Faculty Bibliography

OBJECTIVES. To compare the cellular composition of benign prostatic hyperplasia (BPH) in Chinese and Caucasian-American men. METHODS. Surgical specimens of the prostate were obtained from 9 Chinese and 8 Caucasian-American men undergoing cystoprostatectomy for invasive transitional cell carcinoma. The mean ages of the Chinese and Caucasian-American men were 66.8 years and 66.4 years, respectively (P = 0.94). The mean prostate weight of the Chinese and Caucasian-American men was 53.4 g and 32.1 g, respectively (P = 0.01). Double immunoenzymatic staining with antibodies against actin and prostatic acid phosphatase and computer-assisted color image analysis were performed on whole-mount tissue sections. The percent area density of smooth muscle (SM), connective tissue (CT), epithelium (E), and epithelial lumen (L) were obtained by analyzing 30 fields from each specimen. RESULTS. The mean percent area density of SM, CT, E, and L in the prostate of Chinese men was 32%, 9.1%, 10.8%, and 48.5%, respectively. The mean percent area density of SM, CT, E, and L in the prostate of Caucasian-American men was 52.5%, 27.9%, 12.8%, and 7%, respectively. Overall, the prostates of Chinese men contained significantly more glandular lumen and significantly less SM and CT. CONCLUSIONS. The present study demonstrates that the cellular composition of BPH in the prostates of Caucasian-American and Chinese men is different. These cellular differences may account for previously observed differences in the incidence of clinical BPH

PURPOSE: We determined the tissue localization of the alpha 1a-adrenoceptor in the human prostate. MATERIALS AND METHODS: Autoradiographic localization of the alpha 1a-adrenoceptor in the human prostate was determined by performing competitive displacement experiments on slide mounted tissue sections using the ligand 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat), and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, 3 x 10(-7) M.). Under these experimental conditions, WB-4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a-adrenoceptor antagonists, respectively. The autoradiographs were quantitatively analyzed using a computer image analysis system. RESULTS: Specific 125I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100% of the specific 125I-Heat binding in the stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha 1a subtype. WB-4101 inhibited none of the specific 125I-Heat binding in the epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the alpha 1b subtype. SNAP 5272 displaced only 25% of the specific 125I-Heat binding in the epithelium, suggesting that a relatively small percentage of the epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. CONCLUSIONS: To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor

Six cases of suspected multiple cholesterol emboli syndrome were identified by a review of reports contained in the company's records of adverse event reports. Antecedent risk factors in these reports included cardiac catheterization, thrombolytic therapy, translumbar aortography, renal arteriography, subclavian arteriography, abdominal aortography, and heparinization. Unlike the commonly reported subacute presentation, onset occurred during or immediately after catheterization in 5 of the 6 patients reported. Acute renal failure; hypertension; back, leg, and/or abdominal pain; and livedo reticularis were the events most frequently reported. Angiographers should consider multiple cholesterol embolization when multiple organ system dysfunction occurs during or immediately after intraarterial catheterization

The pathophysiology of clinical BPH has been attributed to bladder outlet obstruction resulting from the enlarged prostate. A direct relationship does not exist between prostate size, symptom severity, or bladder outlet obstruction. The pathophysiology of prostatism is most likely multifactorial. Elucidating the factors contributing to symptoms will likely provide the foundation for the development of new pharmacological alternatives for the medical treatment of BPH

OBJECTIVES. To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS. EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS. These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates

Basic fibroblast grown factor (bFGF) is a potent mitogen for mesenchymal cells, including fibroblasts cultured from prostate, and has been postulated to play a role in the development of benign prostatic hyperplasia (BPH). If this is the case, it might be expected that bFGF levels would be elevated in the adenomas of BPH and in the periurethral region of the prostate where BPH is believed to arise. This study was undertaken to test this hypothesis. The concentration of bFGF was evaluated in 31 prostates, 13 normal glands and 18 with BPH. A method for quantitating bFGF by radioimmunoassay was developed that enabled growth factor levels to be correlated to the geographic region of the prostate and the histopathology of the specimen. A 2- to 3-fold higher concentration of bFGF (ng./g. of tissue) was noted in the benign hyperplastic prostates when compared with the adult normal glands. Pubertal specimens demonstrated low growth factor levels comparable to those observed in the normal adult group. Two prepubertal prostates analyzed had high levels similar to those measured in the hyperplastic glands. While the levels of bFGF in the normal adult prostates were highest in the periurethral region, statistical analysis failed to demonstrate a significant difference. Similarly, quantitative morphometric evaluation failed to demonstrate any significant differences in bFGF concentration related to the proportion of stromal, epithelial, or lumenal elements in the tissue sections

The present study was designed to compare the binding and functional properties of alpha-1 adrenoceptors and the area density of smooth muscle in the human, canine and rat prostates. Chloroethylclonidine (CEC)-sensitive and -insensitive alpha-1 adrenoceptors were characterized on slide-mounted prostatic tissue sections using the ligand [3H]prazosin. The mean equilibrium dissociation constants (Kd) for [3H]prazosin binding sites were not significantly different among the three different species. The densities (Bmax) of CEC insensitive [3H]prazosin binding sites in the human, canine and rat prostates were 1.71 +/- 0.32, 0.35 +/- 0.04 and 0.84 +/- 0.11 fmol/mg of wet weight, respectively. The Bmax of CEC-sensitive [3H]prazosin binding sites in the human, canine and rat prostates were 1.32 +/- 0.83, 0.44 +/- 0.11 and 0.25 +/- 0.10 fmol/mg of wet weight, respectively. The contractile response elicited by the rat prostate in the presence of phenylephrine was consistently negligible. The mean maximal force after phenylephrine challenge (phenylephrine Emax) in the human and canine prostates were 0.125 +/- 0.025 g of force/mm2 cross-sectional area and 0.096 +/- 0.014 g of force/mm2 cross-sectional area, respectively. CEC inactivated 80 and 53% of the phenylephrine contractile response in man and dog, respectively. The mean percentage of area densities of smooth muscle in the human, canine and rat prostates were 38.8, 12.9 and < 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVES. The present study was designed to determine the relationship between serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes. METHODS. Forty-two men between the ages of 50 and 79 years of age with either an abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL underwent transrectal ultrasonography (TRUS) and ultrasound-guided random systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and transition zone (TZ) were calculated, assuming that the total prostate and TZ are ellipsoidal structures. Six random systematic biopsies were directed into the PZ and four random systematic biopsies were directed into the TZ under ultrasound guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy specimens of the subjects without histologic evidence of prostate cancer were stained with Mallory trichrome stain, and the percentage area density of epithelium in the biopsy cores was determined using computer-assisted color image analysis. The relationships between serum PSA and total, PZ, and TZ epithelial volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined using regression analysis. RESULTS. The difference between the mean percentage epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2 values for the relationship between serum PSA and total prostatic volume were 0.016 and 0.260, respectively. Statistically significant correlations were also observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 = 0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically significant correlations were not observed between serum PSA levels and the following parameters: PZ volume, PZ epithelial volume, and total prostatic epithelial volume. CONCLUSIONS. Although the PZ contains a significantly greater area density and absolute volume of epithelium than the TZ, the serum PSA level is most strongly correlated only with the volume of epithelium in the TZ