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Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.
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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/genética , Endoglina/genética , Japón/epidemiología , Mutación , Pruebas Genéticas , Receptores de Activinas Tipo II/genéticaRESUMEN
PURPOSE: Surgical manipulation of the lungs increases the number of circulating tumor cells and the subsequent risk of metastasis in patients with lung cancer. This study investigated whether or not ligating the tumor-draining pulmonary vein first during lobectomy could improve the prognosis of these patients. METHODS: We retrospectively evaluated patients who underwent curative lobectomy for solitary nonsmall-cell lung carcinoma between January 2012 and December 2016. We divided the patients into the vein-first group, in which all associated pulmonary veins were dissected and severed before cutting the pulmonary artery, bronchus, or pulmonary fissure, and the other procedure group. RESULTS: Overall, we included 177 and 413 patients in the vein-first and other procedure groups, respectively. Propensity score matching yielded 67 pairs of patients. The 5-year overall survival (85.6% [95% confidence interval, 77.3-94.8%] vs. 69.4% [58.7-81.9%], P = 0.03%) and recurrence-free survival (73.4% [63.3-85.1%] vs. 53.5% [42.5-67.3%], P = 0.02) were significantly better in the vein-first group than in the other procedure group. The cumulative recurrence rate at 5 years post-surgery was significantly lower in the vein-first group than in the other procedure group (21.7% vs. 38.3%, P = 0.04). CONCLUSION: Our study suggests that ligating the pulmonary vein first during lobectomy for lung cancer can improve the overall survival, recurrence-free survival, and cumulative recurrence rate.
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[Fe]-hydrogenase catalyzes the heterolytic cleavage of H2 and reversible hydride transfer to methenyl-tetrahydromethanopterin. The iron-guanylylpyridinol (FeGP) cofactor is the prosthetic group of this enzyme, in which mononuclear Fe(II) is ligated with a pyridinol and two CO ligands. The pyridinol ligand fixes the iron by an acyl carbon and a pyridinol nitrogen. Biosynthetic proteins for this cofactor are encoded in the hmd co-occurring (hcg) genes. The function of HcgB, HcgC, HcgD, HcgE, and HcgF was studied by using structure-to-function analysis, which is based on the crystal structure of the proteins and subsequent enzyme assays. Recently, we reported the catalytic properties of HcgA and HcgG, novel radical S-adenosyl methionine enzymes, by using an inâ vitro biosynthesis assay. Here, we review the properties of [Fe]-hydrogenase and the FeGP cofactor, and the biosynthesis of the FeGP cofactor. Finally, we discuss the expected engineering of [Fe]-hydrogenase and the FeGP cofactor.
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Hidrogenasas , Proteínas Hierro-Azufre , Hidrogenasas/metabolismo , Carbono/metabolismo , Proteínas Hierro-Azufre/química , Hierro/químicaRESUMEN
Glucocorticoids (GCs), immunosuppressive, and anti-inflammatory agents have various effects on T cells. However, the long-term influence of GCs on the T cell-mediated immune response remain to be elucidated. We demonstrated that the administration of GC during the TCR-mediated activation phase induced long-lasting suppression of glycolysis, even after the withdrawal of GC. The acquisition of the effector functions was inhibited, while the expression of PD-1 was increased in CD8 T cells activated in the presence of GC. Furthermore, adoptive transfer experiments revealed that GC-treated CD8 T cells reduced memory T cell formation and anti-tumor activity. These findings reveal that GCs have long-lasting influence on the T cell-mediated immune response via modulation of T cell metabolism.
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Linfocitos T CD8-positivos/metabolismo , Glucocorticoides/farmacología , Glucosa/metabolismo , Inmunidad , Terapia de Inmunosupresión , Animales , Antígenos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Femenino , Glucólisis/efectos de los fármacos , Inmunidad/efectos de los fármacos , Memoria Inmunológica/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Prednisolona/farmacologíaRESUMEN
BACKGROUND: The endovascular treatment of large, wide-necked basilar apex aneurysms (BAAs) remains challenging. Although horizontal stent deployment across both P1 segments of the posterior cerebral arteries (PCAs) would be an optimal strategy in coil embolization of wide-necked BAAs, this is only feasible in cases with anatomically favorable access. In rare circumstances, large-diameter conduits of extracranial-intracranial (EC-IC) bypass can also provide a good access route for endovascular treatment of complex intracranial aneurysms. METHODS: We describe the technique of accessing the PCA via EC-IC bypass grafts and deploying a stent horizontally across the neck of BAA and its coil embolization. We provide a detailed technical review and describe some pitfalls of the procedure. RESULTS: Two patients underwent EC-IC bypass surgery prior to the treatment of a large, wide-necked BAA. The radial artery and saphenous vein were used as grafts, respectively. To facilitate coil embolization for a large BAA, a PCA-to-PCA horizontal stent was deployed via the bypass graft. Trans-cell and jailing techniques were used, respectively. Both aneurysms were completely occluded, and the patients were discharged without any neurological deficit. CONCLUSION: Horizontal stent deployment via EC-IC bypass grafts can be performed safely, providing proper closure of the aneurysmal neck and apposition to both PCAs, facilitating complete coil embolization.
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Embolización Terapéutica , Aneurisma Intracraneal , Embolización Terapéutica/métodos , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Arteria Cerebral Posterior , Stents , Resultado del TratamientoRESUMEN
INTRODUCTION: We evaluated the effects of secondary bone grafting (SBG) on oral health-related and generic health-related quality of life (OHRQOL and HRQOL, respectively) in preadolescent orthodontic patients with alveolar bone defects. METHODS: We divided 101 orthodontic patients aged 8-10 years into 3 groups: 39 general orthodontic patients, 18 patients with orofacial clefts who did not require SBG, and 44 patients with alveolar defects who required SBG using particulate cancellous bone and marrow obtained from the iliac crest. The participants completed the self-report Child Perceptions Questionnaire (CPQ) and Paediatric Quality of Life Inventory (version 4.0) for OHRQOL and HRQOL, respectively, and their scores were assessed. The quality of life (QOL) of patients who required SBG was examined before, 1 month, and 6 months after SBG. The relationships between OHRQOL or HRQOL and potential patient factors were also evaluated. RESULTS: Physical HRQOL subscale scores worsened 1 month after SBG, whereas the total OHRQOL and HRQOL scores before and after SBG showed no significant changes. OHRQOL and HRQOL showed no significant differences among the 3 groups before SBG. The presence of oronasal fistula was associated with poorer OHRQOL in patients with cleft lip and/or palate. CONCLUSIONS: SBG and orthodontic treatment had a relatively small impact on the QOL of the preadolescent children in this study. Understanding the influence of SBG and patient factors on QOL would enable better treatment and care for these patients.
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A 23-year-old man was referred to our department for chest abnormal shadow. Computed tomography (CT) of the chest revealed a well-defined 1.2 cm nodule in the S4 segment of the right middle lobe and a well-defined 1.8 cm nodule in the S10 segment of the right lower lobe. The patient was found to have a fracture in the left fifth rib due to the falling accident at playing snowboard, two months before. He was diagnosed with a benign tumor in the right middle lobe and the right lower lobe and was performed surgery. Thoracoscopy revealed a yellowish-brown tumor in the right middle lobe( S4) and a yellow-brown tumor in the right lower lobe( S10). Both lesions were diagnosed as clots by rapid intraoperative pathologic diagnosis. Histopathological diagnosis was an intrapulmonary hematoma.
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Enfermedades Pulmonares , Neoplasias Pulmonares , Traumatismos Torácicos , Adulto , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/cirugía , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/cirugía , Adulto JovenRESUMEN
Extracranial carotid artery aneurysms (ECAAs) are rare, with the etiology mainly classified as degeneration or dissection. Pseudoaneurysms in the region are even rarer and are seen following trauma, iatrogenic injury, or infection. We report a case of extracranial carotid artery pseudoaneurysm (pseudo-ECAA) with a rare clinical course and pathological features. A 58-year-old man presented with swelling and purpura on the left side of his neck after sneezing. Radiological examinations suggested a ruptured left common carotid artery aneurysm. The operative findings were consistent with a pseudoaneurysm. Pathological examination revealed disarrangement and degeneration of smooth muscle fibers in the media, in addition to scattered foci of mucoid accumulation and irregular-shaped cavitation in the medial extracellular matrix, raising the possibility of an intrinsic dysfunction of the vascular wall in the pathological process of pseudoaneurysm formation.
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Aneurisma Falso/complicaciones , Aneurisma Falso/patología , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/patología , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Aneurisma Roto/diagnóstico , Angiografía , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/cirugía , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , PénfigoRESUMEN
Diseases associated with the RNF213 gene include moyamoya disease, with the p.R4810K (c.14429G>A, rs112735431) homozygous variant thought to be the most pathogenic and significantly associated with severe manifestation such as early onset or cerebral infarction at onset. We report a case of a unique Japanese pedigree associated with RNF213. A 53-year-old woman with no arteriosclerotic risk factors experienced coronary artery disease, followed by coronary artery bypass surgery. In 8 years, she suffered sudden abdominal pain. Her abdominal contrast computed tomography revealed stenosis of abdominal artery and superior mesenteric artery. Though her 2 children and uncle had a typical moyamoya disease with RNF213 p.R4810K heterozygous variant, she has had no clinical and radiological evidence of moyamoya disease. Due to a family history of moyamoya disease, a genetic investigation was performed and revealed RNF213 p.R4810K homozygous variant. A possible role of RNF213 influencing systemic artery stenosis can be further be understood from this rare case harboring the homozygous variant carrier.
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Adenosina Trifosfatasas/genética , Variación Genética , Enfermedad de Moyamoya/genética , Enfermedad Arterial Periférica/genética , Ubiquitina-Proteína Ligasas/genética , Femenino , Predisposición Genética a la Enfermedad , Herencia , Homocigoto , Humanos , Persona de Mediana Edad , Enfermedad de Moyamoya/diagnóstico , Linaje , Enfermedad Arterial Periférica/diagnóstico , Fenotipo , Factores de RiesgoRESUMEN
The lateral supraorbital approach(LSOA)is widely accepted as a less invasive surgical technique compared with the conventional pterional approach(PA). However, only a few studies have reported less invasiveness associated with LSOA. To evaluate this issue, we retrospectively investigated the surgical outcomes in 133 patients who underwent LSOA and 28 patients who underwent PA for unruptured anterior circulation aneurysms. We analyzed operation time, postoperative symptoms and complications, and the length of postoperative hospitalization(in days)for each method. All aneurysms were successfully clipped regardless of the approach. The operation time was significantly shorter, the postoperative headache rate was lower, resumption of oral intake was more rapid, and length of hospitalization was shorter in the LSOA group. Statistical significance was not observed in the postoperative complication rates. Compared with conventional PA, LSOA was associated with less invasiveness and better patient satisfaction. LSOA is a safe and effective alternative to conventional PA, following optimal patient selection.
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Aneurisma Roto , Aneurisma Intracraneal , Aneurisma Roto/cirugía , Craneotomía , Humanos , Aneurisma Intracraneal/cirugía , Procedimientos Neuroquirúrgicos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Homozygosity of this p.R4810K founder variant of RNF213moyamoya disease (MMD) susceptibility gene is known to influence the severity of the clinical disease phenotype at disease onset. However, the association between this genotype and long-term clinical manifestations has remained unclear. OBJECTIVES: The principal goal of this study was to investigate whether and how the p.R4810K variant of RNF213influences the long-term phenotype in Japanese patients with MMD. METHOD: This retrospective cohort study included 94 Japanese patients with MMD who underwent direct or combined bypass for revascularization with the p.R4810K genotype determined in our hospital. The following phenotypic parameters were analyzed at disease onset and over a long-term period: age and initial presentation at onset, recurrent stroke after initial revascularization, and final modified Rankin Scale. RESULTS: The p.R4810K genotype was significantly associated with the phenotype at onset, especially in younger patients. Over a median follow-up period of 100 months, recurrent stroke occurred in 6 out of 94 patients: none out of 5 patients with the homozygous variant, 5 out of 64 with the heterozygous variant, and 1 out of 25 in the wild-type group. There were no significant differences among the genotypes. In particular, recurrent cerebral hemorrhage occurred in 5 patients, all possessing the heterozygous variant. The log-rank test showed no difference between the genotypes in the stroke-free survival rate. Furthermore, the p.R4810K genotype was not associated with a poor functional condition. CONCLUSIONS: The p.R4810K founder variant of RNF213 affects the phenotype at disease onset. However, the optimal revascularization may be effective, regardless of the genotype, even for the homozygous variant, which has been thought to be the most pathogenic. This genotype may not strongly influence the long-term clinical manifestations or poor prognosis in MMD.
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Adenosina Trifosfatasas/genética , Infarto Encefálico/genética , Hemorragia Cerebral/genética , Variación Genética , Ataque Isquémico Transitorio/genética , Enfermedad de Moyamoya/genética , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Infarto Encefálico/diagnóstico , Infarto Encefálico/cirugía , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/cirugía , Hemorragia Cerebral Intraventricular/diagnóstico , Hemorragia Cerebral Intraventricular/genética , Hemorragia Cerebral Intraventricular/cirugía , Revascularización Cerebral , Niño , Preescolar , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lactante , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/cirugía , Persona de Mediana Edad , Enfermedad de Moyamoya/diagnóstico , Enfermedad de Moyamoya/terapia , Fenotipo , Supervivencia sin Progresión , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tokio , Adulto JovenRESUMEN
OBJECTIVEEffectively retaining the patency of the extracranial-intracranial (ECIC) bypass is one of the most important factors in improving long-term results; however, the factors influencing bypass patency have not been discussed much. Therefore, the authors investigated factors influencing the development of the bypass graft.METHODSIn this retrospective study, the authors evaluated 49 consecutive hemispheres in 47 adult Japanese patients who had undergone ECIC bypass for chronic steno-occlusive cerebrovascular disease. To evaluate objectively the development of the ECIC bypass graft, the change in the area of the main trunk portion of the superficial temporal artery (STA) from before to after bypass surgery (postop/preop STA) was measured. Using the interquartile range (IQR), the authors statistically analyzed the factors associated with excellent (> 3rd quartile) and poor development (< 1st quartile) of the bypass graft.RESULTSThe postop/preop STA ranged from 1.08 to 6.13 (median 1.97, IQR 1.645-2.445). There was a significant difference in the postop/preop STA between the presence and absence of concurrent diabetes mellitus (p = 0.0432) and hyperlipidemia (0.0069). Furthermore, logistic regression analysis revealed that only concurrent diabetes mellitus was significantly associated with poor development of the bypass graft (p = 0.0235).CONCLUSIONSDiabetes mellitus and hyperlipidemia influenced the development of the ECIC bypass graft. In particular, diabetes mellitus is the only factor associated with poor development of the bypass graft.
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Revascularización Cerebral/métodos , Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/cirugía , Grado de Desobstrucción Vascular/fisiología , Adulto , Anciano , Revascularización Cerebral/tendencias , Trastornos Cerebrovasculares/epidemiología , Diabetes Mellitus/diagnóstico por imagen , Diabetes Mellitus/epidemiología , Diabetes Mellitus/cirugía , Femenino , Estudios de Seguimiento , Humanos , Hiperlipidemias/diagnóstico por imagen , Hiperlipidemias/epidemiología , Hiperlipidemias/cirugía , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Angiosarcoma is a very rare tumor. The malignancy is high grade and the prognosis is extremely poor. A 51-year-old man was admitted to our hospital with the main complaint of asymptomatic macroscopic hematuria. Since right ureteral cancer was suspected by the imaging examination, laparoscopic right total nephroureterectomy was planned. However, strong adhesion was found between the tumor and the surrounding tissue, and the tumor could not be completely resected from the distal ureter. Pathological diagnosis was primary ureteral angiosarcoma, and staging was right middle ureteral angiosarcoma T3N0M0. However, since surgical findings strongly suspected that the peeled surface was positive, adjuvant radiation therapy was added. He is alive without disease recurrence at one year and eight months after surgery.
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Hemangiosarcoma , Uréter , Neoplasias Ureterales , Hemangiosarcoma/diagnóstico , Hemangiosarcoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nefroureterectomía , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/cirugíaRESUMEN
Plasmacytomas are characterized by a monoclonal proliferation of plasma cells, and constitute the bulk of multiple myeloma. A solitary plasmacytoma is a rare entity, and is even more unlikely to occur intracranially. Here we present a 62-year-old man with an intracranial tumor. Magnetic resonance imaging revealed a large mass on the surface of the right fronto-parieto-temporal region, with extradurally directed growth. The tumor was enhanced homogenously by gadolinium, with dural tail-like findings, which resembled a meningioma. Head computed tomography scan showed osteolytic changes of the calvarium. Tumor removal following intravascular embolization was performed. The tumor seemed to have developed from the dura mater because it was firmly adhered to the dura but not to the calvarium. Histopathological analysis revealed monoclonal proliferation of plasma cells, which were positive for CD56, CD138, and lambda chain, on immunostaining. Since a systemic examination showed no evidence of other lesions, we diagnosed the tumor as a solitary dural plasmacytoma. There was no recurrence after postoperative radiotherapy. Rare entities, such as a solitary plasmacytoma, should be considered when an intracranial lesion with atypical radiological features is observed. If the lesion is anatomically resectable, histopathological evaluation is essential.
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Neoplasias Encefálicas/cirugía , Plasmacitoma/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Plasmacitoma/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Delayed traumatic intracerebral hematoma (DTICH) is a rare complication of head injury that appears suddenly after an interval of several days or months. Here, we report a case of DTICH during antiplatelet therapy for vasospasm following surgeries for a ruptured left internal carotid-posterior communicating (ICPC) aneurysm and right acute epidural hematoma (EDH). A 77-year-old man with no medical history was diagnosed with a subarachnoid hemorrhage (SAH) due to rupturing of a left ICPC aneurysm and a right linear fracture of the right parietal bone due to a head injury following the rupture. On day 2, the patient underwent successful clipping of the left ICPC aneurysm. Computed tomography (CT) performed post-clipping revealed a right acute EDH below the linear fracture of the right parietal bone, which was removed immediately. A next-day CT revealed minor contusions in both temporal poles. Fasudil, ozagrel, and cilostazol were administered from Day 3 post-clipping and EDH evacuation to prevent vasospasm. The contusions did not enlarge until Day 10. On Day 11, the patient became comatose, and a huge hematoma was identified in the right temporal lobe to frontal lobe. Although the hematoma was removed immediately, the patient died on Day 13. The hematoma was considered to be a rare case of DTICH that developed from a minor contusion of the right temporal lobe during antiplatelet therapy for vasospasm. In cases of aneurysmal SAH with head injury and contusion, we must pay attention to DTICH and select more deliberate treatment for vasospasm.
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Aneurisma Roto/cirugía , Hemorragia Cerebral Traumática/cirugía , Traumatismos Craneocerebrales , Hematoma/etiología , Aneurisma Intracraneal/cirugía , Hueso Parietal/patología , Fracturas Craneales , Anciano , Angiografía , Humanos , Masculino , Imagen Multimodal , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
In the hydrogenotrophic methanogenic pathway, formylmethanofuran dehydrogenase (Fmd) catalyzes the formation of formylmethanofuran through reducing CO2. Heterodisulfide reductase (Hdr) provides two low potential electrons for the Fmd reaction using a flavin-based electron-bifurcating mechanism. [NiFe]-hydrogenase (Mvh) or formate dehydrogenase (Fdh) complexes with Hdr and provides electrons to Hdr from H2 and formate, or the reduced form of F420, respectively. Recently, an Fdh-Hdr complex was purified as a 3-MDa megacomplex that contained Fmd, and its three-dimensional structure was elucidated by cryo-electron microscopy. In contrast, the Mvh-Hdr complex has been characterized only as a complex without Fmd. Here, we report the isolation and characterization of a 1-MDa Mvh-Hdr-Fmd megacomplex from Methanothermobacter marburgensis. After anion-exchange and hydrophobic chromatography was performed, the proteins with Hdr activity eluted in the 1- and 0.5-MDa fractions during size exclusion chromatography. Considering the apparent molecular mass and the protein profile in the fractions, the 1-MDa megacomplex was determined to be a dimeric Mvh-Hdr-Fmd complex. The megacomplex fraction contained a polyferredoxin subunit MvhB, which contains 12 [4Fe-4S]-clusters. MvhB polyferredoxin has never been identified in the previously purified Mvh-Hdr and Fmd preparations, suggesting that MvhB polyferredoxin is stabilized by the binding between Mvh-Hdr and Fmd in the Mvh-Hdr-Fmd complex. The purified Mvh-Hdr-Fmd megacomplex catalyzed electron-bifurcating reduction of [13C]-CO2 to form [13C]-formylmethanofuran in the absence of extrinsic ferredoxin. These results demonstrated that the subunits in the Mvh-Hdr-Fmd megacomplex are electronically connected for the reduction of CO2, which likely involves MvhB polyferredoxin as an electron relay.
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Dióxido de Carbono , Hidrógeno , Methanobacteriaceae , Methanobacteriaceae/metabolismo , Methanobacteriaceae/enzimología , Hidrógeno/metabolismo , Hidrógeno/química , Dióxido de Carbono/metabolismo , Dióxido de Carbono/química , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Ferredoxinas/metabolismo , Ferredoxinas/química , Oxidación-Reducción , Proteínas Arqueales/metabolismo , Proteínas Arqueales/química , Proteínas Arqueales/genética , Electrones , Hidrogenasas/metabolismo , Hidrogenasas/químicaRESUMEN
General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
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Linfocitos T CD8-positivos , Propofol , Propofol/farmacología , Animales , Ratones , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Inflamación/inmunología , Diferenciación Celular/efectos de los fármacos , Citocinas/metabolismo , Listeriosis/inmunología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , FemeninoRESUMEN
Background: Bilateral vertebral artery dissection aneurysm (VADA) is a rare condition that leads to severe stroke. However, the surgical strategy for its treatment is controversial because the pathology is very complicated and varies in each case. Here, we report a case of bilateral VADA that was successfully treated with staged bilateral VADA occlusion and low-flow bypass. Case Description: A Japanese man in his 40s presented with bilateral VADA with subarachnoid hemorrhage. He had only mild headaches without any other neurological deficits. Subsequently, the ruptured left VADA was surgically trapped. However, on postoperative day 11, the contralateral VADA enlarged. The right VADA was then proximally clipped via a lateral suboccipital approach. Furthermore, a superficial temporal artery-superior cerebellar artery bypass was performed through a subtemporal approach in advance to preserve cerebral flow in the posterior circulation. The bilateral VADA was obliterated, and the patient had an uneventful postoperative course during the 1-year and 6-month follow-up period. Conclusion: Bilateral VADA can be successfully treated with staged bilateral VADA obstruction and low-flow bypass. In this case, as the posterior communicating arteries were the fetal type and the precommunicating segments of the posterior cerebral arteries (P1) were hypoplastic, a low-flow bypass was used to supply the basilar and cerebellar arteries, except the posterior cerebral and posterior inferior cerebellar arteries. Furthermore, low-flow bypass is a less invasive option than high-flow bypass.
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Background. Robotic-assisted thoracic surgery (RATS) is now standard for lung cancer treatment, offering advantages over traditional methods. However, RATS's minimally invasive approach poses challenges like limited visibility and tactile feedback, affecting surgeons' navigation through com-plex anatomy. To enhance preoperative familiarization with patient-specific anatomy, we devel-oped a virtual reality (VR) surgical navigation system. Using head-mounted displays (HMDs), this system provides a comprehensive, interactive view of the patient's anatomy pre-surgery, aiming to improve preoperative simulation and intraoperative navigation. Methods. We integrated 3D data from preoperative CT scans into Perspectus VR Education software, displayed via HMDs for in-teractive 3D reconstruction of pulmonary structures. This detailed visualization aids in tailored preoperative resection simulations. During RATS, surgeons access these 3D images through Tile-ProTM multi-display for real-time guidance. Results. The VR system enabled precise visualization of pulmonary structures and lesion relations, enhancing surgical safety and accuracy. The HMDs offered true 3D interaction with patient data, facilitating surgical planning. Conclusions. VR sim-ulation with HMDs, akin to a robotic 3D viewer, offers a novel approach to developing robotic surgical skills. Integrated with routine imaging, it improves preoperative planning, safety, and accuracy of anatomical resections. This technology particularly aids in lesion identification in RATS, optimizing surgical outcomes.