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1.
IEEE Trans Neural Netw Learn Syst ; 32(11): 4826-4838, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021943

RESUMO

While most deep learning architectures are built on convolution, alternative foundations such as morphology are being explored for purposes such as interpretability and its connection to the analysis and processing of geometric structures. The morphological hit-or-miss operation has the advantage that it considers both foreground information and background information when evaluating the target shape in an image. In this article, we identify limitations in the existing hit-or-miss neural definitions and formulate an optimization problem to learn the transform relative to deeper architectures. To this end, we model the semantically important condition that the intersection of the hit and miss structuring elements (SEs) should be empty and present a way to express Don't Care (DNC), which is important for denoting regions of an SE that are not relevant to detecting a target pattern. Our analysis shows that convolution, in fact, acts like a hit-to-miss transform through semantic interpretation of its filter differences. On these premises, we introduce an extension that outperforms conventional convolution on benchmark data. Quantitative experiments are provided on synthetic and benchmark data, showing that the direct encoding hit-or-miss transform provides better interpretability on learned shapes consistent with objects, whereas our morphologically inspired generalized convolution yields higher classification accuracy. Finally, qualitative hit and miss filter visualizations are provided relative to single morphological layer.


Assuntos
Algoritmos , Aprendizado Profundo/tendências , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão/tendências , Humanos , Reconhecimento Automatizado de Padrão/métodos
2.
Phys Rev Res ; 2(1)2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33870201

RESUMO

Topological defects appear in symmetry breaking phase transitions and are ubiquitous throughout Nature. As an ideal testbed for their study, defect configurations in nematic liquid crystals (NLCs) could be exploited in a rich variety of technological applications. Here we report on robust theoretical and experimental investigations in which an external electric field is used to switch between pre-determined stable chargeless disclination patterns in a nematic cell, where the cell is sufficiently thick that the disclinations start and terminate at the same surface. The different defect configurations are stabilised by a master substrate that enforces a lattice of surface defects exhibiting zero total topological charge value. Theoretically, we model disclination configurations using a Landau-de Gennes phenomenological model. Experimentally, we enable diverse defect patterns by implementing an in-house-developed Atomic Force Measurement scribing method, where NLC configurations are monitored via polarised optical microscopy. We show numerically and experimentally that an "alphabet" of up to 18 unique line defect configurations can be stabilised in a 4x4 lattice of alternating s=±1 surface defects, which can be "rewired" multistably using appropriate field manipulation. Our proof-of-concept mechanism may lead to a variety of applications, such as multistable optical displays and rewirable nanowires. Our studies also are of interest from a fundamental perspective. We demonstrate that a chargeless line could simultaneously exhibit defect-antidefect properties. Consequently, a pair of such antiparallel disclinations exhibits an attractive interaction. For a sufficiently closely-spaced pair of substrate-pinned defects, this interaction could trigger rewiring, or annihilation if defects are depinned.

3.
Surg Endosc ; 33(2): 543-548, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30006844

RESUMO

BACKGROUND: Transanal minimally invasive surgery (TAMIS) offers intra-luminal full-thickness excision of rectal neoplasia. Robotic TAMIS (RT) allows for greater versatility in motion while operating in the limited space of the rectum. We present our experience with this technique in practice using the DaVinci Xi™ platform. METHOD: This is a multi-institutional retrospective analysis for patient undergoing Robotic TAMIS for resection of rectal lesions at two tertiary referral hospitals in the United States. Morbidity, mortality, anatomic measurement, and final pathology were analyzed. RESULTS: Thirty-four patients planned for Robotic TAMIS were identified. Average follow-up was 188 days. The average BMI was 29.5 ± 5.9. All patients had an American Society of Anesthesiologist (ASA) Class of 2 or greater and 21 (62%) were ASA 3 or greater. Rectal lesions located from 2 to 15 cm from the dentate line were successfully resected. Lesions up to 4.5 cm in the longest dimension were successfully resected. The average operative time was 100 ± 70 min, which correlated to a robotic console time of 76 ± 67 min. Patients were placed in Lithotomy in 32 (94%) cases and were prone in only 2 (6%) cases. There were no intraoperative complications or conversions to another technique. The only postoperative complication was a medically managed Clostridium difficile infection in 1 patient. Three patients were upstaged to T2 on final pathology and underwent successful formal resections. BMI was a statistically significant predictor of a longer operation. CONCLUSIONS: With increased reach and operative range of motion, Robotic TAMIS is a safe and effective method for excising low-risk rectal neoplasia with a wide range of anatomical measurements. Higher BMI is a significant predictor of a longer and likely more challenging operation.


Assuntos
Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica Transanal/métodos , Adulto , Idoso , Análise de Variância , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/patologia , Reto/cirurgia , Estudos Retrospectivos
4.
Hum Biol ; 90(1): 45-61, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30387383

RESUMO

Numerous biological and archaeological studies have demonstrated the legitimacy of remote sensing in anthropology. This article focuses on detecting and documenting terrestrial clandestine graves and surface remains (CGSR) of humans using unmanned aerial vehicles (UAVs), sensors, and automatic processing algorithms. CGSR is a problem of complex decision making under uncertainty that requires the identification and intelligent reasoning about direct evidence of human remains and their environmental fingerprints. As such, it is as much an engineering and geospatial problem as it is an anthropology problem. This article is an effort to survey existing work across disciplines and to provide insights and recommendations to assist future research. To support our claims, preliminary experiments were performed at the Forensic Anthropological Research Facility at Texas State University using UAVs, hyperspectral imaging, thermal imaging, and structure from motion. Prior work, our experience, and preliminary results indicate that both great potential and extreme challenges face remote sensing of CGSR.


Assuntos
Restos Mortais/patologia , Cemitérios/estatística & dados numéricos , Antropologia Forense/instrumentação , Tecnologia de Sensoriamento Remoto/métodos , Algoritmos , Documentação , Meio Ambiente , Humanos , Registros , Inquéritos e Questionários
5.
Beilstein J Nanotechnol ; 9: 109-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441256

RESUMO

Using a Landau-de Gennes approach, we study the impact of confinement topology, geometry and external fields on the spatial positioning of nematic topological defects (TDs). In quasi two-dimensional systems we demonstrate that a confinement-enforced total topological charge of m > 1/2 decays into elementary TDs bearing a charge of m = 1/2. These assemble close to the bounding substrate to enable essentially bulk-like uniform nematic ordering in the central part of a system. This effect is reminiscent of the Faraday cavity phenomenon in electrostatics. We observe that in certain confinement geometries, varying the correlation length size of the order parameter could trigger a global rotation of an assembly of TDs. Finally, we show that an external electric field could be used to drag the boojum fingertip towards the interior of the confinement cell. Assemblies of TDs could be exploited as traps for appropriate nanoparticles, opening several opportunities for the development of functional nanodevices.

6.
Soft Matter ; 13(45): 8442-8450, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29083004

RESUMO

Nematic cells patterned with square arrays of strength m = ±1 topological defects were examined as a function of cell thickness (3 < h < 7.5 µm), temperature, and applied voltage. Thicker cells tend to exhibit an escape or partial escape of the nematic director as a means of mitigating the elastic energy cost near the defect cores, whereas thinner cells tend to favor splitting of the integer defects into pairs of half-integer strength defects. On heating the sample into the isotropic phase and cooling back into the nematic, some apparently split defects can reappear as unsplit integer defects, or vice versa. This is consistent with the system's symmetry, which requires a first order transition between the two relaxation mechanisms.

7.
Phys Rev E ; 95(4-1): 042702, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28505708

RESUMO

We study decomposition of geometrically enforced nematic topological defects bearing relatively large defect strengths m in effectively two-dimensional planar systems. Theoretically, defect cores are analyzed within the mesoscopic Landau-de Gennes approach in terms of the tensor nematic order parameter. We demonstrate a robust tendency of defect decomposition into elementary units where two qualitatively different scenarios imposing total defect strengths on a nematic region are employed. Some theoretical predictions are verified experimentally, where arrays of defects bearing charges m=±1 and even m=±2 are enforced within a plane-parallel nematic cell using an atomic force microscopy scribing method.

8.
Am Surg ; 81(6): 573-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26031269

RESUMO

Surgical site infections (SSIs) remain a common and costly morbidity after colorectal surgery. This rate remains high even in the setting of strict adherence to Surgical Care Improvement Project Protocols. The aim of our pilot study was to determine the feasibility and safety of subcutaneous gentamicin injection or pressurized irrigation as adjuncts to reduce SSI. A total of 132 patients who underwent colorectal surgery at the VA North Texas Health Care System were prospectively assigned to a pressurized irrigation group (n = 44), a preincision gentamicin injection group (n = 48), or control (n = 40). The primary objective was to assess safety and feasibility of these strategies. Patient demographics were matched among groups. Univariate and multivariate analyses were performed to identify possible predictions of SSI in this cohort. The rate of SSI in the control group was 25 per cent, 13.5 per cent in the pressurized irrigation group, and 12.5 per cent in the gentamicin group (P = 0.26). Combined, the intervention groups had a 13 per cent SSI versus 25 per cent control (P = 0.09). Operative time was not increased by the interventions and no intraoperative complications specifically related to the interventions were noted. Postoperative complications were not different between groups. Both albumin and body mass index were associated with SSI. Body mass index was and independent predictor of SSI (P = 0.006). In conclusion, this pilot study demonstrates the feasibility of the interventions described. There was no detrimental effect of either intervention. There was trend toward a reduction in SSI in the intervention group, which warrants further investigation.


Assuntos
Antibacterianos/administração & dosagem , Gentamicinas/administração & dosagem , Doenças Inflamatórias Intestinais/cirurgia , Neoplasias Intestinais/cirurgia , Pólipos Intestinais/cirurgia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Irrigação Terapêutica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antibacterianos/efeitos adversos , Índice de Massa Corporal , Cirurgia Colorretal , Estudos de Viabilidade , Gentamicinas/efeitos adversos , Humanos , Infusões Subcutâneas/efeitos adversos , Infusões Subcutâneas/métodos , Injeções Subcutâneas , Pessoa de Meia-Idade , Duração da Cirurgia , Projetos Piloto , Pressão , Estudos Prospectivos , Segurança , Albumina Sérica/análise , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica/efeitos adversos
9.
Phys Rev E Stat Nonlin Soft Matter Phys ; 90(5-1): 052501, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25493804

RESUMO

An atomic force microscope was used to scribe a polyimide-coated substrate with complex patterns that serve as an alignment template for a nematic liquid crystal. By employing a sufficiently large density of scribe lines, two-dimensional topological defect arrays of arbitrary defect strength were patterned on the substrate. When used as the master surface of a liquid crystal cell, in which the opposing slave surface is treated for planar degenerate alignment, the liquid crystal adopts the pattern's alignment with a disclination line emanating at the defect core on one surface and terminating at the other surface.

10.
Am J Surg ; 202(5): 558-60, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21924402

RESUMO

INTRODUCTION: The purpose of this study was to evaluate the long-term complications of surgical site infection (SSI) in the colorectal population, specifically its association with incisional hernia and small bowel obstruction. METHODS: Using standardized definitions of SSI, a retrospective review of patients undergoing transabdominal colorectal surgery from January 2002 to December 2005 was performed. Primary outcomes included incisional hernia and small bowel obstruction in patients with SSIs. RESULTS: A total of 443 patients were analyzed. The median surgical follow-up was 12 months (2-3,091 days). Infections were identified in 101 (23%) cases. There were 99 cases (22%) of incisional hernia and 32 cases (7%) of small bowel obstruction. Logistic regression revealed SSI to be independently associated with incisional hernia after adjusting for clinical covariates (adjusted odds ratio = 2.23, P = .003; 95% confidence interval, 1.3-3.8). Patients with incisional hernia were 1.9 times more likely to have had an SSI (36.3% vs 18.8%, P ≤ .01). They required a longer operative time (224 minutes vs 198 minutes, P = .03), had an increased body mass index (29.0 vs 26.8, P ≤ .01), and had increased estimated blood loss (363 vs 289, mL, P = .03). Small bowel obstruction was significantly associated with operations involving the rectum (11.5% in operations involving the rectum vs 5.9% in nonrectal operations, P = .05), increased estimated blood loss (409 ml vs 297 ml, P = .04), and red blood cell transfusion (15.5% with transfusion vs 5.7% without, P = .01). SSI was not an independent predictor of small bowel obstruction (adjusted odds ratio = 1.05, P = .91; 95% confidence interval, .45-2.5). CONCLUSIONS: Patients with an SSI were 1.9 times more likely to have an incisional hernia than those without an SSI. An SSI after colorectal surgery was a risk factor for the development of incisional hernia but was not a risk factor for small bowel obstruction in our population.


Assuntos
Colo/cirurgia , Hérnia Ventral/etiologia , Obstrução Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Reto/cirurgia , Infecção da Ferida Cirúrgica/complicações , Perda Sanguínea Cirúrgica , Índice de Massa Corporal , Transfusão de Eritrócitos , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
11.
Am Surg ; 77(5): 597-601, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21679594

RESUMO

A process was developed to use a nontraditional operative day (Saturday) to increase the number of inguinal herniorrhaphies (IHs) performed. The purpose of this analysis was to compare operating times and outcomes between patients undergoing IH on Saturday versus the weekday. A retrospective review was conducted that included patients who underwent IH from October 2008 to January 2010. This cohort was divided based on the day on which surgery occurred. The outcome measures were operative times, room turnover time, and complication rates. Operative time was shorter for Saturday IHs (50.7 vs. 67.8 min, P ≤ 0.001). The greatest difference between the two groups occurred in turnover times. We considered Saturday turnover time to be zero, which was possible because of multiple support teams and additional room availability. Turnover times during the week averaged 40.5 ± 2 minutes. There was no difference in complication rates for the two groups (Saturday IHs 17.6% vs. 20.9% for weekday IHs, P = 0.75). Elective cases can be accomplished more rapidly during nontraditional operating times if there are multiple support teams and rooms available.


Assuntos
Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Hérnia Inguinal/cirurgia , Hospitais de Veteranos/organização & administração , Salas Cirúrgicas/organização & administração , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Listas de Espera , Estudos de Coortes , Hérnia Inguinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Controle de Qualidade , Estudos Retrospectivos , Medição de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/métodos , Resultado do Tratamento , Estados Unidos , Carga de Trabalho
12.
Arch Surg ; 146(3): 263-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21079110

RESUMO

OBJECTIVE: To determine if an evidence-based practice bundle would result in a significantly lower rate of surgical site infections (SSIs) when compared with standard practice. DESIGN: Single-institution, randomized controlled trial with blinded assessment of main outcome. The trial opened in April 2007 and was closed in January 2010. SETTING: Veterans Administration teaching hospital. PATIENTS: Patients who required elective transabdominal colorectal surgery were eligible. A total of 241 subjects were approached, 211 subjects were randomly allocated to 1 of 2 interventions, and 197 were included in an intention-to-treat analysis. INTERVENTIONS: Subjects received either a combination of 5 evidenced-based practices (extended arm) or were treated according to our current practice (standard arm). The interventions in the extended arm included (1) omission of mechanical bowel preparation; (2) preoperative and intraoperative warming; (3) supplemental oxygen during and immediately after surgery; (4) intraoperative intravenous fluid restriction; and (5) use of a surgical wound protector. MAIN OUTCOME MEASURE: Overall SSI rate at 30 days assessed by blinded infection control coordinators using standardized definitions. RESULTS: The overall rate of SSI was 45% in the extended arm of the study and 24% in the standard arm (P = .003). Most of the increased number of infections in the extended arm were superficial incisional SSIs (36% extended arm vs 19% standard arm; P = .004). Multivariate analysis suggested that allocation to the extended arm of the trial conferred a 2.49-fold risk (95% confidence interval, 1.36-4.56; P = .003) independent of other factors traditionally associated with SSI. CONCLUSIONS: An evidence-based intervention bundle did not reduce SSIs. The bundling of interventions, even when the constituent interventions have been individually tested, does not have a predictable effect on outcome. Formal testing of bundled approaches should occur prior to implementation.


Assuntos
Cirurgia Colorretal/efeitos adversos , Medicina Baseada em Evidências/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Cirurgia Colorretal/métodos , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prevenção Primária/métodos , Valores de Referência , Medição de Risco , Método Simples-Cego , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
14.
J Med Case Rep ; 4: 207, 2010 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-20604942

RESUMO

INTRODUCTION: Adenoid cystic carcinoma (ACC) of the larynx is a rare malignancy characterized by an indolent course and late pulmonary metastases. Metastases from the larynx to the spleen are an unusual event. In the present report, we discuss a patient with adenoid cystic carcinoma of the larynx metastatic to the spleen. A review of the literature did not yield any other such incidents. We review the clinical presentation and course of adenoid cystic carcinoma, as well as the role of splenectomy for metastases. CASE PRESENTATION: We present a case of laryngeal adenoid cystic carcinoma in a 26-year-old Caucasian man treated with total laryngectomy and ionizing radiation. He initially developed asynchronous pulmonary metastases, which were resected. Our patient subsequently presented with a symptomatic splenic lesion consistent with metastatic disease, for which he underwent laparoscopic splenectomy. CONCLUSIONS: Splenectomy might be indicated for isolated metastases. A splenectomy effectively addresses symptoms and serves as a cytoreduction modality.

15.
Indian J Surg ; 71(6): 356-62, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23133191

RESUMO

The management of rectal cancer has drastically evolved over the past two decades as a result of implementation of circular stapling devices and the introduction of neoadjuvant chemoradiation. In spite of current aggressive multimodality treatments, the recurrence rate remains unacceptably high and the expected 5-year survival in patients who develop recurrent disease is dismal. The management of rectal cancer must involve a multidisciplinary approach. An understanding of the biology of rectal tumours may allow for selection of patients who may have an aggressive phenotype allowing for alterations in the operative and neoadjuvant planning. Efforts to improve local control and survival in rectal cancer are the focus of multiple current clinical and preclinical research efforts. Preoperative chemoradiation for and surgical management of rectal cancer, including the laparoscopic approach are areas of dynamic progression. In the present report, we review the current evidence in the new strategies pertaining to the multimodality approach in the management of rectal cancer.

16.
Vasc Endovascular Surg ; 43(1): 46-50, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18799501

RESUMO

The diagnosis of median arcuate ligament (MAL) syndrome and its correlation with symptoms has been controversial since the disease entity was described. The authors describe a technique that will identify patients who will benefit from intervention. Eight patients with isolated celiac artery compression from MAL were identified by the authors. Their technique involved selective cannulation of the superior mesenteric artery (SMA) and injection of a vasodilator during angiography. Symptom reproduction and loss of collateral filling of the celiac territory represented a positive test: 4 of the 8 patients had a positive test and underwent successful surgical treatment of the condition; 3 of them remained asymptomatic at follow-up; 1 patient continues to have mild abdominal discomfort. Of the 4 patients with a negative test, 2 were found to have other conditions causing their symptoms. Vasodilator injection into the SMA is a useful diagnostic test to identify patients with symptomatic MAL syndrome.


Assuntos
Angiografia Digital , Arteriopatias Oclusivas/diagnóstico por imagem , Artéria Celíaca/diagnóstico por imagem , Circulação Colateral , Isquemia/diagnóstico por imagem , Ligamentos , Vasodilatadores , Adulto , Idoso , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/cirurgia , Artéria Celíaca/fisiopatologia , Artéria Celíaca/cirurgia , Constrição Patológica , Feminino , Humanos , Injeções Intra-Arteriais , Isquemia/fisiopatologia , Isquemia/cirurgia , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Síndrome , Vasodilatadores/administração & dosagem
17.
J Am Chem Soc ; 126(31): 9506-7, 2004 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-15291531

RESUMO

The results described herein support a mechanistic hypothesis for how guanidine-rich transporters attached to small cargos (MW ca. <3000) can migrate across the lipid membrane of a cell and directly enter the cytosol. Arginine oligomers are found to partition almost completely into the aqueous layer of a water-octanol bilayer. However, when the same partitioning experiment is conducted in the presence of sodium laurate, a representative negatively charged membrane constituent, the arginine oligomer partitions almost completely (>95%) into the octanol layer. In contrast, ornithine oligomers partition almost exclusively into the water layer with and without added sodium laurate. The different partitioning between guanidinium-rich and ammonium-rich oligomers in the presence of sodium laurate is consistent with the ability of the former to form a bidentate hydrogen bonded ion pair. Mono- and dimethylated arginine oligomers, which like ornithine can only efficiently form monodentate hydrogen bonds, were prepared and found to exhibit poor cellular uptake. Ion pair formation converts a once water-soluble agent to a lipid-soluble agent, thereby reducing the energetic penalty for passage of guanidine-rich transporters through the lipid bilayer. Uptake of guanidine-rich transporters is known to be an energy-dependent process, and this requirement for cellular ATP is now rationalized by the inhibition of guanidine-rich transporter uptake in the presence of agents that reduce the membrane potential. Specifically, incubation of cells in buffers with high potassium ion concentrations or pretreatment of cells with gramicidin A reduces the cellular uptake of Fl-aca-arg8-CONH2 by >90%. Furthermore, the reciprocal experiment of hyperpolarizing the cell with valinomycin increased uptake by >1.5 times. In summary, we propose that the water-soluble, positively charged guanidinium headgroups of the transporter form bidentate hydrogen bonds with H-bond acceptor functionality on the cell surface. The resultant ion pair complexes partition into the lipid bilayer and migrate across at a rate related to the membrane potential. The complex dissociates on the inner leaf of the membrane, and the transporter enters the cytosol. This hypothesis does not preclude uptake by other mechanisms, including endocytosis, which is likely to dominate with large cargos.


Assuntos
Guanidina/análogos & derivados , Guanidina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Peptídeos/metabolismo , Guanidina/química , Humanos , Ligação de Hidrogênio , Células Jurkat , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Linfócitos/química , Linfócitos/metabolismo , Potenciais da Membrana/fisiologia , Proteínas de Membrana Transportadoras/química , Peptídeos/química , Potássio/química , Potássio/metabolismo
18.
J Immunol ; 172(7): 4235-44, 2004 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15034036

RESUMO

Interleukin-7 is widely accepted as a major homeostatic factor involved in T cell development. To assess the IL-7 responsiveness of thymocytes involved in selection processes, we used a new sensitive flow cytometry-based assay to detect intracellular phosphorylation of STAT-5 induced by IL-7 in defined mouse thymocyte subsets. Using this method, we found the earliest thymocyte subset (CD4(-)CD8(-)CD25(-)CD44(+)) to contain both IL-7-responsive and nonresponsive cells. Transition through the next stages of development (CD4(-)CD8(-)CD25(+)CD44(+ and -)) was associated with responsiveness of all thymocytes within these populations. Passage of thymocytes through beta-selection resulted in a significant reduction in IL-7 sensitivity. In the next phases of development (TCR(-) and TCR(low)CD69(-)), thymocytes were completely insensitive to the effects of IL-7. STAT-5 phosphorylation in response to IL-7 was again observed, however, in thymocytes involved in the positive selection process (TCR(low)CD69(+) and TCR(intermediate)). As expected, CD4 and CD8 single-positive thymocytes were responsive to IL-7. These findings delineate an IL-7-insensitive population between the beta-selection and positive selection checkpoints encompassing thymocytes predicted to die by neglect due to failure of positive selection. This pattern of sensitivity suggests a two-signal mechanism by which survival of thymocytes at these checkpoints is governed.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Interleucina-7/farmacologia , Proteínas do Leite , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Timo/imunologia , Timo/metabolismo , Transativadores/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Separação Celular , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Relação Dose-Resposta Imunológica , Regulação para Baixo/imunologia , Feminino , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas/antagonistas & inibidores , Proteínas/genética , Receptores de Interleucina-7/antagonistas & inibidores , Receptores de Interleucina-7/biossíntese , Receptores de Interleucina-7/genética , Fator de Transcrição STAT5 , Transdução de Sinais/genética , Proteínas Supressoras da Sinalização de Citocina , Subpopulações de Linfócitos T/citologia , Timo/citologia , Transcrição Gênica/imunologia
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