George Christ - Academia.edu (original) (raw)
Papers by George Christ
Tissue Engineering Part A, Jun 1, 2017
Wounds to the head, neck, and extremities have been estimated to account for *84% of reported com... more Wounds to the head, neck, and extremities have been estimated to account for *84% of reported combat injuries to military personnel. Volumetric muscle loss (VML), defined as skeletal muscle injuries in which tissue loss results in permanent functional impairment, is common among these injuries. The present standard of care entails the use of muscle flap transfers, which suffer from the need for additional surgery when using autografts or the risk of rejection when cadaveric grafts are used. Tissue engineering (TE) strategies for skeletal muscle repair have been investigated as a means to overcome current therapeutic limitations. In that regard, human hair-derived keratin (KN) biomaterials have been found to possess several favorable properties for use in TE applications and, as such, are a viable candidate for use in skeletal muscle repair. Herein, KN hydrogels with and without the addition of skeletal muscle progenitor cells (MPCs) and/or insulin-like growth factor 1 (IGF-1) and/or basic fibroblast growth factor (bFGF) were implanted in an established murine model of surgically induced VML injury to the latissimus dorsi (LD) muscle. Control treatments included surgery with no repair (NR) as well as implantation of bladder acellular matrix (BAM). In vitro muscle contraction force was evaluated at two months postsurgery through electrical stimulation of the explanted LD in an organ bath. Functional data indicated that implantation of KN+bFGF+IGF-1 (n = 8) enabled a greater recovery of contractile force than KN+bFGF (n = 8)***, KN+MPC (n = 8)**, KN+MPC+bFGF+IGF-1 (n = 8)**, BAM (n = 8)*, KN+IGF-1 (n = 8)*, KN+MPCs+bFGF (n = 9)*, or NR (n = 9)**, (*p < 0.05, **p < 0.01, ***p < 0.001). Consistent with the physiological findings, histological evaluation of retrieved tissue revealed much more extensive new muscle tissue formation in groups with greater functional recovery (e.g., KN+IGF-1+bFGF) when compared with observations in tissue from groups with lower functional recovery (i.e., BAM and NR). Taken together, these findings further indicate the general utility of KN biomaterials in TE and, moreover, specifically highlight their potential application in the treatment of VML injuries.
American Journal of Physiology-heart and Circulatory Physiology, Aug 1, 1998
The Ca 2ϩ-sensitive K ϩ channel (maxi-K ϩ) is an important modulator of corporal smooth muscle to... more The Ca 2ϩ-sensitive K ϩ channel (maxi-K ϩ) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: 1) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K ϩ channel, and 2) to determine whether transfection of the maxi-K ϩ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMV/Lac Z DNA in 10-wk-old rats resulted in significant incorporation and expression of -galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N ϭ 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N ϭ 5) and 2 mo (N ϭ 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N ϭ 2) and 4 mo (N ϭ 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.
Life Sciences, 1991
Kinetic and steady-state protocols were used to examine the effects of disruption of intercellula... more Kinetic and steady-state protocols were used to examine the effects of disruption of intercellular communication with heptanol, on contractile responses elicited by activation of the alpha 1-adrenergic receptor in human corporal vascular smooth muscle. For the steady-state studies, strips of corporal tissue from 19 patients were submaximally precontracted with phenylephrine (PE) and then relaxed by the cumulative addition of heptanol. Heptanol completely and reversibly relaxed all tissues studied in a concentration-dependent manner. The heptanol concentration response data were then computer fit to the general logistic equation to obtain pEC50 (negative logarithm of the concentration that elicits one-half of the maximal effect) and slope factor values, with Emax (maximal relaxation) set to 100%. The mean pEC50 and slope factor values, respectively, were 2.86 +/- 0.04 and 1.86 +/- 0.17. Furthermore, kinetic studies on corporal tissues from a subset of the patient population (11 patients) revealed that preincubation of tissues with 2 mM heptanol caused a significant decrease in both the rate and magnitude of PE-induced contractions in all tissues studied, without affecting the rate constant for onset of contraction (k(obs)). The present results on intact tissue extend our previous observations on cultured corporal cells, and support the supposition that intercellular communication through gap junctions may play an important role in the initiation, maintenance and modulation of alpha 1-adrenergic contractions in human vascular smooth muscle.
Journal of Biomechanics, Mar 1, 2019
Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in woun... more Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in wound location. Regenerative medicine offers promising alternative treatments, but there is little understanding of the correlation between magnitude of VML injuries and corresponding functional deficits that must be addressed. There is a need for a tool that can elucidate the relationship between VML injury and force loss, as well as the impact on specific mechanisms responsible for force production. The purpose of this study was to develop a novel coupled framework of in situ and in silico methods to more precisely understand the relationship between injury location and force production deficits. We created a threedimensional finite-element model of the pennate latissimus dorsi (LD) muscle in the rat and validated the model experimentally. We found that the model's prediction (2.6 N/g Model I, 2.1 N/g Model V) compared favorably to in situ testing of isometric force generation of the injured rat LD muscle (2.8 ± 0.3 N/g Experimental I, 2.1 ± 0.2 N/g Experimental V). Further model analysis revealed that the contribution from lateral and longitudinal force transmission to the total force varied with injury location and led to a greater understanding of the mechanisms responsible for VML-related force deficits. In the future, the coupled computational and experimental framework can be used to inform development of preclinical VML injury models that better recapitulate the spectrum of VML injuries observed in affected patients, and the mechanistic insight can accelerate the creation of improved regenerative therapeutics for VML injuries.
The Journal of Urology, Apr 1, 2005
Elsevier eBooks, 2009
Abstract Regenerative medicine and tissue engineering technologies are rapidly advancing with pot... more Abstract Regenerative medicine and tissue engineering technologies are rapidly advancing with potentially broad clinical applications, including those in the field of urology. Although all structures of the lower urinary tract (ureters, bladder, sphincter, urethra) would undoubtedly benefit from utilization of tissue engineering technologies, this report will focus on applications in the bladder. In this regard, the results of both preclinical and clinical investigations support the use of engineered bladder constructs/implants for the treatment of end-stage bladder disease. Despite great progress, further optimization and utilization of this groundbreaking technology will require a more complete characterization and understanding of bladder regeneration both in vitro and in vivo. The complexity of normal tissue structure and physiology, in turn, requires a rigorous examination of the engineered ’biomimetics' to ensure that they do indeed provide the required structure, physiology and function. In this chapter we outline an algorithm for evaluation of bladder function that will be useful for such a characterization of the physiological attributes of engineered and regenerating bladders. Briefly, we propose a multidisciplinary ’vertical approach’ that assesses the characteristics of bladder function/phenotype at the genetic, cellular, molecular, tissue and whole animal level. Appropriate methods and instruments are already available to this end, and in this chapter we describe both the methods and rationale for comparison of engineered/regenerating bladders with native bladder.
Cambridge University Press eBooks, Apr 23, 2013
PubMed, Feb 1, 1991
5-Hydroxytryptamine (5-HT), and the selective alpha-1 agonists phenylephrine (PE) and oxymetazoli... more 5-Hydroxytryptamine (5-HT), and the selective alpha-1 agonists phenylephrine (PE) and oxymetazoline (OXY), were used to study the effects of simultaneous coactivation of the 5-HT2 and alpha-1 adrenergic receptors, respectively, on the contractile responses of isolated rat aortic rings. Dissociation constants (KA) were determined for each of the agonists at their respective receptor subtypes. The KA values for PE and OXY at the alpha-1 receptor were 316 nM and 1.82 microM, respectively, while the KA for 5-HT at the 5-HT2 receptor was 478 nM. Concentration-response curves for each agonist were analyzed by the Black and Leff operational model of pharmacological agonism to determine efficacy (tau) and slope factor values. The estimated tau for PE (16.02) was much greater than the tau for either OXY (4.15) or 5-HT (2.95), which had similar efficacies. Using a previously described drug concentration paradigm, a mutual-effect amplification of the 5-HT-induced contractile response was observed with mixtures of 5-HT and PE, whereas mixtures of OXY and 5-HT elicited a mutual-effect amplification of the observed response to OXY alone. In both cases, the theoretical concentration-response curve constructed using the Poch and Holzmann method of equiactive substitution demonstrated that mutual-effect amplification was largely the result of simple additivity of agonist effects. In addition, estimates of tau and slope factor determined from the Black and Leff equation were substituted into the Leff model of mutual-effect amplification and used to accurately predict the location of the concentration-response curves elicited by mixtures of 5-HT and PE, as well as mixtures of OXY and 5-HT. This represents the first time a mathematical model has been used to accurately predict the outcome of coactivation of the alpha-1 and 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Biomaterials Science, 2021
We introduce a scaffold combining 3D structural alignment and electrical conductivity for skeleta... more We introduce a scaffold combining 3D structural alignment and electrical conductivity for skeletal muscle tissue engineering. We show that aligned and conductive scaffolds support myoblast viability, 3D alignment, and early myotube formation.
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Jul 1, 2001
Plastic and reconstructive surgery. Global open, Apr 1, 2018
is feasible and enhanced with local A2AR activation. Dipyridamole and β-tricalcium phosphate have... more is feasible and enhanced with local A2AR activation. Dipyridamole and β-tricalcium phosphate have wellestablished safety profiles, making this regenerative approach highly translatable. Further studies are warranted. Acknowledgements: This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases 5R01AR068593-02 & 3R01AR068593-02S1 References:
The Journal of Urology, Apr 1, 2007
The Journal of Urology, Apr 1, 2005
THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 ... more THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 (56%) patients with missense mutations compared to 3/27 (12%) of patients without these sequence abnormalities (p=O.Ol). CONCLUSIONS: Possession of sequence variants in the ATM gene, particularly those that encode for an amino acid substitution, is predictive for the development of erectile dysfunction among patients treated with 125 I prostate brachytherapy.
Human Gene Therapy, Dec 11, 2006
Elsevier eBooks, 2015
Abstract The aim of this chapter is to give an overview of skeletal muscle and describe some of t... more Abstract The aim of this chapter is to give an overview of skeletal muscle and describe some of the methods used in our laboratories and others to engineer skeletal muscle tissue, highlighting specific benefits of each model and their utility both for transplantation, as applied to the craniofacial region, and in furthering biological understanding of skeletal muscle plasticity in health and disease.
PubMed, Feb 1, 1990
Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultane... more Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultaneous coactivation of the alpha-1 and 5-HT2 receptors, respectively, on the contractile response of isolated rabbit aortic rings. A mutual-effect amplification of the PE-induced contractile response was observed with concentration-response curves (CRC) elicited by mixtures of PE and 5-HT, using a novel drug concentration paradigm. The theoretical CRC constructed using the Poch and Holzman method of equiactive agonist substitution demonstrated that the observed mutual-effect amplification was more than the result of simple additivity. Thus, the Leff model of mutual-effect amplification was utilized to predict the location of observed CRCs to mixtures of PE and 5-HT. Efficacy (tau) and slope factor estimates were determined using the Black and Leff operational model of pharmacological agonism and these values were used to predict the location of CRCs elicited by mixtures of PE and 5-HT. We demonstrated that the Leff model was insufficient to explain the observed degree of mutual-effect amplification.
Journal of Parasitology, Oct 1, 1996
Continuous administration of verapamil significantly reduced the mortality rate of acute murine T... more Continuous administration of verapamil significantly reduced the mortality rate of acute murine Trypanosoma cruzi infection (P < 0.05). The mechanistic basis for these observations was investigated. Verapamil and other calcium-channel blockers did not inhibit the growth of epimastigotes in culture. Furthermore, verapamil did not inhibit the intracellular growth of amastigotes in endothelial cells as determined by the uptake of 3H-uracil. There were no significant differences in parasitemia between infected mice that were untreated and those treated with verapamil. Twenty days postinfection infected, untreated mice had a parasitemia of 5.8 x 10(6) trypomastigotes/ml (SD +/- 2 x 10(6)), whereas infected, verapamil-treated mice had a parasitemia of 2.2 x 10(6) trypomastigotes/ml (SD +/- 0.5 x 10(6)). There was no significant difference in mortality between mice administered verapamil only for the initial 10 days of murine infection compared to those treated continuously. A 3-day delay in the initiation of verapamil administration reduced the mortality rate, but a 10-day delay did not. Propranolol (beta-adrenergic blocker), prazosin (alpha 1-adrenergic blocker), and diltiazem (another calcium-channel blocker) reduced the mortality but not significantly (P = 0.07). In biochemical studies of the beta- adrenergic signal transduction complex, we determined that verapamil and propranolol reversed the infection-associated decrease in myocardial beta- adrenergic adenylyl cyclase activity. In contrast, complementary western blot analysis revealed no significant changes in the G-proteins of the beta- adrenergic receptor complex 45 days postinfection. Therefore, these results suggest that the basis of verapamil's influence on the early critical period of infection is multifactorial and independent of a direct trypanocidal effect.
Tissue Engineering Part A, Jun 1, 2017
Wounds to the head, neck, and extremities have been estimated to account for *84% of reported com... more Wounds to the head, neck, and extremities have been estimated to account for *84% of reported combat injuries to military personnel. Volumetric muscle loss (VML), defined as skeletal muscle injuries in which tissue loss results in permanent functional impairment, is common among these injuries. The present standard of care entails the use of muscle flap transfers, which suffer from the need for additional surgery when using autografts or the risk of rejection when cadaveric grafts are used. Tissue engineering (TE) strategies for skeletal muscle repair have been investigated as a means to overcome current therapeutic limitations. In that regard, human hair-derived keratin (KN) biomaterials have been found to possess several favorable properties for use in TE applications and, as such, are a viable candidate for use in skeletal muscle repair. Herein, KN hydrogels with and without the addition of skeletal muscle progenitor cells (MPCs) and/or insulin-like growth factor 1 (IGF-1) and/or basic fibroblast growth factor (bFGF) were implanted in an established murine model of surgically induced VML injury to the latissimus dorsi (LD) muscle. Control treatments included surgery with no repair (NR) as well as implantation of bladder acellular matrix (BAM). In vitro muscle contraction force was evaluated at two months postsurgery through electrical stimulation of the explanted LD in an organ bath. Functional data indicated that implantation of KN+bFGF+IGF-1 (n = 8) enabled a greater recovery of contractile force than KN+bFGF (n = 8)***, KN+MPC (n = 8)**, KN+MPC+bFGF+IGF-1 (n = 8)**, BAM (n = 8)*, KN+IGF-1 (n = 8)*, KN+MPCs+bFGF (n = 9)*, or NR (n = 9)**, (*p < 0.05, **p < 0.01, ***p < 0.001). Consistent with the physiological findings, histological evaluation of retrieved tissue revealed much more extensive new muscle tissue formation in groups with greater functional recovery (e.g., KN+IGF-1+bFGF) when compared with observations in tissue from groups with lower functional recovery (i.e., BAM and NR). Taken together, these findings further indicate the general utility of KN biomaterials in TE and, moreover, specifically highlight their potential application in the treatment of VML injuries.
American Journal of Physiology-heart and Circulatory Physiology, Aug 1, 1998
The Ca 2ϩ-sensitive K ϩ channel (maxi-K ϩ) is an important modulator of corporal smooth muscle to... more The Ca 2ϩ-sensitive K ϩ channel (maxi-K ϩ) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: 1) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K ϩ channel, and 2) to determine whether transfection of the maxi-K ϩ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMV/Lac Z DNA in 10-wk-old rats resulted in significant incorporation and expression of -galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N ϭ 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N ϭ 5) and 2 mo (N ϭ 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N ϭ 2) and 4 mo (N ϭ 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.
Life Sciences, 1991
Kinetic and steady-state protocols were used to examine the effects of disruption of intercellula... more Kinetic and steady-state protocols were used to examine the effects of disruption of intercellular communication with heptanol, on contractile responses elicited by activation of the alpha 1-adrenergic receptor in human corporal vascular smooth muscle. For the steady-state studies, strips of corporal tissue from 19 patients were submaximally precontracted with phenylephrine (PE) and then relaxed by the cumulative addition of heptanol. Heptanol completely and reversibly relaxed all tissues studied in a concentration-dependent manner. The heptanol concentration response data were then computer fit to the general logistic equation to obtain pEC50 (negative logarithm of the concentration that elicits one-half of the maximal effect) and slope factor values, with Emax (maximal relaxation) set to 100%. The mean pEC50 and slope factor values, respectively, were 2.86 +/- 0.04 and 1.86 +/- 0.17. Furthermore, kinetic studies on corporal tissues from a subset of the patient population (11 patients) revealed that preincubation of tissues with 2 mM heptanol caused a significant decrease in both the rate and magnitude of PE-induced contractions in all tissues studied, without affecting the rate constant for onset of contraction (k(obs)). The present results on intact tissue extend our previous observations on cultured corporal cells, and support the supposition that intercellular communication through gap junctions may play an important role in the initiation, maintenance and modulation of alpha 1-adrenergic contractions in human vascular smooth muscle.
Journal of Biomechanics, Mar 1, 2019
Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in woun... more Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in wound location. Regenerative medicine offers promising alternative treatments, but there is little understanding of the correlation between magnitude of VML injuries and corresponding functional deficits that must be addressed. There is a need for a tool that can elucidate the relationship between VML injury and force loss, as well as the impact on specific mechanisms responsible for force production. The purpose of this study was to develop a novel coupled framework of in situ and in silico methods to more precisely understand the relationship between injury location and force production deficits. We created a threedimensional finite-element model of the pennate latissimus dorsi (LD) muscle in the rat and validated the model experimentally. We found that the model's prediction (2.6 N/g Model I, 2.1 N/g Model V) compared favorably to in situ testing of isometric force generation of the injured rat LD muscle (2.8 ± 0.3 N/g Experimental I, 2.1 ± 0.2 N/g Experimental V). Further model analysis revealed that the contribution from lateral and longitudinal force transmission to the total force varied with injury location and led to a greater understanding of the mechanisms responsible for VML-related force deficits. In the future, the coupled computational and experimental framework can be used to inform development of preclinical VML injury models that better recapitulate the spectrum of VML injuries observed in affected patients, and the mechanistic insight can accelerate the creation of improved regenerative therapeutics for VML injuries.
The Journal of Urology, Apr 1, 2005
Elsevier eBooks, 2009
Abstract Regenerative medicine and tissue engineering technologies are rapidly advancing with pot... more Abstract Regenerative medicine and tissue engineering technologies are rapidly advancing with potentially broad clinical applications, including those in the field of urology. Although all structures of the lower urinary tract (ureters, bladder, sphincter, urethra) would undoubtedly benefit from utilization of tissue engineering technologies, this report will focus on applications in the bladder. In this regard, the results of both preclinical and clinical investigations support the use of engineered bladder constructs/implants for the treatment of end-stage bladder disease. Despite great progress, further optimization and utilization of this groundbreaking technology will require a more complete characterization and understanding of bladder regeneration both in vitro and in vivo. The complexity of normal tissue structure and physiology, in turn, requires a rigorous examination of the engineered ’biomimetics' to ensure that they do indeed provide the required structure, physiology and function. In this chapter we outline an algorithm for evaluation of bladder function that will be useful for such a characterization of the physiological attributes of engineered and regenerating bladders. Briefly, we propose a multidisciplinary ’vertical approach’ that assesses the characteristics of bladder function/phenotype at the genetic, cellular, molecular, tissue and whole animal level. Appropriate methods and instruments are already available to this end, and in this chapter we describe both the methods and rationale for comparison of engineered/regenerating bladders with native bladder.
Cambridge University Press eBooks, Apr 23, 2013
PubMed, Feb 1, 1991
5-Hydroxytryptamine (5-HT), and the selective alpha-1 agonists phenylephrine (PE) and oxymetazoli... more 5-Hydroxytryptamine (5-HT), and the selective alpha-1 agonists phenylephrine (PE) and oxymetazoline (OXY), were used to study the effects of simultaneous coactivation of the 5-HT2 and alpha-1 adrenergic receptors, respectively, on the contractile responses of isolated rat aortic rings. Dissociation constants (KA) were determined for each of the agonists at their respective receptor subtypes. The KA values for PE and OXY at the alpha-1 receptor were 316 nM and 1.82 microM, respectively, while the KA for 5-HT at the 5-HT2 receptor was 478 nM. Concentration-response curves for each agonist were analyzed by the Black and Leff operational model of pharmacological agonism to determine efficacy (tau) and slope factor values. The estimated tau for PE (16.02) was much greater than the tau for either OXY (4.15) or 5-HT (2.95), which had similar efficacies. Using a previously described drug concentration paradigm, a mutual-effect amplification of the 5-HT-induced contractile response was observed with mixtures of 5-HT and PE, whereas mixtures of OXY and 5-HT elicited a mutual-effect amplification of the observed response to OXY alone. In both cases, the theoretical concentration-response curve constructed using the Poch and Holzmann method of equiactive substitution demonstrated that mutual-effect amplification was largely the result of simple additivity of agonist effects. In addition, estimates of tau and slope factor determined from the Black and Leff equation were substituted into the Leff model of mutual-effect amplification and used to accurately predict the location of the concentration-response curves elicited by mixtures of 5-HT and PE, as well as mixtures of OXY and 5-HT. This represents the first time a mathematical model has been used to accurately predict the outcome of coactivation of the alpha-1 and 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Biomaterials Science, 2021
We introduce a scaffold combining 3D structural alignment and electrical conductivity for skeleta... more We introduce a scaffold combining 3D structural alignment and electrical conductivity for skeletal muscle tissue engineering. We show that aligned and conductive scaffolds support myoblast viability, 3D alignment, and early myotube formation.
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Jul 1, 2001
Plastic and reconstructive surgery. Global open, Apr 1, 2018
is feasible and enhanced with local A2AR activation. Dipyridamole and β-tricalcium phosphate have... more is feasible and enhanced with local A2AR activation. Dipyridamole and β-tricalcium phosphate have wellestablished safety profiles, making this regenerative approach highly translatable. Further studies are warranted. Acknowledgements: This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases 5R01AR068593-02 & 3R01AR068593-02S1 References:
The Journal of Urology, Apr 1, 2007
The Journal of Urology, Apr 1, 2005
THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 ... more THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 (56%) patients with missense mutations compared to 3/27 (12%) of patients without these sequence abnormalities (p=O.Ol). CONCLUSIONS: Possession of sequence variants in the ATM gene, particularly those that encode for an amino acid substitution, is predictive for the development of erectile dysfunction among patients treated with 125 I prostate brachytherapy.
Human Gene Therapy, Dec 11, 2006
Elsevier eBooks, 2015
Abstract The aim of this chapter is to give an overview of skeletal muscle and describe some of t... more Abstract The aim of this chapter is to give an overview of skeletal muscle and describe some of the methods used in our laboratories and others to engineer skeletal muscle tissue, highlighting specific benefits of each model and their utility both for transplantation, as applied to the craniofacial region, and in furthering biological understanding of skeletal muscle plasticity in health and disease.
PubMed, Feb 1, 1990
Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultane... more Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultaneous coactivation of the alpha-1 and 5-HT2 receptors, respectively, on the contractile response of isolated rabbit aortic rings. A mutual-effect amplification of the PE-induced contractile response was observed with concentration-response curves (CRC) elicited by mixtures of PE and 5-HT, using a novel drug concentration paradigm. The theoretical CRC constructed using the Poch and Holzman method of equiactive agonist substitution demonstrated that the observed mutual-effect amplification was more than the result of simple additivity. Thus, the Leff model of mutual-effect amplification was utilized to predict the location of observed CRCs to mixtures of PE and 5-HT. Efficacy (tau) and slope factor estimates were determined using the Black and Leff operational model of pharmacological agonism and these values were used to predict the location of CRCs elicited by mixtures of PE and 5-HT. We demonstrated that the Leff model was insufficient to explain the observed degree of mutual-effect amplification.
Journal of Parasitology, Oct 1, 1996
Continuous administration of verapamil significantly reduced the mortality rate of acute murine T... more Continuous administration of verapamil significantly reduced the mortality rate of acute murine Trypanosoma cruzi infection (P < 0.05). The mechanistic basis for these observations was investigated. Verapamil and other calcium-channel blockers did not inhibit the growth of epimastigotes in culture. Furthermore, verapamil did not inhibit the intracellular growth of amastigotes in endothelial cells as determined by the uptake of 3H-uracil. There were no significant differences in parasitemia between infected mice that were untreated and those treated with verapamil. Twenty days postinfection infected, untreated mice had a parasitemia of 5.8 x 10(6) trypomastigotes/ml (SD +/- 2 x 10(6)), whereas infected, verapamil-treated mice had a parasitemia of 2.2 x 10(6) trypomastigotes/ml (SD +/- 0.5 x 10(6)). There was no significant difference in mortality between mice administered verapamil only for the initial 10 days of murine infection compared to those treated continuously. A 3-day delay in the initiation of verapamil administration reduced the mortality rate, but a 10-day delay did not. Propranolol (beta-adrenergic blocker), prazosin (alpha 1-adrenergic blocker), and diltiazem (another calcium-channel blocker) reduced the mortality but not significantly (P = 0.07). In biochemical studies of the beta- adrenergic signal transduction complex, we determined that verapamil and propranolol reversed the infection-associated decrease in myocardial beta- adrenergic adenylyl cyclase activity. In contrast, complementary western blot analysis revealed no significant changes in the G-proteins of the beta- adrenergic receptor complex 45 days postinfection. Therefore, these results suggest that the basis of verapamil's influence on the early critical period of infection is multifactorial and independent of a direct trypanocidal effect.