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Bone adaptation to load: microdamage as a stimulus for bone remodelling

Lee, TC; Staines, A; Taylor, D
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /12/2002 Português
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Mechanical loading in the proximal radius was increased by ulnar osteotomy (Group O), altered by Steinmann pinning (Group P) or unaltered in sham operated controls (Group C) in skeletally mature female sheep, aged 2–4 years. A series of intravenous fluorochromes were given to label bone formation and fuchsin-stained microdamage assessed at intervals of up to 24 weeks. Microcracks were present in all groups and were found in the original cortex near the periosteal surface. No microcracks were found in the new, fibrolamellar bone laid down at periosteal orendosteal surfaces. Mean microcrack length (49 μm, SD 10 μ m) did not differ between groups or over time. Microcrack numerical and surface densities and resorption cavity density peaked in all groups at 6 weeks, consistent with a regional acceleratory phenomenon (RAP), but the peaks were significantly greater in Group O. The density of refilling or secondary osteons peaked at 10 weeks and the mean time required for the formation of an osteon was 7.51 ± 0.59 weeks. Fatigue-induced microdamage is normally present in bone and is increased due to repetitive loading of the mechanically overloaded radius. The location and timing of microcracks, resorption cavities and secondary osteons are consistent with the activation-resorption-formation remodelling cycle and suggest that microdamage is a stimulus for bone remodelling.

Age related compliance of the lamina cribrosa in human eyes

Albon, J.; Purslow, P.; Karwatowski, W.; Easty, D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/2000 Português
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AIMS—To investigate changes in the mechanical compliance of ex vivo human lamina cribrosa with age.
METHODS—A laser scanning confocal microscope was used to image the surface of the fluorescently labelled lamina cribrosa in cadaver eyes. A method was developed to determine changes in the volume and strain of the lamina cribrosa created by increases in pressure. The ability of the lamina cribrosa to reverse its deformation on removal of pressure was also measured.
RESULTS—Volume and strain measurements both demonstrated that the lamina cribrosa increased in stiffness with age and the level of pressure applied. The ability of the lamina cribrosa to regain its original shape and size on removal of pressure appeared to decrease with age, demonstrating an age related decrease in resilience of the lamina cribrosa.
CONCLUSIONS—The mechanical compliance of the human lamina cribrosa decreased with age. Misalignment of compliant cribriform plates in a young eye may exert a lesser stress on nerve axons, than that exerted by the rigid plates of an elderly lamina cribrosa. The resilience of the lamina cribrosa also decreased with age, suggesting an increased susceptibility to plastic flow and permanent deformation. Such changes may be of importance in the explanation of age related optic neuropathy in primary open angle glaucoma.



Necessity of the stalk region for immunoglobulin E interaction with CD23

Chen, Bing-Hung; Ma, Check; Caven, Timothy H; Chan-Li, Yee; Beavil, Andrew; Beavil, Rebecca; Gould, Hannah; Conrad, Daniel H
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /11/2002 Português
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Previously, a soluble mouse CD23 chimera, composed of an N-terminal trimeric isoleucine zipper motif (lz) followed by the entire extracellular region (amino acids 48–331) of CD23 (lz-CD2348–331), was prepared and exhibited strong binding to rodent immunoglobulin E (IgE). In the current study, we report the construction of a similar human chimeric protein (lz-huCD2345–321), as well as a series of murine chimeric lz-CD23 mutants with incremental portions of stalk deleted, to further investigate the role of the stalk region in mediating the CD23–IgE interaction. All chimeric proteins were designed such that the predicted heptad structure of the stalk was retained. IgE binding, as determined by the capacity to inhibit 125I-IgE from binding to Fc∈RI-bearing RBL-2H3 cells, and by surface plasmon-resonance analysis using an IgE-coated sensor chip, was unchanged from the original lz chimera and the binding parameters were similar to those of cell-surface CD23. The minimal murine chimera that retained IgE-binding activity was lz-CD23139–331, which still contains 35 amino acids of the stalk region. When the lz motif was linked to CD23 amino acid 157 (or higher), significant IgE-binding capacity was lost. With human lz-CD23, as with mouse...

Three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, retain their immunogenicity and tolerogenicity in a linked peptide

Yoshitomi, Tomomi; Hirahara, Kazuki; Kawaguchi, Junko; Serizawa, Nobufusa; Taniguchi, Yoshifumi; Saito, Saburo; Sakaguchi, Masahiro; Inouye, Sakae; Shiraishi, Akio
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /12/2002 Português
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It has been demonstrated in detail that administration of a dominant T-cell determinant to animals induces activation or immunological tolerance of T cells. However, it has not been determined whether multiple T-cell determinants, when integrated into a single peptide, retain their potential to induce T-cell activation and tolerance. We prepared a synthetic peptide comprising three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, and investigated the immunogenicity and tolerogenicity of each T-cell determinant in the linked peptide by means of lymph node cell proliferation assays using mice. Lymph node cells from mice immunized with each of the three T-cell determinants proliferated against the linked peptide in a dose-dependent manner, similar to that of the immunized peptide. Lymph node cells from mice immunized with the linked peptide proliferated against all of the three T-cell determinants. In addition, the degree of proliferation against the three T-cell determinants occurred according to their original immunogenicity, as observed in the native protein antigens. Oral administration of the linked peptide to mice before they were immunized with Cry j 1 and Cry j 2 inhibited lymph node cell proliferation against the three T-cell determinants...

Interferon-α disables dendritic cell precursors: dendritic cells derived from interferon-α-treated monocytes are defective in maturation and T-cell stimulation

Dauer, Marc; Pohl, Katrin; Obermaier, Bianca; Meskendahl, Tobias; Röbe, Julian; Schnurr, Max; Endres, Stefan; Eigler, Andreas
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /09/2003 Português
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Dendritic cells (DC) can be derived from monocytes in vitro by culture with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). It is unknown whether this regimen reflects DC differentiation from blood precursors under physiological conditions. Induction of DC development from monocytes by interferon-α (IFN-α) may occur in vivo during infection or inflammation and thus may represent a more physiological approach to DC differentiation in vitro. Here, we show that incubation of GM-CSF-cultured monocytes with IFN-α does not induce DC differentiation: cells maintain their original phenotype and cytokine secretion pattern. Even after stimulation with pro-inflammatory or T-cell-derived activation signals, IFN-α-treated monocytes do not develop DC characteristics. Addition of IL-4 during stimulation of IFN-α-treated monocytes results in the rapid development of DC-like cells expressing co-stimulatory molecules, CD83 and chemokine receptor CCR7, indicating that some degree of developmental plasticity is preserved. However, DC pre-activated with IFN-α are less effective in inducing allogeneic or antigen-specific autologous T-cell proliferation, produce less IL-12 and express lower levels of CCR7 compared to DC generated by culture with GM-CSF and IL-4. Incubating GM-CSF-cultured monocytes simultaneously with IFN-α and IL-4 does not affect phenotypic maturation of DC...

Evaluation of CD4+ T cells proliferating to grass pollen in seasonal allergic subjects by flow cytometry

RIMANIOL, A C; GARCIA, G; TILL, S J; CAPEL, F; GRAS, G; BALABANIAN, K; EMILIE, D; HUMBERT, M
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2003 Português
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Our objective was to characterize T-cell responses to Phleum pratense in grass pollen allergic individuals and healthy controls using the fluorescent dye PKH26. Peripheral blood mononuclear cells were stimulated with P. pratense, or with recall antigens, and CD3+/CD4+ and CD3+/CD8+ T-cells that had proliferated were analysed by flow cytometry. In the presence of P. pratense CD4+/CD3+ T-cells proliferated more in grass pollen sensitive atopic patients than in nonallergic controls or in nongrass pollen sensitive atopic subjects. PPD and TT recall antigens elicited uniformly high proliferation in all T-cell subsets. Only half of pollen sensitive patients also had an increased proliferation of CD3+/CD8+ T-cells in response to P. pratense. We determined precursor frequency of CD4+ T cells in the original population that responded to P. pratense and found values ranging from 1 × 10−3 to 0·6 × 10−1, in the same range as those measured for PPD and TT. In conclusion, grass pollen sensitive atopic patients show enhanced CD4+ T-cell reactivity to P. pratense, and this could be related to the presence of elevated numbers of circulating allergen-specific CD4+ T cells. This flow cytometric method should allow the identification of other phenotypic markers such as intracellular cytokines in allergen specific responding CD4+ T cells.

Naive T-cell receptor transgenic T cells help memory B cells produce antibody

Duffy, Darragh; Yang, Chun-Ping; Heath, Andrew; Garside, Paul; Bell, Eric B
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /11/2006 Português
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Injection of the same antigen following primary immunization induces a classic secondary response characterized by a large quantity of high-affinity antibody of an immunoglobulin G class produced more rapidly than in the initial response – the products of memory B cells are qualitatively distinct from that of the original naive B lymphocytes. Very little is known of the help provided by the CD4 T cells that stimulate memory B cells. Using antigen-specific T-cell receptor transgenic CD4 T cells (DO11.10) as a source of help, we found that naive transgenic T cells stimulated memory B cells almost as well (in terms of quantity and speed) as transgenic T cells that had been recently primed. There was a direct correlation between serum antibody levels and the number of naive transgenic T cells transferred. Using T cells from transgenic interleukin-2-deficient mice we showed that interleukin-2 was not required for a secondary response, although it was necessary for a primary response. The results suggested that the signals delivered by CD4 T cells and required by memory B cells for their activation were common to both antigen-primed and naive CD4 T cells.

Down-regulatory role of surface CD4 molecules on autoreactive helper T cells during B cell activation

AIZAWA, K; HAMANO, T; IWASAKI, T; KAKISHITA, E
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/1997 Português
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MS202 is an IL-2-dependent Th2 clone reactive to auto-MHC class II antigens as previously reported. It expresses CD4, TCR-αβ, Thy 1.2 and H-2k on the cell membrane, as well as CD40 ligand. In order to investigate a functional role of surface CD4 molecules on Th2 cells during B cell activation, we attempted to establish a CD4− variant subclone derived from the CD4+ MS202, and its effect on B cell activation was examined. Briefly, MS202 was incubated with ethyl methanesulfonate to induce mutation followed by extensive treatment with anti-CD4 MoAb and complement. MS1.1.2, a representative subclone of resulting cell lines, was shown to lack CD4 molecules on the cell membrane, although it possessed almost the same amount of surface molecules other than CD4 compared with the original MS202 by analysis with flow cytometry. Interestingly, MS1.1.2 induced the maturation of B cells into IgM-producing cells more potently than MS202. This differentiative effect was markedly greater on activated B cells than resting B cells; each population was prepared from splenic B cells by a gradient separation method, but after treatment with anti-IgM antibodies, resting B cells responded to MS1.1.2, resulting in the secretion of a comparative amount of IgM. Furthermore...

Cell structure of developing downfeathers in the zebrafinch with emphasis on barb ridge morphogenesis

Alibardi, L; Sawyer, R H
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /05/2006 Português
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The present ultrastructural and immunocytochemical study on the embryonic feathers of the zebrafinch, an altricial passerine bird, describes cellular differentiation of developing downfeathers. Barb ridges are folds of the original epidermis of the embryonic feather germ in which the basal–apical polarity of epidermal cells is upset. The result is the loss of most germinal activity of basal cells of the barb ridges so that only the embryonic epidermal layers remain. The more external layer is the primary periderm, followed by 4–6 layers of inner-periderm cells that mature into feather sheath and barb vane ridge cells. The following layer, the subperiderm, produces a small type of beta-keratin typical of feathers. In barb ridges, the subperiderm layer is displaced to form barbule plates and barb cells. The formation of branching barbules occurs by the presence of barb vane ridge cells that function as spacers between barbule cells. The fourth layer is homologous to the germinal layer of the epidermis, but in barb ridges it rapidly loses the germinal capability and becomes the cyclindrical layer of marginal plates. The study indicates that a necrotic process determines the carving out of the final feather shape, although apoptosis may also play a role. In fact...

Long-term morphology of a healing bone–tendon interface: a histological observation in the sheep model

Newsham-West, R; Nicholson, H; Walton, M; Milburn, P
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2007 Português
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The purpose of this study was to examine and describe the sequence of events involved in long-term biological reconstruction of a tendon–bone interface following surgical reattachment. Patellar tendon re-attachment in the adult sheep was used to investigate and describe the biological components involved in healing and repair of a tendon enthesis. Light microscopy was used to describe the healing morphology at time intervals of 8, 12, 26, 52 and 104 weeks. By 8 weeks a collagen continuum was observed between the tendon and bone. Over time this fibrous bridge became anchored into the original tissues (tendon and bone), with the resultant enthesis resembling more a fibrous rather than the original fibrocartilagenous enthesis. The associated collagen fibrils between the two tissues gradually changed in morphology over time to reflect the fibres seen in the original tendon tissue. The fibrous tissue of the forming enthesis remained hypercellular when compared with the controls. The resultant long-term morphology may be a reflection of functional adaptation rather than anatomical replication.

Partial urethral obstruction of rabbit urinary bladder: stereological evidence that the increase in muscle content is mostly driven by changes in number, rather than size, of smooth muscle cells

de Castro Sasahara, Tais H; Mayhew, Terry M; Rahal, Sheila C; Fioretto, Emerson T; Balieiro, Júlio C C; Ribeiro, Antonio A C M
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2007 Português
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The effects of partial urethral obstruction on the detrusor muscle of rabbit urinary bladder were investigated using stereological sampling and estimation tools. Twelve female Norfolk rabbits (2.5–3.0 kg body weight) were divided into four groups: 3, 7 and 12 weeks after surgical intervention to produce a standard partial obstruction and unobstructed controls. Following removal, bladder axes (craniocaudal, dorsoventral and laterolateral) and organ weights were recorded. Bladders were prepared for light microscopy by multistage random sampling procedures. Stereological methods were used to estimate the volume of muscle and the packing density and total number of myocyte nuclei in each bladder. We also estimated mean myocyte volume and the mean cross-sectional area and length of myocytes. Group comparisons were made by one-way analysis of variance. Changes in bladder axes were mainly laterolateral and craniocaudal. Mean bladder weight increased roughly six-fold by 3 weeks and 17-fold by 12 weeks and was accompanied, on average, by 12- and 33-fold increases in total muscle volume. These variables did not differ at 3 and 7 weeks post-obstruction. Increases in muscle content were not accompanied by changes in packing densities but were associated with increases in the total numbers of myocyte nuclei (13-fold by 3 weeks...

Ultrastructural and immunocytochemical analyses of osteopontin in reactionary and reparative dentine formed after extrusion of upper rat incisors

Cajazeira Aguiar, Marcio; Arana-Chavez, Victor E
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2007 Português
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Reactionary dentine and reparative dentine are two strategies used by the dentine–pulp complex to respond to injury. The reactionary dentine is secreted by original odontoblasts, while the reparative dentine is formed by odontoblast-like cells. Osteopontin (OPN) is a non-collagenous protein usually present in the repair of mineralized tissues. It is likely to be present in newly formed dentine but there are no studies attempting to detect it in reactionary and reparative dentine. The aim of the present study was to examine the ultrastructural characteristics, as well as the presence and distribution of OPN in reactionary and reparative dentine by provoking extrusion of the rat incisor. The right upper incisors of 3-month-old male rats were extruded 3 mm and then repositioned into their original sockets. At 3, 7, 10, 15, 20, 30 and 60 days after surgery, the incisors were fixed in glutaraldehyde–formaldehyde and then processed for scanning and transmission electron microscopy and for immunocytochemistry for OPN. After extrusive trauma, the dentine–pulp interface showed the presence of reactionary and reparative dentine, which varied in aspect, thickness and related cells. OPN was not detected in the physiological and reactionary dentine...

The evolution of amphibian metamorphosis: insights based on the transformation of the aortic arches of Pelobates fuscus (Anura)

Kolesová, Hana; Lametschwandtner, Alois; Roček, Zbyněk
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2007 Português
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In order to gain insights into how the aortic arches changed during the transition of vertebrates to land, transformations of the aortic arches during the metamorphosis of Pelobates fuscus were investigated and compared with data from the early development of a recent ganoid fish Amia calva and a primitive caudate amphibian Salamandrella keyserlingi. Although in larval Pelobates, as in other non-pipid anurans, the gill arches serve partly as a filter-feeding device, their aortic arches maintain the original piscine-like arrangement, except for the mandibular and hyoid aortic arches which were lost. As important pre-adaptations for breathing of atmospheric oxygen occur in larval Pelobates (which have well-developed, though non-respiratory lungs and pulmonary artery), transformation of aortic arches during metamorphosis is fast. The transformation involves disappearance of the ductus Botalli, which results in a complete shunting of blood into the lungs and skin, disappearance of the ductus caroticus, which results in shunting of blood into the head through the arteria carotis interna, and disappearance of arch V, which results in shunting blood to the body through arch IV (systemic arch). It is supposed that the branching pattern of the aortic arches of permanently water-dwelling piscine ancestors...

Detection of bilayer phospholipid-binding antibodies using flow cytometry

ESCHWÈGE, V; LAUDE, I; TOTI, F; PASQUALI, J-L; FREYSSINET, J-M
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /01/1996 Português
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Antiphospholipid antibodies (APL) are usually detected using solid-phase immunoassays, where cardiolipin is the most common capture antigen. Phosholipids are believed to adopt a monolayer organization when coated onto polystyrene after evaporation of the solvent. However, bilayer phospholipids are probably those evidenced as microparticles or cell fragments circulating in vivo under various pathological circumstances. The surface density of monolayer phospholipids on polystyrene is six times lower than that of bilayer phospholipids. In order to assess the influence of phospholipid organization on the detection of APL, we prepared glass microspheres coated with bilayer phospholipids (cardiolipin, phosphatidylcholine, cholesterol). Such lipospheres enabled us to study the binding of antibodies in 1:100 diluted plasma samples from patients with anti-cardiolipin antibodies of IgG isotype previously diagnosed by ELISA. Among the 39 plasma samples analysed by flow cytometry, 17 showed positive IgG binding to lipospheres. Only four additional samples became positive when adding 20 μg/ml apolipoprotein H. The specificity of the binding was demonstrated by complete reversibility with 1.4 μm annexin V and with a large excess of liposomes of the same composition. The absence of correlation between liposphere and ELISA results suggests that different subgroups of antibodies are detected depending on the method. The detection of APL using bilayer phospholipids is an original assay and may represent a more physiopathological approach to the specificity of APL.

A combined mechanical and X-ray diffraction study of stretch potentiation in single frog muscle fibres

Linari, M; Lucii, L; Reconditi, M; Casoni, M E Vannicelli; Amenitsch, H; Bernstorff, S; Piazzesi, G; Lombardi, V
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em 01/08/2000 Português
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The nature of the force (T) response during and after steady lengthening has been investigated in tetanized single muscle fibres from Rana temporaria (4 °C; 2.15 μm sarcomere length) by determining both the intensity of the third order myosin meridional X-ray reflection (IM3) and the stiffness (e) of a selected population of sarcomeres within the fibre.With respect to the value at the isometric tetanus plateau (T0), IM3 was depressed to 0.67 ± 0.04 during steady lengthening at ≈160 nm s−1 (T≈ 1.7) and recovered to 0.86 ± 0.05 during the 250 ms period of after-stretch potentiation following the rapid decay of force at the end of lengthening (T≈ 1.3); under the same conditions stiffness increased to 1.25 ± 0.02 and to 1.12 ± 0.03, respectively.After subtraction of the contribution of myofilaments to the half-sarcomere compliance, stiffness measurements indicated that (1) during lengthening the cross-bridge number rises to 1.8 times the original isometric value and the average degree of cross-bridge strain is similar to that induced by the force-generating process in isometric conditions (2.3 nm), and (2) after-stretch potentiation is explained by a residual larger cross-bridge number.Structural data are compatible with mechanical data if the axial dispersion of attached heads is doubled during steady lengthening and recovers half-way towards the original isometric value during after-stretch potentiation.

Response properties of isolated mouse olfactory receptor cells

Reisert, Johannes; Matthews, Hugh R
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em 01/01/2001 Português
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Response properties of isolated mouse olfactory receptor cells were investigated using the suction pipette technique. Cells were exposed to the odour cineole or to solutions of modified ionic content by rapidly changing the solution superfusing the cilia. All experiments were performed at 37°C.Mouse olfactory receptor cells displayed a steep dependence of action potential frequency on stimulus concentration, a 3-fold increase in stimulus concentration often saturating the firing frequency at 200-300 Hz. The receptor current increased more gradually with increasing cineole concentration and did not saturate within the 100-fold range of cineole concentrations applied.When stimulated for 30 s with a low odour concentration, cells responded with sporadic spike firing. Higher concentrations led to the generation of a large receptor current at the onset of stimulation which returned to baseline levels within a few seconds, accompanied during its rising phase by a short burst of action potentials. Thereafter an oscillating response pattern was observed during the remainder of the stimulus, consisting of repetitive increases in receptor current of around 1 s duration accompanied by short bursts of action potentials.Olfactory adaptation was studied by comparing the responses to two closely spaced odour stimuli. The response to the second odour stimulus recovered to 80% of its original magnitude when the cell was superfused with Ringer solution during the 5 s interval between odour exposures. In contrast...

Neuroanthropology: a humanistic science for the study of the culture–brain nexus

Domínguez Duque, Juan F.; Turner, Robert; Lewis, E. Douglas; Egan, Gary
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
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In this article, we argue that a combined anthropology/neuroscience field of enquiry can make a significant and distinctive contribution to the study of the relationship between culture and the brain. This field, which can appropriately be termed as neuroanthropology, is conceived of as being complementary to and mutually informative with social and cultural neuroscience. We start by providing an introduction to the culture concept in anthropology. We then present a detailed characterization of neuroanthropology and its methods and how they relate to the anthropological understanding of culture. The field is described as a humanistic science, that is, a field of enquiry founded on the perceived epistemological and methodological interdependence of science and the humanities. We also provide examples that illustrate the proposed methodological model for neuroanthropology. We conclude with a discussion about specific contributions the field can make to the study of the culture–brain nexus.

Palliative Medicine and Decision Science: The Critical Need for a Shared Agenda To Foster Informed Patient Choice in Serious Illness

Bakitas, Marie; Kryworuchko, Jennifer; Matlock, Dan D.; Volandes, Angelo E.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em /10/2011 Português
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Assisting patients and their families in complex decision making is a foundational skill in palliative care; however, palliative care clinicians and scientists have just begun to establish an evidence base for best practice in assisting patients and families in complex decision making. Decision scientists aim to understand and clarify the concepts and techniques of shared decision making (SDM), decision support, and informed patient choice in order to ensure that patient and family perspectives shape their health care experience. Patients with serious illness and their families are faced with myriad complex decisions over the course of illness and as death approaches. If patients lose capacity, then surrogate decision makers are cast into the decision-making role. The fields of palliative care and decision science have grown in parallel. There is much to be gained in advancing the practices of complex decision making in serious illness through increased collaboration. The purpose of this article is to use a case study to highlight the broad range of difficult decisions, issues, and opportunities imposed by a life-limiting illness in order to illustrate how collaboration and a joint research agenda between palliative care and decision science researchers...

Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (–)-γ chain (–) (NRG) mice is similar but not identical to the original stem cell donor

Harris, D T; Badowski, M; Balamurugan, A; Yang, O O
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Português
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The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1null-γ chainnull (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34+ stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be ‘humanized’ long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system.

Duas décadas de pesquisa em tuberculose no Brasil: estado da arte das publicações científicas; Two decades of research on tuberculosis in Brazil: state of the art of scientific publications

Kritski, Afrânio Lineu; Villa, Tereza Scatena; Trajman, Anete; Lapa e Silva, José Roberto; Medronho, Roberto A.; Ruffino-Netto, Antonio
Fonte: Universidade de São Paulo. Faculdade de Saúde Pública Publicador: Universidade de São Paulo. Faculdade de Saúde Pública
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf; application/pdf
Publicado em 01/09/2007 Português
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A tendência das publicações brasileiras em tuberculose referente ao período de foi analisada no período 1986 a 2006. Esta análise incluiu dissertações e teses registradas da Capes e artigos indexados na base de dados Medline e no SciELO. A seleção das publicações foi realizada por busca pela palavra "tuberculose" e instituições brasileiras a que se afiliavam os autores. A análise mostrou inicialmente publicações do tipo relatos de caso e revisões, e posteriormente artigos originais em ciência, tecnologia e inovação científica. Estas mudanças podem refletir o incremento das atividades de pesquisa nas instituições acadêmicas e novas atitudes relativas aos objetivos da pesquisa em tuberculose nos últimos anos. Embora muitas teses tenham utilizado metodologia qualitativa, poucos artigos nessa modalidade foram encontrados, possivelmente refletindo a orientação quantitativa das revistas. Discutem-se pesquisa quantitativa versus qualitativa e educação versus pesquisa, assim como políticas públicas e estratégias para incluir a pesquisa como instrumento de controle das doenças. Sugere-se a utilização da mesma metodologia para analisar as tendências da pesquisa em outras doenças negligenciadas.; The trends of scientific articles about tuberculosis in Brazil published between 1986 and 2006 were analyzed. This analysis included Capes database-indexed dissertations and theses and papers indexed in Medline and SciELO. Papers containing the word "tuberculosis" and authors affiliated to Brazilian institutions were included in the assessment. The analysis showed initially case report and review publications...