Pham, V. Luu, Christopher Meinzen, Rafael S. Arias, Noah G. Schwartz, Adi Rattner, Catherine H. Miele, Philip L. Smith, Hartmut Schneider, J. Jaime Miranda, Robert H. Gilman, Vsevolod Y. Polotsky, William Checkley, and Alan R. Schwartz. comparative cross-sectional study of sleep-disordered breathing in the original Peruvian highlands and lowlands. High Alt Med Biol. 18: 11-19, 2017.
BACKGROUND Altitude can highlight irregular sleep breathing (SDB), which has been associated with cardiovascular and metabolic diseases. SDB on the plateau is not marked in large controlled studies. The purpose of this study was to compare the prevalence and severity of SDB in the highlands and lowlands.
METHOD 170 age, body-mass Index, (BMI), and gender couples (age 58.2 ± 12.4 years, BMI 27.2 ± 3.5 kg / m2, and 86 male and 84 female) from Crónicas Cohort Study recruited at sea level (Lima) and high altitude (Puno, 3825 m) arrangements in Peru. Participants underwent nocturnal polygraph simultaneously and actigraphy to characterize patterns of breathing, movement arousals, and sleep / wake state. We compared the prevalence of SDB, type, and severity between the highlands and lowlands as measured by the apnea-hypopnea index (AHI) and pulse oximetry (SpO2) during sleep.
RESULTS Greater prevalence of sleep apnea in the highlands than in the lowlands (77% vs 54%, p <0.001). Compared with the lowlands, highlands have a two-fold increase in AHI due to the increase in the central rather than obstructive apnea. On the plateau compared with the lowlands, lower SpO2 during wakefulness and a further decrease during sleep (p <0.001). Hypoxemia during wakefulness predict sleep apnea in the highlands, and it seems to mediate the effects of altitude on the prevalence of sleep apnea. Surprisingly, hypoxemia also quite common in the lowlands, and it is also associated with an increased likelihood of sleep apnea.
CONCLUSION high altitude and hypoxemia at both high and low altitudes associated with an increased prevalence and severity of SDB. Our findings show that most of the highlands remain at risk for SDB sequelae.
Cross-Sectional Comparison of Sleep-Disordered Breathing in Native Peruvian Highlanders and Lowlanders.
Increased Cardiometabolic Risk and Worsening hypoxemia at High Altitude.
Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. June, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde and William Checkley. Increased risk of cardiometabolic and worsening hypoxemia at high altitude. High Alt Med Biol. 17: 93-100 syndrome, 2016.-Metabolic, insulin resistance, diabetes, and dyslipidemia associated with an increased risk of cardiovascular disease.
While excessive erythrocytosis is associated with cardiovascular complications, it is not clear how the worsening hypoxemia of any level affecting cardiometabolic risk factors in a population of high altitude. We studied the relationship between lunch break oxyhemoglobin saturation and cardiometabolic risk factors in adult participants who stay in Puno, Peru (3825 m asl). We used multivariable logistic regression model to study the relationship between having a lower oxyhemoglobin saturation and cardiometabolic risk markers.
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth, and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling, and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of an appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant Human BMP-7 is a 28.8 kDa homodimeric glycoprotein consisting of two 117 amino acid subunits, which correspond to amino acid residues 315 to 431 of the full-length BMP-7 precursor.
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth, and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling, and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of an appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant Human BMP-7 is a homodimeric glycoprotein consisting of two 117 amino acid subunits, which correspond to amino acid residues 315 to 431 of the full-length BMP-7 precursor. Recombinant Human BMP-7 has a calculated molecular weight of 26.4 kDa; however, due to glycosylation, the BMP-7 homodimer migrates at an apparent molecular weight of approximately 25-35 kDa by SDS-PAGE analysis under non-reducing conditions.
Description: A polyclonal antibody for detection of BMP-7 from Human, Mouse, Rat. This BMP-7 antibody is for WB , IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human BMP-7
Description: A polyclonal antibody for detection of BMP-7 from Human, Mouse, Rat. This BMP-7 antibody is for WB , IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human BMP-7
Description: A polyclonal antibody for detection of BMP-7 from Human, Mouse, Rat. This BMP-7 antibody is for WB , IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human BMP-7
Description: BMP7 encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients.
Description: BMP7 encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients.
Description: BMP7 encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients.
Description: Bone morphogenetic protein 7 (BMP7), also known as osteogenic protein 1 (OP1), is a widely expressed TGFβ superfamily member with important functions during embryogenesis, in the adult, and in disease. Human BMP7 is synthesized with a 29 amino acid (aa) signal sequence, a 263 aa propeptide, and a 139 aa growth factor domain. The growth factor domain of human BMP7 shares 98% aa sequence identity with mouse and rat BMP7. The BMP7 propeptide is cleaved intracellularly but often remains associated with the mature Cterminus. Based on in vivo and in vitro studies, BMP 7 has the potential to be secreted as a disulfidelinked mature homodimer, or particularly as a heteromeric complex that consists of two propeptides noncovalently associated with a mature disulfidelinked homodimer. The presence of the propeptides in BMP7 appears to stabilize the molecule and provide a docking mechanism for extracellular storage on molecules such as fibrillin 1 and 2 . The propeptides themselves do not impart latency to the complex. BMP7 binding to type II receptors rapidly displaces the prodomain:mature molecule interaction and has no effect on activity. But it is suggested that immobilized BMP7 (via prodomain:fibrillin) is inactive, allowing for possible longterm storage of the molecule. BMP 7 interacts with the type 2 receptors Activin RIIA, Activin RIIB, and BMPRII and the type 1 receptors Activin RIA, BMPRIA, and BMPRIB. BMP7 may also be processed into a disulfidelinked heterodimer with either BMP2 or BMP4. Such complexes may show increased potency and range of activity compared to BMP7 homodimers. BMP7 plays a role in a variety of organ systems. It promotes new bone formation and nephron development (10, 11), inhibits the branching of prostate epithelium (12), and antagonizes epithelialmesenchymal transition (EMT).
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant human BMP-7 is a 28.8 kDa homodimeric glycoprotein consisting of two 116 amino acid subunits, which correspond to amino acid residues 316 to 431 of the full-length BMP-7 precursor.
Description: Bone morphogenetic protein 7 (BMP7), also known as osteogenic protein 1 (OP1), is a widely expressed TGFβ superfamily member with important functions during embryogenesis, in the adult, and in disease. Human BMP7 is synthesized with a 29 amino acid (aa) signal sequence, a 263 aa propeptide, and a 139 aa growth factor domain. The growth factor domain of human BMP7 shares 98% aa sequence identity with mouse and rat BMP7. The BMP7 propeptide is cleaved intracellularly but often remains associated with the mature Cterminus. Based on in vivo and in vitro studies, BMP 7 has the potential to be secreted as a disulfidelinked mature homodimer, or particularly as a heteromeric complex that consists of two propeptides noncovalently associated with a mature disulfidelinked homodimer. The presence of the propeptides in BMP7 appears to stabilize the molecule and provide a docking mechanism for extracellular storage on molecules such as fibrillin 1 and 2 . The propeptides themselves do not impart latency to the complex. BMP7 binding to type II receptors rapidly displaces the prodomain:mature molecule interaction and has no effect on activity. But it is suggested that immobilized BMP7 (via prodomain:fibrillin) is inactive, allowing for possible longterm storage of the molecule. BMP 7 interacts with the type 2 receptors Activin RIIA, Activin RIIB, and BMPRII and the type 1 receptors Activin RIA, BMPRIA, and BMPRIB. BMP7 may also be processed into a disulfidelinked heterodimer with either BMP2 or BMP4. Such complexes may show increased potency and range of activity compared to BMP7 homodimers. BMP7 plays a role in a variety of organ systems. It promotes new bone formation and nephron development (10, 11), inhibits the branching of prostate epithelium (12), and antagonizes epithelialmesenchymal transition (EMT).
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant human BMP-7 is a 28.8 kDa homodimeric glycoprotein consisting of two 116 amino acid subunits, which correspond to amino acid residues 316 to 431 of the full-length BMP-7 precursor.
Description: Bone morphogenetic protein 7 (BMP-7), also known as osteogenic protein 1 (OP1), is a widely expressed TGFβ superfamily member with important functions during embryogenesis, in the adult, and in disease. Human BMP-7 is synthesized with a 29 amino acid (aa) signal sequence, a 263 aa propeptide, and a 139 aa growth factor domain. The growth factor domain of human BMP-7 shares 98% aa sequence identity with mouse and rat BMP-7. The BMP-7 propeptide is cleaved intracellularly but often remains associated with the mature C-terminus. Based on in vivo and in vitro studies, BMP-7 has the potential to be secreted as a disulfide-linked mature homodimer, or particularly as a heteromeric complex that consists of two propeptides noncovalently associated with a mature disulfide linked homodimer. The presence of the propeptides in BMP-7 appears to stabilize the molecule and provide a docking mechanism for extracellular storage on molecules such as fibrillin1 and 2. The propeptides themselves do not impart latency to the complex. BMP-7 binding to type II receptors rapidly displaces the prodomain: mature molecule interaction and has no effect on activity.BMP-7 plays a role in a variety of organ systems. It promotes new bone formation and nephron development, inhibits the branching of prostate epithelium, and antagonizes epithelial mesenchymal transition (EMT). In pathological conditions, BMP-7 inhibits tumor growth and metastasis, ameliorates fibrotic damage in nephritis, and promotes neuro regeneration following brain ischemia.
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant human BMP-7 is a homodimeric glycoprotein consisting of two 117 amino acid subunits, which correspond to amino acid residues 315 to 431 of the full-length BMP 7 precursor. Recombinant human BMP-7 has a calculated molecular weight of 26.4 kDa; however, due to glycosylation, the BMP-7 homodimer migrates at an apparent molecular weight of approx. 25-35 kDa by SDS-PAGE analysis under non-reducing conditions.
Description: TGF-β family members are key modulators of cell proliferation, differentiation, matrix synthesis, and apoptosis. As implied by their name, BMPs initiate, promote, and regulate the development, growth and remodeling of bone and cartilage. In addition to this role, BMPs are also involved in prenatal development and postnatal growth, remodeling and maintenance of a variety of other tissues and organs. BMP-7, also known as osteogenic protein-1 or OP-1, is a potent bone inducing agent, which in the presence of appropriate osteoconductive carrier (e.g. collagen sponge or synthetic hydroxyapatite) can be used in the treatment of bone defects. A bone-graft substitute, called OP-1TM implant, made of recombinant human BMP-7 associated with bovine bone-derived collagen, has recently been approved by the FDA as a device for treating critical-size bone fractures. The potential use of BMP-7 in dental reconstructive surgeries is currently under investigation. Recombinant human BMP-7 is a homodimeric glycoprotein consisting of two 117 amino acid subunits, which correspond to amino acid residues 315 to 431 of the full-length BMP 7 precursor. Recombinant human BMP-7 has a calculated molecular weight of 26.4 kDa; however, due to glycosylation, the BMP-7 homodimer migrates at an apparent molecular weight of approx. 25-35 kDa by SDS-PAGE analysis under non-reducing conditions.
Description: Bone Morphogenetic Protein 7 is one of the BMPs, some of which belong to the TGF-beta superfamily (BMP2-7). There are more than thirteen BMPs have been discovered nowadays and they are involved in inducing cartilage and bone formation. BMP-7 is mainly expressed in kidney and bladder. It is also present in developing eyes, brain and ear during embryogenesis. BMP-7 also named osteogenic protein-1 (OP-1) is a potent osteoinductive cytokine and plays role in osteoblast differentiation, SMAD1 production and renal development and repair. Human BMP-7 is synthesized with a signal sequence (29 a.a.), a propeptide (263 a.a.), and a growth factor domain (139 a.a.). The growth factor domain of human BMP-7 shares 98 % a.a. sequence identity with mouse and rat BMP-7.
Description: Bone Morphogenetic Protein 7 is one of the BMPs, some of which belong to the TGF-beta superfamily (BMP2-7). There are more than thirteen BMPs have been discovered nowadays and they are involved in inducing cartilage and bone formation. BMP-7 is mainly expressed in kidney and bladder. It is also present in developing eyes, brain and ear during embryogenesis. BMP-7 also named osteogenic protein-1 (OP-1) is a potent osteoinductive cytokine and plays role in osteoblast differentiation, SMAD1 production and renal development and repair. Human BMP-7 is synthesized with a signal sequence (29 a.a.), a propeptide (263 a.a.), and a growth factor domain (139 a.a.). The growth factor domain of human BMP-7 shares 98 % a.a. sequence identity with mouse and rat BMP-7.
Nine hundred and fifty-four participants (average age 55 years, 52% men) have information available in pulse oximetry and cardiometabolic risk markers. average oxyhemoglobin saturation was 90% (interquartile range 88% -92%) and 43 (4.5%) had excessive erythrocytosis. older age, decreased lung function height-adjustable, and a higher body mass index (BMI) is associated with having ≤85% oxyhemoglobin saturation.
