The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Leif Jansson - One of the best experts on this subject based on the ideXlab platform.
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Evidence of a Negative Feedback System regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants.
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:The aim of the present study was to investigate the long-term regulation of pancreatic beta-cell volume after pancreas transplantation into adult rats. A syngeneic pancreaticoduodenal transplantation was made in normoglycemic Wistar-Furth rats. By this means, the recipients doubled their pancreatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insulin from both the native and transplanted pancreata, and in the native pancreas of age-matched Wistar-Furth rats that did not receive transplants. No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and transplanted pancreas when compared with that of age-matched controls. However, the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pancreas in control animals. No signs of increased apoptosis in any of the glands could be seen during the first postoperative week or after 9 months. These findings provide evidence of a Negative Feedback System, which regulates the total beta-cell volume to the levels seen in age-matched rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished replicatory rate of the beta-cells.
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evidence of a Negative Feedback System regulating the total beta cell volume in nondiabetic rats that received pancreas transplants
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:Evidence of a Negative feed-back System regulating the total s-cell volume in pancreas transplanted non-diabetic rats.
Toshiro Shibano - One of the best experts on this subject based on the ideXlab platform.
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Antithrombin-independent thrombin inhibitors, but not direct factor Xa inhibitors, enhance thrombin generation in plasma through inhibition of thrombin-thrombomodulin-protein C System
Thrombosis and haemostasis, 2011Co-Authors: Taketoshi Furugohri, Yoshiyuki Morishima, Nobutoshi Sugiyama, Toshiro ShibanoAbstract:There is increasing concern that some anticoagulants can paradoxically increase thrombogenesis under certain circumstances. Previously, we demonstrated that at certain doses a direct thrombin inhibitor, melagatran, worsens the coagulation status induced by tissue factor (TF) injection in a rat model. We utilised an in vitro thrombin generation (TG) assay to determine if direct thrombin inhibitors could enhance TG in human plasma, and whether inhibition of the Negative-Feedback System [thrombin-thrombomodulin (TM)-protein C] contributed to the TG enhancement. TG in human plasma was assayed by means of the calibrated automated thrombography. In this assay, direct factor Xa (FXa) inhibitors such as edoxaban and antithrombin (AT)-dependent anticoagulants such as heparin did not increase, but simply suppressed TG. AT-independent thrombin inhibitors (melagatran, lepirudin, and active site blocked thrombin (IIai)) increased peak levels of TG (2.0, 1.6, and 2.2-fold, respectively) in the presence of 12 nM recombinant human soluble TM (rhsTM). Melagatran and lepirudin at higher concentrations began to suppress TG. In the absence of rhsTM, the enhancement of peak TG by melagatran decreased to 1.2-fold. Furthermore, in protein C-deficient plasma, AT-independent thrombin inhibitors failed to enhance TG. In addition, a human protein C neutralising antibody increased the peak height of TG in the presence of rhsTM. These results suggest that AT-independent thrombin inhibitors may activate thrombogenesis by suppression of the thrombin-induced Negative-Feedback System through inhibition of protein C activation. In contrast, direct FXa inhibitors are more useful than AT-independent thrombin inhibitors in terms of lower possibility of activation of the coagulation pathway.
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Antithrombin-Independent Thrombin Inhibitors, but Not Factor Xa Inhibitors, Enhance Thrombin Generation in Human Plasma Via Inhibition of Thrombin-Thrombomodulin-Protein C System.
Blood, 2006Co-Authors: Yoshiyuki Morishima, Taketoshi Furugohri, Yoko Shiozaki, Nobutoshi Sugiyama, Toshiro ShibanoAbstract:Rebound like recurrent thrombotic events are concerns about anticoagulant therapies. Withdrawal of heparins and a direct thrombin inhibitor is reported to be associated with evidence of rebound coagulation phenomenon in patients with coronary artery diseases (Ref 1). Previously we have shown that low-dose administration of a direct thrombin inhibitor, melagatran, enhances coagulation induced by tissue factor (TF) in rats (Ref 2). Objectives: To determine whether anticoagulants enhance thrombin generation in human plasma, and whether the Negative-Feedback System [thrombin-thrombomodulin (TM)-protein C] contributes to the enhancement. Methods: Thrombin generation in pooled human plasma was assayed by means of the calibrated automated thrombography (CAT) with the thrombinoscope software in vitro. Thrombin generation was induced by 2.5 pM tissue factor (TF) and 4 μM phospholipids. The effects of following anticoagulants were assessed: antithrombin (AT)-independent thrombin inhibitors [melagatran, recombinant hirudin (lepirudin), and active site blocked thrombin (IIai)], AT-dependent anticoagulants (heparin, dalteparin, and fondaparinux), and AT-independent FXa inhibitors (DU-176b and DX-9065a). Results: Melagatran, lepirudin, and IIai increased peak levels of thrombin generation in the presence of 8 nM recombinant human soluble TM. The effects reached maximal at 200 nM of melagatran (2.3-fold), 8.95 nM of lepirudin (1.6-fold), and 405 nM of IIai (2.2-fold). At higher concentrations, melagatran and lepirudin turned to suppress thrombin generation. Heparin, dalteparin, fondaparinux, DU-176b, and DX-9065a did not enhance thrombin generation, just exerted inhibitory effects. In the absence of TM, the enhancement by melagatran of peak thrombin generation was only 1.2-fold, suggesting the significant role of the Negative-Feedback System in this aggravation of thrombin generation. Since thrombin acts both the pro- and anti-coagulant, the inhibition of the Negative-Feedback System by these thrombin inhibitors may cause enhancement of thrombin generation. To test this hypothesis, we examined thrombin generation in protein C-deficient plasma. AT-independent thrombin inhibitors failed to enhance thrombin generation in protein C-deficient plasma. Conclusions: These results indicate that AT-independent thrombin inhibitors at low concentrations enhance thrombin generation probably due to suppression of the Negative Feedback System by inhibiting protein C activation. This in vitro aggravation of thrombin generation may be a possible explanation of hypercoagulation by melagatran in a rat model of TF-induced intravascular coagulation. Furthermore this phenomenon would contribute to clinical rebound like recurrent thrombotic events associated with anticoagulant therapies with these inhibitors. In contrast, AT-independent FXa inhibitors like DU-176b are less prone to induce the rebound because of lack of increase in thrombin generation.
Jeanette Wahlberg Topp - One of the best experts on this subject based on the ideXlab platform.
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Evidence of a Negative Feedback System regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants.
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:The aim of the present study was to investigate the long-term regulation of pancreatic beta-cell volume after pancreas transplantation into adult rats. A syngeneic pancreaticoduodenal transplantation was made in normoglycemic Wistar-Furth rats. By this means, the recipients doubled their pancreatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insulin from both the native and transplanted pancreata, and in the native pancreas of age-matched Wistar-Furth rats that did not receive transplants. No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and transplanted pancreas when compared with that of age-matched controls. However, the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pancreas in control animals. No signs of increased apoptosis in any of the glands could be seen during the first postoperative week or after 9 months. These findings provide evidence of a Negative Feedback System, which regulates the total beta-cell volume to the levels seen in age-matched rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished replicatory rate of the beta-cells.
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evidence of a Negative Feedback System regulating the total beta cell volume in nondiabetic rats that received pancreas transplants
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:Evidence of a Negative feed-back System regulating the total s-cell volume in pancreas transplanted non-diabetic rats.
Minoru Saito - One of the best experts on this subject based on the ideXlab platform.
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a size dependent multiple loop Negative Feedback System describes biological segment formation based on the clock and wavefront mechanism
Biophysical Reviews and Letters, 2018Co-Authors: Yusuke Shibasaki, Chikako Yoshidanoro, Minoru SaitoAbstract:We proposed a new mathematical model for biological segment formation based on the clock and wavefront mechanism suggested in 1970s. Here, we chose an invertebrate, Enchytraeus japonensis, as a mod...
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A Size-Dependent Multiple-Loop Negative Feedback System Describes Biological Segment Formation Based on the Clock and Wavefront Mechanism
Biophysical Reviews and Letters, 2018Co-Authors: Yusuke Shibasaki, Chikako Yoshida-noro, Minoru SaitoAbstract:We proposed a new mathematical model for biological segment formation based on the clock and wavefront mechanism suggested in 1970s. Here, we chose an invertebrate, Enchytraeus japonensis, as a model animal and adopted multiple-loop Negative Feedback System based on its physiological features. We numerically showed the segment number of the model animal is autopoietically controlled by a size-dependent function. Additionally, we discussed two cases of the irregular oscillations by applying the biological conditions for abnormal development. The present model showed robustness under local noise perturbations like many other biological oscillators and qualitatively described unique development of the model animal. As a result, we suggested that a global interaction of chemical signals in the body can also drive “segmentation clock”.
Nils Welsh - One of the best experts on this subject based on the ideXlab platform.
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Evidence of a Negative Feedback System regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants.
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:The aim of the present study was to investigate the long-term regulation of pancreatic beta-cell volume after pancreas transplantation into adult rats. A syngeneic pancreaticoduodenal transplantation was made in normoglycemic Wistar-Furth rats. By this means, the recipients doubled their pancreatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insulin from both the native and transplanted pancreata, and in the native pancreas of age-matched Wistar-Furth rats that did not receive transplants. No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and transplanted pancreas when compared with that of age-matched controls. However, the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pancreas in control animals. No signs of increased apoptosis in any of the glands could be seen during the first postoperative week or after 9 months. These findings provide evidence of a Negative Feedback System, which regulates the total beta-cell volume to the levels seen in age-matched rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished replicatory rate of the beta-cells.
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evidence of a Negative Feedback System regulating the total beta cell volume in nondiabetic rats that received pancreas transplants
Transplantation, 1998Co-Authors: Jeanette Wahlberg Topp, Olle Korsgren, Nils Welsh, Leif JanssonAbstract:Evidence of a Negative feed-back System regulating the total s-cell volume in pancreas transplanted non-diabetic rats.