Oxygen/glucose deprivation (OGD) has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra', ...Oxygen/glucose deprivation (OGD) has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra', where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD (pOGD) protocol in a rat brain slice. This model met two requirements: oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid (GABAA) receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.展开更多
The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the...The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease (ALD). The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice (lacking a functional ASGP receptor) to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas (CD95) antibody, carbon tetrachloride (CCh) and lipopolysaccharide (LPS)/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.展开更多
Objective To determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the β 3 adrenergic receptor (β 3 AR) gene with type 2 diabetes mel...Objective To determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the β 3 adrenergic receptor (β 3 AR) gene with type 2 diabetes mellitus (DM) and its intermediate phenotypes in the Chinese population Methods Polymerase chain reaction oligonucleotide ligation assay and restriction fragment length polymorphism assay were used to evaluate the GYS1 and β 3 AR gene polymorphisms in 102 pairs of case control Chinese spouses Results Subjects with Met416Val variant had a significantly higher 2 hour post glucose level than subjects without this variant had in diabetic group ( P =0 032) The Met416Val polymorphism of GYS1 gene was not significantly associated with the risk of type 2 DM (adjusted OR=1 67; 95% CI: 0 73-3 81, P =0 223) Subjects with Trp64Arg variant had a significantly higher serum uric acid level than subjects without this variant had in diabetic group ( P =0 034) The combination of BMI and Arg64 allele carrier of the β 3 AR gene increased the diabetic risk over four fold (adjusted OR=4 00; 95%CI: 1 53-10 45, P =0 005) Conclusions In the Chinese population, Met416Val polymorphism is identified in a subgroup of diabetic subjects with high 2 hour post glucose It will explain why some diabetic patients appear to be genetically predisposed to developing high postpradial glucose level The presence of the Arg64 allele in the β 3 AR gene may predispose patients to higher serum uric acid level展开更多
Background Hemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy wit...Background Hemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy with glucocorticoids is the mainstay treatment, but there is no consensus on therapeutic regimens or candidate selection, therapeutic efficacy vaires, and the mechanism mediating the beneficial effects of glucocorticoids remains unclear. This study was performed to investigate the expression patterns of the glucocorticoid receptor (GR) and its α isoform (GRα) in cutaneous hemangiomas and vascular malformations.Methods SP immunohistochemical technique was used to examine the expression of GR(e-20) (GR) and GR (p-20) (GRα) on vascular endothelial cells in 80 specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas, 7 vascular malformations as well as 8 normal skin tissues, all obtained from infants and children. GR and GRα expression in prepared tissue slides were examined using automated computer-assisted microscopic analysis. Mean gray scale values were compared among the various tumor types.Results The mean gray scale values of GR were 127.0±6.4 and 121.4±6.6 in hemangiomas and vascular malformations respectively, but this difference was not statistically significant ( P =0.104). However, these values were all markedly higher than that of normal skin, which was only 108.6±6.8 ( P =0.001 and P =0.000 for comparison with hemangiomas and vascular malformations respectively). The gray scale of GR in proliferation and involuting hemangiomas were 127.9±4.8 and 126.0±5.8 respectively, but this difference was not significant ( P =0.146). However, GRα expression in hemangiomas, vascular malformations and normal skin declined gradually in stepwise fashion (127.3±5.4, 120.4±6.1 and 109.9±5.3 respectively; P <0.001). GRα expression was higher in proliferating hemangiomas than in involuting hemangiomas (127.2±6.3 and 122.5±6.3; P =0.004).Conclusions GR and GRα are strongly expressed in hemangiomas and vascular malformations. The expression of GRα is closely related to the phase of the hemangioma. Determination of GR and GRα may be a positive significance to understand the information of hemangiomas and vascular malformations and may further help determining proper strategies of steroid therapy for hemangiomas and vascular malformations.展开更多
文摘Oxygen/glucose deprivation (OGD) has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra', where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD (pOGD) protocol in a rat brain slice. This model met two requirements: oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid (GABAA) receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.
基金Supported by The National Institute on Alcohol Abuse and Alcoholismthe Department of Veterans Affairs
文摘The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease (ALD). The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice (lacking a functional ASGP receptor) to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas (CD95) antibody, carbon tetrachloride (CCh) and lipopolysaccharide (LPS)/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.
文摘Objective To determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the β 3 adrenergic receptor (β 3 AR) gene with type 2 diabetes mellitus (DM) and its intermediate phenotypes in the Chinese population Methods Polymerase chain reaction oligonucleotide ligation assay and restriction fragment length polymorphism assay were used to evaluate the GYS1 and β 3 AR gene polymorphisms in 102 pairs of case control Chinese spouses Results Subjects with Met416Val variant had a significantly higher 2 hour post glucose level than subjects without this variant had in diabetic group ( P =0 032) The Met416Val polymorphism of GYS1 gene was not significantly associated with the risk of type 2 DM (adjusted OR=1 67; 95% CI: 0 73-3 81, P =0 223) Subjects with Trp64Arg variant had a significantly higher serum uric acid level than subjects without this variant had in diabetic group ( P =0 034) The combination of BMI and Arg64 allele carrier of the β 3 AR gene increased the diabetic risk over four fold (adjusted OR=4 00; 95%CI: 1 53-10 45, P =0 005) Conclusions In the Chinese population, Met416Val polymorphism is identified in a subgroup of diabetic subjects with high 2 hour post glucose It will explain why some diabetic patients appear to be genetically predisposed to developing high postpradial glucose level The presence of the Arg64 allele in the β 3 AR gene may predispose patients to higher serum uric acid level
文摘Background Hemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy with glucocorticoids is the mainstay treatment, but there is no consensus on therapeutic regimens or candidate selection, therapeutic efficacy vaires, and the mechanism mediating the beneficial effects of glucocorticoids remains unclear. This study was performed to investigate the expression patterns of the glucocorticoid receptor (GR) and its α isoform (GRα) in cutaneous hemangiomas and vascular malformations.Methods SP immunohistochemical technique was used to examine the expression of GR(e-20) (GR) and GR (p-20) (GRα) on vascular endothelial cells in 80 specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas, 7 vascular malformations as well as 8 normal skin tissues, all obtained from infants and children. GR and GRα expression in prepared tissue slides were examined using automated computer-assisted microscopic analysis. Mean gray scale values were compared among the various tumor types.Results The mean gray scale values of GR were 127.0±6.4 and 121.4±6.6 in hemangiomas and vascular malformations respectively, but this difference was not statistically significant ( P =0.104). However, these values were all markedly higher than that of normal skin, which was only 108.6±6.8 ( P =0.001 and P =0.000 for comparison with hemangiomas and vascular malformations respectively). The gray scale of GR in proliferation and involuting hemangiomas were 127.9±4.8 and 126.0±5.8 respectively, but this difference was not significant ( P =0.146). However, GRα expression in hemangiomas, vascular malformations and normal skin declined gradually in stepwise fashion (127.3±5.4, 120.4±6.1 and 109.9±5.3 respectively; P <0.001). GRα expression was higher in proliferating hemangiomas than in involuting hemangiomas (127.2±6.3 and 122.5±6.3; P =0.004).Conclusions GR and GRα are strongly expressed in hemangiomas and vascular malformations. The expression of GRα is closely related to the phase of the hemangioma. Determination of GR and GRα may be a positive significance to understand the information of hemangiomas and vascular malformations and may further help determining proper strategies of steroid therapy for hemangiomas and vascular malformations.