Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vesiculodeferentography (VDG) plays an important role in diagnosing male infertility and staging of prostatic cancer; the techniques of performing the examination are, today, well codified: 1) retrograde, by endoscopic cannulation of ejaculatory ducts; 2) anterograde, by cannulation of the deferent duct surgically prepared at the scrotum. In order to avoid the difficulties of the first method and the risks in the second (like stenosis and fibrosis of the deferent duct) we propose a new simple and safe method based on the direct transperineal puncture of the seminal vesicle under direct echographic control with a transrectal probe. We have studied 16 patients, mainly in order to stage prostatic cancer; the procedure was easy to perform, well tolerated and without consequences at seminal level. It required only 30 minutes, without anaesthesia and with a very low cost. The method permits a clear visualisation of anatomical structures and of possible pathologies with particular reference to vesicular invasion by a prostatic cancer.
 ...
PMID:Transperineal vesiculodeferentography under ultrasound control: first experiences. 150 68

Clinical usefulness of the alpha 1-blocker and beta-stimulant combined therapy for idiopathic male infertility has already been reported by Yamamoto et al. But the same trial followed by us revealed only a slight effectiveness and substantial adverse effects due to beta-stimulation. The mechanism of the alpha 1-blocker and beta-stimulant combined therapy is not yet established. In order to investigate its mechanism, fundamental study of alpha 1-receptor assay in the specimens of testis and various parts of male accessory sex organs obtained at the time of operation was done in this study. In addition the usefulness of alpha 1-blocker therapy for idiopathic male infertility was also examined clinically. The tissues used in this study were obtained from patients with prostatic cancer (23 cases), benign prostatic hyperplasia (24 cases), bladder cancer (6 cases), chronic epididymitis (3 cases), azoospermia due to disorders of vas deferens (5 cases) and a vasectomized man. Tritium labeled bunazosin was used as the ligand. The crude membrane fraction was extracted from the sample, with or without phentolamine incubated for 20 min at 37 degrees C. Maximal binding sites (Bmax) and the dissociation constant (Kd) were obtained by Scatchard plot analysis. Twenty-two infertile men were treated by oral administration of alpha 1-blocker (bunazosin, 3 mg/day) for 24 weeks. The results were as follows: 1) Bmax in the testis, epididymis, vas deferens and prostate, expressed as fmol, per mg. protein, was 2.27 +/- 1.74, 16.62 +/- 6.19, 29.44 +/- 17.81, 27.77 +/- 12.0, respectively (mean +/- S.D.). 2) Bmax in the rete testis was relatively high among various parts of the testis and seminiferous tubules. 3) Overall effective rates of sperm density and the sperm motility were noted in 36% at 12 weeks and 60% at 24 weeks after the therapy. 4) There was no clinical effect in patients with azoospermia and a slight effectiveness in patients with elevated plasma gonadotropin levels. 5) Adverse effect was reduced to 9.1%. These results suggest that the alpha 1-blocker therapy for idiopathic male infertility is clinically useful and that the mechanism of the therapy is through the action on male accessory sex organs behind the testis.
 ...
PMID:[Fundamental and clinical studies on alpha 1-blocker therapy for idiopathic male infertility]. 168 30

In order to investigate the presence of androgen insensitivity in patients with male infertility, intratubular androgen receptor (AR) was measured in patients with idiopathic oligozoospermia and azoospermia. The specimens were obtained by testicular biopsy or orchiectomy from 56 patients with oligozoospermia and 5 with azoospermia for clinical study, and 17 with varicocele, 22 with vas disorders and prostatic cancer, which had a mean germinal epithelium score count of 8.5 or greater by the method of Johnsen (JSC) for deciding the cut-off levels, as the control group. Intratubular AR was measured by a 5-point micro-receptor assay, an exchange assay with the DCC method, using 40 microliters of each sample extract and 3H-methyltrienolone as the ligand. The genital skin AR assay was also conducted simultaneously in 34 patients. The results were as follows: 1) No significant correlation was noted between intratubular ARs and genital skin ARs. 2) The maximum binding (Bmax) of AR in the total intratubular extract was intermediate between that of the cytosol fraction and the nuclear extract. 3) Significant correlation was noted between the Bmax of ARs by the micro-receptor assay and those by the conventional assay. 4) The Bmax of AR in the control group (n = 22) was 30.38 +/- 9.89 fmol/mg protein (mean +/- S.D.) and was over 11 fmol/mg protein in all cases. Therefore, 11 fmol/mg protein was decided as the cut-off level for androgen insensitivity. 5) Comparative studies were undertaken between two groups, i.e., low AR group and normal AR group, with AR as a parameter for male infertility.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[A study on the intratubular androgen receptor in male infertility]. 228 16

The androgen receptor (AR) is a ligand-dependent DNA transcription factor that binds androgens which cause masculinisation of the developing male fetus. Classical abnormalities of receptor function result in the syndrome of androgen resistance, with resultant failure of normal male differentiation. In more recent years, however, mutations in the AR gene have been described in a number of diverse clinical conditions, from male infertility to prostate and breast cancer through to a form of motor neurone disease (Kennedy's disease). This review discusses the various AR gene mutations found in androgen insensitivity syndrome (AIS) and the other conditions described above, and relates how different mutations, or disruption of different functional domains, contributes to the various phenotypes. Mutations that cause complete AIS usually disrupt the DNA or steroid binding ability of the receptor. In partial AIS, mutations generally decrease receptor affinity for ligand, affect thermostability of the protein, or affect the ability of the receptor to activate transcription of responsive genes. Isolated mutations occur in the steroid binding domain of the receptor in prostate cancer, and many cancers have an identical mutation. Similarly, in the two cases of male breast cancer in which AR gene mutations have been described, the mutations in the DNA binding domain of the receptor are alike. In Kennedy's disease a trinucleotide repeat expansion occurs in exon A of the AR gene, which appears to affect ability of the receptor to bind ligand and activate transcription, although the mechanism of neuronal degeneration remains unknown.
 ...
PMID:Defects of androgen receptor function: from sex reversal to motor neurone disease. 748 16

Generally it is believed that mammalian sperm mature during their transit through the whole epididymis. However spermatozoa aspirated from the epididymal duct or vasa defferentia have been recently reported to move actively in azoospermic patients with seminal tract obstruction. We examined whether the testicular sperm move which would provide useful information in the diagnosis of male infertility. Testicular biopsy materials were obtained from 38 testes of 37 patients as follows; 19 cases with azoospermia, 11 with oligozoospermia, and 8 orchiectomized for prostatic cancer (3), testicular cancer (2), epididymal abscess (1), and cryptorchid (2). All materials were obtained from either open biopsy or from the normal portion of the orchiectomized testis. The material was minced with a sharp knife or scissors in an Eppendorf tube containing Ham's F12 solution. Then a couple of drops of sperm suspension were placed on a warmed (37 degrees C) slide glass which was then covered with a coverglass. The prepared slide was immediately examined by phase-contrast microscopy. Another part was used for preparing a touch smear for confirming the presence of testicular sperm and then was fixed in Bouin's solution and stained with H-E. Spermatogenesis was evaluated by Johnsen's mean score (JMS). Eleven of the 19 azoospermic cases revealed the presence of testicular sperm, and ten of them demonstrated the presence of motile sperm. The mean JMS in these cases was 8.8 (normal spermatogenesis). After surgical exploration or vasography, these patients were diagnosed with obstructive azoospermia (post-vasectomy (4 cases), congenital absence of vas deferens (2 cases), secondary epididymal duct obstruction (4 cases)).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Significance of the motile sperm presented in the testis]. 759 83

We report here the influence of intratesticular aromatase activity and intratesticular estrogen concentration on spermatogenesis. In the present study, we measured the levels of aromatase activity and the concentrations of intratesticular testosterone (T) and estradiol (E2) in 21 testicular tissues from biopsy of 20 idiopathic male infertility patients, 5 testicular tissues from castration of 4 prostatic cancer patients and a testicular tissue from an autopsy. Serum T, Free T, E2, LH and FSH were also measured if possible. Aromatase activity in the testis were assayed by measuring the amount of 3H2O formed during the conversion of [1 beta-3H] androstenedione to estrogen. Histological evaluation of the testes were performed using the Johnsen's score count (JSC) method. The rate of aromatase activity was linear in regard to time and amount of tissue. The production of 3H2O was inhibited by 4-hydroxyandrostenedione. The apparent Km (Michaelis constant) of the reaction was 23.2 nM. The rate of aromatase activity increased linearly as JSC level decreased (r = 0.67). Also, it significantly correlated with intratesticular T (r = 0.69), E2 (r = 0.88) and T/E2 ratio (r = -0.85), whereas it was not correlated with serum T, free T, E2, T/E2 ratio and free T/E2 ratio. Therefore, our results suggest the possibility that the increase in the rate of aromatase activity and the concentration of E2 may influence spermatogenesis.
 ...
PMID:[A study on intratesticular aromatase activity in male infertility]. 777 64

The X-linked androgen receptor (AR) gene contains two polymorphic trinucleotide repeat segments that code for polyglutamine and polyglycine tracts in the N-terminal trans-activation domain of the AR protein. Changes in the lengths of these polymorphic repeat segments have been associated with increased risk of prostate cancer, an androgen-dependent tumor. Expansion of the polyglutamine tract causes a rare neuromuscular disease, spinal bulbar muscular atrophy, that is associated with low virilization, reduced sperm production, testicular atrophy, and infertility. As spermatogenesis is exquisitely androgen dependent, it is plausible that changes in these two repeat segments could have a role in some cases of male infertility associated with impaired spermatogenesis. To test this hypothesis, we examined the lengths of the polyglutamine and polyglycine repeats in 153 patients with defective sperm production and compared them to 72 normal controls of proven fertility. There was no significant association between the polyglycine tract and infertility. However, patients with 28 or more glutamines (Gln) in their AR had more than 4-fold (95% confidence interval, 4.9-3.2) increased risk of impaired spermatogenesis, and the more severe the spermatogenic defect, the higher the proportion of patients with a longer Gln repeat. Concordantly, the risk of defective spermatogenesis was halved when the polyglutamine tract was short (< or = 23 Gln). Whole cell transfection experiments using AR constructs harboring 15, 20, and 31 Gln repeats and a luciferase reporter gene with an androgen response element promoter confirmed an inverse relationship between Gln number and trans-regulatory activity. Immunoblot analyses indicated that the reduced androgenicity of the AR was unlikely to be due to a change in AR protein content. The data indicate a direct relation between length of the AR polyglutamine tract and the risk of defective spermatogenesis that is attributable to the decreased functional competence of AR with longer glutamine tracts.
 ...
PMID:Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. 936 May 40

Mice lacking the functional cAMP responsive element modulator (CREM) gene, a component of cAMP-mediated signal transduction, exhibit a specific arrest of round spermatid development although follicle stimulating hormone (FSH) and androgen secretion are not impaired. We studied testicular expression of CREM protein by immunocytochemistry in four patients with complete spermatogenesis (obstructive azoospermia), in 20 infertile patients with round spermatid maturation arrest (n = 10) or mixed atrophy (n = 10) and in six prostate cancer patients undergoing orchidectomy. Concentrations of testosterone were below normal in three patients. Concentrations of luteinizing hormone (LH) were lowered in two patients and elevated in one patient. FSH concentrations were above normal in ten patients. During normal spermatogenesis, CREM was expressed in nuclei of round spermatids in stages I-III of spermatogenesis but not in elongating spermatids. Western blot analysis of testes from prostate cancer patients indicated a major CREM band of approximately 35 kDa. Among patients with predominant round spermatid maturation arrest, CREM expression was significantly reduced (P < 0.05) or undetectable as revealed by quantitative image analysis. CREM-negative spermatids failed to progress beyond stage III of spermatogenesis. Our observations suggest a role for CREM in human spermatid development and raise the possibility that altered CREM expression could be associated with spermatid maturation defects in some cases of idiopathic male infertility.
 ...
PMID:Testicular cAMP responsive element modulator (CREM) protein is expressed in round spermatids but is absent or reduced in men with round spermatid maturation arrest. 951 6

Genetic defects of the human androgen receptor (AR) can cause a wide spectrum of androgen insensitivity syndromes (AIS) ranging from phenotypic females in those with complete AIS; ambiguous genitalia in partial AIS; to male infertility in minimal AIS. The majority of these defects are due to point mutations resulting in amino acid substitutions. It is however unclear why certain mutations result in partial AIS, whereas others in the same exon cause the complete syndrome. We present a case of partial AIS due to a point mutation affecting codon 758 of the AR ligand-binding domain (LBD) that changed the sense of the codon from asparagine to threonine (N758T). The mutant receptor displayed normal binding affinity to DHT but abnormal dissociation kinetics in both patient's fibroblasts and transfected COS-7 cells. The mutant AR was thermolabile, and resulted in approximately 50% reduction in receptor transactivation capacity when examined with a reporter gene incorporating an androgen-response-element. Although the 3-D structure of AR LBD is not known, the homologous region in a member of the steroid receptor superfamily, retinoid-X receptor (RXR-alpha), has been crystallized, allowing comparison of aligned amino-acid sequences of RXR-alpha and AR. The mutation, N758T, lies in a predicted linker region between the fifth alpha-helix (H5) and the first beta-strand (S1). Generally, mutations leading to partial AIS tend to cluster in the predicted linker regions located between the structural helices of the AR LBD. Most strikingly, the predicted linker regions contain over 70% of the mutant ARs associated with prostate cancer in the LBD. The occurrence of mutations associated with both partial AIS and prostate cancer in the same predicted linker regions, suggest that this clustering is not coincidental and that the predicted linker regions are likely to have important, but subtle, roles in defining androgen binding and ligand specificity.
 ...
PMID:Partial androgen insensitivity and correlations with the predicted three dimensional structure of the androgen receptor ligand-binding domain. 960 27

Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.
 ...
PMID:Androgen receptor transactivation domain and control of spermatogenesis. 982 47


1 2 3 4 5 Next >>