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INTRODUCTION/OBJECTIVE: The management of potential treatment-related complications and bleeding events in haemophilia is challenging in developing countries. Providing optimal care among these patients improve their quality of life (QOL) and life expectancy. This study explores the demographic characteristics and treatment outcome in a major haemophilia treatment centre in Malaysia. MATERIALS AND METHODS: A total of 260 patients were recruited in this retrospective cross-sectional analysis. Clinical data, including treatment regimens and outcome, were collected and analysed. RESULTS: A total of 211 patients were diagnosed with haemophilia A (HA) (severe disease, 72.5%) and 49 patients had haemophilia B (HB) (severe disease, 65.3%). The median age was 31 (IQR;2-84) years. Majority of the patients had at least one episode of musculoskeletal bleeding since diagnosis. The mean annual bleeding event (ABE) was 4.91 (SD±6.07) in 2018. Target joints were identified in 80.4% of the patients. Chronic arthropathy and synovitis collectively accounted for more than half of the musculoskeletal complications. 30.1% of the patients had contracted hepatitis C with less than half received treatment. Thirty-one patients (16.8%) with severe haemophilia developed inhibitor and 12 patients successfully underwent immune tolerance induction. More than three-quarters of the severe haemophilia patients were treated with factor concentrate prophylaxis. The mean prophylaxis dose for HA and HB were 41.3 (SD±19.1) and 48.6 (SD±21.5) IU/kg/week, respectively. In patients with severe disease, prophylaxis significantly reduced the ABE (5.45,9.03;p=0.005). CONCLUSION: The importance of utilising a low to moderate dose regimen as prophylaxis in haemophilic patients is highlighted in our study. Future studies should include QOL assessment will further improve the management in haemophilia.
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Hemofilia A , Adulto , Estudios Transversales , Hemofilia A/complicaciones , Hemofilia A/epidemiología , Hemofilia A/terapia , Humanos , Malasia/epidemiología , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We investigate the relationship between the excess volume and undercoolability of Zr-Ti and Zr-Hf alloy liquids by using electrostatic levitation. Unlike in the case of Zr-Hf alloy liquids in which sizes of the constituent atoms are matched, a remarkable increase of undercoolability and negative excess volumes are observed in Zr-Ti alloy liquids as a function of their compositional ratios. In this work, size mismatch entropies for the liquids were obtained by calculating their hard sphere diameters, number densities, and packing fractions. We also show that the size mismatch entropy, which arises from the differences in atomic sizes of the constituent elements, plays an important role in determining the stabilities of metallic liquids.
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BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. METHODS: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.
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Neoplasias Pulmonares/inmunología , Linfocitos/inmunología , Neutrófilos/inmunología , Carcinoma Pulmonar de Células Pequeñas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recuento de Plaquetas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Resultado del TratamientoRESUMEN
ExpA (GacA) is a global response regulator that controls the expression of major virulence genes, such as those encoding plant cell wall-degrading enzymes (PCWDEs) in the model soft rot phytopathogen Pectobacterium wasabiae SCC3193. Several studies with pectobacteria as well as related phytopathogenic gammaproteobacteria, such as Dickeya and Pseudomonas, suggest that the control of virulence by ExpA and its homologues is executed partly by modulating the activity of RsmA, an RNA-binding posttranscriptional regulator. To elucidate the extent of the overlap between the ExpA and RsmA regulons in P. wasabiae, we characterized both regulons by microarray analysis. To do this, we compared the transcriptomes of the wild-type strain, an expA mutant, an rsmA mutant, and an expA rsmA double mutant. The microarray data for selected virulence-related genes were confirmed through quantitative reverse transcription (qRT-PCR). Subsequently, assays were performed to link the observed transcriptome differences to changes in bacterial phenotypes such as growth, motility, PCWDE production, and virulence in planta. An extensive overlap between the ExpA and RsmA regulons was observed, suggesting that a substantial portion of ExpA regulation appears to be mediated through RsmA. However, a number of genes involved in the electron transport chain and oligogalacturonide metabolism, among other processes, were identified as being regulated by ExpA independently of RsmA. These results suggest that ExpA may only partially impact fitness and virulence via RsmA.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Redes Reguladoras de Genes , Pectobacterium/genética , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/metabolismo , Factores de Virulencia/metabolismo , Perfilación de la Expresión Génica , Análisis por Micromatrices , Mutación , Pectobacterium/patogenicidad , Enfermedades de las Plantas/microbiología , Plantas/microbiología , Proteínas de Unión al ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Ultrasound (US)-guided subclavian vein (SCV) catheterization via the supraclavicular (SC) or infraclavicular (IC) approaches can be useful in children. The purpose of this study was to compare the efficacy of these approaches. METHODS: This prospective, randomized study included 98 children who were <3 years old, and who were divided into two groups: the SC group (n=49) and the IC group (n=49). All SCV catheterizations were guided by US and performed by a single experienced anaesthesiologist. Data regarding puncture time, number of attempts, successful guidewire insertion, catheter insertion time, and complications were analysed. RESULTS: The median puncture time was longer in the IC group than the SC group (48 vs 36 s, P=0.02). Multiple attempts (number of attempts >3) were more frequently required in the IC group than the SC group (24.5 vs 6.1%, P=0.01). The incidence of guidewire misplacement was higher in the IC group than that of the SC group [10 (20.4%) vs 0 (0%), P=0.001]. Catheterization was successfully performed in all patients. No pneumothoraces or arterial punctures occurred in either group. CONCLUSION: During SCV catheterization under US guidance in paediatric patients, the SC approach yielded a shorter puncture time and decreased the incidence of guidewire misplacement when compared with the IC approach.
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Cateterismo Periférico/métodos , Vena Subclavia/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Cateterismo Periférico/instrumentación , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
In this paper, we fabricate planar-type Silicon-Oxide-High-k-Oxide-Silicon (SOHOS) and the planar-type SOHOS devices with N2 implantation of 3 x 10(15) dose in a tunneling oxide to determine the impact of N2 implantation in the tunneling oxide of a memory device. The N2 implantation device has better retention characteristics than the device with no implantation. In order establish the correlation between N2 implantation and retention characteristic improvement, the low frequency noise (1/f noise) characteristic is investigated. The normalized drain current noise (S(ID)/I(D)2) level of the N2 implantation device is higher than that of the device with no implantation, which means that N2 implantation causes more trap formation near the interface. Considering that N2 implantation does not affect the DC transfer characteristics, such as mobility and sub-threshold slope, this finding indicates that the increase in the 1/f noise level is due to oxide traps rather than to interface traps. Therefore, the retention characteristic improvement in the N2 implantation device can be explained by the generation of higher number of oxide traps and an increase in the potential barrier blocking the leakage path in the tunneling oxide.
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Equipos de Almacenamiento de Computador , Nanoestructuras/química , Nanoestructuras/ultraestructura , Semiconductores , Dióxido de Silicio/química , Diseño de Equipo , Análisis de Falla de Equipo , Ensayo de MaterialesRESUMEN
The solution combustion process is used to synthesize Fe1.9925P0.0075O3 nano-powders. The sintered Fe1.9925P0.0075O3 bodies are alpha-Fe2O3-based single phase with the rhombohedral structure. The electrical conductivity increases with an increase in sintering temperature because of an increase in grain size and density. The absolute value of the Seebeck coefficient escalates with an increase in sintering temperature up to 1000 degrees C, and then decreases with a further rise in its sintering temperature. The Fe1.9925P0.0075O3 sintered at 1000 degrees C shows the highest power factor, i.e., 1.39 x 10(-5) W m(-1) K(-2) at 700 degrees C.
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Cristalización/métodos , Compuestos Férricos/química , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Campos Electromagnéticos , Calor , Ensayo de Materiales , Tamaño de la Partícula , Conductividad TérmicaRESUMEN
This study carried out an electrical characteristic analysis using low-frequency noise (LFN) in top gate p-type low-temperature polysilicon thin film transistors (LTPS TFTs) with different active layer thicknesses between 40 nm and 80 nm. The transfer characteristic curves show that the 40-nm device has better electrical characteristics compared with the 80-nm device. The carrier number fluctuation, with and without correlated mobility fluctuation model in both devices, has modeled well the measured noise. On the other hand, the trap density and coulomb scattering in the 40-nm device are smaller compared with the 80-nm device. To confirm the effectiveness of the LFN noise analysis, the trap densities at a grain boundary are extracted using in both devices the similar methods of Proano et al. and Levinson et al. That is, coulomb scattering, caused by the trapped charges at or near the interface, has a greater effect on the device with inferior electrical properties. Based on the LFN and the quantitative analysis of the trap density at a grain boundary, the interface traps between the active layer and the gate insulator can explain the devices' electrical degradation.
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Different treatment outcomes and prognoses in patients with breast cancer can be observed with similar clinical predictors; this is because the biology of breast cancer is complex and heterogenous, involving multiple unknown contributing factors. We looked for plasma human mammaglobin (hMAM) mRNA by RT-PCR in 82 Korean patients with breast cancer to determine if there is an association between the presence of plasma hMAM mRNA in these patients and known prognostic factors. The prognostic usefulness of detection of plasma hMAM mRNA expression in these patients was also evaluated by determining overall survival and event-free survival. A significant difference was observed in the rate of positivity of plasma hMAM mRNA between the early stages of cancer (stages I-II, 23.4%) and advanced stages (stages III-IV, 82.9%). The expression rates of estrogen receptor, progesterone receptor, and HER-2/neu in the breast tissue of these patients, by immunohistochemistry, were 69.5, 75.6, and 20.7%, respectively. In the univariate analysis, plasma hMAM expression was significantly correlated with high histological and nuclear grades, nodal metastasis, and negative estrogen receptor and progesterone receptor status. Patients negative for plasma hMAM mRNA had significantly higher rates of event-free survival compared to the patients positive for plasma hMAM mRNA. However, no significant association with overall survival was observed for expression of plasma hMAM mRNA (P = 0.16). Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer.
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Mamoglobina A/sangre , Mamoglobina A/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Persona de Mediana Edad , ARN Mensajero/sangre , ARN Mensajero/genéticaRESUMEN
BACKGROUND: To analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr). RESULTS: Median age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum ß(2) microglobulin level, and platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.
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Inmunoglobulina D/sangre , Mieloma Múltiple/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The sintered Ca(1-x-y)Dy(x)CeyMnO3 bodies were a single phase with a perovskite structure without any impurity phases. The calculated crystallite sizes of the Ca(1-x-y)Dy(x)CeyMnO3 were in the range of 43.3 to 63.3 nm. The composition significantly affected their microstructural and thermoelectric characteristics. The doped Dy led to both an increase in the electrical conductivity as well as the absolute value of the Seebeck coefficient, resulting in an enhanced power factor. The highest power factor (5.1 x 10(-4) Wm(-1) K(-2)) was obtained for Ca(0.8)Dy(0.2)MnO3 at 800 degrees C. In this study, we systematically discussed the thermoelectric properties of the Ca(1-x-y)Dy(x)CeyMnO3, with respect to the substitution of Dy and/or Ce for Ca.
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We present the results of a structural study of metallic alloy liquids from high temperature through the glass transition. We use high energy X-ray scattering and electro-static levitation in combination with molecular dynamics simulation and show that the height of the first peak of the structure function, S(Q) - 1, follows the Curie-Weiss law. The structural coherence length is proportional to the height of the first peak, and we suggest that its increase with cooling may be related to the rapid increase in viscosity. The Curie temperature is negative, implying an analogy with spin-glass. The Curie-Weiss behavior provides a pathway to an ideal glass state, a state with long-range correlation without lattice periodicity, which is characterized by highly diverse local structures, reminiscent of spin-glass.
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BACKGROUND: Although cancer screening tests are not mentioned under brain-dead organ donor care guidelines in Korea, we assessed the level of prostate-specific antigen (PSA), an important prostate cancer marker, and performed prostate biopsies when needed in brain-dead organ donors. We believe that insisting on a screening test for cancer diagnosis in donors' organs is important. MATERIALS AND METHODS: Data were collected between January 2010 and July 2015 from Ajou University Hospital. We retrospectively analyzed the PSA levels and prostate biopsy results in 111 male brain-dead organ donors (mean age, 48.4 years). RESULTS: The mean PSA level was 7.395 ng/mL (range, 0.062 to 61.780; reference, 0 to 4 ng/mL). Ultrasonography or computed tomographic examination did not reveal prostate cancer, and a rectal examination was not performed. After checking the PSA levels, prostate biopsies were performed in 16 patients based on the recommendations of a urologist, and 4 patients (3.6% of 111) were diagnosed with prostate cancer. All cancers involved adenocarcinomas (acinar type) histopathologically. In 2 patients, the Gleason score was 6 (3 + 3), whereas the other 2 showed a score of 7 (3 + 4). Among the patients diagnosed with prostate cancer, 1 donated his liver and corneas, and the remaining 3 could not donate. CONCLUSION: Well-defined cancer screening tests are needed in Korea. Additionally, when the probability of organ transplantation-induced cancer metastasis is low or a recipient is at a high risk owing to not receiving organs, the law should allow organ donation even if prostate cancer is diagnosed in the donor.
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Muerte Encefálica/sangre , Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Obtención de Tejidos y Órganos/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Anciano , Biopsia , Detección Precoz del Cáncer/normas , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/química , Próstata/patología , Neoplasias de la Próstata/patología , República de Corea , Estudios Retrospectivos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/normasRESUMEN
A lambda cDNA library was prepared from polyadenylated RNA isolated from quiescent human diploid FS-4 fibroblasts stimulated with tumor necrosis factor for 3 h. Differential screening was used to isolate cDNA sequences that are stimulated by tumor necrosis factor. Eight distinct tumor necrosis factor-stimulated gene sequences (designated TSG-1, -6, -8, -12, -14, -21, -27, and -37) were partially sequenced and compared with known sequences from GenBank. TSG-1 was identical to the gene for interleukin-8. TSG-8 corresponded to the gene for monocyte chemotactic and activating factor. TSG-21 and -27 were identical to the genes for collagenase and stromelysin, respectively. The other four sequences showed no homologies with known genes. Patterns of induction of mRNAs corresponding to the eight cloned cDNAs by various cytokines, growth factors, and activators of second messenger pathways were analyzed in FS-4 cells.
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Regulación de la Expresión Génica/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Secuencia de Bases , Factores Biológicos/farmacología , Factores Quimiotácticos/genética , Clonación Molecular , Citocinas , ADN/genética , Fibroblastos , Biblioteca de Genes , Humanos , Interleucina-8 , Interleucinas/genética , Cinética , Datos de Secuencia Molecular , ARN Mensajero/genéticaRESUMEN
INTRODUCTION: Anatomical reduction of displaced acetabular fracture is not without its' limitations and complications. This study is conducted to assess clinical and radiological outcomes as well as complications of treating displaced acetabular fractures with emphasis on anatomical reduction in weight-bearing area, mainly the posterior column, and imperfect reduction of the anterior column is acceptable. However, stability of both columns is mandatory. METHODS: It was a retrospective study carried out in a Level 1 arthroplasty and trauma centre. 23 patients (17 males, 6 females) with average age of 50.1 years (range, 36-68 years) with displaced acetabular fracture treated with combined incisions and plate-cable systems were included. There were 3 elementary and 18 associated fractures according to Letournel classification. Average follow-up was 23.5 months (range, 12-38.7 months). Mean operation time was 160min (range: 75-320min). Functional scores were evaluated using Harris Hip Score (HHS) whilst reduction was assessed by Matta criteria. Any displacement of reduction, osteoarthritis, heterotopic ossification, and other complications was recorded. RESULT: 65.2% (15/23) of the patients obtained excellent HHS and 21.7% (5/23) had good HHS. There were 12 anatomical, 6 imperfect, and 5 poor reductions. No displacement was recorded in final follow-up. Complications documented: three lateral femoral cutaneous nerve injuries, two conversions to total hip arthroplasty, three Brooker stage 1 heterotrophic ossification, one pulmonary embolism and one screw irritation. No incidence of wound breakdown, infection and radiological osteoarthritis was reported. CONCLUSIONS: Imperfect reduction of the anterior column provided clinical outcomes that are as good as total anatomical reduction. This approach minimizes soft tissue damage and reduces perioperative morbidities.
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Acetábulo/cirugía , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Radiografía , Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Adulto , Anciano , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Curación de Fractura , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/patología , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Resultado del Tratamiento , Soporte de PesoRESUMEN
X-ray diffraction and electrostatic levitation measurements, together with the ab initio molecular dynamics simulation of liquid Al(75)Cu(25) alloy have been performed from 800 to 1600 K. Experimental and ab initio molecular dynamics simulation results match well with each other. No abnormal changes were experimentally detected in the specific heat capacity over total hemispheric emissivity and density curves in the studied temperature range for a bulk liquid Al(75)Cu(25) alloy measured by the electrostatic levitation technique. The structure factors gained by the ab initio molecular dynamics simulation precisely coincide with the experimental data. The atomic structure analyzed by the Honeycutt-Andersen index and Voronoi tessellation methods shows that icosahedral-like atomic clusters prevail in the liquid Al(75)Cu(25) alloy and the atomic clusters evolve continuously. All results obtained here suggest that no liquid-liquid transition appears in the bulk liquid Al(75)Cu(25) alloy in the studied temperature range.
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The death of embryonic central nervous system (CNS) neurons deprived of a target is well established. In adult rats, similar cell death of corticospinal and rubrospinal motor neurons occurs as a delayed response to spinal cord transection. We document the loss of neurons in Clarke's column, secondary ascending spinocerebellar neurons in adult rats, after complete spinal cord transection at T-9. Twenty-five weeks after spinal cord transection, horseradish peroxidase (HRP) studies showed a dramatic loss of labeled cells in rats with transected spinal cords as compared to matched control rats. Cresyl echt violet-stained sections failed to support the hypothesis that unlabeled cells persist in a shrunken, inactive state; instead we found far fewer identifiable neurons in Clarke's column. Although we saw little gliosis in the area of cell loss, gliosis was evident in the adjacent corticospinal tract which was severed in the original surgical injury. Amputation of the right hind limb resulted in a paradoxical increase in labeled Clarke's column cells on the right. Total cells stained with cresyl echt violet in amputated animals were not different from right to left. The increase in labeled cells on the amputated side may have been caused by an increase in metabolic activity of these deafferentated neurons which resulted in more effective axoplasmic transport of the HRP label.
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Médula Espinal/citología , Animales , Axones/cirugía , Supervivencia Celular , Sistema Nervioso Central/embriología , Femenino , Peroxidasa de Rábano Silvestre , Neuronas/citología , Ratas , Ratas Endogámicas , Médula Espinal/cirugíaRESUMEN
Regeneration and tolerance factor (RTF) is a novel membrane protein that has a diverse expression pattern and immunoregulatory properties. RTF is expressed in vivo on the surface of individuals with B cell chronic lymphocytic leukemia and on activated T lymphocytes of HIV infected individuals as determined by their coexpression with CD38 and HLA-DR. The unique expression patterns of this protein in vivo lead us to investigate its expression in vitro. The activation of human PBMCs through the TCR, using anti-CD3 antibody and PMA, upregulated cell surface expression of RTF from 2. 3% to 91.2% (mean channel fluorescence [MCF] increased threefold). The activation of Jurkat T cells through the TCR upregulated surface expression of RTF from 8.3% (MCF-1.3) to 58.7% (MCF-13.1). The Jurkat T-cell line was used as a model system to explore RTF's role in cellular activation. Using the Jurkat T-cell model, we found anti-RTF antibody induces apoptosis. The addition of anti-RTF antibody increased annexin V binding by threefold compared with the IgG1 kappa isotype control antibody (p < 0.00002) and activated caspase 3. These data indicate that RTF is expressed during T-cell activation and may be associated with apoptosis.
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Apoptosis , Activación de Linfocitos , Proteínas Gestacionales/metabolismo , Factores Supresores Inmunológicos/metabolismo , Linfocitos T/inmunología , Anticuerpos/inmunología , Caspasa 3 , Caspasas/metabolismo , Activación Enzimática , Humanos , Células Jurkat , Leucocitos Mononucleares/inmunología , Proteínas Gestacionales/inmunología , Factores Supresores Inmunológicos/inmunologíaRESUMEN
Regeneration and tolerance factor (RTF) is a protein cloned from the thymus and expressed on B lymphocytes in normal pregnancy, B lymphocytic leukemia lines, and T and B lymphocytes in individuals with HIV infection. Findings, using the Jurkat T-cell model, revealed that RTF is upregulated after activation and anti-RTF antibody-induced apoptosis. In this article anti-RTF antibody-induced apoptosis of both unstimulated and activated T lymphocytes. RTF expression was examined in human PBMC or purified T lymphocytes after their in vitro activation. Kinetic studies indicated maximal RTF cell surface expression on activated T lymphocytes occurred between expression of the early activation antigen CD69 and the IL-2alpha receptor (CD25) by multiparameter flow cytometry. RTF receptor expression correlated with Fas (CD95) and CD25 receptor expression (r2 = 0.6 and 0.5, respectively). RTF surface expression was dependent on the stimuli used to activate T lymphocytes. T lymphocytes obtained maximal RTF expression when activated through the TCR signal complex using anti-CD3epsilon antibody alone when compared with T lymphocytes activated with costimulation provided by anti-CD28 antibody alone or with anti-CD28 and anti-CD3epsilon antibody. RTF is expressed under conditions of both activation and anergy. The RTFs increased concentration on the surface of anergic T cells may protect these cells from apoptosis because increased RTF concentrations inhibited anti-RTF induced apoptosis. These data further characterize the expression of RTF on activated T lymphocytes and the role of anti-RTF antibody in T-lymphocyte apoptosis.