Pathomorphological and Immunohıstochemical Evaluation of Unilateral Progressive Mooren’s Ulcer in a Cat

Background: Mooren’s ulcer is a chronic and painful ulceration of the cornea. It begins progressively in the periphery and spread centrally in cornea. In human, it is seen uniaterally in most of cases. Mooren ulcer has not been reported in any kind of animals up to now. Although its aetiology is not completely enlighted, it has been suspected of the inflammatoryreaction against injuries-microbiological and immun mediated effects. Immun response in presence of accumulation of immune complexes into the limbal vessels.As a result of the deficit in the regulatory mechanism because the number of suppressor cells control over B and T lymphocytes, These situations can result in a progressive tendancy to inflammationbecause the production of autoantibodies and/or lymphokine from cytotoxic T-lymhocytes creates an immune-mediated vasculitis. Numerous immigrant inflammatory cells and proteins are evaded from vessels. After triggering inflammatory cells and releasing of meditors, corneal vascularization, scar tissue and re-epithelization develop. This regenerative-reperative process plays an important role during post-inflammatory process.Case: In this case, it was aimed to detect pathomorphological structure and immunologic relations in progressive Mooren’s ulcer (MU). A 1 year-old mix breed cat was submitted to clinic with complaints of progressive painful and eyesight loss in left eye. There were 1 cm-ulceration, opacification and old haemorrhagic areas at peripheral cornea. Histopathologically, there was wide ulceration including all layers of corneal epithelium and particularly vacuolar degeneration at suprabasal cells. In corneal stroma, numerous neutrophiles and mononuclear cells were infiltrated. Neovascularisation and fibrosis beginning from limbus were also present. This fibrotic progress was confirmed by Masson’s trichrome staining method. Immunohistochemically, Cytokeratin 3 (CK3) and cytokeratin 12 (CK12) positivities showing regenerative activity of suprabasal and basal cells were not widespread. Epidermal Growth Factor (EGF) positivities were generally weak in epithelialcells. In stroma, moderate vimentin positivities were detected proliferated in fibrocytes originating from limbus. α1-antichymotrypsin (A1AC) was mildly reacted in neutrophiles. CD3 and CD4 confirmed the presence of regulatory and helper T lymphocytes. CD3 and CD8 marked cytotoxic T lymphocytes and CD20 marked B lymphocytes in inflammatory areas. CD34 were also positive in peripheral corneal stem cells derived from limbal basal epitheliums in partly regenerated area. CD57 positivity in T lymphocytes and NK cells and CD68 positivity in macrophages were attended to the area.Discussion: CD1a positivity in T lymphocytes proved mediating lipid and microbial origin glycolipid antigens. TUNEL reactions showing DNA in situ fragmentation were present in the destructive and aging epithelial cells at periphery. In conclusion, the case has been found as unique in terms of its immunohistochemical characterization. The markers show that CD1a and CD68 expressions follow different progress in animals unlike in humanbeings even though the ulcer of pathogenetic mechanism is found identical to humanbeings.. The roles of CD20 and CD57 markers have potential roles in this ulcer. It is also concluded that insufficient epithelial regeneration, fibrosis, inflammation and apoptosis showed progressive Mooren’s ulcers having possibly microbial origin.Keywords: Mooren’s ulcer, pathomorphology, immunohistochemistry, cat.

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Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies

Blood ◽

10.1182/blood.v67.4.898.898 ◽

1986 ◽

Vol 67 (4) ◽

pp. 898-902 ◽

Cited By ~ 49

Author(s):

P Hokland ◽

G Kerndrup ◽

JD Griffin ◽

J Ellegaard

Keyword(s):

Bone Marrow ◽

Monoclonal Antibodies ◽

T Lymphocytes ◽

Peripheral Blood ◽

Defense Mechanisms ◽

Mononuclear Cells ◽

Myeloid Cells ◽

Suppressor Cells ◽

Refractory Anemia ◽

Differentiation Antigens

Abstract Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.

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Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies

Blood ◽

10.1182/blood.v67.4.898.bloodjournal674898 ◽

1986 ◽

Vol 67 (4) ◽

pp. 898-902

Author(s):

P Hokland ◽

G Kerndrup ◽

JD Griffin ◽

J Ellegaard

Keyword(s):

Bone Marrow ◽

Monoclonal Antibodies ◽

T Lymphocytes ◽

Peripheral Blood ◽

Defense Mechanisms ◽

Mononuclear Cells ◽

Myeloid Cells ◽

Suppressor Cells ◽

Refractory Anemia ◽

Differentiation Antigens

Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.

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T Lymphocyte Proliferative Responses Induced by Recombinant Factor VIII in Hemophilia A Patients with Inhibitors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650515 ◽

1996 ◽

Vol 76 (01) ◽

pp. 017-022 ◽

Cited By ~ 27

Author(s):

Sylvia T Singer ◽

Joseph E Addiego ◽

Donald C Reason ◽

Alexander H Lucas

Keyword(s):

T Lymphocytes ◽

Factor Viii ◽

Cellular Proliferation ◽

Mononuclear Cells ◽

Hemophilia A ◽

Normal Subjects ◽

Normal Male ◽

Cell Fractionation ◽

Severe Hemophilia ◽

Human Factor Viii

SummaryIn this study we sought to determine whether factor VUI-reactive T lymphocytes were present in hemophilia A patients with inhibitor antibodies. Peripheral blood mononuclear cells (MNC) were obtained from 12 severe hemophilia A patients having high titer inhibitors, 4 severe hemophilia A patients without inhibitors and 5 normal male subjects. B cell-depleted MNC were cultured in serum-free medium in the absence or presence of 2 µg of recombinant human factor VIII (rFVIII) per ml, and cellular proliferation was assessed after 5 days of culture by measuring 3H-thymidine incorporation. rFVIII induced marked cellular proliferation in cultures of 4 of 12 inhibitor-positive hemophilia patients: fold increase over background (stimulation index, SI) of 7.8 to 23.3. The remaining 8 inhibitor-positive patients, the 4 hemophilia patients without inhibitors and the 5 normal subjects, all had lower proliferative responses to rFVIII, SI range = 1.6 to 6.0. As a group, the inhibitor-positive subjects had significantly higher proliferative responses to rFVIII than did the inhibitor-negative and normal subjects (p < 0.05 by t-test). Cell fractionation experiments showed that T lymphocytes were the rFVIII-responsive cell type, and that monocytes were required for T cell proliferation. Thus, rFVIII-reactive T lymphocytes are present in the peripheral circulation of some inhibitor-positive hemophilia A patients. These T cells may recognize FVIII in an antigen-specific manner and play a central role in the regulation of inhibitor antibody production

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Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection

Microorganisms ◽

10.3390/microorganisms8121995 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1995

Author(s):

Yoku Hayakawa ◽

Yoshihiro Hirata ◽

Masahiro Hata ◽

Mayo Tsuboi ◽

Yukiko Oya ◽

...

Keyword(s):

Epithelial Cells ◽

Immune Responses ◽

Cell Fate ◽

Knockout Mice ◽

Suppressor Cells ◽

Inflammatory Cells ◽

Immune Disorder ◽

Host Immune Responses ◽

Epithelial Homeostasis ◽

H Pylori

The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.

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Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage

Translational Neuroscience ◽

10.1515/tnsci-2021-0003 ◽

2021 ◽

Vol 12 (1) ◽

pp. 58-66

Author(s):

Doan Nguyen ◽

Vi Tran ◽

Alireza Shirazian ◽

Cruz Velasco-Gonzalez ◽

Ifeanyi Iwuchukwu

Keyword(s):

Intracerebral Hemorrhage ◽

Negative Correlation ◽

Mononuclear Cells ◽

Inflammatory Cells ◽

Favorable Outcome ◽

Hospital Length Of Stay ◽

Spontaneous Intracerebral Hemorrhage ◽

Hematoma Volume ◽

Peripheral Blood Mononuclear ◽

Anti Inflammatory

Abstract Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

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A proteomic approach towards understanding the pathogenesis of Mooren's ulcer

Experimental Eye Research ◽

10.1016/j.exer.2021.108509 ◽

2021 ◽

pp. 108509

Author(s):

Hao Chi ◽

Wenpei Hao ◽

Xia Qi ◽

Ting Zhang ◽

Yanling Dong ◽

...

Keyword(s):

Proteomic Approach ◽

Mooren’S Ulcer ◽

Mooren's Ulcer

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Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00438.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. R591-R599 ◽

Cited By ~ 39

Author(s):

Mitsuharu Okutsu ◽

Kenji Ishii ◽

Kai Jun Niu ◽

Ryoichi Nagatomi

Keyword(s):

T Lymphocytes ◽

Mononuclear Cells ◽

Cxcr4 Expression ◽

Peripheral Blood Mononuclear ◽

Cycling Exercise ◽

Ru 486 ◽

Before And After ◽

Stromal Cell Derived Factor ◽

Chemokine Receptor 4

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1α/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.

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