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C P Nelson

Publications and source records attributed to C P Nelson.

9 recordsLinked to original sources
PubMed2001

GSTA1 expression in normal, preneoplastic, and neoplastic human prostate tissue.

BACKGROUND: Glutathione S-transferases (GSTs), inducible enzymes that catalyze the detoxification of reactive electrophiles and oxidants, protect against neoplastic transformation. Prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) fail to express GSTP1, a major class of GST. This failure of expression is associated with methlyation of the GSTP1 promoter, a somatic alteration proposed to be a critical step in prostatic carcinogenesis. However, simple atrophy and post-atrophic hyperplasia-proliferative lesions associated with chronic inflammation, which we have termed "proliferative inflammatory atrophy" (PIA)-express elevated levels of GSTP1. We postulated that this increase in GSTP1 expression in PIA occurs in response to increased oxidative stress. We examined the expression of another major class of GST, GSTA1, in the human prostate. METHODS: We performed immunohistochemistry against GSTA1 on formalin-fixed radical prostatectomies (n = 45). A stereological grid point counting method was used to estimate the percent of cells staining positive for GSTA1 in normal prostate, PIA, HGPIN, and adenocarcinoma. RESULTS: In contrast to GSTP1, normal peripheral zone epithelium was virtually devoid of GSTA1. Strikingly, though, epithelial cells in PIA demonstrated strong staining for GSTA1 (median of percent of cells staining positive = 44) as compared to those in normal peripheral zone (median = 3.0, P <.00001), HGPIN (median = 2.9, P <.00001), and adenocarcinoma (median = 3.8, P <.00001). Variations in GSTA1 were also detected between normal anatomic zones: the central zone showed an increase in the percentage of cells staining positive (median = 20.9) as compared to the transition (median = 0.47, P <.0002) and the peripheral (P <.0001) zones. CONCLUSIONS: Expression of GSTA1 is increased in PIA, supporting the concept that cells within these lesions are subject to localized increases in oxidative stress. Low levels of GSTA1 and GSTP1 in HGPIN and adenocarcinoma suggest a broad lack of detoxification activity in these cells, which may be associated with carcinogenesis in the prostate.

Adenocarcinoma↗
PubMed2001

Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1.

The prostate has been identified as a target for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced carcinogenesis. Humans are exposed to PhIP through ingestion of well-done cooked meats, and there is evidence from epidemiological studies that implicates red meat consumption in prostate carcinogenesis. The alpha and pi class isoforms of glutathione S-transferases (GSTs) have been shown to inhibit adduction of activated PhIP metabolites to DNA in cell-free systems. In humans, silencing of GST pi(GSTP1) through CpG island hypermethylation is found in nearly all prostate carcinomas and is believed to be an early event in prostate carcinogenesis. We hypothesized that suppressed GSTP1 expression in prostate cells would increase their vulnerability to cytotoxicity and DNA adduct formation mediated by activated PhIP metabolites. To test this hypothesis, the human prostate adenocarcinoma cell line, LNCaP, which contains a silenced GSTP1 gene, was genetically modified to constitutively express high levels of GSTP1. Both LNCaP and LNCaP-GSTP1 cells exposed to N-OH-PhIP, but not parent PhIP, for 24 h showed a dose-dependent decrease in cell viability. GSTP1-overexpressing cells had LC50s 30-40% higher than cells transfected with the vector alone. PhIP-DNA adducts isolated from LNCaP-derived cells and primary human prostate tissue cultures exposed to N-OH-PhIP were analyzed by liquid chromatography/electrospray ionization mass spectrometry. Primary cultures of human prostate tissue and LNCaP-GSTP1 cells had approximately 50% lower adduct levels than parental LNCaP and vector control cells. Bioactivation assays using LNCaP cytosols showed that enzymatic activation of N-OH-PhIP to a DNA binding species was dependent on ATP and could be inhibited by recombinant human GSTP1 in the presence of glutathione. This evidence confirms that N-OH-PhIP can be bioactivated to a DNA binding species in human prostate and human prostate-derived cells. These observations provide the basis for using LNCaP and LNCaP-GSTP1 cells as a model system for studying the role of this enzyme in protection against N-OH-PhIP induced DNA damage in prostate carcinogenesis. Loss of GSTP1 expression in human prostate may, therefore, enhance its susceptibility to carcinogenic insult by compounds such as N-OH-PhIP. Conversely, induction of GSTs in early-stage prostate carcinogenesis may be a useful protective strategy.

Adenocarcinoma↗
PubMed2001

Sales and science: changing patterns of pharmaceutical and medical device advertising in peer reviewed urology publications, 1975-2000.

PURPOSE: The effects of advertising on urological practice are controversial. We studied patterns of pharmaceutical and medical device marketing in peer reviewed urological journals in 1975 and 2000. MATERIALS AND METHODS: Pharmaceutical and medical device advertising in 1 European and 2 American peer reviewed urological journals were evaluated in 4 randomly selected issues of each journal published in 1975 and 2000, respectively. Advertising quantity and the qualitative characteristics of each advertisement were analyzed. RESULTS: We analyzed 574 advertisements in 24 issues. Advertising decreased between 1975 and 2000 based on the number of pages per issue (55.3 to 31.9, p = 0.04), number of advertisements per issue (30.4 to 17.4, p = 0.0098) and the ratio of advertising-to-scientific pages (0.399 to 0.151, p = 0.0016). Mean advertisement length was stable at 1.8 pages. The top 3 advertisers in 1975 were Eaton, Roche and Warner compared with Pfizer, AstraZeneca and Merck in 2000. Advertising for antibiotics comprised 70.3% of all pharmaceutical advertisements in 1975 but only 15.2% in 2000 (p = 0.0001), while advertising for benign prostatic hyperplasia, erectile dysfunction and hormonal therapy increased sharply. Nutritional supplement marketing increased from 0.5% of all advertisements in 1975 to 4.3% in 2000 (p = 0.0026). The incidence of advertisements citing peer reviewed literature increased from 16.7% to 33% (p = 0.0001) with a greater increase in the European than in the American journals. CONCLUSIONS: Advertising in peer reviewed urological journals has decreased since 1975 and fewer companies now market more products. Few advertisements cite the scientific literature. Better understanding of pharmaceutical marketing patterns may improve awareness of these efforts to influence physician practice.

Advertising↗
PubMed2001

Comparison of shockwave lithotripsy outcomes in patients receiving sufentanil or lidocaine spinal anesthesia.

PURPOSE: To determine whether the use of intrathecal sufentanil, which allows the patient to move during shockwave lithostripsy (SWL), affects treatment outcomes and operative and recovery times compared with standard lidocaine spinal anesthesia. PATIENTS AND METHODS: We retrospectively studied a series of 62 SWL procedures performed on an unmodified Dornier HM3 lithotripter. The mean calculus size was 10.7 mm. There were 46 renal calculi, 13 ureteral calculi, and 4 patients with calculi in both locations. Of the 63 procedures, 25 were performed using intrathecal sufentanil alone, and 37 were performed with intrathecal lidocaine with or without additional agents. We compared treatment outcomes, as well as treatment time, fluoroscopy time, postanesthesia care unit (PACU) time, time to voiding, and time to ambulation. RESULTS: Sufentanil use was associated with a significantly higher rate of successful treatment, defined as residual fragments absent or <4 mm on follow-up imaging, compared with lodocaine: 68% v. 40% (p = 0.0394). There was no significant difference between the groups in treatment time or fluoroscopy time. Use of sufentanil was associated with significantly shorter PACU time, time to ambulation, and time to voiding postoperatively. These differences persisted when men and women were analyzed separately, although the differences were less significant in women. CONCLUSIONS: The use of intrathecal sufentanil for anesthesia during SWL does not adversely affect treatment outcome; it is, in fact, associated with better outcomes. The advantages of this agent in shortening recovery times and in easing patient transfer into the HM3 gantry argue for increasing its use.

Adult↗
PubMed2001

Preneoplastic prostate lesions: an opportunity for prostate cancer prevention.

Environmental factors, especially the diet, play a prominent role in the epidemic of prostate cancer (PCA), in the United States. Many candidate dietary components have been proposed to influence human prostatic carcinogenesis, including fat, calories, fruits and vegetables, anti-oxidants, and various micronutrients, but the specific roles dietary agents play in promoting or preventing PCA remain controversial. We have collected evidence to suggest that GSTP1, the gene encoding the pi-class glutathione S-transferase (GST), may serve a "caretaker" function for prostatic cells. Although GSTP1 can be detected in normal prostatic epithelium, in almost all PCA cases, PCA cells fail to express GSTP1 polypeptides, and lack of GSTP1 expression most often appears to be the result of somatic "CpG island" DNA methylation changes. Loss of GSTP1 function also appears to be characteristic of prostatic epithelial neoplasia (PIN) lesions, thought to represent PCA precursors. We have recently learned that a new candidate early PCA precursor lesion, proliferative inflammatory atrophy (PIA), characterized by proliferating prostatic cells juxtaposed to inflammatory cells, contains epithelial cells that express high levels of GSTP1. These findings have formed the basis for a new model of prostatic carcinogenesis, in which prostatic cells in PIA lesions, subjected to a barrage of inflammatory oxidants, induce GSTP1 expression as a defense against oxidative genome damage. When cells with defective GSTP1 genes appear amongst the PIA cells, such cells become vulnerable to oxidants and electrophiles that inflict genome damage that tends to promote neoplastic transformation to PIN and PCA cells. Subsequently, PIN and PCA cells with defective GSTPI genes remain vulnerable to similar stresses tending to promote malignant progression. This new model for prostatic carcinogenesis has implications for the design of new prostate cancer prevention strategies. Rational prevention approaches might include: (i) restoration of GSTPI expression via treatment with inhibitors of CpG methylation, (ii) compensation for inadequate GSTPI activity via treatment with inducers of general GST activity, and (iii) abrogation of genome-damaging stresses via avoidance of exogenous carcinogens and/or reduction of endogenous carcinogenic (particularly oxidant) stresses.

Adenocarcinoma↗
PubMed2000

Activation of epithelial Na(+) channel activity in the rabbit urinary bladder by cAMP.

The rabbit urinary bladder actively absorbs Na(+) from the urine. The rate-limiting step in this process is the diffusion of Na(+) across the apical membrane of bladder epithelial cells, mediated by amiloride-sensitive epithelial Na(+) channels. We have investigated the effects of cAMP on epithelial Na(+) channel activity in the rabbit bladder by measuring the amiloride-sensitive short-circuit current across bladders mounted in Ussing chambers. Three agents that raise intracellular cAMP levels (forskolin, dibutyryl-cAMP and 3-isobutyl-1-methylxanthine (IBMX)) increased the amiloride-sensitive short-circuit current relative to control preparations. The forskolin-induced increase in amiloride-sensitive short-circuit current was significantly inhibited by the vesicle fusion inhibitor brefeldin A and the protein synthesis inhibitor cycloheximide. These findings, together with the magnitude and protracted time course of the cAMP effects, suggests that cAMP stimulates the insertion of new Na(+) channels into the apical membrane of the rabbit bladder epithelium.

1-Methyl-3-isobutylxanthine↗
PubMed1994

ELISA of IgG antibody to oxidized low-density lipoprotein: effects of blocking buffer and method of data expression.

We describe an ELISA for serum IgG antibodies against malondialdehyde-modified low-density lipoprotein (mLDL). Optimal antigen concentration, serum dilution, and dilution of enzyme-conjugated second antibody were 25 mg/L, 1:250, and 1:5000, respectively, when 5 g/L human serum albumin was used for blocking. When data were expressed as mLDL/LDL (the ratio of IgG binding to mLDL vs LDL), within-run and between-run CVs were 7.0% and 8.9%, respectively. Antibody concentrations expressed as mLDL/LDL or as mLDL-LDL (the difference between IgG binding to mLDL and to LDL) were higher in women with systemic lupus erythematosus (n = 20) than in controls (n = 20) (P < 0.001). With bovine serum albumin or Superblock blocking buffers, only the mLDL-LDL data were significant. Thus, the choice of blocking agent and the method of data expression should be carefully considered when assaying IgG antibodies against mLDL.

Adolescent↗
PubMedDate not supplied

EUTUBS: a mnemonic for the complete endoscopic examination of the lower urinary tract.

Urethrocystoscopy is now routinely done in standard Urological practice. The availability of the flexible cystoscope for outpatient procedures has further increased the number of cystoscopists. However, there are currently no formal training schedules for urethrocystoscopy. This mnemonic has been developed to serve as a template for complete endoscopic examination of the lower urinary tract to which the cystoscopist may refer when undertaking this operation. It focuses on the common abnormalities that the endoscopist may encounter, and is not intended to be an exhaustive list of all abnormalities of the lower urinary tract. Furthermore, it is not meant to obviate the need for practical training of those wishing to carry out the procedure as part of their clinical practice.

Abbreviations as Topic↗