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Successful propagation throughout the step cycle is contingent on adequate regulation of whole-limb stiffness by proprioceptive feedback. Following spinal cord injury (SCI), there are changes in the strength and organization of proprioceptive feedback that can result in altered joint stiffness. In this study, we measured changes in autogenic feedback of five hindlimb extensor muscles following chronic low thoracic lateral hemisection (LSH) in decerebrate cats. We present three features of the autogenic stretch reflex obtained using a mechanographic method. Stiffness was a measure of the resistance to stretch during the length change. The dynamic index documented the extent of adaptation or increase of the force response during the hold phase, and the impulse measured the integral of the response from initiation of a stretch to the return to the initial length. The changes took the form of variable and transient increases in the stiffness of vastus (VASTI) group, soleus (SOL), and flexor hallucis longus (FHL), and either increased (VASTI) or decreased adaptation (GAS and PLANT). The stiffness of the gastrocnemius group (GAS) was also variable over time but remained elevated at the final time point. An unexpected finding was that these effects were observed bilaterally. Potential reasons for this finding and possible sources of increased excitability to this muscle group are discussed.
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Reflejo de Estiramiento , Traumatismos de la Médula Espinal , Animales , Estado de Descerebración , Miembro Posterior , Músculo Esquelético , Reflejo , Regulación hacia ArribaRESUMEN
The Therapeutic Education System (TES), an Internet version of the Community Reinforcement Approach plus prize-based motivational incentives, is one of few empirically supported technology-based interventions. To date, however, there has not been a study exploring differences in substance use outcomes or acceptability of TES among racial/ethnic subgroups. This study uses data from a multisite (N = 10) effectiveness study of TES to explore whether race/ethnicity subgroups (White [n = 267], Black/African American [n = 112], and Hispanic/Latino [n = 55])moderate the effect of TES. Generalized linear mixed models were used to test whether abstinence, retention, social functioning, coping, craving, or acceptability differed by racial/ethnic subgroup. Findings demonstrated that race/ethnicity did not moderate the effect of TES versus TAU on abstinence, retention, social functioning, or craving. A three-way interaction (treatment, race/ethnicity, and abstinence status at study entry) showed that TES was associated with greater coping scores among nonabstinent White participants (p = .008) and among abstinent Black participants (p < .001). Acceptability of the TES intervention, although high overall, was significantly different by race/ethnicity subgroup with White participants reporting lower acceptability of TES compared to Black (p = .006) and Hispanic/Latino (p = .008) participants. TES appears to be a good candidate treatment among a diverse population of treatment-seeking individuals with substance use disorders.
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Internet , Motivación , Aceptación de la Atención de Salud/estadística & datos numéricos , Trastornos Relacionados con Sustancias/terapia , Adaptación Psicológica , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/etnología , Trastornos Relacionados con Sustancias/psicología , Resultado del Tratamiento , Población Blanca/psicología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
The properties of blood and the relative ease of access to which it can be retrieved make it an ideal source to gauge different aspects of homeostasis within an individual, form an accurate diagnosis, and formulate an appropriate treatment regime. Tests used to determine blood parameters such as the erythrocyte sedimentation rate, hemoglobin concentration, hematocrit, bleeding and clotting times, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean cell volume, and determination of blood groups are routinely used clinically, and deviations outside the normal range can indicate a range of conditions such as anemia, pregnancy, dehydration, overhydration, infectious disease, cancer, thyroid disease, and autoimmune conditions, to mention a few. As these tests can be performed relatively inexpensively and do not require high levels of technical expertise, they are ideally suited for use in the teaching laboratory, enabling undergraduate students to link theory to practice. The practicals described here permit students to examine their own blood and that of their peers and compare these with clinically accepted normal ranges. At the end of the practicals, students are required to answer a number of questions about their findings and to link abnormal values to possible pathological conditions by answering a series of questions based on their findings.
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Fenómenos Fisiológicos Sanguíneos/inmunología , Educación en Salud/métodos , Pruebas Hematológicas/métodos , Aprendizaje Basado en Problemas/métodos , Estudiantes del Área de la Salud , Sangre/inmunología , Sedimentación Sanguínea , Recuento de Eritrocitos/métodos , Índices de Eritrocitos/fisiología , Hematócrito/métodos , HumanosRESUMEN
Nuclear reactions induced during high-energy radiotherapy produce secondary neutrons that, due to their carcinogenic potential, constitute an important risk for the development of iatrogenic cancer. Experimental and epidemiological findings indicate a marked energy dependence of neutron relative biological effectiveness (RBE) for carcinogenesis, but little is reported on its physical basis. While the exact mechanism of radiation carcinogenesis is yet to be fully elucidated, numerical microdosimetry can be used to predict the biological consequences of a given irradiation based on its microscopic pattern of energy depositions. Building on recent studies, this work investigated the physics underlying neutron RBE by using the microdosimetric quantity dose-mean lineal energy (yâ¾D) as a proxy. A simulation pipeline was constructed to explicitly calculate the yâ¾D of radiation fields that consisted of (i) the open source Monte Carlo toolkit Geant4, (ii) its radiobiological extension Geant4-DNA, and (iii) a weighted track-sampling algorithm. This approach was used to study mono-energetic neutrons with initial kinetic energies between 1 eV and 10 MeV at multiple depths in a tissue-equivalent phantom. Spherical sampling volumes with diameters between 2 nm and 1 µm were considered. To obtain a measure of RBE, the neutron yâ¾D values were divided by those of 250 keV X-rays that were calculated in the same way. Qualitative agreement was found with published radiation protection factors and simulation data, allowing for the dependencies of neutron RBE on depth and energy to be discussed in the context of the neutron interaction cross sections and secondary particle distributions in human tissue.
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Neutrones , Radiobiología , Radiometría , Humanos , Cinética , Método de Montecarlo , Efectividad Biológica RelativaRESUMEN
Many modern radiotherapy centers now have image-guided intensity-modulated radiotherapy (IG-IMRT) tools available for clinical use, and the technique offers many options for patients requiring palliative radiotherapy. We describe a single-institution experience with IG-IMRT for short-course palliative radiotherapy, highlighting the unique situations in which the technique can be most effectively used.
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The microalga Acutodesmus obliquus was investigated as a feedstock in semi-continuously fed anaerobic digestion trials, where A. obliquus was co-digested with pig slurry and maize silage. Maize silage was substituted by both 10% and 20% untreated, and 20% ultrasonicated microalgae biomass on a VS (volatile solids) basis. The substitution of maize silage with 20% of either ultrasonicated and untreated microalgae led to significantly lower biogas yields, i.e., 560 dm³ kg-1 VScorr in the reference compared to 516 and 509 dm³ kg-1VScorr for untreated and ultrasonicated microalgae substitution. Further, the viscosities in the different reactors were measured at an OLR of 3.5 g VS dm-3 d-1. However, all treatments with microalgae resulted in significantly lower viscosities. While the mean viscosity reached 0.503 Pa s in the reference reactor, mean viscosities were 53% lower in reactors where maize was substituted by 20% microalgae, i.e. 0.239 Pa s, at a constant rotation speed of 30 rpm. Reactors where maize was substituted by 20% ultrasonicated microalgae had a 32% lower viscosity, for 10% microalgae substitution a decrease of 8% was measured. Decreased viscosities have beneficial effect on the bioprocess and the economy in biogas plants. Nonetheless, with regard to other parameters, no positive effect on biogas yields by partial substitution with microalgae biomass was found. The application of microalgae may be an interesting option in anaerobic digestion when fibrous or lignocellulosic substances lead to high viscosities of the digested slurries. High production costs remain the bottleneck for making microalgae an interesting feedstock.
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Biocombustibles , Reactores Biológicos , Microalgas/metabolismo , Ensilaje , Zea mays/química , Animales , Biomasa , Fermentación , Estiércol , Porcinos , Viscosidad , Eliminación de Residuos LíquidosRESUMEN
BACKGROUND: Partial breast irradiation has been tested in limited pilot studies and shown to provide acceptable cosmesis, minimal toxicity and adequate local control. The aim of this study was to determine the feasibility of using quadrant high-dose intraoperative radiation therapy (IORT) for the treatment of early-stage breast cancer. METHODS: Fifty-two women with early-stage breast cancer were treated with breast-conserving therapy and IORT between October 2002 and January 2006. The first 18 women received a radiation dose of 20 Gy. The protocol was then amended and the remaining 34 women were treated with 18 Gy. Each patient was evaluated after surgery, and at 3, 6 and 12 months; complications, toxicity and cosmetic outcomes were recorded by the breast surgeon. RESULTS: Women treated with 18 Gy appeared to have a more favourable cosmetic outcome compared with the earlier treatment group. At last follow-up, none of the women treated on the protocol had a breast recurrence. CONCLUSION: Experience suggests that this IORT technique is feasible, although further follow-up is necessary to assess its therapeutic value.
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Neoplasias de la Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Estudios de Factibilidad , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
OBJECTIVES: The primary objective of this work was to examine the acquisition and spread of multi-drug resistant (MDR) tuberculosis (TB) in Ireland. METHODS: All available Mycobacterium tuberculosis complex (MTBC) isolates (n = 42), from MDR-TB cases diagnosed in Ireland between 2001 and 2014, were analysed using phenotypic drug-susceptibility testing, Mycobacterial-Interspersed-Repetitive-Units Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping, and whole-genome sequencing (WGS). RESULTS: The lineage distribution of the MDR-TB isolates comprised 54.7% Euro-American, 33.3% East Asian, 7.2% East African Indian, and 4.8% Indo-Oceanic. A significant association was identified between the East Asian Beijing sub-lineage and the relative risk of an isolate being MDR. Over 75% of MDR-TB cases were confirmed in non-Irish born individuals and 7 MIRU-VNTR genotypes were identical to clusters in other European countries indicating cross-border spread of MDR-TB to Ireland. WGS data provided the first evidence in Ireland of in vivo microevolution of MTBC isolates from drug-susceptible to MDR, and from MDR to extensively-drug resistant (XDR). In addition, they found that the katG S315T isoniazid and rpoB S450L rifampicin resistance mutations were dominant across the different MTBC lineages. CONCLUSIONS: Our molecular epidemiological analyses identified the spread of MDR-TB to Ireland from other jurisdictions and its potential to evolve to XDR-TB.
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Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Mycobacterium tuberculosis/genética , Adulto , Tuberculosis Extensivamente Resistente a Drogas/transmisión , Femenino , Genoma Bacteriano , Genotipo , Humanos , Irlanda/epidemiología , Masculino , Epidemiología Molecular , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Secuenciación Completa del GenomaRESUMEN
Lymphedema is a problem for breast cancer survivors. The proliferation of limb measurement techniques makes it difficult to know how best to measure an at-risk limb. Using a sample of healthy volunteers and individuals with lymphedema, this study: 1) examined the relationship between more commonly used circumferential limb measurement methods and newer measurement methods of infrared laser perometry and bioelectrical impedance; 2) compared self-reported arm symptoms in healthy volunteers and breast cancer survivors with known lymphedema; and 3) explored the relationships among self-reported arm symptoms and circumferential tape measurement, infrared laser (perometry), and single and multi-frequency bioelectrical impedance. Lymphedema index ratios were calculated to allow comparison among measurement methods. Measurement methods correlated strongly with each other. Fourteen symptoms were reported by one or more participants in the lymphedema group while participants in the healthy volunteer group reported only eight symptoms over the same time frames. Using p < 0.001, all measurement methods correlated with self-reported arm swelling in the past year, while only circumferential and impedance measurements correlated with firmness. Future research needs to include serial arm measurements to explore arm volume variation in healthy and lymphedema volunteers and to further investigate possible lymphedema index ratios cut points as lymphedema diagnostic criteria.
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Antropometría/métodos , Linfedema/patología , Extremidad Superior/patología , Adulto , Análisis de Varianza , Brazo/patología , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Impedancia Eléctrica , Femenino , Humanos , Rayos Infrarrojos , Persona de Mediana Edad , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To characterize rifampicin-resistant strains missed by the Mycobacteria Growth Indicator Tube (MGIT) 960 system but not by egg-based media in the UK and Ireland and to ascertain their prevalence. METHODS: All strains sent for second-line susceptibility testing were prospectively collected. Drug Susceptibility Testing was performed by Resistance Ratio (RR), Proportion Method (PM), MGIT 960 and MIC determination by microdilution. Rifampicin-resistance-conferring mutations were detected with line probe assays and sequencing. At the end of the study period, retrospective archived strains from 2010 to 2014 showing key mutations were analysed phenotypically and genotypically. RESULTS: Seventeen of 7234 prospective isolates were included. All of them were susceptible by MGIT. One was borderline by RR (MIC to rifampicin of 4 mg/L) and was resistant by PM. Eight were resistant and eight were highly resistant on RR. These 16 isolates had MICs between 1 and 8 mg/L on microdilution. With PM, 16/17 were susceptible to rifampicin. 17/17 had mutations in the rpoB gene. D516Y was the mutation most frequently found (13/17). Retrospectively, ten additional strains with key genotypes were found in our collection: 6/10 were susceptible in the MGIT and resistant in RR. Of the 27 studied strains, the MGIT only detected resistance in four. CONCLUSIONS: Rifampicin resistance is missed by the MGIT system. In the UK and Ireland the prevalence of these strains is low. The introduction of routine molecular testing would detect false susceptibility. Further research is needed to ascertain the role of these strains in clinical failure and their prevalence in other settings.
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Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Genotipo , Humanos , Irlanda/epidemiología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Fenotipo , Vigilancia de la Población , Prevalencia , Reino Unido/epidemiologíaRESUMEN
The cocarcinogenic action of five agents which increase microsomal mixed-function oxidase activity in vivo was examined in the C3H10T 1/2 CL8 transformation assay. The compounds studied were benz(a)anthracene, 5,6-benzoflavone, phenobarbital, pregnenolone-16 alpha-carbonitrile, and Aroclor 1254. After a 48-hr pretreatment with the agent, the cells were then treated with benzo(a)pyrene [B(a)P] and the agent for an additional 24 hr. All agents except for Aroclor 1254 increased B(a)P-mediated transformation in C3H10T 1/2 CL8 cells. Benz(a)anthracene, 5,6-benzoflavone, phenobarbital, and pregnenolone-16 alpha-carbonitrile also increased the overall metabolism of B(a)P in C3H10T 1/2 CL8 cells to 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene; 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9-hydroxybenzo(a)pyrene, and 3-hydroxybenzo(a)pyrene. Growth studies indicated that all four agents had no stimulatory effect which might have explained the increases in transformation frequency. This suggests that these agents exert their cocarcinogenic action via increases in the enzyme-mediated pathways of B(a)P metabolism.
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Transformación Celular Neoplásica/efectos de los fármacos , Cocarcinogénesis , Animales , Arocloros/farmacología , Benzo(a)Antracenos/farmacología , Benzo(a)pireno , Benzoflavonas/farmacología , Benzopirenos/metabolismo , Benzopirenos/farmacología , División Celular/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Ratones , Ratones Endogámicos C3H , Microsomas Hepáticos/efectos de los fármacos , Oxigenasas de Función Mixta/metabolismo , Fenobarbital/farmacología , Carbonitrilo de Pregnenolona/farmacologíaRESUMEN
In a V-2 model of solitary hepatic metastasis, residual tumor was histologically identified in the treatment field in only three of 14 (21%) animals subjected to microsphere embolization of tumor arterioles plus focal (43 degrees C, 40 min) hyperthermia compared with seven of ten (70%) subjected to focal (43 degrees C, 40 min) hyperthermia alone (P less than or equal to 0.05), five of seven (71%) (P less than or equal to 0.05) treated by occlusion plus sham heating, and five of five (100%) (P less than or equal to 0.01) sham-treated controls. Prior occlusion tended to reduce the radiofrequency power required for heat up and steady-state temperature maintenance of tumors (P less than or equal to 0.09 and P less than or equal to 0.06, respectively) and reduced the cooling rate after heating compared to unoccluded tumors (P less than or equal to 0.02) but did not affect mean time to temperature, maximum and minimum temperature measured at the tumor-normal tissue interface, and animal core temperature compared with that of the hyperthermia alone treatment group. In ten other animals with hepatic V-2 tumors of comparable size subjected to focal hyperthermia plus or minus arteriolar embolization, temperatures were continuously monitored at four additional intratumor sites in a fixed geometric orientation around the heating probe. No significant differences were noted in maximum and minimum temperatures in comparably oriented probes over a 40-min heating period between the hyperthermia and the occlusion-hyperthermia treatment groups. In five other animals with solitary V-2 hepatic implants, comparable microembolization plus or minus focal tumor heating to 43 degrees C, 40 min, did not significantly reduce tumor interstitial pH compared with pretreatment values. This study reproduces previously observed synergism between arteriolar embolization and hyperthermia but suggests the mechanism may be unrelated to observable differences in intratumor pH and thermal profile and may result from other mechanisms, perhaps by mimicking the angioocclusive effects of hyperthermia itself.
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Neoplasias Hepáticas/secundario , Neoplasias Experimentales/terapia , Animales , Embolización Terapéutica , Concentración de Iones de Hidrógeno , Hipertermia Inducida , Neoplasias Hepáticas/irrigación sanguínea , ConejosRESUMEN
Restriction of food intake (R) in the C57BL/KsJ db/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (AL) results in spontaneous diabetes. Previous results showed that coxsackievirus B4 (CB4)-infected genetically identical db/db mice with and without diabetes could be distinguished by the levels of CB4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cells. Our results show that the diabetic genotype db/db R was deficient in total spleen lymphocytes and lymphocyte subsets and was unable to produce agglutinating antibody to sheep erythrocytes (SRBCs) or specific antibody to noninfectious CB4. The db/db AL mutant expressing the diabetic phenotype was not as deficient in spleen cell parameters. The response to noninfectious CB4 was delayed but substantial. The db/db AL mouse was also unique with its higher agglutinating antibody levels after virus infection than its uninfected control or the infected or uninfected db/db R mouse. In vitro SRBC immunization of spleen lymphocytes determined that this enhanced response was largely dependent on the diabetic milieu and was not a property of the cells. Genetic predisposition to diabetes is characterized by immunodeficiency as evident from inadequate levels of antibodies to infectious or noninfectious antigens and absolute and relative deficiency in spleen lymphocyte subsets and total numbers of spleen cells. Phenotypic expression of diabetes results in partial amelioration of the immunodeficiency evident in diabetic genotype db/db R without disease.
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Infecciones por Coxsackievirus/inmunología , Diabetes Mellitus/genética , Tolerancia Inmunológica/genética , Animales , Células Productoras de Anticuerpos/patología , Infecciones por Coxsackievirus/sangre , Infecciones por Coxsackievirus/patología , Diabetes Mellitus/patología , Enterovirus Humano B , Ensayo de Inmunoadsorción Enzimática , Hemaglutinación , Tolerancia Inmunológica/inmunología , Inmunización , Linfocitos/patología , Ratones , Ratones Mutantes , Fenotipo , Bazo/patologíaRESUMEN
The C3H10T1/2CL8 mouse embryo oncogenic transformation bioassay system detects a wide variety of chemical carcinogens. However, one carcinogen that does not transform C3H10T1/2CL8 cells is the liver carcinogen N-2-fluorenylacetamide (FAA). Previous reports indicate that an activated form of FAA, N-acetoxy-FAA (N-OAc-FAA), transforms these fibroblasts. In an effort to understand these results, the metabolism and binding to cellular macromolecules of FAA and N-OAc-FAA using C3H10T1/2CL8 cells was investigated. C3H10T1/2CL8 cells metabolized FAA to 7-hydroxy-FAA, 2-fluorenylamine and N-hydroxy-FAA (N-OH-FAA) at rates of 5.03, 2.22 and 3.33 pmol/h/10(6) cells, respectively. N-O-Ac-FAA was bound to the DNA and RNA in C3H10T1/2CL8 cells to the extent of 10.6 and 3.6 FAA residues/10(6) nucleotides, respectively, and to protein at 21.9 pmol FAA residues/mg protein. However, binding of FAA to DNA and RNA at similar concentrations to N-OAc-FAA was less than 0.3 and 0.6 residues/10(6) nucleotides, respectively. These results strongly indicate that the inability of FAA to transform C3H10T1/2CL8 cells residues in the cells' inability to metabolize it sufficiently to the proximate carcinogen N-OH-FAA and not an inherent insensitivity to its activated forms.
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2-Acetilaminofluoreno/metabolismo , Transformación Celular Neoplásica/efectos de los fármacos , Animales , Biotransformación , Línea Celular , Ratones , Ácidos Nucleicos/metabolismo , Unión ProteicaRESUMEN
Recent investigations have demonstrated internucleosomal DNA fragmentation in ischemic neuronal tissue. This type of fragmentation is characteristic of programmed cell death or apoptosis and suggests that neuronal death in stroke may be more complex than simple necrotic death. The present experiments provide a detailed examination of the regional localization and time course for apoptotic DNA fragmentation in the cerebral cortex following focal cerebral ischemia. Spontaneously hypertensive rats were subjected to permanent right middle cerebral artery occlusion and the cerebral cortices were examined for evidence of DNA fragmentation using electrophoretic, flow cytometric, and histological approaches. An electrophoretic examination of cortical DNA at 24 h after the occlusion indicated that the majority of nucleosomal ladders were in the transition zone or penumbra and the core of the infarction, with no fragmentation apparent in the contralateral normal cortex. A flow cytometric analysis of DNA fragmentation in intact cells revealed a similar pattern, with increased fragmentation observed in ischemic cortex vs. the contralateral cortex. Saggital sections taken 1.5 mm lateral to midline were collected from animals at 1, 4, and 24 h after the infarction and DNA fragmentation was examined histologically by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining. Quantitative analysis of these sections indicated that DNA fragmentation can be observed in the anterior and central area of the infarctions as soon as 1 h after the occlusion and that the extent and magnitude of the fragmentation increases at 4 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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Apoptosis/genética , Enfermedades Arteriales Cerebrales/genética , Corteza Cerebral/patología , ADN/química , Ataque Isquémico Transitorio/genética , Animales , Enfermedades Arteriales Cerebrales/patología , Infarto Cerebral/etiología , Infarto Cerebral/patología , Enfermedad Crónica , Constricción , Citometría de Flujo , Procesamiento de Imagen Asistido por Computador , Ataque Isquémico Transitorio/patología , Ratas , Ratas Endogámicas SHR , Coloración y EtiquetadoRESUMEN
BACKGROUND: The optimal sentinel lymph node (SLN) biopsy technique remains undefined in breast cancer. Injecting radiotracer or blue dye by a variety of routes seems to stage the axilla with comparable accuracy, and we have hypothesized that the dermal and the parenchymal lymphatics of the breast drain to the same SLN in most patients. Two previous studies from our institution support this concept: (1) a single-surgeon series of 200 consecutive SLN biopsy procedures demonstrating a high dye-isotope concordance for both intradermal (ID) and intraparenchymal (IP) isotope injection, and (2) a series of 100 procedures validated by a backup axillary dissection (ALND) in which the false-negative rate following ID isotope injection was comparable to that of our previous results with IP injection. Here, we directly compare the results of SLN biopsy using either ID or IP isotope injection for our entire experience of SLN biopsy procedures in which a backup ALND was done. METHODS: This is a retrospective, nonrandomized study of 298 clinical stage I to II breast cancer patients having SLN biopsy with a backup ALND planned in advance, comparing the results of ID (n = 164) and IP (n = 134) isotope injection. All patients had IP injection of blue dye. Endpoints included (1) successful SLN identification, (2) false-negative rate, (3) dye-isotope concordance, and (4) the SLN/axillary background isotope count ratio. RESULTS: ID isotope was more successful than IP, identifying the SLN in 98% versus 89% of cases, respectively. False-negative results (4.8% vs 4.4%) and dye-isotope concordance (92% vs 93%) were comparable between the 2 groups, and SLN/axillary background isotope count ratios were significantly higher with ID than with IP injection (288/1 vs 59/1). CONCLUSIONS: ID isotope injection identifies the SLN more often than IP, stages the axilla with comparable accuracy, and is associated with higher levels of SLN isotope uptake. The dermal and parenchymal lymphatics of the breast drain to the same axillary SLN in most breast cancer patients, and ID isotope injection is the procedure of choice in this setting.
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Neoplasias de la Mama/patología , Mama/patología , Radioisótopos/administración & dosificación , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila/cirugía , Reacciones Falso Negativas , Femenino , Humanos , Inyecciones , Inyecciones Intradérmicas , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
BACKGROUND: Optimal T-cell activation requires not only ligation of the T-cell receptor (TcR) but also delivery of costimulatory signals by various accessory molecules. The interaction of the costimulatory molecule B7.1 (CD80) with its receptor CD28 provides a strong positive signal to T cells. METHODS: The B7.1 gene was transduced into cultured human ovarian, breast, and pancreatic tumor cells by using a retroviral vector. Autologous as well as allogeneic naive T-cells were stimulated with either wild-type or B7.1-transduced tumor cells in a mixed lymphocyte tumor cell culture (MLTC). In addition to cytolytic activity, T-cell proliferation, T-cell subset composition, and the frequencies of TcR variable (V) alpha and beta genes were compared in T cells from both types of MLTC. RESULTS: Introduction of the B7.1 gene into tumor cells was successful in all tumors to a varying degree. Those tumors expressing high levels of B7.1 induced significantly higher levels of T-cell proliferation than wild-type tumor cells. T-cell subset composition did not markedly differ between T cells stimulated with wild-type tumor cells or B7.1-expressing tumor cells. However, T cells stimulated with B7.1-expressing tumor cells showed a significantly increased cytolytic potential. The increased cytotoxic T lymphocyte activity was associated with a higher frequency of specific TcR V alpha and V beta genes. In addition, B7.1 costimulation promoted oligoclonality among the responding T cells. CONCLUSIONS: These data suggest that costimulation through B7.1 promotes T-cell proliferation and cytotoxic activity through clonal expansions of T cells bearing antigen-specific TcR V alpha and V beta genes and through promotion of oligoclonality. The data also suggest that promoting B7.1-mediated costimulation is an important aspect of immune therapies.
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Antígeno B7-1/fisiología , Citotoxicidad Inmunológica , Activación de Linfocitos , Neoplasias/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología , Humanos , Linfocitos T Citotóxicos/inmunología , Células Tumorales CultivadasRESUMEN
Untrained, moderately trained (runners, 15 to 25 mi/wk), and highly trained (runners, greater than 45 mi/wk) men participated in graded treadmill exercise at 50%, 70%, and 90% of their maximal oxygen consumption to quantify the relation between intensity of exercise and sympathetic nervous system and metabolic responses. Sympathetic system activation was noted at all intensities tested and was proportional to the relative exercise intensity. The magnitudes of the norepinephrine (NE) and epinephrine (E) responses were similar in all three groups of men at each relative exercise intensity and correlated with the magnitudes of change in levels of circulating plasma adrenocorticotropin hormone, cortisol, lactate (La), phosphate (Pi), and glucose (GI). The magnitudes of change in concentrations of La, Pi, and GI were also similar for the three groups at each relative exercise intensity. In contrast, a lower degree of sympathetic system activation in response to a given absolute workload was noted in the moderately and highly trained men as compared to that of the untrained men. Sympathetic and metabolic responses to exercise are similar under conditions of comparable relative exercise intensities, regardless of conditioning level. The sympathetic-adrenal medullary system is more sensitive to exercise than the hypothalamic-pituitary-adrenal axis. For a given absolute workload, the degree of activation significantly lower in trained individuals.
Asunto(s)
Glucemia/metabolismo , Ejercicio Físico , Frecuencia Cardíaca , Hormonas/sangre , Consumo de Oxígeno , Esfuerzo Físico , Hormona Adrenocorticotrópica/sangre , Adulto , Epinefrina/sangre , Humanos , Hidrocortisona/sangre , Lactatos/sangre , Masculino , Norepinefrina/sangreRESUMEN
To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/- 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn.
Asunto(s)
Líquidos Corporales/metabolismo , Frío , Inmersión , Adulto , Análisis Químico de la Sangre , Volumen Sanguíneo , Ritmo Circadiano , Humanos , Iones , Masculino , Factores de Tiempo , Orina/análisisRESUMEN
A phototrophic enrichment culture, using acetate as carbon source, reductively dechlorinated 2,3,5,6-tetrachlorobiphenyl. ortho chlorines were removed preferentially over meta chlorines. Tri- and dichlorobiphenyls were the major products. During 14 months incubation, chlorine was removed from 58% of the target molecules; 19% of the total chlorines were removed. Dechlorination did not occur in a control culture incubated in the dark.