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1.
J Clin Ultrasound ; 46(3): 231-232, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28568285

ABSTRACT

A 38-year-old woman was diagnosed with systemic lupus erythematosus and received immunosuppressive therapy. After 6 months of treatment, workup for low-grade fever yielded elevated enzyme-linked immunosorbent assay titers for Aspergillus antigen in serum and ascites, leading to the diagnosis of disseminated aspergillosis. Transthoracic echocardiography revealed a claviform vegetation attached to the left ventricular anterior septum. Two days after the start of antifungal Amphotericin-B therapy, the patient suffered from several neurologic disorders. A second transthoracic echocardiography revealed that the vegetation decreased in size. Two weeks later, the vegetation increased again. Combination therapy of Amphotericin-B and Voriconazole was initiated, and the vegetation eventually disappeared completely. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:231-232, 2018.


Subject(s)
Aspergillosis/diagnosis , Echocardiography/methods , Heart Diseases/diagnosis , Heart Ventricles/microbiology , Lupus Erythematosus, Systemic/complications , Adult , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/complications , Aspergillosis/drug therapy , Aspergillus/isolation & purification , Female , Heart Diseases/complications , Heart Diseases/drug therapy , Heart Ventricles/diagnostic imaging , Humans , Voriconazole/therapeutic use
2.
Int J Cardiovasc Imaging ; 32(9): 1357-1361, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27240601

ABSTRACT

Cardiac involvement in hypereosinophilic syndrome (HES) patients entails significant morbidity and mortality. Left ventricular (LV) endocardial damage is important for the development of cardiac involvement in HES patients. However very early stage LV endocardial damage, such as prior to the first stage of an acute necrotic stage, remains uncertain. We studied 32 HES patients, all with normal conventional echocardiographic findings. Global radial and circumferential strain (GRS and GCS) were determined for each peak global strain curve from the mid-LV short-axis view, and global longitudinal strain (GLS) was averaged each peak global strain curve from standard apical views by means of two-dimensional speckle-tracking method. Thirty-one age-, gender-, LV ejection fraction-matched normal subjects were studied for comparison. GRS and GRS were similar for HES patients and normal controls, but GLS for HES patients was significantly lower than that for normal controls (16.2 ± 3.3 % vs 19.3 ± 2.9 %, p < 0.001). Furthermore, receiver operating characteristic curve analysis identified GLS ≤17.0 % as the best predictor of LV endocardial dysfunction with a sensitivity of 66 %, specificity of 78 %, and area under the curve of 0.781 (p = 0.0001). In conclusions, LV endocardial dysfunction pre-existed even in HES patients without apparent cardiac involvement. GLS as assessed with the two-dimensional speckle-tracking method is a promising tool for the better management of very early stage of HES patients.


Subject(s)
Endocardium/physiopathology , Hypereosinophilic Syndrome/complications , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left , Adult , Aged , Area Under Curve , Early Diagnosis , Echocardiography, Doppler , Endocardium/diagnostic imaging , Female , Humans , Hypereosinophilic Syndrome/diagnosis , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Retrospective Studies , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
3.
Mod Rheumatol ; 23(1): 89-96, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22447557

ABSTRACT

OBJECTIVES: Recent studies have shown that mycophenolate mofetil (MMF) is similar to intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis (LN), but that treatment response may vary according to location and race/ethnicity. Moreover, no studies have been conducted to compare the efficacy of MMF with that of IVC for a Japanese population. We therefore conducted a retrospective study to clarify the efficacy and safety of MMF compared with that of IVC for induction therapy for active LN, classes III and IV, in a Japanese population of 21 patients, 11 of whom received MMF and 10 IVC. METHODS: The primary endpoint was expressed as the percentage of responders, who in turn were defined as the patients who met complete or partial response criteria according to the European consensus statement. The secondary endpoints comprised the renal activity component and serological activity. RESULTS: The primary endpoint was achieved in nine (81.8 %) patients receiving MMF and in four (40.0 %) receiving IVC, with no significant difference between the two groups (p = 0.081), while there was also no significant difference between them in terms of secondary endpoints. However, the MMF group suffered significantly fewer hematologic toxic effects than the IVC group. CONCLUSIONS: MMF may be used as an alternative to IVC for inducing renal remission of LN in Japanese patients.


Subject(s)
Cyclophosphamide/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Mycophenolic Acid/analogs & derivatives , Adult , Asian People/ethnology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Drug Therapy, Combination , Endpoint Determination , Female , Glucocorticoids/therapeutic use , Hematologic Diseases/chemically induced , Humans , Immunosuppressive Agents/adverse effects , Induction Chemotherapy , Injections, Intravenous , Japan/epidemiology , Lupus Nephritis/ethnology , Male , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Remission Induction , Retrospective Studies
4.
Biochem Biophys Res Commun ; 417(1): 582-7, 2012 Jan 06.
Article in English | MEDLINE | ID: mdl-22178074

ABSTRACT

SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52(low) HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H(2)O(2)- or diamide-induced oxidative stress, IFN-α, IFN-γ and anti-Fas antibody, etoposide, or γ-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.


Subject(s)
Apoptosis/immunology , Oxidative Stress/immunology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Ribonucleoproteins/physiology , Active Transport, Cell Nucleus , Apoptosis/genetics , Cell Nucleus/enzymology , Diamide/pharmacology , Gene Knockdown Techniques , HeLa Cells , Humans , Hydrogen Peroxide/pharmacology , Interferon-alpha/pharmacology , Interferon-gamma/pharmacology , Oxidative Stress/genetics , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism
5.
J Exp Clin Cancer Res ; 29: 163, 2010 Dec 13.
Article in English | MEDLINE | ID: mdl-21144016

ABSTRACT

BACKGROUND: In spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML)-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs) or mesenchymal stromal cells rather than to hematopoietic cells. METHODS: To examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis. RESULTS: HPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3+ T-cell proliferation was suppressed in the presence of HPB-AML-I cells. CONCLUSIONS: We conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells.


Subject(s)
Cell Line, Tumor/cytology , Cell Line, Tumor/physiology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Neoplastic Stem Cells/cytology , Neoplastic Stem Cells/physiology , Cell Differentiation/physiology , Cell Lineage , Humans
6.
J Rheumatol ; 34(10): 2035-43, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17896802

ABSTRACT

OBJECTIVE: To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sjögren's syndrome (SS). METHODS: Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-gamma (IFN-gamma) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-gamma and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining. RESULTS: Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-gamma-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX. CONCLUSION: Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.


Subject(s)
Antioxidants/metabolism , Oxidative Stress , Salivary Glands , Sjogren's Syndrome , Thioredoxins/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Adult , Aged , Aldehydes/metabolism , Apoptosis/physiology , Biomarkers/metabolism , Cysteine Proteinase Inhibitors/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Female , Humans , Hydrogen Peroxide/metabolism , Interferon-gamma/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Middle Aged , Oxidants/metabolism , Saliva/chemistry , Salivary Glands/cytology , Salivary Glands/metabolism , Salivary Glands/pathology , Sjogren's Syndrome/metabolism , Sjogren's Syndrome/pathology , Thioredoxins/genetics , Tyrosine/analogs & derivatives , Tyrosine/metabolism
7.
Free Radic Biol Med ; 40(10): 1721-31, 2006 May 15.
Article in English | MEDLINE | ID: mdl-16678011

ABSTRACT

Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.


Subject(s)
Arthritis, Rheumatoid/prevention & control , Joints/drug effects , Joints/pathology , Thioredoxins/therapeutic use , 8-Hydroxy-2'-Deoxyguanosine , Animals , Apoptosis/drug effects , Arthritis, Rheumatoid/pathology , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/biosynthesis , Disease Models, Animal , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Mice , Mice, Transgenic , Reverse Transcriptase Polymerase Chain Reaction , Thioredoxins/genetics , Tumor Necrosis Factor-alpha/metabolism
8.
J Rheumatol ; 32(11): 2156-63, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16265694

ABSTRACT

OBJECTIVE: Programmed death-1 (PD-1) mediates a negative signal and introduces tolerance for lymphocytes. Dysfunction of the PD-1 pathway is thought to result in autoimmune diseases such as rheumatoid arthritis (RA). To investigate the role of the PD-1/PD-L system in the pathology of Sjögren's syndrome (SS), we examined the expression of PD-1 and its ligand PD-L1 in salivary lymphocytes and salivary glands from patients with SS. METHODS: Flow cytometry analysis was used to determine expression of PD-1 in SS salivary lymphocytes. Intracellular staining of interleukin 10 (IL-10) was performed after stimulation with PMA and ionomycin. Indirect immunohistochemistry was used to investigate the expression of PD-1 and PD-L1. RESULTS: The mean fluorescence intensity of PD-1 expression in SS salivary lymphocytes was significantly higher than that from healthy controls and patients with RA or systemic lupus erythematosus. PD-1-positive SS salivary lymphocytes expressed IL-10 intracellularly upon PMA/ionomycin stimulation. Immunohistochemical analysis showed that PD-1 was expressed on infiltrating lymphocytes in salivary gland from 52% of SS patients, and PD-L1 was expressed on ductal and acinar epithelial cells from 68% of SS patients. In vitro analysis using HSG cells revealed that PD-L1 was induced by interferon-gamma but not by tumor necrosis factor-alpha and IL-1beta. CONCLUSION: PD-1 is expressed on T lymphocytes and PD-L1 on epithelial cells from inflamed salivary glands of patients with SS, which suggests that dysfunction of the PD-1/PD-L1 pathway may be related to tolerance for lymphocytes, which causes SS.


Subject(s)
Antigens, Surface/metabolism , Apoptosis Regulatory Proteins/metabolism , B7-1 Antigen/metabolism , Membrane Glycoproteins/metabolism , Peptides/metabolism , Salivary Glands/pathology , Sjogren's Syndrome/immunology , Sjogren's Syndrome/pathology , Antigens, CD , Antigens, Surface/immunology , Antineoplastic Agents/pharmacology , Apoptosis Regulatory Proteins/immunology , B7-1 Antigen/immunology , B7-H1 Antigen , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/metabolism , Flow Cytometry , Humans , Immune Tolerance , Interferon-gamma/pharmacology , Membrane Glycoproteins/immunology , Peptides/immunology , Programmed Cell Death 1 Receptor , Salivary Glands/immunology , Salivary Glands/metabolism , Sjogren's Syndrome/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
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