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1.
Nature ; 597(7876): 393-397, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34433967

RESUMEN

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.


Asunto(s)
Linaje de la Célula/genética , Células Clonales/metabolismo , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Mutación , ADN Mitocondrial/genética , Embrión de Mamíferos/embriología , Femenino , Humanos , Masculino , Tasa de Mutación
2.
J Neurol Surg A Cent Eur Neurosurg ; 83(3): 231-235, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34192784

RESUMEN

OBJECTIVE: Posterior subaxial cervical screw fixation is commonly performed using the cervical pedicle screws (CPS) and lateral mass screws (LMS); however, their compatibility is low. Modified lateral mass screws (mLMS, also called paravertebral foramen screw) fixation was introduced as a salvage technique for LMS fixation and has features of both LMS and CPS techniques. In the present study, the use of mLMS as an alternative to CPS was analyzed based on clinical results. METHODS: Seventy-eight screws (38 CPSs and 40 mLMSs) were inserted into 12 patients. The misplacement of the screws was evaluated by computed tomography (CT). The failure of instrumentation and instability were evaluated using plain radiographs. RESULTS: The total number of CPS misplacements was 3 (10.5%); however, neurologic complications were not observed. mLMSs were used in the middle segments of the fusion in 10 patients and 2 patients had mLMS fixation for single-level fusion. An additional bridging implant was not required for connecting both CPSs and mLMSs. Instability was not observed during the observation period (4-51 months). Complete fusion was seen in 10 patients. CONCLUSIONS: The alternative mLMS fixation can decrease the risk of screw misplacement compared with CPS fixation alone and achieves adequate stability leading to fusion.


Asunto(s)
Tornillos Pediculares , Fusión Vertebral , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Humanos , Fusión Vertebral/métodos , Tomografía Computarizada por Rayos X
3.
Tissue Eng Regen Med ; 19(1): 105-116, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34626334

RESUMEN

BACKGROUND: Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata. METHODS: Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8+ T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry. RESULTS: Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I+ cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8+ T cells were increased during the transition from mid-anagen to late catagen. CONCLUSION: Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege.


Asunto(s)
Alopecia Areata , Privilegio Inmunológico , Alopecia Areata/metabolismo , Alopecia Areata/terapia , Factor de Crecimiento Epidérmico/metabolismo , Folículo Piloso/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Recién Nacido
4.
Eur Spine J ; 19(5): 828-32, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20174836

RESUMEN

This paper reports a morphometric study of the C2 laminae to provide quantitative anatomical data for safe crossing laminar screw placement. A valid trajectory is essential for C2 crossing laminar screw placement. Although several clinical technique notes and modifications to define a safe screw trajectory have been introduced in the recent years, no morphometric analysis has been performed to confirm the accuracy of screw trajectory using this technique. In this study, morphometric analysis was performed on 100 Korean C2 three-dimensional reconstruction CT images. The reconstructive C2 vertebrae from the post-edge of the spinal canal to the spinal process were divided into several zones, 1 mm each. Each zone was chosen as the entry point to imitate a crossing laminar screw (3.5 mm diameter) placement. In each 1-mm zoned trajectory, the screw pass ratio (PR), safe screw angle range (SAR) and maximum screw length (MSL) were measured and compared with the data from the other zoned trajectories. The zone '5-6 mm posterior to the post-edge of the spinal canal' was found to be a more feasible and safer entry point for guiding a crossing laminar screw placement than the other zones because this zone could provide a trajectory with maximal PR (85%), SAR (9.57 +/- 4.36 masculine) and a larger MSL (21.74 +/- 2.44 mm) than the other areas. The recommended safe screw angle in the axial plane is 49.68 +/- 4.94 to 59.19 +/- 4.70 masculine. However, the screw angle can vary considerably according to the individual variance. A preoperative evaluation of the screw trajectory is essential for safe screw placement using this technique.


Asunto(s)
Tornillos Óseos , Vértebras Cervicales/diagnóstico por imagen , Procedimientos Ortopédicos/instrumentación , Adulto , Vértebras Cervicales/cirugía , Simulación por Computador , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Procedimientos Ortopédicos/métodos , Radiografía
5.
Clin Neuroradiol ; 30(1): 159-169, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31123775

RESUMEN

PURPOSE: To investigate the long-term outcome of stent angioplasty for symptomatic severe intracranial artery stenosis. METHOD: In this study 95 consecutive patients with intracranial atherosclerotic stenosis (>70%) underwent stent angioplasty using Wingspan stents. The primary endpoints were stroke or death within 30 days of the procedure and subsequent stroke attributed to the stented vessel. Disabling stroke was defined as stroke with a modified Rankin scale > 3. Secondary endpoints included transient ischemic attacks, contralateral stroke, nonstroke death, and other events. Patients underwent prestent balloon dilation with or without poststent balloon dilation, close restenosis follow-up, and selective retreatment, as required. RESULT: The mean follow-up duration was 34.9 ± 23.3 months. Primary endpoint events occurred in 23% of the patients. The median infarction volume was 2.6 ml, and 11 (68%) of 16 infarctions were <5 ml in volume. Disabling stroke occurred in 3% of patients. The primary endpoint rates were 17.9% within 30 days and 2.1% from 30 days to 1 year. Secondary endpoint events occurred in 27.3% of the patients. Mean stenosis was reduced from 76.8 ± 6.1% to 7.5 ± 13.4%. Of 80 patients who underwent angiographic follow-up, 11 (14%) experienced restenosis (≥50%) and 7 (9%) exhibited restenosis-related symptoms of transient ischemic attack. The rate of symptomatic restenosis was significantly higher in patients who underwent prestent balloon dilation alone than in patients who underwent prestent and poststent balloon dilation (p = 0.016). CONCLUSION: The postprocedural stroke rate was similar to that observed in the SAMMPRIS study. Symptomatic restenosis may be reduced by poststent dilation, close angiographic follow-up, and retreatment.


Asunto(s)
Angioplastia/instrumentación , Angioplastia/métodos , Oclusión de Injerto Vascular/prevención & control , Arteriosclerosis Intracraneal/cirugía , Stents , Anciano , Anciano de 80 o más Años , Angioplastia de Balón , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/cirugía , Angiografía por Tomografía Computarizada , Imagen de Difusión por Resonancia Magnética , Diseño de Equipo , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tiempo , Resultado del Tratamiento
6.
Clin Neuroradiol ; 30(1): 171, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32034460

RESUMEN

Correction to: Clin Neuroradiol 2019 https://doi.org/10.1007/s00062-019-00793-1The original version of this article unfortunately contained some mistakes. The Institutional Review Board number was given wrongly in the Methods/Participants section and in the Compliance with ethical guidelines/Ethical.

7.
Proteomics ; 9(19): 4445-56, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19688726

RESUMEN

Transforming growth factor-beta1 (TGF-beta1) has a wide range of biological functions such as the regulation of cell growth, differentiation, and immunological response in various types of cells. Particularly, TGF-beta1 induces plasminogen activator inhibitor-1 (PAI-1) as a major target protein. PAI-1 is associated with fibrosis, thrombosis, and metabolic disorders. In this study, to identify proteins potentially involved in TGF-beta1-induced fibrosis processes, we performed a proteomic analysis of TGF-beta1-induced normal rat kidney cells exposed to ascofuranone (AF). In these cells, we detected 1500 proteins, with 74 differentially expressed proteins identified by MALDI-TOF and reference to the NCBI and Swiss-Prot databases, including PAI-1, peroxisome prdifesator-activated receptor, prohibitin, glutamate formyltransferase, LIM domain protein 1, LASP-1, porphobilinogen deaminase, and peroxiredoxin 2. We also found that AF suppresses expression of profibrotic factors induced by TGF-beta in renal fibroblasts, including matrix proteins and PAI-1. AF was also shown to inhibit selectively phosphorylation of epidermal growth factor receptor, and downstream kinases such as extracellular signal-regulated kinase 1/2 (ERK-1/2). Further ongoing analysis of fibrosis-related proteins will determine AF's potential for application in fibrotic diseases and therapeutics.


Asunto(s)
Fibroblastos , Riñón , Proteoma/análisis , Sesquiterpenos/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Línea Celular , Electroforesis en Gel Bidimensional , Inhibidores Enzimáticos/metabolismo , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis/metabolismo , Fibrosis/patología , Riñón/citología , Riñón/efectos de los fármacos , Riñón/patología , Quinasas Quinasa Quinasa PAM/metabolismo , Datos de Secuencia Molecular , Estructura Molecular , Inhibidor 1 de Activador Plasminogénico/metabolismo , Ratas , Sesquiterpenos/química , Transducción de Señal/fisiología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Factor de Crecimiento Transformador beta1/genética
8.
PLoS One ; 14(7): e0219119, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31318904

RESUMEN

Thus far, anatomical studies have reported data on the cervical pedicle, with the focus remaining on the pedicle itself. It was necessary to obtain more comprehensive data about the relationships between the lateral mass, pedicle, and transverse foramen for cervical pedicle screwing (CPS) and paravertebral foramen screwing (PVFS), a new technique. The purpose of this study was to describe the relationships between the lateral mass, pedicle, and transverse foramen. This study analyzed computed tomography images from 77 patients (42 female, 35 male; mean age: 63.95 years). The anatomical pedicle transverse angle (PTA) and linear parameters of the lateral mass were measured, and the relationship between the calculated angles and the anatomical PTA was investigated. θp was defined as the convergence angle from the posterolateral edge of the lateral mass to the pedicle, and θc was defined as the convergence angle from the posterolateral edge of the lateral mass to the anterolateral corner of the vertebral foramen. The thickness of the cortical bone of the medial wall of the lateral mass (cT) and the medial (mT) and lateral (lT) walls of the pedicle at C3-7 were also measured. The PTA was similar to θp and θc at C3-6, but different at C7. In all cases, the transverse foramen was located more anterior to the posterior wall of the cervical body at C3-6, but not at C7. mT and cT were significantly thicker than lT at all levels. Lateral fluoroscopic images show that when the probe is inserted along θc, it meets the counter corner of the lateral mass at C3-6 without invasion of the transverse foramen if it does not cross the posterior wall of the vertebral body. This can be significant when performing CPS and PVFS.


Asunto(s)
Vértebras Cervicales/cirugía , Tornillos Pediculares , Anciano , Vértebras Cervicales/anatomía & histología , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/cirugía , Tomografía Computarizada por Rayos X
9.
J Orthop Res ; 36(1): 217-223, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28621468

RESUMEN

This study aimed to report the mechanical strength and characteristics of the lateral mass and pedicle considering BMD for the safe insertion of pedicle screws in the subaxial cervical level. We evaluated BMD and Hounsfield unit (HU) values of cortical bones at the lateral mass and pedicle of C3-7 from CT images in 99 patients. Patients were divided into three groups (Group A, T-score ≥ -1; Group B, -2.5 < T-score < -1.0; Group C, T-score ≤ -2.5). The HU numbers of cortical bone in the vertebral canal (medial wall of the lateral mass; cHU), posterior wall of the transverse foramen (fHU), and medial wall, lateral wall, and trabecular area of the pedicle (mHU, lHU, and pHU, respectively) were measured on the CT images in the middle of the pedicle. A mechanical study was also performed to measure cortical bone strength using 10 fresh cadavers. The cHU and mHU values in Group C were higher than lHU and fHU in Groups A and B, and there was a wide gap between the pHU value and other areas. The penetrating force also had a close correlation with HU number. The mean penetrating force of the medial wall of the lateral mass and the posterior wall of the transverse foramen were 210.08 ± 110.46 and 50.51 ± 46.09 N, respectively. The cortical bones in the vertebral canal and medial wall of the pedicle were stronger than the lateral wall and the trabecular area. The cHU and mHU in the osteoporotic group were higher than fHU and pHU in the normal group. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:217-223, 2018.


Asunto(s)
Densidad Ósea , Vértebras Cervicales/cirugía , Tornillos Pediculares , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/fisiología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
10.
Artif Organs ; 31(11): 801-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18001389

RESUMEN

We tested the effects on the early-stage wound healing of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofiber matrices cultured with hair follicular cells. PHBV only, PHBV/collagen, and PHBV/gelatin at a 7/3 weight ratio were produced by electrospinning, and their in vitro cell culture and in vivo wound healing as biological dressings were examined. In cell attachment and growth on matrices, dermal sheath (DS) cells attached to hydrophilic PHBV/collagen and PHBV/gelatin faster than hydrophobic PHBV at the early incubation stage (up to 6 h). From 6- to 24-h incubation, PHBV/collagen showed the best results in cell culture. Furthermore, PHBV/collagen cocultured for 3-5 days with DS and epithelial outer root sheath (ORS) cells expressed more extracellular materials, such as type I collagen, elastin, and alpha-smooth muscle actin, than cocultured PHBV with the same cells. However, there was no significant difference between PHBV and PHBV/collagen in the amounts of cytokeratin 8 expressed. Grafting of PHBV and PHBV/collagen matrices cocultured with ORS/DS cells for 3-5 days showed that PHBV promoted wound closure and re-epithelization more obviously than PHBV/collagen in both cocultured matrices and matrices alone. Cocultured matrices would heal wounds better than the corresponding matrices alone. Thus, PHBV cocultured with ORS/DS cells could be used as a cell-seeded biological dressing, thereby reducing preparation time as well as regenerating the epidermis efficiently during the early stage of wound healing.


Asunto(s)
Apósitos Biológicos , Poliésteres/farmacología , Ingeniería de Tejidos/métodos , Cicatrización de Heridas/fisiología , Heridas y Lesiones/terapia , Animales , Células Cultivadas , Técnicas de Cocultivo , Dermis/citología , Modelos Animales de Enfermedad , Células Epiteliales/citología , Folículo Piloso/citología , Humanos , Ratones , Ratones Desnudos , Distribución Aleatoria , Sensibilidad y Especificidad
11.
J Neurosurg Spine ; 7(2): 131-8, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17688051

RESUMEN

OBJECT: The purpose of this prospective controlled study was to evaluate possible factors that could affect postoperative segmental range of motion (ROM) after lumbar total disc replacement (TDR) using the ProDisc II prosthesis. METHODS: Thirty-two consecutive patients with intractable discogenic pain underwent lumbar TDR using the ProDisc II prosthesis, 30 of whom were followed up for at least 24 months. Segmental ROM was assessed preoperatively and every 6 months postoperatively using dynamic x-ray films. Segmental ROM at the reference level was assessed in relation to patient age, sex, body mass index (BMI), levels with implants, preoperative ROM, prosthesis size, and prosthesis position. RESULTS: At the last follow-up visit, mean ROM of the disc prostheses was significantly increased from 4.23 +/- 3.12 degrees to 6.81 +/- 3.76 degrees at L3-4, and from 3.66 +/- 2.47 degrees to 6.09 +/- 2.11 degrees at L4-5. Mean ROM at L5-S1, however, was decreased from 3.12 +/- 1.56 degrees to 2.86 +/- 1.26 degrees (p > 0.05). This difference in the changes in postoperative ROM between L5-S1 and the other operated levels was the only statistically significant factor (p = 0.025) among the variables related to the postoperative ROM that the authors assessed, but other factors such as patient age, sex, BMI, disc height, and the size and position of the prosthesis were not related to segmental ROM. CONCLUSIONS: The data demonstrate that after TDR using the ProDisc II prosthesis, ROM of the prosthesis at L5-S1 is significantly lower compared with ROM at the other levels. In preserving ROM, the advantage of lumbar TDR using the ProDisc II might be minimal at L5-S1. Among the variables related to postoperative ROM, the level at which the ProDisc II prosthesis was implanted was the only one found to be statistically significant.


Asunto(s)
Disco Intervertebral/fisiopatología , Disco Intervertebral/cirugía , Vértebras Lumbares/fisiopatología , Vértebras Lumbares/cirugía , Prótesis e Implantes , Rango del Movimiento Articular , Adulto , Femenino , Estudios de Seguimiento , Humanos , Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Radiografía , Sacro/fisiopatología , Factores de Tiempo
12.
Elife ; 62017 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-28695824

RESUMEN

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.


Asunto(s)
Folículo Piloso/fisiología , Cabello/crecimiento & desarrollo , Animales , Ratones , Modelos Biológicos , Regeneración , Análisis Espacio-Temporal
13.
J Invest Dermatol ; 136(1): 34-44, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26763421

RESUMEN

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.


Asunto(s)
Ciclo Celular/fisiología , Folículo Piloso/crecimiento & desarrollo , Cabello/fisiología , Animales , Apoptosis/fisiología , Biopsia con Aguja , Células Cultivadas , Guías como Asunto , Folículo Piloso/anatomía & histología , Xenoinjertos , Humanos , Inmunohistoquímica , Ratones , Ratones SCID
14.
Neuroreport ; 16(12): 1357-61, 2005 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-16056139

RESUMEN

Mesenchymal stem cells are able to trans-differentiate into nonmesodermal lineage cells. Here, we identified downstream signaling molecules required for acquisition of neuron-like traits by mesenchymal stem cells following the elevation of intracellular cAMP levels. We found that forskolin induced neuron-like morphology and expression of neuron-specific enolase and neurofilament-200 in mesenchymal stem cells. Forskolin sequentially activated protein kinase A and B-regulation of alpha-fetoprotein (Raf), which led to phosphorylation of extracellular signal-regulated kinase. Importantly, blockade of extracellular signal-regulated kinase phosphorylation with a mitogen-activated protein kinase (MAPK) kinase inhibitor abrogated the forskolin-induced morphological changes and induction of neuronal proteins. These results indicate that extracellular signal-regulated kinase/MAPK mediates both cAMP-induced early cytoskeletal rearrangement and the later induction of neuronal markers in mesenchymal stem cells.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , AMP Cíclico/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Adolescente , Western Blotting/métodos , Células Cultivadas , Niño , Colforsina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Humanos , Células Madre Mesenquimatosas/citología , Fosforilación/efectos de los fármacos , Factores de Tiempo , Quinasas raf/metabolismo
15.
Arch Dermatol Res ; 297(5): 210-7, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16231146

RESUMEN

We have developed liposomal formulation of 5-aminolevulinic acid (ALA) to enhance topical delivery and examined ALA-induced protoporpyrin (PpIX) expression in rat pilosebaceous unit throughout hair cycle. Two types of liposomes--glycerol dilaulate (GDL) and phosphatidylcholine (PC)--were formulated and both liposomal ALA increased PpIX expression in rat dorsal skin and pilosebaceous units when compared with free ALA. However, iontophoresis combined with liposomal ALA reduced the expression intensity of PpIX in hair bulbs although it achieved deeper and wider expression of PpIX through transfollicular pathway. After topical application in intact or depilated rat skin, liposomal ALA produced excellent PpIX expression in pilosebaceous units. The expression pattern and intensity of PpIX changed in hair cycle-dependent manner: specific expression only in sebaceous glands was observed at telogen; strong expression in whole pilosebaceous units was shown at anagen with intense expressions in hair bulbs and sebaceous glands; and a pattern similar to anagen but reduced intensity in the hair bulbs was seen at catagen. Throughout hair cycle, the expression pattern and intensity were dramatically changed in hair follicular epithelial cells depending on the cell density and proliferation activity of those cells, whereas those were consistent in sebaceous glands regardless of hair cycle. Little expression was shown in dermis. Photoactivation effect of 20% liposomal ALA-PDT using a red filtered-halogen lamp damaged sebaceous glands, hair follicles and epidermal layers. Formation of a thicker epidermal layer was observed, and hair induction after depilation was inhibited along with damage in sebaceous glands.


Asunto(s)
Ácido Aminolevulínico/administración & dosificación , Folículo Piloso/química , Protoporfirinas/análisis , Glándulas Sebáceas/química , Animales , Concentración de Iones de Hidrógeno , Liposomas , Fotoquimioterapia , Ratas , Ratas Sprague-Dawley
16.
Spine (Phila Pa 1976) ; 40(15): 1181-6, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-25996541

RESUMEN

STUDY DESIGN: Cadaver study and clinical application; a pilot study. OBJECTIVE: To minimize muscle dissection and enhance accuracy of cervical pedicle screw (CPS) placement by using a percutaneous cannula system. SUMMARY OF BACKGROUND DATA: Many studies have reported that the most frequent misplacement of CPSs is breach of the lateral wall; thus, an easy technique for securing medial convergence is required. We developed a percutaneous cannula system for this purpose and report the results of a cadaver study and its clinical application. METHODS: A cadaver study was conducted to confirm the possibility of this percutaneous technique in 5 specimens (50 CPSs, C3-C7). Then, the technique was applied in 8 patients (40 CPSs, C3-C7). The surgical technique was a hybrid of miniopen surgery and the use of percutaneous cannula system under lateral fluoroscopic guidance. Entry holes were made in the open field and a cannula was used for tapping and insertion of CPSs. A stiff pedicle probe through the cannula was used to locate the pedicle in the lateral mass. RESULTS: In the cadaver study, there were 12 (24%) misplacements among 50 CPSs used. The hybrid technique was applied clinically in 4 traumatic, 2 degenerative, and 2 failed back surgery lesions. Thirty CPSs were inserted using the percutaneous cannula system and 10 were inserted using a cannula as a retractor. Misplacement occurred in 6.7% (n = 2) and 20% (n = 2) pedicles, respectively, and there were no symptomatic complications (total incidence, 10%). An additional incision for the cannula system can be made for 2-level CPS insertions. CONCLUSION: Use of the percutaneous cannula system facilitated a secure convergence angle for CPS insertion without extending muscle dissection or shifting cervical alignment because of muscle retraction. Moreover, this system can be used for CPS insertion in bull-necked patients. LEVEL OF EVIDENCE: 3.


Asunto(s)
Tornillos Óseos , Vértebras Cervicales/cirugía , Procedimientos Ortopédicos/instrumentación , Procedimientos Ortopédicos/métodos , Traumatismos de la Espalda/cirugía , Cadáver , Catéteres , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Proyectos Piloto , Enfermedades de la Columna Vertebral/cirugía
17.
Int J Mol Med ; 12(3): 319-25, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12883647

RESUMEN

Serial subcultures of normal human oral keratinocytes (NHOKs) and normal human epidermal keratinocytes (NHEKs) to the postmitotic stage result in terminal differentiation and replicative senescence. In order to investigate the common mode of differentiation and/or senescence between mucosal and epidermal keratinocytes, gene expression profiling on both NHOKs and NHEKs was performed by a cDNA microarray analysis. Primary NHOKs and NHEKs were serially subcultured, and the expression level of 3,063 genes was compared between the exponentially growing and senescent cultures. The senescent NHOKs and NHEKs highly expressed 55 and 37 genes, respectively. Among these genes, 16 genes were common in both NHOKs and NHEKs while the other genes were upregulated either in the NHOKs or in the NHEKs. Furthermore, the expression levels of the common genes did not change in the human diploid fibroblasts during the subcultures. These results suggest that subculture-induced differentiation and/or replicative senescence in NHOKs and NHEKs has similar characteristics, but that the pathways leading to these processes are distinct and keratinocyte specific.


Asunto(s)
Diferenciación Celular/genética , Senescencia Celular/genética , Queratinocitos/fisiología , Northern Blotting , Diferenciación Celular/fisiología , Senescencia Celular/fisiología , Epidermis/fisiología , Humanos , Membrana Mucosa/fisiología , Análisis de Secuencia por Matrices de Oligonucleótidos
18.
Biotechnol Prog ; 19(3): 1011-5, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12790669

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world. To identify the histological subtype-specific genes of HCC, we analyzed the gene expression profile of 10 HCC patients by means of cDNA microarray. We proposed a systematic approach for determining the discriminatory genes and revealing the biological phenomena of HCC with cDNA microarray data. First, normalization of cDNA microarray data was performed to reduce or minimize systematic variations. On the basis of the suitably normalized data, we identified specific genes involved in histological subtype of HCC. Two classification methods, Fisher's discriminant analysis (FDA) and support vector machine (SVM), were used to evaluate the reliability of the selected genes and discriminate the histological subtypes of HCC. This study may provide a clue for the needs of different chemotherapy and the reason for heterogeneity of the clinical responses according to histological subtypes.


Asunto(s)
Algoritmos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/clasificación , Carcinoma Hepatocelular/genética , Diagnóstico por Computador/métodos , Perfilación de la Expresión Génica/métodos , Pruebas Genéticas/métodos , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica/genética , Predisposición Genética a la Enfermedad/clasificación , Predisposición Genética a la Enfermedad/genética , Humanos , Neoplasias Hepáticas/clasificación , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
J Cerebrovasc Endovasc Neurosurg ; 15(2): 85-95, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23844352

RESUMEN

OBJECTIVE: The purpose of this study is to investigate the results of treatment using stent-angioplasty for symptomatic middle cerebral arterial (MCA) stenosis and comparison of in-stent restenosis between drug-eluting stents (DES), bare metal coronary stents (BMS) and self-expanding stents (SES). MATERIALS AND METHODS: From Jan. 2007 to June. 2012, 34 patients (mean age ± standard deviation: 62.9 ± 13.6 years) with MCA stenosis were treated. Inclusion criteria were acute infarction or transient ischemic attacks (TIAs) and angiographically proven symptom related severe stenosis. Stents used for treatment were DES (n = 8), BMS (n = 13) and SES (n = 13). National Institutes of Health Stroke Scale (NIHSS) at admission was 2.5 ± 3.1 and mean stenosis rate was 79.0 ± 8.2%. Assessment of clinical and angiographic results was performed retrospectively. RESULTS: Among 34 patients, periprocedural complications occurred in four cases (11.8%), however, only two cases (6.0%) were symptomatic. All patients were followed clinically (mean follow-up period; 40.7 ± 17.7 months) and 31 were followed angiographically (91.2%. 13.4 ± 8.5 months). There was no occurrence of repeat stroke in all patients; however, mild TIAs related to restenosis occurred in three of 34 patients (8.8%). The mean NIHSS after stent-angioplasty was 1.7 ± 2.9 and 0.8 ± 1.1 at discharge. The modified Rankin score (mRS) at discharge was 0.5 ± 0.9 and 0.3 ± 0.8 at the last clinical follow-up. In-stent restenosis over 50% occurred in five of 31 angiographically followed cases (16.1%), however, all of these events occurred only in patients who were treated with BMS or SES. Restenosis rate was 0.0% in the DES group and 20.8% in the other group (p = 0.562); it did not differ between BMS and SES (2/11 18.2%, 3/13 23.1%, p = 1.000). CONCLUSION: Stent-angioplasty appears to be effective for symptomatic MCA stenosis. As for restenosis, in our study, DES was presumed to be more effective than BMS and SES; meanwhile, the results did not differ between the BMS and SES groups.

20.
J Korean Neurosurg Soc ; 54(1): 25-9, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24044076

RESUMEN

OBJECTIVE: To clarify the landmark for deciding the entry point for C1 lateral mass screws via the posterior arch by using 3-dimensional (3D) computed images. METHODS: Resnick insisted that the C1 posterior arch could be divided into pure posterior and lateral lamina (C1 pedicle). Authors studied where this transition point (TP) is located between the posterior lamina and the C1 pedicle and how it can be recognized. The 3D computed images of 86 cadaver C1s (M : F=45 : 41) were used in this study. RESULTS: The superior ridge of the C1 posterior arch had 2 types of orientation. One was in the vertical direction in the C1 posterior lamina and the other was in the horizontal direction in the C1 pedicle. The TP was located at the border between the 2 areas, the same site as the posterior end of the groove of the vertebral artery. On posterior-anterior projection, the posterior arch was sharpened abruptly at TP. We were unable to identify the TP in 6.4% of specimens due to complete or partial osseous bridges. A total of 93.8% of the TP were located between the most enlarged point of the spinal canal and the medial wall of the vertebral artery. CONCLUSION: The anatomic entry zone of C1 lateral laminar screws was clarified and identified based on the TP by using preoperative 3D computed images.

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