WorldCat Identities

Kopchick, John J.

Overview
Works: 6 works in 12 publications in 1 language and 363 library holdings
Roles: Editor
Publication Timeline
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Most widely held works by John J Kopchick
Laron syndrome - from man to mouse : lessons from clinical and experimental experience by Zvi Laron( )

7 editions published in 2011 in English and held by 358 WorldCat member libraries worldwide

Laron syndrome (LS), or primary growth hormone (GH) insensitivity, was first described in 1966. Since then, many patients worldwide have been diagnosed with LS, which involves defects in the GH receptor that cause combined congenital deficiency of GH and IGF-I activities. In this comprehensive book the authors draw upon 50 years of multidisciplinary clinical and investigative follow-up of the large Israeli cohort of LS patients. The genetic basis of the syndrome is fully considered, and all aspects of the pathophysiology of IGF-I deficiency are described
Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

ABSTRACT: Adipose tissue (AT) is a well-established target of growth hormone (GH) and is altered in clinical conditions associated with excess, deficiency and absence of GH action. Due to the difficulty in collecting AT from clinical populations, genetically modified mice have been useful in better understanding how GH affects this tissue. Recent findings in mice would suggest that the impact of GH on AT is beyond alterations of lipolysis, lipogenesis or proliferation/ differentiation. AT depot-specific alterations in immune cells, extracellular matrix, adipokines, and senescence indicate an expanded role for GH in AT physiology. These mouse data will guide additional studies necessary to evaluate the therapeutic potential and safety of GH for conditions associated with altering AT, such as obesity. In this review, we introduce several relatively new intricacies of GH's effect on AT, focusing on recent studies in mice. Finally, we summarize the clinical implications of these findings
Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

Abstract Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer’s disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer’s disease
Increased fibrosis: A novel means by which GH influences white adipose tissue function( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Abstract: Objective: White adipose tissue (WAT) fibrosis – the buildup of extracellular matrix (ECM) proteins, primarily collagen – is now a recognized hallmark of tissue dysfunction and is increased with obesity and lipodystrophy. While growth hormone (GH) is known to increase collagen in several tissues, no previous research has addressed its effect on ECM in WAT. Thus, the purpose of this study is to determine if GH influences WAT fibrosis. Design: This study examined WAT from four distinct strains of GH-altered mice (bGH and GHA transgenic mice as well as two tissue specific GH receptor gene disrupted lines, fat growth hormone receptor knockout or FaGHRKO and liver growth hormone receptor knockout or LiGHRKO mice). Collagen content and adipocyte size were studied in all cohorts and compared to littermate controls. In addition, mRNA expression of fibrosis-associated genes was assessed in one cohort (6 month old male bovine GH transgenic and WT mice) and cultured 3T3-L1 adipocytes treated with GH. Results: Collagen stained area was increased in WAT from bGH mice, was depot-dependent, and increased with age. Furthermore, increased collagen content was associated with decreased adipocyte size in all depots but more dramatic changes in the subcutaneous fat pad. Notably, the increase in collagen was not associated with an increase in collagen gene expression or other genes known to promote fibrosis in WAT, but collagen gene expression was increased with acute GH administration in 3T3-LI cells. In contrast, evaluation of 6 month old GH antagonist (GHA) male mice showed significantly decreased collagen in the subcutaneous depot. Lastly, to assess if GH induced collagen deposition directly or indirectly (via IGF-1), fat (Fa) and liver (Li) specific GHRKO mice were evaluated. Decreased fibrosis in FaGHRKO and increased fibrosis in LiGHRKO mice suggest GH is primarily responsible for the alterations in collagen. Conclusions: Our results show that GH action is positively associated with an increase in WAT collagen content as well as a decrease in adipocyte size, particularly in the subcutaneous depot. This effect appears to be due to GH and not IGF-1 and reveals a novel means by which GH regulates WAT accumulation. Highlights: GH action is positively associated with collagen content in adipose tissue (AT). Effect of GH on AT is depot-dependent with the subcutaneous fat pad most impacted. Fibrosis-related RNA expression is not related to AT collagen levels in bGH mice. WAT fibrosis appears to be a direct consequence of GH action and not IGF-1. Acute GH stimulation in vitro increases collagen mRNA expression
Depot-specific and GH-dependent regulation of IGF binding protein-4, pregnancy-associated plasma protein-A, and stanniocalcin-2 in murine adipose tissue( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Abstract: Introduction: Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF)-I action through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. Most members of the IGF system are expressed in adipose tissue (AT), but there is a relative paucity of information on the distribution of IGFBP-4, PAPP-A, and STC2 in different AT depots. Since IGF-I expression in AT is highly GH-dependent, we used bovine GH transgenic (bGH) and GH receptor knockout (GHR−/−) mice to investigate AT depot-specific expression patterns of IGFBP-4, PAPP-A, and STC2, and whether the regulation is GH-dependent. Methods: Seven-month-old male bGH, GHR−/− and wild type (WT) control mice were used. Body composition was determined, and subcutaneous, epididymal, retroperitoneal, mesenteric and brown adipose tissue (BAT) depots were collected. RNA expression of Igfbp4, Pappa, and Stc2 was assessed by reverse transcription quantitative PCR and IGFBP-4 protein by Western blotting. Results: Igfbp4, Pappa, and Stc2 RNA levels were differentially expressed in an AT depot-dependent manner in WT mice. Igfbp4 RNA levels were significantly higher in all white AT depots than in BAT. Pappa was most highly expressed in the mesenteric depot: levels were 7.5-fold higher in mesenteric than in subcutaneous AT ( p <.001). Although intraabdominal in origin, epididymal and retroperitoneal Pappa expression levels were 69% and 68% lower, respectively, as compared to mesenteric levels ( p <.001). Stc2 RNA expression was significantly higher in all intraabdominal white AT as compared to subcutaneous AT and BAT; levels in epididymal, retroperitoneal, and mesenteric were all more than three-fold higher than in subcutaneous AT ( p <.001) and 12-fold higher than in BAT ( p <.001). Gene expression patterns in bGH and GHR−/− mice mimicked those in WT mice, suggesting that GH does not affect the transcription of the STC2-PAPP-A-IGFBP-4-axis in AT. However, proteins levels of intact IGFBP-4 were significantly increased in bGH mice and decreased in GHR−/− mice, whereas the PAPP-A-generated IGFBP-4 fragment level was unaltered. Conclusion: Expression of Igfbp4, Pappa, and Stc2 differ between AT depots and is generally higher in white AT than in BAT. The transcription appears to occur in a GH-independent manner, whereas IGFBP-4 protein levels are highly influenced by altered GH activity. Highlights: IGFBP-4, PAPP-A and STC2 are expressed in murine adipose tissue in a depot-dependent manner. The proteins appear to play a more pronounced role in white than brown adipose tissue. The regulation of the RNA expressions likely occurs in an GH-independent manner. Interestingly, IGFBP-4 protein levels differ significantly between the genotypes, despite unaltered gene expression levels. Adipose tissue depots appear inherently distinct and cannot be analyzed interchangeably with regard to the IGF system
Growth Hormone Research Society perspective on biomarkers of GH action in children and adults( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Abstract : Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly
 
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Audience level: 0.45 (from 0.44 for Laron synd ... to 0.88 for Depot-spec ...)

Laron syndrome - from man to mouse : lessons from clinical and experimental experience
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English (12)