Search results for: Recombinant Human GH Proteins
#32423203 2020/06/04 To Up
Long-Acting Human Growth Hormone Receptor Antagonists Produced in and Conjugated with Polyethylene Glycol.Growth hormone (GH) is a peptide hormone that mediates actions through binding to a cell surface GH receptor (GHR). The GHR antagonist, B2036, combines an amino acid substitution at 120 that confers GHR antagonist activity, with eight additional amino acid substitutions. Conjugation to polyethylene glycol (PEG) increases the serum half-life of these proteins due to reduced renal clearance. Recombinant forms of GH and its antagonists are mainly produced in prokaryotic expression systems, such as . However, efficient production in is problematic, as these proteins form aggregates as inclusion bodies resulting in poor solubility. In the present study, we demonstrate that N-terminal fusion to a thioredoxin (Trx) fusion partner improves soluble expression of codon-optimized B2036 in when expressed at 18 °C. Expression, purification and PEGylation protocols were established for three GHR antagonists: B2036, B20, and G120Rv. Following purification, these antagonists inhibited the proliferation of Ba/F3-GHR cells in a concentration-dependent manner. PEGylation with amine-reactive 5 kDa methoxy PEG succinimidyl propionate yielded a heterogeneous mixture of conjugates containing four to seven PEG moieties. PEGylation significantly reduced in vitro bioactivity of the conjugates. However, substitution of lysine to arginine at amino acid residue 120 in B2036 improved the in vitro activity of the PEGylated protein when compared to unmodified PEGylated B2036. Pharmacokinetic analysis demonstrated that the circulating half-life of PEGylated B20 was 15.2 h in mice. Taken together, we describe an effective strategy to produce biologically active PEGylated human GHR antagonists.
Yue Wang, Ries J Langley, Kyle Tamshen, Stephen M Jamieson, Man Lu, Heather D Maynard, Jo K Perry
1752 related Products with: Long-Acting Human Growth Hormone Receptor Antagonists Produced in and Conjugated with Polyethylene Glycol.100.00 ug96T1 mg1000 100 μg100ug Lyophilized100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug96 wells (1 kit)
#32386344 2020/05/09 To Up
A New Glycogen Storage Disease Caused by a Dominant PYGM Mutation.Glycogen storage diseases (GSDs) are severe human disorders resulting from abnormal glucose metabolism, and all previously described GSDs segregate as autosomal recessive or X-linked traits. In this study, we aimed to molecularly characterize the first family with a dominant GSD.
Andoni Echaniz-Laguna, Xavière Lornage, Pascal Laforêt, Mette C Orngreen, Evelina Edelweiss, Guy Brochier, Mai T Bui, Roberto Silva-Rojas, Catherine Birck, Béatrice Lannes, Norma B Romero, John Vissing, Jocelyn Laporte, Johann Böhm200 1 mg1 mL1 mg10050ug
#32233176 // To Up
Local Injection of Growth Hormone for Temporomandibular Joint Osteoarthritis.Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA.
Soo Min Ok, Jin Hwa Kim, Ji Su Kim, Eun Gyo Jeong, Yang Mi Park, Hye Mi Jeon, Jun Young Heo, Yong Woo Ahn, Sun Nyoung Yu, Hae Ryoun Park, Kyung Hee Kim, Soon Cheol Ahn, Sung Hee Jeong
2659 related Products with: Local Injection of Growth Hormone for Temporomandibular Joint Osteoarthritis.96 Wells/Kit1mg1 kit(96 Wells)96T5 mg1 mg100 96T1 mg500 ìg1 mg1 mg
#31852826 2019/12/18 To Up
Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity.Host-pathogen interactions are central to understanding microbial pathogenesis. The staphylococcal pore-forming cytotoxins hijack important immune molecules but little is known about the underlying molecular mechanisms of cytotoxin-receptor interaction and host specificity. Here we report the structures of a staphylococcal pore-forming cytotoxin, leukocidin GH (LukGH), in complex with its receptor (the α-I domain of complement receptor 3, CD11b-I), both for the human and murine homologs. We observe 2 binding interfaces, on the LukG and the LukH protomers, and show that human CD11b-I induces LukGH oligomerization in solution. LukGH binds murine CD11b-I weakly and is inactive toward murine neutrophils. Using a LukGH variant engineered to bind mouse CD11b-I, we demonstrate that cytolytic activity does not only require binding but also receptor-dependent oligomerization. Our studies provide an unprecedented insight into bicomponent leukocidin-host receptor interaction, enabling the development of antitoxin approaches and improved animal models to explore these approaches.
Nikolina Trstenjak, Dalibor Milić, Melissa A Graewert, Harald Rouha, Dmitri Svergun, Kristina Djinović-Carugo, Eszter Nagy, Adriana Badarau
2138 related Products with: Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity.100ug Lyophilized100ug Lyophilized0.1 mg100ug Lyophilized 100ul100 ug 100ug96T100ug Lyophilized5mg100ug Lyophilized50 ug
#31829160 2019/12/11 To Up
No increased risk of glucose metabolism disorders in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from an observational, longitudinal study.To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study.
Paolo Beck-Peccoz, Charlotte Höybye, Robert D Murray, Suat Simsek, Markus Zabransky, Hichem Zouater, Günter Stalla
1198 related Products with: No increased risk of glucose metabolism disorders in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from an observational, longitudinal study.100 μg 0.1 mg 2 Pieces/Box100 μg100 μg100 μg1 mg100.00 ug
#31760824 // To Up
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence). This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH-stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document. This updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH-stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH-stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH-stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement. = American Association of Clinical Endocrinologists; = American College of Endocrinology; = alpha-2-HS-glycoprotein; = adult-onset growth hormone deficiency; = arginine; = best evidence level; = bone mineral density; = body mass index; = confidence interval; = childhood-onset growth hormone deficiency; = clinical practice guideline; = C-reactive protein; = diabetes mellitus; = dual-energy X-ray absorptiometry; = evidence level; = Food and Drug Administration; = fixed-dose glucagon stimulation test; = Genetics and Neuroendocrinology of Short Stature International Study; = growth hormone; = growth hormone deficiency; = growth hormone-releasing hormone; = glucagon stimulation test; = high-density lipoprotein; = Hypopituitary Control and Complications Study; = insulin-like growth factor-1; = insulin-like growth factor-binding protein; = isolated growth hormone deficiency; = insulin tolerance test; = Kabi International Metabolic Surveillance; = long-acting growth hormone; = low-density lipoprotein; = leukemia inhibitory factor; = multiple pituitary hormone deficiencies; = magnetic resonance imaging; = procollagen type-III amino-terminal pro-peptide; = pituitary hormone deficiencies; = quality of life; = recombinant human growth hormone; = receiver operating characteristic; = relative risk; = subarachnoid hemorrhage; = standard deviation score; = standardized incidence ratio; = secondary neoplasms; = triiodothyronine; = traumatic brain injury; = vitamin D-binding protein; = World Anti-Doping Agency; = weight-based glucagon stimulation test.
Kevin C J Yuen, Beverly M K Biller, Sally Radovick, John D Carmichael, Sina Jasim, Kevin M Pantalone, Andrew R Hoffman
1948 related Products with: AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.5 G25 mg
#31721610 2019/11/13 To Up
Adult growth hormone deficiency: clinical advances and approaches to improve adherence.: There have been significant clinical advances in the understanding of the diagnosis and benefits of long-term recombinant human growth hormone (rhGH) replacement in adults with GH deficiency (GHD) since its approval in 1996 by the United States Food and Drug Administration.: We searched PubMed, Medline, CINAHL, EMBASE and PsychInfo databases between January 2000 and June 2019 for published studies evaluating adults with GHD. We reviewed the data of the oral macimorelin test compared to the GHRH plus arginine and the insulin tolerance tests that led to its approval by the United States FDA and European Medicines Agency for adult diagnostic testing. We summarize the clinical advances of long-term benefits of rhGH therapy and the potential effects of GH receptor polymorphisms on individual treatment responsiveness. We identify that non-adherence and discontinuation rates are high and recommend strategies to support patients to improve adherence. We also provide an overview of several long-acting GH (LAGH) preparations currently under development and their potential role in improving treatment adherence.: This article summarizes recent clinical advances in rhGH replacement therapy, the biological and molecular aspects that may influence rhGH action, and offers practical strategies to enhance adherence in adults with GHD.
Kevin C J Yuen, Sofia Llahana, Bradley S Miller
1015 related Products with: Adult growth hormone deficiency: clinical advances and approaches to improve adherence.1 kit(96 Wells)96 wells (1 kit)5 mg1 mg100.00 ug96T100 1mg96T200
#31711427 2019/11/11 To Up
Novel HDGF/HIF-1α/VEGF axis in oral cancer impacts disease prognosis.Hepatoma-derived growth factor (HDGF) participates in angiogenesis and represents a negative prognostic factor in oral cancer. The current study was designed to elucidate the regulatory mechanism between HDGF and vascular endothelial growth factor (VEGF) and the clinical impact of oral cancer.
Yu-Wei Lin, Shih-Tsung Huang, Jian-Ching Wu, Tian-Huei Chu, Shih-Chung Huang, Ching-Chih Lee, Ming-Hong Tai
#31666193 2019/10/27 To Up
Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis.The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis.
Jian Mao, Binghui Qiu, Fen Mei, Fan Liu, Zhanpeng Feng, Jun Fan, Jing Nie, Lijun Huang, Xixian Liao, Zhenhao Wang, Jiahui Zeng, Zelin Weng, Nailiang Zang, Songtao Qi, Yun Bao
1058 related Products with: Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis.96 wells (1 kit)96 wells (1 kit)96T96 wells (1 kit)50μg1 mg5ug100.00 ug5ug10 0.1 mg 10
#31645449 2020/01/06 To Up
A Recombinant Rhesus Monkey Rhadinovirus Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses.A replication-competent, recombinant strain of rhesus monkey rhadinovirus (RRV) expressing the Gag protein of SIVmac239 was constructed in the context of a glycoprotein L (gL) deletion mutation. Deletion of gL detargets the virus from Eph family receptors. The ability of this gL-minus Gag recombinant RRV to infect, persist, and elicit immune responses was evaluated after intravenous inoculation of two RRV-naive rhesus monkeys. Both monkeys responded with an anti-RRV antibody response, and quantitation of RRV DNA in peripheral blood mononuclear cells (PBMC) by real-time PCR revealed levels similar to those in monkeys infected with recombinant gL RRV. Comparison of RRV DNA levels in sorted CD3 versus CD20 versus CD14 PBMC subpopulations indicated infection of the CD20 subpopulation by the gL-minus RRV. This contrasts with results obtained with transformed B cell lines , in which deletion of gL resulted in markedly reduced infectivity. Over a period of 20 weeks, Gag-specific CD8 T cell responses were documented by major histocompatibility complex class I (MHC-I) tetramer staining. Vaccine-induced CD8 T cell responses, which were predominantly directed against the Mamu-A*01-restricted GagCM9 epitope, could be inhibited by blockade of MHC-I presentation. Our results indicate that gL and the interaction with Eph family receptors are dispensable for the colonization of the B cell compartment following high-dose infection by the intravenous route, which suggests the existence of alternative receptors. Further, gL-minus RRV elicits cellular immune responses that are predominantly canonical in nature. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with a substantial disease burden in sub-Saharan Africa, often in the context of human immunodeficiency virus (HIV) infection. The related rhesus monkey rhadinovirus (RRV) has shown potential as a vector to immunize monkeys with antigens from simian immunodeficiency virus (SIV), the macaque model for HIV. KSHV and RRV engage cellular receptors from the Eph family via the viral gH/gL glycoprotein complex. We have now generated a recombinant RRV that expresses the SIV Gag antigen and does not express gL. This recombinant RRV was infectious by the intravenous route, established persistent infection in the B cell compartment, and elicited strong immune responses to the SIV Gag antigen. These results argue against a role for gL and Eph family receptors in B cell infection by RRV and have implications for the development of a live-attenuated KSHV vaccine or vaccine vector.
Alexander S Hahn, Georg F Bischof, Anna K Großkopf, Young C Shin, Aline Domingues, Lucas Gonzalez-Nieto, Eva G Rakasz, David I Watkins, Armin Ensser, Mauricio A Martins, Ronald C Desrosiers
1291 related Products with: A Recombinant Rhesus Monkey Rhadinovirus Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses.1mg25 Tests5024 tests
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