Cellular adhesion molecules and atherogenesis.
Explore the source record for details and available documents.
Arteriosclerosis↗
Biomedical subjects
D T Price
Publications and source records attributed to D T Price.
Giant hepatoid yolk sac tumor in a black man.
Explore the source record for details and available documents.
Black People↗
Transient lumbosacral polyradiculopathy after prostatectomy: association with spinal stenosis.
Mononeuropathies are common after pelvic surgery. They are usually the result of unnatural positioning during surgery or faulty restraining devices. Polyneuropathy in the postoperative setting is rare. We report two cases of polyradiculopathy after radical prostatectomy using two different patient positions. Both patients complained of paresthesias and weakness in their lower extremities on postoperative day 1. Neurologic examination in each case was consistent with a polyradiculopathy. Significant spinal stenosis of the lumbosacral spine was found in both patients by magnetic resonance imaging. We propose that spinal stenosis is a risk factor for this type of neurologic injury.
Anti-Inflammatory Agents↗
Activation of extracellular signal-regulated kinase in human prostate cancer.
PURPOSE: To investigate the level of expression, activation state, and functional significance of extracellular signal regulated kinase (ERK) in prostate cancer. MATERIALS AND METHODS: Human prostate tissue samples (n = 22) were obtained from patients undergoing radical prostatectomy for localized adenocarcinoma of the prostate (n = 16, age range 44 to 72 years) or normal prostate specimens (n = 6, age ranges 19 to 47 years) obtained from rapid autopsy. Immunoblots, in vitro kinase assays, and immunohistochemistry were used to determine the expression and activation state of ERK in human prostate cancer. RESULTS: Immunoblot and in vitro kinase assays demonstrated a 15-fold increase in ERK activation in prostate cancer specimens compared with normal human prostate tissue; however, ERK expression levels were only 1.3-fold higher in cancer. Immunohistochemical analysis demonstrated similar expression of ERK in cancer and normal tissues; however, phosphorylated ERK demonstrated greater intensity in the cancer specimens. Experiments conducted on a prostate cancer cell line demonstrated that EGF induced activation of ERK and cellular proliferation was partially inhibited by PD98059, a chemical inhibitor of the immediate upstream signaling component responsible of activation of ERK. CONCLUSIONS: Collectively, these data demonstrate a dramatic increase in ERK activation in prostate cancer compared with normal prostate tissue and suggest that inhibitors designed to target this signal transduction cascade might have therapeutic benefit in the treatment of prostate cancer.
Adenocarcinoma↗
Characterization of alpha-adrenoceptor subtypes in the corpus cavernosum of patients undergoing sex change surgery.
PURPOSE: To characterize the subtypes of alpha1- and alpha2-adrenoceptors in the human corpus cavernosum from patients undergoing sex change surgery. MATERIALS AND METHODS: Saturation and competition radioligand binding studies were performed for characterization at the protein level. Alpha1-adrenoceptors were labeled with [3H]prazosin and [3H]tamsulosin, while alpha2-adrenoceptors were labeled with [3H]RX 821002. Alpha1-adrenoceptor subtype mRNA was additionally determined by reverse-transcriptase polymerase chain reaction and RNase protection assays. RESULTS: Human corpus cavernosum expressed approximately 32 and approximately 22 fmol./mg. protein alpha1- and alpha2-adrenoceptors, respectively. Competition studies with the alpha1A-selective antagonists 5-methylurapidil and (+)-niguldipine and the alpha1D-selective BMY 7378 revealed a mixed alpha1A/alpha1B-adrenoceptor population with no evidence for alpha1D-adrenoceptor protein. In contrast alpha1D-adrenoceptors were readily detected at the mRNA level. Competition binding studies with the alpha2A-selective oxymetazoline and the alpha2B-selective prazosin and ARC 239 revealed a homogeneous population of alpha2A-adrenoceptors. CONCLUSIONS: We conclude that human corpus cavernosum expresses predominantly alpha1A-, alpha1B- and alpha2A-adrenoceptor protein; additionally the alpha1D-adrenoceptor is present at the mRNA level.
Adrenergic alpha-Antagonists↗
Factor V Leiden mutation as a risk factor for recurrent pregnancy loss.
BACKGROUND: Recurrent pregnancy loss may result from hypercoagulability. OBJECTIVE: To determine whether women with factor V Leiden mutation, a common inherited defect of coagulation, are at increased risk for recurrent pregnancy loss. DESIGN: Case-control study. SETTING: University hospital. PATIENTS: 113 consecutive women referred for evaluation of recurrent spontaneous abortion (case-patients) and 437 postmenopausal women with at least one successful pregnancy and no history of pregnancy loss (controls). An additional survey of 387 postmenopausal women with at least one pregnancy loss was also conducted. MEASUREMENTS: Prevalence of factor V Leiden mutation determined by a second-generation screening test for resistance to activated protein C with genetic confirmation of all borderline and low-value results. RESULTS: Prevalence of the factor V Leiden mutation was greater among case-patients (8.0%) than among controls (3.7%) (odds ratio, 2.3 [95% CI, 1.0 to 5.2]; P = 0.050). In the subgroup of case-patients with three or more pregnancy losses and no successful pregnancies, prevalence of the mutation was 9.0% (odds ratio, 2.6 [CI, 1.0 to 6.7]; P = 0.048). Among the additional women surveyed, the prevalence of the mutation in those with three or more pregnancy losses (7.5%) was almost identical to that in case-patients. Thus, in all evaluated women with several pregnancy losses, the prevalence of factor V Leiden was increased 2.2-fold (P = 0.026). CONCLUSION: These data are compatible with the hypothesis that factor V Leiden mutation may play a role in some cases of unexplained recurrent pregnancy loss.
Abortion, Habitual↗
Alpha1-adrenergic receptor subtypes in human detrusor.
PURPOSE: To identify and quantitate alpha1-adrenergic receptor (alpha1AR) subtype expression in human detrusor. MATERIALS AND METHODS: Initial studies to determine alpha1AR expression in human detrusor were performed using saturation binding with [125I]HEAT. Once the presence of alpha1ARs was documented, subtype (alpha1a, alpha1b, alpha1d) expression at the mRNA level (and comparison with rat) was determined with RNase protection assays (human detrusor) and RT-PCR (human detrusor, rat whole bladder). Competition binding analysis with the alpha1dAR-selective ligand BMY7378 was used to measure alpha1AR subtype expression at a protein level in human detrusor. RESULTS: Alpha1AR expression in human detrusor was low but reproducible (6.3 +/- 1.0 fmol./mg. total protein). RNase protection assays performed on total RNA extracted from human detrusor revealed the following alpha1AR subtype expression: alpha1d (66%) > alpha1a (34%), and no alpha1b. RT-PCR confirmed alpha1AR subtype mRNA distribution in human detrusor with alpha1d (approximately 60-70%) > alpha1a (approximately 30-40%), and a lack of alpha1b mRNA. Rat whole bladder expressed different alpha1AR subtype mRNA than human detrusor, with alpha1a approximately alpha1b approximately alpha1d. The presence of alpha1d > alpha1a expression in human detrusor was confirmed at a protein level by competition analysis utilizing BMY7378 which revealed a two-site fit, with Ki and high affinity binding (66%) consistent with the alpha1dAR subtype. CONCLUSIONS: Human detrusor contained two alpha1AR subtypes (alpha1d > alpha1a), a finding that is different from rat, another commonly used animal model. Since non-subtype selective alpha1AR antagonists ameliorate irritative bladder symptoms (in men and women with/without outlet obstruction), and Rec 15/2739 (alpha1a selective antagonist) does not improve symptom scores in BPH, our findings suggest bladder alpha1dARs may provide a potentially novel mechanism underlying these therapeutic benefits.
Animals↗
Transient lower extremity neurapraxia associated with radical perineal prostatectomy: a complication of the exaggerated lithotomy position.
PURPOSE: We assess the incidence and risk factors associated with lower extremity neurapraxia following radical perineal prostatectomy. MATERIALS AND METHODS: The medical records of 111 consecutive patients undergoing radical perineal prostatectomy at Duke University Medical Center between June 1994 and June 1995 were retrospectively reviewed. Patients were interviewed by telephone to ascertain whether symptoms had resolved. RESULTS: Neurapraxia developed in 23 patients (21%). Symptomatology was variable, including sensory and motor deficits of the lower leg and foot. Although lower extremity neurapraxia occurred in a significant number of patients undergoing radical perineal prostatectomy, it appeared to resolve in most. CONCLUSIONS: Careful attention to detail when positioning the patient and limiting the time in the exaggerated lithotomy position appear to be the most critical aspects to prevent neurapraxia.
Aged↗
Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective.
BACKGROUND: A single point mutation in the gene coding for coagulation factor V results in a form of factor Va that is resistant to degradation by activated protein C and leads to a relative hypercoagulable state. This mutation, factor V Leiden, is found in 4% to 6% of the U.S. population. PURPOSE: To review clinical data on factor V Leiden mutation, with emphasis on prevalence of and risks for thromboembolism and implications for screening and management. DATA SOURCES: A MEDLINE search of the English-language literature published between 1993 and April 1997 and an extensive bibliography review. STUDY SELECTION: Case-control and prospective cohort studies were reviewed if clinical features of thromboembolic disease associated with factor V Leiden mutation or resistance to activated protein C were presented. Original research articles were reviewed if they addressed the identification of the laboratory abnormality of activated protein C or factor V Leiden mutation. Case reports and case series were reviewed when no analytic data were available. DATA EXTRACTION: Review of the identified articles. DATA SYNTHESIS: Factor V Leiden mutation is associated with three- to sixfold increases in risks for primary and recurrent venous thromboembolism, especially in patients without transient risk factors, such as surgery or trauma. Risks for venous thromboembolism in genetically affected persons are substantially higher among patients with coexistent predispositions for thrombosis, such as advanced age, use of oral contraceptives, hyperhomocystinemia, and deficiencies of protein C and protein S. Factor V Leiden mutation does not seem to increase risks for arterial thrombosis. Whether patients with the mutation would benefit from more intense or prolonged anticoagulation is unknown. CONCLUSIONS: The presence of factor V Leiden mutation predisposes patients to venous thromboembolism, but screening for this disorder is of uncertain utility. Decisions about whether to screen for the mutation will depend on the results of clinical trials designed to evaluate the benefit-to-risk ratio of long-term anticoagulation in the secondary prevention of venous thromboembolism in patients with resistance to activated protein C.
Contraceptives, Oral↗
Effects of androgen deprivation on prostate alpha 1-adrenergic receptors.
OBJECTIVES: Benign prostatic hyperplasia (BPH), the most common benign tumor in men, consists of two components-static (enlargement regulated by androgens) and dynamic (smooth muscle contraction through alpha 1-adrenergic receptors [alpha 1-ARs]). Because medical therapy of BPH involves tissue androgen deprivation, we studied the influence of androgen deprivation and replacement on regulation of rat ventral prostate alpha 1-ARs. METHODS: Prostate weight, alpha 1-AR density, autoradiographic images, histologic features, and cell-specific protein were examined before and after castration and androgen replacement. RESULTS: Castration decreases ventral prostate wet weight, a process reversed by testosterone administration. In contrast, there is an apparent increase in alpha 1-AR density (29 +/- 4 versus 65 +/- 6 fmol/mg total protein, mean +/- SEM) after castration, returning to baseline with testosterone replacement; alpha 1-AR density remains constant in control liver membranes. Alpha 1-ARs predominate in stroma throughout androgen deprivation therapy. Epithelially derived cells decrease (83% to 67%) after castration, resulting in a relative doubling in stroma (17% to 33%); the protein content of epithelial and stromal cells remains identical. Therefore, prostate-specific increases in alpha 1-ARs appear to result from relative increases in the ratio of smooth muscle to epithelium after castration rather than from direct upregulation of alpha 1-AR protein. CONCLUSIONS: Because alpha 1-AR density does not decrease with androgen deprivation, these studies suggest that alpha 1-AR antagonists remain an important component in BPH therapy, even when 5-alpha-reductase inhibitors are utilized.
Animals↗
Vesical endometriosis: report of two cases and review of the literature.
Endometriosis is a common gynecologic disease in which endometrial tissue is deposited outside the normal confines of the uterine cavity. In rare instances, endometriosis involves the urinary tract, with the bladder the most frequent organ affected. Classic presenting symptoms include cyclic irritative voiding symptoms and suprapubic discomfort with or without hematuria. Both medical and surgical management have been advocated, but surgical extirpation is probably more efficacious. Two cases of endometriosis involving the the bladder are presented and contrasted in terms of pathophysiology. Contemporary management of this condition is reviewed, and guidelines for diagnosis and treatment are proposed.
Adult↗
Laparoscopic radical prostatectomy in the canine model.
The purpose of this study was to determine the feasibility of performing laparoscopic radical prostatectomy in a canine model. Laparoscopic radical prostatectomy was performed on six adult male canines. A new endoscopic needle driver was used to construct a secure vesicourethral anastomosis. Average operative time required to complete the procedure was 304 min (range 270-345 min). Dissection of the prostate gland took an average of 67 min (range 35-90 min), and construction of the vesicourethral anastomosis took 154 min (rage 80-240 min). There were no intraoperative complications and only one postoperative complication (anastomotic leak). Five of the six animals recovered uneventfully from the procedure, and their foley catheters were removed 10-14 days postoperatively after a retrograde cystourethrogram demonstrated an intact vesicourethral anastomosis. Four (80%) of the surviving animals were clinically continent within 10 days after catheter removal. Post mortem examination confirmed that the vesicourethral anastomosis was intact with no evidence of urine extravasation. These data demonstrate the feasibility of laparoscopic radical prostatectomy in a canine model, and suggest that additional work with this technique should be continued to develop its potential clinical application.
Animals↗
Distribution of beta 3-adrenoceptor mRNA in human tissues.
The beta 3-adrenoceptor is a G protein-coupled receptor which mediates metabolic functions of the endogenous catecholamines epinephrine and norepinephrine. Questions exist regarding distribution of the beta 3-adrenoceptor in human tissue. In order to examine the distribution of beta 3-adrenoceptor mRNA in human tissues, we used sensitive and specific RNase protection assays without previous PCR amplification in an extensive list of human tissues. We confirm the presence of beta 3-adrenoceptor mRNA in human white fat from several locations, gall bladder, and small intestine, as well as extend the distribution of beta 3-adrenoceptor mRNA to previously uncharacterized human tissues such as stomach and prostate. The presence of beta 3-adrenoceptor mRNA in human white adipose tissue has important implications regarding possible use of beta 3-adrenoceptor selective agonists as anti-obesity agents, and the demonstration of beta 3-adrenoceptor mRNA in a number of gastrointestinal tissues and prostate raises the question of the role of the beta 3-adrenoceptor in motility and secretory processes.
Animals↗
Down-regulation of transforming growth factor beta receptor type I, II, and III during liver regeneration.
BACKGROUND: After partial hepatectomy (PH), it has been shown that hepatocytes are resistant to the mitoinhibitory effects of transforming growth factor beta (TGF-beta). Three types of TGF-beta receptors have been characterized in mammals. MATERIALS AND METHODS: In this study, changes in the protein and mRNA expression of TGF-beta types I, II, and III receptors relative to DNA synthesis were studied as a function of time after PH in the rat. RESULTS: There was a significant decrease in the protein and mRNA for all three receptor subtypes immediately after PH. All three receptors reached a nadir at 24 hours after PH, which correlated to the time of peak DNA synthesis. The type II receptor recovered to preoperative levels by 120 hours after PH, whereas the types I and III receptors remained at 60% of prehepatectomy levels. Sham-operated rats did not experience a significant drop in receptor protein or mRNA levels. CONCLUSIONS: This decrease in TGF-beta type II receptor expression may account for the reduction in the sensitivity of hepatocytes to TGF-beta after PH. Furthermore, the TGF-beta receptors appear to represent a class of immediate-early genes that are negatively, rather than positively, regulated after PH.
Animals↗
Localization of messenger RNA for three distinct alpha 2-adrenergic receptor subtypes in human tissues. Evidence for species heterogeneity and implications for human pharmacology.
BACKGROUND: alpha 2-Adrenergic receptor (alpha 2AR) agonists have become important adjuncts as anesthetic agents. They act by binding to alpha 2ARs on the surface of cell membranes and cause centrally mediated sedation and analgesia. alpha 2ARs also contribute to other aspects of physiologic regulation. Three subtypes of alpha 2ARs (alpha 2-C2, alpha 2-C4, and alpha 2-C10) have been described using molecular and pharmacologic techniques. We recently demonstrated species heterogeneity in the distribution of alpha 1-adrenergic receptor subtypes, therefore making it imperative to analyze the distribution of alpha 2AR subtypes in human tissues. This information may have importance in the understanding of potential side effects of administration of alpha 2AR subtype-selective agonists for anesthesia in humans. METHODS: RNA extracted from human tissues was analyzed by using quantitative ribonuclease protection assays to determine alpha 2AR subtype messenger RNA (mRNA) expression in cardiovascular, central nervous system, and peripheral tissues. RESULTS: alpha 2AR mRNA is present in greatest concentrations in human kidney, followed by aorta > spleen > heart = lung. alpha 2-C4 mRNA predominates in heart, lung, aorta, cerebral cortex, cerebellum, spleen, kidney, and adrenal gland; alpha 2-C2 mRNA in liver; and alpha 2-C10 mRNA in pancreas and small intestine. Hence alpha 2AR subtype mRNA distribution is tissue-selective and differs from that reported for rat. CONCLUSIONS: (1) On comparison with previous research we find possible species heterogeneity in alpha 2AR subtype mRNA distribution (rat vs. human) for all three alpha 2AR subtypes. (2) We demonstrate the presence and subtype heterogeneity of alpha 2AR subtype mRNA in both brain and peripheral tissues. (3) Significant concentrations of alpha 2AR mRNA are present in adult human heart. These findings have important implications for our understanding of human adrenergic physiology, provide a possible explanation for the existence of pharmacologically similar yet distinct alpha 2AR subtypes, and may be important for the rational development of alpha 2AR subtype-selective anesthetics and other therapeutic agents for use in treating human diseases.
Adult↗
Expression of alpha 1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: implications for alpha 1-adrenergic receptor subtype classification.
At least three subtypes of alpha 1-adrenergic receptors (alpha 1ARs) have been identified using molecular techniques (alpha 1a/d, alpha 1b, and alpha 1c), whereas two subtypes of alpha 1ARs have been identified pharmacologically (alpha 1A and alpha 1B); however, controversies exist regarding how these two classification schemes relate to each other. In an attempt to clarify some of the controversies regarding classification of alpha 1AR subtypes, we have re-evaluated the distribution of mRNA for the cloned alpha 1AR subtypes (alpha 1a/d, alpha 1b, and alpha 1c) in various rat tissues thought to express alpha 1AR subtypes, as well as the human neuronal cell line SK-N-MC (a recently described model for pharmacologically defined alpha 1AAR and alpha 1BAR subtypes), using sensitive ribonuclease protection assay techniques. Total RNA extracted from various rat tissues and SK-N-MC cells was hybridized with rat and human alpha 1AR subtype-specific probes, respectively. In contrast to previously reported Northern blot analyses, alpha 1cAR mRNA is expressed in many rat tissues. Expression of alpha 1cAR mRNA is highest in those tissues that have been previously characterized by radioligand binding as expressing the classical, pharmacologically defined alpha 1AAR. Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological alpha 1AAR and alpha 1BAR subtypes, expresses both alpha 1a/dAR and alpha 1cAR mRNA and no alpha 1bAR mRNA. Collectively, these data suggest that the cloned alpha 1cAR subtype may represent the pharmacological alpha 1AAR, and they have important implications for merging pharmacological and molecular classifications of alpha 1AR subtypes.
Animals↗
Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology.
alpha 1-Adrenergic receptors (alpha 1ARs) are virtually ubiquitous in human tissues and mediate important physiological functions as diverse as smooth muscle contraction, glycogenolysis, and myocardial inotropy. At least three alpha 1AR subtypes (alpha 1A/D, alpha 1B, and alpha 1C) have been described using molecular and pharmacological techniques. The identification of species heterogeneity (rat versus rabbit) in alpha 1AR subtype distribution has made it imperative to determine the distribution of alpha 1AR subtypes in human tissues. Accordingly, RNA extracted from human tissues was analyzed using RNase protection assays to determine alpha 1AR subtype expression. Of the cloned alpha 1ARs, alpha 1CAR mRNA predominates in many human tissues (heart, liver, cerebellum, and cerebral cortex), in contrast to its restricted distribution in both rats and rabbits. alpha (1B)AR mRNA is present in highest concentrations in human spleen, kidney, and fetal brain. alpha 1A/DAR mRNA is present in highest concentrations in human aorta and cerebral cortex. Hence, alpha 1AR subtype mRNA distribution is tissue selective and differs from that reported for rats and rabbits. These results have potentially significant implications for understanding human adrenergic physiology and are important for the rational development of alpha 1AR subtype-selective drugs.
Adrenal Glands↗