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2.
Sci Rep ; 8(1): 11087, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30038363

RESUMO

Thulium iron garnet (TmIG) films with perpendicular magnetic anisotropy (PMA) were grown on gadolinium gallium garnet (GGG) (111) substrates by off-axis sputtering. High-resolution synchrotron radiation X-ray diffraction studies and spherical aberration-corrected scanning transmission electron microscope (Cs-corrected STEM) images showed the excellent crystallinity of the films and their sharp interface with GGG. Damping constant of TmIG thin film was determined to be 0.0133 by frequency-dependent ferromagnetic resonance (FMR) measurements. The saturation magnetization (Ms) and the coercive field (Hc) were obtained systematically as a function of the longitudinal distance (L) between the sputtering target and the substrate. A 170% enhancement of PMA field (H⊥) was achieved by tuning the film composition to increase the tensile strain. Moreover, current-induced magnetization switching on a Pt/TmIG structure was demonstrated with an ultra-low critical current density (jc) of 2.5 × 106 A/cm2, an order of magnitude smaller than the previously reported value. We were able to tune Ms, Hc and H⊥ to obtain an ultra-low jc of switching the magnetization, showing the great potential of sputtered TmIG films for spintronics.

3.
ACS Nano ; 12(6): 5913-5922, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29874030

RESUMO

There is a need to monitor patients with cancer of the head and neck postradiation therapy, as diminished swallowing activity can result in disuse atrophy and fibrosis of the swallowing muscles. This paper describes a flexible strain sensor comprising palladium nanoislands on single-layer graphene. These piezoresistive sensors were tested on 14 disease-free head and neck cancer patients with various levels of swallowing function: from nondysphagic to severely dysphagic. The patch-like devices detected differences in (1) the consistencies of food boluses when swallowed and (2) dysphagic and nondysphagic swallows. When surface electromyography (sEMG) is obtained simultaneously with strain data, it is also possible to differentiate swallowing vs nonswallowing events. The plots of resistance vs time are correlated to specific events recorded by video X-ray fluoroscopy. Finally, we developed a machine-learning algorithm to automate the identification of bolus type being swallowed by a healthy subject (86.4%. accuracy). The algorithm was also able to discriminate between swallows of the same bolus from either the healthy subject or a dysphagic patient (94.7% accuracy). Taken together, these results may lead to noninvasive and home-based systems for monitoring of swallowing function and improved quality of life.


Assuntos
Deglutição/fisiologia , Eletromiografia/métodos , Grafite/química , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/radioterapia , Nanopartículas Metálicas/química , Monitorização Fisiológica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Paládio/química , Adulto Jovem
4.
Nat Commun ; 9(1): 223, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29335558

RESUMO

Harnessing the spin-momentum locking of topological surface states in conjunction with magnetic materials is the first step to realize novel topological insulator-based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron garnet (YIG) bilayers manifested as large interfacial in-plane magnetic anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance. The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3 film approaches its two-dimensional limit, indicating that topological surface states play an important role in the magnetization dynamics of YIG. Temperature-dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the magnetic proximity effect of TC as high as 180 K, an emerging low-temperature perpendicular magnetic anisotropy competing the high-temperature IMA, and an increasing exchange effective field of YIG steadily increasing toward low temperature. Our study sheds light on the effects of topological insulators on magnetization dynamics, essential for the development of topological insulator-based spintronic devices.

5.
Eye (Lond) ; 31(5): 762-770, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28106889

RESUMO

PurposeTo report the incidence and associated factors for the development of vitreomacular interface abnormality (VMIA) in patients with diabetic macular edema (DME) who received intravitreal injection (IVI) of anti-VEGF (Bevacizumab and Ranibizumab) treatment.MethodsA retrospective observational study. Patients with DME followed at least 6 months were reviewed. Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT) and final BCVA, CRT in eyes with and without VMIA were compared. Multiple logistic regression was also used to investigate the risk factors of VMIA formation in patients with DME treated by anti-VEGF.ResultsA total of 201 eyes in 142 patients met the inclusion criteria of the study. VMIA developed in 44 eyes (21.89%) of patients during a mean follow-up period of 40.84 months. The estimated mean incidence of VMIA formation was 6.43% per year. Poor baseline BCVA was found to be a risk factor for VMIA development (P=0.001, odds ratio=5.299, 95% confidence interval: 1.972 to 14.238). There was no difference between eyes with and without VMIA formation in improving BCVA (P=0.557) and lowering the macular edema (eyes without VMIA formation: -107.72±171.91 µm; eyes with VMIA formation: -155.02±212.27 µm, P=0.133).ConclusionsThis study revealed the incidence of VMIA formation in IVI anti-VEGF treated DME eyes was 6.43%. Poor baseline BCVA was found to be a risk factor for VMIA formation. Both eyes with and without VMIA development had favorable response to anti-VEGF treatment.


Assuntos
Bevacizumab/efeitos adversos , Doenças da Coroide/epidemiologia , Retinopatia Diabética/tratamento farmacológico , Oftalmopatias Hereditárias/epidemiologia , Edema Macular/tratamento farmacológico , Ranibizumab/efeitos adversos , Degeneração Retiniana/epidemiologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Doenças da Coroide/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Oftalmopatias Hereditárias/etiologia , Feminino , Seguimentos , Humanos , Incidência , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Ranibizumab/administração & dosagem , Retina/patologia , Degeneração Retiniana/etiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
8.
J Bone Joint Surg Br ; 92(4): 500-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20357325

RESUMO

Components from 73 failed knee replacements (TKRs) consisting of rotating-platform, mobile-bearing and fixed-bearing implants were examined to assess the patterns of wear. The patterns were divided into low-grade (burnishing, abrasion and cold flow) and high-grade (scratching, pitting/metal embedding and delamination) to assess the severity of the wear of polyethylene. The rotating-platform group had a higher incidence of low-grade wear on the upper surface compared with the fixed-bearing group. By contrast, high-grade wear comprising scratching, pitting and third-body embedding was seen on the lower surface. Linear regression analysis showed a significant correlation of the wear scores between the upper and lower surfaces of the tibial insert (R(2) = 0.29, p = 0.04) for the rotating-platform group, but no significant correlation was found for the fixed-bearing counterpart. This suggests that high-grade wear patterns on the upper surface are reduced with the rotating-platform design. However, the incidence of burnishing, pitting/third-body embedding and scratching wear patterns on the lower surface was higher compared with that in the fixed-bearing knee.


Assuntos
Prótese do Joelho , Falha de Prótese , Tíbia/cirurgia , Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Análise de Falha de Equipamento/métodos , Feminino , Humanos , Masculino , Desenho de Prótese , Reoperação , Estresse Mecânico
10.
Mol Endocrinol ; 15(12): 2078-92, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11731610

RESUMO

The presence of progesterone response element (PRE) in the 5'-flanking region of the human GnRH receptor (GnRHR) suggests the possible regulation of this gene by progesterone (P). In the present study, we examined the effects of P in transcriptional regulation of human GnRHR gene expression at the pituitary and placenta levels since the GnRHR has been detected in both tissues. By the use of transient transfection assays, a differential regulation of human GnRHR promoter activity by P was observed. P treatment resulted in a decrease in promoter activity in the pituitary alphaT3-1 cells, suggesting a P-mediated inhibitory action. Interestingly, P is found to have a stimulatory role at the placental expression of this gene. Addition of RU486 to, or inhibition of endogenous P production by, the placental JEG-3 cells leads to a decrease in promoter activity, which is reversed by the replacement of P. Further studies have identified a putative PRE, namely human GR-PRE (located between -535 and -521, related to translation start site), that may be responsible for the P action since the mutation of these motifs reversed the P-mediated effects. The binding of PR to this element is confirmed by antibody supershift assays. The physiological effects of P are mediated through two PR isoforms, namely PR-A and PR-B. In the present study, overexpression of human PR-A resulted in a decrease in human promoter activity in both pituitary and placental cells. Interestingly, overexpression of PR-B exhibits a cell-dependent transcriptional activity, whereby it functions as a transcription activator in the placenta but as a transcription repressor in the pituitary. In summary, our results demonstrated a differential usage of PR-A and PR-B in transcriptional regulation of human GnRHR gene expression by P at the pituitary and placenta levels.


Assuntos
Regulação da Expressão Gênica/fisiologia , Receptores LHRH/genética , Receptores de Progesterona/fisiologia , Aminoglutetimida/farmacologia , Animais , Western Blotting , Dexametasona/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Glucocorticoides/farmacologia , Antagonistas de Hormônios/farmacologia , Humanos , Camundongos , Mifepristona/farmacologia , Mutagênese Sítio-Dirigida , Placenta/metabolismo , Placenta/fisiologia , Gravidez , Progesterona/farmacologia , Isoformas de Proteínas , Receptores LHRH/análise , Receptores LHRH/biossíntese , Transcrição Gênica/fisiologia , Transfecção , Células Tumorais Cultivadas
11.
Anaesth Intensive Care ; 29(5): 548-51, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11669441

RESUMO

We present a case of a ten-month-old boy with Goldenhar's syndrome and significant retrognathia in whom a tracheostomy was performed to relieve upper airway obstruction. Tracheal intubation was facilitated by direct suspension laryngoscopy using a slotted rigid laryngoscope. We propose this technique as an alternative method for tracheal intubation in infants and young children with a difficult airway. The management of the difficult airway in children with Goldenhar's syndrome is discussed.


Assuntos
Síndrome de Goldenhar , Intubação Intratraqueal/métodos , Humanos , Lactente , Laringoscopia , Masculino
12.
Oncol Rep ; 8(4): 811-3, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11410789

RESUMO

We present a case of resected serous cystadenoma of the pancreas inducing marked dilatation of the main distal pancreatic duct. A 68-year-old woman, previously diagnosed with chronic pancreatitis, presented with upper abdominal pain. Abdominal US revealed a highly echoic mass in the pancreas. A CT scan disclosed a low density mass in the pancreas and dilatation of the main peripheral pancreatic duct. The mass demonstrated homogeneous and high signal intensity on T2-weighted magnetic resonance imaging (MRI). Selective abdominal arteriography showed the mass strained by the celiac artery. The tumor markers were CEA (2.4 ng/ml) and CA19-9 (6.1 U/ml). After the diagnosis of serous cystadenoma of the pancreas, the patient underwent distal pancreatectomy and splenectomy. The tumor (2.5 cm in diameter) consisted of grayish-white nodules and occupied the body of the pancreas. The tail of the pancreas was atrophic. Histopathological examination of the specimen showed a multilocular lesion containing numerous cysts with the inner surfaces evenly lined by one layer of cuboid or flat epithelial cells which stained positive for periodic acid-Schiff (PAS), evidencing serous cystadenoma. The patient is doing quite well one and a half years after the operation.


Assuntos
Cistadenoma Seroso/patologia , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Idoso , Antígeno CA-19-9/análise , Antígeno Carcinoembrionário/análise , Cistadenoma Seroso/química , Cistadenoma Seroso/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pancreatectomia , Ductos Pancreáticos/química , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia
13.
Clin Biomech (Bristol, Avon) ; 14(10): 717-21, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10545626

RESUMO

OBJECTIVE: To investigate the influence of contact alignment of the tibiofemoral joint of the prostheses in in vitro biomechanical testing. DESIGN: An experimental set-up was used to measure the total contact areas of the tibiofemoral joint of the prostheses subjected to a compressive load, and the malalignment situations were simulated. BACKGROUND: The contact alignment of the femoral component related to the tibial component in the literature was not described clearly and the effect of malalignment on the testing method has not been reported well. METHODS: Three commercial knee prostheses (Omnifit, Genesis, and AMK) were used for testing under a compression load (3000 N) at flexion 0 degrees and 10 degrees. After aligning the normal contact alignment, the simulated malalignment was done to evaluate the influence on the total contact areas in these conditions relative to the normal contact alignment. The simulated malalignment includes the medial-lateral translation (0.5 and 1 mm), anterior-posterior translation (2 and 4 mm) and internal-external rotation (1 degrees, 3 degrees and 5 degrees ) of the femoral component relative to the tibial component. RESULTS: The ratios of total contact areas of malalignment relative to normal contact alignment ranged from 1.06 to 0.93 in medial-lateral malalignment in these three prostheses. In anterior-posterior malalignment, the ratios ranged from 0.69 to 0.79 in Omnifit, 0.93-0. 96 in Genesis and 0.96-1.04 in AMK. In internal-external malrotation, the ratios ranged from 0.90 to 1.03 in these prostheses. CONCLUSIONS: This study proposes that contact alignment would affect the contact characteristics, especially in anterior-posterior alignment when high conformity knee prosthesis is tested. The contact alignment must be standardized in the procedure in in vitro biomechanical testing, which will be more objective to evaluate the contact characteristics of different knee prostheses. RELEVANCE: This study revealed the importance of contact alignment of the tibiofemoral joint of the prosthesis in in vitro biomechanical testing. Many published reports of the biomechanical evaluations on different designs of knee prostheses would show different results due to contact alignment. Furthermore, this study indicates that the ideal contact characteristics of the tibiofemoral joint in original design will be changed when the prosthesis under the malalignment condition which was caused by surgery technique or soft tissues imbalance.


Assuntos
Articulação do Joelho/fisiologia , Prótese do Joelho , Fenômenos Biomecânicos , Fêmur/fisiologia , Humanos , Técnicas In Vitro , Tíbia/fisiologia
14.
J Arthroplasty ; 14(7): 822-6, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10537257

RESUMO

The relative motion of 3 different bipolar endoprostheses was evaluated in vitro. A paired fresh acetabulum was frozen at 0 degrees C and defrosted 12 hours before the experiment. Three bipolar endoprostheses were evaluated: UNIQHIP system (United Orthopedics), UHR system (Osteonics), and AML system (Depuy). The surface roughness and spherical roundness of outer shells and inner heads of the bipolar prostheses were measured before the experiments. The acetabulum and outer shell of the bipolar prostheses were fixed on a Bionix 858 material testing system axially by separate fixation tools. The axial load of 1,400 N and 2,800 N was than applied on the specimen. The axis was rotated from 0 degrees to 90 degrees at the speed of 1 degree/s. All 3 outer shells were tested to this paired acetabulum randomly and separately. The frictional torque on the outer bearing surface of the different prostheses was recorded by the material testing system. The frictional torque on the inner bearing surface was also measured by the same procedure as was done for the outer bearing. The final results were statistically compared by the 1-way analysis of variance test method. Bipolar prostheses of the UHR system showed the largest frictional torque on outer bearing when it was loaded with 1,400 N and 2,800 N. The final results showed that all the bipolar prostheses had ideal motion behavior when functioning under the loading of 1,400 N. The frictional torque on the inner bearing was found to be larger than the frictional torque on the outer bearing in some prostheses when the loading was increased to 2,800 N. Thus, the bipolar endoprostheses functioned as unipolar prostheses. The only relative motion remained between the outer bearing surface and the acetabulum. This effect causes complications, such as implant protrusion in the acetabulum.


Assuntos
Prótese de Quadril , Humanos , Desenho de Prótese , Torque
15.
Arch Orthop Trauma Surg ; 118(1-2): 85-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9833114

RESUMO

From 1984 to 1987, a complete, single-layered, porous-coated femoral component (Roy-Camille type) was used for primary cementless total hip replacement in 80 patients. Seventy-two patients (77 hips) with a minimal follow-up of 5 years (mean 7.2 years) were assessed clinically and radiographically. Thigh pain occurred in 4 hips. Osteolysis appeared in 5 hips. Cortical thinning around the femoral component was significant at the proximal and middle levels. In total, 6 femoral components failed, which led to reoperation due to aseptic loosening (4 hips) and septic loosening (2 hips). The hip rating score (modified d'Aubigne and Postel rating system) in the surviving hips progressed from 9.0 (range 6-10) preoperatively to 16.3 (range 12-18) points at the latest follow-up. From this study, we found that the complete, single-layered, porous-coated stem had a low loosening rate after 5 years. Bone ingrowth into the porous coating was found in most of the cases. A lower stress shielding effect in comparison with the complete, multi-layered, porous-coated prosthesis was also noted.


Assuntos
Prótese de Quadril , Adulto , Idoso , Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Artroplastia de Quadril/estatística & dados numéricos , Cimentos Ósseos , Feminino , Fêmur , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese/estatística & dados numéricos , Falha de Prótese , Radiografia , Fatores de Tempo
16.
J Biomed Mater Res ; 39(1): 153-60, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9429106

RESUMO

From January 1985 to December 1990, 598 consecutive New Jersey low-contact stress (LCS) total knee arthroplasties (TKAs) were performed for gonarthrosis. Among these 598 operations, 322 were with rotating platform elements and 276 were with meniscal bearing elements. During 5 to 8 years of follow-up, eight knees had severe symptomatic polyethylene failure that required revision surgery; all eight cases were meniscal bearing types. The failed polyethylene inserts were retrieved and studied. It was observed that there were four probable failure mechanisms associated with the catastrophic polyethylene wear. First, insufficient thickness of the meniscal bearing was the major reason for wear. Second, the malpositioning of the metal tibial tray in the transverse plane resulted in the breaking of the meniscal bearing. Third, the inability of the patellar to rotate due to tissue ingrowth made the polyethylene break. Last, yellowing of the subsurface of the meniscal bearing was a sign of polyethylene failure. These four possible failure mechanisms are all associated with the design of the meniscal bearing type of LCS knee prostheses. Therefore, it is suggested that the design of the LCS knee prosthesis should be modified.


Assuntos
Artroplastia do Joelho , Materiais Biocompatíveis , Prótese do Joelho , Polietilenos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Biomed Mater Eng ; 8(3-4): 155-65, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10065882

RESUMO

To more understand the influence of the walking speed on the spinal joint force distribution, a three-dimensional biomechanical model was used to estimate the spine loads during human gait with three different walking speeds. This previously developed and validated model included a dynamic external model and an internal model with forces of disc, 8 major muscles, 2 ligaments and 2 facet joints at L5/S1 level. A linear optimization method was used to solve the internal model to estimate the L5/S1 spinal joint force distribution. The results of five young male subjects showed that the mean peak L5/S1 disc compressive forces on the slow, preferred and fast speeds were 2.28, 2.53, 2.95 body weight, respectively. The peak forces happened right after the heel strike and before completely toe off. The facet joint forces were generally increased with the walking speed increase, too. To reduce the loads on the spine, the slow walking is then recommended for the patients with low back pain or after spinal surgery.


Assuntos
Marcha/fisiologia , Vértebras Lombares/fisiologia , Sacro/fisiologia , Caminhada/fisiologia , Aceleração , Adulto , Peso Corporal/fisiologia , Simulação por Computador , Calcanhar/fisiologia , Humanos , Disco Intervertebral/fisiologia , Modelos Lineares , Ligamentos Longitudinais/fisiologia , Dor Lombar/fisiopatologia , Masculino , Modelos Biológicos , Músculo Esquelético/fisiologia , Coluna Vertebral/fisiopatologia , Coluna Vertebral/cirurgia , Estresse Mecânico , Dedos do Pé/fisiologia , Suporte de Carga/fisiologia
18.
Invest Ophthalmol Vis Sci ; 37(11): 2318-25, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8843916

RESUMO

PURPOSE: Proliferative vitreoretinopathy (PVR) remains the most common cause of failed retinal detachment (RD) surgery. The authors compared the effectiveness of two intraocular sustained-release codrugs in suppressing PVR in a rabbit model a surgically implantable pellet releasing 5-fluorouracil (FU) and dexamethasone (DX) for 1 week and an injectable intravitreal sustained-release suspension releasing 5-FU and triamcinolone acetonide for 1 month. METHODS: Sustained-release devices and suspensions were prepared to deliver equimolar quantities of corticosteroid and 5-FU. In group 1, devices were implanted surgically into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received surgical implantation of the suture only. In group 2, drug suspension was injected into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received injection of the vehicle only. One day later, each rabbit was injected intravitreally with 250,000 homologous rabbit dermal fibroblasts. Severity of PVR was graded clinically by two masked observers on days 3, 7, 10, 14, 21, and 28. RESULTS: In group 1, clinical severity of PVR was less in the experimental group than in the control group at all time points, this was only statistically significant on day 10 (P = 0.04). Six eyes developed moderate to severe tractional RD or bullous RD in the control group by day 10 compared with none in the experimental group (P = 0.01). In group 2, the median clinical grading of eyes in the experimental group was significantly less than that in the control group at all time points through day 21 (P < or = 0.01). CONCLUSIONS: Both the intravitreal sustained-release dexamethasone-5-FU device and the triamcinolone-5-FU suspension effectively inhibit the progression of PVR in a rabbit model. Simultaneous delivery of 5-FU and corticosteroid may target different components of the wound-healing process in this disease.


Assuntos
Antimetabólitos/administração & dosagem , Dexametasona/administração & dosagem , Fluoruracila/administração & dosagem , Glucocorticoides/administração & dosagem , Triancinolona/administração & dosagem , Vitreorretinopatia Proliferativa/tratamento farmacológico , Animais , Preparações de Ação Retardada , Modelos Animais de Doenças , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Implantes de Medicamento , Feminino , Masculino , Coelhos , Descolamento Retiniano/etiologia , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/fisiopatologia , Corpo Vítreo
19.
Cancer Lett ; 105(2): 211-5, 1996 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-8697446

RESUMO

The activity of protein kinase C (PKC) in human liver cancer and adjacent normal liver tissue was determined. It was found that the activity of the membrane-bound PKC was significantly decreased in cancer tissue compared with that of the adjacent normal tissues (245.3 +/- 49.3 versus 396.9 +/- 82.4 pmol 32P/min per mg, P < 0.05); while the PKC activity in the cytosolic fraction was not significantly different (50.6 +/- 11.3 versus 40.0 +/- 6.6 pmol 32P/min per mg) concerning protein concentration. The reduced expression of membrane-bound PKC activity was observed at least in 8 of 9 patients. Moreover, the cancer tissue showed a significant decrease in total membranous PKC activity compared with the adjacent normal tissue of each patient (163.1 +/- 38.8 versus 433.8 +/- 92.4 pmol 32P/min per g tissue; P < 0.005) and no difference in total cytosolic PKC activity (285.9 +/- 58.8 versus 311.6 +/- 44.0 pmol 32P/min per g tissue). These results indicate that the progression of the human liver cancer might be associated with the decrease of membrane-bound PKC activity.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/enzimologia , Membrana Celular/enzimologia , Neoplasias Hepáticas/enzimologia , Proteína Quinase C/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Citosol/enzimologia , Feminino , Humanos , Fígado/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
20.
J Invest Dermatol ; 103(5 Suppl): 90S-95S, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7963691

RESUMO

The introduction of the techniques of molecular biology as tools to study skin carcinogenesis has provided more precise localization of biochemical pathways that regulate the tumor phenotype. This approach has identified genetic changes that are characteristic of each of the specific stages of squamous cancer pathogenesis: initiation, exogenous promotion, premalignant progression, and malignant conversion. Initiation can result from mutations in a single gene, and the Harvey allele of the ras gene family has been identified as a frequent site for initiating mutations. Heterozygous activating mutations in c-rasHa are dominant, and affected keratinocytes hyperproliferate and are resistant to signals for terminal differentiation. An important pathway impacted by c-rasHa activation is the protein kinase C (PKC) pathway, a major regulator of keratinocyte differentiation. Increased activity of PKC alpha and suppression of PKC delta by tyrosine phosphorylation contribute to the phenotypic consequences of rasHa gene activation in keratinocytes. Tumor promoters disturb epidermal homeostasis and cause selective clonal expansion of initiated cells to produce multiple benign squamous papillomas. Resistance to differentiation and enhanced growth rate of initiated cells impart a growth advantage when the epidermis is exposed to promoters. The frequency of premalignant progression varies among papillomas, and subpopulations at high risk for progression have been identified. These high-risk papillomas overexpress the alpha 6 beta 4 integrin and are deficient in transforming growth factor beta 1 and beta 2 peptides, two changes associated with a very high proliferation rate in this subset of tumors. The introduction of an oncogenic rasHa gene into epidermal cells derived from transgenic mice with a null mutation in the TGF beta 1 gene have an accelerated rate of malignant progression when examined in vivo. Thus members of the TGF beta gene family contribute a tumor-suppressor function in carcinogenesis. Accelerated malignant progression is also found with v-rasHa transduced keratinocytes from skin of mice with a null mutation in the p53 gene. The similarities in risk for malignant conversion by initiated keratinocytes from TG beta 1 and p53 null geneotypes suggest that a common, growth-related pathway may underly the tumor-suppressive functions of these proteins in the skin carcinogenesis model.


Assuntos
Genes Supressores de Tumor , Neoplasias Experimentais/genética , Oncogenes , Animais , Transformação Celular Neoplásica , Genes ras , Substâncias de Crescimento/fisiologia , Humanos , Estadiamento de Neoplasias , Neoplasias Experimentais/patologia , Proteína Supressora de Tumor p53/genética
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