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BACKGROUND: We previously reported that JAK-STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE. RESULTS: We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4+ T cells (SLE mice) and CD3+ T cells (human SLE patients) were measured by DNA microarray and qRT-PCR. TOFA treatment resulted in reduced levels of anti-dsDNA antibodies, decreased proteinuria, and amelioration of nephritis as compared with those observed in control animals. Moreover, we observed the rebalance in the populations of naïve CD4+ T cells and effector/memory cells in TOFA-treated mice; however, treatment with a combination of TOFA and dexamethasone (DEXA) elicited a stronger inhibitory effect toward the effector/memory cells than did TOFA or DEXA monotherapy. We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively. CONCLUSION: Modulation of type I IFN signalling via JAK-STAT inhibition may exert a beneficial effect in SLE patients, and our results suggest that TOFA could be utilised for the development of new SLE-specific therapeutic strategies.
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Linfocitos T CD4-Positivos/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Furanos/farmacología , Furanos/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Subgrupos de Linfocitos T/efectos de los fármacos , Adulto , Anciano , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Linfocitos T CD4-Positivos/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dexametasona/farmacología , Dexametasona/uso terapéutico , Regulación hacia Abajo/inmunología , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Ratones , Ratones Endogámicos MRL lpr , Ratones Endogámicos NZB , Persona de Mediana Edad , Proteínas/genética , Proteínas/metabolismo , Transducción de Señal/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Adulto JovenRESUMEN
Type I interferons (IFN-Is) play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Double-filtration plasmapheresis (DFPP) is a treatment option for SLE; however, its effect on IFN-Is remains unclear. Therefore, we investigated the effects of DFPP on IFN-Is. Plasma from patients with SLE (n = 11) who regularly underwent DFPP was analysed using a cell-based reporter system to detect the bioavailability and inducing activity of IFN-I. The concentration of plasma dsDNA was measured, and western blotting analysis was used to assess the phosphorylation of the STING pathway. A higher IFN-I bioavailability and inducing activity were observed in patients compared to healthy controls, and both parameters decreased after DFPP. The reduction in IFN-I-inducing activity was particularly prominent in patients with high disease activity. Notably, this reduction was not observed in STING-knockout reporter cells. Additionally, plasma dsDNA levels decreased after DFPP treatment, suggesting that inhibition of the STING pathway was responsible for the observed decrease in activity. Western blotting analysis revealed suppression of STING pathway phosphorylation after DFPP. DFPP reduced IFN-I bioavailability and the inducing activity of plasma. This reduction is likely attributable to the inhibition of the STING pathway through the elimination of dsDNA.
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BACKGROUND AND OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease is a multi-organ disorder that can include the lungs. IgG4-related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed. METHODS: Forty-eight patients suspected of having IgG4-related lung disease, with a high serum concentration of IgG4 and abundant IgG4-positive plasma cell infiltration into the intrathoracic organs, were retrospectively evaluated. Their clinical features, chest imaging findings and pathological findings were examined, with final diagnoses made by an open panel conference. RESULTS: Of the 48 patients, 18 with extrathoracic manifestations were diagnosed as having IgG4-related lung disease. Most of these patients were middle-aged to elderly men. IgG4-related lung disease was characterized by high serum concentrations of IgG and IgG4, normal white blood cell count and serum C-reactive protein concentration and a good response to corticosteroids. Common radiological findings included mediastinal lymphadenopathy and thickening of the perilymphatic interstitium, with or without subpleural and/or peribronchovascular consolidation. Pathological examination showed massive lymphoplasmacytic infiltration with fibrosis in and around the lymphatic routes, with distribution well correlated with radiological manifestations. CONCLUSIONS: The findings suggest that the intrathoracic manifestations of IgG4-related lung disease develop through lymphatic routes of the lungs and show various clinical characteristics. Because some lymphoproliferative disorders show similar findings, the correlation of clinicoradiological and pathological characteristics is crucial for the diagnosis of IgG4-related lung disease.
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Inmunoglobulina G/inmunología , Enfermedades Pulmonares/inmunología , Pulmón/diagnóstico por imagen , Pulmón/patología , Paraproteinemias/inmunología , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Broncoscopía , Femenino , Humanos , Inmunoglobulina G/sangre , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Paraproteinemias/diagnóstico , Paraproteinemias/metabolismo , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Estudios RetrospectivosRESUMEN
A 45-year-old Chinese woman with active systemic lupus erythematosus, lupus anticoagulant positive, was admitted to our hospital. Electrocardiography on admission was normal. Though anti-Sjögren's syndrome A (anti SS-A/Ro) antibodies were negative and ultrasound cardiographic findings were normal, she developed various arrhythmias/conduction disturbances shortly after starting corticosteroid. Nearly all were resolved with continuous corticosteroid and aspirin therapy before discharge. Vasculitis, the presence of antiphospholipid antibodies, and platelet aggregation due to corticosteroid were possible mechanisms underlying the arrhythmias/conduction disturbances.
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Corticoesteroides/efectos adversos , Síndrome Antifosfolípido/tratamiento farmacológico , Bloqueo Cardíaco/inducido químicamente , Lupus Eritematoso Sistémico/tratamiento farmacológico , Síndrome Antifosfolípido/inmunología , Electrocardiografía , Femenino , Bloqueo Cardíaco/diagnóstico , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana EdadRESUMEN
Histo-blood group ABH antigens are widely distributed in human tissues. The epitopes of ABH antigens are carried by at least four different peripheral core isotypes of internal carbohydrate backbones (type 1-4). Each type of ABH antigen is expressed tissue specifically, and aberrant expression of ABH antigens is often observed during oncogenesis. We immunohistochemically examined the expression of A type 3 antigens in wounded and diseased skin tissues (A and AB blood groups). In uninjured skin, the expression of A type 3 antigens was restricted to the eccrine sweat gland. In addition to the sweat glands, A type 3 antigens were found in vascular endothelial cells of the wound sites. The extent of A type 3 antigens expression related to postinfliction intervals. A significantly higher expression rate of A type 3 antigens in endothelial cells was also observed in diseased skin, suggesting that inflammation might induce A type 3 antigen expression in endothelial cells. Double-color immunofluorescence staining of the specimens showed that von Willebrand factor (vWF) was a core-protein of A type 3 determinants aberrantly expressed in endothelial cells in inflamed tissues, suggesting that aberrant expression of A type 3 antigens is involved in stabilization of vWF in inflammation.
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Sistema del Grupo Sanguíneo ABO/biosíntesis , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Enfermedades de la Piel/metabolismo , Piel/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Inmunohistoquímica , Inflamación/metabolismo , Persona de Mediana Edad , Piel/lesiones , Factor de von Willebrand/biosíntesisRESUMEN
We report a fatal intoxication case by the ingestion of an herbicide, 2-methyl-4-chlorophenoxyacetic acid (MCPA). A 23-year-old male was found dead in his car. The forensic autopsy revealed no remarkable morphological changes. However, in a toxicological screening test, MCPA was qualitatively detected from the extracts of stomach contents. Then MCPA in the extract of each body fluid and organ tissue was determined by gas chromatography-mass spectrometry with trimethylsilyl-derivatization as follows (microg/g): 888.3 in the heart blood, 578.1 in the peripheral blood, 52.2 in the urine, 770.9 in the brain, 1362 in the right lung, 1135 in the liver, 755.5 in the right kidney, and 10,200 in the stomach contents. These data strongly suggested that the male orally ingested MCPA. Moreover, p-chloro-o-cresol (4-chloro-2-methylphenol) was also determined in the body fluids and organ tissues, suggesting a metabolite of MCPA. From these toxicological data, together with autopsy findings, the cause of his death was diagnosed as acute MCPA poisoning.
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Ácido 2-Metil-4-clorofenoxiacético/envenenamiento , Causas de Muerte , Herbicidas/envenenamiento , Suicidio , Ácido 2-Metil-4-clorofenoxiacético/análisis , Ácido 2-Metil-4-clorofenoxiacético/metabolismo , Adulto , Cresoles/análisis , Cresoles/metabolismo , Toxicología Forense , Cromatografía de Gases y Espectrometría de Masas , Contenido Digestivo/química , Herbicidas/análisis , Herbicidas/metabolismo , Humanos , Masculino , Reproducibilidad de los Resultados , Detección de Abuso de SustanciasRESUMEN
A 57-year-old Japanese man was admitted to the hospital with back pain and fever, multiple lung nodules, and abdominal aortic aneurysm (AAA). Laboratory tests performed at admission showed an increased proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) level. Video-associated thoracoscopic lung biopsy was performed; pathologic examination showed granulation tissue with necrosis and multinucleated giant cells. The diagnosis of granulomatosis with polyangiitis (GPA) was confirmed on the basis of the clinical presentation, laboratory findings, and lung biopsy. All symptoms were ameliorated, and the serum level of PR3-ANCA declined following treatment with prednisolone and cyclophosphamide. Although the association of GPA with AAA is rare, GPA may be included among the large vessel vasculitides that can give rise to aortic aneurysm.
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BACKGROUND: Connective tissue growth factor (CTGF) is a multifunctional cellular protein and playing a role as a central mediator in tissue remodeling and fibrosis. The physiological function of CTGF in psoriasis is unknown. OBJECTIVE: The purpose of this study was to investigate the function of CTGF in psoriasis using the established imiquimod (IMQ)-induced psoriasis murine model and psoriasis patients. METHODS: Anti-CTGF monoclonal antibody was applied to IMQ induced psoriasis mice and those skin were clinically, pathologically and immunologically analyzed. Additionally, CTGF expression was analyzes using skin samples and plasma from psoriasis patients. RESULTS: CTGF expression was observed in the dermis from both IMQ-induced psoriatic mice and psoriasis patients. CTGF inhibition using an anti-CTGF antibody slightly worsened IMQ-induced dermatitis. In addition, the increase of CTGF showed tendency to suppress the psoriatic dermatitis through inhibition of suprabasal cells proliferation and macrophage infiltration in the skin. CTGF was also detected significantly higher in plasma from psoriasis patients comparing with healthy control. CONCLUSION: Our findings suggest that CTGF could contribute to the healing rather than the worsening of psoriasis skin lesions.
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Objective The objective of this study was to confirm the efficacy of low-dose mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients with an inadequate response to various combination therapies of MTX, other synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs. Methods Low-dose MZR was administered to 56 uncontrolled RA patients being treated with MTX and various biological DMARDs. The observation period was 12 months, and the disease activity was evaluated based on the Disease Activity Score in 28 joints (DAS28)-ESR, Simplified Disease Activity Index (SDAI) and serum MMP-3 level. Results All of the disease activity indices were significantly improved within three months, and the serum MMP-3 levels were also significantly decreased around four months after starting low-dose MZR therapy. No patients experienced any adverse effects. Conclusion The present preliminary findings suggest that low-dose MZR therapy with MTX should be considered for the treatment of RA patients with an inadequate response to various combination therapies including MTX, other synthetic DMARDs and biological DMARDs or in whom increasing the dose of MTX is difficult for reasons such as adverse effects and complications.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Ribonucleósidos/uso terapéutico , Anciano , Antirreumáticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Metotrexato/administración & dosificación , Persona de Mediana Edad , Proyectos Piloto , Ribonucleósidos/administración & dosificación , Resultado del TratamientoRESUMEN
We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.
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Antirreumáticos/farmacología , Artritis Reumatoide/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Somatomedina/antagonistas & inhibidores , Receptores de Somatomedina/metabolismo , Animales , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor Estimulante de Colonias de Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos/farmacología , Ratones , Neovascularización Patológica/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/farmacología , Pirroles/farmacología , Ligando RANK/metabolismo , Ligando RANK/farmacología , Receptor IGF Tipo 1 , Transducción de Señal/efectos de los fármacosRESUMEN
It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1alpha and MIP-2 was significantly enhanced at 1 and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge.
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Citocinas/genética , Sustancias de Crecimiento/genética , Herbicidas/farmacología , Pulmón/metabolismo , Paraquat/farmacología , Animales , Colágeno/metabolismo , Citocinas/metabolismo , Técnica del Anticuerpo Fluorescente , Patologia Forense , Expresión Génica , Sustancias de Crecimiento/metabolismo , Hidroxiprolina/metabolismo , Inmunohistoquímica , Pulmón/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/metabolismoRESUMEN
We previously reported the importance of connective tissue growth factor (CTGF) in rheumatoid arthritis (RA). CTGF contains four distinct modules connected in tandem, namely insulin-like growth factor-binding protein (IGFBP)-like, von Willebrand factor (vWF) type C repeat, thrombospondin type 1 (TSP-1) repeat, and carboxyl-terminal (CT) modules. The relationships between each of these modules of CTGF and RA remain unknown. Here, we analyzed how inhibition of each CTGF module affects the pathophysiology of RA. We conducted stimulation and suppression experiments on synovial cells (MH7A) obtained from patients with RA. Moreover, we examined angiogenesis by means of a tube-formation assay performed using human umbilical vein endothelial cells (HUVECs), and we used tartrate-resistant acid phosphatase (TRAP) staining to analyze osteoclastogenesis. Our results showed that M-CSF/RANKL-mediated osteoclastogenesis was enhanced when CTGF was added, but the effect of CTGF was neutralized by mAbs against CTGF modules 1-4. Furthermore, CTGF treatment of HUVECs induced formation of tubular networks, which resulted in acceleration of the angiogenesis of RA synoviocytes, and quantification showed that this tubular-network formation was also disrupted by anti-CTGF module 1-4 mAbs. Lastly, TNF-α enhanced the expression of CTGF and matrix metalloproteinase-3 (MMP3) in MH7A cells, and this enhancement was potently neutralized by mAbs against CTGF modules 1, 3 and 4. Thus, our results indicate that not only a mAb against CTGF but also mAbs against each specific module of CTGF might serve as potential therapeutic agents in the treatment of RA.
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Artritis Reumatoide/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/antagonistas & inhibidores , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Anticuerpos Monoclonales/farmacología , Artritis Reumatoide/tratamiento farmacológico , Resorción Ósea/metabolismo , Línea Celular , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/química , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Factor Estimulante de Colonias de Macrófagos/farmacología , Metaloproteinasa 3 de la Matriz/metabolismo , Terapia Molecular Dirigida , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ligando RANK/farmacología , Membrana Sinovial/citología , Membrana Sinovial/metabolismoRESUMEN
We report a case of fatal water intoxication due to polydipsia. A 69-year-old schizophrenic male was found dead at his room of the hospital in which he had been admitted. Medico-legal autopsy was carried out to determine the cause of his death. The autopsy revealed no severe trauma leading him to the death. Internally, it was noticed that the stomach was vigorously expanded, including fluid contents. Intracardiac blood, being dark-red in color, seemed to be diluted. The both lungs ballooned aqueously, showing apparently edema. However, there was neither macroscopic nor histopathological lesion, being responsible for his death. Postmortem biochemical analyses revealed severe hyponatremia of 92 mEq/ml. In cases with short postmortem interval, serum sodium level almost similarly reflected antemortem level. According to his psychiatric doctor, he had been diagnosed as water intoxication due to polydipsia. Moreover, at 2 h before the discovery of his body, he had been found to drink much running water. It was concluded the cause of his death as fatal water intoxication.
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Psicología del Esquizofrénico , Intoxicación por Agua/patología , Intoxicación por Agua/psicología , Anciano , Fenómenos Fisiológicos Sanguíneos , Duodeno/patología , Resultado Fatal , Medicina Legal , Humanos , Hiponatremia/diagnóstico , Intestino Delgado/patología , Pulmón/patología , Masculino , Estómago/patologíaRESUMEN
OBJECTIVE: We have shown that connective tissue growth factor (CTGF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Insulin-like growth factor binding proteins (IGFBPs) are modules of CTGF. IGFBPs bind IGF-I and IGF-II. IGF-I plays a role in the regulation of immunity, bone metabolism and inflammation. Therefore, we investigated how the IGF system is associated with RA disease progression. METHODS: Serum samples were collected from RA patients. IGF-I and IGFBP-3 production were evaluated by enzyme-linked immunosorbent assay, real-time RT-PCR and indirect immunofluorescence microscopy. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay and osteoclast-specific enzyme production. Angiogenesis was examined by a tube formation assay using human umbilical vein endothelial cells. RESULTS: The serum concentrations of IGFBP-3 in RA patients were greater than those in normal controls. IGF-I and IGFBP-3 were produced primarily by macrophages in the RA synovium. Furthermore, tumor necrosis factor-α could induce aberrant IGF-I and IGFBP-3 production in synovial fibroblasts. IGF-I and IGFBP-3 promoted the induction of osteoclast generation and morphological changes, in combination with M-colony stimulating factor and the receptor activator of NF-κB ligand. In addition, IGF-I and IGFBP-3 induced angiogenesis, as determined by the tube formation assay. These effects were neutralized by anti-IGF-IR monoclonal antibody (mAb). CONCLUSIONS: These results indicate that aberrant IGF-I and IGFBP-3 production plays a role in abnormal osteoclastic activation and angiogenesis in RA. This work supports future clinical exploration of anti-IGF-IR mAb in drug repositioning as a new treatment for RA.
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Artritis Reumatoide/metabolismo , Somatomedinas/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales/farmacología , Artritis Reumatoide/sangre , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Proteína C-Reactiva/metabolismo , Línea Celular , Progresión de la Enfermedad , Femenino , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Osteoclastos/metabolismo , Ligando RANK/metabolismo , Receptor IGF Tipo 1 , Receptores de Somatomedina/antagonistas & inhibidores , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismoRESUMEN
Localization and ultrastructural features of immunoreactive fibers and terminals against RT-97, a mouse monoclonal antibody that recognizes subunit of a 200-kD neurofilament, were examined in the spinal dorsal horn of adult rats. Under a light-microscope, many RT-97 immunoreactive fibers were detected in the dorsal root, collaterals of the dorsal root in the dorsal funiculus, and laminae III and IV in the dorsal horn. Few immunoreactive fibers were found in laminae I and II. Electron microscopic observation demonstrated that almost all RT-97 immunoreactive fibers in the dorsal root were myelinated, and unmyelinated fibers immunonegative. The immunoreactive fibers entered into the dorsal horn passing through the collaterals of the dorsal root along the superficial gray lamina. In the dorsal horn, these fibers ascended into and then terminated in lamina II. RT-97 immunoreactive central terminals were semicircular or ellipsoid in appearance and contained many flat-type presynaptic vesicles. Some terminals made synaptic contact with dendritic profiles in lamina II. Our present results indicate that RT-97 is a useful marker for ultrastructural examination of terminals served by non-nociceptive A-fibers.
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Anticuerpos Monoclonales , Proteínas de Neurofilamentos/inmunología , Proteínas de Neurofilamentos/metabolismo , Células del Asta Posterior/metabolismo , Células del Asta Posterior/ultraestructura , Animales , Inmunohistoquímica , Masculino , Ratones , Microscopía Inmunoelectrónica , Fibras Nerviosas/inmunología , Fibras Nerviosas/metabolismo , Fibras Nerviosas/ultraestructura , Células del Asta Posterior/inmunología , Terminales Presinápticos/inmunología , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Ratas , Ratas WistarRESUMEN
A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.
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Agammaglobulinemia/complicaciones , Infecciones por Campylobacter/etiología , Campylobacter fetus , Huésped Inmunocomprometido , Pleuresia/etiología , Bacteriemia/etiología , Campylobacter fetus/aislamiento & purificación , Empiema Pleural/etiología , Humanos , Inmunización Pasiva , Pulmón/diagnóstico por imagen , Masculino , Meropenem , Derrame Pleural/microbiología , Pleuresia/diagnóstico por imagen , Radiografía , Tienamicinas/uso terapéutico , Adulto JovenRESUMEN
A 23-year-old woman was admitted with complaints of swelling and pain in the left breast, fever, polyarthralgia and erythema nodosum. A fine-needle biopsy of the mass in the left breast revealed non-caseous granulomatous lobulitis. A diagnosis of granulomatous mastitis was thus made. The administration of prednisolone 40 mg/day resulted in the resolution of the patient's symptoms, and the breast mass thereafter decreased in size. The mass relapsed during the subsequent prednisolone taper. Additional therapy with methotrexate resulted in complete remission. Granulomatous mastitis should therefore be included in the differential diagnosis of polyarthralgia.
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Artralgia/tratamiento farmacológico , Eritema Nudoso/tratamiento farmacológico , Mastitis Granulomatosa/tratamiento farmacológico , Metotrexato/administración & dosificación , Prednisolona/administración & dosificación , Artralgia/complicaciones , Artralgia/diagnóstico , Diagnóstico Diferencial , Quimioterapia Combinada , Eritema Nudoso/complicaciones , Eritema Nudoso/diagnóstico , Femenino , Mastitis Granulomatosa/complicaciones , Mastitis Granulomatosa/diagnóstico , Humanos , Resultado del Tratamiento , Adulto JovenRESUMEN
A 47-year-old man with Cushingoid appearance was admitted to our hospital showing excessive secretion of cortisol at intervals of a few days. Cyclic Cushing's disease was confirmed. Two years earlier, results of hormonal assessment had been within normal limits and macroadenoma had been incidentally detected in the pituitary. Dexamethasone suppression testing revealed various responses and a small lung tumor was detected, therefore his condition was misinterpreted as ectopic ACTH-producing tumor or pituitary cyclical Cushing's disease, leading to lung resection that confirmed cryptococcal pneumonia. The pituitary tumor was finally identified as the cause of cyclic Cushing's syndrome and fully removed, allowing remission.
Asunto(s)
Síndrome de ACTH Ectópico/diagnóstico , Criptococosis/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Neumonía Bacteriana/diagnóstico , Síndrome de ACTH Ectópico/complicaciones , Criptococosis/complicaciones , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Neoplasias Hipofisarias/complicaciones , Neumonía Bacteriana/complicacionesRESUMEN
A 54-year-old woman with a past history of silicone augmentation mammoplasty was admitted with fever and dyspnea with diffuse interstitial shadows on computed tomography (CT). Although radiological findings were atypical, we diagnosed sarcoidosis by laboratory, microbiological, and bronchoalveolar lavage fluid analysis. Corticosteroids ameliorated the condition, but she had recurrent of fever and CT revealed miliary nodules while interstitial shadows disappeared. Liver biopsy showed that noncaseating granuloma and Ziehl-Neelsen stain was positive. We diagnosed miliary tuberculosis which developed during corticosteroid therapy. Antituberculotic therapy resulted in favorable outcome. Possibility exists that onset of sarcoidosis was induced by mammoplasty, namely, human adjuvant disease.
RESUMEN
A 26-year-old man was hospitalized with a 1-month history of fever. Cervical lymph node biopsy showed necrosis in the paracortical area with abundant nuclear debris and proliferation of histiocytes. A diagnosis of histiocytic necrotizing lymphadenitis (HNL) (Kikuchi's disease) was made. He received methylprednisolone pulse therapy (MPT) (0.5 g/day for 3 days) without maintenance therapy and experienced dramatic improvement. We also used MPT for another 12 cases of HNL. All patients became afebrile within 1 day without adverse events. Four patients relapsed after the initial MPT, but only 1 patient relapsed during the following year. Our results suggest that MPT is warranted in HNL patients with prolonged fever.