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1.
Ann Hematol ; 103(1): 89-96, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37962621

RESUMO

Thrombopoietin (THPO) is an essential factor for platelet production. Hereditary thrombocythemia (HT) is caused by a germline mutation of THPO, MPL, or JAK2 and is inherited in an autosomal-dominant manner. We identified a Japanese family with HT due to a point mutation of the splicing donor site of the THPO gene (THPO c.13 + 1G > A). Bone marrow biopsy showed increased megakaryocytes mimicking essential thrombocythemia. One affected family member developed chronic myeloid leukemia. We cloned the mutation and developed mutated and wild type THPO expression vectors. Molecular analysis showed that the mutation causes an exon 3 skipping transcript of THPO that abrogates a suppressive untranslated upstream open reading frame. Although the transcript levels of THPO mRNA were comparable, mutated transcripts were more efficiently translated and THPO protein expression was significantly higher than that of the wild type.


Assuntos
Trombocitose , Trombopoetina , Humanos , Japão , Mutação , Trombocitose/genética , Trombopoetina/genética
2.
Acta Neurochir (Wien) ; 166(1): 263, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864949

RESUMO

BACKGROUND: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. METHODS: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. RESULTS: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. CONCLUSION: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Isocitrato Desidrogenase , Mutação , Humanos , Isocitrato Desidrogenase/genética , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Masculino , Glioma/genética , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/terapia , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Prognóstico , Imageamento por Ressonância Magnética , Adulto Jovem
3.
Support Care Cancer ; 31(3): 168, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36781507

RESUMO

PURPOSE: To identify the factors associated with employment status among mothers of childhood cancer survivors (CCSs). METHODS: We conducted a questionnaire survey on mothers of survivors of childhood cancer to clarify practical factors such as care demands, psychological factors such as motivation to work, and support. After calculating descriptive statistics for all variables, binary logistic regression analysis was performed. RESULTS: Of 171 mothers, 129 (75.4%) were employed. The most common form of employment was non-regular (n = 83; 48.5%), including part-time, dispatched, and fixed-term workers. At the time of the survey, compared with nonworking mothers, working mothers tended to be more motivated to work and have lower scores for "Long-term Uncertainty" on the Parent Experience of Child Illness Scale. The results of the binary logistic regression analysis indicated that employment was related to higher motivation to work, the continuation of employment during treatment, more outpatient visits, and a higher amount of support. CONCLUSION: As employment of CCSs' mothers is associated with psychological factors such as motivation to work and long-term uncertainty, psychological support for CCSs' mothers might promote employment. In addition, because the continuation of employment during treatment affects the employment of mothers after the end of cancer treatment, a leave system that covers the treatment period for childhood cancer needs to be established.


Assuntos
Sobreviventes de Câncer , Neoplasias , Feminino , Humanos , Criança , Neoplasias/terapia , Neoplasias/psicologia , Sobreviventes de Câncer/psicologia , Estudos Transversais , Emprego , Mães/psicologia
4.
Neuropathology ; 43(5): 413-420, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36942363

RESUMO

Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Encondromatose , Glioma , Oligodendroglioma , Feminino , Humanos , Adulto Jovem , Adulto , Oligodendroglioma/genética , Oligodendroglioma/patologia , Encondromatose/complicações , Encondromatose/genética , Encondromatose/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Hibridização in Situ Fluorescente , Isocitrato Desidrogenase/genética , Glioma/genética , Astrocitoma/genética , Astrocitoma/patologia , Mutação
5.
Brain ; 144(8): 2401-2415, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-33711152

RESUMO

Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.


Assuntos
Astrócitos/patologia , Encéfalo/patologia , Ativação do Complemento/fisiologia , Neuromielite Óptica/patologia , Idoso , Aquaporina 4/imunologia , Astrócitos/imunologia , Autoanticorpos , Encéfalo/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/imunologia
6.
Neuroradiology ; 64(2): 393-396, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34812918

RESUMO

The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.


Assuntos
Neoplasias Meníngeas , Meningioma , Neurofibromatose 2 , Humanos , Imageamento por Ressonância Magnética , Meningioma/diagnóstico por imagem , Neurofibromatose 2/diagnóstico por imagem , Estudos Retrospectivos
7.
Int Immunol ; 32(5): 335-346, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31930291

RESUMO

Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection.


Assuntos
Rejeição de Enxerto/imunologia , Nefropatias/imunologia , Transplante de Rim/efeitos adversos , Orosomucoide/metabolismo , Animais , Biomarcadores/análise , Linhagem Celular , Doença Crônica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Nefropatias/diagnóstico , Nefropatias/terapia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Orosomucoide/análise , Orosomucoide/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Transplante Homólogo/efeitos adversos
8.
Pathol Int ; 71(6): 420-426, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33792098

RESUMO

Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.


Assuntos
Neoplasias do Colo , Infecções por Vírus Epstein-Barr/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Colo/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , RNA Viral/análise , Receptor EphA2/análise
9.
Neuropathology ; 41(3): 236-242, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33899270

RESUMO

The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case.


Assuntos
Neoplasias Encefálicas/genética , Mutação , Recidiva Local de Neoplasia/genética , Oligodendroglioma/genética , Regiões Promotoras Genéticas , Telomerase/genética , Adulto , Neoplasias Encefálicas/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Oligodendroglioma/patologia , Oligodendroglioma/cirurgia
10.
Adv Exp Med Biol ; 1155: 313-321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468410

RESUMO

This study surveyed that the relationship between the frequencies of intake of taurine-contained nutritional drinks (TCND), and lifestyle and the purposes of intake it. The study was conducted a cross-sectional survey using 265 people (203 male, 62 female) aged 18-64 worked in two companies in Mie Prefecture, Japan between December 2017 and February 2018. The questionnaires gathered characteristics, demographic, socioeconomic, lifestyle habits and purpose of TCND intake. We divided the frequency of intake of TCND of at least a few times every month as the high-frequency TCND (HF-TCND) group, and the remaining as the low-frequency TCND (LF-TCND) group. Multivariate logistic regression analysis was used to investigate the relationship between characteristics, demographic, socioeconomic, lifestyle habits and purpose of TCND intake and HF-TCND after controlling for individual variables. Of all participants, 13.4% was evaluated as HT-CND. 16.3% for male or 4.3% for female were evaluated as HF-TCND (p < 0.05). The most reason for frequent choosing a TCND was fatigue recovery. Logistic regression analysis showed that sex, occupation, purpose of TCND intake and stressful are related to HF-TCND. Our study indicates that purpose of TCND intake, such as fatigue recovery and reducing stress, may partly affect the frequency of intake of TCND. Therefore, we must continue to show scientific evidence for taurine by enlightenment activity etc.


Assuntos
Alimentos Fortificados , Estilo de Vida , Taurina/administração & dosagem , Adolescente , Adulto , Bebidas , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
11.
Radiographics ; 38(7): 1934-1948, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30289734

RESUMO

Immunoglobulin G4 (IgG4)-related disease can affect the cardiovascular system, including the coronary arteries and pericardium and especially the walls of large and medium-sized vessels. The presence of coronary involvement is critical, as this condition can cause myocardial ischemia or sudden cardiac death. Although histopathologic examination remains the reference standard for detecting organ involvement and diagnosing IgG4-related disease, obtaining biopsy or surgical specimens from the vessel wall is still challenging. Because patients may be only mildly symptomatic, noninvasive imaging evaluation of IgG4-related cardiovascular disease (CVD) has an essential role in not only the diagnosis but also the management of this condition. Multidetector CT is a useful noninvasive examination for establishing the primary diagnosis and defining anatomic landmarks and their relationships. The spectrum of vessel involvement is vast, with varied manifestations. Radiologists should be familiar with inflammatory vasculitis, aneurysmal change, and pseudotumor formation in all vessels and the distribution of these conditions throughout the body. Electrocardiographically gated CT enables accurate, fast, and noninvasive characterization of coronary pathologic conditions and thus has an important advantage over catheter angiography. Combined PET/CT can depict inflammatory processes and help distinguish IgG4-related CVD from atherosclerosis. Familiarity with the PET/CT and CT findings of inflammatory processes involved in IgG4-related CVD is important for accurate diagnosis and evaluation of therapeutic response during follow-up. The multidetector CT and PET/CT characteristics of IgG4-related CVD, such as aortitis, periaortitis, arteritis, and periarteritis and including coronary artery involvement and pericarditis, are reviewed. In addition, the inflammatory process, quantification of active inflammation, and therapeutic response during follow-up associated with IgG4-related CVD are described. Online DICOM image stacks are available for this article. ©RSNA, 2018.


Assuntos
Doenças Autoimunes/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/imunologia , Imunoglobulina G/imunologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos
12.
J Infect Chemother ; 24(8): 660-663, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29373264

RESUMO

Disseminated fusariosis (DF) is a rare life threatening fungal infection in immunocompromised hosts. We herein report a case of a fatal DF mimicking varicella zoster virus (VZV) infection that was emerged from a localized genital infection during cord blood transplantation (CBT) in a patient with severe aplastic anemia (SAA). The patient developed an ulcer following small painful vesicles mimics herpes simplex virus infection (HSV) on the glans penis before CBT, but a Fusarium species was identified. Despite administration of voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion was extended to extensive skin looked like VZV infection and the patients died after CBT. Massive fusarium infiltration was detected in multiple organs at autopsy. A genetic analysis of the mold identified Fusarium solani after his death. It should be noted that in patients with fusarium infection, localized and disseminated lesions of fusarium infection sometimes mimic HSV and VZV infections, which hampers an early diagnosis.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Fusariose/imunologia , Hospedeiro Imunocomprometido , Adulto , Antifúngicos/uso terapêutico , Antivirais , Diagnóstico Diferencial , Evolução Fatal , Sangue Fetal/transplante , Fusariose/diagnóstico , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Fusarium/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Humanos , Masculino , Pênis/microbiologia , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico
13.
Pathol Int ; 67(7): 342-349, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28590047

RESUMO

Intraocular lymphoma is a rare neoplasm that occurs only in the eyes and/or central nervous system. Diagnosis of intraocular lymphoma is difficult because its clinical manifestations mimic chronic uveitis. Pathological examination of the vitreous is one of the main diagnostic tools for intraocular lymphoma, but this is challenging due to the sparse cellularity and specimen degeneration. Here, we reviewed 33 cell block preparations from vitreous perfusion fluid in order to examine the significance of cytopathological findings for differential diagnosis using vitreous samples. The cases comprised 12 intraocular lymphomas and 21 non-lymphomatous diseases. Cytologically, vitreous samples from non-lymphoma cases showed lower cellularity than the lymphoma cases. Whereas vitreous material from cases with infectious endophthalmitis showed prominent neutrophilic infiltration, material from sarcoidosis cases showed infiltration of small lymphoid cells, especially CD4-positive T cells. On the other hand, lymphoma cases showed higher cellularity, with large, irregular and atypical lymphoid cells, frequent necrotic cells in the background, and less pronounced neutrophil infiltration. Immunocytochemically, 11 of the 12 lymphoma cases were of the B-cell phenotype and the remaining case was of the T/NK-cell phenotype. In conclusion, careful cytopathological examination or immunocytochemistry of vitreous material facilitates appropriate diagnosis of intraocular lymphoma.


Assuntos
Linfoma Intraocular/diagnóstico , Sarcoidose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma Intraocular/metabolismo , Linfoma Intraocular/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/metabolismo , Sarcoidose/patologia , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Adulto Jovem
14.
Lipids Health Dis ; 16(1): 36, 2017 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-28179022

RESUMO

BACKGROUND: High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. METHODS: Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce apoptosis and the effect caused by the addition of ApoM and S1P analyzed. RESULTS: The addition of HDL+ApoM or recombinant ApoM-bound S1P promoted cell viability and blocked apoptosis, whereas HDL-ApoM had no protective effect. Remarkably, S1P exerted a more potent anti-apoptotic effect when carried by ApoM as compared to albumin, or when added as free molecule. Mechanistically, cooperation between S1P1 and S1P3 was required for the HDL/ApoM/S1P-mediated anti-apoptotic ability. Furthermore, AKT and ERK phosphorylation was also necessary to achieve the anti-apoptotic effect of the HDL/ApoM/S1P complex. CONCLUSIONS: Altogether, our results indicate that ApoM and S1P are key elements of the anti-apoptotic activity of HDL and promote optimal endothelial function.


Assuntos
Apolipoproteínas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipocalinas/metabolismo , Lipoproteínas HDL/metabolismo , Lisofosfolipídeos/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Esfingosina/análogos & derivados , Apolipoproteínas/genética , Apolipoproteínas/farmacologia , Apolipoproteínas M , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/química , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipocalinas/genética , Lipocalinas/farmacologia , Lipoproteínas HDL/genética , Lipoproteínas HDL/farmacologia , Lisofosfolipídeos/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Lisoesfingolipídeo/genética , Albumina Sérica/farmacologia , Esfingosina/metabolismo , Esfingosina/farmacologia
16.
Surg Endosc ; 30(10): 4640-5, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26715023

RESUMO

BACKGROUND: Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks. METHODS: Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last-known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks. RESULTS: The median tumor diameter was 5.0 cm (range 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9 cases. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 min (range 73-513) and 10 mL (range 0-1020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6 cases. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/renal vein (n = 2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n = 2). In recent cases, 3D-CT was helpful for preoperative planning. CONCLUSIONS: Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.


Assuntos
Ganglioneuroma/cirurgia , Laparoscopia/métodos , Neurilemoma/cirurgia , Paraganglioma/cirurgia , Neoplasias Retroperitoneais/cirurgia , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Conversão para Cirurgia Aberta , Feminino , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/patologia , Humanos , Imageamento Tridimensional , Rim , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Duração da Cirurgia , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Cuidados Pré-Operatórios , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga Tumoral , Gravação de Videoteipe , Adulto Jovem
17.
J Biol Chem ; 288(30): 21569-80, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23754290

RESUMO

The staphylococcal superantigen-like protein (SSL) family is composed of 14 exoproteins sharing structural similarity with superantigens but no superantigenic activity. Target proteins of four SSLs have been identified to be involved in host immune responses. However, the counterparts of other SSLs have been functionally uncharacterized. In this study, we have identified porcine plasma prothrombin as SSL10-binding protein by affinity purification using SSL10-conjugated Sepharose. The resin recovered the prodomain of prothrombin (fragment 1 + 2) as well as factor Xa in pull-down analysis. The equilibrium dissociation constant between SSL10 and prothrombin was 1.36 × 10(-7) M in surface plasmon resonance analysis. On the other hand, the resin failed to recover γ-carboxyglutamic acid (Gla) domain-less coagulation factors and prothrombin from warfarin-treated mice, suggesting that the Gla domain of the coagulation factors is essential for the interaction. SSL10 prolonged plasma clotting induced by the addition of Ca(2+) and factor Xa. SSL10 did not affect the protease activity of thrombin but inhibited the generation of thrombin activity in recalcified plasma. S. aureus produces coagulase that non-enzymatically activates prothrombin. SSL10 attenuated clotting induced by coagulase, but the inhibitory effect was weaker than that on physiological clotting, and SSL10 did not inhibit protease activity of staphylothrombin, the complex of prothrombin with coagulase. These results indicate that SSL10 inhibits blood coagulation by interfering with activation of coagulation cascade via binding to the Gla domain of coagulation factor but not by directly inhibiting thrombin activity. This is the first finding that the bacterial protein inhibits blood coagulation via targeting the Gla domain of coagulation factors.


Assuntos
Ácido 1-Carboxiglutâmico/imunologia , Proteínas de Bactérias/imunologia , Fator Xa/imunologia , Protrombina/imunologia , Staphylococcus aureus/imunologia , Superantígenos/imunologia , Ácido 1-Carboxiglutâmico/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/metabolismo , Sítios de Ligação/imunologia , Ligação Competitiva/imunologia , Coagulação Sanguínea/imunologia , Cálcio/imunologia , Cálcio/metabolismo , Coagulase/imunologia , Coagulase/metabolismo , Eletroforese em Gel de Poliacrilamida , Fator Xa/metabolismo , Humanos , Soros Imunes/imunologia , Soros Imunes/metabolismo , Camundongos , Dados de Sequência Molecular , Ligação Proteica/imunologia , Protrombina/metabolismo , Staphylococcus aureus/metabolismo , Superantígenos/metabolismo , Ressonância de Plasmônio de Superfície , Suínos , Trombina/imunologia , Trombina/metabolismo
18.
Am J Ophthalmol Case Rep ; 34: 102043, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38584718

RESUMO

Purpose: Choroidal melanocytoma is a rare benign melanocytic tumor. We report a case of choroidal melanocytoma that was definitively diagnosed by histopathological findings after local resection. Observation: A 71-year-old female complained of blurred vision in her left eye. Her best-corrected visual acuity (BCVA) was 1.0. A dark-brown elevated lesion, measuring 5 papilla-diameter was found in the periphery of the fundus in her left eye. The mass showed hyperfluorescence on fluorescein angiography, early hypofluorescence and late hyperfluorescence on indocyanine green angiography. B-mode echography indicated the mass was originated from the choroid. Orbital magnetic resonance imaging showed isointense signal intensity on T1-weighted images (WI) and hypointense signal intensity on T2-WI, and poor Gadolinium enhancement on T1WI. The tumor was suspected to be melanocytoma, but it was difficult to differentiate from malignant melanoma. Transscleral tumor resection combined with 25-gauge vitrectomy was performed. Histopathological examinations led to the diagnosis of choroidal melanocytoma. Two years after local resection, her BCVA was 1.0 with no tumor recurrence. Conclusions/importance: Local resection was useful as a diagnostic treatment for choroidal tumors confined to the periphery of the fundus that were difficult to clinically differentiate from malignant melanoma.

19.
Nurs Open ; 10(3): 1726-1734, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36271482

RESUMO

AIM: To clarify the details of mothers' employment status after the completion of their child's cancer treatment. DESIGN: A cross-sectional exploratory study. METHODS: Data are collected from 62 mothers of childhood cancer survivors using self-report questionnaires. Fisher's exact test was used to determine the statistical significance of factors between the mothers who worked and those who did not work after their child's cancer treatment had been completed. RESULTS: Thirty-two mothers worked after the completion of their child's cancer treatment. There were significant differences in age, education level, employment status at the diagnosis and time elapsed since the diagnosis between the working mothers and non-working mothers. Twenty-two non-working mothers reported that they had some motivation to work, but the most common reason for not working was "To nurse or care for the child with cancer". Some mothers also stated that they did not work due to anxiety about cancer recurrence.


Assuntos
Emprego , Neoplasias , Feminino , Humanos , Criança , Estudos Transversais , Mães , Inquéritos e Questionários , Escolaridade , Neoplasias/terapia
20.
Clin Case Rep ; 11(4): e7250, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37102100

RESUMO

Trichuris trichiura parasitizes only humans through fecal-oral transmission. In non-endemic areas, the frequency of endoscopic identification has been increasing due to the increasing number of immigrants from endemic countries. To prevent infection, it is important to pay attention to sanitary conditions such as soil and water sources.

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