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1.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(4): 340-344, 2021 Apr 24.
Artigo em Zh | MEDLINE | ID: mdl-33874683

RESUMO

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.


Assuntos
Diuréticos , Insuficiência Cardíaca , Idoso , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Ultrafiltração
2.
J Eur Acad Dermatol Venereol ; 34(3): 485-490, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31419354

RESUMO

BACKGROUND: Basal cell carcinoma with large subclinical extension (BCC-LSE) is a tumour whose extensive spread becomes apparent during Mohs surgery histopathology review. Not recognizing BCC-LSE preoperatively may result in a greater number of Mohs layers and in larger than anticipated postoperative defects. OBJECTIVE: To evaluate the characteristics of BCC-LSE. METHODS: This retrospective study reviewed BCC treated with Mohs surgery at a single academic surgical centre between March 2007 and February 2012. A total of 2044 cases met the criteria of BCC-LSE, which was defined as a lesion requiring at least three Mohs stages and a final surgical margin (difference between preoperative and postoperative measurements in either vertical or horizontal dimensions) of ≥1 cm. RESULTS: In adjusted multivariable analysis, male sex (P = 0.05), Fitzpatrick skin type I (P = 0.002), history of prior BCC (P = 0.003) and subtypes of basosquamous, metatypical, micronodular, infiltrative, morpheaform and sclerosing (P = 0.005) remained significant BCC-LSE predictors. CONCLUSIONS: Demographic factors, including personal history of BCC, skin type, anatomic location, gender and age, in addition to tumour histologic subtype assessed through incisional biopsy, can help predict occurrence of BCC-LSE and assist physicians in optimizing preoperative assessment of surgical time and complexity.


Assuntos
Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Cirurgia de Mohs , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 45(7): 608-612, 2017 Jul 24.
Artigo em Zh | MEDLINE | ID: mdl-28738490

RESUMO

Objective: To evaluate the efficacy and safety of ultrafiltration in patients with heart failure. Methods: One hundred and thirty four cases of patients with heart failure, who hospitalized in our hospital from June 2010 to June 2016 were enrolled in this study. Random serial number was generated using SPSS 22.0 software, patients were then randomly divided into control group and ultrafiltration group with the proportion of 1∶1 (67 cases in each group). Patients in the control group received standard therapy. Patients in the ultrafiltration group received ultrafiltration therapy for 8 hours. Curative effect was evaluated after 8 hours treatment in the control group and after 12 hours in the ultrafiltration group. Following parameters were compared between the two groups: body weight, dyspnea score and 6 minutes walking distance as well as blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, BUN levels. Results: (1)Two patients died during run-in process and eventually 132 cases were chosen for final analysis (65 cases in control group and 67 cases in the ultrafiltration group). Gender, age, type of heart failure, dyspnea score, body weight at baseline were similar between the two groups. (2)Post therapy, patients' body weight decreased obviously, while dyspnea score and 6 minutes walking distance increased significantly in the ultrafiltration group compared to baseline(all P<0.05), and the improvement was significantly greater compared to control group(all P<0.05). (3)The safety index comparison of two groups: blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, and BUN were similar between the two groups at baseline and post therapy. Conclusion: Ultrafiltration therapy is safe and effective to treat patients with heart failure.


Assuntos
Insuficiência Cardíaca , Ultrafiltração , Pressão Sanguínea , Peso Corporal , Dispneia , Insuficiência Cardíaca/terapia , Humanos
5.
Zhonghua Xin Xue Guan Bing Za Zhi ; 44(6): 489-93, 2016 Jun 24.
Artigo em Zh | MEDLINE | ID: mdl-27346261

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of a new ultrafiltration device for treating refractory heart failure patients. METHODS: A total of 52 patients (37 male, age 29-85(33±44)years) with refractory heart failure were treated using a new ultrafiltration device (FQ-16). Body weight, dyspnea score, oxygen saturation (SatO2), left ventricular ejection fraction(LVEF), BUN, creatinine, electrolytes and blood gas analysis were assessed before and after the treatment. Hypotension event and other main adverse events were recorded. RESULTS: Ultrafiltration duration ranged between 8-22 hours. Total ultrafiltration volume was (4 489±1 548) ml. Compared with baseline, patients' body weight decreased from (75.3±8.74) kg to (69.8±8.39) kg (P<0.01), dyspnea score improved from 2.47±1.55 to 12.87±3.61 (P<0.01) and SatO2 increased from 91.0±6.01 to 96.4±2.52 (P<0.01) and LVEF increased from (30.0±4.1)% to (36.0±4.3)% (P<0.01) after ultrafiltration. Blood creatinine, BUN, electrolytes and blood gas analysis values were similar at baseline and post ultrafiltration. No hypotension event and other main adverse events occurred during the ultrafiltration treatment. CONCLUSIONS: The novel ultrafiltration device adequately relieved hypervolemia and dyspnea in patients with refractory heart failure and the treatment process is safe in this patient cohort.


Assuntos
Insuficiência Cardíaca/terapia , Ultrafiltração/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Nitrogênio da Ureia Sanguínea , Peso Corporal , Creatinina/sangue , Dispneia/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda
6.
Genet Mol Res ; 13(3): 6582-92, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-25177939

RESUMO

Polymorphism 17q12 rs4430796 within HNF1ß is a genetic variant associated with both diabetes mellitus and prostate cancer, but findings on the correlations of rs4430796 with prostate cancer risk specifically are not in agreement, especially among diverse populations. To shed some light on the contradictory findings, therefore, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of all currently available case-control studies located within PubMed and Embase databases up to December 2012. A total of 16 studies comprising 30 datasets that collectively involved 25,535 prostate cancer patients and 25,726 controls were ultimately included in this analysis. The meta-analysis of all the studies revealed that the rs4430796 polymorphism was significantly associated with an increased risk of prostate cancer in all contrast models (ORA vs G = 1.25, 95%CI = 1.21-1.30, POR < 0.001; ORAA vs GG = 1.53, 95%CI = 1.45-1.62, POR < 0.001; ORAG vs GG = 1.24, 95%CI = 1.16-1.34, POR < 0.001; ORAA vs AG+GG = 1.36, 95%CI = 1.30-1.42, POR < 0.001; ORAA+AG vs GG = 1.37, 95%CI = 1.30-1.44, POR < 0.001). After subgroup analyses stratified by ethnicity, however, the rs4430796 polymorphism was significantly associated with prostate cancer in both Caucasians and Asians but not in African-Americans. In conclusion, our meta-analysis identified a significant association between the 17q12 rs4430796 polymorphism and prostate cancer risk, although the degree of this association and frequency of the causative allele varied among men of different races.


Assuntos
Diabetes Mellitus/genética , Predisposição Genética para Doença/genética , Fator 1-beta Nuclear de Hepatócito/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Cromossomos Humanos Par 17/genética , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Razão de Chances , Neoplasias da Próstata/etnologia , Fatores de Risco , População Branca/genética , População Branca/estatística & dados numéricos
7.
Genet Mol Res ; 13(2): 3165-75, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24841648

RESUMO

Okra (Abelmoschus esculentus L.) is not only a nutrient-rich vegetable but also an important medicinal herb. Inter-simple sequence repeat (ISSR) markers were employed to investigate the genetic diversity and differentiation of 24 okra genotypes. In this study, the PCR products were separated by electrophoresis on 8% nondenaturing polyacrylamide gel and visualized by silver staining. The 22 ISSR primers produced 289 amplified DNA fragments, and 145 (50%) fragments were polymorphic. The 289 markers were used to construct the dendrogram based on the unweighted pair-group method with arithmetic average (UPGMA) cluster analysis. The dendrogram indicated that 24 okras were clustered into 4 geographically distinct groups. The average polymorphism information content (PIC) was 0.531929, which showed that the majority of primers were informative. The high values of allele frequency, genetic diversity, and heterozygosity showed that primer-sample combinations produced measurable fragments. The mean distances ranged from 0.045455 to 0.454545. The dendrogram indicated that the ISSR markers succeeded in distinguishing most of the 24 varieties in relation to their genetic backgrounds and geographical origins.


Assuntos
Abelmoschus/genética , Variação Genética , Repetições de Microssatélites/genética , Biomarcadores , Genótipo , Humanos , Filogeografia
8.
J Exp Med ; 174(6): 1557-63, 1991 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-1836013

RESUMO

Human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (gp120 and gp41) elicit virus-neutralizing antibodies (VNAB) and also antibodies enhancing HIV-1 infection (EAB). Several epitopes eliciting VNAB have been defined, the principal virus-neutralizing determinant being assigned to the V3 loop of gp120. To provide a background for a rational design of anti-HIV vaccines, it also appears important to define domains eliciting EAB. This was accomplished by screening antisera against synthetic peptides covering almost the entire sequence of gp120/gp41 for their enhancing effects on HIV-1 infection of MT-2 cells, a continuous T cell line. Many (16/30) of the antisera significantly enhanced HIV-1 in the presence of human complement. Antibodies to complement receptor type 2 (CR2) abrogated the antibody-mediated enhancement of HIV-1 infection. Antisera to V3 hypervariable loops of 21 distinct HIV-1 isolates were also tested for their enhancing effects on HIV-1IIIB infection. 11 of these sera contained VNAB and 10 enhanced HIV-1IIIB infection. All antisera with virus-enhancing activity contained antibodies crossreactive with the V3 loop of HIV-1IIIB, and the virus-enhancing activity increased with increasing serological crossreactivity. These results suggest that immunization with antigens encompassing V3 loops may elicit EAB rather than protective antibodies if epitopes on the immunogen and the predominant HIV-1 isolate infecting a population are insufficiently matched, i.e., crossreactive serologically but not at the level of virus neutralization.


Assuntos
Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , HIV-1/crescimento & desenvolvimento , Soros Imunes/imunologia , Animais , Antígenos de Diferenciação de Linfócitos B/fisiologia , Linhagem Celular , Proteínas do Sistema Complemento/fisiologia , Temperatura Alta , Coelhos , Receptores de Complemento/fisiologia , Receptores de Complemento 3d , Linfócitos T/imunologia
9.
J Exp Med ; 168(6): 2207-19, 1988 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-3199067

RESUMO

CTL and NK cells resist self-mediated killing and lysis by their own pore-forming protein (PFP; perforin). Perforin, like C, lyses RBC. Efficient C-mediated lysis of RBC occurs when both C and RBC are from different species (homologous species restriction). A protective surface protein (C8-binding protein, homologous restriction factor) has been reported to mediate both homologous species restriction in C-dependent cytolysis and protection of some target cells against perforin-induced lysis. We show here that perforin, unlike C, lyses target cells across a variety of species, including the homologous one, while the same target cell populations resist the attack by homologous C. Perforin-containing extracts of CTL and LAK/NK cells from three species (rat, mouse, and human) and purified mouse perforin were tested against RBC from 10 different species, several nucleated target cell lines, and one primary cell population (thymocytes). While resisting lysis by homologous C, most of these cell types were lysed effectively by perforin without any homologous restriction pattern. CTL and NK cells, like other nucleated targets, are resistant to lysis by homologous but not heterologous C; however, these cell types are resistant to both homologous and heterologous perforin. Together, our results suggest that the protective mechanisms associated with C- and perforin-mediated lysis are distinct.


Assuntos
Proteínas do Sistema Complemento/fisiologia , Linfócitos/efeitos dos fármacos , Glicoproteínas de Membrana , Proteínas de Membrana/farmacologia , Animais , Linhagem Celular , Eritrócitos/efeitos dos fármacos , Hemólise , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Perforina , Proteínas Citotóxicas Formadoras de Poros , Ratos , Especificidade da Espécie
10.
Artigo em Inglês | MEDLINE | ID: mdl-31976004

RESUMO

BACKGROUND: There are many possible ways to treat verruca, but no one is the single perfect treatment. YIKEER is a kind of compound preparation of Chinese traditional medicine, which has been used in the treatment of verruca for several years. AIM: To confirm the effects of YIKEER for verruca. METHOD: Patients with verruca vulgaris, verruca plantaris, or verruca plana were instructed to apply YIKEER stock solution or diluent to the lesions once or twice daily for 5-7 days. Then, the YIKEER was ceased for 3-4 days, and sea buckthorn oil was used for wound repairing. The total procession was defined as one session. RESULT: Respective 88.05% verruca vulgaris patients, 86.03% verruca plantaris patients, and 82.42% verruca plana patients achieved complete response. Most patients gained complete or partial responses after 4 treatment sessions. The percentage of patients who achieved at least 50% improvement was 90.34% for verruca vulgaris, 90.60% for verruca plantaris, and 80.91% for verruca plana after 4-session treatment. The efficacy of verruca vulgaris or verruca plantaris was better than that of verruca plana. CONCLUSION: YIKEER is an effective, safe, and well-tolerated agent for treating verruca including verruca vulgaris, verruca plantaris, and verruca plana.

11.
Phys Med Biol ; 52(17): 5443-56, 2007 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-17762097

RESUMO

In this work we develop techniques that can derive the tumor position from external respiratory surrogates (abdominal surface motion) through periodically updated internal/external correlation. A simple linear function is used to express the correlation between the tumor and surrogate motion. The function parameters are established during a patient setup session with the tumor and surrogate positions simultaneously measured at a 30 Hz rate. During treatment, the surrogate position, constantly acquired at 30 Hz, is used to derive the tumor position. Occasionally, a pair of radiographic images is acquired to enable the updating of the linear correlation function. Four update methods, two aggressive and two conservative, are investigated: (A1) shift line through the update point; (A2) re-fit line through the update point; (C1) re-fit line with extra weight to the update point; (C2) minimize the distances to the update point and previous line fit point. In the present study of eight lung cancer patients, tumor and external surrogate motion demonstrate a high degree of linear correlation which changes dynamically over time. It was found that occasionally updating the correlation function leads to more accurate predictions than using external surrogates alone. In the case of high imaging rates during treatment (greater than 2 Hz) the aggressive update methods (A1 and A2) are more accurate than the conservative ones (C1 and C2). The opposite is observed in the case of low imaging rates.


Assuntos
Artefatos , Movimento , Neoplasias/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Mecânica Respiratória , Técnica de Subtração , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Humanos , Neoplasias/fisiopatologia , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Eur Rev Med Pharmacol Sci ; 21(16): 3705-3713, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28925470

RESUMO

OBJECTIVE: To investigate the effect of autophagy on acute myocardial infarction (AMI), and its mechanism in rats. MATERIALS AND METHODS: A total of 75 Sprague Dawley (SD) rats were randomly divided into three groups (n=25): sham operation (S) group, the AMI group and rapamycin (RAPA) treatment group. The model of AMI was established and the myocardial infarction size was calculated by triphenyltetrazolium chloride (TTC) staining. Morphological changes in myocardium were observed by hematoxylin and eosin (HE) staining. Expression levels of autophagy-related proteins LC3-phosphatidylethanolamine conjugate (LC3-II) and p62 were detected by semi-quantitative polymerase chain reaction (PCR) and Western blot. RESULTS: Compared with the S group, the heart-to-body weight ratio on the 21st day in AMI group was significantly increased. TTC staining results showed that compared with the S group, the size of left ventricular infarction area was significantly increased in the AMI group, and that in the RAPA group was significantly decreased. HE staining results showed that the anterior wall of the left ventricle of rats became thinner, and myocardial cells were degenerated and lost seriously in the AMI group 21 days later. Compared with the S group, the expression level of LC3-II in the infarcted peripheral area was significantly increased and that of p62 was significantly increased in the AMI group. Compared with the AMI group, the expression level of LC3-II in the infarction-peripheral area was significantly increased and that of p62 was significantly decreased after the treatment with RAPA. CONCLUSIONS: Autologous activation could protect myocardium by the left anterior descending (LAD) ligation in rats. Autophagy could reduce the area of myocardial infarction after LAD ligation and improve cardiac function.


Assuntos
Autofagia/fisiologia , Infarto do Miocárdio/fisiopatologia , Animais , Peso Corporal , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Sirolimo/farmacologia
13.
Brachytherapy ; 15(3): 387-398, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27216118

RESUMO

PURPOSE: Current clinical brachytherapy dose calculations are typically based on the Association of American Physicists in Medicine Task Group report 43 (TG-43) guidelines, which approximate patient geometry as an infinitely large water phantom. This ignores patient and applicator geometries and heterogeneities, causing dosimetric errors. Although Monte Carlo (MC) dose calculation is commonly recognized as the most accurate method, its associated long computational time is a major bottleneck for routine clinical applications. This article presents our recent developments of a fast MC dose calculation package for high-dose-rate (HDR) brachytherapy, gBMC, built on a graphics processing unit (GPU) platform. METHODS AND MATERIALS: gBMC-simulated photon transport in voxelized geometry with physics in (192)Ir HDR brachytherapy energy range considered. A phase-space file was used as a source model. GPU-based parallel computation was used to simultaneously transport multiple photons, one on a GPU thread. We validated gBMC by comparing the dose calculation results in water with that computed TG-43. We also studied heterogeneous phantom cases and a patient case and compared gBMC results with Acuros BV results. RESULTS: Radial dose function in water calculated by gBMC showed <0.6% relative difference from that of the TG-43 data. Difference in anisotropy function was <1%. In two heterogeneous slab phantoms and one shielded cylinder applicator case, average dose discrepancy between gBMC and Acuros BV was <0.87%. For a tandem and ovoid patient case, good agreement between gBMC and Acruos BV results was observed in both isodose lines and dose-volume histograms. In terms of the efficiency, it took ∼47.5 seconds for gBMC to reach 0.15% statistical uncertainty within the 5% isodose line for the patient case. CONCLUSIONS: The accuracy and efficiency of a new GPU-based MC dose calculation package, gBMC, for HDR brachytherapy make it attractive for clinical applications.


Assuntos
Braquiterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Software , Anisotropia , Computadores , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Radiometria , Dosagem Radioterapêutica , Água
14.
Phys Med Biol ; 50(5): 891-907, 2005 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-15798263

RESUMO

This paper reviews the effect of statistical uncertainties on radiotherapy treatment planning using Monte Carlo simulations. We discuss issues related to the statistical analysis of Monte Carlo dose calculations for realistic clinical beams using various variance reduction or time saving techniques. We discuss the effect of statistical uncertainties on dose prescription and monitor unit calculation for conventional treatment and intensity-modulated radiotherapy (IMRT) based on Monte Carlo simulations. We show the effect of statistical uncertainties on beamlet dose calculation and plan optimization for IMRT and other advanced treatment techniques such as modulated electron radiotherapy (MERT). We provide practical guidelines for the clinical implementation of Monte Carlo treatment planning and show realistic examples of Monte Carlo based IMRT and MERT plans.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Processamento de Imagem Assistida por Computador/métodos , Aceleradores de Partículas/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Simulação por Computador , Relação Dose-Resposta à Radiação , Humanos , Modelos Estatísticos , Método de Monte Carlo , Distribuição Normal , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Espalhamento de Radiação
15.
Mol Immunol ; 27(9): 839-45, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2215476

RESUMO

Cytotoxic T lymphocytes (CTL) release from their granules a 70 kDa protein, called PFP, perforin or cytolysin, which inserts into the target cell plasma membrane in its monomeric form. Here it polymerizes into a macromolecular complex forming pores as large as 20 nm. Although purified PFP/perforin can effectively lyze all target cells tested. CTL are refractory to lysis. The mechanism underlying the resistance of CTL is currently unknown. This study represents a search for membrane structural properties that could confer resistance to CTL against PFP/perforin-mediated lysis. The fluorescent dye merocyanine 540 was used to measure the lipid head group packing of CTL and several target cells, and 1-[4-(trimethylamine)phenyl]-6-phenylhexa-1,3,5-triene was used to estimate the fluidity of the membrane hydrocarbon region. The resistance against PFP/perforin-mediated lysis was determined by the 51Cr release assay. A comparison of the membrane rigidity with cell resistance led to the conclusion that the membrane lipid structure cannot account for the unusually high resistance of CTL. In particular, the resistant CTL line CTLL-2 has a lipid head group packing that is looser than that of Yac-1, and the sensitive target cells Jy-25 and EL-4 have membrane acyl chains that are less fluid than those of the effector CTLL-R8.


Assuntos
Membrana Celular/fisiologia , Glicoproteínas de Membrana , Proteínas de Membrana/fisiologia , Linfócitos T Citotóxicos/fisiologia , Animais , Linhagem Celular , Difenilexatrieno/análogos & derivados , Membrana Eritrocítica/fisiologia , Álcoois Graxos , Corantes Fluorescentes , Hemólise/fisiologia , Fluidez de Membrana , Lipídeos de Membrana/fisiologia , Camundongos , Perforina , Proteínas Citotóxicas Formadoras de Poros , Pirimidinonas
16.
Mol Immunol ; 28(9): 1011-8, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1922107

RESUMO

Cytotoxic T lymphocytes (CTL) contain a potent cytolytic pore-forming protein (PFP, perforin or cytolysin) localized in their cytoplasmic granules. In the presence of calcium, perforin lyses a variety of target cells (TC) non-specifically. CTL, however, are generally resistant to the lytic effect of perforin. In this work, cytoplasts from CTL and susceptible TC were made by centrifuging cells on a Ficoll density gradient in the presence of cytochalasin B. Characterization by electron microscopy and a serine esterase assay established that both CTL and TC cytoplasts were completely devoid of nuclei and CTL cytoplasts contained essentially no granules. CTL cytoplasts are just as resistant to perforin-mediated lysis as the intact CTL, and both TC and their corresponding cytoplasts are very sensitive to lysis. Furthermore, CTL cytoplasts are less effective than TC cytoplasts in inhibiting hemolysis, a property shared by the respective intact cells. These results indicate that soluble granular components do not confer resistance on CTL, and suggest that the protective agent(s) acts by impeding perforin binding to the CTL membrane.


Assuntos
Glicoproteínas de Membrana , Proteínas de Membrana/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Animais , Centrifugação com Gradiente de Concentração , Esterases/biossíntese , Técnicas In Vitro , Camundongos , Microscopia Eletrônica , Perforina , Proteínas Citotóxicas Formadoras de Poros
17.
J Immunol Methods ; 126(1): 29-37, 1990 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-2303723

RESUMO

Perforin-mediated lysis consists of at least three steps: perforin binding to the target cell, insertion into the plasma membrane, and polymerization to form pores. Perforin binding, the first step, is critical for pore formation. Accordingly, a competition assay was here established for detecting the perforin-binding activities of nucleated cells and lipid membrane vesicles such as cytoplasts or liposomes. The competition assay has certain advantages over the 51Cr release assay, since no isotope and less perforin are needed for the competition assay, and the perforin-binding activity of liposomes and proteolytic enzyme-treated and fixed nucleated cells can also be detected. The competition assay was used to study the mechanism of resistance of cytolytic T lymphocytes (CTL) to perforin-mediated lysis. The results from this assay indicate that perforin-binding activity is not a function of membrane rigidity, and that there is a direct correlation between the ability of cells to bind perforin and their susceptibility to lysis by perforin, i.e., resistant CTL and their corresponding cytoplasts bind perforin much less effectively than susceptible tumor cells and their cytoplasts. A model is proposed whereby a surface molecule or complex of molecules on CTL interferes with perforin-binding activity, thus protecting CTL from perforin-mediated lysis.


Assuntos
Glicoproteínas de Membrana , Lipídeos de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Ligação Competitiva , Álcoois Graxos/farmacologia , Lipossomos/metabolismo , Proteínas de Membrana/farmacologia , Camundongos , Perforina , Proteínas Citotóxicas Formadoras de Poros , Linfócitos T Citotóxicos/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo
18.
Med Phys ; 25(5): 668-75, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9608477

RESUMO

Recently the compensator has been shown to be an in expensive and reliable dose delivery device for photon beam intensity-modulated radiation therapy (IMRT). The goal of IMRT compensator design is to produce an optimized primary fluence profile at the patient's surface obtained from the optimization procedure. In this paper some of the problems associated with IMRT compensator design, specifically the beam perturbations caused by the compensator, are discussed. A simple formula is derived to calculate the optimal compensator thickness profile from an optimized primary fluence profile. The change of characteristics of a 6 MV beam caused by the introduction of cerrobend compensators in the beam is investigated using OMEGA Monte Carlo codes. It is found that the compensator significantly changes the energy spectrum and the mean energy of the primary photons at the patient's surface. However, beam hardening does not have as significant an effect on the percent depth dose as it does on the energy spectrum. We conclude that in most situations the beam hardening effect can be ignored during compensator design and dose calculation. The influence of the compensator on the contaminant electron buildup dose is found to be small and independent of the compensator thickness of interest. Therefore, it can be ignored in the compensator design and included as a correction into the final dose distribution. The scattered photons from the compensator are found to have no effect on the surface dose. These photons produce a uniform low fluence distribution at the patient's surface, which is independent of compensator shape. This is also true for very large fields and extremely asymmetric and nonuniform compensator thickness profiles. Compared to the primary photons, the scattered photons have much larger angular spread and similar energy spectrum at the patient's surface. These characteristics allow the compensator thickness profile and the dose distribution to be calculated from the optimized fluence profile of primary photons, without considering the scattered photons.


Assuntos
Aceleradores de Partículas , Imagens de Fantasmas , Fótons , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia/métodos , Calibragem , Desenho de Equipamento , Humanos , Modelos Teóricos , Método de Monte Carlo , Radioterapia/instrumentação , Planejamento da Radioterapia Assistida por Computador/instrumentação
19.
Med Phys ; 27(1): 180-91, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10659756

RESUMO

A hybrid approach for commissioning electron beam Monte Carlo treatment planning systems has been studied. The approach is based on the assumption that accelerators of the same type have very similar electron beam characteristics and the major difference comes from the on-site tuning of the electron incident energy at the exit window. For one type of accelerator, a reference machine can be selected and simulated with the Monte Carlo method. A multiple source model can be built on the full Monte Carlo simulation of the reference beam. When commissioning electron beams from other accelerators of the same type, the energy spectra in the source model are tuned to match the measured dose distributions. A Varian Clinac 2100C accelerator was chosen as the reference machine and a four-source beam model was established based on the Monte Carlo simulations. This simplified beam model can be used to generate Monte Carlo dose distributions accurately (within 2%/2 mm compared to those calculated with full phase space data) for electron beams from the reference machine with various nominal energies, applicator sizes, and SSDs. Three electron beams were commissioned by adjusting the energy spectra in the source model. The dose distributions calculated with the adjusted source model were compared with the dose distributions calculated using the phase space data for these beams. The agreement is within 1% in most of cases and 2% in all situations. This preliminary study has shown the capability of the commissioning approach for handling large variation in the electron incident energy. The possibility of making the approach more versatile is also discussed.


Assuntos
Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Radioterapia de Alta Energia/métodos , Algoritmos , Fenômenos Biofísicos , Biofísica , Elétrons , Humanos , Modelos Estatísticos , Método de Monte Carlo , Aceleradores de Partículas , Imagens de Fantasmas , Radioterapia de Alta Energia/estatística & dados numéricos
20.
Med Phys ; 28(1): 55-66, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11213923

RESUMO

A simple analytical approach has been developed to model extrafocal radiation and monitor chamber backscatter for clinical photon beams. Model parameters for both the extrafocal source and monitor chamber backscatter are determined simultaneously using conventional measured data, i.e., in-air output factors for square and rectangular fields defined by the photon jaws. The model has been applied to 6 MV and 15 MV photon beams produced by a Varian Clinac 2300C/D accelerator. Contributions to the in-air output factor from the extrafocal radiation and monitor chamber backscatter, as predicted by the model, are in good agreement with the measurements. The model can be used to calculate the in-air output factors analytically, with an accuracy of 0.2% for symmetric or asymmetric rectangular fields defined by jaws when the calculation point is at the isocenter and 0.5% when the calculation point is at an extended SSD. For MLC-defined fields, with the jaws at the recommended positions, calculated in-air output factors agree with the measured data to within 0.3% at the isocenter and 0.7% at off-axis positions. The model has been incorporated into a Monte Carlo dose algorithm to calculate the absolute dose distributions in patients or phantoms. For three MLC-defined irregular fields (triangle shape, C-shape, and L-shape), the calculations agree with the measurements to about 1% even for points at off-axis positions. The model will be particularly useful for IMRT dose calculations because it accurately predicts beam output and penumbra dose.


Assuntos
Fótons/uso terapêutico , Radiometria/métodos , Fenômenos Biofísicos , Biofísica , Humanos , Modelos Teóricos , Radiometria/instrumentação , Radiometria/estatística & dados numéricos , Dosagem Radioterapêutica , Radioterapia de Alta Energia , Espalhamento de Radiação
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