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E Shapiro

Publications and source records attributed to E Shapiro.

At least 109 records · Page 6Linked to original sources
PubMed1993

The alpha-adrenoceptor subtype mediating the tension of human prostatic smooth muscle.

We have characterized the alpha 1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the alpha 1 subtype mediating the tension of prostatic smooth muscle. Fresh human tissue was obtained from 9 males between 50 and 80 years of age undergoing prostatectomy for BPH. The incubation of prostatic tissue with the irreversible antagonist chlorethyclonidine (CEC) resulted in an 80% reduction of the maximal contractile response produced by phenylephrine. However, the alpha 1A-selective antagonists WB-4101 and 5-methylurapidil (5-MU) competitively inhibited the contractile response induced by phenylephrine, with KB = 2.64 and 4.46 nM, respectively, consistent with their affinity at the alpha 1A receptor subtype. The pharmacological profile of the alpha 1-receptor-mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an alpha 1A or alpha 1B subtype. Alternatively, when compared with the properties of the cloned alpha 1 receptors, our results suggest that the alpha 1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine alpha 1C receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the alpha 1-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective alpha 1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH).

Adrenergic alpha-Antagonists↗
PubMed1993

Binding and functional properties of alpha1 adrenoceptors in different regions of the human prostate.

The objective of the present study was to determine the density and functional properties of alpha 1 adrenoceptors in different regions of the human prostate. Binding and functional studies were performed on eight different topographical regions of the prostate. The contractile response (gm. force/mm.2 cross-sectional area [CSA]) was determined at varying concentrations of phenylephrine, and saturation experiments were performed at seven different concentrations of 125I-Heat. The maximal response to phenylephrine (Emax) ranged from 0.067 to 0.272 gm. force/mm.2 The CSA and the EC50 ranged from 25 to 41 microM. The differences between EC50 and Emax were not significantly different among the eight prostatic regions. A 1.8-fold difference between the Emax for peripheral and central regions of the prostate was statistically significant (p = 0.04). The equilibrium dissociation constant (Kd) of 125I-Heat and the receptor density Bmax were determined from the Scatchard plots. The mean Kd and Bmax ranged from 0.15 to 0.26 nM. and 0.30 to 0.72 fmol. per mg. wet weight, respectively. There were no statistically significant differences between mean Kd and mean Bmax for the eight prostatic regions. The 1.7-fold difference between central and peripheral mean Bmax was not statistically significant (p = 0.07). A direct relationship was not observed between phenylephrine mean Emax and mean Bmax. The present study demonstrates regional differences of the binding and functional properties of prostatic alpha 1 adrenoceptors in the human prostate. These regional differences must be taken into account when investigating the pharmacologic and physiologic properties of the prostate.

Humans↗
PubMed1993

Endothelin-1 in the human prostate: tissue levels, source of production and isometric tension studies.

Endothelins mediate contractile responses in many types of vascular and nonvascular smooth muscle. The present study represents the first detailed characterization of endothelins in the human prostate. The objectives of this study were to determine the tissue levels and source of endogenous endothelin-1 (ET1) in the human prostate. The contractile effects of ET1 were also investigated using in vitro isometric tension studies. The mean tissue level of ET1 was 0.58 +/- 0.08 pg./mg. tissue wet weight. Endothelin-like activity was markedly prominent in the glandular epithelium of the human prostate, whereas minimal endothelin-like activity was observed in the prostatic stroma. Strips of human prostatic tissue were suspended in isolated tissue chambers and challenged to a concentration response of ET1. The mean EC50 and Emax for ET1 was 3.2 x 10(-8) M. and 0.12 +/- 0.02 gm. force per mm.2 cross-sectional area (CSA), respectively. Preincubation with indomethacin, terazosin, or nifedipine did not alter the concentration-dependent response to ET1. A calcium-free buffer abolished the contractile response to ET1. Thus, ET1 mediates a potent contraction of human prostatic smooth muscle that is not mediated via alpha 1 adrenergic or dihydropyridine sensitive calcium channels or prostaglandin synthesis. The presence of marked endothelin-like immunoreactivity strongly suggests a biological significance for endogenous endothelins in the human prostate.

Adrenergic alpha-Antagonists↗
PubMed1993

Pediatric urological manpower report. Pediatric Urological Manpower Committee of the American Association of Pediatric Urology.

The American Association of Pediatric Urology initiated a Pediatric Urological Manpower Study in 1991. A 24-question survey was distributed to the members of the Society of Pediatric Urology and the American Academy of Pediatrics Section on Urology. The objective of the questionnaire was to obtain information related to fellowship training, regional distribution of pediatric urologists, and practice patterns and attitudes. As of December 31, 1991, 345 questionnaires were distributed, and 244 (71%) were completed and entered into a computer program. The number of pediatric urologists was evenly distributed among 3 consecutive 10-year age groups ranging between age 31 and 60 years. The majority (78%) of urologists practicing 100% pediatric urology were between 31 and 50 years old. Approximately 60% of the responders practiced full-time (100%) pediatric urology and 59% of this group were university based. Pediatric urologists were practicing in 42 states and the District of Columbia. Based upon the United States Department of Commerce 1990 census, the number of pediatric urologists practicing in each state in relation to the total pediatric (less than 18 years old) populations was determined. The number of pediatric urology fellowships has steadily increased since the mid 1950s. Currently, more than 10 fellows are trained annually. Of the 172 responders practicing at least 75% pediatric urology 24% indicated that practice was "too busy" and 53% indicated that practice was "just right." Approximately 44% of the responders were considering adding a partner: 21 indicated that they planned to add a partner in 1 year, 65 in 5 years and 10 in 10 years. Hopefully, the Pediatric Urological Manpower Study will serve as a useful instrument for assessing the pediatric practice patterns and training needs in the United States, thereby enhancing the quality of urological care for children.

Humans↗
PubMed1993

Response of the newborn ureteropelvic junction complex to induced and later reversed partial ureteral obstruction in the rabbit model.

The clinical controversy regarding the timing of surgery for asymptomatic newborns with obstructed hydronephrosis was addressed using a model of reversible partial ureteral obstruction in the newborn rabbit. The histomorphometric changes in the ureteropelvic junction complex (for example, pelvis, ureteropelvic junction and upper ureter) and kidney in 44 normal cases were determined and compared with the effects of 47 cases of ongoing partial obstruction and timed reversal of partial obstruction at 1 week in 9 cases, at 2 weeks in 10 or at 4 weeks in 10 (end of the study at age 8 weeks). After partial obstruction hydronephrosis appeared by 1 week postoperatively. There were progressive increases in the thickness of the lamina muscularis and mass index of smooth muscle and collagen (all p < 0.001). However, since the per cent surface area of smooth muscle did not change significantly in comparison to normal, there was disproportionately more collagen. For reversals at 1 week the muscle and collagen in the lamina muscularis were not significantly different from normal. For reversals at 2 weeks the mass index of collagen was greater than normal (p < 0.05) and reversal at 1 week (p < 0.05). For reversals at 4 weeks the lamina muscularis was thicker, and the mass index of collagen and muscle was greater than the earlier reversal groups and normal (all p < 0.05). In conclusion, partial ureteral obstruction causes progressive thickening of the lamina muscularis by collagen and muscle with a disproportionately greater increase in collagen than muscle. The earlier the obstruction can be reversed, the more normal is the ureteropelvic junction complex histology. The functional significance of these changes needs to be determined.

Animals↗
PubMed1993

Characterization and localization of prostatic alpha 1 adrenoceptors using radioligand receptor binding on slide-mounted tissue section.

Alpha 1 adrenoceptor binding sites have been characterized in prostatic tissue homogenates using radioligand receptor binding studies. The objective of the present study was to characterize and localize prostatic alpha 1 adrenoceptor binding sites using slide-mounted tissue sections and the ligand 3H-prazosin. The present study demonstrated that preincubation is not required; the optimal incubation interval is 40 minutes; and a 1-minute wash (once or twice) maximizes the proportion of specific 3H-prazosin binding. Saturation studies were performed at 8 different concentrations of 3H-prazosin ranging between 0.0625 nM. to 8.0 nM. The binding of 3H-prazosin was consistently saturable and of high affinity. The mean Kd and Bmax determined from 6 saturation studies was 4.16 x 10(-10) M. and 1.30 fmol./mg. wet weight, respectively. The pharmacology of these 3H-prazosin binding sites was characterized using competitive displacement experiments. The mean IC50 corrected for prazosin, phentolamine and yohimbine was 7.8 x 10(-10) M., 6.0 x 10(-9) M. and 2.1 x 10(-6) M. The rank order of the IC50 corrected values indicates that alpha 1 binding sites were measured under the assay conditions. In the present study, the mean values for Kd, Bmax and IC50 corrected are similar to values previously reported using prostatic tissue homogenates. Prostatic tissue sections were apposed to x-ray film after being incubated with 3 nM. 3H-prazosin (total prazosin binding) and 3 nM. 3H-prazosin + 8 microM. prazosin (nonspecific prazosin binding). The autoradiograms were analyzed using a computerized analyzing system. The specific radioactive densities of 3H-prazosin in the stroma and glandular epithelium were 1099 +/- 48 pCi/mg. and 163 +/- 42 pCi/mg. The present study validates the technique of assaying alpha 1 adrenoceptor binding sites on slide-mounted prostatic tissue sections and provides further evidence that alpha 1 adrenoceptor binding sites are localized primarily to the stromal elements of the prostate.

Autoradiography↗
PubMed1993

Alpha 1 adrenoceptor subtypes in the human prostate.

High affinity alpha 1 adrenoceptors have been characterized in the human prostate. The tension of prostatic smooth muscle is mediated by the alpha 1 adrenoceptor. The present study represents the first characterization of human alpha 1 adrenoceptor subtypes using radioligand receptor binding techniques. Binding studies were performed on tissue homogenates obtained from the human prostate. Competitive inhibition studies were performed in the presence of an 80 pM. 125I-Heat and 16 concentrations of unlabelled 5-methylurapidil (5 MU) or WB-4101 (10(-10) M. to 10(-5) M.). Saturation experiments were also performed with and without chloroethylclonidine (CEC, 10(-5) M.), a compound that selectively inactivates the alpha 1B subtype. The individual displacement plots for WB-4101 and 5-MU in the human prostate were consistently best fit by a 2 binding site model. WB-4101 and 5-MU exhibited a 594- and 186-fold higher affinity for the prostatic alpha 1A binding site relative to the alpha 1B binding site. The ratios of prostatic alpha 1A/alpha 1B binding sites discriminated by WB-4101 and 5-MU were 1.8 and 1.6, respectively. CEC inactivated 44% of the prostatic alpha 1 binding sites. The binding studies suggest that the dominant alpha 1 subtype in the human prostate is the alpha 1A. We are characterizing the functional properties of the alpha 1 subtypes in the human prostate.

Adrenergic alpha-Antagonists↗
PubMed1993

Manitoba's single-entry system to long-term care.

A single-entry system does not solve all the problems related to continuity of care, but it gives physicians the opportunity to refer those who may be at risk of losing their capacity to remain in the community to professionals who are qualified to assess the situation, to have their patients who need help access the most appropriate resources, and to have the cooperation of the continuing care workers in providing high-quality care to their patients.

Continuity of Patient Care↗
PubMed1993

The vulnerable elderly. Predicting necessary resources.

This article describes elderly patients who are at risk and the resources they need. It goes on to describe an efficient system that makes optimum use of resources, provides a continuum of care, and makes it easier to predict the resources that a community will require.

Aged↗
PubMed1992

Waiting times for nursing-home placement: the impact of patients' choices.

OBJECTIVE: To identify patient characteristics and characteristics of long-term care facilities that significantly affect the waiting time for transfer from hospital to nursing home. DESIGN: Cohort study. PARTICIPANTS: All patients designated to be transferred from four Winnipeg hospitals between June 1, 1988, and May 31, 1989. The patients were followed up until placement, death or May 31, 1990. MAIN OUTCOME MEASURE: Length of time waiting for nursing-home placement and relative rates of placement. RESULTS: The variable found to shorten the waiting time the most was the patient's choice of a for-profit or nonprofit secular facility; other significant variables were male sex, age of 75 to 84 years and occupancy of an acute care bed during the wait. CONCLUSION: The province has three policy options: it can increase the proportion of secular nursing-home beds when new facilities are built; it can require that hospital patients accept an interim nursing-home placement pending transfer to the nursing home of their choice; or it can tie the sponsorship of new facilities to a formula based on the ethnoreligious distribution of the population currently aged 55 to 64 years.

Age Factors↗
PubMed1992

Alpha 1-adrenoceptor properties of terazosin HCl and its enantiomers in the human prostate and canine brain.

The objective of the present study was to characterize the alpha 1-adrenoceptor binding properties of terazosin and its enantiomers in human prostate and canine brain. Human prostate adenomas were obtained from 7 males undergoing prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from 6 male beagles. Competitive displacement experiments were carried out on these tissue homogenates in the presence of a constant concentration ([180 pM]) of 125I-Heat and varying concentrations of unlabelled terazosin and its enantiomers. The Ki of terazosin and its enantiomers were determined from these binding studies. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in human prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between these mean Ki values were not statistically significant. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in canine brain were 6.7 nM, 8.4 nM, and 5.6 nM, respectively. The differences between these mean Ki values were not significantly different. The mean Ki of terazosin and its enantiomers were consistently lower in the human prostate compared to canine brain (P less than 0.05). The present study does not provide any evidence suggesting differential effects of terazosin enantiomers on the human prostate. The twofold difference between the Ki values in the prostate and brain suggests that different subtypes of the alpha 1-receptor might be present in these tissues.

Adrenergic alpha-Antagonists↗
PubMed1992

Anti-desmin vs. anti-actin for quantifying the area density of prostate smooth muscle.

Anti-desmin and anti-actin are commercially available antibodies that bind to smooth muscle. The present study was designed to compare the staining properties of anti-desmin and anti-actin in the human prostate in order to determine the optimal antibody for quantifying the smooth muscle content of the human prostate. Nineteen male subjects with symptomatic BPH underwent needle biopsy of the prostate. Double-immunoenzymatic staining was performed with peroxidase-anti-peroxidase (PAP) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) techniques. Rabbit anti-desmin:mouse anti-human prostatic acid phosphatase and mouse anti-actin:rabbit anti-human prostatic acid phosphatase were utilized. Computer assisted color image analysis was performed using the Bioquant image analysis system. The percent area density of stroma and epithelium was independent of the antibodies used. The percent area density of smooth muscle in the anti-actin stained tissue sections was twofold greater than the anti-desmin stained tissue sections. A direct relationship was observed for the area density of smooth muscle (r = 0.71; P = 0.0006) and the area density of connective tissue (r = 0.82; P less than 0.001) determined from anti-desmin and anti-actin stained tissue sections. Anti-actin represents the optimal antibody for quantifying the area density of prostate smooth muscle. The reproducibility of the immunoenzymatic staining technique is inferred from the direct relationship observed for area density of epithelium between the different staining techniques.

Actins↗
PubMed1992

The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle.

The objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long-acting selective alpha 1 blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer-assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonresponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1992

A conical model to describe the nonuniformity of the left ventricular twisting motion.

The systolic contraction and fiber shortening in the left ventricle (LV) produces torsional moments in the myocardium, resulting in a gradient of angular displacements about the long axis. This is manifested as a counterclockwise rotation of the apex relative to the base, when viewed from the apex. Recent studies with magnetic resonance imaging (MRI), using noninvasive magnetic tags, have revealed three important properties of the LV twist: (a) The angle of twist (i.e., the angular rotation of a slice relative to the basal slice) is consistently higher at the endocardium as compared to the epicardium; (b) The twist increases towards the apex; and (c) Straight MRI-tagged radial lines at end-diastole (ED) are slightly curved at end-systole (ES), implying a nonlinear transmural variation of the twist. The present study suggests that the geometry of the LV at ES can be represented by a thick-walled hollow cone, and that the transmural twist patterns from ED to ES can be described using the continuum mechanics approach and a small strain analysis of an isotropic cone subjected to external torque. The predicted results are compared with the noninvasive MRI measurements of transmural twist in eight human volunteers. Given the epicardial angles of twist of each slice, the predicted endocardial angles of twist are in good correlation with the experimental findings (r = 0.86, slope = 1.09, SEE = 4.1 degrees). In addition, the model reliably describes the changes in the twist magnitude from apex to base (no significant difference from experimental values, P = 0.2), and predicts the curvilinear pattern at ES of the originally straight ED radial lines. Thus, the conical model with uniform properties of the LV, reliably predicts the nonuniformity of the twist patterns, implying that the LV twist is strongly affected by LV geometry.

Adult↗
PubMed1992

Quantitative morphometry of the adult human bladder.

The primary objective of the present retrospective study was to characterize the effects of aging and BPH on bladder morphometry. Eighty-six bladder specimens were obtained from the autopsy archives of the Milwaukee County Medical Complex. The bladder specimens were divided into 4 groups based upon age and gender: Group I: males between the ages of 35-45 years; Group II: males between the ages of 65-75 years; Group III: females between the ages of 35-45 years; and Group IV: females between the ages of 65-75 years. The age groups were selected in order to identify a group of males with and without BPH. The area density of smooth muscle:connective tissue was determined in bladder specimens using color assisted computer image analysis. Masson-trichrome and double immunoenzymatic staining techniques were used to discriminate the smooth muscle and connective tissue elements of the bladder. The area density of smooth muscle:connective tissue in the Masson-trichrome stained sections was significantly greater in Group I vs. Group II (2.90 +/- 0.22 vs. 2.33 +/- 0.16) and in Group III vs. Group IV (2.85 +/- 0.13 vs. 2.03 +/- 0.20). Aging was associated with a decrease in the area density of smooth muscle:connective tissue ratio in both males and females. The area density of smooth muscle:connective tissue was not significantly different in younger males and females (Group I vs. Group III) and older males and females (Group II vs. Group IV). The present morphometric study suggests that aging and not BPH, is associated with a relative increase in detrusor fibrosis. Infravesical obstruction in BPH may effect bladder function via mechanisms unrelated to the histologic composition of the bladder.

Adult↗
PubMed1992

The effect of obstruction on the developing bladder.

Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to-deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation.

Actins↗