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Lesion Formation (lesion + formation)
Selected AbstractsHuman Pathologic Validation of Left Ventricular Linear Lesion Formation Guided by Noncontact MappingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2002BRADLEY P. KNIGHT M.D. Linear Lesions Guided by Noncontact Mapping. This case report describes the histopathologic findings associated with two left ventricular, linear radiofrequency lesions in a patient who underwent cardiac transplantation shortly after an ablation procedure for ventricular tachycardia. The lesions were created with conventional ablation equipment guided by a noncontact mapping system. The findings provide pathologic validation that continuous, linear lesions are feasible using a noncontact mapping system for guidance. [source] Effect of a Photo-synthetic Inhibitor on Tryptamine Pathway-mediated Sekiguchi Lesion Formation in Lesion Mimic Mutant of Rice Infected with Magnaporthe griseaJOURNAL OF PHYTOPATHOLOGY, Issue 9 2008A. Imaoka Abstract A lesion-mimic mutant of rice (cv. Sekiguchi-asahi) showed enhanced resistance to Magnaporthe grisea infection, thereby inducing Sekiguchi lesion (sl) formation and tryptamine accumulation under light. Both Sekiguchi lesion formation and tryptamine accumulation in leaves infected with M. grisea were inhibited by pretreatment with the photosynthetic inhibitor, 3-(3, 4-Dichlorophenyl)-1,1-dimethylurea (DCMU), which suppressed the gene expression of tryptophan decarboxylase (TDC), monoamine oxidase activity, H2O2 generation and DNA fragmentation. Catalase activity was inhibited by M. grisea infection under light, but magnitude of the inhibition was reduced in leaves pretreated with DCMU. Furthermore, tryptophan accumulated in M. grisea- infected leaves under light but not in DCMU-pretreated ones. Interestingly, such DCMU inhibition was reduced in the presence of tryptophan. Our studies suggest that chloroplasts function as the inhibitor of anti-oxidant system such as catalase activity and the supplier of a precursor of tryptamine and tryptophan in the sl mutant infected with M. grisea. [source] Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid-associated osteonecrotic lesionsARTHRITIS & RHEUMATISM, Issue 10 2009Ge Zhang Objective To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits. Methods Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated. Results Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR,) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR, rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR, rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR, rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR, rabbits from week 2 to week 6. Conclusion Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low- level MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions. [source] Atypical pityriasis rosea or psoriasis guttata?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2002Early examination is the key to a correct diagnosis Pityriasis rosea is a self-limited, mild, inflammatory skin disease characterized by scaly lesions, possibly due to an unidentified infectious agent. It may occur at any age, but is seen most frequently in young adults. This paper reports a patient who presented with a skin condition which was initially diagnosed as pityriasis rosea; however, due to the persistence and change in appearance of the lesions, the diagnosis was later altered to psoriasis guttata. Changes in pityriasis rosea lesions over the course of the disease may make a correct diagnosis difficult, unless the patient is seen during the early stages of lesion formation. The final diagnosis in this case was of the rare variant known as pityriasis rosea irritata. This case highlights the importance of an excellent patient history in order to correctly diagnose the disease. [source] Temporary Occlusion of the Great Cardiac Vein and Coronary Sinus to Facilitate Radiofrequency Catheter Ablation of the Mitral IsthmusJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2008ANDRE D'AVILA M.D. Introduction: Ablation of the mitral isthmus to achieve bidirectional conduction block is technically challenging, and incomplete block slows isthmus conduction and is often proarrhythmic. The presence of the blood pool in the coronary venous system may act as a heat-sink, thereby attenuating transmural RF lesion formation. This porcine study tested the hypothesis that elimination of this heat-sink effect by complete air occlusion of the coronary sinus (CS) would facilitate transmural endocardial ablation at the mitral isthmus. Methods: This study was performed in nine pigs using a 30 mm-long prototype linear CS balloon catheter able to occlude and displace the blood within the CS (the balloon was inflated with ,5 cc of air). Using a 3.5 mm irrigated catheter (35 W, 30 cc/min, 1 minute lesions), two sets of mitral isthmus ablation lines were placed per animal: one with the balloon deflated (CS open) and one inflated (CS Occluded). After ablation, gross pathological analysis of the linear lesions was performed. Results: A total of 17 ablation lines were placed: 7 with CS Occlusion, and 10 without occlusion. Despite similar biophysical characteristics of the individual lesions, lesion transmurality was consistently noted only when using the air-filled CS balloon. Conclusions: Temporary displacement of the venous blood pool using an air-filled CS balloon permits transmurality of mitral isthmus ablation; this may obviate the need for ablation within the CS to achieve bidirectional mitral isthmus conduction. [source] Circumferential Ultrasound Ablation for Pulmonary Vein Isolation: Analysis of Acute and Chronic FailuresJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2002WALID SALIBA M.D. Circumferential Ultrasound Ablation for PV Isolation.Introduction: In patients undergoing circumferential isolation of the pulmonary veins with an ultrasound ablation system, we analyzed the temperatures achieved while delivering circumferential ostial lesions in the pulmonary veins. We also reviewed the angiograms obtained during the procedure and identified anatomic variants that could be responsible for ineffective lesion formation. Methods and Results: During the early clinical use in 33 patients, a total of 85 veins were ablated. A mean of 16.9 ± 12.3 ablations were delivered per patient, and a mean of 6.7 ablations per vein were applied. Entry block was assessed by placing a deflectable octapolar or a circular catheter in the vein. The following anatomic characteristics and technical limitations were identified as possible reasons for ineffective energy delivery: (1) funnel-shaped ostium; (2) ostial diameter larger than the balloon diameter; (3) inability to deliver the catheter to the right inferior or other vein ostia; (4) ostial instability; (5) early branching of the vein; and (6) eccentric position of the ultrasound transducer in the vein. In patients with recurrence of atrial fibrillation, 40% of the ostial lesions reached a temperature > 60°C. However, in patients cured by the ablation, 64% of the ostial lesions reached a temperature > 60°C (P < 0.06). At least 12 of the 20 chronic recurrences could have been related to technical limitations of the first system. Duration of atrial fibrillation and eccentric deployment of the ultrasound transducer were more frequent in patients with recurrence of arrhythmias at follow-up. Conclusion: Ostial anatomy of the veins may affect delivery of ultrasound energy to achieve circumferential lesions. Energy delivery at the ostium with a temperature > 60°C may be important to maximize success. Reconfiguration of the system to overcome the shortcomings identified in the initial experience could increase its performance. [source] Abfraction Lesions: Myth or Reality?JOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 5 2003J.S. REES BDS ABSTRACT Loss of tooth substance in the cervical region is usually attributed to toothbrush abrasion, erosion, or a combination of both factors. Recently the role of occlusal loading has become increasingly prominent. It is suggested that high occlusal loads cause large cervical stress concentrations, resulting in a disruption of the bonds between the hydroxyapatite crystals and the eventual loss of cervical enamel. This process has been called noncarious cervical tooth loss or abfraction. This article reviews the available evidence to support the thesis that occlusal loading can contribute to the process of abfraction. It also reviews the potential interactions between occlusal loading and erosion that may contribute to abfraction lesion formation. CLINICAL SIGNIFICANCE It is important to recognize the potential role of occlusal loading in the loss of cervical tooth tissue so that management of the occlusion can be incorporated into a treatment plan for a patient with abfraction lesions. [source] Rabeprazole treatment attenuated Helicobacter pylori -associated gastric mucosal lesion formation in Mongolian gerbilsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2003HIDEKAZU SUZUKI Abstract Background and Aim: Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium. In the present study, we investigated the effect of RPZ on H. pylori -associated gastric mucosal lesion formation. Methods: Sixty-two male Mongolian gerbils were inoculated with H. pylori (ATCC43504) (Hp group) and 60 gerbils with the culture media alone (control group). Some gerbils in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for 7 days) at the 5th week. Gerbils were evaluated at the 12th, 24th and 48th weeks. Results: In the Hp group, all gerbils were persistently infected for 24 weeks, but 36% became negative for H. pylori at the 48th week. In the Hp + RPZ group, 18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week, became negative for H. pylori. The level of neutrophil infiltration was significantly decreased in the Hp + RPZ group in comparison to the Hp group, possibly through the effects of RPZ on initial bacterial colonization and resultant inflammation. Even in the gerbils that became H. pylori -negative, the level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp group. RPZ treatment significantly increased the level of the reduced form of glutathione (GSH) at the 48th week. The elevated levels of the reduced form of GSH may have been reduced by an antioxidation process in the H. pylori -positive Hp + RPZ group. Conclusion: Administration of RPZ not only inhibited gastric H. pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH. © 2003 Blackwell Publishing Asia Pty Ltd [source] Effect of Exogenous and Endogenous Antioxidants on 3-Nitropionic Acid-Inducedin vivo Oxidative Stress and Striatal LesionsJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Insights into Huntington's Disease Abstract: 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of complex II in the mitochondria. 3-NP toxicity has gained acceptance as an animal model of Huntington's disease (HD). In the present study, we confirmed that rats injected with 3-NP (20 mg/kg, i.p., daily for 4 days) exhibit increased oxidative stress in both striatum and cortical synaptosomes as well as lesions in the striatum. Synaptosomal membrane proteins from rats injected with 3-NP exhibited a decrease in W/S ratio, the relevant electron paramagnetic resonance (EPR) parameter used to determine levels of protein oxidation, and western blot analysis for protein carbonyls revealed direct evidence of increased synaptosomal protein oxidation. Treatment of rats with the brain-accessible free radical spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N -oxide (DEPMPO; 30 mg/kg, i.p., daily 2 h before 3-NP injection) or with N -acetylcysteine (NAC; 100 mg/kg, i.p., daily 2 h before 3-NP injection), a known glutathione precursor, before 3-NP treatments protects against oxidative damage induced by 3-NP as measured by EPR and western blot analysis for protein carbonyls. Furthermore, both DEMPMPO and NAC treatments before 3-NP administration significantly reduce striatal lesion volumes. These data suggest oxidative damage is a prerequisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against 3-NP neurotoxicity and perhaps against HD as well. [source] Antibody responses to Porphyromonas gingivalis infection in a murine abscess model , involvement of gingipains and responses to re-infectionJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2003Masahiro Yoneda Background:,Porphyromonas gingivalis is one of the most important periodontopathogens. It produces cysteine proteinases named gingipains. We previously examined the effect of gingipains on abscess formation in a murine model. The rgpA rgpB double and kgp mutants induced smaller abscesses than the wild type. Moreover, the rgpA rgpB kgp triple (gingipain-null) mutant hardly showed lesion formation at all under the experimental conditions used, indicating that genes encoding gingipains are important for P. gingivalis virulence. Objectives:, Here, we further report the humoral immune responses induced by P. gingivalis strains. Methods:, After the lesions were apparently cured, sera were collected from the mice and immunoglobulin G (IgG) responses against the whole cell antigens of wild-type P. gingivalis were measured. Results:, Wild-type strain was found to induce a strong antibody reaction. On the other hand, the rgpA rgpB kgp triple and kgp mutants induced significantly lower antibody responses compared to the wild type. Western blotting analysis confirmed the differences in antibody production. Next, these mice were re-infected with wild-type strain. Mice that were first infected with wild-type strain showed significantly smaller lesion formation than control mice that were first infected with medium only. On the other hand, mice that were first infected with mutant strains devoid of gingipain activities did not show resistance to re-infection and immunoglobulins directed against gingipains may be protective. Conclusions:, These results suggest that gingipains play an important role in abscess formation in mice, and humoral immune responses seem to be partly responsible for the resistance to re-infection by P. gingivalis. [source] Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2003Kanyarat Suthin Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 µg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema. [source] Accumulation of Elsinochrome Phytotoxin does not Correlate with Fungal Virulence among Elsinoë fawcettii Isolates in FloridaJOURNAL OF PHYTOPATHOLOGY, Issue 10 2009Li-Yuan Wang Abstract Citrus scab caused by Elsinoë fawcettii is cosmopolitan in humid citrus-growing areas. We have previously demonstrated that production of non-host selective elsinochrome phytotoxin is a prerequisite for fungal full virulence and lesion formation. In this study we evaluated 71 field-collected isolates from Florida for pathogenicity and toxin production and found most of the isolates to be pathogenic to rough lemon, grapefruit and sour orange and able to produce elsinochromes in axenic culture. Elsinochromes were recovered, for the first time, from leaf lesions infected by 21 isolates, including four isolates that did not produce any measurable toxin in culture. There was no direct correspondence between the level of elsinochrome production in culture and virulence among the isolates. However, Elsinoë isolates failed to produce elsinochromes in culture and in planta were non-pathogenic to citrus hosts tested. Several isolates were non-pathogenic or only moderately virulent to the citrus hosts tested even though they could produce elsinochromes in culture, a phenotype not previously described in Florida. [source] Effect of a Photo-synthetic Inhibitor on Tryptamine Pathway-mediated Sekiguchi Lesion Formation in Lesion Mimic Mutant of Rice Infected with Magnaporthe griseaJOURNAL OF PHYTOPATHOLOGY, Issue 9 2008A. Imaoka Abstract A lesion-mimic mutant of rice (cv. Sekiguchi-asahi) showed enhanced resistance to Magnaporthe grisea infection, thereby inducing Sekiguchi lesion (sl) formation and tryptamine accumulation under light. Both Sekiguchi lesion formation and tryptamine accumulation in leaves infected with M. grisea were inhibited by pretreatment with the photosynthetic inhibitor, 3-(3, 4-Dichlorophenyl)-1,1-dimethylurea (DCMU), which suppressed the gene expression of tryptophan decarboxylase (TDC), monoamine oxidase activity, H2O2 generation and DNA fragmentation. Catalase activity was inhibited by M. grisea infection under light, but magnitude of the inhibition was reduced in leaves pretreated with DCMU. Furthermore, tryptophan accumulated in M. grisea- infected leaves under light but not in DCMU-pretreated ones. Interestingly, such DCMU inhibition was reduced in the presence of tryptophan. Our studies suggest that chloroplasts function as the inhibitor of anti-oxidant system such as catalase activity and the supplier of a precursor of tryptamine and tryptophan in the sl mutant infected with M. grisea. [source] Age-dependent Grey Mould Susceptibility and Tissue-specific Defence Gene Activation of Grapevine Berry Skins after Infection by Botrytis cinereaJOURNAL OF PHYTOPATHOLOGY, Issue 5 2007M. Kretschmer Abstract The correlation between the degree of maturity of grapevine berries and their susceptibility to infection by the grey mould fungus Botrytis cinerea was studied. Artificial inoculation with B. cinerea conidia of detached berries from cultivars Riesling and Pinot noir revealed an increasing susceptibility during the last weeks of berry ripening. Wound inoculation resulted in increased lesion formation when compared with inoculation of non-wounded berry skins. Lesion development after non-wounding inoculation was stimulated by the addition of nutrients. Riesling berries were more readily infected than Pinot noir berries, indicating that the Riesling berry skin is more easily colonized by the grey mould fungus. Analysis of defence gene activation in the berry skin tissue revealed increased transcript levels of phenylalanine ammonium lyase and stilbene synthase after inoculation with B. cinerea conidia, while mRNA abundance of osmotin was similar in inoculated and non-inoculated tissue. Our data indicate that properties of the grape berry skin, including its ability for infection-induced defence gene activation, are important for the outcome of grey mould infections. [source] Indole-related Compounds Induce the Resistance to Rice Blast Fungus, Magnaporthe grisea in BarleyJOURNAL OF PHYTOPATHOLOGY, Issue 11-12 2004M. Ueno Abstract When barley leaves pretreated with indole-3-acetic acid (IAA), tryptamine and tryptophan solutions at 50 ,g/ml, which did not show antifungal activity, were inoculated with Magnaporthe grisea spores 24 h after chemical pretreatments, both blast lesion and infection-hypha formations were significantly inhibited. Such resistance to M. grisea in barley was induced from 12 h after the pretreatment. In barley leaves pretreated with IAA, tryptamine and tryptophan at 50 ,g/ml, phenylalanine ammonia-lyase (PAL), peroxidase and chitinase activities were already significantly enhanced before M. grisea inoculation, when compared with that in distilled water (DW)-treated leaves as a control. In chemical-pretreated leaves, furthermore, H2O2 generation was observed by M. grisea inoculation before lesion formation, but not in DW-pretreated leaves as a control even by M. grisea inoculation. These results suggested that indole-related compounds IAA, tryptamine and tryptophan can protect barley from M. grisea as functioning as the plant activator. Studies on indole-related compounds may contribute to develop new plant activators for disease control. [source] Polaprezinc attenuates the Helicobacter pylori -induced gastric mucosal leucocyte activation in Mongolian gerbils,a study using intravital videomicroscopyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001H. Suzuki Background: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. Aim: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori -colonized Mongolian gerbils. Methods: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 × 108 CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. Results: In all H. pylori -inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). Conclusion: Polaprezinc inhibited H. pylori -associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils. [source] Linear Radiofrequency Microcatheter Ablation Guided by Phased Array Intracardiac Echocardiography Combined with Temperature DecayPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 12 2009DAVID KEANE M.D., Ph.D. Background:Fluoroscopy-guided catheter placement is limited in its ability to determine electrode-endocardial contact and involves radiation exposure. We hypothesized that (1) intracardiac echocardiography (ICE) would provide superior assessment of linear electrode contact compared to fluoroscopy and (2) slow temperature decay upon discontinuation of the radiofrequency current (time for temperature to fall 90% after a 10-second test application of the radiofrequency current T90) would indicate optimal electrode-myocardial contact. Methods:Sixty endocardial lesions were created in the atria and ventricles of six goats by simultaneous delivery of the radiofrequency current through two linear electrodes of a microcatheter with a central interelectrode thermocouple. Catheter placement was guided by fluoroscopy. A 7.5-MHz ICE transducer in the right atrium or ventricle assessed electrode contact. T90 and previously reported parameters of electrode contact and lesion formation were recorded. Histomorphometry was performed on the lesions. Results:T90 was 4.27 ± 4.98 seconds. Lesion depth significantly correlated with ICE assessment of electrode contact (r = 0.56, P = 0.001); T90 upon radiofrequency current offset (r = 0.48, P = 0.008), impedance fall upon radiofrequency current onset (r = 0.37, P = 0.008), bipolar pacing threshold preablation (r =,0.56, P = 0.001), bipolar electrogram amplitude preablation (r = 0.43, P = 0.02), but not with fluoroscopic assessment of the electrode contact (r = 0.18, n.s.). For the prediction of achieving a lesion depth of >2 mm, a T90 of >4.0 seconds yielded a specificity of 86% and a sensitivity of 52%, ICE yielded a specificity and sensitivity of 58% and 68%, respectively, while the specificity and sensitivity of fluoroscopy were 26% and 68%, respectively. Both ICE and T90 provide additional clinical relevance during guidance of cardiac microcatheter ablation. [source] An F-box gene, CPR30, functions as a negative regulator of the defense response in ArabidopsisTHE PLANT JOURNAL, Issue 5 2009Mingyue Gou Summary Arabidopsis gain-of-resistance mutants, which show HR-like lesion formation and SAR-like constitutive defense responses, were used well as tools to unravel the plant defense mechanisms. We have identified a novel mutant, designated constitutive expresser of PR genes 30 (cpr30), that exhibited dwarf morphology, constitutive resistance to the bacterial pathogen Pseudomonas syringae and the dramatic induction of defense-response gene expression. The cpr30 -conferred growth defect morphology and defense responses are dependent on ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), PHYTOALEXIN DEFICIENT 4 (PAD4), and NONRACE-SPECIFIC DISEASE RESISTANCE 1 (NDR1). Further studies demonstrated that salicylic acid (SA) could partially account for the cpr30 -conferred constitutive PR1 gene expression, but not for the growth defect, and that the cpr30 -conferred defense responses were NPR1 independent. We observed a widespread expression of CPR30 throughout the plant, and a localization of CPR30-GFP fusion protein in the cytoplasm and nucleus. As an F-box protein, CPR30 could interact with multiple Arabidopsis-SKP1-like (ASK) proteins in vivo. Co-localization of CPR30 and ASK1 or ASK2 was observed in Arabidopsis protoplasts. Based on these results, we conclude that CPR30, a novel negative regulator, regulates both SA-dependent and SA-independent defense signaling, most likely through the ubiquitin-proteasome pathway in Arabidopsis. [source] Characterization of Arabidopsis mur3 mutations that result in constitutive activation of defence in petioles, but not leavesTHE PLANT JOURNAL, Issue 5 2008Jennifer D. Tedman-Jones Summary A screen was established for mutants in which the plant defence response is de-repressed. The pathogen-inducible isochorismate synthase (ICS1) promoter was fused to firefly luciferase (luc) and a homozygous transgenic line generated in which the ICS1:luc fusion is co-regulated with ICS1. This line was mutagenized and M2 seedlings screened for constitutive ICS1:luc expression (cie). The cie mutants fall into distinct phenotypic classes based on tissue-specific localization of luciferase activity. One mutant, cie1, that shows constitutive luciferase activity specifically in petioles, was chosen for further analysis. In addition to ICS1, PR and other defence-related genes are constitutively expressed in cie1 plants. The cie1 mutant is also characterized by an increased production of conjugated salicylic acid and reactive oxygen intermediates, as well as spontaneous lesion formation, all confined to petiole tissue. Significantly, defences activated in cie1 are sufficient to prevent infection by a virulent isolate of Hyaloperonospora parasitica, and this enhanced resistance response protects petiole tissue alone. Furthermore, cie1 -mediated resistance, along with PR gene expression, is abolished in a sid2-1 mutant background, consistent with a requirement for salicylic acid. A positional cloning approach was used to identify cie1, which carries two point mutations in a gene required for cell wall biosynthesis and actin organization, MUR3. A mur3 knockout mutant also resists infection by H. parasitica in its petioles and this phenotype is complemented by transformation with wild-type MUR3. We propose that perturbed cell wall biosynthesis may activate plant defence and provide a rationale for the cie1 and the mur3 knockout phenotypes. [source] Loss of TIP1;1 aquaporin in Arabidopsis leads to cell and plant deathTHE PLANT JOURNAL, Issue 6 2004Shisong Ma Summary Arabidopsis TIP1;1 (,TIP) is a member of the tonoplast family of aquaporins (AQP). Using RNA interference (RNAi) we reduced TIP1;1 to different extent in various lines. When most severely affected, miniature plants died, a phenotype partially complemented by the TIP1;1 homolog McMIP-F. Less severely affected lines produced small plants, early senescence, and showed lesion formation. The relative water content in TIP1;1 RNAi plants was not significantly affected. Global expression profiling suggested a disturbance in carbon metabolism in RNAi lines with upregulated transcripts for functions in carbon acquisition and respiration, vesicle transport, signaling and transcription, and radical oxygen stress. Metabolite profiles showed low glucose, fructose, inositol, and threonic, succinic, fumaric, and malic acids, but sucrose levels were similar to WT. Increased amounts were found for raffinose and several unknown compounds. TIP1;1 RNAi plants also contained high starch and apoplastic carbohydrate increased. A GFP-TIP1;1 fusion protein indicated tonoplast location in spongy mesophyll cells, and high signal intensity in palisade mesophyll associated with vesicles near plastids. Signals in vascular tissues were strongest not only in vesicle-like structures but also outlined large vacuoles. Compromised routing of carbohydrate and lack of sucrose provision for cell-autonomous functions seems to characterize this RNAi phenotype. We suggest a function for TIP1;1 in vesicle-based metabolite routing through or between pre-vacuolar compartments and the central vacuole. Phenotype and expression characteristics support a view of TIP1;1 functioning as a marker for vesicles that are targeted to the central vacuole. [source] High humidity suppresses ssi4 -mediated cell death and disease resistance upstream of MAP kinase activation, H2O2 production and defense gene expressionTHE PLANT JOURNAL, Issue 6 2004Fasong Zhou Summary The Arabidopsis ssi4 mutant, which exhibits spontaneous lesion formation, constitutive expression of pathogenesis-related (PR) genes and enhanced resistance to virulent bacterial and oomycete pathogens, contains a gain-of-function mutation in a TIR-NBS-LRR type R gene. Epistatic analyses revealed that both PR gene expression and disease resistance are activated via a salicylic acid (SA)- and EDS1 -dependent, but NPR1 - and NDR1 -independent signaling pathway. In this study, we demonstrate that in moderate relative humidity (RH; 60%), the ssi4 mutant accumulates H2O2 and SA prior to lesion formation and displays constitutive activation of the MAP kinases AtMPK6 and AtMPK3. It also constitutively expresses a variety of defense-associated genes, including those encoding the WRKY transcription factors AtWRKY29 and AtWRKY6, the MAP kinases AtMPK6 and AtMPK3, the powdery mildew R proteins RPW8.1 and RPW8.2, EDS1 and PR proteins. All of these ssi4 -induced responses, as well as the chlorotic, stunted morphology and enhanced disease resistance phenotype, are suppressed by high RH (95%) growth conditions. Thus, a humidity sensitive factor (HSF) appears to function at an early point in the ssi4 signaling pathway. All ssi4 phenotypes, except for MAP kinase activation, also were suppressed by the eds1-1 mutation. Thus, ssi4 -induced MAP kinase activation occurs downstream of the HSF but either upstream of EDS1 or on a separate branch of the ssi4 signaling pathway. SA is a critical signaling component in ssi4 -mediated defense responses. However, exogenously supplied SA failed to restore lesion formation in high RH-grown ssi4 plants, although it induced defense gene expression. Thus, additional signals also are involved. [source] Substantial early, but nonprogressive neuronal loss in multiple sclerosis (ms) spinal cord,ANNALS OF NEUROLOGY, Issue 5 2009Lucas Schirmer MD Research in multiple sclerosis (MS) has recently been focusing on the extent of neuroaxonal damage and its contribution to disease outcome. In the present study, we examined spinal cord tissue from 30 clinically well-characterized MS patients. MS, amyotrophic lateral sclerosis (ALS), and control spinal cord tissue were subjected to morphometric analysis and immunohistochemistry for markers of cell damage and regeneration. Data were related to disease duration and age at death. Here, we present evidence for substantial, nonprogressive neuronal loss on the cervical and lumbar levels early in the disease course of MS. Chromatolytic neurons and immunoreactivity for c-Jun and GAP43 were observed in the ventral gray matter in and adjacent to actively demyelinating lesions, pointing toward neuronal damage and regeneration as an early response to lesion formation. Ann Neurol 2009;66:698,704 [source] Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesionsANNALS OF NEUROLOGY, Issue 2 2008Jacqueline T. Chen PhD Objective To assess demyelination and remyelination in vivo in acute gadolinium (Gd)-enhancing lesions of multiple sclerosis (MS). Methods We measured significant changes in magnetization transfer ratio (MTR) consistent with demyelination and remyelination of individual lesion voxels, as well as the mean normalized MTR over all lesion voxels during and after contrast enhancement, in MS patients participating in a 3-year Canadian trial assessing immunoablation and autologous stem cell transplantation for treatment of MS. Results The average mean normalized lesion MTR over all lesions exhibited partial recovery over 2 to 4 months after Gd enhancement. Voxel-based analysis demonstrated that approximately 70% of the initially enhancing lesion volume (GdLV) was left with stably low MTR over 39 months of evaluation. The percentage of the GdLV undergoing significant increases in MTR consistent with remyelination increased for approximately 7 months after enhancement and then stabilized at 21 %GdLV. Significant decreases in MTR consistent with demyelination were ongoing for approximately 33 months after enhancement, stabilizing at 9 %GdLV. The estimated error of these measurements, based on scan/rescan analysis, was less than 0.4 %GdLV. Interpretation We found significant changes in MTR consistent with demyelination and remyelination that followed different temporal evolutions and were ongoing in different lesion regions for at least 3 years after lesion formation. Ann Neurol 2008 [source] Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiationARTHRITIS & RHEUMATISM, Issue 3 2006Annegret Kuhn Objective To examine whether apoptosis contributes to the pathogenesis of skin lesions in patients with cutaneous lupus erythematosus (CLE) after ultraviolet (UV) irradiation. Methods In situ nick translation and TUNEL were performed to detect apoptosis in 85 skin biopsy specimens from patients with various subtypes of CLE. Specimens from normal healthy donors and patients with polymorphous light eruption were used as controls. In addition to assessment of primary lesions, provocative phototesting was carried out to investigate events occurring secondary to UV irradiation during a very early stage of lesion formation. Results A significant increase in apoptotic nuclei was found in the upper epidermal layer of primary and UV light,induced skin lesions of CLE patients compared with controls. In tissue sections obtained from control subjects at 24 hours after a single exposure to UV light, a slight increase in the count of epidermal apoptotic nuclei was present as compared with skin tissue from CLE patients obtained under the same conditions before lesion formation. In sections obtained from controls at 72 hours after irradiation, a significant decrease in the apoptotic nuclei count was observed, consistent with a proper clearance of apoptotic cells in the period between 24 and 72 hours after irradiation. In striking contrast, the number of apoptotic nuclei increased significantly within this period in tissue sections from patients with CLE. Conclusion These data support the hypothesis that apoptotic cells accumulate in the skin of patients with CLE after UV irradiation, as a result of impaired or delayed clearance. The nonengulfed cells may undergo secondary necrosis and release proinflammatory compounds and potential autoantigens, which may contribute to the inflammatory micromilieu that leads to formation of skin lesions in this disease. [source] Molecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic InsultBRAIN PATHOLOGY, Issue 4 2003Ursula Graumann Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source] Black holes in multiple sclerosis: definition, evolution, and clinical correlationsACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010M. A. Sahraian Sahraian MA, Radue E-W, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand: 2010: 122: 1,8. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy. The formation of new T2-hyperintense MRI lesions is commonly used to measure disease activity, but lacks specificity because edema, inflammation, gliosis, and axonal loss all contribute to T2 lesion formation. As the role of neurodegeneration in the pathophysiology of MS has become more prominent, the formation and evolution of chronic or persistent Tl-hypointense lesions (black holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. Despite the use of various detection methods, including advanced imaging techniques such as magnetization transfer imaging and magnetic resonance spectroscopy, correlation of persistent black holes with clinical outcomes in patients with MS remains uncertain. Furthermore, although axonal loss and neuronal tissue destruction are known to contribute to irreversible disability in patients with MS, there are limited data on the effect of therapy on longitudinal change in Tl-hypointense lesion volume. Measurement of black holes in clinical studies may elucidate the underlying pathophysiology of MS and may be an additional method of evaluating therapeutic efficacy. [source] Emergence of a ,hyperinfectious' bacterial state after passage of Citrobacter rodentium through the host gastrointestinal tractCELLULAR MICROBIOLOGY, Issue 8 2005Siouxsie Wiles Summary Citrobacter rodentium belongs to a family of human and animal enteric pathogens that includes the clinically significant enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens exploit attaching and effacing (A/E) lesions to colonize the host gastrointestinal tract. However, both EHEC and EPEC are poorly pathogenic in mice. In contrast, C. rodentium, which is genetically highly related to E. coli, relies on A/E lesion formation as an essential step in both colonization and infection of the murine mucosa, providing an excellent in vivo model. In this study we have used bioluminescence imaging (BLI) to investigate the organ specificity and dynamics of colonization of mice by LB-grown and mouse-passaged C. rodentium in situ and in real time. We have demonstrated the appearance of a ,hyperinfectious' state after passage of C. rodentium through the murine gastrointestinal tract. The ,hyperinfectious' state was found to dramatically reduce the dose required to infect secondary individuals, and also influenced the tissue distribution of colonizing bacteria, removing the requirement for primary colonization of the caecal patch. In addition, the ,hyperinfectious' phenotype was found to be transient with one overnight passage in rich medium sufficient to return C. rodentium to ,culture' infectivity. [source] Rituximab in refractory autoimmune bullous diseasesCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2006E. Schmidt Summary Treatment of autoimmune blistering diseases consists of systemic glucocorticosteroids usually in combination with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators such as dapsone, antibiotics, intravenous immunoglobulins, and immunoadsorption. In some patients, these treatment regimens are not sufficient to control disease activity and/or lead to intolerable adverse events. Rituximab, originally developed for the treatment of non-Hodgkin's lymphoma, is an anti-CD20 humanized monoclonal antibody leading to transitory B-cell depletion. For this indication, rituximab is widely employed, and severe side-effects rarely observed. Subsequently, the B-cell-depleting effect of rituximab has been exploited successfully in various autoimmune disorders, including autoimmune blistering diseases. Here, we review the effect of rituximab in such diseases. To date, application of rituximab has been reported in 26 treatment-resistant patients with the vulgaris, foliaceus, and paraneoplastic variants of pemphigus as well as in bullous pemphigoid and epidermolysis bullosa acquisita. All but a single patient showed clinical improvement with reduction of lesion formation. In about a third, a clinical remission requiring further immunsuppressive medication was achieved, and in about a quarter, complete remission was induced. In addition, the mode of action and adverse events of rituximab as well as adjuvant immunosuppressive treatments, and the effect on levels of circulating autoantibodies in these patients are discussed. [source] Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen-induced preneoplastic lesions formationINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Anne Mathieu Abstract In humans, initial events of pancreatic carcinogenesis remain unknown, and the question of whether this cancer, which has a ductal phenotype, exclusively arises from duct cells has been raised. Previous studies have demonstrated that transgenic expression of the CCK2 receptor in acinar cells of ElasCCK2 mice plays a role in the development of pancreatic neoplasia. The aim of our study was to examine initial steps of carcinogenesis in ElasCCK2 mice, adding a supplementary defect by using a chemical carcinogen, azaserine. Results of posttreatment sequential immunohistochemical examinations and quantifications demonstrate that mice responded to azaserine. Transition of acinar cells into duct-like cells expressing Pdx1 and gastrin, as well as proliferation of acinar cells, were transiently observed in both transgenic and control mice. The carcinogen also induced formation of preneoplastic lesions, adenomas, exhibiting properties of autonomous growth. Importantly, expression of the CCK2 receptor increased the susceptibility of pancreas to azaserine. Indeed, treated ElasCCK2 mice exhibited larger areas of pancreatic acinar-ductal transition, increased cellular proliferation as well as larger adenomas areas vs. control mice. These amplified responses may be related to auto/paracrine stimulation of CCK2 receptor by gastrin expressed in newly formed duct-like cells. Our results demonstrate that activation of CCK2 receptor and azaserine result in cumulative effects to favor the emergence of a risk situation that is a potential site for initiation of carcinogenesis. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||