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1.
NMC Case Rep J ; 11: 169-174, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974118

RESUMO

We report a male patient with a ruptured persistent primitive trigeminal artery variant aneurysm that resulted in a fistula with the cavernous sinus. He presented with left conjunctival hyperemia and exophthalmos. Cerebral angiography revealed a left direct carotid-cavernous fistula; however, a balloon occlusion test determined that the source was actually a ruptured aneurysm located on the trunk of a persistent primitive trigeminal artery. Endovascular trapping of the persistent primitive trigeminal artery was performed, which resulted in fistula occlusion and symptom resolution.

2.
J Immunol ; 212(12): 1891-1903, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38683146

RESUMO

Foxp3+ T regulatory (Treg) cells prevent allograft rejection and graft-versus-host disease. Although polyclonal Tregs have been used both in animal models and in humans, the fine specificity of their suppressive function is poorly defined. We have generated mouse recipient-derived alloantigen-specific Tregs in vitro and explored the fine specificity of their suppressive function and their mechanism of action in vitro and in vivo. In vitro, when alloantigen and peptide Ag were both presented on the same dendritic cell, both responses were suppressed by iTregs specific either for the alloantigen or for the peptide Ag. In vivo, iTreg suppression was limited to the cognate Ag, and no bystander suppression was observed when both allo-antigen and peptide Ag were present on the same dendritic cell. In vitro, alloantigen-specific Tregs captured cognate MHC but failed to capture noncognate MHC. Our results demonstrate that a polyclonal population of iTregs generated from naive T cells can mediate highly specific function in vivo and support the view that Treg therapy, even with unselected polyclonal populations, is likely to be target antigen-specific and that bystander responses to self-antigens or to infectious agents are unlikely.


Assuntos
Células Dendríticas , Antígenos de Histocompatibilidade Classe II , Isoantígenos , Linfócitos T Reguladores , Animais , Camundongos , Linfócitos T Reguladores/imunologia , Células Dendríticas/imunologia , Isoantígenos/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C , Apresentação de Antígeno/imunologia , Camundongos Transgênicos
3.
J Control Release ; 369: 283-295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522816

RESUMO

Pancreatic cancer is characterized by a densely fibrotic stroma. The fibrotic stroma hinders the intratumoral penetration of nanomedicine and diminishes therapeutic efficacy. Fibrosis is characterized by an abnormal organization of extracellular matrix (ECM) components, namely the abnormal deposition and/or orientation of collagen and fibronectin. Abnormal ECM organization is chiefly driven by pathological signaling in pancreatic stellate cells (PSCs), the main cell type involved in fibrogenesis. However, whether targeting signaling pathways involved in abnormal ECM organization improves the intratumoral penetration of nanomedicines is unknown. Here, we show that targeting transforming growth factor-ß (TGFß)/Rho-associated kinase (ROCK) 1/2 signaling in PSCs normalizes ECM organization and concomitantly improves macromolecular permeability of the fibrotic stroma. Using a 3-dimensional cell culture model of the fibrotic pancreatic cancer microenvironment, we found that pharmacological inhibition of TGFß or ROCK1/2 improves the permeation of various macromolecules. By using an isoform-specific pharmacological inhibitor and siRNAs, we show that targeting ROCK2, but not ROCK1, alone is sufficient to normalize ECM organization and improve macromolecular permeability. Moreover, we found that ROCK2 inhibition/knockdown attenuates Yes-associated protein (YAP) nuclear localization in fibroblasts co-cultured with pancreatic cancer cells in 3D. Finally, pharmacological inhibition or siRNA-mediated knockdown of YAP normalized ECM organization and improved macromolecular permeability. Our results together suggest that the TGFß/ROCK2/YAP signaling axis may be therapeutically targeted to normalize ECM organization and improve macromolecular permeability to augment therapeutic efficacy of nanomedicines in pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Células Estreladas do Pâncreas , Permeabilidade , Fator de Crescimento Transformador beta , Microambiente Tumoral , Quinases Associadas a rho , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Humanos , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/patologia , Fator de Crescimento Transformador beta/metabolismo , Fibrose , Matriz Extracelular/metabolismo , Proteínas de Sinalização YAP/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
4.
Int J Radiat Biol ; 100(1): 131-138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37555698

RESUMO

PURPOSE: Zebrafish, a small fish model, exhibits a multipotent ability for retinal regeneration after damage throughout its lifetime. Compared with zebrafish, birds and mammals exhibit such a regenerative capacity only during the embryonic period, and this capacity decreases with age. In medaka, another small fish model that has also been used extensively in biological research, the retina's inner nuclear layer (INL) failed to regenerate after injury in the hatchling at eight days postfertilization (dpf). We characterized the regenerative process of the embryonic retina when the retinal injury occurred during the early embryonic period in medaka. METHODS: We employed a 10 Gy dose of gamma-ray irradiation to initiate retinal injury in medaka embryos at 3 dpf and performed histopathological analyses up to 21 dpf. RESULTS: One day after irradiation, numerous apoptotic neurons were observed in the INL; however, these neurons were rarely observed in the ciliary marginal zone and the photoreceptor layer. Numerous pyknotic cells were clustered in the irradiated retina until two days after irradiation. These disappeared four days after irradiation, but the abnormal bridging structures between the INL and ganglion cell layer (GCL) were present until 11 days after irradiation, and the neural layers were completely regenerated 18 days after irradiation. After gamma-ray irradiation, the spindle-like Müller glial cells in the INL became rounder but did not lose their ability to express SOX2. CONCLUSIONS: Irradiated retina at 3 dpf of medaka embryos could be completely regenerated at 18 days after irradiation (21 dpf), although the abnormal layer structures bridging the INL and GCL were transiently formed in the retinas of all the irradiated embryos. Four days after irradiation, embryonic medaka Müller glia were reduced in number but maintained SOX2 expression as in nonirradiated embryos. This finding contrasts with previous reports that 8 dpf medaka larvae could not fully regenerate damaged retinas because of loss of SOX2 expression.


Assuntos
Oryzias , Animais , Peixe-Zebra , Retina/lesões , Retina/patologia , Neuroglia , Desenvolvimento Embrionário , Mamíferos
5.
Neurol Med Chir (Tokyo) ; 63(6): 258-263, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37005245

RESUMO

Horizontal stenting protects the aneurysm neck with stent deployment across the aneurysm neck via the circle of Willis. A saccular aneurysm associated with intracranial arterial fenestration is very rare. Herein, we describe the first case of an unruptured aneurysm related to intracranial arterial fenestration treated with horizontal stenting. A 23-year-old woman presented with a 7-mm broad-necked aneurysm at the fenestration of the right intracranial vertebral artery (VA), which was incidentally found on magnetic resonance imaging. The patient underwent endovascular treatment with horizontal stenting via the vertebrobasilar junction from the contralateral left VA, followed by coil embolization using a jailed microcatheter from the ipsilateral right VA. The procedure was finished with sufficient embolization, and no complications occurred. Horizontal stent delivery via the vertebrobasilar junction for coil embolization of a broad-necked aneurysm arising from the fenestration of the VA is a safe and effective therapeutic strategy.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Feminino , Humanos , Adulto Jovem , Adulto , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgia , Resultado do Tratamento , Angiografia Cerebral/métodos , Stents , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Embolização Terapêutica/métodos
6.
Cancers (Basel) ; 15(3)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36765684

RESUMO

Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10-200 nm) selectively accumulate in tumors. Nanomedicine has thus been suggested to be the "magic bullet"-both effective and safe-to treat pancreatic cancer. However, the densely fibrotic tumor microenvironment of pancreatic cancer impedes nanomedicine delivery. The EPR effect is thus insufficient to achieve a significant therapeutic effect. Intratumoral fibrosis is chiefly driven by aberrantly activated fibroblasts and the extracellular matrix (ECM) components secreted. Fibroblast and ECM abnormalities offer various potential targets for therapeutic intervention. In this review, we detail the diverse strategies being tested to overcome the fibrotic barriers to nanomedicine in pancreatic cancer. Strategies that target the fibrotic tissue/process are discussed first, which are followed by strategies to optimize nanomedicine design. We provide an overview of how a deeper understanding, increasingly at single-cell resolution, of fibroblast biology is revealing the complex role of the fibrotic stroma in pancreatic cancer pathogenesis and consider the therapeutic implications. Finally, we discuss critical gaps in our understanding and how we might better formulate strategies to successfully overcome the fibrotic barriers in pancreatic cancer.

7.
Gynecol Oncol Rep ; 44(Suppl 1): 101108, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36506037

RESUMO

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

8.
Gynecol Oncol Rep ; 44: 101120, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36589509

RESUMO

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

9.
J Med Case Rep ; 15(1): 482, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556154

RESUMO

BACKGROUND: Tubulointerstitial nephritis and uveitis syndrome is a rare lymphocyte-related oculorenal inflammatory disease presumed to be associated with drug use and infectious agents. Toxoplasma gondii is one of such pathogens that could exhibit encephalitis, meningitis, and uveitis in immunocompromised or in some immunocompetent individuals. If the immunoglobulin M of Toxoplasma is positive on screening, the interpretation of the result is not simple, especially when immunoglobulin M stays positive persistently. CASE PRESENTATION: A 34-year-old Asian male developed fever, headache, and lymphadenopathy with tenderness, which was initially diagnosed as meningitis. Antibiotics were started, and diclofenac sodium was used for the fever. Although his symptoms were alleviated in a week by the treatment, gradual decline in renal function was noted, prompting a renal biopsy that indicated acute granulomatous interstitial nephritis. A week later, tenderness in both eyes with blurred vision appeared and revealed iritis and keratic precipitations in both eyes; hence, the diagnosis of acute tubulointerstitial nephritis and bilateral uveitis syndrome was made. Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M titers were both positive. Although we could not rule out recent infection of Toxoplasma gondii, which may cause uveitis initially, Toxoplasma immunoglobulin G avidity test indicated a distant infection, which allowed us to rule out meningitis and uveitis as responsible for the complication of recent Toxoplasma gondii infection. Drug-induced lymphocyte stimulation test, or lymphocyte transformation test of diclofenac sodium, was solely positive among the tested drugs. Uveitis was alleviated only with ophthalmic steroid, and renal function returned to normal without administration of systemic steroid. CONCLUSIONS: We experienced a case of diclofenac-induced tubulointerstitial nephritis and uveitis syndrome. In ruling out infections, Toxoplasma immunoglobulin M was persistently positive, and Toxoplasma immunoglobulin G avidity test indicated a "distant" infection. From these two results, we ruled out recent infection. However, it should be noted that "distant" infection indicated by commercial immunoglobulin G avidity is still a multiplex profile consisting of reinfection, reactivation, and latent infection. Narrowing down the infection profile of Toxoplasma is challenging in some cases. Therefore, careful diagnosis and extended follow-up of such patients are needed.


Assuntos
Linfadenopatia , Meningite , Nefrite Intersticial , Toxoplasma , Uveíte , Adulto , Humanos , Imunoglobulina M , Masculino , Meningite/diagnóstico , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
10.
J Neuroendovasc Ther ; 15(4): 240-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37501693

RESUMO

Objective: Rupture of intracranial aneurysms after tissue plasminogen activator (t-PA) administration for acute ischemic stroke with an unruptured cerebral aneurysm is rare. We report a case of ruptured cerebral aneurysm after t-PA administration. Case Presentation: A 74-year-old woman with dysarthria and left hemiparesis was admitted to our hospital, and acute lacunar infarction was found in the right corona radiata. One hour after t-PA administration, she complained of sudden headache and nausea, and her consciousness level deteriorated. Subarachnoid hemorrhage due to rupture of the anterior communicating aneurysm was confirmed and coil embolization was performed. Conclusion: T-PA administration for acute ischemic stroke with an unruptured cerebral aneurysm risks rupture of the cerebral aneurysm, and careful judgment is needed in each case.

11.
J Neuroendovasc Ther ; 15(7): 438-443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37502789

RESUMO

Objective: We report a rare complication, carotid cavernous fistula (CCF), due to vessel perforation during thrombectomy for acute ischemic stroke (AIS). Case Presentation: An 88-year-old woman underwent thrombectomy for left C4 occlusion of the internal carotid artery. There was strong resistance at the medial C4 while the microguidewire was guided distally, and a CCF was found after deploying and retrieving the stent. It was thought to have been caused by perforation due to intracranial atherosclerotic stenosis of the internal carotid artery. Conclusion: During thrombectomy for intracranial large vessel occlusion underlying intracranial atherosclerotic stenosis, the risk of vascular injury should be kept in mind.

12.
Biomaterials ; 251: 120077, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32388166

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted.

13.
J Infect Chemother ; 24(2): 110-116, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29054459

RESUMO

Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune suppressive drugs are prescribed. RA patients receiving treatments are in a kind of immunosuppressive condition that presents increased risk of developing active tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is recommended for RA. QuantiFERON®-TB Gold Plus (QFT-Plus), a novel IGRA, has two tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses, with expected increased sensitivity. We conducted a cross-sectional study to compare two IGRAs, QFT-Plus and T-SPOT®.TB (TSPOT), in RA. One hundred fifty-two RA patients (median age: 66.5 yrs) were enrolled. QFT-Plus and TSPOT were concurrently conducted. Lymphocyte subsets (CD4 T-cell and CD8 T-cell) were also measured. The positivity rates of QFT-Plus and TSPOT were 9.7% and 4.5%, respectively, with the difference being significant (P < 0.01). The positivity rates in TB1 and TB2 were 9.1% and 7.1%, respectively; the difference was not significant (P = 0.18). Patients with CD4 T-cell ≥650/µL and CD8 T-cell ≥400/µL had significantly higher positivity rates in both QFT-Plus and TSPOT in comparison with other groups (P < 0.01 and P < 0.05, respectively). QFT-plus demonstrated a higher positivity rate than TSPOT. However, there was little additional effect for detecting LTBI by TB2. Lymphocyte subsets were strongly associated with immune response in both QFT-Plus and TSPOT. LTBI should not be ruled out even with a negative IGRA result in patients with CD4 T-cell <650/µL or CD8 T-cell <400/µL.


Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Contagem de Células , Estudos Transversais , Feminino , Humanos , Imunossupressores/uso terapêutico , Tuberculose Latente/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia
14.
Neuroradiol J ; 30(6): 600-606, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29171364

RESUMO

Objectives The aim of this study was to examine the feasibility, technique, and clinical and angiographic outcomes of endovascular coiling to treat a cerebral aneurysm with a branch incorporated into the aneurysmal wall. Methods From 2012 to 2016, 25 patients with 26 cerebral aneurysms having a branch incorporated into the aneurysm (9 unruptured, 17 ruptured) were treated to prevent rupture or re-bleeding from the sac while preserving the incorporated branch by using single-catheter ( n = 18), balloon-remodeling ( n = 4), stent-assisted coiling ( n = 3), or double-catheter ( n = 1) techniques. Results Endovascular coiling was conducted in 26 procedures without angiographic occlusion of the incorporated branch. Post-embolization angiography revealed near-complete occlusion ( n = 8; 30.7%), neck remnant ( n = 13; 50%), and incomplete occlusion ( n = 5; 19.3%) aneurysms. Thromboembolisms were observed in four (15.4%) patients during or after the procedure. A procedure-related neurological deficit was observed in one (3.8%) patient. When patients with a preictal modified Rankin Scale (mRS) score of 3 presenting with grade 5 subarachnoid hemorrhage were excluded, all patients had favorable outcomes (mRS 0-2). Six (23.1%) recurrent aneurysms were observed during follow-up, five of which were treated endovascularly at 5-22 months without complication. The location of an aneurysm at the ICA-posterior communicating artery associated with the dominant-type posterior communicating artery was significantly associated with recurrence ( p = 0.041). Conclusions Cerebral aneurysms with an incorporated branch were safely treated using conventional endovascular coiling. However, treatment durability was unsatisfactory, especially for dominant-type ICA-posterior communicating artery aneurysms.


Assuntos
Embolização Terapêutica/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do Tratamento
15.
PLoS One ; 11(11): e0166616, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27851825

RESUMO

BACKGROUND AND OBJECTIVES: Although morning stiffness has long been recognized as a characteristic feature of rheumatoid arthritis (RA), it is no more included in the 2010 ACR/EULAR Classification Criteria or in the current major instruments for evaluating disease activity of RA. In this cross-sectional study, we aimed to determine the independent value and the optimal measurement of morning stiffness by clarifying the associations between morning stiffness and synovial inflammation. PATIENTS AND METHODS: We enrolled 76 consecutive RA patients who underwent musculoskeletal ultrasound examination and agreed to participate in the study. In addition to asking the duration of morning stiffness, we asked patients to complete a diagram which represents the time course of their morning stiffness in the dominant hand. Based on this diagram, we calculated the severity and the diurnal improvement of morning stiffness. We also determined the activity of intra-articular synovitis in 11 joints and tenosynovitis in 8 tendons/tendon compartments in the same hand by using power Doppler (PD) ultrasound with a semiquantitative score (0-3). RESULTS: For intra-articular synovitis, swollen/tender joint counts more strongly correlated with total PD scores (ρ = 0.379-0.561, p ≤ 0.001) than did any parameters of morning stiffness (ρ = 0.217-0.314, p = 0.006-0.021). For tenosynovitis, however, the severity on awakening and the improvement of morning stiffness more strongly correlated with total PD scores (ρ = 0.503-0.561, p < 0.001) than did swollen/tender joint counts (ρ = 0.276-0.388, p = 0.001-0.016). Multivariate analyses identified the severity on awakening and the improvement but not the duration of morning stiffness as factors that independently associate with the total tenosynovial PD score. CONCLUSIONS: Our data demonstrate a pathophysiological link between morning stiffness and tenosynovitis and also give an insight into the optimal measurement of morning stiffness. Our data support an independent value of evaluating morning stiffness in the management of RA.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Ritmo Circadiano , Tenossinovite/complicações , Tenossinovite/fisiopatologia , Artrite Reumatoide/diagnóstico por imagem , Fenômenos Biomecânicos , Feminino , Mãos/diagnóstico por imagem , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tenossinovite/diagnóstico por imagem , Ultrassonografia Doppler
17.
Allergol Int ; 65(1): 44-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26666495

RESUMO

BACKGROUND: Patients with house dust mite (HDM) allergy or Ascariasis produce serum IgE specific to the antigens of HDM or nematode Ascaris, respectively. Although human IgE cross-reactivity has been reported between HDM and Ascaris antigens, it remains unclear whether it contributes to the pathogenesis of allergic diseases. We herein investigated the induction of cross-reactive antibodies and T cells in mice and effects of airway exposure to HDM antigens after preimmunization with Ascaris antigens. METHODS: Mice were intraperitoneally immunized with HDM or Ascaris antigens with Alum, followed by the intranasal administration of HDM antigens. Serum antigen-specific IgE and IgG were measured by ELISA. Cytokine release in splenocytes from Ascaris-immunized mice upon in vitro restimulation with HDM antigens were measured by ELISA. RESULTS: Immunization with Ascaris or HDM antigens induced cross-reactive IgG1. Splenocytes from Ascaris-immunized mice released IL-5 and IL-13 in response to the restimulation with HDM antigens. Subsequent airway exposure to HDM antigens promoted the induction of HDM-specific IgE and upregulation of HDM-specific IgG1 in Ascaris-immunized mice, whereas these responses were not detected or smaller without the Ascaris presensitization. CONCLUSIONS: We demonstrated that the immunization of naïve mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris.


Assuntos
Antígenos de Dermatophagoides/imunologia , Antígenos de Helmintos/imunologia , Ascaris/imunologia , Hipersensibilidade/imunologia , Imunização , Imunoglobulina E/imunologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Baço/citologia , Baço/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/imunologia
18.
PLoS One ; 10(6): e0131822, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26120840

RESUMO

PURPOSE: Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach. METHOD: A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis. RESULTS: The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments. CONCLUSION: Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.


Assuntos
Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Interpretação de Imagem Radiográfica Assistida por Computador , Humanos , Masculino , Tamanho do Órgão , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem
20.
Biosci Biotechnol Biochem ; 77(1): 145-50, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23291773

RESUMO

There are controversial reports on the relationship between helminthic infection and allergic diseases. Although IgE cross-reactivity between nematode Ascaris antigens and house dust-mite allergens in allergic patients have been reported, whether Ascaris or the mite is the primary sensitizer remains unknown. Here we found that immunization of naïve animals with Ascaris lumbricoides (Al) antigens induced production of antibodies cross-reactive to mite antigens from Dermatophagoides farinae (Df). Sera from Bangladeshi children showed IgE reactivity to Ascaris and mite extracts. IgG from rabbits immunized with Al extract exhibited reactivity to Df antigens. Treatment of the anti-Al antibody with Df antigen-coupled beads eliminated the reactivity to Df antigens. In immunoblot analysis, an approximately 100-kDa Df band was the most reactive to anti-Al IgG. The present study is the first step towards the establishment of animal models to study the relationship between Ascaris infection and mite-induced allergic diseases.


Assuntos
Alérgenos/imunologia , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Dermatophagoides/imunologia , Antígenos de Helmintos/imunologia , Ascaris lumbricoides/imunologia , Dermatophagoides farinae/imunologia , Hipersensibilidade/prevenção & controle , Animais , Anticorpos Anti-Helmínticos/biossíntese , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/administração & dosagem , Ascaris lumbricoides/química , Reações Cruzadas , Dermatophagoides farinae/química , Hipersensibilidade/imunologia , Imunização , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Coelhos
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