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At least 559 records · Page 31Linked to original sources
PubMed2003

Sex steroid hormone metabolism takes place in human ocular cells.

Steroids are potentially important mediators in the pathophysiology of ocular diseases. In this study, we report on the gene expression in the human eye of a group of enzymes, the 17beta-hydroxysteroid dehydrogenases (17HSDs), involved in the biosynthesis and inactivation of sex steroid hormones. In the eye, the ciliary epithelium, a neuroendocrine secretory epithelium, co-expresses the highest levels of 17HSD2 and 5 mRNAs, and in lesser level 17HSD7 mRNA. The regulation of gene expression of these enzymes was investigated in vitro in cell lines, ODM-C4 and chronic open glaucoma (GCE), used as cell models of the human ciliary epithelium. The estrogen, 17beta-estradiol (10(-7) M) and androgen agonist, R1881 (10(-8) M) elicited in ODM-C4 and GCE cells over a 24 h time course a robust up-regulation of 17HSD7 mRNA expression. 17HSD2 was up-regulated by estradiol in ODM-C4 cells, but not in GCE cells. Under steady-state conditions, ODM-C4 cells exhibited a predominant 17HSD2 oxidative enzymatic activity. In contrast, 17HSD2 activity was low or absent in GCE cells. Our collective data suggest that cultured human ciliary epithelial cells are able to metabolize estrogen, androgen and progesterone, and that 17HSD2 and 7 in these cells are sex steroid hormone-responsive genes and 17HSD7 is responsible to keep on intra/paracrine estrogenic milieu.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

Somatostatin modulates PI3K-Akt, eNOS and NHE activity in the ciliary epithelium.

Somatostatin (SST) is a biologically active peptide produced in neuroendocrine cells. In the present study, we provide evidence of pro-SST and SST receptor (SSTR1 and 2A) mRNA expression in ocular ciliary epithelium (CE). SST or SST-like immunoreactivity was detected by radioimmunoassay in tissue extract from ciliary processes and in aqueous humor. The distinct immunolabeling of CE with SST and proprotein convertases PC1 and PC2 antibodies suggested a tissue and cell-specific processing of pro-SST. SST (10(-8) to 10(-4)M) added exogenously to the CE, elicited the following effects: (i) a dose-dependent attenuation of Na+/H+-exchanger (NHE) activity; (ii) up to a two-fold increase phosphorylation of p-Akt-Ser473 and of p-eNOS-Ser617, and (iii) lack of response on intracellular cyclic GMP production. LY294002, a PI3K-inhibitor, blocked SST-induced p-Akt-Ser473 and partially p-eNOS-Ser617, however, it did not reverse SST-induced NHE attenuation. Collectively, these results suggested involvement of SST in multiple intracellular signaling pathways in the CE.

Animals↗
PubMed2005

Osmotin is a homolog of mammalian adiponectin and controls apoptosis in yeast through a homolog of mammalian adiponectin receptor.

The antifungal activity of the PR-5 family of plant defense proteins has been suspected to involve specific plasma membrane component(s) of the fungal target. Osmotin is a tobacco PR-5 family protein that induces apoptosis in the yeast Saccharomyces cerevisiae. We show here that the protein encoded by ORE20/PHO36 (YOL002c), a seven transmembrane domain receptor-like polypeptide that regulates lipid and phosphate metabolism, is an osmotin binding plasma membrane protein that is required for full sensitivity to osmotin. PHO36 functions upstream of RAS2 in the osmotin-induced apoptotic pathway. The mammalian homolog of PHO36 is a receptor for the hormone adiponectin and regulates cellular lipid and sugar metabolism. Osmotin and adiponectin, the corresponding "receptor" binding proteins, do not share sequence similarity. However, the beta barrel domain of both proteins can be overlapped, and osmotin, like adiponectin, activates AMP kinase in C2C12 myocytes via adiponectin receptors.

Adiponectin↗
PubMed2004

The bovine iris-ciliary epithelium expresses components of rod phototransduction.

Earlier studies have documented that the iris in lower vertebrates is photosensitive. In the present work, we examined whether the bovine iris which exhibits a common embryonic origin with the ocular ciliary epithelium and the neural retina, expresses components of phototransduction. By Northern blot and RT-PCR amplification we detected in the iris, rhodopsin, rhodopsin kinase and arrestin transcripts and DNA products, respectively, of the same size as in the retina. By Western blot, antibodies to rhodopsin, rhodopsin kinase and arrestin detected low levels of protein with similar molecular masses as in the retina. Transient transfections of bovine iris cells in vitro with rhodopsin promoter-luciferase-reporter constructs (p130-Luc, p176-Luc, 1225-Luc and p2000-Luc) containing proximal and distal promoter elements led to a significant stimulation of promoter activity over the basal activity. In particular, the construct p225-Luc containing proximal promoter elements upstream of the transcription start site (-225 to +70 bp) led to 3.1-fold stimulation of activity over p176-Luc, 2.1-fold over p130 or p2000-Luc and 190-fold over the basal activity. These results suggested that the bovine iris cells contain factors that could either stimulate or attenuate rhodopsin transcription. The data also supported the view that components associated with non-visual phototransduction are expressed in extraretinal sites including the ciliary epithelium and the iris.

Animals↗
PubMed2006

Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample.

BACKGROUND AND AIM: The ankle-brachial index (ABI) is being used increasingly to diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity and mortality. The aim of this study is to determine the prevalence of PAD and associated risk factors in a Spanish random population sample of age > or =40. METHODS AND RESULTS: PAD is defined as an ABI<0.9 in either leg. 784 participants of age > or =40 were randomly selected in a Spanish province. 55.4% of them were female. The prevalence of PAD in this sample was 10.5% (95% confidence interval (CI) 8.4-12.8); 9.7% in females and 11.4% in males. In logistic regression analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR) 1.40, 95% CI 1.23-1.58), hypertension (OR 1.85, 95% CI 1.05-3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04-2.98), and diabetes (OR 1.80, 95% CI 1.04-3.11) were positively associated with prevalent PAD. More than 91% of persons with PAD had one or more cardiovascular disease risk factors. CONCLUSIONS: We conclude that in our study hypertension, hypercholesterolemia, diabetes mellitus and smoking are associated with PAD. The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment.

Adult↗
PubMed2004

Comparison of several combinations of free, complexed, and total PSA in the diagnosis of prostate cancer in patients with urologic symptoms.

OBJECTIVES: To compare the diagnostic efficacy of prostate-specific antigen (PSA) and the PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between prostate cancer and benign prostatic hyperplasia. METHODS: We measured the serum levels of total PSA (tPSA; Hybritech and Bayer), fPSA (Hybritech), and cPSA (Bayer) in 72 patients with prostate cancer and 128 patients with benign prostatic hyperplasia. RESULTS: Receiver operating characteristic curves were used for comparison of these tests. The greatest area under the curve was observed for the fPSA/cPSA ratio and the fPSA/tPSA ratio (0.757 and 0.754, respectively). The substitution of the fPSA/tPSA ratio with the fPSA/cPSA ratio in the diagnostic scheme of prostate cancer improved the diagnostic accuracy, with similar sensitivity and an increment in specificity (41% versus 45%). CONCLUSIONS: The fPSA/cPSA ratio ensures a reduction in negative biopsies in the PSA gray zone. We suggest substituting the fPSA/tPSA ratio with the fPSA/cPSA ratio for patients with a PSA level between 4 and 10 ng/mL.

Aged↗
PubMed2006

Monitoring temperatures in the vaccine cold chain in Bolivia.

This study monitored vaccine cold chain temperatures during routine DTP-HB-Hib vaccine shipments from central stores to 11 communities in 3 provinces of Bolivia. In all 11 monitored shipments, vaccines were exposed to freezing temperatures at one or more points. In each of the shipments, temperatures below 0 degrees C were recorded for 2-50% of the monitoring period. Freezing occurred at almost every level of the cold chain distribution system, especially during district and health center storage and during transport to the province and district levels. Seven of the 11 shipments were exposed to temperatures above 8 degrees C, although none were exposed to excessive heat longer than 1.3% of the total monitoring period.

Bolivia↗
PubMed2004

[Is there a link between the food-cobalamin malabsorption and the pernicious anemia?].

BACKGROUND: A relation between food-cobalamin malabsorption and pernicious anemia has been suggested, particularly in the event of food-cobalamin malabsorption related to hypochlorhydric atrophic gastritis. STUDY DESIGN: This work describes three cases of well-documented cobalamin deficiency related to food-cobalamin malabsorption in three women aged 56, 82 and 68 Years who had atrophic gastritis (not associated with Helicobacter pylori infection) and later developed authentic pernicious anemia. CONCLUSIONS: This work illustrates the potential relation between these two disorders responsible for cobalamin deficiency.

Adult↗
PubMed2003

Production, purification, and functional analysis of recombinant human and mouse 17beta-hydroxysteroid dehydrogenase type 7.

17beta-Hydroxysteroid dehydrogenases (17HSDs) have a central role in the regulation of the biological activity of sex steroid hormones. There is increasing evidence that in addition to their importance in gonads, these hormones also have substantial metabolic roles in a variety of peripheral tissues. In the present study, the cDNA of human 17HSD type 7 was cloned. In silico, the gene corresponding to the cDNA was localized on chromosome 1q23, close to the locus of hereditary prostate cancer 1 (HPC1) (1q24-25) and primary open-angle glaucoma (GLC1A) (1q23-25). Further, a pseudogene was found on chromosome 1q44, close to the locus of predisposing for early-onset prostate cancer (PCaP) (1q42.2-43). Both human (h17HSD7) and mouse 17HSD type 7 (m17HSD7) were for the first time produced as recombinant proteins and purified for functional analyses. Further, kinetic parameters and specific activities were described. h17HSD7 converted estrone (E1) to a more potent estrogen, estradiol (E2), and dihydrotestosterone (DHT), a potent androgen, to an estrogenic metabolite 5alpha-androstane-3beta, 17beta-diol (3betaA-diol) equally, thereby catalyzing the reduction of the keto group in either 17- or 3-position of the substrate. Minor 3betaHSD-like activity towards progesterone (P) and 20-hydroxyprogesterone (20-OH-P), leading to the inactivation of P by h17HSD7, was also detected. m17HSD7 efficiently catalyzed the reaction from E1 to E2 and moderately converted DHT to an inactive metabolite 5alpha-androstane-3alpha,17beta-diol (3alphaA-diol) and to an even lesser degree 3betaA-diol. The mouse enzyme did not metabolize P or 20-OH-P. The expression of 17HSD type 7 was observed widely in human tissues, most distinctly in adrenal gland, liver, lung, and thymus. Based on the enzymatic characteristics and tissue distribution, we conclude that h17HSD7 might be an intracrine regulator of steroid metabolism, fortifying the estrogenic milieu in peripheral tissues.

17-Hydroxysteroid Dehydrogenases↗
PubMed2003

CRALBP transcriptional regulation in ciliary epithelial, retinal Müller and retinal pigment epithelial cells.

Cellular retinaldehyde binding protein (CRALBP) functions in the visual cycle and mutations in the RLBP1 gene can lead to blindness. RLBP1 promoter analyses have been pursued in vitro as an approach to deciphering the mechanism controlling cell-specific expression of CRALBP. Reporter activity of wildtype and mutant RLBP1 promoter constructs suggest that CRALBP transcriptional regulation may be similar in the ciliary epithelium (CE) and retinal pigment epithelium (RPE) but different in Müller cells. Results in RPE cells refine the location of an RLBP1 enhancer element to within -1826 to -1749 bp and a repressor element to within -702 to -635 bp.

Base Sequence↗
PubMed1995

Immortalization of cat iris sphincter smooth muscle cells by SV40 virus: growth, morphological, biochemical and pharmacological characteristics.

The purpose of this study was to establish immortalized cell cultures of cat iris sphincter smooth muscle cells for a model investigating ocular receptors and their signal transduction pathways. Cultured cat iris sphincter muscle cells were immortalized by viral transformation with SV40 virus and the morphological and immunocytochemical properties of the normal and immortalized cells were investigated. The transformed cell clone, SV-CISM-2, was further characterized biochemically and pharmacologically. The normal muscle cells showed characteristics of smooth muscle cells, as judged by their growth and the presence of smooth muscle alpha-actin and desmin. After seven passages the normal cells ceased to proliferate. In contrast, the immortalized cells retained their proliferative ability for more than 220 population doublings over 55 passages. The transformation phenotype in these cells was confirmed by their expression of the large T-antigen, the incorporation of viral DNA into cellular DNA, growth in agarose and in low-serum medium, and complete loss of contact inhibition. The immortalized cells expressed smooth muscle alpha-actin, desmin and MLC protein. Biochemical and pharmacological studies on the SV-CISM cells revealed the presence of several functional receptors including muscarinic cholinergic, beta-adrenergic, peptidergic (substance P and endothelin). Platelet-activating factor, and prostaglandin (PG). Muscarinic stimulation of these cells resulted in: (a) a dose-dependent increase in the release of arachidonic acid (AA) and (PGs) and enhancement in the production of inositol trisphosphate (IP3); and (b) a substantial increase in MLC phosphorylation (118%), an indicator of smooth muscle contractility. The stimulatory effects of carbachol on these responses were completely blocked by atropine, a muscarinic receptor antagonist. This study constitutes the first successful immortalization of iris sphincter smooth muscle cells. The SV-CISM-2 cells can serve as an important model system for investigations on the biochemical and pharmacological properties of receptors and their signal transduction pathways in smooth muscle. The advantage of these cells over normal iris sphincter cells is that they can be propagated over many generations without alterations in their morphological, biochemical and physiological characteristics.

Animals↗
PubMed1992

Regulatory volume decrease by cultured non-pigmented ciliary epithelial cells.

Cells (ODM C1-2/SV40) derived from human non-pigmented ciliary epithelial cells were studied by electronic cell sizing. The time course of the cell volume (vc) was monitored after suspending cells in paired experimental and control, isosmotic and hyposmotic solutions of identical ionic composition. Following anisosmotic cell swelling, the cells displayed the regulatory volume decrease (RVD) previously described. The RVD primarily reflects loss of cell KCl since: (1) the K(+)-channel blockers quinidine and Ba2+ both inhibit the RVD; and (2) replacement of external Cl- with gluconate or addition of the Cl- channel blocker NPPB also inhibits the RVD. Bicarbonate has previously been reported to speed the RVD. This action likely reflects pH dependence of the channels since: (1) increasing the external pH speeds the RVD, whether or not HCO3- is present; and (2) DIDS (a blocker of Cl- channels and of Cl-/HCO3- exchange) is an effective inhibitor of the RVD, even after blocking Cl-/HCO3- exchange by removing external HCO3-. The RVD could also be inhibited by reducing the availability of Ca2+, either by omitting Ca2+ from the external medium or by blocking mobilization of intracellular Ca2+ with TMB-8. Furthermore, the RVD was slowed and incomplete in the presence of the calcium/calmodulin blocker trifluoperazine. We conclude that anisosmotic swelling triggers a series of events, mediated at least in part by calcium/calmodulin, leading to the extrusion of KCl through parallel K+ and Cl- channels.

Bicarbonates↗
PubMed1986

Growth of non-pigmented ciliary epithelial cells in serum-free hormone-supplemented media.

Bovine non-pigmented ciliary epithelial (NPE) cells are cultured following a dissecting procedure that preserves the original cellular polarity. Cell growth of primary cultures of NPE cells is supported by hormonally defined serum-free culture media and an artificial substrate with high binding affinity to attach cells in culture. Cell proliferation of primary cultures of bovine NPE cells was limited to 3-5 weeks. Nerve growth factor (NGF) was found to have a profound effect on the cellular junctions of growing NPE cells when added to the culture media. Nerve growth factor induced the formation abundant microfilament bundles associated with junctional complexes of undetermined nature between adjacent cells. Electron microscopy of NPE in culture shows a high intracellular transport activity with abundant coated pits and clathrin-coated vesicles, a complex network of microfilaments, microtubules and intermediate filaments associated with desmosomes.

Actin Cytoskeleton↗
PubMed1997

Cloning and characterization of subtracted cDNAs from a human ciliary body library encoding TIGR, a protein involved in juvenile open angle glaucoma with homology to myosin and olfactomedin.

A group of cDNAs isolated from a subtractive ciliary body library of a normal human eye donor revealed 100% identity with TIGR a candidate gene responsible for juvenile open zangle glaucoma [Science 275 (1997) 668-670]. Several structural features of the deduced human protein have been noted: a cleavable N-terminal signal peptide, a periodic repetition at the N-terminus of leucine and arginine residues at every seventh and eleven position respectively in helix conformation (leucine zipper-like motif) exhibiting homology with myosin, and with olfactomedin in the C-terminus. The mRNA for TIGR is abundantly expressed in the ciliary body, iris, heart and skeletal muscle.

Amino Acid Sequence↗
PubMed2002

Characterization of polyarylamide fibers by inverse gas chromatography.

Two types of commercial polyaramide fibers have been characterized by inverse gas chromatography. Using the fibers as stationary phases, adsorption isotherms for nonane, decane and undecane were obtained. Specific surface areas and isosteric heats of adsorption were also obtained by this method. Experimental results have been discussed as a function of hydrocarbon--fiber interaction and fiber crystallinity.

Adsorption↗
PubMed2000

[Relationship between cardiovascular risk profile and anti-hypertensive drug use. GEDEC (Spanish group of cardiovascular studies].

BACKGROUND: Hypertension guidelines emphasize the selection of antihypertensive treatment on the basis of absolute cardiovascular risk. Moreover, compelling and possible indications for each antihypertensive drug class are recommended for patients with other concomitant conditions. The aim of the present study was to analyze the relationship between the cardiovascular risk profile and co-morbid conditions on antihypertensive drug class use. METHODS: This is an observational, multicenter, cross-sectional study performed in 2,850 essential hypertensive patients. Antihypertensive drug treatment has been evaluated on the basis of the presence of other cardiovascular risk factors, target organ damage or cardiovascular diseases, as well as the absolute cardiovascular risk profile. RESULTS: Patients with diabetes were treated more frequently with calcium channel blockers (CCB) and ACE inhibitors. However, the presence of hypercholesterolemia or smoking habit did not influence the use of antihypertensive drug classes. The presence of cerebrovascular disease increased the use of CCB and ACE inhibitors, whereas coronary disease increased the use of CCB and betablockers. The use of diuretics and angiotensin II receptor antagonists was increased in patients with cardiac failure, whereas neither betablockers nor ACE inhibitors were affected by this concomitant disease. Patients with the highest cardiovascular risk received more antihypertensive treatment than those with lower risk, but this was not accompanied by switching from old classes to new ones. CONCLUSION: Cardiovascular risk profile seems to have little influence on the use of antihypertensive drug classes, particularly the presence of hypercholesterolemia or cardiac failure. It seems adequate to emphasize the necessity of an individualization of antihypertensive treatment, based on the presence of concomitant conditions that influence the absolute cardiovascular risk.

Adult↗