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1.
J Environ Manage ; 181: 681-686, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27566937

RESUMO

Environmental quality standards (EQS) specify the maximum permissible concentration or level of a specific environmental stressor. Here, a procedure is proposed to derive EQS that are specific to a representative species pool and conditional on confounding environmental factors. To illustrate the procedure, a dataset was used with plant species richness observations of grasslands and forests and accompanying soil nitrate-N and pH measurements collected from 981 sampling sites in the Netherlands. Species richness was related to soil nitrate-N and pH with quantile regression allowing for interaction effects. The resulting regression models were used to derive EQS for nitrate conditional on pH, quantified as the nitrate-N concentrations at a specific pH level corresponding with a species richness equal to 95% of the species pool, for both grasslands and forest communities. The EQS varied between 1.8 mg/kg nitrate-N at pH 9-65 mg/kg nitrate-N at pH 4. EQS for forests and grasslands were similar, but EQS based on Red List species richness were considerably lower (more stringent) than those based on overall species richness, particularly at high pH levels. The results indicate that both natural background pH conditions and Red List species are important factors to consider in the derivation of EQS for soil nitrate-N for terrestrial ecosystems.


Assuntos
Monitoramento Ambiental/normas , Nitratos/análise , Plantas , Solo/química , Biodiversidade , Ecossistema , Monitoramento Ambiental/métodos , Florestas , Pradaria , Concentração de Íons de Hidrogênio , Países Baixos , Análise de Regressão
3.
J Fish Dis ; 37(6): 521-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23991936

RESUMO

There is growing use of hybrid catfish (Ictalurus punctatus ♀ X Ictalurus furcatus ♂) in commercial aquaculture to utilize hybrid vigour to improve production A conjoined twin specimen found during the course of production studies by the United States Department of Agriculture Catfish Genetic Research Unit (USDA-CGRU) was submitted to the Aquatic Research and Diagnostic Laboratory (ARDL). After preliminary inspection, it was transported to Mississippi State University, College of Veterinary Medicine for further evaluation. The specimen was examined using both computed radiography and computed tomography antemortem. Following humane euthanasia, the specimen was examined both grossly and histologically. Tissues from both fish were also submitted for genetic analysis to determine whether twins were derived from the same egg. This report records the presentation and examination of a pair of conjoined hybrid catfish (I. punctatus X Ictalurus furcatus).


Assuntos
Anormalidades Congênitas/veterinária , Ictaluridae/anormalidades , Ictaluridae/anatomia & histologia , Animais , Aquicultura , Anormalidades Congênitas/diagnóstico por imagem , Anormalidades Congênitas/patologia , Hibridização Genética , Ictaluridae/genética , Repetições de Microssatélites , Mississippi , Tomografia Computadorizada por Raios X/veterinária
4.
Transl Vis Sci Technol ; 12(2): 10, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36749581

RESUMO

Purpose: The scotopic macular integrity assessment (S-MAIA) can perform scotopic assessment to detect localized changes to scotopic rod and cone function. This study is an exploratory investigation of the feasibility of using the S-MAIA in a rod-cone dystrophy population to identify the pattern of loss in scotopic photoreceptor function. Methods: Twenty patients diagnosed with a rod-cone dystrophy underwent visual acuity testing, full-field stimulus threshold assessment, and multiple S-MAIA tests after dark adaptation periods of 20 minutes and 45 minutes performed separately. Only right eyes were tested. Three tests were performed following a learning test. A Bland-Altman analysis was used to assess repeatability and agreement between tests after the two time periods. Spatial interpolation maps were created from the group plots to display the pattern of rod and cone loss. Results: Learning effects took place between testing sessions 1 and 2 but not 2 and 3. Limits of agreement were larger in the patient eyes than control eyes, but within previously reported values. Using longer adaptation time of 45 minutes did not offer a significant advantage over 20 minutes. Patterns for the cyan and red sensitivities were different, indicating different patterns of loss for rods and cones. Conclusions: A dark adaptation time of 20 minutes before testing is sufficient for thresholding. The S-MAIA is suitable for use in patients with a logarithm of the minimum angle of resolution vision of at least 0.7 and provides a viable outcome measure for patients with rod-cone dystrophies and preserved central vision. The spatial information about scotopic function from the S-MAIA provides information about disease processes and progression. Translational Relevance: There is a need for scotopic measures for use in clinical trials. Scotopic microperimetry works well in patients with early disease, allowing the extension of recruitment criteria for novel therapies of rod-cone dystrophies.


Assuntos
Distrofias de Cones e Bastonetes , Degeneração Retiniana , Humanos , Células Fotorreceptoras de Vertebrados/fisiologia , Adaptação à Escuridão , Células Fotorreceptoras Retinianas Cones/fisiologia
5.
Transl Vis Sci Technol ; 12(5): 21, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219509

RESUMO

Purpose: Microperimetry provides an accurate assessment of central retinal sensitivity due to its fundus-tracking capability, but it has limited reliability indicators. One method currently employed, fixation loss, samples the optic nerve blind spot for positive responses; however, it is unclear if these responses arise from unintentional button presses or from tracking failure leading to stimuli misplacement. We investigated the relationship between blind spot scotoma positive responses (termed scotoma responses) and fixation. Methods: Part 1 of the study involved a custom grid of 181 points centered on the optic nerve that was constructed to map physiological blind spots in primary and simulated eccentric fixation positions. Scotoma responses and the 63% and 95% fixation bivariate contour ellipse areas (BCEA63 and BCEA95) were analyzed. In Part 2, fixation data from controls and patients with retinal diseases (234 eyes from 118 patients) were collected. Results: Part 1, a linear mixed model of 32 control participants, demonstrated significant (P < 0.001) correlation between scotoma responses and BCEA95. In Part 2, the upper 95% confidence intervals for BCEA95 were 3.7 deg2 for controls, 27.6 deg2 for choroideremia, 23.1 deg2 for typical rod-cone dystrophies, 21.4 deg2 for Stargardt disease, and 111.3 deg2 for age-related macular degeneration. Incorporating all pathology groups into an overall statistic resulted in an upper limit BCEA95 = 29.6 deg2. Conclusions: Microperimetry reliability is significantly correlated to fixation performance, and BCEA95 provides a surrogate marker for test accuracy. Examinations of healthy individuals and patients with retinal disease are deemed unreliable if BCEA95 > 4 deg2 and BCEA95 > 30 deg2, respectively. Translational Relevance: Microperimetry reliability should be assessed using fixation performance as summarized by BCEA95 rather than the level of fixation losses.


Assuntos
Doenças Retinianas , Escotoma , Humanos , Reprodutibilidade dos Testes , Testes de Campo Visual , Fundo de Olho
6.
Microsc Microanal ; 18(6): 1253-62, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23237545

RESUMO

Ionoluminescence (IL) is the emission of light from a material due to excitation by an ion beam. In this work, a helium ion microscope (HIM) has been used in conjunction with a luminescence detection system to characterize IL from materials in an analogous way to how cathodoluminescence (CL) is characterized in a scanning electron microscope (SEM). A survey of the helium ion beam induced IL characteristics, including images and spectra, of a variety of materials known to exhibit CL in an SEM is presented. Direct band-gap semiconductors that luminesce strongly in the SEM are found not do so in the HIM, possibly due to defect-related nonradiative pathways created by the ion beam. Other materials do, however, exhibit IL, including a cerium-doped garnet sample, quantum dots, and rare-earth doped LaPO4 nanocrystals. These emissions are a result of transitions between f electron states or transitions across size dependent band gaps. In all these samples, IL is found to decay with exposure to the beam, fitting well to double exponential functions. In an exploration of the potential of this technique for biological tagging applications, imaging with the IL emitted by rare-earth doped LaPO4 nanocrystals, simultaneously with secondary electron imaging, is demonstrated at a range of magnifications.


Assuntos
Hélio , Íons , Luminescência , Microscopia/métodos , Anticorpos/química , Fluorescência , Corantes Fluorescentes/química , Microscopia Eletrônica de Varredura , Nanopartículas/química , Pontos Quânticos
7.
Am J Ophthalmol Case Rep ; 28: 101698, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36393903

RESUMO

Purpose: To report on the presence of autosomal dominant and compound dominant-null RP1-related retinitis pigmentosa in the same non-consanguineous family. Observation: The father was minimally symptomatic and referred by his optometrist aged 38. He was diagnosed with rod-cone dystrophy, confirmed to be caused by the previously reported RP1 c.2613dupA mutation. He was reassured that his 11-year-old daughter had a 50% chance of inheriting the same mutation and that the condition, if she had it, would most likely be similar. Clinical phenotyping of his daughter however revealed an early onset cone-rod dystrophy. The mother was entirely asymptomatic and clinically normal. Sanger sequencing of the RP1 gene in the daughter confirmed the presence of biallelic mutations - the dominant c.2613dupA variant from her father and a c.3843dupT truncating variant inherited from her mother, both located in exon 4 of the RP1 gene. The maternal c.3843dupT has previously been reported. Conclusions and importance: Pathogenic variants in exon 4 of RP1 are known to cause differential dominant and recessive disease. The presence of both phenotypes in a single family has not yet been reported. The father, being minimally symptomatic, is affected by a known dominant variant which truncates the RP1 protein more proximally. However, inheritance of both variants in a compound heterozygous state in the daughter resulted in a much more severe, early onset cone-rod phenotype in a pattern akin to recessive disease. This raises challenges for genetic counselling and development of gene-based therapies for RP1 mutations.

8.
Br J Ophthalmol ; 106(2): 256-261, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33127827

RESUMO

BACKGROUND: Loss of photoreceptors cause degeneration in areas of the retina beyond the photoreceptors. The pattern of changes has implications for disease monitoring and measurement of functional changes. The aim of the study was to study the changes in inner retinal structure associated with photoreceptor disease, and the impact of these on microperimetry threshold. METHODS: This retrospective cohort study was conducted on optical coherence tomography (OCT) images and microperimetry tests collected between 2013 and 2019. 22 eyes with RPGR retinitis pigmentosa completed both OCT imaging and microperimetry assessment. 18 control eyes underwent OCT imaging. Photoreceptor layer and inner retinal thickness calculated for different eccentric areas were obtained. The relationship between the photoreceptor layer and inner retinal thickness, and microperimetry threshold was explored. RESULTS: Central 1° photoreceptor layer and inner retinal thickness were 96±34 and 139±75 µm in RPGR patients, and 139±15 and 62±14 µm in controls. Photoreceptor layer thickness differed between patient and control groups across increasing visual field areas (p<0.01, Kruskal-Wallis 1-way ANOVA), whereas the inner retinal thickness significantly differed between groups for the central 1° and 3° only. Microperimetry thresholds were explained by a combination of photoreceptor thickness (coefficient 0.15, 95% CI 0.13 to 0.18) and inner retinal thickness (coefficient 0.05, 95% CI 0.03 to 0.06). CONCLUSION: OCT shows evidence of remodelling in the inner retinal layers secondary to photoreceptor disease. This appears to have an impact on microperimetry threshold measurements.


Assuntos
Retinose Pigmentar , Testes de Campo Visual , Proteínas do Olho , Humanos , Retina , Retinose Pigmentar/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
9.
Transl Vis Sci Technol ; 11(5): 15, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35576214

RESUMO

Purpose: Peripheral visual fields have not been as well defined by static automated perimetry as kinetic perimetry in RPGR-related retinitis pigmentosa. This study explores the pattern and sensitivities of peripheral visual fields, which may provide an important end point when assessing interventional clinical trials. Methods: A retrospective observational cross-sectional study of 10 genetically confirmed RPGR subjects was performed. Visual fields were obtained using the Octopus 900 perimeter. Interocular symmetry and repeatability were quantified. Visual fields were subdivided into central and peripheral subfields for analysis. Results: Mean patient age was 32 years old (20 to 49 years old). Average mean sensitivity was 7 dB (SD = 3.67 dB) and 6.8 dB (SD = 3.4 dB) for the right and left eyes, respectively, demonstrating interocular symmetry. Coefficient of repeatability for overall mean sensitivity: <2 dB. Nine out of 10 subjects had a preserved inferotemporal subfield, whose mean sensitivity was highly correlated to the central field (r2 = 0.78, P = 0.002 and r2 = 0.72, P = 0.002 for the right and left eyes, respectively). Within the central field, sensitivities were greater in the temporal than the nasal half (t-test, P = 0.01 and P = 0.03 for the right and left eyes, respectively). Conclusions: Octopus static-automated perimeter demonstrates good repeatability. Interocular symmetry permits use of the noninterventional eye as an internal control. In this cohort, the inferotemporal and central visual fields are preserved into later disease stages likely mapping to populations of surviving cones. Translational Relevance: A consistently preserved inferotemporal island of vision highly correlated to that of the central visual field may have significance as a possible future therapeutic site.


Assuntos
Retinose Pigmentar , Testes de Campo Visual , Adulto , Animais , Estudos Transversais , Proteínas do Olho , Humanos , Pessoa de Meia-Idade , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Estudos Retrospectivos , Testes de Campo Visual/métodos , Campos Visuais , Adulto Jovem
10.
Acta Ophthalmol ; 99(8): 819-825, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33783139

RESUMO

Microperimetry, or fundus-tracked perimetry, is a precise static-automated perimetric technique to assess central retinal function. As visual acuity only deteriorates at a late disease stage in RPGR-related retinitis pigmentosa (RP), alternative markers for disease progression are of great utility. Microperimetry assessment has been of critical value as an outcome measure in a recently reported phase I/II gene therapy trial for RPGR-related RP, both in terms of detecting safety and efficacy signals. Here, we performed a review of the literature. We describe the principles of microperimetry before outlining specific parameters that may be useful as outcome measures in clinical trial settings. The current state of structure-function correlations between short-wavelength autofluorescence, optical coherence tomography and adaptive optics in RPGR-related retinitis pigmentosa are also summarized.


Assuntos
DNA/genética , Proteínas do Olho/genética , Mutação , Retina/diagnóstico por imagem , Retinose Pigmentar/diagnóstico , Testes de Campo Visual/métodos , Análise Mutacional de DNA , Eletrorretinografia , Proteínas do Olho/metabolismo , Humanos , Linhagem , Retina/fisiopatologia , Retinose Pigmentar/genética , Retinose Pigmentar/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual
11.
Transl Vis Sci Technol ; 10(2): 28, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34003913

RESUMO

Introduction: Choroideremia and RPGR-associated retinitis pigmentosa (RP) are two distinct inherited rod-cone degenerations, where good visual acuity (VA) is maintained until late disease stages, limiting its usefulness as a disease marker. Low luminance VA and low luminance deficit (standard VA minus low luminance VA) may be more sensitive visual function measures. Methods: Standard VA was obtained using Early Treatment Diabetic Retinopathy Study letter charts (Precision Vision, Bloomington, IL, USA). Low luminance VA was assessed using a 2.0-log unit neutral density filter, with the same chart setup, without formal dark adaptation. Mean central retinal sensitivity was assessed using MAIA microperimetry (Centervue SpA, Padova, Italy). Optical coherence tomography imaging was attained with Heidelberg Eye Explorer software (Heidelberg Engineering, Heidelberg, Germany). Results: Twenty-four male participants with confirmed pathogenic RPGR mutations, 44 male participants with confirmed pathogenic CHM mutations, and 62 age-matched controls underwent clinical assessment prior to clinical trial recruitment. Low luminance VA was significantly reduced in both disease groups compared to controls. The low luminance deficit correlated with microperimetry retinal sensitivity and ellipsoid zone width. Eleven participants with moderate VA had poor low luminance VA (subsequently a large low luminance deficit), no detectable microperimetry sensitivity, and severely constricted ellipsoid zone widths. Conclusions: Low luminance VA and subsequently low luminance deficit are useful markers of central macular visual function in both choroideremia and RPGR-associated RP, when standard VA is preserved. Translational Relevance: Low luminance visual acuity and low luminance deficit are useful vision measures in two distinct rod-cone degenerations and may be useful in other retinal degenerations.


Assuntos
Coroideremia , Retinose Pigmentar , Coroideremia/genética , Proteínas do Olho , Alemanha , Humanos , Itália , Masculino , Retinose Pigmentar/diagnóstico , Acuidade Visual , Campos Visuais
12.
Transl Vis Sci Technol ; 10(7): 12, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34110386

RESUMO

Purpose: Mean retinal sensitivity is the main output measure used in microperimetry. It is, however, of limited use in patients with poor vision because averaging is weighted toward zero in those with significant scotomas creating an artificial floor effect. In contrast, volumetric measures avoid these issues and are displayed graphically as a hill of vision. Methods: An open-source program was created to manipulate raw sensitivity threshold data files obtained from MAIA microperimetry. Thin plate spline interpolated heat maps and three-dimensional hill of vision plots with an associated volume were generated. Retrospective analyses of microperimetry volumes were undertaken in patients with a range of retinal diseases to assess the qualitative benefits of three-dimensional visualization and volumetric measures. Simulated pathology was applied to radial grid patterns to investigate the performance of volumetric sensitivity in nonuniform grids. Results: Volumetric analyses from microperimetry in RPGR-related retinitis pigmentosa, choroideremia, Stargardt disease, and age-related macular degeneration were analyzed. In simulated nonuniform testing grids, volumetric sensitivity was able to detect differences in retinal sensitivity where mean sensitivity could not. Conclusions: Volumetric measures do not suffer from averaging issues and demonstrate superior performance in nonuniform testing grids. Additionally, volume measures enable detection of localized retinal sensitivity changes that might otherwise be undetectable in a mean change. Translational Relevance: As microperimetry has become an outcome measure in several gene-therapy clinical trials, three-dimensional visualization and volumetric sensitivity enables a complementary analysis of baseline disease characteristics and subsequent response to treatment, both as a signal of safety and efficacy.


Assuntos
Testes de Campo Visual , Campos Visuais , Proteínas do Olho , Humanos , Retina/diagnóstico por imagem , Estudos Retrospectivos , Acuidade Visual
13.
Science ; 225(4659): 326-8, 1984 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-6204379

RESUMO

Growth hormone-releasing factors (GRF's) from two human pancreatic tumors (hpGRF's) that caused acromegaly and from the rat hypothalamus ( rhGRF ) were recently isolated and characterized. Although these peptides are potent growth hormone secretagogues, they have not until now been described to have actions outside the pituitary. These GRF's were shown to stimulate digestive enzyme secretion from an exocrine pancreatic preparation in vitro, rhGRF being more than 100 times as potent as hpGRF. Adenosine 3',5'-monophosphate mediates this action of the GRF's.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Pâncreas/efeitos dos fármacos , Amilases/metabolismo , Animais , AMP Cíclico/metabolismo , Cobaias , Humanos , Pâncreas/enzimologia , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Hipófise/metabolismo , Ratos , Peptídeo Intestinal Vasoativo/farmacologia
14.
Neuroscience ; 155(4): 1048-58, 2008 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-18664375

RESUMO

The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. To directly test whether intact neurogenesis is required for gains in behavioral performance from exercise in C57BL/6J mice, neurogenesis was reduced using focal gamma irradiation (3 sessions of 5 Gy). Two months after treatment, mice (total n=42 males and 42 females) (Irradiated or Sham), were placed with or without running wheels (Runner or Sedentary) for 54 days. The first 10 days mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. The last 14 days mice were tested on water maze (two trials per day for 5 days, then 1 h later probe test), rotarod (four trials per day for 3 days), and contextual fear conditioning (2 days), then measured for neurogenesis using immunohistochemical detection of BrdU and neuronal nuclear protein (NeuN) mature neuronal marker. Consistent with previous studies, in Sham animals, running increased neurogenesis fourfold and gains in performance were observed for the water maze (spatial learning and memory), rotarod (motor performance), and contextual fear (conditioning). These positive results provided the reference to determine whether gains in performance were blocked by irradiation. Irradiation reduced neurogenesis by 50% in both groups, Runner and Sedentary. Irradiation did not affect running or baseline performance on any task. Minimal changes in microglia associated with inflammation (using immunohistochemical detection of cd68) were detected at the time of behavioral testing. Irradiation did not reduce gains in performance on rotarod or contextual fear, however it eliminated gain in performance on the water maze. Results support the hypothesis that intact exercise-induced hippocampal neurogenesis is required for improved spatial memory, but not motor performance or contextual fear in C57BL/6J mice.


Assuntos
Proliferação de Células , Condicionamento Psicológico/fisiologia , Medo , Aprendizagem em Labirinto/fisiologia , Atividade Motora/fisiologia , Neurônios/fisiologia , Condicionamento Físico Animal/métodos , Análise de Variância , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Bromodesoxiuridina/metabolismo , Proliferação de Células/efeitos da radiação , Condicionamento Psicológico/efeitos da radiação , Medo/efeitos da radiação , Feminino , Masculino , Aprendizagem em Labirinto/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos da radiação , Neuroglia/citologia , Neuroglia/fisiologia , Neurônios/citologia , Fosfopiruvato Hidratase/metabolismo , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Lesões por Radiação/reabilitação , Tempo de Reação/fisiologia , Tempo de Reação/efeitos da radiação , Fatores de Tempo
15.
Exp Hematol ; 18(3): 219-22, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2303117

RESUMO

There is a well-documented correlation between the number of T-lymphocytes in the bone marrow graft and subsequent development of acute graft-versus-host disease after allogeneic bone marrow transplantation. The incidence of acute graft-versus-host disease may be decreased with elimination of mature T-lymphocytes from the bone marrow graft. We have developed an immunomagnetic separation procedure using an avidin-based magnetic affinity cobalt colloid. Bone marrow cells were incubated with a combination of CD2, CD3, CD4, and CD8 monoclonal antibodies. The cells were washed and then incubated with the biotinylated, affinity-purified IgG fraction of goat anti-mouse immunoglobulins followed by an avidin-based magnetic affinity colloid. The cells were then run through a high-magnetic gradient separation column utilizing an external samarium cobalt magnet. The number of residual T-lymphocytes was assessed by limiting dilution analysis of clonogenic T-lymphocytes. This procedure produces an approximately 1.7-log reduction of antibody-reactive cells with 45% recovery of hematopoietic progenitors (granulocyte-macrophage colony-forming cells, GM-CFC). This causes a reduction of T-lymphocytes in the bone marrow graft to approximately 5 x 10(5) cells/kg body weight.


Assuntos
Células da Medula Óssea , Separação Celular/métodos , Coloides , Magnetismo , Linfócitos T/citologia , Anticorpos Monoclonais , Antígenos CD/análise , Avidina , Transplante de Medula Óssea , Radioisótopos de Cobalto , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , Indicadores e Reagentes , Microscopia Eletrônica , Linfócitos T/imunologia
16.
Cell Death Differ ; 22(1): 96-107, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25168239

RESUMO

Natural killer cells (NK) are important effectors of anti-tumor immunity, activated either by the downregulation of HLA-I molecules on tumor cells and/or the interaction of NK-activating receptors with ligands that are overexpressed on target cells upon tumor transformation (including NKG2D and NKP30). NK kill target cells by the vesicular delivery of cytolytic molecules such as Granzyme-B and Granulysin activating different cell death pathways, which can be Caspase-3 dependent or Caspase-3 independent. Multiple myeloma (MM) remains an incurable neoplastic plasma-cell disorder. However, we previously reported the encouraging observation that cord blood-derived NK (CB-NK), a new source of NK, showed anti-tumor activity in an in vivo murine model of MM and confirmed a correlation between high levels of NKG2D expression by MM cells and increased efficacy of CB-NK in reducing tumor burden. We aimed to characterize the mechanism of CB-NK-mediated cytotoxicity against MM cells. We show a Caspase-3- and Granzyme-B-independent cell death, and we reveal a mechanism of transmissible cell death between cells, which involves lipid-protein vesicle transfer from CB-NK to MM cells. These vesicles are secondarily transferred from recipient MM cells to neighboring MM cells amplifying the initial CB-NK cytotoxicity achieved. This indirect cytotoxicity involves the transfer of NKG2D and NKP30 and leads to lysosomal cell death and decreased levels of reactive oxygen species in MM cells. These findings suggest a novel and unique mechanism of CB-NK cytotoxicity against MM cells and highlight the importance of lipids and lipid transfer in this process. Further, these data provide a rationale for the development of CB-NK-based cellular therapies in the treatment of MM.


Assuntos
Imunidade Celular , Células Matadoras Naturais/imunologia , Mieloma Múltiplo/imunologia , Vesículas Secretórias/imunologia , Caspase 3/imunologia , Feminino , Sangue Fetal , Granzimas/imunologia , Humanos , Células K562 , Células Matadoras Naturais/patologia , Masculino , Mieloma Múltiplo/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Espécies Reativas de Oxigênio/imunologia
17.
Environ Pollut ; 200: 120-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25705854

RESUMO

Quantifying relationships between species richness and single environmental factors is challenging as species richness typically depends on multiple environmental factors. Recently, various methods have been proposed to tackle this challenge. Using a dataset comprising field observations of grassland vegetation and measured pH values, we compared three methods for deriving species richness response curves. One of the methods estimates species richness close to the maximum species richness observed at the sites, whereas the other two provide estimates of the potential species richness along the environmental gradient. Our response curves suggest that potential species richness of grasslands is slightly more sensitive to acidification than realized plant species richness. However, differences in corresponding environmental quality standards (EQS) for acidification were small compared to intrinsic spatial differences in natural soil pH, indicating that natural background values are more important to consider in the derivation of EQS for pH than methodological differences between the three approaches.


Assuntos
Biodiversidade , Monitoramento Ambiental/métodos , Plantas/classificação , Meio Ambiente , Solo
18.
Leuk Res ; 11(12): 1067-77, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3695563

RESUMO

A colloidal suspension of Co2B with avidin irreversibly adsorbed to the surface has been used with biotinylated antibodies and lectins to eliminate specific cell populations from mixtures with peripheral blood or bone marrows. Using the monoclonal antibodies CF-1 and PM-81 with this magnetic affinity colloid (MAC), we can eliminate five logs of K562 cells from mixtures with peripheral blood or marrow cells as determined by a linear limiting dilution clonogenic assay. We have also used this separation to eliminate clonogenic leukemia cells from fresh samples of peripheral blood and bone marrow from relapsed acute leukemia patients. Using CF-1 alone or in combination with PM-81, we eliminated two logs of colonies and clusters of leukemia cells from the fresh samples. The same antibodies used with MAC separation of hematologically normal marrows allow recovery of greater than 30% of the hematopoietic progenitors.


Assuntos
Células da Medula Óssea , Separação Celular/métodos , Leucemia/patologia , Coloides , Células-Tronco Hematopoéticas/citologia , Humanos , Magnetismo , Microscopia Eletrônica
19.
Phys Ther ; 76(3): 248-59, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8602410

RESUMO

BACKGROUND AND PURPOSE: The extent of a patient's impairment can be established by comparing measurements of that patient's performance with normative values obtained from apparently unimpaired individuals. Only a few studies have described normative values for muscle strength measured by hand-held dynamometry. The purpose of this study of older adults, therefore, was to obtain normative values of maximum voluntary isometric force using hand-held dynamometers. SUBJECTS: One hundred fifty-six asymptomatic adults (77 men, 70 women) participated in this study. The subjects' mean age was 64.4 years (SD=8.3, range=50-79). The male subjects' mean age was 64.5 years (SD=8.4, range=50-79), and the female subjects' mean age was 64.3 years (SD=8.2, range=50-79). METHODS: Gender, age, dominant side, height, weight, and activity level were recorded. Eight upper-extremity movements (shoulder flexion, extension, abduction, and medial and lateral rotation; elbow flexion and extension; and wrist extension) and five lower-extremity movements (hip flexion and abduction, knee flexion and extension, and ankle dorsiflexion) were resisted by one of three experienced testers using a strain-gauge hand-held dynamometer. RESULTS: Gender, age, and weight were identified as independent predictors of force for all muscle actions on both the dominant and nondominant sides. These variables were used, therefore, to create regression equations and normative values for the force of each muscle action. CONCLUSION AND DISCUSSION: The reference values provided may allow clinicians who follow the described testing protocol to estimate the severity of force-generating impairments in patients aged 50 to 79 years.


Assuntos
Músculo Esquelético/fisiologia , Idoso , Cotovelo/fisiologia , Feminino , Humanos , Joelho/fisiologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Ombro/fisiologia , Punho/fisiologia
20.
J Wildl Dis ; 30(3): 457-9, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7933297

RESUMO

Diagnosis of Trichomonas gallinae infection can reliably be made by the demonstration of organisms in material taken from a bird's mouth and crop. This can be examined directly or incubated in a growth medium until organisms are numerous enough to be easily found in aliquots examined with the microscope. We compared two methods of culture diagnosis of Trichomonas gallinae infection in pigeons. A commercially available kit, In-Pouch TF, proved as sensitive for this purpose as in vitro Diamond's medium, but had practical advantages over the usual in vitro system.


Assuntos
Doenças das Aves/diagnóstico , Columbidae/parasitologia , Tricomoníase/veterinária , Trichomonas/isolamento & purificação , Animais , Papo das Aves/parasitologia , Meios de Cultura , Boca/parasitologia , Kit de Reagentes para Diagnóstico/veterinária , Sensibilidade e Especificidade , Tricomoníase/diagnóstico
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