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Histologic Lesions (histologic + lesion)
Selected AbstractsThe Molecular Phenotype of Heart Transplant Biopsies: Relationship to Histopathological and Clinical VariablesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010M. Mengel Histopathology of endomyocardial biopsies (EMB) is the standard rejection surveillance for heart transplants. However, ISHLT consensus criteria for interpreting biopsies are arbitrarily defined. Gene expression offers an independent re-evaluation of existing diagnostic systems. We performed histologic and microarray analysis on 105 EMB from 45 heart allograft recipients. Histologic lesions, diagnosis and transcripts were compared to one another, time posttransplantation, indication for biopsy and left ventricular ejection fraction (LVEF). Histologic lesions presented in two groups: myocyte,interstitial and microcirculation lesions. Expression of transcript sets reflecting T cell and macrophage infiltration, and ,-interferon effects correlated strongly with each other and with transcripts indicating tissue/myocardium injury. This molecular phenotype correlated with Quilty (p < 0.005), microcirculation lesions (p < 0.05) and decreased LVEF (p < 0.007), but not with the histologic diagnosis of rejection. In multivariate analysis, LVEF was associated (p < 0.03) with ,-interferon inducible transcripts, time posttransplantation, ischemic injury and clinically indicated biopsies, but not the diagnosis of rejection. The results indicate that (a) the current ISHLT system for diagnosing rejection does not reflect the molecular phenotype in EMB and lacks clinical relevance; (b) the interpretation of Quilty lesions has to be revisited; (c) the assessment of molecules in heart biopsy can guide improvements of current diagnostics. [source] Diagnosis of Helicobacter pyloriHELICOBACTER, Issue 2008Marta Granstrom Abstract The different invasive and noninvasive diagnostic tests for Helicobacter pylori have been applied mainly in emerging countries. Molecular methods have been developed, especially a test for detection of H. pylori and its clarithromycin resistance directly from stools. The long-term effects of eradication on histologic lesions have been studied in a meta-analysis and the prognostic value of post-treatment in gastric mucosa-associated lymphoid tissue lymphoma has been assessed. An operating link for gastritis assessment (the OLGA staging) has also been published. Attempts to simplify the urea breath test protocol have been made, and new stool antigen tests have been proposed and compared to those previously available. [source] Deficiency in OGG1 Protects against Inflammation and Mutagenic Effects Associated with H. pylori Infection in MouseHELICOBACTER, Issue 5 2006Eliette Touati Abstract Background:,Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. Materials and Methods:, Big Blue Ogg1,/, C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. Results:, Inflammatory lesions induced in the gastric mucosa of H. pylori -infected mice, corresponding to a moderate gastritis, were less severe in Ogg1,/, than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1,/, than in the Wt mice. In these conditions, the H. pylori -SS1 infection in the Ogg1,/, mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. Conclusions:, The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection. [source] Fractal dimension can distinguish models and pharmacologic changes in liver fibrosis in ratsHEPATOLOGY, Issue 4 2002Frédéric Moal Fractal analysis measures the complexity of geometric structures. The aim of this study was to evaluate the feasibility and accuracy of fractal analysis in liver fibrosis. A total of 77 rats were included: 10 sham, 46 with fibrosis secondary to bile duct ligation (BDL), and 21 with fibrosis due to CCl4 intoxication. Measurements included the fractal dimension of Kolmogorov (Dk), histologic lesions, the area of fibrosis by image analysis, liver hydroxyproline content, messenger RNA fibronectin, serum hyaluronate level, and portal pressure. Fibrotic rats were given placebo, octreotide, or O2 -vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO). Intraobserver agreement of Dk was excellent with the intraclass (ic) correlation coefficient ric = 0.91 (P < .0001) as well as the interobserver agreement with ric = 0.88 (P < .001). Dk was correlated with other measurements or markers of fibrosis: the area of fibrosis (r = 0.75; P < .0001), hydroxyproline content (r = 0.51; P < .001), serum hyaluronate level (r = 0.52; P < .001), and portal pressure (r = 0.52; P < .01). Dk was significantly different between the 2 models of fibrosis (P < .0001), unlike the area of fibrosis, and this relationship was independent of other histologic lesions. The significant decrease in fibrosis observed with octreotide or V-PYRRO/NO was similarly reflected by Dk or the area of fibrosis. The diagnostic accuracy for the fibrosis model was 97% with the 5 main measurements or markers of fibrosis studied, with Dk isolated at the first step by stepwise analysis. In conclusion, fractal analysis is suitable for analyzing liver fibrosis and has excellent reproducibility. This is the only quantitative morphometric method that can discriminate among the models of fibrosis and is sensitive enough to detect pharmacologically induced changes in liver fibrosis. [source] Clinical and pathological effects of short-term cyanide repeated dosing to goatsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005B. Soto-Blanco Abstract The purpose of this work is to determine and describe the effects of subacute cyanide toxicity to goats. Eight female goats were divided into two groups. The first group of five animals was treated with 8.0 mg KCN kg,1 body weight day,1 for seven consecutive days. The second group of three animals was treated with water as controls. Complete physical examination, including observation for behavior changes, was conducted before and after dosing. One treated animal was euthanized immediately after dosing. Later, two of the remaining treated animals and a control goat were euthanized after a 30-day recovery period. Euthanized animals were necropsied and tissues were collected and prepared for histologic studies. Clinical signs in treated goats were transient and included depression and lethargy, mild hyperpnea and hyperthermia, arrhythmias, abundant salivation, vocalizations, expiratory dyspnea, jerky movements and head pressing. Two goats developed convulsions after day 3 of treatment. One animal developed more permanent behavioral changes as she became less dominant and aggressive. Histologic changes included mild hepatocellular vacuolation and degeneration, mild vacuolation and swelling of the proximal convoluted tubules of the kidneys and spongiosis of the white matter (status spongiosis) of the cerebral white tracts, internal capsule, cerebellar peduncles, spinal cord and peripheral nerves. In summary, sub-lethal cyanide intoxication in goats resulted in behavioral changes, and during the treatment period animals showed delayed signs of toxicity. Significant histologic lesions in goats were observed and need to be characterized further. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effect of Tissue Processing on Assessment of Endoscopic Intestinal Biopsies in Dogs and CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010M.D. Willard Background: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. Hypothesis: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. Animals: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. Methods: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while , statistics determined agreement between pathologists on histologic lesions. Results: There was poor agreement (,=,0.013 to 0.3) between pathologists, and institution of origin of slides had effect (,= 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum ,= 0.69 using 4-point scale versus maximum ,= 1.0 using 2-point scale). Significant association (P= .019, .04; 95% OR = 3.14,10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. Conclusions and Clinical Importance: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists. [source] Quantification of Angiogenesis in Otosclerosis,THE LARYNGOSCOPE, Issue 5 2005Robert W. Jyung MD Abstract Objectives/Hypothesis: The determinants of clinical versus histologic otosclerosis are unknown, but angiogenesis is associated with active disease. We hypothesized that quantification of angiogenesis in otosclerotic human temporal bones could reveal significant differences between clinical and histologic cases. Study Design: We reviewed all otosclerosis specimens meeting criteria from the temporal bone collection of the Massachusetts Eye and Ear Infirmary and 10 normal controls. Methods: Digital images were taken at predilection sites, followed by computer-assisted analysis. Canalicular area (CA), the aggregate of vascular spaces within bone, microvessel density (MVD), area, and depth were the main measures. Evidence of a direct connection between local vessels and the vasculature of the otosclerotic focus was also recorded for each specimen. Results: The average area (mm2) and depth (number of sections containing otosclerosis) of clinical lesions was significantly greater than histologic lesions. Total microvessel counts were significantly greater in clinical versus histologic lesions, and both clinical and histologic lesions contained significantly greater numbers of microvessels than the normal otic capsule. CA was also significantly higher in clinical lesions. MVD was slightly but not significantly higher in clinical lesions. Importantly, a direct connection between named vessels and the otosclerotic vasculature was significantly more frequent in clinical lesions. Conclusions: Computer-assisted quantification revealed significantly greater measures of angiogenesis in clinical versus histologic otosclerosis. Direct connection to adjacent vessels may support angiogenesis in this disease. Sustained angiogenesis may be an important determinant of clinical otosclerosis. [source] Loss of Solute Carriers in T Cell-Mediated Rejection in Mouse and Human Kidneys: An Active Epithelial Injury,Repair ResponseAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010G. Einecke T cell-mediated rejection of kidney allografts causes epithelial deterioration, manifested by tubulitis, but the mechanism remains unclear. We hypothesized that interstitial inflammation triggers a stereotyped epithelial response similar to that triggered by other types of injury such as ischemia-reperfusion. We identified solute carrier transcripts with decreased expression in mouse allografts, and compared their behavior in T cell-mediated rejection to native kidneys with ischemic acute tubular necrosis (ATN). Average loss of solute carrier expression was similar in ATN (77%) and T cell-mediated rejection (75%) with high correlation of individual transcripts. Immunostaining of SLC6A19 confirmed loss of proteins. Analysis of human kidney transplant biopsies confirmed that T cell-mediated rejection and ATN showed similar loss of solute carrier mRNAs. The loss of solute carrier expression was weakly correlated with interstitial inflammation, but kidneys with ATN showed decreased solute carriers despite minimal inflammation. Loss of renal function correlated better with decreased solute carrier expression than with histologic lesions (r = 0.396, p < 0.001). Thus the loss of epithelial transcripts in rejection is not a unique consequence of T cell-mediated rejection but an active injury,repair response of epithelium, triggered by rejection but also by other injury mechanisms. [source] Cluster Analysis of Lesions in Nonselected Kidney Transplant Biopsies: Microcirculation Changes, Tubulointerstitial Inflammation and ScarringAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010B. Sis Banff classification empirically established scoring of histologic lesions, but the relationships of lesions to each other and to underlying biologic processes remain unclear. We hypothesized that class discovery tools would reveal new relationships between individual lesions, and relate lesions to C4d staining, anti-HLA donor-specific antibody (DSA) and time posttransplant. We studied 234 nonselected renal allograft biopsies for clinical indications from 173 patients. Silhouette plotting and principal component analysis revealed three groups of lesions: microcirculation changes, including inflammation (glomerulitis, capillaritis) and deterioration (double contours, mesangial expansion); scarring/hyalinosis; and tubulointerstitial inflammation. DSA and C4d grouped with microcirculation inflammation, whereas time posttransplant grouped with scarring/hyalinosis lesions. Intimal arteritis clustered with DSA, C4d and microcirculation inflammation, but also showed correlations with tubulitis. Fibrous intimal thickening in arteries clustered with scarring/hyalinosis. Capillary basement membrane multilayering showed intermediary relationships between microcirculation deterioration and time-dependent scarring. Correlation analysis and hierarchical clustering confirmed the lesion relationships. Thus, we propose that the pathologic lesions in biopsies are not independent but are members of groups that represent distinct pathogenic forces: microcirculation changes, reflecting the stress of DSA; scarring, hyalinosis and arterial fibrosis, reflecting the cumulative burden of injury over time; and tubulointerstitial inflammation. Interpretation of lesions should reflect these associations. [source] De Novo Donor-Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009L. G. Hidalgo We studied whether de novo donor-specific antibodies (DSA) in sera from patients undergoing kidney transplant biopsies associate with specific histologic lesions in the biopsy and prognosis. DSA were assessed in 145 patients at the time of biopsy between 7 days to 31 years posttransplant. DSA was detected in 54 patients (37%), of which 32 represented de novo DSA. De novo DSA was more frequent in patients having late biopsies (34%) versus early biopsies (4%), and was usually either against class II alone or class I and II but rarely against class I alone. Microcirculation inflammation (glomerulitis, capillaritis) and damage (glomuerulopathy, capillary basement membrane multilayering), and C4d staining were associated with de novo DSA. However, the degree of scarring, arterial fibrosis and tubulo-interstitial inflammation did not correlate with the presence of de novo DSA. De novo DSA correlated with reduced graft survival after the biopsy. Thus, de novo DSA at the time of a late biopsy for clinical indication is primarily against class II, and associates with microcirculation changes in the biopsy and subsequent graft failure. We propose careful assessment of de novo DSA, particularly against class II, be performed in all late kidney transplant biopsies. [source] | ||||||||||