14 results on '"Grose, Randall H."'
Search Results
2. Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3
- Author
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Dwivedi, Prem P., Grose, Randall H., Filmus, Jorge, Hii, Charles S.T., Xian, Cory J., Anderson, Peter J., and Powell, Barry C.
- Published
- 2013
- Full Text
- View/download PDF
3. Maternal milk, but not formula, regulates the immune response to [beta]-lactoglobulin in allergy-prone rat pups
- Author
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Tooley, Katie L., Merhibi, Adaweyah El-, Cummins, Adrian G., Grose, Randall H., Lymn, Kerry A., DeNichilo, Mark, and Penttila, Irmeli A.
- Subjects
Allergy desensitization -- Methods ,Biological response modifiers -- Research ,Immune response -- Management ,Breast milk -- Health aspects ,Company business management ,Food/cooking/nutrition - Abstract
Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to [beta] Iactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway a[lergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, of 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast ce[I protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp[3.sup.+] [CD4.sup.+] regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII, and intestinal mast cells but reduced MLN Foxp[3.sup.+] cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-1 O, and interferon-[gamma] (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and [CD4.sup.+] Foxp[3.sup.+] cells (P< 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response. J. Nutr. 139: 2145-2151, 2009. doi: 10.3945/jn.109.108845
- Published
- 2009
4. Deficiency of 6B11+ Invariant NK T-Cells in Celiac Disease
- Author
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Grose, Randall H., Thompson, Fiona M., and Cummins, Adrian G.
- Published
- 2008
- Full Text
- View/download PDF
5. Deficiency of Invariant NK T Cells in Crohn's Disease and Ulcerative Colitis
- Author
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Grose, Randall H., Thompson, Fiona M., Baxter, Alan G., Pellicci, Daniel G., and Cummins, Adrian G.
- Published
- 2007
- Full Text
- View/download PDF
6. Measurement of autophagic flux in humans: an optimized method for blood samples.
- Author
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Bensalem, Julien, Hattersley, Kathryn J., Hein, Leanne K., Teong, Xiao Tong, Carosi, Julian M., Hassiotis, Sofia, Grose, Randall H., Fourrier, Célia, Heilbronn, Leonie K., and Sargeant, Timothy J.
- Subjects
RAPAMYCIN ,MONONUCLEAR leukocytes ,ETHYLENEDIAMINETETRAACETIC acid ,BLOOD sampling ,TRANSMISSION electron microscopy ,DIMETHYL sulfoxide - Abstract
Autophagic flux is a critical cellular process that is vastly under-appreciated in terms of its importance to human health. Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling. To date, translation of this knowledge has been hampered because there has been no way to directly measure autophagic flux in humans. In this study we detail a method whereby human macroautophagic/autophagic flux can be directly measured from human blood samples. We show that whole blood samples can be treated with the lysosomal inhibitor chloroquine, and peripheral blood mononuclear cells isolated from these samples could be used to measure autophagic machinery protein LC3B-II. Blocking of autophagic flux in cells while still in whole blood represents an important advance because it preserves genetic, nutritional, and signaling parameters inherent to the individual. We show this method was reproducible and defined LC3B-II as the best protein to measure autophagic flux in these cells. Finally, we show that this method is relevant to assess intra-individual variation induced by an intervention by manipulating nutrition signaling with an ex vivo treatment of whole blood that comprised leucine and insulin. Significantly, this method will enable the identification of factors that alter autophagic flux in humans, and better aid their translation in the clinic. With further research, it could also be used as a novel biomarker for risk of age-related chronic disease. Abbreviations: AMPK: AMP-activated protein kinase; ACTB: actin beta; ATG5: autophagy related 5; BAF: bafilomycin A
1 ; CQ: chloroquine; DMSO: dimethyl sulfoxide; DPBS: Dulbecco's phosphate-buffered saline; EDTA: ethylenediaminetetraacetic acid; KO: knockout; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; PBMCs: peripheral blood mononuclear cells; PMNs: polymorphonuclear cells; RPMI: Roswell Park Memorial Institute; SQSTM1: sequestosome 1; TBST: Tris-buffered saline containing 0.1% (v:v) Tween 20; TEM: transmission electron microscopy. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
7. Expression of B7 costimulatory molecules by cells infiltrating the colon in experimental colitis induced by oral dextran sulfate sodium in the mouse
- Author
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Grose, Randall H, Howarth, Gordon S, Xian, Cory J, and Hohmann, Arthur W
- Published
- 2001
8. Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms.
- Author
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Centenera, Margaret M., Carter, Sarah L., Gillis, Joanna L., Marrocco-Tallarigo, Deborah L., Grose, Randall H., Tilley, Wayne D., and Butler, Lisa M.
- Subjects
ANDROGEN receptors ,PROSTATE cancer treatment ,CANCER cells ,MOLECULAR chaperones ,HEAT shock proteins - Abstract
Persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) underpins the urgent need for therapeutic strategies that better target this pathway. Combining classes of agents that target different components of AR signaling has the potential to delay resistance and improve patient outcomes. Many oncoproteins, including the AR, rely on the molecular chaperone heat shock protein 90 (Hsp90) for functional maturation and stability. In this study, enhanced anti-proliferative activity of the Hsp90 inhibitors 17-allylamino-demethoxygeldanamycin (17-AAG) and AUY922 in androgen-sensitive and CRPC cells was achieved when the agents were used in combination with AR antagonists bicalutamide or enzalutamide. Moreover, significant caspasedependent cell death was achieved using sub-optimal agent doses that individually have no effect. Expression profiling demonstrated regulation of a broadened set of AR target genes with combined 17-AAG and bicalutamide compared with the respective single agent treatments. This enhanced inhibition of AR signaling was accompanied by impaired chromatin binding and nuclear localization of the AR. Importantly, expression of the AR variant AR-V7 that is implicated in resistance to AR antagonists was not induced by combination treatment. Likewise, the heat shock response that is typically elicited with therapeutic doses of Hsp90 inhibitors, and is a potential mediator of resistance to these agents, was significantly reduced by combination treatment. In summary, the co-targeting strategy in this study more effectively inhibits AR signaling than targeting AR or HSP90 alone and prevents induction of key resistance mechanisms in prostate cancer cells. These findings merit further evaluation of this therapeutic strategy to prevent CRPC growth. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
9. Comparison of Blood and Synovial Fluid Th17 and Novel Peptidase Inhibitor 16 Treg Cell Subsets in Juvenile Idiopathic Arthritis.
- Author
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GROSE, RANDALL H., MILLARD, DEBORAH J., MAVRANGELOS, CHRIS, BARRY, SIMON C., ZOLA, HEDDY, NICHOLSON, IAN C., WENG TARNG CHAM, BOROS, CHRISTINA A., and KRUMBIEGEL, DOREEN
- Published
- 2012
- Full Text
- View/download PDF
10. Maternal Milk, but Not Formula, Regulates the Immune Response to β-Lactoglobulin in Allergy-Prone Rat Pups.
- Author
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Tooley, Katie L., El-Merhibi, Adaweyah, Cummins, Adrian G., Grose, Randall H., Lymn, Kerry A., Mark DeNichilo, and Penttila, Irmeli A.
- Subjects
BREAST milk ,LACTATION ,FOOD allergy ,CYTOKINES ,MESSENGER RNA ,MAST cells ,IMMUNOGLOBULIN E ,DIET ,LABORATORY rats - Abstract
Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to β-Iactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total gE, BLG-specific lgGl, and rat mucosal mast cell protease II (RMCPI I; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 )CCR7I expression by real-time PCR and immunostained for Foxp3
+ CD4+ regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgGl, RMCPII, and intestinal mast cells but reduced MLN Foxp3+ cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (lL)-4, IL-b, and interferon-γ(P< 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4+ Foxp3+ cells (P < 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
11. A novel fluorescent probe reveals starvation controls the commitment of amyloid precursor protein to the lysosome.
- Author
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Hein, Leanne K., Hattersley, Kathryn, Proud, Christopher G., Sargeant, Timothy J., Apaja, Pirjo M., Grose, Randall H., and Xie, Jianling
- Subjects
- *
FLUORESCENT probes , *AMYLOID , *LYSOSOMES , *FLOW cytometry , *ENDOSOMES - Abstract
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry. This permits rapid analysis or screening of genes and compounds that alter APP processing in the cell. Using our novel molecular probe, we determined that starvation induces trafficking of APP and APP-carboxy-terminal fragments (APP-CTFs) to the degradative endo-lysosomal network. In line with this finding, suppression of mTOR signalling using AZD8055 also strongly induced trafficking of APP to the endo-lysosomal system. Remarkably, activation of mTOR signalling via RHEB over-expression inhibited the starvation-induced autophagy but did not affect trafficking of tf-APP. These results show tf-APP can be used to determine how APP is trafficked through the lysosomal system of the cell. This molecular probe is therefore useful for determining the molecular mechanism behind the commitment of APP to the degradative pathway or for screening compounds that can induce this effect. This is important as clearance of APP and APP-CTF provides an important potential therapeutic strategy for Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
12. Measurement of autophagic flux in humans: an optimized method for blood samples
- Author
-
Julian M. Carosi, Kathryn J. Hattersley, Julien Bensalem, Timothy J. Sargeant, Leonie K. Heilbronn, Randall H. Grose, Sofia Hassiotis, Célia Fourrier, Leanne K. Hein, Xiao Tong Teong, Bensalem, Julien, Hattersley, Kathryn J, Hein, Leanne K, Teong, Xiao Tong, Carosi, Julian M, Hassiotis, Sofia, Grose, Randall H, Fourrier, Celia, Heilbronn, Leonie K, and Sargeant, Timothy J
- Subjects
0301 basic medicine ,autophagy ,Biology ,chloroquine ,03 medical and health sciences ,Human health ,blood ,Lysosome ,medicine ,Autophagy ,Humans ,human ,LC3B ,Molecular Biology ,030102 biochemistry & molecular biology ,Cellular process ,PBMC ,Cell Biology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Leukocytes, Mononuclear ,lysosome ,Biomarker (medicine) ,biomarker ,Lysosomes ,Toolbox ,Flux (metabolism) - Abstract
Autophagic flux is a critical cellular process that is vastly under-appreciated in terms of its importance to human health. Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling. To date, translation of this knowledge has been hampered because there has been no way to directly measure autophagic flux in humans. In this study we detail a method whereby human macroautophagic/autophagic flux can be directly measured from human blood samples. We show that whole blood samples can be treated with the lysosomal inhibitor chloroquine, and peripheral blood mononuclear cells isolated from these samples could be used to measure autophagic machinery protein LC3B-II. Blocking of autophagic flux in cells while still in whole blood represents an important advance because it preserves genetic, nutritional, and signaling parameters inherent to the individual. We show this method was reproducible and defined LC3B-II as the best protein to measure autophagic flux in these cells. Finally, we show that this method is relevant to assess intra-individual variation induced by an intervention by manipulating nutrition signaling with an ex vivo treatment of whole blood that comprised leucine and insulin. Significantly, this method will enable the identification of factors that alter autophagic flux in humans, and better aid their translation in the clinic. With further research, it could also be used as a novel biomarker for risk of age-related chronic disease. Abbreviations: AMPK: AMP-activated protein kinase; ACTB: actin beta; ATG5: autophagy related 5; BAF: bafilomycin A1; CQ: chloroquine; DMSO: dimethyl sulfoxide; DPBS: Dulbecco’s phosphate-buffered saline; EDTA: ethylenediaminetetraacetic acid; KO: knockout; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; PBMCs: peripheral blood mononuclear cells; PMNs: polymorphonuclear cells; RPMI: Roswell Park Memorial Institute; SQSTM1: sequestosome 1; TBST: Tris-buffered saline containing 0.1% (v:v) Tween 20; TEM: transmission electron microscopy.
- Published
- 2021
13. PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20
- Author
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Nicholson, Ian C., Mavrangelos, Christos, Bird, Daniel R.G., Bresatz-Atkins, Suzanne, Eastaff-Leung, Nicola G., Grose, Randall H., Gundsambuu, Batjargal, Hill, Danika, Millard, Debbrah J., Sadlon, Timothy J., To, Sarah, Zola, Heddy, Barry, Simon C., and Krumbiegel, Doreen
- Subjects
- *
GENE expression , *PEPTIDASE , *ENZYME inhibitors , *MONOCLONAL antibodies , *CHEMOKINES , *PHENOTYPES - Abstract
Abstract: The peptidase inhibitor PI16 was shown previously by microarray analysis to be over-expressed by CD4-positive/CD25-positive Treg compared with CD4-positive/CD25-negative Th cells. Using a monoclonal antibody to the human PI16 protein, we found that PI16-positive Treg have a memory (CD45RO-positive) phenotype and express higher levels of FOXP3 than PI16-negative Treg. PI16-positive Treg are functional in suppressor assays in vitro with potency similar to PI16-negative Treg. Further phenotyping of the PI16-positive Treg revealed that the chemokine receptors CCR4 and CCR6 are expressed by more of the PI16-positive/CD45RO-positive Treg compared with PI16-negative/CD45RO-positive Treg or Th cells. PI16-positive Treg showed enhanced in vitro migration towards the inflammatory chemokines CCL17 and CCL20, suggesting they can migrate to sites of inflammation. We conclude that PI16 identifies a novel distinct subset of functional memory Treg which can migrate to sites of inflammation and regulate the pro-inflammatory response at those sites. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
14. Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups
- Author
-
Irmeli A. Penttila, Adaweyah El-Merhibi, Mark DeNichilo, Randall H. Grose, Kerry A. Lymn, Katie Tooley, Adrian G. Cummins, Tooley, Katie L, El-Merhibi, Adaweyah, Cummins, Adrian G, Grose, Randall H, Lymn, Kerry A, DeNichilo, Mark, and Penttila, Irmeli A
- Subjects
Receptors, CCR7 ,Chemokine ,medicine.medical_specialty ,medicine.medical_treatment ,Medicine (miscellaneous) ,Lactoglobulins ,formula feeding ,Immunoglobulin E ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,immune response ,Immune system ,Ileum ,Rats, Inbred BN ,Internal medicine ,Hypersensitivity ,medicine ,Animals ,Mast Cells ,RNA, Messenger ,Nutrition and Dietetics ,biology ,Nutrition & Dietetics ,Degranulation ,Mast cell ,allergic foods ,Infant Formula ,Rats ,Interleukin 10 ,Cytokine ,Endocrinology ,medicine.anatomical_structure ,Immunoglobulin G ,Allergic response ,biology.protein ,Cytokines ,breast milk ,Female ,Milk Hypersensitivity - Abstract
Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to p-lactoglobulin (BLG), one of the main allergenic proteins in cow milk, Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR, DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+) regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4(+)Foxp3(+) cells (P< 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response. Refereed/Peer-reviewed
- Published
- 2009
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