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PURPOSE: This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality in adults with stroke sequelae during the subacute to chronic rehabilitation phase. MATERIALS AND METHODS: In this systematic review and meta-analysis of randomized controlled trials (RCT), electronic databases, including PubMed, Web of Science, CINAHL, and MEDLINE, were searched. We included RCTs that investigated the outcomes of adjuvant therapy (i.e. other therapies) added to CIMT compared with CIMT alone. Key trial findings were qualitatively synthesized and analyzed. This meta-analysis examined variables, such as mean scores and standard deviations, using the following outcome measures: Fugl-Meyer Assessment (FMA) upper limb items, Action Research Arm Test (ARAT), Amount of Use (AOU) of Motor Activity Log (MAL), and Quality of Movement (QOM) of MAL. RESULTS: Eighteen eligible RCTs were included in the analysis. Adding CIMT to adjunctive therapy significantly improved FMA compared with CIMT alone (mean difference [MD] 4.02, 95% confidence interval [CI] 2.60-5.44; I2 = 85%; 15 studies; 330 participants). Similarly, the ARAT and MAL-AOU scores improved significantly. CONCLUSIONS: CIMT combined with several adjunctive therapies effectively improved upper limb function.
In recent years, clinical trials combining other therapies with Constraint-induced movement therapy (CIMT) have become increasingly common.This study shows that combining CIMT with adjuvant therapy improves upper limb function.Different protocols of the CIMT in each study could be factor that impacted the results of Motor Activity Log.In clinical practice, the findings of this study into their treatment protocols to improve patient outcomes and ensure the effective application of evidence-based rehabilitation strategies.
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BACKGROUND: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. METHODS: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. RESULTS: Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth. CONCLUSIONS: Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis. TRIAL REGISTRATION: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .
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Atresia Esofágica , Neoplasias Esofágicas , Estenosis Esofágica , Humanos , Estenosis Esofágica/etiología , Estenosis Esofágica/cirugía , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Constricción Patológica/complicaciones , Mucosa Bucal/trasplante , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Resultado del Tratamiento , Células Epiteliales/trasplante , Estudios RetrospectivosRESUMEN
We developed a wearable swallowing assessment device using a hetero-core fiber-optic pressure sensor for the detection of laryngeal movement during swallowing. The proposed pressure sensor (comfortably attached to the skin of the neck) demonstrated a high sensitivity of 0.592 dB/kPa and a linearity of R2 = 0.995 within a 14 kPa pressure band, which is a suitable pressure for the detection of laryngeal movement. In addition, since the fabricated hetero-core fiber-optic pressure sensor maintains appreciable sensitivity over the surface of the sensor, the proposed wearable swallowing assessment device can accurately track the subtle pressure changes induced by laryngeal movements during the swallowing process. Sixteen male subjects and one female subject were evaluated in a variety of age groups ranging from 30 to 60 years old. For all subjects, characteristic swallowing waveforms (with two valleys based on laryngeal movements consisting of upward, forward, backward, and downward displacements) were acquired using the proposed wearable swallowing assessment device. Since the denoted time of the first valley in the acquired waveform determines the "aging effect", significant differences in swallowing functions among the different age groups were ultimately determined based on the time of the first valley. Additionally, by analyzing each age group using the proposed device, due to p-values being consistently less than 0.05, swallowing times were found to exhibit statistically significant differences within the same groups.
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Deglución , Tecnología de Fibra Óptica , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Envejecimiento , Ambiente , OjoRESUMEN
OBJECTIVE: This study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). METHODS: Twenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. RESULTS: The rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). CONCLUSIONS: Our findings demonstrate the significant differences in power and functional connectivity between outcome groups. SIGNIFICANCE: This study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.
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Hormona Adrenocorticotrópica , Espasmos Infantiles , Lactante , Humanos , Hormona Adrenocorticotrópica/uso terapéutico , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/tratamiento farmacológico , Resultado del Tratamiento , Electroencefalografía , Síndrome , EspasmoRESUMEN
BACKGROUND: Congenital esophageal atresia postoperative anastomotic stricture occurs in 30-50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. METHODS: Epithelial cell sheets were fabricated from a patient's oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. RESULTS: The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. CONCLUSIONS: These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. TRIAL REGISTRATION: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .
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Atresia Esofágica , Estenosis Esofágica , Niño , Constricción Patológica/complicaciones , Constricción Patológica/terapia , Atresia Esofágica/complicaciones , Atresia Esofágica/cirugía , Estenosis Esofágica/prevención & control , Estenosis Esofágica/cirugía , Humanos , Mucosa Bucal/trasplante , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements. METHODS: We enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae. RESULTS: Of the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12-24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12-24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively. CONCLUSIONS: The appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.
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Encefalopatías/diagnóstico , Discinesias/diagnóstico , Convulsiones/diagnóstico , Encefalopatías/complicaciones , Encefalopatías/fisiopatología , Preescolar , Discinesias/etiología , Discinesias/fisiopatología , Femenino , Escala de Coma de Glasgow , Humanos , Lactante , Masculino , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/fisiopatologíaRESUMEN
Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) often causes various neurological sequelae, necessitating early and objective differentiation of AESD from a febrile seizure (FS). Therefore, we developed a scoring system that predicts AESD onset using only early laboratory data. Methods: We selected patients with AESD or FS admitted to the Tottori University Hospital between November 2005 and September 2020 and collected laboratory data from onset to discharge in patients with FS and from onset to the second neurological events in patients with AESD. Results: We identified 18 patients with AESD and 181 patients with FS. In comparison with patients with FS, patients with AESD showed statistically significant increases in ammonia (NH3), blood sugar (BS), and serum creatinine (Cr) levels, and the white blood cell (WBC) count, and a significant decrease in pH at <3 h from onset. We set the cut-off values and adjusted the weight of each of these parameters based on data obtained <3 h from onset and proposed a scoring system for predicting AESD. This system showed 91% sensitivity and 94% specificity for distinguishing AESD from FS. These accuracies were only slightly improved by the addition of information related to consciousness and seizure duration (sensitivity, 91%; specificity, 96%). Conclusion: NH3, BS, and Cr levels, WBC count, and pH were significantly different between patients with AESD and patients with FS at <3 h from seizure onset. This scoring system using these data may enable the prediction of AESD onset for patients under sedation or without precise clinical information.
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OBJECTIVE: Upper limb paralysis, which is a sequela of stroke, limits patients' activities of daily living and lowers quality of life. The objective of this study was to examine the effects of peripheral nerve stimulation on hemiparetic upper limb functional recovery in chronic stroke patients undergoing low-frequency repetitive transcranial magnetic stimulation and occupational therapy. METHODS: The subjects were chronic stroke patients who participated in a two-week inpatient programme including repetitive transcranial magnetic stimulation and occupational therapy. There were two groups of patients: the peripheral nerve stimulation group (11 patients who underwent peripheral nerve stimulation) and the control group (11 patients who previously participated in the same inpatient programme but without peripheral nerve stimulation, selected via propensity score matching). The peripheral nerve stimulation group had 1 h of peripheral nerve stimulation on the median and ulnar nerves during occupational therapy. The outcome measures were the Wolf Motor Function Test, Fugl-Meyer Assessment, and Motor Activity Log. RESULTS: Wolf Motor Function Test, Fugl-Meyer Assessment, and Motor Activity Log showed significant improvement after the intervention in the peripheral nerve stimulation group. Particularly, the Fugl-Meyer Assessment hand score significantly improved in the peripheral nerve stimulation group compared to that in the control group (median change: 2 versus 0; p = 0.021, r = 0.49). CONCLUSION: The combined use of peripheral nerve stimulation with occupational therapy after repetitive transcranial magnetic stimulation may result in a better functional recovery of in hemiparetic upper limb. Peripheral nerve stimulation with stimulation above the sensory threshold and below the motor threshold is easy to combine with occupational therapy upper limb function training and is therefore clinically useful.
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Sonodynamic therapy (SDT) is a minimally invasive anticancer therapy involving a chemical sonosensitizer and high-intensity focused ultrasound (HIFU). SDT enables the reduction of drug dose and HIFU irradiation power compared to those of conventional monotherapies. In our previous study, mouse models of colon and pancreatic cancer were used to confirm the effectiveness of SDT vs. drug-only or HIFU-only therapy. To validate its usefulness, we performed a clinical trial of SDT using an anticancer micelle (NC-6300) and our HIFU system in four pet dogs with spontaneous tumors, including chondrosarcoma, osteosarcoma, hepatocellular cancer, and prostate cancer. The fact that no adverse events were observed, suggests the usefulness of SDT.
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Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes. The MSC sheets were endoscopically transplanted to the inflamed area in electrocoagulation and DNBS colitis model. The effect of the transplantation was verified using endoscopic scoring and histological analysis. In the electrocoagulation model, the AD-MSC group showed significantly decreased ulcer size in the transplanted regions. In the DNBS colitis model, the AD-MSC group showed decreased inflammation and colitis in the transplanted regions. Histologic analysis showed that the MSC sheets had successfully attached to the inflamed mucosa in both the electrocoagulation and DNBS colitis model. Our results show that endoscopic transplantation of MSC sheets could be a new effective mode of stem cell therapy for IBD treatment.
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Colitis/terapia , Inflamación/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Colitis/inducido químicamente , Colitis/genética , Colitis/patología , Dinitrofluorobenceno/análogos & derivados , Dinitrofluorobenceno/toxicidad , Modelos Animales de Enfermedad , Endoscopios , Proteínas Fluorescentes Verdes/genética , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Ratones , Ratas , Ratas Transgénicas/genéticaRESUMEN
Sonodynamic therapy (SDT) is currently considered as one of the promising minimally invasive treatment options for solid cancers. SDT is based on the combined use of a sonosensitizer drug and high-intensity focused ultrasound (HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well known as effective sonosensitizers after interaction with focused ultrasound. Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed that comprises EPI through an acid-labile hydrazone bond. In previous in vivo studies, NC-6300 showed basic drug safety and an excellent concentration property of EPI, and recently has been tested in clinical trials. For realizing minimally invasive cancer treatment, the present study demonstrated the effectiveness and feasibility of DDS-based SDT, which combined a small dose of NC-6300 and low energy of HIFU in mouse models of colon cancer and pancreatic cancer.
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Antibióticos Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Epirrubicina/administración & dosificación , Terapia por Ultrasonido/métodos , Animales , Terapia Combinada/métodos , Relación Dosis-Respuesta a Droga , Ratones , Modelos AnimalesRESUMEN
Background and study aims: Epidermal cell sheet (ECS) transplantation immediately after aggressive endoscopic submucosal dissection (ESD) has been shown to be safe and effective in the prevention of esophageal strictures. This study evaluated the feasibility of ECS transplantation after endoscopic balloon dilation (EBD) in a porcine model. Methods: Six pigs underwent circumferential esophageal ESD under general anesthesia. Two weeks later, two pigs underwent EBD and transplantation of an autologous ECS, two underwent EBD alone, and two underwent endoscopic observation only (control). Results: The two pigs in the transplantation group underwent six ECS transplants after EBD with five of the six (83â%) being successful, as shown by engraftment of transplanted ECSs after 7 days. No adverse events were observed. Stricture rates were lower in the two transplanted pigs (55â% and 60â%) than in the control (92.2â% and 87.7â%) and EBD-treated (71.7â% and 78.2â%) pigs. Infiltration of inflammatory cells was significantly lower in the transplanted pigs than in the control and EBD-treated pigs. Conclusion: Preliminary results indicate the stability of the ECS transplantation procedure and the engraftment of transplanted ECS in the tears after EBD. This proof-of-concept study suggests that covering tears with ECSs after EBD may avoid re-strictures.
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We have fabricated Si nanoparticles from Si swarf using the beads milling method. The mode diameter of produced Si nanoparticles was between 4.8 and 5.2 nm. Si nanoparticles in hexane show photoluminescence (PL) spectra with peaks at 2.56, 2.73, 2.91, and 3.09 eV. The peaked PL spectra are attributed to the vibronic structure of adsorbed dimethylanthracene (DMA) impurity in hexane. The PL intensity of hexane with DMA increases by ~3000 times by adsorption on Si nanoparticles. The PL enhancement results from an increase in absorption probability of incident light by DMA caused by adsorption on the surface of Si nanoparticles.
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BACKGROUND: To prevent severe esophageal stenosis after aggressive endoscopic submucosal dissection (ESD), our group previously reported an efficient treatment using cell sheets that had been fabricated from patient cells. However, this transplantation procedure had not been easy for every endoscopist and needed to be improved to derive the full effect of epithelial cell sheets. OBJECTIVE: To develop an endoscopic device that enables easy and effective cell sheet transplantation and to evaluate its performance and clinical feasibility. DESIGN: Animal study. SETTING: Animal experimentation laboratory. INTERVENTION: Three pigs underwent circumferential esophageal ESD while under general anesthesia. A total of 12 cell sheets were endoscopically transplanted to the ESD site; 6 cell sheets were transplanted by using an endoscopic device that we developed, and 6 cell sheets were transplanted by using the conventional method. MAIN OUTCOME MEASUREMENTS: Procedure time, transplanted area on the ESD site, transplantation success rate, and monitoring of adverse events or incidents. RESULTS: The device allowed successful transplantation of all cell sheets with a shorter procedure time than with the conventional method (4.8 ± 0.8 minutes vs 13.3 ± 5.7 minutes, respectively) (P = .005) and onto a larger area (111.3 ± 56.3 mm(2) vs 41.8 ± 4.2 mm(2), respectively) (P = .023) with a higher success rate (100% vs 83%, respectively). No adverse incidents were monitored in each method. LIMITATIONS: Animal study, small sample. CONCLUSION: A newly designed endoscopic cell sheet transplantation device would be useful.
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Estenosis Esofágica/prevención & control , Esofagectomía , Esofagoscopía/instrumentación , Queratinocitos/trasplante , Complicaciones Posoperatorias/prevención & control , Impresión Tridimensional , Animales , Estenosis Esofágica/etiología , Esofagectomía/métodos , Esofagoscopía/métodos , Estudios de Factibilidad , Femenino , Humanos , Porcinos , Ingeniería de Tejidos/métodosRESUMEN
OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)G4-related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4-related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4-related disease. STUDY DESIGN: Retrospective review in a tertiary referral hospital. METHODS: Twenty-three consecutive patients with IgG4-related disease, six allergic rhinitis (AR) patients, and eight healthy subjects (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and laboratory data were examined. Mucosal tissues from the inferior turbinate were obtained from all subjects before treatment. The level of IgG4-positive plasma cells and other infiltrating cells, and the number of nasal glands in the nasal subjects were compared among the three groups. RESULTS: Ten (43.4%) of 23 cases had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the IgG4-related disease group than in the HS and AR groups, whereas the number of nasal glands in the IgG4-related disease group was significantly lower than in the HS and AR groups. CONCLUSIONS: The inflammatory lesions associated with IgG4-related disease exist on the nasal membrane. Thus, the nasal manifestations of IgG4-related disease were thought to be different from AR.
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Hipergammaglobulinemia/diagnóstico , Inmunoglobulina G , Enfermedades Nasales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipergammaglobulinemia/complicaciones , Masculino , Persona de Mediana Edad , Enfermedades Nasales/etiología , Células Plasmáticas/patología , Estudios RetrospectivosRESUMEN
In this work, we developed a portable device to perform microcontact printing in a safety cabinet for cell culture. The device was designed to be small and non-bulky, easy to sterilize, while not requiring the use of electricity, and which requires very little manual handling. Moreover, the portable microcontact printer is reproducibly fabricated with a rapid prototyping system, and allows for the easy micropatterning of biomolecules with a resolution ranging from 20 to 500 µm. This opens new horizons in the direct and simple micropatterning of culture dishes and the mimicking and biofabrication of complex architectures of tissues.
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Técnicas de Cultivo de Célula/instrumentación , Animales , Bovinos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fibronectinas/farmacología , Técnica del Anticuerpo Fluorescente , Microscopía de Contraste de Fase , Presión , TemperaturaRESUMEN
Regenerative medicine with transplantable cell sheets fabricated on temperature-responsive culture surfaces has been successfully achieved in clinical applications, including skin and cornea treatment. Previously, we reported that transplantation of fibroblast cell sheets to wounded lung had big advantages for sealing intraoperative air leaks compared with conventional materials. Here, we report a novel device for minimally invasive transplantation of cell sheets in endoscopic surgery, such as video-assisted thoracoscopic surgery (VATS). The novel device was designed with a computer-aided design (CAD) system, and the three-dimensional (3D) data were transferred to a 3D printer. With this rapid prototyping system, the cell sheet transplantation device was fabricated using a commercially available photopolymer approved for clinical use. Square cell sheets (24 x 24 mm) were successfully transplanted onto wound sites of porcine lung placed in a human body model, with the device inserted through a 12 mm port. Such a device would enable less invasive transplantation of cell sheets onto a wide variety of internal organs.
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Trasplante de Células , Equipos y Suministros , Toracoscopía , Células 3T3 , Animales , Humanos , Ratones , Modelos Animales , Medicina Regenerativa , PorcinosRESUMEN
Interleukin (IL)-21 shows pleiotropic effects on the proliferation, differentiation, and effector functions of leukocytes. However, the influence of IL-21 on dendritic cell (DC) activation of natural killer T (NKT) cells has not yet been elucidated. In the present study, we examined the effect of IL-21 on murine myeloid DC ability to induce NKT cell production of interferon-gamma (IFN-gamma) and IL-4. Pretreatment of DCs with IL-21 and alpha-galactosylceramide (alpha-GalCer), an NKT cell-specific ligand, resulted in the enhanced ability of the DCs to induce NKT cell production of IFN-gamma but not IL-4 in vitro compared to DCs pretreated with alpha-GalCer alone. A similar effect of IL-21 was observed when DCs pretreated with IL-21 and alpha-GalCer in vitro were transferred into naïve mice. Direct administration of IL-21 to the mice also enhanced IFN-gamma production after injection of alpha-GalCer. Thus, IL-21 can modify DC ability to selectively enhance NKT cell production of IFN-gamma upon stimulation with alpha-GalCer.
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Células Dendríticas/inmunología , Interferón gamma/biosíntesis , Interleucinas/inmunología , Células Asesinas Naturales/inmunología , Animales , Antígeno B7-2/inmunología , Células Dendríticas/metabolismo , Femenino , Galactosilceramidas/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-4/biosíntesis , Células Asesinas Naturales/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB CRESUMEN
Macrophage migration inhibitory factor (MIF) plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-IIC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We found that MIFTg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIFTg mice and significantly increased numbers of CD69+ T cells were detected in the spleens of these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with agr;-galactosylceramide (alpha-GalCer). Further, repeated administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play an ameliorating role upon stimulation with alpha-GalCer in the inflammatory process in MIFTg mice.
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Artritis Experimental/inmunología , Células Asesinas Naturales/inmunología , Factores Inhibidores de la Migración de Macrófagos/fisiología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Artritis Experimental/genética , Artritis Experimental/patología , Colágeno Tipo II/inmunología , Galactosilceramidas/administración & dosificación , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Lectinas Tipo C , Lipopolisacáridos/inmunología , Factores Inhibidores de la Migración de Macrófagos/genética , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
BACKGROUND: Birch pollen is the major pollen allergen in Hokkaido, Northern Japan. We reported a Betula masting model based on the resource budget model hypothesis. In addition to weather conditions, cumulative hours of sunlight and mean temperature from May to July of the previous year, this model used the amount of annual pollen dispersed in previous and penultimate years as a parameter based on data from 1990 to 2000. OBJECTIVE: We compared the predicted and observed amount of pollen dispersed for 3 years from 2001 to 2003 and evaluated the usefulness of each parameter in this model. METHODS: Birch pollen was measured using the Durham sampler at the Hokkaido University Graduate School of Medicine Research Institute in Sapporo. RESULTS: The difference between predicted and observed amounts of pollen dispersal was about 200-500 grains cm(-2). The annual pollen dispersed in the previous year was found to be the most useful parameter. CONCLUSION: This model is useful in predicting whether the amount of birch pollen will be less than average, about average, more than average, or much more than average.