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glycine - and gaba - activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. in the superfused retinal slice, a cell was voltage clamped at 0 mv in the presence of cobalt ; then glycine or gaba was puffed onto the axon terminal. types cba1, cba2, and a few cba1 - 2 cells demonstrated larger glycine - activated currents than gaba - activated ones. however, some off cells ( cba2 ( n ), cba1 - 2 ( n ), cba1 ( w ) ), most cba1 - 2, and most on cells ( cbb3, cbb3 - 4, cbb3 ( n ), and cbb4 ) displayed larger gaba - activated currents. the on cell, cbb5, possessed only a gaba - activated current. the predominance of glycinergic currents in cba1, cba2, and a few cba1 - 2 cells suggests a major input from the glycinergic aii amacrine cell and thus a key role for these cells in the rod bipolar pathway. certain off cells ( most cba1 - 2 ) expressed larger gaba - activated currents. all types expressed both gaba ( a ) and gabac currents about equally, although most off types ( cba1, cb a2 ( n )
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the distribution of gaba in the perifoveal and the near and far peripheral region of human retina was studied with peroxidase anti - peroxidase immunocytochemistry applied on semithin epoxy resin sections. among the labeled amacrine cells in these regions, four types can be identified : putative diffuse a2 amacrines, stratified semilunar amacrines, interstitial amacrines and small displaced amacrines. gaba - immunoreactive interplexiform cells and ganglion cells also occur. contrary to previous post - embedding studies, our preparations show that some bipolar cells in the near and far peripheral region are gaba - immunopositive. this indicates that a number of bipolar cells in human retina does have an enhanced gaba content.
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indications and perspectives in onco - hematology. bispecific antibodies, currently under active development, are a new and effective therapeutic tool in malignant hematological diseases. those used in clinical practice aim to restore the recognition of tumor cells by immune effector cells, leading to their direct and targeted cytotoxicity through the formation of an immune synapse. the main current indications are acute lymphoblastic leukemias, diffuse large b - cell lymphomas, and multiple myeloma, refractory or in relapsed after conventional treatment. due to their efficacy and tolerance profile, research on bispecific antibodies is highly active and aims to expand their indications.
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patients with primary sjogren's disease ( sjd ) have an increased risk of b cell lymphoma. the aim of this study was to determine serum protein biomarkers for lymphoma development and to advance our understanding of the functional mechanisms underlying lymphomagenesis in sjd.
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indications and perspectives in onco - hematology. bispecific antibodies, currently under active development, are a new and effective therapeutic tool in malignant hematological diseases. those used in clinical practice aim to restore the recognition of tumor cells by immune effector cells, leading to their direct and targeted cytotoxicity through the formation of an immune synapse. the main current indications are acute lymphoblastic leukemias, diffuse large b - cell lymphomas, and multiple myeloma, refractory or in relapsed after conventional treatment. due to their efficacy and tolerance profile, research on bispecific antibodies is highly active and aims to expand their indications.
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the distribution of gaba in the perifoveal and the near and far peripheral region of human retina was studied with peroxidase anti - peroxidase immunocytochemistry applied on semithin epoxy resin sections. among the labeled amacrine cells in these regions, four types can be identified : putative diffuse a2 amacrines, stratified semilunar amacrines, interstitial amacrines and small displaced amacrines. gaba - immunoreactive interplexiform cells and ganglion cells also occur. contrary to previous post - embedding studies, our preparations show that some bipolar cells in the near and far peripheral region are gaba - immunopositive. this indicates that a number of bipolar cells in human retina does have an enhanced gaba content.
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in alzheimer's disease ( ad ), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. amyloid precursor protein ( app ), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in ad pathogenesis via its secretase - mediated processing to release the c - terminal 99 - residue transmembrane fragment ( c99 ) that is further cleaved to yield amyloid - β peptides. voltage - gated proton channels ( hv1 ) have been implicated in microglial activation and release of inflammatory mediators, but the potential role of these channels in human microglia and ad pathogenesis remains unclear. here, we demonstrate that human induced pluripotent stem cell - derived microglia ( img ) express native hv1 channels with biophysical and pharmacological attributes determined by their coassembly with app and that app knockdown decreases hv1 currents, suppressing cytokine and reactive oxygen species release. in hek293t cells, app is shown to increase current by favoring channel opening at more negative membrane potentials. c99 is sufficient to assemble with hv1 and alters channel function even more significantly than app. coimmunoprecipitation, total internal reflection fluorescence microscopy, and altered pharmacology further demonstrate that c99 forms stable complexes with hv1 in the plasma membrane. in addition, we find that two early - onset ad mutations in app ( e682
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extracellular vesicles ( evs ) have been investigated as nanotherapeutics and drug delivery systems for a wide range of disease indications. however, translational application of evs is challenging due to their physical heterogeneity and variation in functional potency. the current study generated a novel hybrid ev formulation by membrane fusion of mesenchymal stem / stromal cell - derived evs with astrocyte - derived evs and defined its physicochemical and functional properties. both ev populations have translational potential for neurodegenerative disease applications - a disease area with limited treatment strategies due to its complex disease biology requiring multi - faceted therapeutic approaches. however, individual ev sources lack the full set of therapeutic properties needed for comprehensive treatment. stem cell - derived evs possess general neuroprotective and anti - inflammatory effects but lack widespread blood - brain barrier penetration and specific neurodegenerative pathology targeting. astrocytes are uniquely involved in key neuronal processes but are prone to adopting neuroinflammatory phenotypes in disease states. using super resolution microscopy and quantitative proteomic analysis, we characterized, optimized, and validated a hybrid ev formulation for its brain cell targeting, neuroprotective function, and immunomodulatory capability. these results establish a platform for ev engineering through ev - ev hybridization and demonstrate the potential of one formulation for neurodegenerative applications.
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hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis ( ra ). it alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. the mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. this study was undertaken to evaluate whether the protein lysine - specific demethylase 1 ( lsd1 ) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis.
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in alzheimer's disease ( ad ), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. amyloid precursor protein ( app ), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in ad pathogenesis via its secretase - mediated processing to release the c - terminal 99 - residue transmembrane fragment ( c99 ) that is further cleaved to yield amyloid - β peptides. voltage - gated proton channels ( hv1 ) have been implicated in microglial activation and release of inflammatory mediators, but the potential role of these channels in human microglia and ad pathogenesis remains unclear. here, we demonstrate that human induced pluripotent stem cell - derived microglia ( img ) express native hv1 channels with biophysical and pharmacological attributes determined by their coassembly with app and that app knockdown decreases hv1 currents, suppressing cytokine and reactive oxygen species release. in hek293t cells, app is shown to increase current by favoring channel opening at more negative membrane potentials. c99 is sufficient to assemble with hv1 and alters channel function even more significantly than app. coimmunoprecipitation, total internal reflection fluorescence microscopy, and altered pharmacology further demonstrate that c99 forms stable complexes with hv1 in the plasma membrane. in addition, we find that two early - onset ad mutations in app ( e682
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people living with hiv - 1 ( pwh ) and chronically using opioids have elevated risks of developing hiv - associated neurological disorders ( hand ) that are often correlated with persistent inflammation. microglia, innate immune cells in the brain, are the principal hiv - 1 reservoir in the central nervous system and regulate neuroinflammation. our group previously showed that hiv - 1 infection of induced pluripotent stem cell ( ipsc ) - derived microglia and viral intron - containing rna ( icrna ) expression triggers inflammatory responses. microglia express μ opioid receptor, mor, yet the immunomodulatory effects of opioids on hiv - 1 infection in microglia are unclear. here, we report that mor activation impacts hiv - 1 infection establishment and hiv - 1 - induced innate responses in microglia. morphine pretreatment enhanced reverse transcription ( rt ), integration, viral transcription, and p24 < sup > gag < / sup > secretion in hiv - 1 - infected ipsc - derived microglia, which was blocked by treatment with naloxone, a mor antagonist. in contrast, morphine treatment did not impact hiv - 1 infection in mor - deficient monocyte - derived macrophages, although, induced exogenous expression of mor in macrophages conferred morphine - mediated enhancement of hiv - 1 infection. interestingly, viral transcriptome analysis by digital - drop pcr revealed selective enhancement of hiv - 1 icrna expression in morphine - exposed
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monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, fc gamma ri and fc gamma rii. in contrast, we have observed that aids monocytes express significant levels of a third fc gamma r, fc gamma riii ( cd16 ), which is normally associated with activation or maturation of the monocyte population. by dual - fluorescence analysis using a monoclonal antibody specific for fc gamma riii ( mab 3g8 ), 38. 5 + / - 3. 2 % of the leum3 ( cd14 ) - positive monocytes in aids patients were cd16 positive as compared to 10. 4 + / - 1. 0 % for healthy individuals ( n = 29 ; p less than 0. 005 ). furthermore, aids monocytes expressed fc gamma riii - specific mrna which is expressed minimally or not at all in control monocytes. as a recently identified inducer of fc gamma riii expression on blood monocytes, transforming growth factor - beta ( tgf - beta ) was found to be elevated in the serum and / or plasma of aids patients. moreover, incubation of normal monocytes with aids serum or plasma induced cd16 expression which correlated with serum tgf - beta levels ( r = 0. 74, p less than 0. 001 ) and was inhibited with a neutralizing antibody to tgf - beta. thus
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human monocyte - derived dendritic cells ( modc ) are commonly used as a research tool to investigate interactions between antigen - presenting cells and t cells. generation of these cells involves the isolation of cd14 positive monocytes from peripheral blood and their in vitro differentiation into immature modc by the cytokines gm - csf and il - 4. their functional characteristics can then be manipulated by maturing these cells with a cocktail of agents, which can be tailored to induce either immune activating or tolerogenic properties. here, we describe a protocol for the generation of modc with stable tolerogenic function, referred to as tolerogenic dendritic cells. these cells have been developed as an immunotherapeutic tool for the treatment of autoimmune disease but have also proven useful to dissect mechanisms of t cell tolerance induction in vitro.
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hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis ( ra ). it alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. the mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. this study was undertaken to evaluate whether the protein lysine - specific demethylase 1 ( lsd1 ) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis.
|
pretreatment with dithiothreitol ( dtt ) is necessary to dissolve mucus in samples of induced sputum prior to analysis. however, dtt may affect cell surface markers which are essential for lymphocyte subtyping. therefore, the aim of this study was to evaluate the effect of dtt on an appropriate panel of surface markers. peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without dtt treatment. peripheral blood from healthy donors was incubated with either dtt according to standard sputum procedures or phosphate - buffered saline ( pbs ), washed and incubated with fluorochrome - labelled antibodies. after lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. leukocyte populations were identified by their light scattering properties. for analysis, fluorescence intensity was compared between dtt - and pbs - treated samples. after treatment with dtt, fluorescence intensity was significantly increased in cd16 - positive granulocytes ; it was reduced in cd2 - positive lymphocytes, cd45 - positive lymphocytes and cd14 - positive monocytes ( p < or = 0. 001 ). these changes occurred in all samples. the fluorescence intensity of cd3 -, cd4 -, cd8 -, cd19 -, cd56 - and histocompatibility leukocyte antigen dr - positive lymphocytes was not altered by dtt. however, there were statistically significant ( p < 0. 001 ), although small, changes
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pemphigus foliaceus ( pf ) is a rare autoimmune blistering disease, occasionally associated with lymphoproliferative disorders. urticarial vasculitis ( uv ) is classified as normocomplementemic or hypocomplementemic ( huv ), the latter linked to systemic involvement and increased risk of malignancy. we present a rare case of atypical huv syndrome in a 55 - year - old female with a 24 - year history of pf. she presented with recurrent heat, redness, and discoloration of the right hand. examination revealed an erythematous - violaceous, edematous lesion with irregular but well - defined borders over the thenar region, without urticarial lesions. laboratory evaluation showed marked hypocomplementemia ( c3 0. 73 g / l, c4 0. 01 g / l ), thrombocytopenia ( 32×10³ / µl ), leukocytosis, and positive ana. hepatomegaly was noted on systemic examination. hematology consultation revealed a cd5 - negative, cd19 - positive b - cell lymphoproliferative disorder. genetic testing excluded hereditary cancer mutations. this case underscores the clinical importance of recognizing atypical huv presentations without urticaria and highlights the association of hypocomplementemia and thrombocytopenia with underlying hematologic malignancy. in patients with autoimmune background and cutaneous vasculitic lesions, hematologic malignancies
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relapsed b - cell acute lymphoblastic leukemia ( b - all ) remains a therapeutic challenge, particularly in children, adolescents, and young adults. blinatumomab, a bispecific t - cell engager targeting cd19 - positive leukemic cells, has emerged as an alternative to conventional chemotherapy in post - induction consolidation. this meta - analysis aimed to evaluate its impact on survival outcomes, relapse rates, and treatment - related toxicities.
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indications and perspectives in onco - hematology. bispecific antibodies, currently under active development, are a new and effective therapeutic tool in malignant hematological diseases. those used in clinical practice aim to restore the recognition of tumor cells by immune effector cells, leading to their direct and targeted cytotoxicity through the formation of an immune synapse. the main current indications are acute lymphoblastic leukemias, diffuse large b - cell lymphomas, and multiple myeloma, refractory or in relapsed after conventional treatment. due to their efficacy and tolerance profile, research on bispecific antibodies is highly active and aims to expand their indications.
|
pemphigus foliaceus ( pf ) is a rare autoimmune blistering disease, occasionally associated with lymphoproliferative disorders. urticarial vasculitis ( uv ) is classified as normocomplementemic or hypocomplementemic ( huv ), the latter linked to systemic involvement and increased risk of malignancy. we present a rare case of atypical huv syndrome in a 55 - year - old female with a 24 - year history of pf. she presented with recurrent heat, redness, and discoloration of the right hand. examination revealed an erythematous - violaceous, edematous lesion with irregular but well - defined borders over the thenar region, without urticarial lesions. laboratory evaluation showed marked hypocomplementemia ( c3 0. 73 g / l, c4 0. 01 g / l ), thrombocytopenia ( 32×10³ / µl ), leukocytosis, and positive ana. hepatomegaly was noted on systemic examination. hematology consultation revealed a cd5 - negative, cd19 - positive b - cell lymphoproliferative disorder. genetic testing excluded hereditary cancer mutations. this case underscores the clinical importance of recognizing atypical huv presentations without urticaria and highlights the association of hypocomplementemia and thrombocytopenia with underlying hematologic malignancy. in patients with autoimmune background and cutaneous vasculitic lesions, hematologic malignancies
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chimeric antigen receptor ( car ) t ‑ cell therapy represents a novel and highly effective immunotherapeutic approach in the treatment of malignant b ‑ cell neoplasms. although the term b ‑ cell non - hodgkin's lymphoma ( b - nhl ) is still frequently used in clinical practice, the pathologically accurate designation according to the 2022 world health organization ( who ) classification is mature b ‑ cell neoplasms. the use of car t ‑ cell therapy is currently approved for several subtypes of these diseases, including large b ‑ cell lymphoma ( lbcl ), primary mediastinal b ‑ cell lymphoma ( pmbl ), mantle cell lymphoma ( mcl ) and follicular lymphoma ( fl ). the approach involves the ex vivo genetic modification of autologous t ‑ cells to express a car targeting the b ‑ cell surface antigen cd19, enabling the selective elimination of malignant cd19 - positive cells. clinical studies and register data have demonstrated a high overall response rate, significant improvements in progression - free survival ( pfs ) and sometimes also in overall survival ( os ) in the various lymphoma entities. despite these promising results, car t ‑ cell therapy remains complex and requires careful selection of the indications and specialized management of associated toxicities. typical, but mostly manageable side effects of car t ‑ cell therapy include cytokine release syndrome ( crs ),
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monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, fc gamma ri and fc gamma rii. in contrast, we have observed that aids monocytes express significant levels of a third fc gamma r, fc gamma riii ( cd16 ), which is normally associated with activation or maturation of the monocyte population. by dual - fluorescence analysis using a monoclonal antibody specific for fc gamma riii ( mab 3g8 ), 38. 5 + / - 3. 2 % of the leum3 ( cd14 ) - positive monocytes in aids patients were cd16 positive as compared to 10. 4 + / - 1. 0 % for healthy individuals ( n = 29 ; p less than 0. 005 ). furthermore, aids monocytes expressed fc gamma riii - specific mrna which is expressed minimally or not at all in control monocytes. as a recently identified inducer of fc gamma riii expression on blood monocytes, transforming growth factor - beta ( tgf - beta ) was found to be elevated in the serum and / or plasma of aids patients. moreover, incubation of normal monocytes with aids serum or plasma induced cd16 expression which correlated with serum tgf - beta levels ( r = 0. 74, p less than 0. 001 ) and was inhibited with a neutralizing antibody to tgf - beta. thus
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crohn's disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in crohn's.
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genome - wide association studies ( gwas ) have revealed risk alleles for ulcerative colitis ( uc ). to understand their cell type specificities and pathways of action, we generate an atlas of 366, 650 cells from the colon mucosa of 18 uc patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including best4 < sup > + < / sup > enterocytes, microfold - like cells, and il13ra2 < sup > + < / sup > il11 < sup > + < / sup > inflammatory fibroblasts, which we associate with resistance to anti - tnf treatment. inflammatory fibroblasts, inflammatory monocytes, microfold - like cells, and t cells that co - express cd8 and il - 17 expand with disease, forming intercellular interaction hubs. many uc risk genes are cell type specific and co - regulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. using this observation, we nominate and infer functions for specific risk genes across gwas loci. our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.
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indications and perspectives in onco - hematology. bispecific antibodies, currently under active development, are a new and effective therapeutic tool in malignant hematological diseases. those used in clinical practice aim to restore the recognition of tumor cells by immune effector cells, leading to their direct and targeted cytotoxicity through the formation of an immune synapse. the main current indications are acute lymphoblastic leukemias, diffuse large b - cell lymphomas, and multiple myeloma, refractory or in relapsed after conventional treatment. due to their efficacy and tolerance profile, research on bispecific antibodies is highly active and aims to expand their indications.
|
emerging evidence has shown the importance of inflammasome activation in the progression of autoimmune diseases. in this study, we aimed to identify the main cell types activating inflammasome in autoimmune diseases and to clarify the intracellular pathway of inflammasome activation in systemic lupus erythematosus ( sle ).
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pretreatment with dithiothreitol ( dtt ) is necessary to dissolve mucus in samples of induced sputum prior to analysis. however, dtt may affect cell surface markers which are essential for lymphocyte subtyping. therefore, the aim of this study was to evaluate the effect of dtt on an appropriate panel of surface markers. peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without dtt treatment. peripheral blood from healthy donors was incubated with either dtt according to standard sputum procedures or phosphate - buffered saline ( pbs ), washed and incubated with fluorochrome - labelled antibodies. after lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. leukocyte populations were identified by their light scattering properties. for analysis, fluorescence intensity was compared between dtt - and pbs - treated samples. after treatment with dtt, fluorescence intensity was significantly increased in cd16 - positive granulocytes ; it was reduced in cd2 - positive lymphocytes, cd45 - positive lymphocytes and cd14 - positive monocytes ( p < or = 0. 001 ). these changes occurred in all samples. the fluorescence intensity of cd3 -, cd4 -, cd8 -, cd19 -, cd56 - and histocompatibility leukocyte antigen dr - positive lymphocytes was not altered by dtt. however, there were statistically significant ( p < 0. 001 ), although small, changes
|
glycine - and gaba - activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. in the superfused retinal slice, a cell was voltage clamped at 0 mv in the presence of cobalt ; then glycine or gaba was puffed onto the axon terminal. types cba1, cba2, and a few cba1 - 2 cells demonstrated larger glycine - activated currents than gaba - activated ones. however, some off cells ( cba2 ( n ), cba1 - 2 ( n ), cba1 ( w ) ), most cba1 - 2, and most on cells ( cbb3, cbb3 - 4, cbb3 ( n ), and cbb4 ) displayed larger gaba - activated currents. the on cell, cbb5, possessed only a gaba - activated current. the predominance of glycinergic currents in cba1, cba2, and a few cba1 - 2 cells suggests a major input from the glycinergic aii amacrine cell and thus a key role for these cells in the rod bipolar pathway. certain off cells ( most cba1 - 2 ) expressed larger gaba - activated currents. all types expressed both gaba ( a ) and gabac currents about equally, although most off types ( cba1, cb a2 ( n )
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emerging evidence has shown the importance of inflammasome activation in the progression of autoimmune diseases. in this study, we aimed to identify the main cell types activating inflammasome in autoimmune diseases and to clarify the intracellular pathway of inflammasome activation in systemic lupus erythematosus ( sle ).
|
monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, fc gamma ri and fc gamma rii. in contrast, we have observed that aids monocytes express significant levels of a third fc gamma r, fc gamma riii ( cd16 ), which is normally associated with activation or maturation of the monocyte population. by dual - fluorescence analysis using a monoclonal antibody specific for fc gamma riii ( mab 3g8 ), 38. 5 + / - 3. 2 % of the leum3 ( cd14 ) - positive monocytes in aids patients were cd16 positive as compared to 10. 4 + / - 1. 0 % for healthy individuals ( n = 29 ; p less than 0. 005 ). furthermore, aids monocytes expressed fc gamma riii - specific mrna which is expressed minimally or not at all in control monocytes. as a recently identified inducer of fc gamma riii expression on blood monocytes, transforming growth factor - beta ( tgf - beta ) was found to be elevated in the serum and / or plasma of aids patients. moreover, incubation of normal monocytes with aids serum or plasma induced cd16 expression which correlated with serum tgf - beta levels ( r = 0. 74, p less than 0. 001 ) and was inhibited with a neutralizing antibody to tgf - beta. thus
|
the distribution of gaba in the perifoveal and the near and far peripheral region of human retina was studied with peroxidase anti - peroxidase immunocytochemistry applied on semithin epoxy resin sections. among the labeled amacrine cells in these regions, four types can be identified : putative diffuse a2 amacrines, stratified semilunar amacrines, interstitial amacrines and small displaced amacrines. gaba - immunoreactive interplexiform cells and ganglion cells also occur. contrary to previous post - embedding studies, our preparations show that some bipolar cells in the near and far peripheral region are gaba - immunopositive. this indicates that a number of bipolar cells in human retina does have an enhanced gaba content.
|
the improvement of hematopoietic stem and progenitor cell ( hspc ) engraftment remains a high - priority goal when limited cell doses are available, such as in cord blood ( cb ) transplantation and hsc gene therapy. we observed that monocytes are highly effective at improving the engraftment of both cb - cd34 < sup > + < / sup > and lentivirus - transfected cd34 < sup > + < / sup > cells in a xenogeneic model of hsc transplantation. moreover, monocytes, in particular the cd14 < sup > + < / sup > cd16 < sup > - < / sup > classical subset, in co - culture systems increase survival and stemness of cb - cd34 < sup > + < / sup > cells. both soluble factors and direct - cell contact interactions, such as jag / notch and cox - 2 / pge2 pathways, are critically involved in the hsc - monocyte crosstalk. our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.
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hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis ( ra ). it alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. the mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. this study was undertaken to evaluate whether the protein lysine - specific demethylase 1 ( lsd1 ) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis.
|
glycine - and gaba - activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. in the superfused retinal slice, a cell was voltage clamped at 0 mv in the presence of cobalt ; then glycine or gaba was puffed onto the axon terminal. types cba1, cba2, and a few cba1 - 2 cells demonstrated larger glycine - activated currents than gaba - activated ones. however, some off cells ( cba2 ( n ), cba1 - 2 ( n ), cba1 ( w ) ), most cba1 - 2, and most on cells ( cbb3, cbb3 - 4, cbb3 ( n ), and cbb4 ) displayed larger gaba - activated currents. the on cell, cbb5, possessed only a gaba - activated current. the predominance of glycinergic currents in cba1, cba2, and a few cba1 - 2 cells suggests a major input from the glycinergic aii amacrine cell and thus a key role for these cells in the rod bipolar pathway. certain off cells ( most cba1 - 2 ) expressed larger gaba - activated currents. all types expressed both gaba ( a ) and gabac currents about equally, although most off types ( cba1, cb a2 ( n )
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< i > objective. < / i > restoration of central vision loss in patients with age - related macular degeneration ( amd ) by implanting a retinal prosthesis is associated with an intriguing situation wherein the central prosthetic vision co - exists with natural normal vision. of major interest are the interactions between the prosthetic and natural vision. here we studied the effect of the light - adaptive state of the normal retina on the electrical visual evoked potentials ( veps ) arising from the retinal prosthesis. < i > approach. < / i > we recorded electrical vep elicited by prosthetic retinal stimulation in wild - type rats implanted with a 1 mm photovoltaic subretinal array. cortical responses were recorded following overnight dark adaption and compared to those recorded following bleaching of the retina by light ( 520 nm ) at various intensities and durations. < i > main results. < / i > compared to dark - adapted responses, bleaching induced a 2 - fold decrease in the prosthetic cortical response, which returned to the dark - adapted baseline within 30 min to several hours, depending on the degree of bleaching. this reduction was neither observed in royal college of surgeons ( rcs ) rats with a degenerated photoreceptor layer nor following intravitreal injection of a gabaa receptor blocker ( bicuculine ), suggesting the involvement of photoreceptors and a
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glycine - and gaba - activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. in the superfused retinal slice, a cell was voltage clamped at 0 mv in the presence of cobalt ; then glycine or gaba was puffed onto the axon terminal. types cba1, cba2, and a few cba1 - 2 cells demonstrated larger glycine - activated currents than gaba - activated ones. however, some off cells ( cba2 ( n ), cba1 - 2 ( n ), cba1 ( w ) ), most cba1 - 2, and most on cells ( cbb3, cbb3 - 4, cbb3 ( n ), and cbb4 ) displayed larger gaba - activated currents. the on cell, cbb5, possessed only a gaba - activated current. the predominance of glycinergic currents in cba1, cba2, and a few cba1 - 2 cells suggests a major input from the glycinergic aii amacrine cell and thus a key role for these cells in the rod bipolar pathway. certain off cells ( most cba1 - 2 ) expressed larger gaba - activated currents. all types expressed both gaba ( a ) and gabac currents about equally, although most off types ( cba1, cb a2 ( n )
|
hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis ( ra ). it alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. the mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. this study was undertaken to evaluate whether the protein lysine - specific demethylase 1 ( lsd1 ) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis.
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