PubMed Health⌕ Search

Biomedical subjects

P Humphrey

Publications and source records attributed to P Humphrey.

At least 19 recordsLinked to original sources
PubMed1997

Cell anchorage regulates apoptosis through the retinoblastoma tumor suppressor/E2F pathway.

Epithelial cells are dependent upon adhesion to extracellular matrix for survival. We show that loss of beta1 integrin receptor contact with extracellular matrix signals the inhibition of G1 cyclin-dependent kinase activity. This loss of cyclin-dependent kinase activity leads to accumulation of the hypophosphorylated (active) form of the retinoblastoma tumor suppressor protein (Rb). We present evidence that in epithelial cells deprived of matrix contact, the growth suppression signal elicited by hypophosphorylated Rb opposes stimulatory signals from serum growth factors, leading to a cell cycle conflict that triggers apoptosis. This apoptotic pathway is modulated by Bcl-2 through a novel mechanism that regulates Rb phosphorylation. We present evidence that the Rb-dependent apoptotic pathway functions in vivo in the apoptosis of the prostate glandular epithelium following castration.

Animals↗
PubMed1995

Evaluation of optimal stent size after endourologic incision of ureteral strictures.

The stent size necessary to promote optimal ureteral healing after an endoureterotomy is not known. We compared healing of an endoureterotomy over a 7F indwelling ureteral stent with healing over a 14F endopyelotomy stent. A midureteral stricture was created in each of 25 anesthetized female minipigs using an electrified stone basket passed retrograde. Six weeks later, the stricture was incised with a 24F cutting balloon device. Twenty pigs were randomized to receive a 7F or a 14F stent; four control pigs received neither incisions nor stents. At 1 week, a radiograph was performed to confirm proper stent position, and the stents were removed. At 3 months, a retrograde ureterogram was performed, and the ureters were examined grossly and harvested for histologic studies. Two of the ten pigs in each study group developed a recurrent stricture. The use of a 14F stent provided no advantage over the use of a smaller, more easily positioned 7F stent.

Animals↗
PubMed1995

Morphometric analysis and clinical followup of isolated prostatic intraepithelial neoplasia in needle biopsy of the prostate.

PURPOSE: We evaluate the significance of grade and extent of isolated prostatic intraepithelial neoplasia in prostate needle biopsies as a predictor of cancer on repeat biopsy. MATERIALS AND METHODS: We reviewed our experience with 58 men 50 years or older who had isolated prostatic intraepithelial neoplasia on initial prostate needle biopsy during a prostate specific antigen (PSA) based screening trial for prostate cancer. All 58 men underwent repeat biopsy to follow the initial findings of prostatic intraepithelial neoplasia. We assessed the relationship of patient age, digital rectal examination, serum PSA concentration, PSA density, prostatic intraepithelial neoplasia grade, number of foci of neoplasia and linear extent of prostatic intraepithelial neoplasia in the initial biopsy specimen to the finding of cancer on the repeat biopsy. We also compared the cancer detection rate in the 58 men with and 427 without prostatic intraepithelial neoplasia in the same screening trial. RESULTS: Of 21 men with low grade and 37 with high grade prostatic intraepithelial neoplasia 4 (19%) and 19 (51%), respectively, had cancer on repeat biopsy (p < 0.02), compared to 82 of 427 (19%) without cancer or prostatic intraepithelial neoplasia on the initial biopsy. High grade prostatic intraepithelial neoplasia was a significant predictor of malignancy on repeat biopsy (p < 0.05). The number of foci of neoplasia and the linear extent of prostatic intraepithelial neoplasia on initial biopsy were not predictive of cancer on repeat biopsy. CONCLUSIONS: Our results demonstrate that the presence of high grade prostatic intraepithelial neoplasia is a strong predictor of prostate cancer in men with elevated serum PSA concentrations and they should be followed with repeat biopsy.

Aged↗
PubMed1994

Comparison of retrograde endo-pyelotomy and endo-balloon rupture of the ureteropelvic junction in a porcine model.

Excellent results and durable success have been achieved with antegrade and retrograde endo-pyelotomy for treating primary and secondary ureteropelvic junction obstruction. Recently, a 30F dilating balloon was used to rupture the ureteropelvic junction (ENDOBRST) with encouraging results. While balloon distention of the ureteropelvic junction is a technically simpler procedure than endo-pyelotomy, clinical and laboratory data comparing the 2 methods are lacking. In an acute and chronic animal study we compared endo-pyelotomy via a ureteral cutting balloon incision to balloon rupture (that is 30F) of the normal ureteropelvic junction in each of 20 female farm pigs. Eight pigs were harvested acutely after treatment, and a macroscopic and histological examination of the treated ureteropelvic junction was completed. In 11 chronic pigs after endo-pyelotomy a 7F double pigtail ureteral stent was placed bilaterally and then removed after 6 weeks. Evaluation in the chronic group consisted of a furosemide washout renogram and retrograde pyelogram immediately preoperatively and 6 weeks after stent removal. The animals were likewise harvested 6 weeks after stent removal. One control pig underwent passage of the balloon cutting catheter and balloon dilating catheters without activation or dilation, respectively. Ureteral stents were placed bilaterally for 6 weeks and the pig was otherwise treated similarly to the other chronic study animals. In the acute group all ureters after endo-pyelotomy demonstrated retroperitoneal extravasation of contrast material. At harvest the ureters had been cleanly incised along a length of 3 to 4 cm. through the adventitial layer. In contrast, the balloon treated ureters showed free retroperitoneal extravasation in only half of the animals. Among the balloon treated ureters 7 of 8 had a linear tear of varying length (1 to 5 cm.) involving all but a thin adventitial layer of tissue. Histologically, the endo-pyelotomy ureters demonstrated a clean, linear transmural incision with virtually no destruction of surrounding tissue in 6 cases. In the remaining 2 cases an incision into but not completely through the muscular layer was observed. The balloon treated ureters showed a perforation through the muscular wall in 7 cases. However, periureteral hemorrhage and urothelial loss were common findings. In the chronic group infection and continued urine extravasation from the endo-pyelotomy site resulted in a 45% mortality rate. Of the surviving 6 pigs 83% of the balloon treated and 67% of the endo-pyelotomy pigs had a patent ureteropelvic junction by retrograde pyelogram and renogram. Histologically, the 2 sides were indistinguishable, with both showing mild fibrosis and chronic inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Development of a mouse model for nonbacterial prostatitis.

Nonbacterial prostatitis is a common clinical entity which is often difficult to diagnose and treat. Little is known with regard to the etiology and pathogenesis of this disease process. To develop an animal model and characterize the immune parameters of nonbacterial prostatitis, we harvested the prostates from SJL, AJ, Balb/c, C57bl/6 and C57bl/6 lpr mice. These prostates were homogenized and injected into syngeneic mice. Controls were injected with Freund's complete adjuvant only. Mice from each group were sacrificed 30 days after injection, and the prostates were harvested. Prostatic tissue was examined histologically for degree of inflammation. None of the Balb/c mice exhibited prostatic inflammation. The SJL and AJ mice exhibited varying degrees of prostatic inflammation. All of the C57bl/6 mice were found to have lymphocytic infiltration of the stroma and periglandular region. The C57bl/6 lpr mice did not appear to be more susceptible than the parental strain. Adoptive transfer studies demonstrated the prostatic inflammation to be at least in part immune mediated. We conclude that injection of syngenic prostate antigen induces prostatic inflammation similar to clinical nonbacterial prostatitis. Nonbacterial prostatitis may be an autoimmune process.

Animals↗
PubMed1993

Atypical adenomatous hyperplasia of the prostate: morphologic criteria for its distinction from well-differentiated carcinoma.

Atypical adenomatous hyperplasia (AAH) is a localized proliferation of small glands within the prostate that may be mistaken for carcinoma. To determine the diagnostic criteria for separating AAH from carcinoma, seven observers independently evaluated 54 selected lesions from 44 transurethral resection specimens. Three patterns of glandular proliferation were observed, all arising in association with nodular hyperplasia: AAH (38 foci), atypical small acinar proliferation of uncertain significance (eight foci), and well-differentiated carcinoma (eight foci). Of 24 architectural and cytologic features evaluated, the following were useful in separating these three patterns: variation in nuclear size (14%, 22%, and 25%, respectively), mean nucleolar diameter (0.69 micron, 1.43 microns, and 1.78 microns, respectively), largest nucleolar diameter (mean, 1.66 microns, 2.71 microns, and 2.81 microns, respectively), percentage of nucleoli greater than 1 micron in diameter (17.6%, 58.1%, and 77.5%, respectively), crystalloids within suspicious glands (16%, 13%, and 75%, respectively), luminal basophilic mucinous secretions, infiltrative borders, discontinuity of the basal cell layer in AAH (compared with complete absence in carcinoma; shown with basal cell-specific anti-keratin monoclonal antibody 34 beta E12 immunostaining), and intact basement membrane in AAH (compared with discontinuity in carcinoma; shown with type IV collagen immunostaining). Features that could not reliably separate AAH from carcinoma included lesion shape, circumscription, multifocality, average gland size, variation in gland size and shape, nuclear shape, chromatin pattern, and amount and tinctorial quality of cytoplasm. Although the biologic significance of AAH is uncertain, its light microscopic appearance and immunophenotype allow it to be distinguished from carcinoma in most cases.

Adenoma↗
PubMed1993

Prevalence of pseudorabies (Aujeszky's disease) virus antibodies in feral swine in Florida.

Serum samples collected from feral swine (Sus scrofa) throughout Florida (USA) from 1980 to 1989 were tested for antibodies to pseudorabies virus (PRV) by the serum neutralization test, the latex agglutination test, or by the enzyme-linked immunosorbent assay. Seropositive swine were detected at 11 of 13 sites with a composite seroprevalence of 34.8% (579 of 1,662 samples; range = 5.9% to 58.2%) for sites with seropositive swine. Data on age and sex of the swine were available from three sites. Seroprevalence in males and females did not differ significantly (P = 0.62 for the combined data). Seroprevalence in adult (> or = 8 mo) and juvenile swine (< 8 mo) was significantly different at all sites (P < 0.05 for the combined data). From these data, PRV infections appear to occur widely in populations of Florida feral swine and may seriously undermine efforts to eradicate this virus from the domestic swine population of the USA.

Age Factors↗
PubMed1993

Prevalence of Brucella sp. antibodies in feral swine in Florida.

Serum samples collected from feral swine (Sus scrofa) throughout Florida (USA) from 1974 to 1989 were tested for antibodies to Brucella sp. by the card test, the standard tube test, the rivanol test or the complement fixation test. Seropositive swine were detected at six of 18 sites with a composite prevalence of 23.4% (238 of 1,015 samples; range = 5.5% to 33.3%) for sites with seropositive swine. At one site for which age and sex data were available there was no significant difference (P = 0.50) in seroprevalence between males and females. Antibody prevalence in adult (> or = 8 mo) and juvenile swine (< 8 mo), however, was significantly different (P < 0.05). Based on these data, Brucella sp. infections are limited only to certain populations of feral swine. To avoid the spread of Brucella sp. organisms, however, relocation of feral swine is not recommended.

Age Factors↗
PubMed1992

Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation.

BACKGROUND: It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer. PURPOSE: The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin. METHODS: DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at five loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene. RESULTS: In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors. CONCLUSIONS: The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin. IMPLICATIONS: These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer.

Alleles↗