Potent induction of carcinogen defence enzymes with sulforaphane, a putative prostate cancer chemopreventive agent.
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Journal Article↗
Biomedical subjects
J D Brooks
Publications and source records attributed to J D Brooks.
Partial nephrectomy and caval thrombectomy for renal cell carcinoma in a solitary kidney with an accessory renal vein.
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Adult↗
Streptococcus waius sp. nov., a thermophilic Streptococcus from a biofilm.
Thermophilic streptococci were isolated from biofilms on stainless steel samples exposed to pasteurized skimmed milk and from dairy products from a dairy manufacturing plant. The phenotypic characters of these isolates were distinct from those of other thermophilic streptococci of dairy origin (Streptococcus thermophilus and Streptococcus bovis). Genotypic data [restriction endonuclease analysis, ribotyping, random amplified polymorphic DNA (RAPD) profiles, DNA-DNA hybridization and G + C contents] support the classification of these isolates as a new species. The sequence of the 16S rRNA was compared with that of 29 species of streptococci and shown to be significantly different. The sequence of the 16S-23S rRNA intergenic spacer region also differed from published sequences of closely related species. A fluorescent in situ hybridization probe prepared to a specific part of the 16S rRNA gene sequence was able to distinguish the unknown isolates from reference isolates of S. thermophilus and S. bovis. It is proposed that these thermophilic streptococcal isolates from a dairy environment be classified in the genus Streptococcus as a new species, Streptococcus waius (from waiu, the New Zealand Maori word for milk). The type strain is 3/1T (= NZRCC 20100T).
Animals↗
Male pelvic anatomy reconstructed from the visible human data set.
PURPOSE: To improve understanding of the male pelvic anatomy pertinent to urological surgery we performed computer generated, 3-dimensional reconstruction of the male pelvis from the Visible Human data set. MATERIALS AND METHODS: A total of 18 discrete anatomical structures, including the prostate, bladder, urethra, rectum and pelvic musculature, was segmented from the Visible Human cross-sectional data obtained from the National Library of Medicine. Using high speed computing and rendering software, 3-dimensional models of each structure were generated and assembled into composite figures. RESULTS: These reconstructions offer a revised view of pelvic anatomy as it has been traditionally depicted. The lateral surfaces of the levator ani muscle are oriented vertically in the pelvis and directly applied to the entire lateral surface of the prostate. The bladder rests primarily anterior to the prostate rather than directly above it, as has been commonly depicted. In the cross-sectional data and reconstructions the trigone and anterior fibromuscular stroma of the prostate appear as a single unit in continuity, which may have functional implications for understanding the mechanisms of continence at the bladder neck. The striated urethral sphincter appears circular with abundant tissue posteriorly. This sphincteric muscle has greater length anteriorly than posteriorly. CONCLUSIONS: These 3-dimensional reconstructions provide unique insights into male pelvic anatomy. They are a useful teaching tool for investigation and virtual reality modeling of the male pelvis.
Adult↗
CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia.
Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor lesion and a candidate biomarker for efficacy assessment in prostate cancer chemoprevention trials. Loss of expression of the pi-class glutathione S-transferase enzyme GSTP1, which is associated with the hypermethylation of deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene, is a near-universal finding in human prostate cancer. GSTP1 expression was assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide expression was evident in all normal prostatic tissues, all samples of high-grade PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the 10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both alleles; whereas 3 samples displayed no DNA methylation changes at either allele. GSTP1 CG island methylation changes were present in each of the five homozygous samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve as an important molecular genetic biomarker for both prostate cancer and PIN. The finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports a role for PIN lesions as a prostate cancer precursor and may provide insight to the molecular pathogenesis of prostate cancer.
Adenocarcinoma↗
The Swedish prostate cancer paradox.
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Humans↗
Methylation of the 5' CpG island of the endothelin B receptor gene is common in human prostate cancer.
Production of the potent vasoconstrictor endothelin-1 (ET-1) by human prostate cancer cells accompanies prostate cancer progression in vivo. The predominant endothelin receptor expressed by normal prostate epithelium, ETB, is not expressed by any of the established human prostate cancer cell lines, and ETB binding is decreased on prostate cancer tissues. ETB, which may mediate ET-1 clearance and may inhibit ET-1 secretion, is encoded by a gene that contains a 5' CpG island encompassing the transcriptional regulatory region. We examined this regulatory region of the ETB receptor gene (EDNRB) to determine whether hypermethylation of cytidine nucleotides accompanies decreased ETB expression in human prostate cancer. We found somatic methylation of CpG island sequences in EDNRB in 5 of 5 human prostate cancer cell lines, 15 of 21 primary prostate cancer tissues, and 8 of 14 prostate cancer metastases (70% of samples overall). Normal tissues contained only unmethylated EDNRB. Treatment of human prostatic carcinoma cell line cultures with 5-azacytidine induced ETB mRNA expression, suggesting that CpG island methylation changes might accompany the apparent transcriptional silencing of EDNRB in vivo.
Dinucleoside Phosphates↗
Pentachlorophenol dermal absorption and disposition from soil in swine: effects of occlusion and skin microorganism inhibition.
Residue of the environmentally relevant biocide pentachlorophenol (PCP) is found mainly in soil, making dermal contact one of the primary routes for PCP exposure. To quantify exposure effects on dermal absorption and systemic disposition, [14C-UL]PCP was dosed nonocclusively or occlusively at 40 micrograms/cm2 in a soil-based mixture in an in vivo swine model. Additionally, antibiotics were also codosed with occlusive PCP in soil to examine the impacts of skin microbial PCP biodegradation on total dermal absorption. Under nonocclusive, occlusive, and occlusive-antibiotic conditions, total radiolabel absorption by 408 hr was 29.08, 100.72, and 86.21% dose, respectively. Tissue accumulation of PCP and its labeled metabolite(s) was very significant in swine since one-half to two-thirds of the absorbed dose was still present in tissues by 17 days after PCP dermal exposure. High 14C concentrations were found in liver, kidney, lung, ovary, and uterus. Urine and fecal routes were equally important for label excretion from the body. Occlusion enhanced total dermal absorption and changed the shape of the absorption profiles in the blood and plasma. Skin microorganism inhibition retarded 14C dermal absorption, altered local and systemic tissue distribution, and increased plasma/blood concentration ratios, suggesting skin microbial PCP degradation might play an important role in the altered absorption and disposition by occlusion. This study demonstrated significant dermal absorption and extensive tissue persistence of PCP after soil exposure. Occlusion and skin microflora growth may greatly impact dermal absorption, cutaneous disposition, and systemic toxic input. Therefore, exposure-specific PCP absorption and disposition profiles must be taken into consideration in risk analysis.
Animals↗
Differentiation of colonic metaplasia from adenocarcinoma of urinary bladder.
Colonic metaplasia and primary bladder adenocarcinoma are relatively uncommon entities that can have similar gross clinical appearances. Examples of colonic metaplasia histologically mimicking cancer have only rarely been reported. We retrospectively analyzed 38 cases of cystitis glandularis (18 cases of colonic metaplasia), 12 cases of adenocarcinoma of urinary bladder (two well-differentiated, WDA), and one in situ adenocarcinoma from the surgical pathology files of Johns Hopkins Hospital. Nine patients with colonic metaplasia had widespread lesions. Two showed superficial muscularis propria involvement, mimicking adenocarcinoma; one of these cases had been diagnosed as infiltrating WDA at both an academic center and a community hospital. Dissecting mucin pools were focally seen in four cases of widespread colonic metaplasia, also mimicking cancer. One of the nine cases showed minimal cytological atypia, but no cases showed mitoses or signet ring cells. Distinguishing WDA from colonic metaplasia was the finding in WDA of infiltrative architectural pattern (two of two), extensive muscle invasion (two of two), moderate anaplasia (one of two), mitotic figures (two of two), and extensive mucinous pools (one of two). The diagnosis of adenocarcinoma in situ was based on anaplasia. Clinically, colonic metaplasia may resemble cancer. Histologically, colonic metaplasia may mimic cancer based on extensive involvement of the lamina propria, focal mucinous pools, focal muscularis propria involvement, focal mild cytological atypia, and rare mitoses. Despite overlapping features with colonic metaplasia, the diagnosis of WDA is based on the greater degree and extent of these atypical findings in cancer.
Adenocarcinoma↗
Use of the Malthus conductance growth analyser to determine numbers of thermophilic streptococci on stainless steel.
The use of the Malthus conductance growth analyser for the detection of Streptococcus bovis attached to stainless steel surface was evaluated. A comparison between the results from acridine orange epifluorescence direct counts, swab recovery viable count and conductance estimates of attached cell concentrations, based on calibrations for planktonic cells, showed that the conductance results were up to 2 log10 greater than the epifluorescence results and the swab counts. The growth rates of planktonic and attached cells were similar over 16 h using the Malthus technique. This suggests that the Malthus technique detects more attached cells of Strep. bovis than epifluorescence microscopy or swab recovery.
Acridine Orange↗
The influence of cell surface properties of thermophilic streptococci on attachment to stainless steel.
The quality of milk products is threatened by the formation of biofilms of thermophilic streptococci on the internal surfaces of plate heat exchangers used in milk processing. Although attachment to stainless steel surfaces is one of the first stages in the development of a biofilm, the mechanisms involved in attachment have not been reported. The cell surface properties of 12 strains of thermophilic streptococci were examined to determine their importance in attachment to stainless steel surfaces. Hydrophobicity, extracellular polysaccharide production and cell surface charge varied between the different strains but could not be related to numbers attaching. Treating the cells with sodium metaperiodate, lysozyme or trichloroacetic acid to disrupt cell surface polysaccharide had no effect on attachment. Treatment with trypsin or sodium dodecyl sulphate to remove cell surface proteins resulted in a 100-fold reduction in the number of bacteria attaching. This result suggests that the surface proteins of the thermophilic streptococci are important in their attachment to stainless steel.
Bacterial Adhesion↗
An uncertain role for p53 gene alterations in human prostate cancers.
Inactivation of the p53 gene has been implicated in prostate cancer progression. To determine the role of p53 inactivation in the progression of clinical prostatic carcinomas, we assessed 67 tumors derived from patients with clinically localized disease for chromosome 17p and p53 gene allelic loss, p53 gene mutations using single-strand conformational polymorphism and direct sequencing, and p53 protein expression using immunohistochemical staining. Of 55 informative tumors, 10 demonstrated loss of 17p or the p53 gene; however, only a single tumor had a mutation in its remaining p53 allele. Significant p53 overexpression was observed in 2 of 38 tumors, and 9 others had faint staining of a few nuclei ( < 1%). p53 overexpression occurred in no informative tumor with allelic loss or mutation. In a 1-7-year follow-up, positive immunohistochemical staining did not confer an increased risk of recurrence (risk of recurrence, 0.86, P = 0.78), whereas allelic loss of chromosome 17p appeared to be highly correlated with recurrence (risk of recurrence, 3.7, P = 0.003). In an unrelated group of 42 patients with metastatic prostate cancer, p53 overexpression was found in 26 tumors (62%), and 15(36%) had high grade staining. Neither the presence nor the degree of expression correlated with time to progression or time to death. This series suggests that p53 gene inactivation is rare in primary prostatic tumors, not essential to the development of prostate cancer metastases, and of limited use as a prognostic marker in patients with primary or metastatic disease. Another gene or genes on chromosome 17p may be involved in prostate cancer progression.
Base Sequence↗
Quantitative percutaneous absorption and cutaneous distribution of binary mixtures of phenol and para-nitrophenol in isolated perfused porcine skin.
Chemical exposure to skin remains an important route by which systemic toxicity may occur. However, chemicals are seldom contacted singly in neat form and generally are present as a mixture. A total of 56 8-hr isolated perfused porcine skin flap (IPPSF) topical experiments were used to study the percutaneous absorption and cutaneous distribution of binary mixtures (solute/solvent) of 14C-labeled phenol vs p-nitrophenol (PNP) at two concentrations (4 micrograms/cm2 vs 40 micrograms/cm2) in two vehicles (acetone vs ethanol) under occluded vs nonoccluded dosing conditions. Pertinent comparisons were made to determine if dose, vehicle, or occlusion had a significant effect on absorption, localization of the test compounds, or total recoveries. Total recoveries were much greater in all cases for PNP than phenol. Absorption, penetration into tissues, and total recoveries of phenol were greater under occluded conditions than nonoccluded. Absorption and penetration of phenol into tissues were greater with ethanol than with acetone under nonoccluded conditions, but the opposite was observed under occluded conditions. Percentage of applied dose penetration into tissues was greater from low-dose phenol in acetone than high-dose, suggesting a fixed absorption rate. This was also seen for PNP, but only under occluded conditions. Neither phenol dose,vehicle, or occlusion had any significant effect on the labeled phenol seen in the stratum corneum or on time of peak flux, a finding which limits the usefulness of noninvasive stratum corneum sampling to assess topical penetration. There was greater absorption and penetration into tissues of PNP from acetone than from ethanol. PNP dose had a significant effect on time of peak dose, with low-dose PNP taking longer to reach its peak. Neither PNP dose, vehicle, nor occlusion had any significant effect on total recovery of labeled PNP. The results suggest that comparative absorption of phenol and PNP are vehicle-, occlusion-, and penetrant-dependent. These factors must be considered when comparing absorption data between studies. These findings suggest that single chemical data (the compound applied neat) is not predictive of even binary mixtures and that exposure conditions further modulate disposition.
Animals↗
The use of mechanistically defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals. I. Studies with parathion mixtures in isolated perfused porcine skin.
Recently, attention has been directed to the risk assessment of cutaneous exposure to chemical mixtures rather than to only a single compound since this is the exposure scenario in the environment, residence, and work place. Using acetone or dimethylsulfoxide (DMSO) (80% in water) as a vehicle, percutaneous absorption and cutaneous disposition of parathion (PA) were studied following PA (40 microg/cm2) dosing on isolated perfused porcine skin as mechanistically defined chemical mixtures (MDCM) consisting of the surfactant sodium lauryl sulfate (SLS), the rubefacient methyl nicotinate (MNA), and the reducing agent stannous chloride (SnCl2). A full 2 x 4 factorial design was used to asses treatment effects and potential interactions. More radiolabel was absorbed with DMSO than with acetone albeit an earlier peak flux time but lower peak flux was observed with acetone than with DMSO. The absorption flux rate profiles with DMSO continued increasing but bipeak-featured profiles were observed with acetone. SLS enhanced PA absorption with both DMSO and acetone. The presence of MNA in both vehicles blunted the absorption rate curves without significantly changing total absorption. SnCl2 blocked PA absorption and increased residue level on the skin surface and in the stratum corneum (SC). The venous flux profiles were mixture-dependent and highly reproducible within treatment groups. Higher level interactions were also noted. This study indicated multiple levels of interactive effects on PA absorption which must be incorporated into any effort to identify critical mechanisms which affect risk assessment of topically exposed mixtures. It was suggested that the chemicals selected in a topically applied mixture may have significant effects on the penetration/distribution pattern and percutaneous absorption profile of a toxicant/drug in the mixture. The MDCM approach may be useful in a screening or triage approach to identify mixture components which affect marker chemical absorption as well as identify potential mechanisms which deserve further attention. Risk assessment efforts could then be focused on those mixtures, containing these critical components, which would be expected to have the greatest penetration and absorption.
Animals↗
Frequent loss of chromosome arms 8p and 13q in collecting duct carcinoma (CDC) of the kidney.
Collecting duct carcinoma (CDC) is a malignant renal neoplasm that is believed to arise from the epithelium of the ducts of Bellini in the distal nephron. These tumors are clinically aggressive and more often occur in a younger population than is typical of the more common clear cell renal carcinoma (RCC). Using highly informative polymorphic microsatellite markers on chromosome arms 3p, 5q, 6q, 9p, 9q, 11p, 13q, 17p, and 18q, we analyzed DNA from nonmalignant and tumor tissue in 6 cases of CDC. We found no evidence of 3p loss of heterozygosity (LOH) in these renal tumors by using multiple markers, a finding that distinguishes CDC from RCC in which 3p LOH has frequently been observed. We found LOH of 8p in 50% of the tumors examined; in addition, we observed LOH of 13q in 50% of the tumors studied. Interestingly, 8p LOH may be associated with high stage and poor clinical prognosis. These data suggest that the molecular events responsible for the development of CDC differ from those associated with the origin of RCC, and that tumor suppressor genes on 8p and 13q may be involved in the pathogenesis of CDC.
Adolescent↗
Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas.
Inactivation of the retinoblastoma (Rb) gene has been implicated in the genesis and progression of a number of tumor types, including prostatic adenocarcinomas. We have analyzed a series of 46 surgically-resected human prostatic adenocarcinomas for allelic loss of the Rb gene with PCR amplification of a highly polymorphic region of the gene. 41 of 46 tumors (89%) were informative and 11 of these (27%) had lost one Rb allele. The relative frequency of this occurrence suggests that inactivation of the retinoblastoma gene may be an important event in prostate carcinogenesis.
Adenocarcinoma↗
Toxicokinetics of topical sulfur mustard penetration, disposition, and vascular toxicity in isolated perfused porcine skin.
Sulfur mustard bis(2-chloroethyl) sulfide (HD) is a bifunctional alkylating agent that causes cutaneous vesication. The isolated perfused porcine skin flap is an in vitro model that has been used to study this toxic response. The purpose of this study was to formulate a toxicokinetic model of HD penetration and cutaneous disposition as an aid in correlating critical steps in the pathogenesis of vesication to HD concentrations in different regions of skin. [14C]HD was dosed topically in ethanol at 10.0 mg/ml in a 7.5-cm2 dosing site and venous efflux samples were collected over 2, 4, or 8 hr. At the termination of the experiment, stratum corneum tape strips, core biopsies for serial sections, and the entire skin flap were collected for radioassay. Peak 14C-radiolabel flux occurred within 5 to 60 min in all skin flaps, much earlier than signs of HD-induced toxicity. A toxicokinetic model was used to quantitate the time profile of HD disposition in different skin compartments. Estimates of vascular and extracellular volume changes due to topical HD toxicity were estimated using radiolabeled albumin and inulin infusions. A second toxicokinetic model, with a time-variant distribution rate, was used to simulate volume changes. In order to accurately predict HD disposition, it was necessary to add another compartment as a reservoir for slowly released metabolites of HD. This model provides a quantitative profile of the time course of HD (or metabolites) disposition within skin which would aid in the interpretation of mechanistic studies of vesication as well as in designing interventive antivesicant drug strategies.
Animals↗
Comparison of open and endourologic approaches to the obstructed ureteropelvic junction.
OBJECTIVES: To compare open pyeloplasty with three minimally invasive modalities: antegrade endopyelotomy, Acucise endopyelotomy (Applied Medical, Laguna Hills, Calif), and laparoscopic pyeloplasty. METHODS: Forty-five adult patients with ureteropelvic junction obstruction were managed by one of the above four techniques. Success rates, analgesic use, length of hospital stay, recovery time, and complications were compared between each of the four groups. RESULTS: Successful relief of obstruction was achieved in 100% of patients undergoing open and laparoscopic dismembered pyeloplasty, 78% undergoing Acucise endopyelotomy, and 77% undergoing antegrade percutaneous endopyelotomy. Acucise endopyelotomy results in shorter convalescence (1 week) than antegrade endopyelotomy (4.7 weeks), laparoscopic pyeloplasty (2.3 weeks) or open pyeloplasty (10.3 weeks). Complication rates appear to be similar among all groups. CONCLUSIONS: Our limited data imply that Acucise endopyelotomy offers low morbidity with success rates comparable to antegrade pyeloplasty, whereas laparoscopic pyeloplasty is as effective as open pyeloplasty with diminished morbidity.
Adult↗