Search PubMed⌕ Search

Biomedical subjects

J Ortego

Publications and source records attributed to J Ortego.

At least 37 records · Page 2Linked to original sources

Differential gene expression in the human ciliary epithelium.

The generation of expression and subtractive libraries from the ocular ciliary body and cultured ciliary epithelial cells has been instrumental in the cloning, identification and characterization of many genes which, overall reflect a representative profile of transcripts expressed in ciliary nonpigmented, ciliary pigmented and ciliary muscle cells. The cell-specific expression of some of these genes (i.e. a neurotrophic factor, a gene associated with juvenile open glaucoma, and a visual component) reveal a degree of cell differentiation with a diversity of functions and properties higher than previously thought. The protection from light-induced oxidative reactions, free radicals and detoxification, may be partially attributed to the high level of expression in the ciliary epithelium of antioxidative enzymes (i.e., glutathione S-transferase, glutathione peroxidases, selenoprotein-P). The expression of genes encoding plasma proteins (i.e., complement component C4, alpha2-macroglobulin, apolipoprotein D) is in contrast with the view that plasma proteins in aqueous humor are synthesized outside the eye (i.e., liver). The identification of neuropeptide-processing enzymes (i.e., prohormone convertases, carboxypeptidase E, peptidyl-glycine-alpha-amidating monoxigenase), neuropeptides (i.e., secretogranin II, neurotensin) and regulatory peptides (i.e., atrial natriuretic peptide and angiotensinogen) with hypertensive and hypotensive activities provide the molecular basis to support the view that the ciliary epithelium is a neuroepithelium with neuroendocrine functions. We propose a working model to demonstrate that aqueous humor and intraocular pressure are under neuroendocrine control through regulatory peptides synthesized and released by the ciliary epithelium and targeting the peptide producing cells at the inflow system by an autocrine mechanism and/or cells at the outflow system (i.e., trabecular meshwork cells) by a paracrine mechanism. Finally, we hypothesize that these mechanisms could be entrained in the light-dark cycle following the circadian rhythm of aqueous humor and intraocular pressure.

Ciliary Body↗

Molecular identification and coexpression of galanin and GalR-1 galanin receptor in the human ocular ciliary epithelium: differential modulation of their expression by the activation of alpha2- and beta2-adrenergic receptors in cultured ciliary epithelial cells.

Here we report the coexpression of the neuropeptide galanin and GalR-1 galanin receptors in the human ciliary epithelium, a bilayer of neuroepithelial cells [nonpigmented (NPE) and pigmented (PE)] with neuroendocrine functions, and in a cell line (ODM-2) derived from the NPE cells. Stimulation of ODM-2 cells with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or forskolin resulted in an up-regulation (two- to threefold) of galanin mRNA expression. Procaterol, a selective beta2-adrenergic agonist, and the catecholamine isoproterenol exerted a long-term down-regulation on galanin mRNA expression when added alone or in combination with PMA or forskolin. These actions exerted by procaterol or isoproterenol were abolished in the presence of ICI 118,551, a selective beta2-adrenergic antagonist. A radioimmunoassay for galanin peptide indicated that galanin or a galanin-like product is present in the human aqueous humor fluid and is accumulated with time in the culture medium of ODM-2 cells. It is interesting that norepinephrine, which exhibited no effect on galanin mRNA expression, induced a down-regulation in the level of galanin or galanin-like product accumulated in the medium of cultured ODM-2 cells to levels even lower than those induced by beta2-adrenergic agonists. This effect is best explained by the concomitant up-regulation (four- to fivefold) of GalR-1 galanin receptor transcripts induced through the activation of alpha2-adrenergic receptors. These findings support the view that pathways elicited by the activation of alpha2- and beta2-adrenergic receptors influence the expression of galanin and GalR-1 galanin receptors in ciliary epithelial cells.

Adrenergic alpha-Agonists↗

Measles virus fusion protein is palmitoylated on transmembrane-intracytoplasmic cysteine residues which participate in cell fusion.

[3H]palmitic acid was metabolically incorporated into the viral fusion protein (F) of Edmonston or freshly isolated measles virus (MV) during infection of human lymphoid or Vero cells. The uncleaved precursor F0 and the F1 subunit from infected cells and extracellular virus were both labeled, indicating that palmitoylation can take place prior to F0 cleavage and that palmitoylated F protein was incorporated into virus particles. [3H]palmitic acid was released from F protein upon hydroxylamine or dithiothreitol treatment, indicating a thioester linkage. In cells transfected with the cloned MV F gene, in which the cysteines located in the intracytoplasmic and transmembrane domains (Cys 506, 518, 519, 520, and 524) were replaced by serine, a major reduction of [3H]palmitic acid incorporation was observed for F mutated at Cys 506 and, to a lesser extent, at Cys 518 and Cys 524. We also observed incorporation of [3H]palmitic acid in the F1 subunit of canine distemper virus F protein. Cell fusion induced by cotransfection of cells with MV F and H (hemagglutinin) genes was significantly reduced after replacement of Cys 506 or Cys 519 with serine in the MV F gene. Transfection with the F gene with a mutation for Cys 518 abolished cell fusion, although less mutant protein was detected on the cell surface. These results suggest that the F protein transmembrane domain cysteines 506 and 518 participate in structures involved in cell fusion, possibly mediated by palmitoylation.

Acylation↗

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↗

Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells.

Lysosomes are considered to be a terminal degradative compartment of the endocytic pathway, into which transport is mostly unidirectional. However, specialized secretory vesicles regulated by Ca2+, such as neutrophil azurophil granules, mast cell-specific granules, and cytotoxic lymphocyte lytic granules, share characteristics with lysosomes that may reflect a common biogenesis. In addition, the involvement of Ca2+ transients in the invasion mechanism of the parasite Trypanosoma cruzi, which occurs by fusion of lysosomes with the plasma membrane, suggested that lysosome exocytosis might be a generalized process present in most cell types. Here we demonstrate that elevation in the intracellular free Ca2+ concentration of normal rat kidney (NRK) fibroblasts induces fusion of lysosomes with the plasma membrane. This was verified by measuring the release of the lysosomal enzyme beta-hexosaminidase, the appearance on the plasma membrane of the lysosomal glycoprotein lgp120, the release of fluid-phase tracers previously loaded into lysosomes, and the release of the lysosomally processed form of cathepsin D. Exposure to the Ca2+ ionophore ionomycin or addition of Ca2+-containing buffers to streptolysin O-permeabilized cells induced exocytosis of approximately 10% of the total lysosomes of NRK cells. The process was also detected in other cell types such as epithelial cells and myoblasts. Lysosomal exocytosis was found to require micromolar levels of Ca2+ and to be temperature and ATP dependent, similar to Ca2+-regulated secretory mechanisms in specialized cells. These findings highlight a novel role for lysosomes in cellular membrane traffic and suggest that fusion of lysosomes with the plasma membrane may be an ubiquitous form of Ca2+-regulated exocytosis.

Adenosine Triphosphate↗

Gene expression of proteases and protease inhibitors in the human ciliary epithelium and ODM-2 cells.

Complementary DNAs (cDNAs), corresponding to the human proteinases cathepsins D and O and proteinase inhibitors alpha2-macroglobulin and PP5/TFPI-2, have recently been isolated and identified from a subtractive human ciliary body library. In the present study we determined: (i) their pattern of expression in the human eye; (ii) the ability of the ciliary body and/or ciliary epithelial cells to synthesize and secrete cathepsin D and alpha1-antitrypsin in vitro; and (iii) whether alpha1-antitrypsin expression in cultured ciliary epithelial cells is modulated by protein kinase C activation. Northern analysis demonstrated that the ciliary body expresses high levels of cathepsins D and O, alpha2-macroglobulin, alpha1-antitrypsin and PP5/TFPI-2 transcripts. Western blot analysis and immunoprecipitation experiments with cathepsin D and alpha1-antitrypsin antibodies indicated that metabolically labeled ciliary body explants and/or ciliary epithelial cells in vitro with 35S-methionine, synthesize and secrete these proteins. Cultured nonpigmented ciliary epithelial ODM-2 cells, in response to phorbol-12-myristate 13-acetate (PMA), but not to the non-protein kinase C binding phorbol ester 4 alpha-phorbol didecanoate (PDBu), elicited up-regulation (up to 5-fold) of transcription, synthesis and secretion of alpha1-antitrypsin. These results provide in vitro evidence that the ciliary epithelium synthesizes and secretes a selective group of proteinases and proteinase inhibitors detected also in aqueous humor. The expression of at least of one of the proteinase inhibitors, alpha1-antitrypsin, can be modulated in response to phorbol ester.

Aged↗

Adaptation of esophageal mucosa to acid- and pepsin-induced damage: role of nitric oxide and epidermal growth factor.

To study whether the esophageal mucosa was able to elicit mucosal adaptation, we induced esophageal damage by perfusing acidified pepsin in rabbits. Mucosal adaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline) for 60 min prior to acidified pepsin (strong irritant). Macroscopic and microscopic esophageal injury, cell proliferation, and mucosal barrier function (H+, K+, hemoglobin flux rates) were studied. Preexposure of the esophageal mucosa to acidified saline significantly decreased both the mucosal damage and the mucosal barrier dysfunction induced by acidified pepsin. The development of this phenomenon was nondependent on cell proliferation. Concomitant treatment with either the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine, or the perfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, an inhibitor of the tyrosine kinase activities ligated to the intracytoplasmatic domain of the EGF receptor, during the preexposure period completely reversed the protection induced by acid. We conclude that the rabbit esophageal mucosa shows mucosal adaptation to acid and pepsin. The development of this phenomenon is fast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxide and EGF-receptor-mediated mechanisms.

Adaptation, Physiological↗

Molecular characterization and differential gene induction of the neuroendocrine-specific genes neurotensin, neurotensin receptor, PC1, PC2, and 7B2 in the human ocular ciliary epithelium.

The ocular ciliary epithelium is a bilayer of neuroepithelial cells specialized in the secretion of aqueous humor fluid and the regulation of intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated neuroendocrine markers including neurotensin receptors (NTrs), the prohormone convertases furin, PC1, and PC2, and the neuroendocrine polypeptide 7B2 in the ciliary epithelium. Using a human cell line, ODM-2, derived from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocorticoid, and activators of adenylate cyclase; (2) NTr expression is up-regulated by selective ligand-activated beta2-adrenergic receptor; and (3) PC1 and PC2 expression are up-regulated via distinct signaling transduction pathways. PC1 gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression. A radioimmunoassay for NT detected an NT-like immunoreactivity in human ciliary epithelium and ODM-2 cell extracts, in aqueous humor, and in conditioned culture medium. The results support the view that the entire ciliary epithelium functions as a neuroendocrine tissue, synthesizing, processing, and releasing NT into the aqueous humor where it may exert important physiological functions through autocrine and/or paracrine mechanisms.

Aspartic Acid Endopeptidases↗

Superoxide anions produced by inflammatory cells play an important part in the pathogenesis of acid and pepsin induced oesophagitis in rabbits.

BACKGROUND: Reactive oxygen metabolites have been associated with gastrointestinal injury. OBJECTIVE: To investigate whether mucosal reactive oxygen metabolites are involved in acid and pepsin induced oesophagitis, and if so, which specific metabolites. METHODS: The effects of free radical scavengers and the anti-inflammatory drug ketotifen on rabbit oesophagitis induced by acidified pepsin were studied. Isolated oesophageal cells were obtained before and after oesophageal injury and the generation of superoxide anion and hydrogen peroxide was analysed by flow cytometry. The presence of inflammatory cells was determined by indirect immunofluorescence with a mouse antirabbit CD11b antibody. RESULTS: Of the free radical scavengers tested, superoxide dismutase, which reacts with the superoxide anion, significantly reduced oesophagitis, whereas catalase, which reacts with hydrogen peroxide, had only a mild effect and dimethylsulphoxide had no effect. Ketotifen significantly reduced the inflammation and also prevented the induction of oesophagitis. Isolated cells obtained from the oesophageal mucosa after acidified pepsin exposure generated increased amounts of superoxide anions, which were mainly produced by CD11b positive cells. CONCLUSIONS: Reactive oxygen metabolites, especially superoxide anion, produced by inflammatory cells play a significant part in the genesis of oesophagitis induced by acid and pepsin in rabbits and might be a target for future medical therapy.

Animals↗

Platelet-derived growth factor reverses the effects induced by NSAIDs on ulcer healing.

BACKGROUND: It is known that non-steroidal anti-inflammatory drug (NSAID) use delays the healing of peptic ulcers and that growth factors play an important role in the ulcer healing process. AIM: To evaluate the effect of platelet-derived growth factor (PDGF) in healing chronic gastric ulcers in rats treated with NSAIDs. METHODS: Chronic gastric ulcers were induced with acetic acid in male Wistar rats and then treated with either aspirin (100 mg/kg/day), indomethacin (2 mg/kg/day), PDGF-BB (0.1 nM/kg/day) or combinations. Gastric secretion and ulcer size, wound contraction, mucosal regeneration and cell proliferation were assessed in histological specimens. RESULTS: Both aspirin and indomethacin delayed the healing rate of gastric ulcers and reduced ulcer contraction, mucosal regeneration and cell proliferation. All these effects were completely reversed by oral treatment with PDGF-BB without affecting gastric acid secretion. CONCLUSION: Oral administration of PDGF accelerates ulcer healing and reverses the effects induced by NSAIDs on ulcer healing without affecting gastric secretion.

Animals↗

Identification of a neuropeptide and neuropeptide-processing enzymes in aqueous humor confers neuroendocrine features to the human ocular ciliary epithelium.

The ocular ciliary epithelium, the site of aqueous humor secretion in the mammalian eye, is believed to play a key function in signaling mechanisms that regulate the rate of secretion, and thus intraocular pressure. One possible way of mediating these signaling functions is through neuropeptides and hormones secreted into the aqueous humor and acting on target tissues. We recently identified a cDNA clone sharing 100% identity with carboxypeptidase E (CPE), a neuropeptide-processing enzyme. Utilizing polymerase chain reaction, we further identified and characterized another processing enzyme, the peptidylglycine alpha-amidating monooxygenase (PAM), and the neuropeptide secretogranin II, a molecular marker restricted to neuroendocrine tissues. Using specific probes, we found that the nonpigmented ciliary epithelial cells express CPE, PAM, and secretogranin II mRNA, and protein. We also found that CPE and secretogranin II are abundant in aqueous humor. Treatment of cultured ciliary epithelial cells with veratridine and phorbol ester up-regulates CPE and PAM. Secretogranin II was found to be induced by veratridine, whereas phorbol ester had little effect, suggesting different mechanisms for secretion. The results demonstrate that secretogranin II, CPE, and PAM represent a specialized group of neuropeptide and neuropeptide-processing enzymes secreted by the ciliary epithelial cells which may confer to them neuroendocrine functions in cell-cell communication or cell signaling.

Adult↗

Prolactin gene expression and secretion during pregnancy and lactation in the rat: role of dopamine and vasoactive intestinal peptide.

It is known that dopamine (DA) is the major PRL-inhibiting factor, and vasoactive intestinal peptide (VIP) is one of the most potent and physiological PRL-releasing factors. We have investigated the implication of DA and VIP in PRL gene expression and peptide secretion regulation during the physiological hyperprolactinemic states of pregnancy and lactation. Pregnant rats were studied on days 8, 15, and 20 of pregnancy. Lactating rats suckled by eight pups were studied on days 3 and 8 of postpartum, and nonsuckling postpartum rats were used as controls. Plasma estradiol, progesterone, and PRL were measured by RIA, as well as pituitary immunoreactive (IR-) PRL, pituitary IR-VIP, and hypothalamic IR-VIP. DA was studied by measuring changes in gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. TH, PRL, and VIP messenger RNA (mRNA) were assessed by Northern blot hybridization. The results showed very high plasma PRL levels in early pregnancy and during lactation, whereas plasma PRL concentrations were normalized at the end of gestation and in nonsuckling control rats. The physiological hyperprolactinemia of both early pregnancy and lactation correlated with higher pituitary PRL mRNA levels and lower pituitary IR-PRL content. Moreover, hypothalamic TH mRNA levels were lower in early pregnancy and lactation than at the end of gestation and in nonsuckling rats, respectively. The hypothalamic IR-VIP content was lower on day 8 of pregnancy than on days 15 and 20. However, VIP gene expression in the hypothalamus did not change throughout pregnancy. During lactation, neither hypothalamic IR-VIP content nor VIP mRNA was significantly altered. In the pituitary, IR-VIP content did not significantly change, and VIP mRNA levels were higher on day 15 of pregnancy than on the other days. During lactation, the pituitary IR-VIP content was very low on day 8 compared with those on day 3 of lactation and in nonsuckling control rats. VIP mRNA 1.0-kilobase transcript levels were higher in the lactating rats than in the control animals. These data show that both early pregnancy and lactation are physiological hyperprolactinemic states in which increased PRL mRNA accumulation coincides with decreased IR-PRL content in the pituitary and higher plasma IR-PRL, indicating regulation at the gene expression level and of PRL secretion. Low TH gene expression also occurs during hyperprolactinemia, suggesting that the diminution of DA activity that occurs during early pregnancy and lactation might be the major regulator of PRL alterations. If hypothalamic VIP plays a role as a neuroendocrine PRL-releasing factor during pregnancy and lactation, this may occur at the secretory level, as suggested by the alterations in IR-VIP, with no modifications in VIP mRNA accumulation, in the hypothalamus. Pituitary VIP does not seem to be a major regulator of PRL secretion during pregnancy, whereas during lactation, it regulates PRL secretion in a paracrine and/or autocrine manner.

Animals↗

Gene expression of the neurotrophic pigment epithelium-derived factor in the human ciliary epithelium. Synthesis and secretion into the aqueous humor.

PURPOSE: To study the expression of the neurotrophic pigment epithelium-derived factor (PEDF), a protein with neurotrophic and neuronal-survival activities, by the human ocular ciliary epithelium. METHODS: Total RNA extracted from human and bovine ocular tissues were screened by Northern blot analysis with cDNA probes for PEDF. Antibodies to PEDF were used to monitor its synthesis and secretion by metabolically labeling ciliary processes in vitro with 35S-methionine, followed by immunoprecipitation. Pigment epithelium-derived factor antibodies also were used to visualize the cellular distribution of PEDF along the human and bovine ciliary epithelium. Polymerase chain reaction (PCR) and reverse transcription (RT)-PCR was used to screen cDNA libraries of tissue and cell lines derived from the ciliary epithelium to demonstrate PEDF expression. RESULTS: From a subtractive library of the human ocular ciliary body, the authors identified a cDNA clone exhibiting nucleotide homology with the PEDF. Northern blot analysis indicated that PEDF transcripts are present in all the ocular tissues in the human eye; in the bovine eye, it is expressed preferentially in the retinal pigment epithelium. RT-PCR and PCR demonstrated that the PEDF gene is still transcriptionally active in cultured cell lines derived from the bilayer of the ciliary epithelium. Immunoprecipitation and Western blot (immunoblot) analyses with antisera to the PEDF protein demonstrated that a predominant PEDF form of 46 kDa is synthesized in the ciliary body and is secreted as a glycoprotein of 50 kDa. By indirect immunofluorescence and immunocytochemistry, PEDF antibodies decorated both cell types that comprise the ciliary epithelium (nonpigmented and pigmented) and, more distinctively, the plasma-membrane domain of nonpigmented cells in the pars plicata region. CONCLUSIONS: These results reveal a new site of synthesis (ciliary epithelium) and accumulation (aqueous humor) of PEDF, and they emphasize its potential importance as a trophic factor in the neuro-differentiated functions of the human ciliary epithelium.

Animals↗

Isolation and characterization of cell-specific cDNA clones from a subtractive library of the ocular ciliary body of a single normal human donor: transcription and synthesis of plasma proteins.

A subtractive cDNA library was developed for the purpose of identifying cell-specific genes expressed within the human ocular ciliary body, a tissue responsible for regulating aqueous humor secretion and intraocular pressure. Partial DNA sequence of a large number of cDNA clones and homology searches of nucleic acid and protein databases revealed significant homologies to at least 90 independently known genes. A group of biologically significant genes that were previously not known to have transcriptional expression in the ciliary body, complement component C4; alpha 2 macroglobulin; selenoprotein-P; and apolipoprotein D, were further demonstrated by Northern hybridization. Antibodies to these and other proteins (i.e., tyrosinase-related protein and pigment epithelium-derived factor) confirmed their cell-restricted expression in ciliary epithelial cells (pigmented, nonpigmented), or vascular endothelial cells. We provide evidence that two human plasma proteins, complement component C4 and alpha 2-macroglobulin are metabolically labeled with [35S]methionine in ciliary processes explants, suggesting that the ciliary body is an organ of synthesis and secretion of plasma proteins present in aqueous humor. These results challenge the notion that plasma proteins in aqueous humor are imported from outside of the eye. The subtractive cDNA library reported in this work should be very useful for identifying potential candidate genes in ocular abnormalities affecting the ciliary body, or involved in the regulation of intraocular pressure.

Adult↗

Aspirin renders the oesophageal mucosa more permeable to acid and pepsin.

OBJECTIVE: To examine the effects of aspirin on the oesophageal mucosa and on acid- and pepsin-induced oesophagitis. DESIGN AND METHODS: The effects both of intraluminal (18 mg/ml) and of parenteral (100 mg/kg per h) aspirin on an in-vivo rabbit model of oesophagitis induced by acidified pepsin (pH 2) were studied. Oesophageal injury was assessed by macroscopic and microscopic scoring including the cell proliferation immunohistochemical parameter mib1. The mucosal barrier function was determined by hydrogen, potassium and haemoglobin flux rates. RESULTS: Acidified saline alone caused no damage, but the addition of aspirin induced mucosal barrier damage (P < 0.05). The exposure of the oesophageal mucosa to acidified aspirin and then acidified pepsin significantly increased mucosal injury and mucosal barrier dysfunction compared with control experiments (exposure to acidified saline and acidified pepsin). This damage was significantly (P < 0.05) reduced (> 40%) by prostaglandin cotherapy (prostaglandin E2) administered before acidified aspirin exposure. Mucosal damage was less severe (P < 0.05) when the oesophageal mucosa was exposed to a pH 6 aspirin solution. Parenterally administered aspirin also increased the oesophageal damage induced by acidified pepsin compared with control experiments, but the damage was 23% lower than that obtained with intraluminal aspirin. Cell proliferation studies showed a significant increase in the number of positive cells in those experiments with a higher degree of damage and in those treated with prostaglandins. CONCLUSION: Aspirin renders the oesophageal mucosa more permeable to acid and pepsin. These effects are in part pH-dependent and might be partially reversed by prostaglandin E2 cotherapy.

Acids↗

Neoplastic colonic polyps in acromegaly.

A high prevalence of neoplastic colorectal polyps has been described in acromegalic patients. The aim of the present report was to confirm the high prevalence of neoplastic colorectal polyps in acromegaly and the existence of special risk factors for this type of polyps among acromegalic patients. A fiberoptic colonoscopy was performed in 27 active acromegalic patients, followed by both polypectomy and biopsy when indicated. Several prognostic variables were analysed a potential risk factors, in all cases. The prevalence of neoplastic colorectal polyps found in our series (22.2%) was similar to that in previous studies, and did not show any apparent increment compared to that in the populations in which it is known. None of the prognostic variables studied were related to the presence of neoplastic colorectal polyps.

Acromegaly↗

[Consistency of the histologic diagnosis of Lauren's classification of gastric cancer].

BACKGROUND: Lauren's classification of gastric cancer is usually followed in epidemiological studies thus requiring evaluation of its reproducibility. This classification defines 2 principal histological types: intestinal and diffuse with different proportions in high and low risk areas possibly being associated to different causal factors. METHODS: The concordance diagnosis in an aleatory sample of 81 gastric carcinomas stratified according to the participation of 14 hospitals in an epidemiological study of 354 cases and 354 controls was analyzed. The initial diagnosis carried out was compared by more than 20 pathologists with the reclassification diagnosis by consensus of 2 pathologists by the proportion of agreement or concordance observed in the kappa index. Keeping the final reclassification by consensus as a reference, sensitivity, specificity and predictive values were also calculated. RESULTS: The proportion of concordance observed was of 78% for the intestinal and 90% for the diffuse with a kappa index of 0.55 and 0.74, respectively. Sensitivity for the intestinal type was of 88% and for the diffuse 81% with specificity being of 67% in the intestinal and 93% in the diffuse. CONCLUSIONS: Subjectivity in the interpretation of certain parameters necessary for histological diagnosis may be reduced by the elaboration of protocols in which the principal histological criteria to follow are detailed. Nonetheless, the distinction made between the two principal types, intestinal and diffuse, is valid enough to be used in multicenter epidemiological studies and in comparative studies.

Case-Control Studies↗