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1.
Br J Anaesth ; 132(5): 1097-1111, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37806932

RESUMO

BACKGROUND: Preprocedural, real-time, and computer-aided three-dimensional ultrasound has been widely used for neuraxial puncture; however, the optimal guidance is unclear. We examined the comparative efficacy of three ultrasound guidance and anatomical landmarks for neuraxial puncture in adults. METHODS: We searched for randomised controlled studies comparing the efficacy of ultrasound guidance and anatomical landmarks for neuraxial puncture in adults using electronic databases and unpublished studies. The primary outcomes were first-pass success and patient satisfaction. A random-effects network meta-analysis (NMA) was used. RESULTS: We identified 74 eligible studies (7090 patients). Preprocedural ultrasound and real-time ultrasound-guided neuraxial puncture improved first-pass success compared with anatomical landmarks (risk ratio [RR] 1.6; 95% credible interval [CrI] 1.3-1.9; RR 1.9; 95% CrI 1.3-2.9, respectively, moderate confidence). Computer-aided ultrasound-guided neuraxial puncture also increased first-pass success (RR 1.8; 95% CrI 0.97-3.3, low confidence), although estimates were imprecise. However, real-time ultrasound-guided neuraxial puncture resulted in minimal difference in first-pass success compared with preprocedural ultrasound (RR 1.2; 95% CrI 0.8-1.8, moderate confidence). Preprocedural ultrasound improved patient satisfaction slightly compared with anatomical landmark use (standardised mean differences 0.28; 95% CrI 0.092-0.47, low confidence). CONCLUSIONS: This NMA provides evidence supporting ultrasound-guided neuraxial puncture compared with use of anatomical landmarks, including indirect comparisons. Among the three ultrasound guidance methods, preprocedural ultrasound appears to be a better adjunctive option.

2.
BMC Nephrol ; 25(1): 134, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622507

RESUMO

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.


Assuntos
Hipocalcemia , Humanos , Estudos de Coortes , Hipocalcemia/induzido quimicamente , Hipocalcemia/epidemiologia , Japão/epidemiologia , Difosfonatos/efeitos adversos , Rim
3.
Sensors (Basel) ; 24(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38610231

RESUMO

The purpose of this study was to investigate the relationship between clinical outcomes and lateral thrust before and after unicompartmental knee arthroplasty (UKA) using inertial measurement sensor units. Eleven knees were evaluated with gait analysis. The varus angular velocity was used to evaluate lateral thrust. The femorotibial angle (FTA) and hip-knee-ankle angle (HKA) were used to evaluate lower-limb alignment, and the Oxford Knee Score (OKS) and Japanese Orthopaedic Association Score (JOA) were used to evaluate clinical outcomes. The mean pre-UKA peak varus velocity was 37.1 ± 9.8°/s, and that for post-UKA was 28.8 ± 9.1°/s (p = 0.00003), such that instabilities clearly improved. Assuming the definition of lateral thrust is when the varus angular velocity is more than 28.1°/s, 81.8% of patients had lateral thrust preoperatively, but this decreased to 55.6% postoperatively, such that the symptoms and objective findings improved. Both OKS and JOA improved after surgery. In addition, HKA was -7.9° preoperatively and -5.8° postoperatively (p = 0.024), and FTA was 181.4° preoperatively and 178.4° postoperatively (p = 0.012). There was a positive correlation between postoperative JOA and FTA, indicating that changes in postoperative alignment affected clinical outcomes. This study quantitatively evaluated the disappearance of lateral thrust by UKA, and it found that the stability can be achieved by UKA for unstable knees with lateral thrust.


Assuntos
Artroplastia do Joelho , Osteoartrite , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Extremidade Inferior , Articulação do Tornozelo
4.
Eur Spine J ; 32(12): 4101-4110, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37798592

RESUMO

PURPOSE: Spinal nerve injections have traditionally been performed under fluoroscopic (FL) and computed tomography (CT) guidance. Recently, ultrasound (US)-guided procedures have provided an alternative guidance approach that does not expose the patient and operator to radiation. The aim of this study was to compare the efficacy and safety of US-guided spinal nerve injections compared with FL- or CT-guided spinal nerve injections. METHODS: MEDLINE, Cochrane Library, EMBASE, international clinical trials registry platform (ICTRP) and ClinicalTrials.gov database searches for inclusion until February 2023 were independently performed by two authors using predefined criteria. Randomized controlled trials (RCTs) were included. Primary outcomes were change in pain score (numeric rating scale or visual analogue scale) and major adverse events. Secondary outcomes were procedure time, change in functional disability score and minor adverse events. Meta-analysis was performed using random-effect model. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment and Development (GRADE) approach. RESULTS: Eight RCTs involving 962 patients were included. There might be little to no difference in the mean score of the pain change between the US-guided methods and the FL- or CT-guided injections (standard mean difference -0.06; 95% confidence interval [CI] -0.26 to 0.15). US guidance probably reduced major adverse events (0.7% [3/433] and 6.5% [28/433], respectively), reduced procedure time (mean difference -4.19 min; 95% CI -5.09 to -3.30), and probably reduced minor adverse events (2.1% [9/433] and 4.2% [18/433], respectively) compared with FL or CT guidance. There was probably little to no difference in the change in functional disability score with either method. CONCLUSION: US-guided spinal nerve injections remained effective and reduced adverse events compared with conventional FL- or CT-guided spinal nerve injections. Further RCTs are required to verify our results. STUDY REGISTRATION: Open Science Forum (Available from: https://osf.io/vt92w/ ).


Assuntos
Dor , Nervos Espinhais , Humanos , Injeções , Fluoroscopia/métodos , Tomografia
5.
Acta Med Okayama ; 77(5): 499-509, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37899261

RESUMO

This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes.


Assuntos
Cauda Equina , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Cauda Equina/cirurgia , Cauda Equina/lesões
6.
Glycoconj J ; 39(2): 291-302, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982351

RESUMO

Gangliosides are important components of the membrane and are involved in many biological activities. St8sia5 is an α2,8-sialyltransferase involved in ganglioside synthesis, and has three isoforms. In this study, we analyzed the features of three isoforms, St8sia5-S, -M, and -L that had not been analyzed, and found that only St8sia5-L was localized in the Golgi, while the majority of St8sia5-M and -S were localized in the ER. The localization of Golgi of St8sia5 depended on the stem region. In addition, the incorporation of exogenous GD3 was upregulated only in St8sia5-L expressing cells. Taken together, the localization of St8sia5 is important for the activity of the enzyme.


Assuntos
Gangliosídeos , Sialiltransferases , Animais , Gangliosídeos/metabolismo , Complexo de Golgi/metabolismo , Camundongos , Isoformas de Proteínas/genética , Sialiltransferases/genética , Sialiltransferases/metabolismo
7.
Medicina (Kaunas) ; 58(8)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-36013524

RESUMO

Background and Objectives: Adequate initial fixation of the uncemented acetabular component in total hip arthroplasty is necessary to achieve long-term survival. Although screw fixation contributes to improved cup stability, there is currently no consensus on the use of this method. This study aimed to assess the existing randomized controlled trials (RCTs) on the efficacy and safety of cup fixation in total hip arthroplasty without screws. Materials and Methods: We searched the EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases to identify RCTs published before February 2022. Primary outcomes were reoperation, cup migration, and Harris Hip Score. Secondary outcomes were the presence of a radiolucent line in the acetabular region, translation and rotation movement, and polyethylene wear. We conducted meta-analyses using the random-effects models. The revised Cochrane risk-of-bias tool was used to assess the risk of bias for outcomes of interest; the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to summarize the body of evidence. Results: We included six reports from four studies. Total hip arthroplasty without screw fixation to the acetabular cup had little to no effect on reoperation (pooled relative risk, 0.98; 95% confidence interval, 0.14-6.68; I2 = 0%), cup migration (pooled relative risk, 1.72; 95% confidence interval, 0.29-10.33; I2 = 1%), Harris Hip Score (mean difference, 1.19; 95% confidence interval, -1.31-3.70; I2 = 0%), radiolucent line (pooled relative risk, 5.91; 95% confidence interval, 0.32-109.35), translation and rotation of all axes, and polyethylene wear (mean difference, 0.01; 95% confidence interval, -0.01-0.04; I2 = 0%), with very low certainty of evidence on all measures. Conclusions: The efficacy of acetabular cups without screw fixation in total hip arthroplasty remains uncertain, suggesting the need for prudent clinical application. Further large-scale, well-designed studies with low risk of bias are required.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acetábulo/cirurgia , Parafusos Ósseos , Seguimentos , Humanos , Polietilenos , Falha de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação
8.
J Orthop Sci ; 26(3): 343-347, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32312565

RESUMO

BACKGROUND: Proximal junctional fractures (PJFx) are the main cause for proximal junctional kyphosis (PJK), a complication of adult spinal deformity surgery. This study investigated risk factors for PJFx when performing long spinopelvic corrective fixation with lateral interbody fusion from T9 to ilium. METHODS: This was a retrospective study of 43 patients with a minimum follow-up of 2 years. Radiographic measurements including thoracic kyphosis (TK), sagittal vertical axis (SVA), T1 pelvic angle (TPA), proximal junctional angle (PJA), lumbar lordosis (LL), lower LL, and pelvic tilt were measured preoperatively, one-month postoperatively, and at final follow up. TK and LL were also measured in a fulcrum backward-bending position preoperatively. RESULTS: At final follow-up, PJK was found in 30/43 patients (69.8%); 20.9% of the cases had PJFx (9 patients). TPA (preoperative, and one-month postoperative) was significantly higher in the PJFx group than in the other groups. The differences in TPA, TK, and PJA between preoperative and one-month postoperative measurements in the PJFx group were significantly higher than those in the other groups. At final follow up, SVA was significantly higher in the PJFx group than in the "PJK without PJFx" group. TPA and TK were significantly higher in the PJFx group than in the other groups. PJA was significantly different between all groups. CONCLUSION: Preoperative large TPA was the only risk factor for PJFx. Preoperative flexibility of the thoracolumbar spine and overcorrection of sagittal deformity were not related to PJFx or PJK.


Assuntos
Cifose , Lordose , Fusão Vertebral , Adulto , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Lordose/diagnóstico por imagem , Lordose/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos
9.
Genesis ; 57(11-12): e23334, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31513343

RESUMO

Nanog is a core transcription factor specifically expressed not only in the pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs), embryonic germ cells (EGCs), and induced PSCs (iPSCs), but also in the unipotent primordial germ cells (PGCs). Although Nanog promoter/enhancer regions are well characterized by in vitro analyses, direct correlations between the regulatory elements for Nanog expression and in vivo expression patterns of Nanog have not been fully clarified. In this study, we generated Nanog-RFP transgenic (Tg) mice in which expression of red fluorescent protein (RFP) is driven by a 5.2 kb Nanog promoter/enhancer region. As expected, RFP was expressed in the inner cell mass of blastocysts, ESCs, and iPSCs. However, RFP fluorescence was not observed in PGCs, although Nanog was expressed in PGCs. Because RFP fluorescence was visible in the PGC-derived pluripotent EGCs in culture, it was suggested that the reporter gene expression was specifically activated in PSCs. In conclusion, we have generated a novel Nanog-RFP Tg mouse line that can selectively tag PSCs over unipotent PGCs.


Assuntos
Proteína Homeobox Nanog/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/patologia , Animais , Células Cultivadas , Células-Tronco Embrionárias/metabolismo , Células Germinativas/metabolismo , Proteínas de Homeodomínio/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Transgênicos , Proteína Homeobox Nanog/fisiologia , Fatores de Transcrição/genética
11.
Pain Pract ; 18(5): 625-630, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29080243

RESUMO

PURPOSE: We aimed to evaluate the incidence of (and risk factors for) postoperative pregabalin and/or limaprost to treat persistent numbness and/or pain of the lower extremities after lumbar spinal stenosis (LSS) surgery. METHODS: Medical records of 329 patients (168 men, 161 women; average age 70 years) were retrospectively reviewed for data on the duration of LSS diagnosis; LSS disease; preoperative medication (limaprost, pregabalin, or combined limaprost/pregabalin; duration); symptoms; preoperative/postoperative intermittent claudication (IC); operation type; and postoperative medication and period. RESULTS: Limaprost, pregabalin, and combined limaprost/pregabalin were prescribed preoperatively for 43%, 7%, and 5% of patients, respectively. At an average of 21 months postoperatively, limaprost, pregabalin, and combined therapy were prescribed in 11%, 8%, 4% of patients, respectively. Medication requirement was significantly lower postoperatively than preoperatively (P < 0.0001). Significant risk factors for required postoperative medication were required preoperative medication (odds ratio [OR] 3.088, 95% confidence interval [CI] 1.679 to 5.681]; postoperative period (OR 1.063, 95% CI 1.031 to 1.096); and postoperative IC (OR 3.868, 95% CI 1.481 to 10.103). A negative impact from postoperative medication was seen in patients who had undergone decompression surgery (OR 0.589, 95% CI 0.377 to 0.918). CONCLUSIONS: Overall, 23% of LSS patients required medication for pain and/or numbness at 21 months postoperatively. Significant factors portending required postoperative medication were preoperative medication, longer postoperative period, and postoperative IC. A negative influence from postoperative medication was seen in patients who had undergone decompression surgery without fusion.


Assuntos
Alprostadil/análogos & derivados , Dor/tratamento farmacológico , Pregabalina/uso terapêutico , Estenose Espinal/tratamento farmacológico , Idoso , Alprostadil/uso terapêutico , Descompressão Cirúrgica , Feminino , Humanos , Hipestesia/tratamento farmacológico , Hipestesia/etiologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Estenose Espinal/complicações , Estenose Espinal/cirurgia
12.
Cureus ; 16(5): e60306, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38882957

RESUMO

Cervical myelopathy is caused by compression of the cervical spinal cord for any reason. Cervical myelopathy most commonly affects the C5-6 level. However, C7-T1 single-level myelopathy is rare, and neurological findings may be atypical, making diagnosis difficult. We report three cases and discuss their clinical manifestations. Unlike other levels of cervical myelopathy, C7-T1 single-level myelopathy may present with gait disturbance without neurological deficits in the upper extremities. In addition, all three of our cases had different levels of spinal cord compression and locations of sensory deficits; at the C7-T1 level, the spinal cord compression may not correspond to the site of the sensory deficit. These features may help clinicians in the diagnosing of myelopathy.

13.
Cureus ; 16(5): e60584, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38894769

RESUMO

INTRODUCTION: The prognostic nutritional index (PNI) is an immune-nutritional index simply provided by a blood test. We retrospectively compared the postoperative outcomes of patients with lumbar disc herniation divided into two groups according to the PNI. MATERIALS AND METHODS: Seventy-three patients who underwent surgery at our hospital were included in the study. All patients had herniation between one of the L3/4, L4/5, or L5/S intervertebral discs and underwent one posterior lumbar interbody fusion. These patients were divided into two groups: patients with a PNI of <50 (poorly nourished (PN) group) and patients with a PNI of ≥50 (well-nourished (WN) group). Evaluation items included patient background characteristics, operative time, blood loss, postoperative complications, and length of hospital stay. RESULTS: The results showed that the body mass index was significantly higher in the WN group than in the PN group (p=0.0221). The rates of collagen disease, steroid use, and postoperative complications were significantly higher (p=0.0475, p=0.0073, and p=0.0211, respectively) and the length of hospital stay was significantly longer (p=0.021) in the PN group than in the WN group. CONCLUSION: In conclusion, this study indicates that postoperative complications and the length of hospital stay are significantly worse in PN patients than in WN patients.

14.
J Appl Physiol (1985) ; 136(3): 555-566, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38234292

RESUMO

Ventricular-vascular coupling in endurance athletes remains incompletely understood. The purpose of this study was to determine the ascending aortic impedance in endurance athletes and explore its associations with traditional cardiovascular measurements. In 15 young male endurance runners and 19 young healthy men, time-resolved (CINE) two-dimensional (2-D) phase-contrast MRI quantified the ascending aortic flow while the pressure waveform was simultaneously collected via a generalized transfer function. The aortic impedance modulus and phase were calculated in the frequency domain while characteristic impedance (ZcF) was calculated by averaging moduli between the 4th and 8th heart rate (HR) harmonics. Stroke volume (SV), left ventricular (LV) morphometry, double product, aortic compliance, and total peripheral resistance (TPR) were also measured. Endurance athletes had higher SV, slower HR, greater LV end-diastolic volume and mass, and lower double product than sedentary participants (all P < 0.05). ZcF was significantly lower in athletes than in sedentary participants (73.3 ± 19.2 vs. 93.4 ± 19.0 dyn·s/cm5, P = 0.005). Furthermore, ZcF was negatively correlated with SV (r = -0.691) and aortic compliance (r = -0.601) but was positively correlated with double product (r = 0.445) and TPR (r = 0.458; all P < 0.05). Multivariate analysis revealed that ZcF was the strongest predictor of SV followed by TPR and HR (adjusted R2 = 0.788, P < 0.001). Therefore, our findings collectively suggest that LV afterload quantified by aortic ZcF is significantly lower in endurance athletes than in sedentary adults. The lower pulsatile LV afterload may contribute to greater SV in endurance athletes.NEW & NOTEWORTHY This is the first study to investigate aortic impedance with the noninvasive, simultaneous recordings of aortic pressure using SphygmoCor XCEL and flow using phase-contrast MRI. We found that the characteristic impedance (Zc) is significantly lower in endurance athletes than sedentary adults, is the strongest predictor of stroke volume (SV), and is inversely associated with aortic compliance. These findings suggest that aortic impedance is a key determinant of the ventricular-vascular coupling adapted to long-term training in endurance athletes.


Assuntos
Atletas , Função Ventricular Esquerda , Adulto , Humanos , Masculino , Impedância Elétrica , Função Ventricular Esquerda/fisiologia , Volume Sistólico/fisiologia , Imageamento por Ressonância Magnética , Resistência Física/fisiologia
15.
J Synchrotron Radiat ; 20(Pt 6): 869-74, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24121330

RESUMO

Lipid liposomes are promising drug delivery systems because they have superior curative effects owing to their high adaptability to a living body. Lipid liposomes encapsulating proteins were constructed and the structures examined using synchrotron radiation small- and wide-angle X-ray scattering (SR-SWAXS). The liposomes were prepared by a sequential combination of natural swelling, ultrasonic dispersion, freeze-throw, extrusion and spin-filtration. The liposomes were composed of acidic glycosphingolipid (ganglioside), cholesterol and phospholipids. By using shell-modeling methods, the asymmetric bilayer structure of the liposome and the encapsulation efficiency of proteins were determined. As well as other analytical techniques, SR-SWAXS and shell-modeling methods are shown to be a powerful tool for characterizing in situ structures of lipid liposomes as an important candidate of drug delivery systems.


Assuntos
Lipossomos , Modelos Químicos , Proteínas/química , Espalhamento de Radiação , Raios X
16.
BMC Cancer ; 13: 555, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24261884

RESUMO

BACKGROUND: Glutamate decarboxylase 1 (GAD1), a rate-limiting enzyme in the production of γ-aminobutyric acid (GABA), is found in the GABAergic neurons of the central nervous system. Little is known about the relevance of GAD1 to oral squamous cell carcinoma (OSCC). We investigated the expression status of GAD1 and its functional mechanisms in OSCCs. METHODS: We evaluated GAD1 mRNA and protein expressions in OSCC-derived cells using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. To assess the critical functions of GAD1, i.e., cellular proliferation, invasiveness, and migration, OSCC-derived cells were treated with the shRNA and specific GAD1 inhibitor, 3-mercaptopropionic acid (3-MPA). GAD1 expression in 80 patients with primary OSCCs was analyzed and compared to the clinicopathological behaviors of OSCC. RESULTS: qRT-PCR and immunoblotting analyses detected frequent up-regulation of GAD1 in OSCC-derived cells compared to human normal oral keratinocytes. Suppression of nuclear localization of ß-catenin and MMP7 secretion was observed in GAD1 knockdown and 3-MPA-treated cells. We also found low cellular invasiveness and migratory abilities in GAD1 knockdown and 3-MPA-treated cells. In the clinical samples, GAD1 expression in the primary OSCCs was significantly (P < 0.05) higher than in normal counterparts and was correlated significantly (P < 0.05) with regional lymph node metastasis. CONCLUSIONS: Our data showed that up-regulation of GAD1 was a characteristic event in OSCCs and that GAD1 was correlated with cellular invasiveness and migration by regulating ß-catenin translocation and MMP7 activation. GAD1 might play an important role in controlling tumoral invasiveness and metastasis in oral cancer.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Glutamato Descarboxilase/fisiologia , Metaloproteinase 7 da Matriz/metabolismo , Neoplasias Bucais/enzimologia , beta Catenina/metabolismo , Ácido 3-Mercaptopropiônico/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Ativação Enzimática , Glutamato Descarboxilase/antagonistas & inibidores , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica , Transporte Proteico
17.
Microbiol Immunol ; 57(3): 163-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23278518

RESUMO

Clostridium septicum alpha-toxin has a unique tryptophan-rich region ((302)NGYSEWDWKWV(312)) that consists of 11 amino acid residues near the C-terminus. Using mutant toxins, the contribution of individual amino acids in the tryptophan-rich region to cytotoxicity and binding to glycosylphosphatidylinositol (GPI)-anchored proteins was examined. For retention of maximum cytotoxic activity, W307 and W311 are essential residues and residue 309 has to be hydrophobic and possess an aromatic side chain, such as tryptophan or phenylalanine. When residue 308, which lies between tryptophans (W307 and W309) is changed from an acidic to a basic amino acid, the cytotoxic activity of the mutant is reduced to less than that of the wild type. It was shown by a toxin overlay assay that the cytotoxic activity of each mutant toxin correlates closely with affinity to GPI-anchored proteins. These findings indicate that the WDW_W sequence in the tryptophan-rich region plays an important role in the cytotoxic mechanism of alpha-toxin, especially in the binding to GPI-anchored proteins as cell receptors.


Assuntos
Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Clostridium septicum/metabolismo , Glicosilfosfatidilinositóis/metabolismo , Proteínas/metabolismo , Triptofano/metabolismo , Animais , Toxinas Bacterianas/genética , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Clostridium septicum/genética , Análise Mutacional de DNA , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas Mutantes/toxicidade , Ligação Proteica , Triptofano/genética , Células Vero
18.
Eur Phys J E Soft Matter ; 36(7): 74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23852578

RESUMO

While the steady-state existence in the size and shape of liquid-ordered microdomains in cell membranes, the so-called "lipid rafts", still remain the subject of debate, glycosphingolipid-cholesterol rich regions in plasma membranes have been considered to have a function as platforms for signaling and sorting. In addition, recent spectroscopic studies show that the interaction between monosialoganglioside and amyloid beta (Aß protein promotes the transition of Aß from the native structure to the cross-beta fold in amyloid aggregates. However, there is few evidence on the dynamics of "lipid rafts" membranes. As the neutron spin-echo (NSE) technique is well known to detect directly slow dynamics of membrane systems in situ, by the combination of NSE and small-angle X-ray scattering we have studied the effect of the interaction between raft-model membrane and amyloid Aß proteins on the structure and dynamics of a large uni-lamellar vesicle (LUV) consisting of monosialoganglioside-cholesterol-phospholipid ternary mixtures as a model of lipid-raft membrane. We have found that the interaction between the Aß proteins and the model membrane at the liquid crystal phase significantly suppresses a bending-diffusion motion with a minor effect on the LUV structure. The present results would suggest a possibility of non-receptor-mediated disorder in signaling through a modulation of a membrane dynamics induced by the association of amyloidogenic peptides on a plasma membrane.


Assuntos
Peptídeos beta-Amiloides/química , Microdomínios da Membrana/química , Peptídeos beta-Amiloides/metabolismo , Colesterol/química , Gangliosídeo G(M1)/química , Microdomínios da Membrana/metabolismo , Ligação Proteica , Espalhamento a Baixo Ângulo , Lipossomas Unilamelares/química , Difração de Raios X
20.
Cureus ; 15(1): e33646, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36788867

RESUMO

Anomalous muscle causes thoracic outlet syndrome (TOS). A 40-year-old man presented with numbness of the left upper extremity, similar to cervical spondylotic radiculopathy. He presented with a positive Bakody's test. However, magnetic resonance imaging showed no significant changes in the cervical spine and revealed an anomalous muscle adjacent to the left brachial plexus. We diagnosed the muscle as the cause of TOS and performed a resection, which resulted in symptomatic improvement.

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