The Experts below are selected from a list of 2226 Experts worldwide ranked by ideXlab platform
Andreas J. Schwab - One of the best experts on this subject based on the ideXlab platform.
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increased hepatocyte permeability surface area product for 86rb with increase in blood flow
Circulation Research, 1997Co-Authors: C A Goresky, Andre Simard, Andreas J. SchwabAbstract:Liver cell recruitment (the equivalent of capillary recruitment in other organs) was explored by carrying out multiple indicator dilution experiments with labeled rubidium across the liver of the anesthetized dog under basal conditions and after bleeding with saline replacement infusion, which increases liver blood flow. A mixture of 51Cr-labeled red blood cells (a vascular reference), 22Na (which immediately equilibrates in the extracellular Space, the sum of the sinusoidal plasma and Disse or interstitial Spaces, the expected distribution Space for labeled rubidium in the absence of cellular entry), and 86Rb was injected into the portal vein, and normalized outflow patterns, expressed as outflowing fractions of each injected tracer per milliliter versus time, were obtained. In relation to the labeled red blood cell curve, the labeled sodium curve is displaced by flow-limited distribution into the Disse or interstitial Space; it is lower on the upslope, reaches a lower and delayed peak, and decays more slowly. The early part of the labeled rubidium curve lies within the labeled sodium curve; it reaches a much reduced peak, and the later return of tracer entering cells is so slow that it is obscured by recirculation. Modeling of the concentrative cellular uptake of rubidium from the Disse Space provided an influx permeability surface area product for labeled rubidium. This increases with flow over the observed flow range, demonstrating that sinusoidal recruitment occurs with increase in hepatic blood flow.
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hepatic uptake of protein bound ligands effect of an unstirred Disse Space
American Journal of Physiology-gastrointestinal and Liver Physiology, 1996Co-Authors: Andreas J. Schwab, C A GoreskyAbstract:Uptake of protein-bound substances by the liver was modeled considering concurrent depletion of unbound ligand (i.e., not bound to protein)along the length of a sinusoid as well as within a 0.5-micron unstirred boundary layer at the surface of the hepatic parenchymal cells. The development completes a previous exploration of Weisiger et al. [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G872-G884, 1991]. Ligand is carried across the unstirred layer by albumin, producing a deviation from binding equilibrium inside and outside the unstirred layer. The resulting differential equations have a closed solution. In the case of tight binding, the unbound ligand in the sinusoid is in a quasi-steady state, and the unbound fraction becomes constant along the flow path, except for a very short section at its beginning. During hepatic oleate uptake, the unbound oleate concentration rises from 39% of the equilibrium value at 0.1 microM albumin and 0.01 microM oleate to 78% at 0.5 microM albumin and 0.05 microM oleate. diffusion through the unstirred layer and across the cell membrane was found, in the model, to contribute to the overall resistance to oleate uptake in a complementary fashion.
C A Goresky - One of the best experts on this subject based on the ideXlab platform.
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increased hepatocyte permeability surface area product for 86rb with increase in blood flow
Circulation Research, 1997Co-Authors: C A Goresky, Andre Simard, Andreas J. SchwabAbstract:Liver cell recruitment (the equivalent of capillary recruitment in other organs) was explored by carrying out multiple indicator dilution experiments with labeled rubidium across the liver of the anesthetized dog under basal conditions and after bleeding with saline replacement infusion, which increases liver blood flow. A mixture of 51Cr-labeled red blood cells (a vascular reference), 22Na (which immediately equilibrates in the extracellular Space, the sum of the sinusoidal plasma and Disse or interstitial Spaces, the expected distribution Space for labeled rubidium in the absence of cellular entry), and 86Rb was injected into the portal vein, and normalized outflow patterns, expressed as outflowing fractions of each injected tracer per milliliter versus time, were obtained. In relation to the labeled red blood cell curve, the labeled sodium curve is displaced by flow-limited distribution into the Disse or interstitial Space; it is lower on the upslope, reaches a lower and delayed peak, and decays more slowly. The early part of the labeled rubidium curve lies within the labeled sodium curve; it reaches a much reduced peak, and the later return of tracer entering cells is so slow that it is obscured by recirculation. Modeling of the concentrative cellular uptake of rubidium from the Disse Space provided an influx permeability surface area product for labeled rubidium. This increases with flow over the observed flow range, demonstrating that sinusoidal recruitment occurs with increase in hepatic blood flow.
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hepatic uptake of protein bound ligands effect of an unstirred Disse Space
American Journal of Physiology-gastrointestinal and Liver Physiology, 1996Co-Authors: Andreas J. Schwab, C A GoreskyAbstract:Uptake of protein-bound substances by the liver was modeled considering concurrent depletion of unbound ligand (i.e., not bound to protein)along the length of a sinusoid as well as within a 0.5-micron unstirred boundary layer at the surface of the hepatic parenchymal cells. The development completes a previous exploration of Weisiger et al. [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G872-G884, 1991]. Ligand is carried across the unstirred layer by albumin, producing a deviation from binding equilibrium inside and outside the unstirred layer. The resulting differential equations have a closed solution. In the case of tight binding, the unbound ligand in the sinusoid is in a quasi-steady state, and the unbound fraction becomes constant along the flow path, except for a very short section at its beginning. During hepatic oleate uptake, the unbound oleate concentration rises from 39% of the equilibrium value at 0.1 microM albumin and 0.01 microM oleate to 78% at 0.5 microM albumin and 0.05 microM oleate. diffusion through the unstirred layer and across the cell membrane was found, in the model, to contribute to the overall resistance to oleate uptake in a complementary fashion.
Victor Nussenzweig - One of the best experts on this subject based on the ideXlab platform.
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Rapid clearance of malaria circumsporozoite protein (CS) by hepatocytes.
Journal of Experimental Medicine, 1994Co-Authors: Carla Cerami, Photini Sinnis, Bela Takacs, Ute Frevert, Victor NussenzweigAbstract:The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria sporozoites. In vitro, CS multimers bind specifically to regions of the hepatocyte plasma membrane that are exposed to circulating blood in the Disse Space. The ligand is in the region II-plus of CS, an evolutionarily conserved stretch of the protein that has amino acid sequence homology to a cell adhesive motif of thrombospondin. We have now found that intravenously injected CS constructs bind rapidly to the basolateral surface of hepatocytes, provided that the recombinant proteins contain region II-plus, and that they are aggregated. Significant amounts of CS were not retained in any other organ. The striking parallelism between these in vitro and in vivo findings with the target specificity of malaria sporozoites, reinforces the hypothesis that the attachment of the parasites to hepatocytes is via region II-plus of CS.
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the basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of plasmodium falciparum sporozoites
Cell, 1992Co-Authors: Carla Cerami, Photini Sinnis, Bela Takacs, Ute Frevert, Pedro Clavijo, Manuel J Santos, Victor NussenzweigAbstract:Abstract Minutes after injection into the circulation, malaria sporozoites enter hepatocytes. The speed and specificity of the invasion process suggest that it is receptor mediated. We show here that recombinant Plasmodium falciparum circumsporozoite protein (CS) binds specifically to regions of the plasma membrane of hepatocytes exposed to circulating blood in the Disse Space. No binding has been detected in other organs, or even in other regions of the hepatocyte membrane. The interaction of CS with hepatocytes, as well as sporozoite invasion of HepG2 cells, is inhibited by synthetic peptides representing the evolutionarily conserved region II of CS. We conclude that region II is a sporozoite ligand for hepatocyte receptors localized to the basolateral domain of the plasma membrane. Our findings provide a rational explanation for the target cell specificity of malaria sporozoites.
Jugoro Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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the role of fat storing cells in Disse Space fibrogenesis in alcoholic liver disease
Hepatology, 2007Co-Authors: Yukihito Minato, Yasushi Hasumura, Jugoro TakeuchiAbstract:Liver biopsy samples from 40 chronic alcoholic patients, including 9 with minimal changes of the liver, 6 with mild hepatic fibrosis, 14 with moderate fibrosis, and 11 with severe fibrosis (cirrhosis) were studied by electron microscopy to assess fibrogenesis in the Disse Space and the role of fat-storing cells in this process. In the Disse Space of normal liver, collagen fibers are few, and while lipid droplets containing fat-storing cells exist, their rough endoplasmic reticulum (RER) is inconspicuous. In the course of progressive hepatic fibrosis, collagen in the Disse Space increased. This was significantly associated with gradual development of RER in fat-storing cells, confirmed by morphometric analysis. It is likely, therefore, that the development of RER in the fat-storing cells is a morphological correlative of their activated fibrogenesis and transformation into fibroblasts. To further clarify this, the rate of collagen synthesis was measured by the method of in vitro incorporation of [3H]proline into collagen in 17 liver biopsy samples from alcoholic patients and compared with the degree of morphological changes of RER in fat-storing cells. In liver samples with well-developed RER in fat-storing cells, a significantly higher rate of collagen synthesis was observed. These results suggest that in alcoholic liver injury, fat-storing cells may play an important role in Disse Space fibrogenesis.
Carla Cerami - One of the best experts on this subject based on the ideXlab platform.
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Rapid clearance of malaria circumsporozoite protein (CS) by hepatocytes.
Journal of Experimental Medicine, 1994Co-Authors: Carla Cerami, Photini Sinnis, Bela Takacs, Ute Frevert, Victor NussenzweigAbstract:The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria sporozoites. In vitro, CS multimers bind specifically to regions of the hepatocyte plasma membrane that are exposed to circulating blood in the Disse Space. The ligand is in the region II-plus of CS, an evolutionarily conserved stretch of the protein that has amino acid sequence homology to a cell adhesive motif of thrombospondin. We have now found that intravenously injected CS constructs bind rapidly to the basolateral surface of hepatocytes, provided that the recombinant proteins contain region II-plus, and that they are aggregated. Significant amounts of CS were not retained in any other organ. The striking parallelism between these in vitro and in vivo findings with the target specificity of malaria sporozoites, reinforces the hypothesis that the attachment of the parasites to hepatocytes is via region II-plus of CS.
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the basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of plasmodium falciparum sporozoites
Cell, 1992Co-Authors: Carla Cerami, Photini Sinnis, Bela Takacs, Ute Frevert, Pedro Clavijo, Manuel J Santos, Victor NussenzweigAbstract:Abstract Minutes after injection into the circulation, malaria sporozoites enter hepatocytes. The speed and specificity of the invasion process suggest that it is receptor mediated. We show here that recombinant Plasmodium falciparum circumsporozoite protein (CS) binds specifically to regions of the plasma membrane of hepatocytes exposed to circulating blood in the Disse Space. No binding has been detected in other organs, or even in other regions of the hepatocyte membrane. The interaction of CS with hepatocytes, as well as sporozoite invasion of HepG2 cells, is inhibited by synthetic peptides representing the evolutionarily conserved region II of CS. We conclude that region II is a sporozoite ligand for hepatocyte receptors localized to the basolateral domain of the plasma membrane. Our findings provide a rational explanation for the target cell specificity of malaria sporozoites.