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At least 667 records · Page 37Linked to original sources
PubMed2003

Effect of long-term irbesartan treatment on endothelium-dependent vasodilation in essential hypertensive patients.

Endothelial dysfunction plays a pivotal role in the development of essential hypertension and its complications. The purpose of this study is to assess the effect of antihypertensive treatment with the angiotensin receptor blocker irbesartan on endothelial function in a group of essential hypertensive patients. Thirty-two untreated hypertensives are examined at baseline and at the end of a six-month period of irbesartan treatment. Endothelium-dependent and -independent responses are determined by measuring changes in forearm blood flow (FBF) by strain gauge plethysmography in response to intrarterial infusions of acetylcholine (endothelium-dependent vasodilation [EDV]), sodium nitroprusside (endothelium-independent vasodilation [EIV]), with and without the addition of the nitric oxide (NO) synthase inhibitor L-NMMA. Plasma endothelin, plasma and urinary nitrates and nitrites, and cyclic GMP are measured at baseline and at the end of treatment. Irbesartan promoted a significant increase in EDV (from 433+/-147% to 488+/-75%; P=0.027) and EIV (from 442+/-130% to 495+/-104%; P=0.041). L-NMMA-induced vasoconstriction was significantly enhanced after irbesartan treatment (relative decrease of FBF from 33.4+/-9.5% to 39.5+/-5.6%; P=0.001). Plasma concentrations of endothelin fell significantly after irbesartan treatment (from 5.78+/-1.86 to 4.16+/-1.52 pg/mL; P=0.001). We concluded that long-term irbesartan treatment enhances both endothelium-dependent and -independent vascular vasodilation capacity. In addition to this non-specific effect, irbesartan restores the vasoconstriction capacity of NO synthase inhibitors, suggesting a direct effect on tonic NO release, and decreases endothelin production. These actions may play an important role in the vascular protecting effects of irbesartan.

Adult↗
PubMed1998

Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1.

We recently reported three truncating mutations of the cytochrome P4501B1 gene (CYP1B1) in five families with primary congenital glaucoma (PCG) linked to the GLC3A locus on chromosome 2p21. This could be the first direct evidence supporting the hypothesis that members of the cytochrome P450 superfamily may control the processes of growth and differentiation. We present a comprehensive sequence analysis of the translated regions of the CYP1B1 gene in 22 PCG families and 100 randomly selected normal individuals. Sixteen mutations and six polymorphisms were identified, illustrating an extensive allelic heterogeneity. The positions affected by these changes were evaluated by building a three-dimensional homology model of the conserved C-terminal half of CYP1B1. These mutations may interfere with heme incorporation, by affecting the hinge region and/or the conserved core structures (CCS) that determine the proper folding and heme-binding ability of P450 molecules. In contrast, all polymorphic sites were poorly conserved and located outside the CCS. Northern hybridization analysis showed strong expression of CYP1B1 in the anterior uveal tract, which is involved in secretion of the aqueous humor and in regulation of outflow facility, processes that could contribute to the elevated intraocular pressure characteristic of PCG.

Amino Acid Sequence↗
PubMed1989

Disturbances of transmembranous sodium transport systems induced by ethanol in human erythrocytes. An approach to the pressor effect of alcohol.

Several epidemiological and clinical studies have established a clear association between alcohol consumption and hypertension. The mechanism of the pressor effect of ethanol is not well understood. We studied the in vitro effects of increasing amounts of ethanol on different Na+ transport systems from human erythrocytes. Ethanol at concentrations higher than 32 mmol/L stimulated ouabain-sensitive Na+ efflux, the Na+ efflux depending on the Na+:Li+ countertransport and Na+ leak. At the same concentrations, ethanol inhibited bumetanide-sensitive Na+ efflux. We conclude that, with the exception of Na+-K+ pump, alcohol-induced alterations and those observed in erythrocytes from essential hypertensives may overlap. Therefore, alcohol consumption could potentiate those genetic abnormalities of Na+ transport and contribute to the pathogenesis of essential hypertension.

Antiporters↗
PubMed1995

Haemophilus paraphrophilus endocarditis: case report and review.

Endocarditis due to Haemophilus paraphrophilus is an uncommon disease. We report a case of H. paraphrophilus endocarditis with embolic complications in which the causative organism was resistant to beta-lactam antibiotics. Before April 1994, 16 cases of H. paraphrophilus endocarditis had been reported. Infection by this organism usually affects a previously damaged mitral valve. We emphasize the fastidiousness of the organism and the high incidence of embolic complications, which determine the outcome. To our knowledge we describe the first patient with endocarditis due to beta-lactam-resistant H. paraphrophilus.

Adult↗
PubMed1995

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↗
PubMed1992

Molecular cloning of the bovine CD9 antigen from ocular ciliary epithelial cells.

The ciliary epithelium is a bilayer of epithelial cells responsible for the formation and secretion of aqueous humor in the mammalian eye. We have isolated a cDNA clone from a lambda gt11 cDNA library of bovine ocular ciliary epithelial cells encoding the CD9 antigen, a member of a new family of transmembrane proteins. The bovine CD9 clone contains an open reading frame of 226 amino acids (M(r) 24,860). The deduced amino acid sequence from the bovine CD9 cDNA clone shows 83.5% identity with the human counterpart isolated from megakaryocytes, and a lower degree of identity with a group of related antigens (TAPA-1, C0-029, CD53, MRC OX-44, ME491, CD63, CD37, and Sm23) involved in growth regulation. Analysis of bovine ocular tissues reveals that the CD9 gene encodes a 1.4 kb mRNA which is detectable predominantly in cornea and at low levels in ciliary epithelium, retina, iris, and lens. Normal and transformed cell lines established from the ocular ciliary epithelium exhibited significant levels of CD9 transcripts. These results raise questions regarding possible roles of CD9 in the anterior segment of the eye.

Amino Acid Sequence↗
PubMed1993

Cloning of the bovine plasma selenium-dependent glutathione peroxidase (GP) cDNA from the ocular ciliary epithelium: expression of the plasma and cellular forms within the mammalian eye.

In the anterior segment of the mammalian eye, the ocular ciliary epithelium produces the aqueous humor, a fluid that nourishes and protects the avascular tissues from oxidative stress. This report details the results of a study of molecular cloning, sequencing, and expression of plasma glutathione peroxidase (GPx-P) from the bovine ocular ciliary epithelium. The bovine GPx-P cDNA contains an open reading frame of 226 amino acids with a calculated molecular weight of 24,860. The corresponding amino acid sequence showed an overall identity of 88% with the human GPx-P, 88.5% with the rat GPx-P, and 46.4% with the cellular bovine glutathione peroxidase (GPx-1). The levels of GPx-P and GPx-1 transcripts in ocular tissues were analyzed and the ciliary epithelium was found to express the highest levels of GPx-P transcripts in human and bovine eyes, whereas the cornea of calf eyes expressed the highest levels of GPx-1 transcripts. Surprisingly, the lens, on which oxidants have profound effects leading to cataract formation, expressed the lowest levels of GPx-P and GPx-1 transcripts in human donor eyes. These results provide new evidence of differential gene expression of the GPx-P and GPx-1 forms in the mammalian eye and stresses the functional role of the ocular ciliary epithelium in protecting the anterior segment of the eye from oxidative damage.

Amino Acid Sequence↗
PubMed2003

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension.

BACKGROUND: Intraocular pressure (IOP) is maintained by a balance between aqueous humour (AH) production (dependent on sodium transport across a ciliary epithelial bi-layer) and drainage (predominantly through the trabecular meshwork). In peripheral epithelial tissues, sodium and water transport is regulated by corticosteroids and the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes (11beta-HSD1 activating cortisol from cortisone, 11beta-HSD2 inactivating cortisol to cortisone). AIM: To analyse expression of 11beta-HSD in the human eye and investigate its putative role in AH formation. DESIGN: Multipart prospective study, including a randomized controlled clinical trial. METHODS: The expression of 11beta-HSD1 in normal human anterior segments was evaluated by in situ hybridization (ISH). RT-PCR for 11beta-HSDs, glucocorticoid and mineralocorticoid receptors (GR, MR) was performed on human ciliary body tissue. AH cortisol and cortisone concentrations were measured by radioimmunoassay on specimens taken from patients with primary open-angle glaucoma (POAG) and age-matched controls. Randomized, placebo-controlled studies of healthy volunteers and patients with ocular hypertension (OHT, raised IOP but no optic neuropathy) assessed the effect of oral carbenoxolone (CBX, an inhibitor of 11beta-HSD) on IOP. RESULTS: ISH defined expression of 11beta-HSD1 in the ciliary epithelium, while RT-PCR analysis of ciliary body tissue confirmed expression of 11beta-HSD1, with additional GR and MR, but not 11beta-HSD2 expression. In both POAG patients and controls, AH concentrations of cortisol exceeded those of cortisone. The CBX-treated healthy volunteers who demonstrated the largest change in urinary cortisol metabolites, indicative of 11beta-HSD1 inhibition, had the greatest fall in IOP. Patients with OHT showed an overall reduction of IOP by 10% following CBX administration, compared to baseline (p<0.0001). DISCUSSION: CBX lowers IOP in patients with ocular hypertension. Our data suggest that this is mediated through inhibition of 11beta-HSD1 in the ciliary epithelium. Selective and topical inhibitors of 11beta-HSD1 could provide a novel treatment for patients with glaucoma.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1992

Development of Hodgkin's disease in the course of primary Sjögren's syndrome.

We report two patients with a definite diagnosis of primary Sjögren's syndrome who developed Hodgkin's disease. Clinical and laboratory features of this transformation comprised prolonged fever, the appearance of lymphadenopathy together with loss of serum autoantibodies and a reduction in serum gammaglobulin levels. We know of only one well documented case of such an association. From these observations, it seems reasonable to include Hodgkin's disease in the clinical spectrum of the lymphoproliferative disorders that may occur in the course of primary Sjögren's syndrome.

Adult↗
PubMed1987

Clear cell syringoid eccrine carcinoma.

A case of syringoid eccrine carcinoma (SEC) is reported. The tumor was mainly formed by clear cells laden with glycogen. This feature, rarely found in syringoma, had not previously been reported in SEC. The authors assume that SEC is an infiltrating and locally destructive but not metastasizing neoplasm. They propose that SEC is a clinicopathologic entity with a histopathologic spectrum from the more differentiated syringomatoid ones to so-called primary cutaneous adenoid cystic carcinoma. A possible nexus between the more syringomatoid cases and the sclerosing sweat duct (syringomatous) carcinoma is also discussed.

Adenocarcinoma↗
PubMed1990

Follicular lymphomatoid papulosis.

A case of follicular lymphomatoid papulosis was studied by light- and electron-microscopic methods. The nature of atypical cells was analyzed with monoclonal antibodies. This case proved to be mainly a type B lymphomatoid papulosis with a predominance of T-helper markers in atypical lymphoid cells. All previously reported cases of this rare variant corresponded to type A lymphomatoid papulosis. Therefore we believe this to be the first case report of type B follicular lymphomatoid papulosis.

Adult↗
PubMed2002

Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity.

Drug-induced renal failure is a relatively common event in patients infected with HIV. This group of patients receives a number of potentially nephrotoxic medications for a variety of illnesses. The acyclic nucleoside phosphonates cidofovir and adefovir are antivirals that possess significant nephrotoxicity. Interestingly, tenofovir disoproxil fumurate (DF) is structurally similar to these 2 agents, yet seems to be less nephrotoxic based on a few published studies in HIV patients with intact renal function. We present a case in which acute renal failure developed after therapy with tenofovir DF in a patient with HIV and stable chronic kidney disease.

Acute Kidney Injury↗
PubMed2005

The role of aldosterone blockers in the management of chronic heart failure.

The neurohormonal model of congestive heart failure (CHF) has replaced the previously accepted hemodynamic model. A shift in this paradigm has allowed alterations in therapy of CHF such that agents that target the neurohormonal axis and specifically the renin-angiotensin-aldosterone system, with drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, are utilized. Employment of these drugs markedly improves survival in patients with CHF. Recent animal and human data demonstrate that aldosterone is directly pathogenic in this disease process and is insufficiently suppressed by these agents. Furthermore, when aldosterone is directly antagonized, vascular and myocardial damage is greatly ameliorated in both experimental animals and humans. Significant mortality benefits of aldosterone antagonists in patients with CHF from systolic dysfunction have been subsequently witnessed. Herein, the pathophysiology of CHF, the beneficial role of aldosterone antagonists in this disease process, and potential adverse consequences of these agents are reviewed.

Aldosterone↗
PubMed1992

Expression of neuronal markers in the so-called ENU-induced schwannomas.

The present data show that the so-called ENU-induced malignant schwannomas express neuronal markers. This finding supports the hypothesis that a population of tumor cells in these neoplasms are neuroblastic in nature, and suggests the classification of ENU-induced schwannomas as primitive neuroectodermal tumors.

Animals↗