Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Until recently metabolism and expression of thyroid hormones was considered not to occur in the tissues of the testes. Lately, specific receptors for triiodothyronine have been found in the nuclei of human testicular cells which shows that testicular tissue requires hormonal action [9]. The aim of the present study was to evaluate if the prohormone thyroxine is converted into triiodothyronine within human testes (resected because of prostatic carcinoma) and if hormonal therapy with dihydrostilbestrol (DES), a testosterone antagonist, affects production of the active thyroid hormone. Our earlier studies showed a complete lack of iodothyronine 5'-deiodinase activity in prostatic carcinoma (PC) [7]. The present material consisted of testes from 21 patients with PCs. According to Whitmore's classification 13 patients were at stage C with mean PSA of 70.15 ng/ml and 8 were at stage D with mean PSA of 308.73 ng/ml. Before castration 6 patients (3 stage C and 3 stage D) were pretreated with 3 mg DES daily for 3 days. The resected testes were homogenized and ultracentrifuged. The obtained microsomal fraction was the source of thyroxine 5'-deiodinase (T4-5'-D). In 15 patients, in whom the primary approach was surgical, the specific T4-5'-D activity was not different between stage C and D patients (mean +/- SD): 19.52 +/- 12.55 vs. 22.07 +/- 12.68 fmol de novo produced triiodothyronine/min/mg of microsomal protein, respectively. However, in 6 patients pretreated with DES the activity was significantly decreased, regardless of the degree of differentiation of the prostate carcinoma: 0.70 +/- 0.68 fmol T3/min/mg for stage C and 2.6 +/- 4.5 fmol/min/mg for stage D patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The deiodination of thyroxine to triiodothyronine in the testes of patients with prostate cancer. 761 74

A new monoclonal antibody, 2E11, was produced by immunizing mice with the microsomal fraction of rat accessory olfactory bulb cells. This IgM recognizes a previously described complex alpha-galactosyl containing glycolipid, as well as N-linked glycoproteins at 170 and 210 kD. These proteins correspond to a new nerve cell adhesion molecule (NCAM) glycoform, Gal-NCAM, which contains a blood group B-like oligosaccharide. During embryonic development, the 2E11 epitope is expressed by a subset of mature olfactory sensory neurons randomly dispersed throughout the olfactory epithelium, whereas in the olfactory bulb, immunostaining is restricted to medial areas of the nerve layer. When compared to PSA-NCAM, another NCAM glycoform, Gal-NCAM has a mutually exclusive distribution pattern both in the olfactory epithelium and in the olfactory bulb. We propose a model for the hierarchy of neuronal maturation in the olfactory epithelium, including a switch from PSA-NCAM expression by immature neurons to the expression of Gal-NCAM by mature neurons.
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PMID:Gal-NCAM is a differentially expressed marker for mature sensory neurons in the rat olfactory system. 1077 Aug 46

In the present investigation, the degradation of the acaricide dicofol (also known as kelthane) was investigated with special emphasis on generation of p,p'-dichlorobenzophenone (DCBP) under alkaline conditions as well as induced by UV-light. Dicofol was also incubated in the presence and absence of microsomal preparations to measure potential metabolic formation of DCBP. The results indicate that the degradation of dicofol to DCBP primarily proceeds as an abiotic process via hydroxide ion catalysed elimination of a trichloromethyl anion. The generated anion picks up a proton from the solvent to generate chloroform. Microsomal metabolism does not appear to play a major role in the degradation of dicofol. DCBP is structurally analogous to the antiandrogen p,p'-dichlorodiphenylethene (DDE). We therefore investigated whether DCBP displays antiandrogenic properties. In an in vitro transactivation system utilising transiently transfected African green monkey kidney (COS-7) cells, DCBP showed potent antiandrogenic efficacy. This finding was confirmed by further studies in T47D human mammary carcinoma cells by measuring mRNA and protein expression of androgen dependent genes i.e. TRMP-2 (testosterone-repressed prostate message-2) mRNA and PSA (prostate-specific antigen) protein.
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PMID:Dicofol degradation to p,p'-dichlorobenzophenone - a potential antiandrogen. 2129 47

Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimization efforts are described targeting improvements in potency, microsomal stability, and PK properties. The low microsomal stability and poor PK properties were addressed through the optimization of the sulfonyl urea and replacement of the benzothiazepinone with other N-heteroaryl glycinamides. For example, the analogous benzoxazine glycinamide 2e has improvements in both affinity (human Y5 K(i) 4 nM vs 1a 27 nM) and microsomal stability (human CL(int) 2.5 L/min vs 1a 35L/min). However the brain penetration (B/P 43/430 nM at 10 mg/kg PO) remained an unresolved issue. Further optimization by decreasing the hydrogen bond donating properties and PSA provided potent and brain penetrant NPY5 antagonists such as 5f (human Y5 K(i) 9 nM, B/P 520/840 nM 10 mg/kg PO).
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PMID:N-Heteroaryl glycinamides and glycinamines as potent NPY5 antagonists. 2178 30

This study checked the existence of a diverse array of aminopeptidase (AP) enzymes in high (HDM) and low (LDM) density microsomal and plasma membrane (MF) fractions from adipocytes of control, monosodium glutamate obese and food deprived rats. Gene expression was detected for ArgAP, AspAP, MetAP, and two AlaAP (APM and PSA). APM and PSA had the highest catalytic efficiency, whereas AspAP the highest affinity. Subcellular distribution of AP activities depended on metabolic status. Comparing catalytic levels, AspAP in HDM, LDM and MF was absent in obese and control under food deprivation; PSA in LDM was 3.5-times higher in obese than in normally fed control and control and obese under food deprivation; MetAP in MF was 4.5-times higher in obese than in food deprived obese. Data show new AP enzymes genetically expressed in subcellular compartments of adipocytes, three of them with altered catalytic levels that respond to whole-body energetic demands.
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PMID:Adipocyte aminopeptidases in obesity and fasting. 2625 41