression of hydronephrosis. Within 30 minutes of obstruction, SGP-2 mRNA expression was localized to the adventitial layers of the hilar arteries and intrarenal arterioles. Increasing time of obstruction resulted in the notable absence or depletion of this layer. In addition, the pattern of SGP-2 expression changed with time to the collecting ducts and distal tubules. This study identifies the vascular support tissue of the kidney as the initial site of reaction and potential cell death following ureteral obstruction. We believe that this observation may be of importance in explaining the early alterations in blood flow associated with hydronephrosis.

Animals↗