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BACKGROUND: Next-generation sequencing (NGS) is essential in treating advanced lung cancer. However, the effectiveness of endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) in NGS remains unclear. This study examined the usefulness of EUS-B-FNA in lung cancer NGS cases where EUS-B-FNA was performed for specimen submission in a nationwide genomic screening platform (LC-SCRUM-Asia) and compared specimens collected using other bronchoscopy methods (endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA] and EBUS-guided transbronchial biopsy with a guide sheath [EBUS-GS-TBB]) during the same period. METHODS: We retrospectively compared the NGS success rates of NGS, DNA and RNA yields for EUS-B-FNA, EBUS-TBNA, and EBUS-GS-TBB from the records of the patients recruited for the Lung Cancer Genomic Screening Project for Individualized Medicine (LC-SCRUM)-Asia. RESULTS: Fifty-one patients were enrolled, and the NGS success rates were comparable for samples obtained by EUS-B-FNA, EBUS-TBNA, and EBUS-GS-TBB (100%, 90.9%, and 81.0%, respectively). Genetic alterations were detected in 73.7%, 90.9%, and 85.7% of patients, respectively, with druggable genetic alterations found in 31.6%, 72.7%, and 61.9% of patients, respectively. The DNA and RNA yields were significantly higher in EUS-B-FNA samples than in EBUS-GS-TBB samples (50.4 (interquartile range (IR): 15.45-72.35) ng/µl and 33.9 (IR: 9-76.8) ng/µl from EUS-B-FNA, and 3.3 (IR: 1.4-7.1) ng/µl and 15.1 (IR: 8.3-31.5) ng/µl from EBUS-GS-TBB, respectively, p < 0.05). CONCLUSION: EUS-B-FNA emerges as a promising bronchoscopic method for obtaining adequate samples for NGS in advanced lung cancer cases.
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Broncoscopía , Carcinoma de Pulmón de Células no Pequeñas , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico por imagen , Broncoscopía/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Femenino , Anciano , Persona de Mediana EdadRESUMEN
BACKGROUND: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. METHODS: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. RESULTS: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. CONCLUSIONS: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
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Endopeptidasas , Fibroblastos , Gelatinasas , Proteínas de la Membrana , Serina Endopeptidasas , Trombosis de la Vena , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Cultivadas , Endopeptidasas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Gelatinasas/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Trombosis de la Vena/patología , Trombosis de la Vena/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. AIMS: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. METHODS AND RESULTS: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5'-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. CONCLUSIONS: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
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Factor VIII , Miocitos del Músculo Liso , Neointima , Trombosis , Conejos , Animales , Neointima/patología , Neointima/sangre , Trombosis/sangre , Trombosis/patología , Masculino , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/efectos de los fármacos , Túnica Íntima/patología , Túnica Íntima/efectos de los fármacos , Humanos , Agregación Plaquetaria/efectos de los fármacos , Arteria Femoral/patología , Arteria Femoral/lesionesAsunto(s)
Braquiuros , Paragonimus westermani , Alimentos de Soja , Trematodos , Animales , Humanos , Alimentos de Soja/análisis , Agua DulceRESUMEN
Inflammatory activity and hypoxia in atherosclerotic plaques are associated with plaque instability and thrombotic complications. Recent studies show that vascular cell metabolism affects atherogenesis and thrombogenicity. This study aimed to identify the metabolites in macrophage-rich unstable plaques that modulate atherogenesis and serve as potential markers of plaque instability. Atherosclerotic plaques were induced by balloon injury in the iliofemoral arteries of rabbits fed on a conventional or 0.5% cholesterol diet. At 3 months post-balloon injury, the arteries and cardiac tissues were subjected to histological, quantitative real-time polymerase chain reaction, and metabolomic analyses. The identified metabolite-related proteins were immunohistochemically analyzed in stable and unstable plaques from human coronary arteries. The factors modulating the identified metabolites were examined in macrophages derived from human peripheral blood mononuclear cells. Metabolomic analysis revealed that choline and guanine levels in macrophage-rich arteries were upregulated compared with those in non-injured arteries and cardiac tissues. Vascular choline levels, but not guanine levels, were positively correlated with the areas immunopositive for macrophages and tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP) 9 mRNA levels in injured arteries. In human coronary arteries, choline transporter-like protein (CTL) 1 was mainly localized to macrophages within plaques. The area that was immunopositive for CTL1 in unstable plaques was significantly higher than that in stable plaques. Intracellular choline levels were upregulated upon stimulation with TNF-α but were downregulated under hypoxia in cultured macrophages. Administration of choline upregulated the expression of TNF-α and CTL1 mRNA in cultured macrophages. The transfection of CTL1 small interfering RNA decreased CTL1, TNF-α, and MMP9 mRNA levels in cultured macrophages. These results suggest that choline metabolism is altered in macrophage-rich atherosclerotic lesions and unstable plaques. Thus, CTL1 may be potential markers of plaque instability.
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Aterosclerosis , Placa Aterosclerótica , Animales , Humanos , Conejos , Placa Aterosclerótica/patología , Regulación hacia Arriba , Leucocitos Mononucleares/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Aterosclerosis/metabolismo , ARN Mensajero/metabolismo , HipoxiaRESUMEN
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
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Neoplasias , Embolia Pulmonar , Trombosis , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/patología , Trombosis de la Vena/etiología , Trombosis de la Vena/patología , Histonas , Neoplasias/complicacionesRESUMEN
Preeclampsia, a multisystem pregnancy-specific hypertensive disorder, results in significant maternal and perinatal morbidity and mortality. This condition is associated with placental histopathological abnormalities and particularly affects the decidual spiral arteries. Reportedly, aspirin prevents preeclampsia, specifically early-onset preeclampsia, although findings in decidual arteries in women treated with aspirin therapy remain unclear. We compared the clinical and histopathological placental findings between women with a history of preeclampsia, who did and did not receive low-dose aspirin therapy (LDA and non-LDA groups, respectively). We identified 26 women with a history of preeclampsia; 9 women received LDA (aspirin ≤ 100 mg/day, initiated at < 16 weeks, LDA group), and 17 women did not receive LDA (non-LDA group). The mean gestational age was higher (36.7 weeks vs. 32.3 weeks, P = 0.0221) and the incidence of preeclampsia was lower (11% vs. 59%, P = 0.0362) in the LDA than in the non-LDA group. Histopathologically, the incidence of decidual arteriopathy, particularly that of fibrinoid necrosis and thrombosis, was lower in the LDA than in the non-LDA group (44% vs. 88%, P = 0.0283). Immunohistologically, endothelial marker (CD31 and CD39) expression was stronger in the LDA than in the non-LDA group. Notably, we observed no significant intergroup differences in inflammatory changes (chronic perivasculitis, protease-activated receptor 1 expression, and CD3-positive cells). This study highlights that LDA inhibits hypertension-induced endothelial injury and thrombosis, and thereby protects maternal placental perfusion and prevents preeclampsia.
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Enfermedades Placentarias , Preeclampsia , Femenino , Embarazo , Humanos , Lactante , Preeclampsia/tratamiento farmacológico , Mujeres Embarazadas , Placenta , Aspirina/uso terapéutico , Edad GestacionalRESUMEN
AIM: Diabetes mellitus (DM) is a major complication in pregnancy. Placental lesions with DM remain unclear and controversial. Recently, the terms of placental pathological findings, such as maternal and fetal vascular malperfusions (MVM and FVM, respectively) were introduced by the Amsterdam Placental Workshop Group Consensus Statement (APWGCS). FVM cases were classified as the partial obstruction type (global FVM) and the complete obstruction type (segmental FVM). The aim of this study was to clarify the pathological characteristics of the placenta with pregestational DM/gestational DM; GDM according to APWGCS. METHODS: We studied the placentas of 182 DM women (27 pregestational DM and 155 GDM) and control placentas of 460 women without DM during 2011-2018. We excluded cases of intrauterine fetal death or multiple pregnancies. We reviewed microscopical findings including, MVM, FVM, chorioamnionitis with the slides according to the APWGCS. RESULTS: Microscopically, the incidence of FVM was significantly higher in GDM patients than control (17% vs. 10%, p = 0.0138), but not significant in pregestational DM (11%, p = 0.7410). Segmental FVM (complete obstruction) was significantly more observed in GDM than control group (5% vs. 0.4%, p = 0.0013). Segmental FVM in GDM showed high incidence of light-for-dates infant (three of seven cases, 43%, p = 0.0288). In addition, several segmental FVM findings (villous stromal-vascular karyorrhexis and stem vessel occlusion) were frequently noted in 2 or 3 points positive of 75 g oral glucose tolerance test than 1 point positive GDM. CONCLUSION: Our placental findings suggest disorder of carbohydrate metabolism might affect the fetal vascular damage, especially complete fetal vascular obstruction.
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Diabetes Gestacional , Enfermedades Placentarias , Diabetes Gestacional/epidemiología , Femenino , Muerte Fetal , Humanos , Placenta , Embarazo , MortinatoRESUMEN
CASE: A 67-year-old woman suffered from chronic diarrhea at 10 years after right total hip arthroplasty. She also had a pseudotumor caused by an adverse local tissue reaction (ALTR) in her right pelvis. We performed revision arthroplasty, in part because we suspected the diarrhea may have been associated with the intrapelvic pseudotumor. She was later diagnosed with eosinophilic gastroenteritis (EGE). CONCLUSION: Although these two diseases were thought be be related through a similar immune reaction, our patient's clinical course suggests that the ALTR and EGE were independent events.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Cromo , Cobalto , Enteritis , Eosinofilia , Femenino , Gastritis , Prótesis de Cadera/efectos adversos , Humanos , Diseño de Prótesis , Falla de Prótesis , ReoperaciónRESUMEN
BACKGROUND AND AIMS: This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (18F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques. METHODS: 18F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and balloon injury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically. TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI). RESULTS: 18F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi. CONCLUSIONS: 18F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques.
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BACKGROUND AND AIMS: The everolimus-eluting stent (EES), one of the effective stents for in-stent restenosis (ISR), has a lower incidence of stent thrombosis; however, the underlying mechanism remains unknown. This study aimed to identify the effects of everolimus on vascular metabolism and thrombogenicity and examine their mechanistic link. METHODS: EESs and bare-metal stents were implanted in rabbit iliac arteries with smooth muscle cell (SMC)-rich neointima induced by endothelial denudation. Four weeks after stent implantation, the stented arteries were examined for histological analysis and metabolomics. Additionally, everolimus effects in coronary artery SMCs metabolism, tissue factor (TF) expression, and procoagulant activity were assessed in vitro. RESULTS: EES-implanted arteries showed decreased neointima formation, less SMCs infiltration, and reduced TF expression. Concomitantly, they were metabolically characterized by increased levels of metabolites in amino acids, such as glutamine. Similarly, everolimus increased intracellular glutamine levels, decreased TF expression, and reduced procoagulant activity in SMCs in vitro. On the contrary, exogenous glutamine administration also increased intracellular glutamine level, decreased TF expression, and reduced procoagulant activity despite enhanced mammalian target of rapamycin (mTOR) activity. CONCLUSIONS: Intracellular glutamine level is likely to determine vascular SMC-related thrombogenicity regardless of mTOR pathway activity. Therefore, increased intracellular glutamine level might contribute partially to the beneficial effect of EES use on stent thrombosis.
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Fármacos Cardiovasculares , Reestenosis Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Animales , Glutamina , Músculo Liso Vascular , Miocitos del Músculo Liso , Diseño de Prótesis , ConejosRESUMEN
It is often straightforward to distinguish glioblastoma (GBM) from metastatic carcinoma by cytology; however, small cell variants of GBM or GBM with primitive neuronal component (GBMPNC) can mimic metastatic small cell carcinoma (SCC). Herein, we report a case of GBMPNC mimicking metastatic SCC and present cytological and ultrastructural findings. A 65-year-old man with memory disturbance was hospitalized. Magnetic resonance imaging revealed the presence of a 6 cm sized tumor in the right anterior temporal lobe. Intraoperative cytology slides indicated that the tumor consisted of small-sized cells with scant cytoplasm showing high cellularity. The initial intraoperative diagnosis was metastatic SCC; however, any primary visceral tumor was not detected clinically. Immunohistochemical and ultrastructural studies of postoperative histological sections revealed that the lesion was GBMPNC. This case shows that some GBMs may have the potential to closely mimic metastatic SCC, which expands the differential diagnosis and emphasizes the importance of clinical correlation.
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Glioblastoma , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/patología , Citodiagnóstico , Diagnóstico Diferencial , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioblastoma/ultraestructura , Humanos , MasculinoRESUMEN
TP53 mutations are important molecular markers in diffuse astrocytic tumors and medulloblastomas. We examined the efficacy of a pre-screening method for high-resolution melting (HRM) analysis of TP53 mutation before direct sequencing using samples from patients with diffuse glioma. Surgical samples from 64 diffuse gliomas were classified based on the 2016 World Health Organization (WHO) histopathological grading system and the cIMPACT-NOW (consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO) update. TP53 mutations from exon 5 to exon 8 were assessed by direct sequencing. The results of HRM and p53 immunohistochemistry (IHC) analysis were compared by recording the sensitivity, specificity, and false negative and false positive rates. Direct sequencing detected TP53 mutations in 18 of 64 samples (28.1%): diffuse astrocytoma, IDH-mutant (n = 3); diffuse astrocytoma, IDH-wild type (n = 1); anaplastic astrocytoma, IDH-mutant (n = 3); anaplastic astrocytoma, IDH-wild type (n = 4); and glioblastoma, IDH-wild type (n = 7). A total of 22 mutations was detected in the 18 samples; 4 samples exhibited duplicate missense mutations. Sensitivity and specificity were 0.96 and 0.96, respectively, for HRM analysis; they were 0.89 and 0.52, respectively, for p53 IHC. Overall accuracy was 0.98 for HRM and 0.63 for IHC. HRM analysis is a good pre-screening method for the detection of TP53 mutation before direct sequencing.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Análisis Mutacional de ADN/métodos , Pruebas Genéticas/métodos , Glioblastoma/genética , Mutación , Proteína p53 Supresora de Tumor/genética , Dermatitis Alérgica por Contacto , Exones/genética , Humanos , Inmunohistoquímica , Metacrilatos/efectos adversos , Mutación Missense , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Arterial thrombus formation is thought to be initiated by platelet adhesion to the subendothelial matrix, but ruptured atherosclerotic plaques are characterized by substantial reduction of matrix proteins compared with stable plaques. Intraplaque erythrocytes and/or fibrin have been reported in high-risk coronary plaques. The aims of the current study were to identify factors that provide scaffolds for platelets at the sites of ruptured coronary plaques and investigate depositions of iron and bilirubin as hemoglobin catabolites in the ruptured plaques. Histological characteristics of plaque components and the thrombus interface were examined in 73 acute coronary aspirated thrombi. Necrotic debris (95%), macrophages (95%), and cholesterin clefts (81%) were observed frequently at the ruptured plaque and thrombus interface. A fibrous matrix (47%), calcification (32%), and extracellular deoxyribonucleic acid (15%) were identified as small foci. Tissue factor was localized in the necrotic core and macrophages. Fibrin and von Willebrand factor were consistently deposited within the plaques and beneath platelet aggregations. The citrullinated histone H3-immunopositive area accounted for only 0.5% of the plaque area. Bilirubin and iron depositions were detected in approximately 20% of the plaques in addition to biliverdin reductase and ferritin expression in macrophages. Fibrin and von Willebrand factor rather than matrix proteins and neutrophil extracellular traps may be major adhesive molecules at the sites of ruptured plaques. Iron and bilirubin deposits may be markers for rupture-prone plaques.
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Plaquetas/patología , Trombosis Coronaria/patología , Fibrina/análisis , Placa Aterosclerótica/patología , Factor de von Willebrand/análisis , Anciano , Anciano de 80 o más Años , Bilirrubina/análisis , Femenino , Humanos , Hierro/análisis , Masculino , Persona de Mediana Edad , Agregación PlaquetariaRESUMEN
AIMS: Inflammation and hypertension contribute to the progression of atherosclerotic aneurysm in the aorta. Vascular cell metabolism is regarded to modulate atherogenesis, but the metabolic alterations that occur in atherosclerotic aneurysm remain unknown. The present study aimed to identify metabolic pathways and metabolites in aneurysmal walls and examine their roles in atherogenesis. METHODS: Gene expression using microarray and metabolite levels in the early atherosclerotic lesions and aneurysmal walls obtained from 42 patients undergoing aortic surgery were investigated (early lesion n=11, aneurysm n=35) and capillary electrophoresis-time-of-flight mass spectrometry (early lesion n=14, aneurysm n=38). Using immunohistochemistry, the protein expression and localization of the identified factors were examined (early lesion n=11, non-aneurysmal advanced lesion n=8, aneurysm n=11). The roles of the factors in atherogenesis were analyzed in macrophages derived from human peripheral blood mononuclear cells. RESULTS: Enrichment analysis using 35 significantly upregulated genes (log2 ratio, ï¼3) revealed the alteration of the kynurenine pathway. Metabolite levels of tryptophan, kynurenine, and quinolinic acid and the kynurenine-to-tryptophan ratio were increased in the aneurysmal walls. Gene and protein expression of kynureninase and kynurenine 3-monooxygenase were upregulated and localized in macrophages in the aneurysmal walls. The silencing of kynureninase in the cultured macrophages enhanced the expression of interleukin-6 and indoleamine 2,3-dioxygenase 1. CONCLUSION: Our study suggests the upregulation of the kynurenine pathway in macrophages in aortic atherosclerotic aneurysm. Kynureninase may negatively regulate inflammation via the kynurenine pathway itself in macrophages.
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Aneurisma de la Aorta/patología , Aterosclerosis/patología , Biomarcadores/análisis , Hidrolasas/metabolismo , Macrófagos/enzimología , Metaboloma , Transcriptoma , Anciano , Aneurisma de la Aorta/enzimología , Aterosclerosis/enzimología , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Inflamación/prevención & control , Masculino , Pronóstico , Regulación hacia ArribaRESUMEN
The effects of antithrombotic therapy on deep vein thrombosis (DVT) can be affected by thrombus age, which cannot be reliably determined by noninvasive imaging modalities. We investigated whether magnetic resonance (MR) diffusion-weighted imaging (DWI) can localize and determine the age of venous thrombus in patients with DVT, animal models, and human blood in vitro. Signal intensity (SI) on DWI and the apparent diffusion coefficient (ADC) of thrombi were assessed in eight patients with DVT using a 1.5-T MR imaging (MRI) system. We assessed the organizing processes as venous thrombus developed in the rabbit jugular vein using a 3.0-T MRI system over time. We also assessed MRI signals of human blood in vitro using the 1.5-T MRI system. Venous thrombi were detected by DWI as areas of high or mixed high and iso SI in all patients. The ADCs were lower in the proximal, than in the distal portion of the thrombi. The thrombi of rabbit jugular veins histologically organized in a time-dependent manner, with high SI on DWI at 4 hours, mixed high and iso SI at 1 and 2 weeks, and iso SI at 3 weeks. The ADC correlated negatively with erythrocyte content, and positively with smooth muscle cells, macrophages, hemosiderin, and collagen content. MRI signals of human blood in vitro showed that ADCs were affected by erythrocyte content, but not by blood clotting. MR-DWI can detect venous thrombus, and high SI on DWI accompanied by a low ADC might reflect erythrocyte-rich, acute-phase thrombi.
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Imagen de Difusión por Resonancia Magnética , Trombosis de la Vena/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Animales , Coagulación Sanguínea , Imagen de Difusión por Resonancia Magnética/métodos , Modelos Animales de Enfermedad , Femenino , Humanos , Venas Yugulares/diagnóstico por imagen , Venas Yugulares/patología , Masculino , Persona de Mediana Edad , Conejos , Trombosis de la Vena/sangre , Trombosis de la Vena/patología , Adulto JovenRESUMEN
Pathologically diagnosed placenta accreta is defined as villi adjacent to the myometrium without decidua. It is classified into the superficial (placental accreta vera [PAV]) and deep invasive (placenta increta [PI] and placenta percreta [PP]) types. Data on the clinicopathological characteristics of PAV are limited. Basal plate myometrium (BPMYO) is found in PAV or placentas in asymptomatic women, but its significance is still controversial. This retrospective study aimed to determine the clinicopathological characteristics of pathologically diagnosed PAV and the significance of BPMYO. We reviewed 84 cases of pathologically diagnosed placenta accreta (PAV, 54; PI, 16; and PP, 14), and compared them with controls (i.e., not pathologically diagnosed of any type of placenta accreta, n = 51). Among the PAV cases, the incidence of in vitro fertilization was high, while that of previous cesarean section or placenta previa was low. The incidence of maternal complications was also high in pathologically diagnosed PAV cases, but some PAV were asymptomatic. The rate of prenatal diagnosis of PAV was low, and a high proportion of patients required emergency transportation to central hospitals. Histologically, BPMYO was found in 7 (14%) of controls and 54 (100%) of PAV cases. PAV cases had a higher rate of advanced stages of BPMYO, larger muscle tissue, and more foci than controls. In conclusion, almost PAV is a clinically symptomatic condition but has distinct risk factors and clinical findings from advanced type placenta accreta. Histological evaluation of BPMYO is useful for the diagnosis of PAV.
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Miometrio/patología , Placenta Accreta/patología , Placenta Previa/patología , Placenta/patología , Adulto , Estudios de Casos y Controles , Cesárea/efectos adversos , Femenino , Humanos , Incidencia , Miometrio/diagnóstico por imagen , Placenta Accreta/diagnóstico , Placenta Accreta/epidemiología , Placenta Previa/epidemiología , Placenta Previa/etiología , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Dysgerminoma is a rare germ cell tumor, accounting for 1% to 2% of all malignant ovarian tumors. Here, we report a case of dysgerminoma diagnosed by aspiration cytology of a cervical lymph node. A 20-year-old woman presented with an abdominal mass and left cervical swelling. CT revealed a large pelvic tumor, along with a nodular lesion on the left side of neck. Fine needle aspiration (FNA) cytology of a cervical lymph node showed large atypical cells and small lymphocytes. Immunocytochemical staining on cell block material revealed that these large tumor cells were positive for placental alkaline phosphatase, D2-40, and c-kit. Dysgerminoma was suggested by FNA cytology. Furthermore, bilateral oophorectomy was performed, and histology confirmed the diagnosis of ovarian dysgerminoma. FNA cytology of metastatic lymph nodes along with immunocytochemistry is a useful tool for diagnosis of dysgerminoma.
Asunto(s)
Disgerminoma , Ganglios Linfáticos , Neoplasias Ováricas , Adulto , Biopsia con Aguja Fina , Disgerminoma/diagnóstico , Disgerminoma/metabolismo , Disgerminoma/patología , Disgerminoma/cirugía , Femenino , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugíaRESUMEN
Chronic intervillositis of unknown etiology (CIUE) is a rare placental lesion associated with infiltration of mononuclear inflammatory cells into the intervillous space, poor perinatal outcomes (intrauterine fetal demise or fetal growth restriction), and high rates of recurrence. CD39 is the ectonucleotidase that protects tissues from inflammatory stress and cell injury, which is localized on the surface of villi in normal placentas; however, its expression and role in CIUE are unknown. The aims of this retrospective study were to determine the expression of CD39 in CIUE and its significance in pregnancy outcomes. We compared the number of CD68- and CD3-positive cells, CD39 expression, and complement 4d (C4d) and fibrin deposition in placental tissues from patients with CIUE (n = 22) and gestational age-matched controls (n = 20), and between CIUE pregnancies with poor and good outcomes. The numbers of CD68- or CD3-positive cells were significantly higher (P < 0.0001), whereas CD39 expression on the surface of villi and endothelial cells of the stem villi was significantly lower in the CIUE group than that in controls (45% vs. 95%, P < 0.0001 and 77% vs. 96%, P < 0.001, respectively). C4d and fibrin deposition were also significantly increased in CIUE compared with those of controls. Furthermore, CD39 downregulation and the number of CD68 cells were strongly associated with poor pregnancy outcomes (P < 0.01 and P < 0.05, respectively), but other histological parameters (CD3, C4d, and fibrin) did not show this association. Our study suggests that CD39 downregulation is a useful marker of CIUE and is associated with poor pregnancy outcomes in patients with CIUE.