12 results on '"Grose, Randall H."'
Search Results
2. 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
3. Measurement of autophagic flux in humans: an optimized method for blood samples
- Author
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Bensalem, Julien, primary, Hattersley, Kathryn J., additional, Hein, Leanne K., additional, Teong, Xiao Tong, additional, Carosi, Julian M., additional, Hassiotis, Sofia, additional, Grose, Randall H., additional, Fourrier, Célia, additional, Heilbronn, Leonie K., additional, and Sargeant, Timothy J., additional
- Published
- 2020
- Full Text
- View/download PDF
4. 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
5. A novel fluorescent probe reveals starvation controls the commitment of amyloid precursor protein to the lysosome
- Author
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Hein, Leanne K., primary, Apaja, Pirjo M., additional, Hattersley, Kathryn, additional, Grose, Randall H., additional, Xie, Jianling, additional, Proud, Christopher G., additional, and Sargeant, Timothy J., additional
- Published
- 2017
- Full Text
- View/download PDF
6. Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms
- Author
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Centenera, Margaret M, primary, Carter, Sarah L, additional, Gillis, Joanna L, additional, Marrocco-Tallarigo, Deborah L, additional, Grose, Randall H, additional, Tilley, Wayne D, additional, and Butler, Lisa M, additional
- Published
- 2015
- Full Text
- View/download PDF
7. 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., primary, El-Merhibi, Adaweyah, additional, Cummins, Adrian G., additional, Grose, Randall H., additional, Lymn, Kerry A., additional, DeNichilo, Mark, additional, and Penttila, Irmeli A., additional
- Published
- 2009
- Full Text
- View/download PDF
8. Deficiency of VA24+/CD3+ (NK T) immunoregulatory cells in coeliac disease
- Author
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Grose, Randall H., primary, Cummins, Adrian G., additional, and Thompson, Fiona M., additional
- Published
- 2000
- Full Text
- View/download PDF
9. Deficiency of VA24+/CD3+(NK T) immunoregulatory cells in coeliac disease
- Author
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Grose, Randall H., Cummins, Adrian G., and Thompson, Fiona M.
- Published
- 2000
- Full Text
- View/download PDF
10. 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
11. Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3
- Author
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Charles S. T. Hii, Prem P. Dwivedi, Randall H. Grose, Barry C. Powell, Jorge Filmus, Peter J. Anderson, Cory J. Xian, Dwivedi, Prem P, Grose, Randall H, Filmus, Jorge, Hii, Charles ST, Xian, Cory J, Anderson, Peter J, and Powell, Barry C
- Subjects
animal structures ,Histology ,Glypican ,Physiology ,Endocrinology, Diabetes and Metabolism ,BMP2 ,Fluorescent Antibody Technique ,Biology ,Bone morphogenetic protein ,Transfection ,bone ,glypican ,Bone morphogenetic protein 2 ,osteogenesis ,Craniosynostosis ,Mesoderm ,Glypicans ,Osteogenesis ,medicine ,Humans ,Immunoprecipitation ,Bone growth ,Fibrous joint ,proteoglycan ,Microscopy, Confocal ,Mesenchymal stem cell ,Anatomy ,Cranial Sutures ,medicine.disease ,Flow Cytometry ,Cell biology ,Bone morphogenetic protein 7 ,craniosynostosis ,medicine.anatomical_structure ,embryonic structures ,Bone Morphogenetic Proteins ,Signal Transduction - Abstract
From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates. One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures. Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation. Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children. Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated. We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media. We show that they inhibit BMP2, BMP4 and BMP7 activities,which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity. In contrast, increased levels of GPC1 and GPC3 as a result of over expression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis. We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways. GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein. The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis,and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how down regulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis.
- Published
- 2013
12. 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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