Control Tissue (control + tissue)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues

ARTHRITIS & RHEUMATISM, Issue 7 2010
Mohammed F. Shamji
Objective Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. Methods Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. Results Immunoreactivity for IL-4, IL-6, IL-12, and interferon-, (IFN,) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. Conclusion Greater IFN, positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration. [source]


Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP-13

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2008
Susanne Wagner
Abstract The objective of this article was to assess whether matrix metalloproteinase-13 (MMP-13) is produced by cells of the peri-implant interface tissues and to further characterize these cells. Tissue specimens were collected from the bone,prosthesis interface at the time of revision surgery of clinically loosened hip and knee arthroplasties (n,=,27). Synovial tissues from osteoarthritic patients and young patients with mild joint deformity were used as controls (n,=,6). Tissue samples were fixed in 4% PFA, decalcified with EDTA, and embedded in paraffin. Sections (4 µm) were stained with hematoxylin/eosin and for the osteoclastic marker enzyme tartrate resistant acid phosphatase. Monocytes/macrophages were characterized with a monoclonal antibody against CD68 and mRNAs encoding MMP-13 and ,1 collagen I (COL1A1) were detected by in situ hybridization. Cells expressing transcripts encoding MMP-13 were found in 70% of the interface tissues. These cells colocalized with a cell population expressing COL1A1 mRNA, and were fibroblastic in appearance. MMP-13 expressing cells were found in the close vicinity of osteoclasts and multinuclear giant cells. No signals for transcripts encoding MMP-13 were detected in multinuclear giant cells or in osteoclasts. Control tissues were negative for transcripts encoding MMP-13 mRNA. Fibroblasts of the interface from aseptically loosened endoprostheses selectively express MMP-13. By the expression and the release of MMP-13, these fibroblastic cells may contribute to the local degradation of the extracellular matrix and to bone resorption. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:143,152, 2008 [source]


Olfactory epithelium influences the orientation of mitral cell dendrites during development

DEVELOPMENTAL DYNAMICS, Issue 2 2005
Laura López-Mascaraque
Abstract We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Developmental Dynamics 232:325,335, 2005. © 2004 Wiley-Liss, Inc. [source]


Heat Shock Protein-27 Is Upregulated in the Temporal Cortex of Patients with Epilepsy

EPILEPSIA, Issue 12 2004
Hans-J Bidmon
Summary:,Purpose: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. Methods: Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry. Results: HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens. Conclusions: These results demonstrate that HSP-27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP-27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP-27 is a marker for cortical regions in which a stress response has been caused by seizures. [source]


Increased Expression of the Neuronal Glutamate Transporter (EAAT3/EAAC1) in Hippocampal and Neocortical Epilepsy

EPILEPSIA, Issue 3 2002
Peter B. Crino
Summary: ,Purpose: To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy. Methods: The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis. Results: The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with nondysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue. Conclusions: Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types. [source]


Multilineage progression of genetically unstable tumor subclones in cutaneous T-cell lymphoma

EXPERIMENTAL DERMATOLOGY, Issue 8 2004
Albert Rübben
Abstract:, Molecular analysis of solid malignant tumors has suggested multilineage progression of genetically unstable subclones during early stages of tumorigenesis as a common mechanism of tumor cell evolution. We have investigated whether multilineage progression is a feature of cutaneous T-cell lymphoma (CTCL). To identify individual tumor cell subclones, we determined the pattern of mutations within microsatellite DNA obtained from multiple histomorphologically confined tumor cell nests of mycosis fungoides (MF) and lymphomatoid papulosis (LyP) lesions. Tumor cells were isolated by laser microdissection, and allelotypes were determined at microsatellite markers D6S260, D9S162, D9S171, D10S215, TP53.PCR15, and D18S65. Nine cases of MF and one patient with anaplastic large cell lymphoma (ALCL) originating from LyP were analyzed at 277 different microdissected areas obtained from 31 individual lesions. Three specimens of cutaneous lichen planus microdissected at 26 areas served as the control tissue. Microsatellite instability in microdissected tissue [MSI(md-tissue)] was detected in tumor tissues of all CTCL patients. One hundred and fifty-seven of 469 analyzed polymerase chain reaction (PCR) amplifications contained mutated microsatellite alleles (34%). In lichen planus, MSI(md-tissue) was seen in only four of 76 PCR products (5%) (P < 0.0001). The distribution of allelotypes in tumor cells from different disease stages was consistent with multilineage progression in five MF cases, as well as in the LyP/ALCL patient. Our results suggest that CTCL may evolve by multilineage progression and that tumor subclones in MF can be detected in early disease stages by mutation analysis of microsatellite DNA obtained from multiple microdissected areas. [source]


Proteomic identification of an upregulated isoform of annexin A3 in the rat brain following reversible cerebral ischemia

GLIA, Issue 16 2007
Heike Junker
Abstract We used proteomics to identify regulated proteins following cerebral ischemia in a rat model. Young rats were subjected to reversible middle cerebral artery (MCA) occlusion and proteins were extracted from the peri-infarcted and the corresponding contralateral area at days 3 and 14 postischemia. Proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry. We report for the first time that an isoform of annexin A3 (ANXA3) was among the upregulated proteins in the postischemic rat brain. The results were confirmed by real-time PCR and by western blotting. Double- and triple-immunostaining with neuronal and microglia/macrophagic markers demonstrated that ANXA3 is produced by resting microglia in control tissue and by activated microglial/macrophage cells in the infarcted area. 3D-images of the infarcted area suggest that ANXA3 is associated with a phagocytic phenotype. Our study identifies ANXA3 as a novel marker of brain microglia, which should be of substantial value in future studies of microglial cells and its role in the postischemic brain. © 2007 Wiley-Liss, Inc. [source]


Anti-inflammatory role of interleukin-15 in Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 3 2005
Manuel A Silva MD
Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source]


Ribosomal DNA sequence analysis of mucosa-associated bacteria in Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 6 2004
Tom Prindiville MD
Abstract Background: Enteric bacteria are implicated in the pathogenesis of Crohn's disease (CD); however, no specific causative organisms have been identified. Aims: This study was undertaken to correlate disease activity with changes in intestinal biota in patients with CD. Subjects: Ribosomal DNA analysis was used to explore the composition of the intestinal biota in patients with (1) CD undergoing colonoscopy, (2) CD undergoing surgical resection, and (3) no inflammatory bowel disease. Methods: Primers targeting bacterial 16S ribosomal DNA (rDNA) were used to amplify bacterial DNA associated with active CD lesions, comparable normal tissue from patients with CD, and normal control tissue. Each amplicon was cloned. Seven hundred thirty-nine rDNA clones were sequenced from 16 biopsies from CD patients, 15 surgical samples, and 10 biopsies from normal control patients. Results: Known extracellular or intracellular pathogens were not found. No rDNA sequence, phylogenetic group, or subgroup was consistently associated with CD lesions compared with normal tissues from the same patients. Colonic biopsies from CD-afflicted patients compared with biopsies from normal control subjects had an increase in facultative bacteria; in small bowel, CD patients had an increase in the Ruminococcus gnavus subgroup with a decrease in the Clostridium leptum and Prevotella nigrescens subgroups. However, differences in small bowel may have reflected individual variation rather than disease association. Surgical samples showed differences when compared with biopsy-derived samples. Conclusions: These findings suggest that CD is not caused by invasive pathogens associated specifically with the sites of lesions but that dysbiosis exists in this condition. [source]


Dysfunction of the ubiquitin,proteasome system in Parkinson's disease

JOURNAL OF NEUROCHEMISTRY, Issue 2003
P. Jenner
The cause of nigral cell degeneration and Lewy body formation in Parkinson's disease (PD) remains unknown but may involve impaired proteolysis. Evidence from both sporadic and familial forms of PD suggest the involvement of alterations in the ubiquitin,proteasomal system. In postmortem tissues from PD cases, there is a loss of 26S proteasomal enzyme activity coupled to a decrease in the expression of ,-subunits in substantia nigra while ,-subunit expression remains unchanged. The expression of PA700 is up-regulated in a number of brain regions in PD but not in substantia nigra. Interestingly, there was little or no expression of PA28 in the nigra in both aged control tissue or in PD. These data suggest that alterations in protein handling may be key to the formation of Lewy bodies in PD. Indeed, in vitro and in vivo inhibition of proteasomal activity causes the death of dopaminergic neurones. Recent evidence suggests that the formation of Lewy bodies may be linked to impaired proteasomal function in centrosomes leading to aggresome formation. [source]


Epithelial,mesenchymal interactions in experimental oral mucosal carcinogenesis

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2001
Alison M. Rich
Abstract: In an effort to come to a better understanding of human oral mucosal carcinogenesis, an animal model was used in which the carcinogen 4-nitroquinoline-1-oxide was applied to rat palatal mucosa for varying periods of time. Histological and histometric analyses showed that there were quantifiable differences in the palatal epithelium to which carcinogen had been applied in comparison with control tissue. Tissue recombination experiments, using various combinations of the palatal mucosa and analysed after recovery from transplantation to hypothymic BALB/c mice, showed that control epithelium recombined with connective tissue from carcinogen-treated mucosa was altered, indicating that the underlying connective tissue modified histomorphological aspects of the epithelium in the later stages of carcinogenesis. [source]


Genome-wide expression analysis of intra- and extraarticular connective tissue

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2009
Richard V. Pearse II
Abstract In comparison to extraarticular ligaments and tendons, the intraarticular ligaments such as the anterior and posterior cruciates exhibit different biochemical, biomechanical, and viscoelastic properties and most importantly, differential abilities to heal after surgical repair. Little is known about the underlying basis for these differences, in large measure due to the paucity of molecular markers distinguishing different classes of tendons and ligaments. To date, there has been no systematic analysis of gene expression differences between different types of connective tissues. We used Affymetrix expression arrays to analyze the differences in gene expression levels between the anterior cruciate, posterior cruciate, and medial collateral ligaments, the patellar and Achilles tendons and the synovium. We have identified five clusters of gene cohorts displaying similar expression patterns. These clusters group into three categories including: (1) genes that are strongly expressed in all connective tissues compared to the synovium control tissue; (2) genes that distinguish intraarticular connective tissues from extraarticular connective tissues; and (3) a group of genes expressed in common by the patellar tendon and the synovium. Our analysis identifies a new marker of tendons and ligaments (fibin2), demonstrates molecular diversity between subtypes of tendons and ligaments, and indicates that the primary molecular subdivision among dense regular connective tissues is intra- versus extraarticular rather than ligament versus tendon. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 427,434, 2009 [source]


cDNA-arrays and real-time quantitative PCR techniques in the investigation of chronic achilles tendinosis

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2003
Håkan Alfredson
The aetiology and pathogenesis of chronic painful Achilles tendinosis are unknown. This investigation aimed to use cDNA arrays and real-time quantitative polymerase chain reaction (real-time PCR) technique to study tendinosis and control tissue samples. Five patients (females mean age 57.1 ± 4.3 (years ±SD)) with chronic painful Achilles tendinosis were included. From all patients, one biopsy was taken from the area with tendinosis and one from a clinically normal area (control) of the tendon. The tissue samples were immediately immersed in RNAlater and frozen at ,80°C until RNA extraction. Portions of pooled RNA from control and tendinosis sites, respectively, were transcribed to cDNA, radioactively labelled (32P), hybridized to cDNA expression arrays, and exposed to phosphoimager screens over night. Expressions of specific genes, shown to be regulated in the cDNA array analysis, were analyzed in the individual samples using real-time PCR. cDNA arrays showed that gene expressions for matrix-metalloproteinase-2 (MMP-2), fibronectin subunit B (FNRB), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase p38 (MAPKp38) were up-regulated, while matrix-metalloproteinase-3 (MMP-3) and decorin were down-regulated, in tendinosis tissue compared with control tissue. Using real-time PCR, , and , patients showed up-regulation of MMP-2 and FNRB mRNA, respectively. For decorin, VEGF, and MAPKp38, real-time PCR revealed a great variability among patients. Interestingly, the mRNAs for several cytokines and cytokine receptors were not regulated, indicating the absence of an inflammatory process in chronic painful Achilles tendinosis. In conclusion, cDNA-arrays and real-time PCR can be used to study differences in gene expression levels between tendinosis and control tendon tissue. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


Ultrastructural and Immunocytochemical Studies on Effects of Barley Yellow Dwarf Virus , Infection on Fusarium Head Blight, Caused by Fusarium graminearum, in Wheat Plants

JOURNAL OF PHYTOPATHOLOGY, Issue 1 2006
Y. Liu
Abstract The interactions between barley yellow dwarf virus (BYDV) and Fusarium head blight (FHB), caused by Fusarium graminearum, were studied in the two winter wheat cultivars (cvs.), Agent (susceptible to FHB) and Petrus (moderately resistant to FHB), using ultrastructural and immunocytochemical methods. Infections of wheat plants of both cvs. by BYDV increased susceptibility to FHB. BYDV infection caused numerous cytological changes in lemma tissue of both cvs. such as formation of vesicles in the cytoplasm, degradation of fine structures of chloroplasts of both cvs. and accumulation of large starch grains in the chloroplasts. Electron microscopical studies showed that the development of F. graminearum on spike surfaces was not affected in BYDV-infected plants. After penetration and intercellular growth in lemma tissue, defence responses to Fusarium infections were markedly reduced in BYDV-diseased plants compared to the tissue of virus-free plants. At sites of contact of fungal cells with host tissue, depositions of cell wall material were distinctly less pronounced than in tissues of virus-free plants of cv. Petrus. Detection of , -1,3-glucanases and chitinases in lemma tissue of cv. Agent revealed no appreciably increased accumulation of both defence enzymes in F. graminearum -infected virus-free and BYDV-infected tissues compared to the non-infected control tissue. On the other hand, in cv. Petrus, infection with F. graminearum induced a markedly enhanced activity of both enzymes 3 days after inoculation. The increase of both enzyme activities was less pronounced in BYDV-infected plants than in tissue exclusively infected with F. graminearum. Cytological studies suggest that in contrast to the susceptible cv. Agent postinfectional defence responses may play still an important role in the resistance of the moderately resistant cv. Petrus to FHB. [source]


Influence of interleukin-1, and hyaluronan on proteoglycan release from equine navicular hyaline cartilage and fibrocartilage

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000
Frean
Proteoglycan (PG) release, in response to recombinant human interleukin-1, (rh-IL-1,), was measured in cartilage explants obtained from the equine distal sesamoid bone (navicular bone). Fibrocartilage from the surface of the navicular bone apposing the deep digital flexor tendon and hyaline cartilage from the surface of the navicular bone articulating with the middle phalanx were labelled with 35SO4. Hyaline cartilage from the distal metacarpus was used as a control tissue. Following radiolabel incorporation, the three cartilage types were treated with rh-IL-1, (100 U/mL) in the presence of hyaluronan (0.2, 2, 20, 200 and 2000 ,g/mL). rh-IL-1,-Induced PG release was measured by scintillation assay of PG-bound radiolabel. Increases in PG release of 94% (P < 0.01), 101% (P < 0.05) and 122% (P < 0.05), in response to rh-IL-1,, were noted in fibrocartilage, navicular hyaline cartilage and metacarpal hyaline cartilage, respectively. Hyaluronan (0.2 ,g/mL) significantly reduced rh-IL-1,-induced PG release in metacarpal hyaline cartilage (P < 0.01). In fibrocartilage and navicular hyaline cartilage, hyaluronan did not reduce PG release and at some concentrations appeared to increase PG release, although this was not statistically significant. These experiments show that (i) fibrocartilage and hyaline cartilage of the navicular bone release PGs in response to rh-IL-1,, and (ii) hyaluronan does not prevent rh-IL-1,-induced breakdown of navicular bone cartilage. [source]


Identification of potato genes induced during colonization by Phytophthora infestans

MOLECULAR PLANT PATHOLOGY, Issue 3 2001
Katinka Beyer
Summary Suppression Subtractive Hybridization (SSH) was applied in a search for genes induced during the compatible interaction between Phytophthora infestans and potato. Using potato leaves that had been treated with benzo(1,2,3)thiadiazole-7-carbothioic acid S-methylester (BTH) as the control tissue, a low redundancy library with a relatively low frequency of the classic plant Pathogenesis-Related (PR) genes was generated. 288 of the clones were screened for induced sequences using Inverse Northern analysis (hybridizing the arrayed clones with radiolabelled cDNA populations). Of the 75 clones that were detectable by this method, 43 appeared to be induced. Eleven of these clones were then analysed by total RNA blot analysis, and elevation of transcript levels during P. infestans infection was confirmed for 10 of them. Some of the cDNAs analysed by RNA blot analysis have homology to genes already known to be induced during infection, e.g. to ,-1,3-glucanase. Another group of cDNAs have homology to enzymes involved in detoxification: gamma-glutamylcysteine synthetase, cytochrome P450, glutathione S-transferase and an MRP-type ABC transporter. Other infection induced cDNAs encode putative proteins that have not previously been reported to be induced by infection: e.g. the ER-located chaperone BiP, and a homologue of Aspergillus nidulans SudD, which was isolated as a suppressor of a mutation in chromosome disjunction. The differential library therefore presents the opportunity to analyse the metabolic changes occurring during infection, and the disease process itself in more detail. [source]


Comparison of global gene expression between porcine testis tissue xenografts and porcine testis in situ

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 6 2007
Wenxian Zeng
Abstract Testis tissue from immature mammalian donor animals, grafted ectopically to immunodeficient mouse hosts, can undergo complete spermatogenesis with the production of fertilization-competent spermatozoa. To further characterize testis tissue xenografts as a model for testis function in situ, the objective of this study was to compare gene expression between porcine testis tissue xenografts and testis tissue in situ. Pieces of testis tissue from 1-week-old piglets were grafted onto immunodeficient male mice and a littermate piglet was raised for comparison as control. Complete spermatogenesis was present in the testis tissue xenografts at 8 months after transplantation into mouse hosts and in the 8-month-old control porcine testis tissue. Total RNA was isolated from xenografts and control tissue, and the RNA was labeled and hybridized to the porcine genome array. By analyzing the expression of 23,256 transcripts, we found that 71 genes were differentially expressed with at least a fourfold difference between xenografts and control tissue. Interestingly, none of the 56 transcripts present on the array that were annotated in porcine testis showed differential expression between xenografts and control testis. This analysis indicates that global gene expression in porcine testis xenografts appears comparable to testis tissue in situ. These findings support the hypothesis that testis tissue xenografts can provide a representative model to study mammalian spermatogenesis. Mol. Reprod. Dev. 74: 674,679, 2007. © 2006 Wiley-Liss, Inc. [source]


Mutational and expression analysis of CDK1, cyclinA2 and cyclinB1 in epilepsy-associated glioneuronal lesions

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2007
V. Schick
Gangliogliomas and focal cortical dysplasias (FCDs) constitute glioneuronal lesions, which are frequently encountered in biopsy specimens of patients with pharmacoresistant focal epilepsy and relate to impaired differentiation and migration of neural precursors. However, their molecular pathogenesis and relationship are still largely enigmatic. Recent data suggest several components of the insulin-pathway, including TSC1 and TSC2 mutated in tuberous sclerosis complex (TSC), to be altered in gangliogliomas and FCD with Taylor type balloon cells (FCDIIb). The proteins tuberin (TSC2) and hamartin (TSC1) constitute a tumour suppressor mechanism involved in cell-cycle control. Hamartin and/or tuberin were reported to colocalize and/or interact with CDK1, cyclinB1 and cyclinA2 that are critically involved in cell-size and cell-growth control. Here, we have carried out mutational and expression analyses of CDK1, cyclinB1 and cyclinA2 in gangliogliomas and FCDIIb. Mutational screening was performed by single-strand conformation polymorphism analysis in gangliogliomas (n = 20), FCDIIb (n = 35) and controls. CyclinB1 revealed a polymorphism (G to A, cDNA Position 966, GenBank: NM_031966) in exon 7 with similar frequencies in FCDIIb, gangliogliomas and control specimens (FCD n = 9/35; gangliogliomas n = 5/20; control n = 20/100). We used real-time reverse transcription polymerase chain reaction to determine expression levels of CDK1, cyclinB1 and cyclinA2 in 10 FCDIIb and nine gangliogliomas compared with unaffected adjacent control tissue of the same patients. We observed significantly lower expression of CDK1 and cyclinA2 in FCDIIb vs. controls whereas no significant expression differences were present for CDK1, cyclinB1 and cyclinA2 in gangliogliomas. Our data strongly argue against mutational events of CDK1, cyclinB1 and cyclinA2 to play a role in gangliogliomas or FCDIIb. However, a potential functional significance of lower expression for the cell-size and cell-cycle regulators CDK1 and cyclinA2 in FCDIIb composed of large dysplastic neurones and balloon cells needs to be further resolved. [source]


Expression of CD34 as a novel marker for glioneuronal lesions associated with chronic intractable epilepsy

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2006
P. Deb
The spectrum of glioneuronal lesions underlying intractable epilepsies includes malformative pathologies like focal cortical dysplasia (FCD); and neoplastic lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours (DNT). These may occur either singly or as dual lesions, having simultaneous presence of both elements. Currently, the relationship between the malformative and neoplastic glioneuronal lesions is poorly understood. Recently, CD34, a stem cell marker transiently expressed during early neurulation, has been identified in these tumours. This study was undertaken to (i) evaluate the role of CD34 as a diagnostic marker for glioneuronal lesions of epilepsy, namely, GG, DNT and FCD, and (ii) attempt to define the relationship among these lesions, using CD34 as a marker. Tissues resected from 47 patients with intractable epilepsy due to glioneuronal lesions (GG, FCD, DNT) were studied. These were evaluated for CD34 expression, using immunohistochemistry. Dysplastic or atypically differentiated neural precursors which could not be identified on routine haematoxylin and eosin (H&E) staining were highlighted by CD34 immunostaining. The pattern of immunostaining was diffuse in GGs, unlike FCDs, wherein cells were present singly or in small clusters. However, cases of DNT and control tissue were largely CD34-immunonegative. Based on these findings, we propose a possible common origin of GG and FCD, from a bipotent precursor that undergoes abnormal glioneuronal development, while DNTs possibly have a different origin. The CD34-immunoreactive cells represent dysplastic or undifferentiated neural precursors, which may signify a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathologies in patients with intractable epilepsy. [source]


Investigating the Effects of High-Dose Phenylephrine in the Management of Prolonged Ischaemic Priapism

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008
Asif Muneer BSc(Hons), FRCS(Urol)
ABSTRACT Introduction., Acute priapism can be managed by corporal blood aspirations and the instillation of , adrenergic agonists such as phenylephrine if patients present early. Following prolonged ischaemic priapism, this regimen is often unsuccessful, and the use of phenylephrine is limited due to systemic cardiovascular side effects. Aim., To investigate the effects of high-dose phenylephrine on human corpus cavernosal smooth muscle obtained from patients presenting with refractory ischaemic priapism. Methods., Strips of corpus cavernosum were obtained from six patients presenting with prolonged ischaemic priapism (duration 60,240 hours), where detumescence was refractory to conventional doses of phenylephrine. The smooth muscle contractile response to high doses of phenylephrine were then compared with that of normal control corpus cavernosum obtained from four patients undergoing a penectomy for penile cancer. The tissue was then analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) to assess its viability. Main Outcome Measures., The in vitro response to high-dose phenylephrine of corpus cavernosum smooth muscle obtained from patients with refractory priapism compared with normal human corpus cavernosum. Results., Corporal blood gas analysis confirmed hypoxia (pO2 1.5,2.3 kPa), acidosis (pH 6.9,7.1), and glucopenia (0,0.3 mmol/L) in all six patients confirming the ischaemic nature of the priapism. Application of high doses of phenylephrine produced a marked muscle contraction in the control tissue, but there was no contractile response at all in any of the priapism patients. Analysis with TUNEL indicated widespread smooth muscle cell apoptosis in all the priapism tissue. Conclusions., This study has shown that patients with ischaemic priapism that fails to respond to conventional doses of an ,-agonist are unlikely to benefit from continual or high-dose phenylephrine administration, as there is usually widespread apoptosis of the cavernosal smooth muscle preventing further contraction. Muneer A, Minhas S, Freeman A, Kumar P, and Ralph DJ. Investigating the effects of high-dose phenylephrine in the management of prolonged ischaemic priapism. J Sex Med 2008;5:2152,2159. [source]


Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues

ARTHRITIS & RHEUMATISM, Issue 7 2010
Mohammed F. Shamji
Objective Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. Methods Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. Results Immunoreactivity for IL-4, IL-6, IL-12, and interferon-, (IFN,) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. Conclusion Greater IFN, positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration. [source]


Identification of novel genes expressed during mouse tooth development by microarray gene expression analysis

DEVELOPMENTAL DYNAMICS, Issue 8 2007
Trevor J. Pemberton
Abstract To identify genes heretofore undiscovered as critical players in the biogenesis of teeth, we have used microarray gene expression analysis of the developing mouse molar tooth (DMT) between postnatal day (P) 1 and P10 to identify genes differentially expressed when compared with 16 control tissues. Of the top 100 genes exhibiting increased expression in the DMT, 29 were found to have been previously associated with tooth development. Differential expression of the remaining 71 genes not previously associated with tooth development was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. Further analysis of seven of the latter genes by mRNA in situ hybridization found that five were specific to the developing tooth in the craniofacial region (Rspo4, Papln, Amtn, Gja1, Maf). Of the remaining two, one was found to be more widely expressed (Sp7) and the other was found to be specific to the nasal serous gland, which is close to, but distinct from, the developing tooth (Vrm). Developmental Dynamics 236:2245,2257, 2007. © 2007 Wiley-Liss, Inc. [source]


Expression of inhibitors of apoptosis family protein in 7,12-dimethylbenz[a]anthracene-induced hamster buccal-pouch squamous-cell carcinogenesis is associated with mutant p53 accumulation and epigenetic changes

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2008
Shui-Sang Hsue
Summary Fifty outbred Syrian golden hamsters were equally divided into three experimental groups and two control groups. The pouches of the experimental groups were painted bilaterally with a 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) solution thrice a week for 3, 7 and 14 weeks. One of the control groups was applied with mineral oil while another control group remained untreated throughout the experiment. Neither survivin nor cIAP2 could be detected in any of the control tissues, whereas survivin and cIAP2 were found to be significantly increased in 3-, 7- and 14-week DMBA-treated pouches compared with the control pouches. Expression of XIAP, cIAP1 and NAIP were noted for both the control and 3-, 7- and 14-week DMBA-treated pouches, but levels were found to be significantly elevated in the experimental groups compared with the control pouches. p53 was not detected in any control tissues, but was significantly increased in 3-, 7- and 14-week DMBA-treated pouches. Direct sequencing revealed a point mutation (C,G) of p53 for pouch tissues treated with DMBA for 3 and 7 weeks, and there was a wide variation in the p53 sequence of the 14-week DMBA-treated pouch tissues, as compared with the control tissues. The control tissues had a survivin - and cIAP2 -methylated allele, whereas the DMBA-treated tissues showed no evidence of survivin - and cIAP2 -methylation. Neither the control nor DMBA-treated pouches showed evidence of XIAP -, cIAP1 - or NAIP -methylation. Our results suggest that the expression of inhibitors of apoptosis family in DMBA-induced hamster buccal-pouch squamous-cell carcinogenesis may be modulated by both genetic (mutant p53) and epigenetic mechanisms. [source]


In vitro studies on the effects of Saccharomyces boulardii and Bacillus cereus var. toyoi on nutrient transport in pig jejunum

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2000
G. Breves
The probiotics Saccharomyces boulardii and Bacillus cereus var. toyoi are nonpathogenic microbes which have been shown to affect certain functions of the mucosal barrier in pig jejunum such as electrogenic ion transport capacity and paracellular permeability. The present studies were performed to investigate potential effects of the probiotics on jejunal nutrient transport such as sodium-dependent glucose transport or proton-dependent dipeptide transport. For this purpose the in vitro Ussing-chamber technique was applied in order to examine net electrogenic ion flux rates (short circuit currents, Isc) across isolated intact jejunal epithelia in the absence and presence of either 10 mmol/l glucose (mucosal side) or two-fold application of 5 mmol/l glycyl- l -sarcosine or glycyl- l -glutamine to the mucosal bathing solution. Brush border membrane vesicles (BBMV) were prepared in order to characterize kinetic parameters (Vmax, Km) of Na-dependent glucose transport. Intestinal tissues were obtained from growing pigs in a weight range between 23 and 33 kg. All animals were fed twice daily and received 0.8,0.9 kg/day of a standard diet. After a 9- to 10-day adaptation period the diets for treated animals were either supplemented for 8 days with 1.7×107 colony-forming units (CFU)/g feed of S. boulardii or for 3 weeks with 106 CFU/g feed B. cereus var. toyoi. Under basal conditions Isc values were not affected by different treatment protocols (controls: 0.74 ± 0.04 µeq/cm2 per h, n=9; S. boulardii: 0.74 ± 0.12 µeq/cm2 per h, n=7; B. cereus 0.68 ± 0.09 µeq/cm2 per h, n=5). Irrespective of dietary treatment, the addition of glucose resulted in significant increases of Isc indicating substantial onset of electrogenic net Na/glucose cotransport. Maximal Isc values occurred within 30 min and reached 2.79 ± 0.41 µeq/cm2 per h in control epithelia. This was significantly lower than found in S. boulardii (4.47 ± 0.43 µeq/cm2 per h, p < 0.05) and B. cereus var. toyoi tissues (4.45 ± 0.31 µeq/cm2 per h, p < 0.05). Gt values were 22.4 ± 1.3 mS/cm2 in control animals and were significantly lower as shown in S. boulardii (p < 0.01) and B. cereus var. toyoi (p < 0.01)-treated animals (28.4 ± 1.3 and 29.9 ± 0.8 mS/cm2, respectively). Vmax values of Na-dependent glucose uptake into BBMV differed significantly between controls (0.64 ± 0.08 nmol/mg protein per 10 s; n=5), S. boulardii (0.89 ± 0.06 nmol/mg protein per 10 s; n=5, p < 0.05) and B. cereus var. toyoi preparations (1.08 ± 0.05 nmol/mg protein per 10 s; n=3, p < 0.01). Km values were not significantly affected (control: 0.31 ± 0.04 mmol/l, S. boulardii: 0.29 ± 0.05 mmol/l, B. cereus var. toyoi: 0.21 ± 0.01 mmol/l). Irrespective of dietary treatment, application of the dipeptide model substances glycyl- l -sarcosine or glycyl- l -glutamine resulted in significant increases of Isc indicating marked stimulation of electrogenic net H+/dipeptide cotransport. Highest Isc responses occurred in B. cereus var. toyoi preparations and lowest were found in control tissues. However, these differences were not significant. Gt values were not affected by different dietary treatments. The results clearly demonstrate that oral administration of either S. boulardii or B. cereus var. toyoi stimulates Na-dependent glucose absorption in pig jejunum. [source]


Mucosal tissue transglutaminase expression in celiac disease

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2009
Vincenzo Villanacci
Abstract Tissue transglutaminase (tTG) plays an important role in celiac disease pathogenesis and antibodies to tTG are a diagnostic marker of gluten-sensitive enteropathy. The aim of this study was to investigate the localization of tTG in the duodenal mucosa in control tissues and in different histological stages of celiac disease by using a commercial and a novel set of anti-tTG monoclonal antibodies, to see whether this assessment can be useful for diagnostic purpose. The distribution of tTG was firstly evaluated in 18 untreated celiac patients by using a commercial monoclonal antibody (CUB7402) against tissue transglutaminase enzyme and directed against the loop-core region of the enzyme. Thereafter, in further 30 untreated celiac patients we employed three newly characterized anti-tTG monoclonal antibodies produced against recombinant human-tTG. The epitopes recognized are located in three distinct domains of the protein corresponding to the core, C1 and C2 protein structure. Eleven age- and sex-matched patients with chronic duodenitis acted as controls. All subjects underwent upper endoscopy to obtain biopsy samples from the duodenum. Overall, we found that (i) tTG is equally expressed in CD at different stages of disease; (ii) tTG is expressed, at similar level, in CD and controls with duodenitis. Assessment of tTG level in biopsy samples by immunohistochemical methods is not useful in the clinical diagnostic work-up of CD. [source]


Downregulation of miR-122 in the rodent and human hepatocellular carcinomas

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006
Huban Kutay
Abstract MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P,=,0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers. J. Cell. Biochem. 99: 671,678, 2006. © 2006 Wiley-Liss, Inc. [source]


Prevalence of human papilloma virus and human herpes virus types 1,7 in human nasal polyposis

JOURNAL OF MEDICAL VIROLOGY, Issue 9 2009
Apostolos Zaravinos
Abstract This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein,Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions. J. Med. Virol. 81:1613,1619, 2009. © 2009 Wiley-Liss, Inc. [source]


Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003
Roland Sedivy
Abstract Background:, The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease. Methods:, Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients. Results:, LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease. Conclusions:, VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases. [source]


TNF-, expression and apoptosis-regulating proteins in oral lichen planus: a comparative immunohistochemical evaluation

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2000
Alexandra Sklavounou
Abstract: Apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue in oral lichen planus (OLP). In the present study, OLP biopsies were immunohistochemically evaluated for TNF-, and apoptosis-regulating proteins in an attempt to compare their phenotypic expression. Deparaffinized tissue sections from 22 OLP and 10 control oral biopsy specimens were immunohistochemically stained with anti-Bcl-2, anti-Bcl-x, anti-Bax and anti-TNF-, antibodies. Keratinocytes did not show any immunoreactivity for Bcl-2, while a uniform intense staining for this protein was evident in the lymphocytic infiltrate of OLP specimens. Immunoreactivity for TNF-, was seen in 17/22 OLP cases. All control tissues were TNF-, negative, thus indicating a possible involvement of this cytokine in the pathogenesis of OLP. The differences in the staining intensities of Bcl-x and Bax between OLP and normal epithelium were slight; therefore an obvious association of the phenotypic TNF-, expression with these apoptosis-regulating proteins was not apparent. [source]


Expression of osteopontin in chronic rhinosinusitis with and without nasal polyps

ALLERGY, Issue 1 2009
X. Lu
Background:, Osteopontin (OPN) is a multifunctional 34-kDa extracellular matrix protein that can influence the inflammatory process. However, the presence of OPN in human sinonasal mucosa and its roles in the inflammatory process of chronic rhinosinusitis (CRS) are not clear. This study investigated the expression of OPN in human sinonasal mucosa, its cytokine-driven expression regulation, and its effect on cytokine production in sinonasal mucosa. Methods:, Surgical samples were investigated by means of quantitative reverse transcriptase polymerase chain reaction for evaluation of OPN messenger RNA (mRNA) expression, and the presence and location of OPN protein expression were analyzed using immunohistochemistry. Furthermore, nasal explant culture was used to investigate the mutual regulatory interactions between interferon (IFN)-,, interleukin (IL)-4, IL-5, IL-13, IL-1,, and tumor necrosis factor (TNF)-, and OPN in sinonasal mucosa. Results:, Osteopontin expression was significantly upregulated in CRS tissues compared with control tissues. There was a further significant increase of OPN expression in patients with nasal polyps (NPs) and asthma. Immunohistochemistry revealed positive staining of OPN in epithelial cells, submucosal glands, infiltrating cells, and extracellular matrix. Osteopontin mRNA was induced by IFN-,, IL-1,, and TNF-,, but inhibited by IL-4 and IL-13. On the contrary, OPN induced IFN-,, IL-4, IL-5, IL-13, IL-1,, and TNF-, production in sinonasal mucosa. Conclusions:, The expression of OPN is upregulated in CRS. The mutual regulatory interactions between OPN and inflammatory cytokines suggest that OPN may play an important role in the pathogenesis of CRS. [source]