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  1. Article ; Online: Are filtered plasma proteins processed in the same way by the kidney?

    Comper, W D / Russo, L M / Vuchkova, J

    Journal of theoretical biology

    2016  Volume 410, Page(s) 18–24

    Abstract: In order to understand the mechanism of albuminuria we have explored how other plasma proteins are processed by the kidney as compared to inert molecules like Ficolls. When fractional clearances are plotted versus protein radius there is a remarkable ... ...

    Abstract In order to understand the mechanism of albuminuria we have explored how other plasma proteins are processed by the kidney as compared to inert molecules like Ficolls. When fractional clearances are plotted versus protein radius there is a remarkable parallelism between protein (molecular weight range 30-150kDa) clearance in healthy controls, in Dent's disease, in nephrotic states and the clearance of Ficolls. Although there are significant differences in the levels of fractional clearances in these states. Dent's disease results in a 2-fold increase in the fractional clearance of proteins as compared to healthy controls whereas in nephrotic states there is a further 3-fold increase in fractional clearance. Previous thinking that albumin uptake was controlled primarily by the megalin/cubilin receptor does not explain the albumin urinary excretion data and is therefore an incorrect concept. Protein clearance in nephrotic states approach the fractional clearance of inert Ficolls for a given radius. It therefore appears that there are two pathways processing these proteins. A low capacity pathway associated with megalin/cubilin that degrades filtered protein (that is inhibited in Dent's disease) and a high capacity pathway that retrieves the filtered protein and returns it to the blood supply (without retrieval nephrotic protein excretion will occur and this will account for hypoproteinemia). On the other hand low molecular weight proteins (<20kDa) are processed entirely differently by the kidney. They are not retrieved but are comprehensively degraded in the kidney with the degradation products predominantly returned to the blood supply.
    MeSH term(s) Albuminuria/metabolism ; Animals ; Blood Proteins/metabolism ; Dent Disease/metabolism ; Humans ; Kidney/metabolism ; Molecular Weight ; Rats
    Chemical Substances Blood Proteins
    Language English
    Publishing date 2016-09-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2016.09.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Charge selectively is a concept that has yet to be demonstrated.

    Comper, W D

    American journal of physiology. Renal physiology

    2001  Volume 281, Issue 5, Page(s) F992–3

    MeSH term(s) Albumins/chemistry ; Albuminuria ; Animals ; Chemical Phenomena ; Chemistry, Physical ; Electrochemistry ; Kidney Glomerulus/metabolism ; Rats
    Chemical Substances Albumins
    Language English
    Publishing date 2001-11
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 1931-857X ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 1931-857X ; 0363-6127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Osmotic flow caused by polyelectrolytes.

    Williams, R P / Comper, W D

    Biophysical chemistry

    2006  Volume 36, Issue 3, Page(s) 223–234

    Abstract: Osmotic flow of water caused by high concentrations of anionic polyelectrolytes across semipermeable membranes, permeable only to solvent and simple electrolyte, has been measured in a newly designed flow cell. The flow cell features small solution and ... ...

    Abstract Osmotic flow of water caused by high concentrations of anionic polyelectrolytes across semipermeable membranes, permeable only to solvent and simple electrolyte, has been measured in a newly designed flow cell. The flow cell features small solution and solvent compartments and an efficient stirring mechanism. We have demonstrated that, while the osmotic pressure of the anionic polyelectrolytes is determined primarily by micro-counterions, the osmotic flow is determined by solution-dependent properties as embodied in the hydrodynamic frictional coefficient which is determined by the polymer backbone segment of the polyelectrolyte. The variation of the osmotic permeability coefficient, L(p)(o), with concentration and osmotic pressure closely correlated with the concentration dependence of this frictional coefficient. These studies confirm previous work that the kinetics of osmotic flow across a membrane impermeable to the osmotically active solute is primarily determined by the diffusive mobility of the solute.
    Language English
    Publishing date 2006-09-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 185052-0
    ISSN 1873-4200 ; 0301-4622
    ISSN (online) 1873-4200
    ISSN 0301-4622
    DOI 10.1016/0301-4622(90)80028-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The thermodynamic and hydrodynamic properties of macromolecules that influence the hydrodynamics of porous systems.

    Comper, W D

    Journal of theoretical biology

    1994  Volume 168, Issue 4, Page(s) 421–427

    Abstract: The water flow across porous, semipermeable membranes associated with osmosis and filtration under a variety of conditions is analysed and compared to macromolecular diffusion across free-liquid boundaries, diffusion and sedimentation in the ... ...

    Abstract The water flow across porous, semipermeable membranes associated with osmosis and filtration under a variety of conditions is analysed and compared to macromolecular diffusion across free-liquid boundaries, diffusion and sedimentation in the ultracentrifuge, and tracer diffusion of water. This study establishes that osmosis can be explained in terms of the irreversible thermodynamics of diffusion. For macromolecular osmotically active solutes in the semidilute concentration regime the water flows across semipermeable porous membranes are interpreted in terms of a rate-limiting solute-solvent exchange layer that exists on the solution side of the membrane adjacent to the membrane pore; both osmosis and filtration will be governed by these exchange layers. These exchange layers also yield unique properties of their constituent molecules in systems where there is osmotic equilibration between solutions of different solutes. This study also establishes the need to consider the internal osmotic pressure of membranes in the pressure balance associated with the flow across the membrane. The complex situation of partially permeable membranes is analysed for the simple case where there are no mechanical gradients and there is only one osmotically active solution that creates a rate-limiting exchange layer. This treatment predicts that the flow will be governed primarily by the osmotic pressure difference associated with the partitioning of the solute at the membrane-solution interface.
    MeSH term(s) Animals ; Cell Membrane/physiology ; Filtration ; Macromolecular Substances ; Models, Biological ; Osmosis ; Porosity ; Thermodynamics ; Water/physiology
    Chemical Substances Macromolecular Substances ; Water (059QF0KO0R)
    Language English
    Publishing date 1994-06-21
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1006/jtbi.1994.1122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Extracellular matrix interactions: sulfation of connective tissue polysaccharides creates macroion binding templates and conditions for dissipative structure formation.

    Comper, W D

    Journal of theoretical biology

    1990  Volume 145, Issue 4, Page(s) 497–509

    Abstract: Evidence is now accumulating that the post-polymer modification process of sulfation of connective tissue polysaccharides is primarily to provide an interactive macroion for enthalpic interactions rather than influence thermodynamic non-ideality which ... ...

    Abstract Evidence is now accumulating that the post-polymer modification process of sulfation of connective tissue polysaccharides is primarily to provide an interactive macroion for enthalpic interactions rather than influence thermodynamic non-ideality which primarily affects water distribution in biological systems. Metabolic energy considerations also distinguish these physicochemical classifications. Thermodynamic non-ideality is embodied in the carboxyl group and polysaccharide chain which are energetically favoured in biosynthesis, whereas considerable energy input is required for sulfation. The sulfation process gives rise to macroions, with a wide variety of negative charge patterns, that may participate in heterotypic macromolecular interactions. This partial informational specificity is discussed in terms of evolutionary flexibility of the extracellular matrix as rationalized on the qualitative aspects of dissipative structure formation. The concept of multiple binding interactions of varying specificity associated with connective tissue polysaccharides raises the awareness of a more random, less highly ordered, extracellular matrix as compared to the tight machine-like organization generally found for processes in the cell. This is discussed in terms of the physiological adaptation and development of multicellular-tissue systems.
    MeSH term(s) Animals ; Connective Tissue/metabolism ; Extracellular Matrix/metabolism ; Models, Biological ; Polysaccharides/metabolism
    Chemical Substances Polysaccharides
    Language English
    Publishing date 1990-08-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/s0022-5193(05)80484-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Tubular inhibition destroys charge selectivity for anionic and neutral horseradish peroxidase.

    Osicka, T M / Comper, W D

    Biochimica et biophysica acta

    1998  Volume 1381, Issue 2, Page(s) 170–178

    Abstract: The fractional clearance of [3H]anionic HRP and [3H]neutral HRP in the isolated perfused kidney as determined by radioactivity analysis was 0.0160+/-0.0028 (n=6) and 0.0388+/-0.0076 (n=8) respectively. The apparent charge selectivity for both the anionic ...

    Abstract The fractional clearance of [3H]anionic HRP and [3H]neutral HRP in the isolated perfused kidney as determined by radioactivity analysis was 0.0160+/-0.0028 (n=6) and 0.0388+/-0.0076 (n=8) respectively. The apparent charge selectivity for both the anionic and neutral forms of HRP observed was destroyed with the inclusion of the tubular uptake inhibitors, 150 mM lysine and 10 mM NH4Cl, in the perfusate. In the presence of 150 mM lysine, the clearances of [3H]anionic HRP and [3H]neutral HRP were 0.0645+/-0.0110 (n=4) and 0. 0784+/-0.0120 (n=4) respectively, and 0.0564+/-0.0035 (n=4) and 0. 0694+/-0.0054 (n=4) respectively in the presence of 10 mM NH4Cl. The clearance for both the anionic and neutral HRP probes in these tubular uptake inhibited systems fits precisely the size selective characteristics of the glomerular capillary wall as determined by transport probes calibrated for hydrodynamic size by size exclusion chromatography. The tubular uptake inhibitors were observed not to alter glomerular permselectivity as determined using polydisperse dextran fractions and the behaviour of neutral HRP. This study demonstrates that charge selectivity for differently charged proteins is not as great as originally thought and suggests that the clearance differences between anionic and neutral forms may be due to differential handling by the tubules.
    MeSH term(s) Ammonium Chloride/pharmacology ; Animals ; Biological Transport, Active/drug effects ; Horseradish Peroxidase/chemistry ; Horseradish Peroxidase/pharmacokinetics ; In Vitro Techniques ; Isoelectric Point ; Kidney Tubules/drug effects ; Kidney Tubules/metabolism ; Lysine/pharmacology ; Male ; Perfusion ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Ammonium Chloride (01Q9PC255D) ; Horseradish Peroxidase (EC 1.11.1.-) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 1998-07-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/s0304-4165(98)00025-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Protein degradation during renal passage in normal kidneys is inhibited in experimental albuminuria.

    Osicka, T M / Comper, W D

    Clinical science (London, England : 1979)

    1997  Volume 93, Issue 1, Page(s) 65–72

    Abstract: 1. Tritium labelled proteins, namely bovine serum albumin ([3H]BSA), rat serum albumin ([3H]RSA), anionic horseradish peroxidase ([3H]aHRP) and immunoglobulin present in urine fractions from rat filtration studies in vivo and isolated perfused rat ... ...

    Abstract 1. Tritium labelled proteins, namely bovine serum albumin ([3H]BSA), rat serum albumin ([3H]RSA), anionic horseradish peroxidase ([3H]aHRP) and immunoglobulin present in urine fractions from rat filtration studies in vivo and isolated perfused rat kidneys (IPKs) have been shown by gel chromatographic analysis to be severely degraded to small peptides. The degradation of RSA and BSA in vivo has been shown to be similar. 2. Degradation of proteins in the urine from IPK experiments was inhibited by including 150 mmol/l lysine in the perfusate. Similarly, [3H]BSA and [3H]aHRP excreted from rats with puromycin aminonucleoside nephrosis was again essentially intact for both IPK and in vivo experiments. 3. It appears that the degradation of proteins observed in urine obtained from control kidneys is due, in part, to proteolytic activity associated with the proximal tubule. Inhibition of proximal tubule function, which occurs for both lysine and puromycin aminonucleoside treatments (as calibrated by lysozyme uptake), results in inhibition of the degradation observed. Glomerular epithelial cells could also contribute to the degradation. 4. There was no generation of low-molecular-weight material in the perfusate or plasma arising from breakdown of circulating proteins or recycling of potential degradation products from the tubules.
    MeSH term(s) Albuminuria/metabolism ; Albuminuria/urine ; Animals ; Antimetabolites ; Chromatography ; Horseradish Peroxidase/metabolism ; Immunoglobulins/metabolism ; Kidney/metabolism ; Male ; Molecular Weight ; Nephrosis/metabolism ; Perfusion ; Proteins/metabolism ; Puromycin Aminonucleoside ; Rats ; Rats, Sprague-Dawley ; Serum Albumin/metabolism ; Serum Albumin, Bovine/metabolism
    Chemical Substances Antimetabolites ; Immunoglobulins ; Proteins ; Serum Albumin ; Serum Albumin, Bovine (27432CM55Q) ; Puromycin Aminonucleoside (58-60-6) ; Horseradish Peroxidase (EC 1.11.1.-)
    Language English
    Publishing date 1997-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 760216-9
    ISSN 0143-5221 ; 0144-9664
    ISSN 0143-5221 ; 0144-9664
    DOI 10.1042/cs0930065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A codiffusing system as a novel model for capillary wall charge selectivity.

    Smit, M F / Comper, W D

    Biophysical chemistry

    1996  Volume 62, Issue 1-3, Page(s) 73–80

    Abstract: The electrostatic interaction associated with polyion-polyion interaction has been thought to be the basis for the differential transport of charged transport probes across the capillary wall. The charge of the transport probe may interact with the ... ...

    Abstract The electrostatic interaction associated with polyion-polyion interaction has been thought to be the basis for the differential transport of charged transport probes across the capillary wall. The charge of the transport probe may interact with the negative charges of capillary wall cell surfaces and the intercellular glycocalyx or extracellular matrix. This study has set out to quantitate the exact nature of the polyion-polyion interaction through the theoretical and experimental study of the partition-diffusion of albumin in solutions of anionic polysaccharides (dextran sulfate or heparin) at concentrations up to 250 meq 1(-1) or at an average intercharge distance of 2.2 nm, as compared with solutions of uncharged dextran at the same volume concentration. The results demonstrate that the albumin partition-diffusion is exactly the same in dextran sulfate, heparin and uncharged dextran matrices of the same polymer volume fraction. These results confirm previous studies from this laboratory that the charge effect through polyion-polyion interaction under physiological conditions is negligible.
    MeSH term(s) Albumins/chemistry ; Capillaries/chemistry ; Capillaries/physiology ; Capillaries/ultrastructure ; Computer Simulation ; Dextrans ; Diffusion ; Extracellular Space/chemistry ; Models, Biological ; Polysaccharides ; Solutions
    Chemical Substances Albumins ; Dextrans ; Polysaccharides ; Solutions
    Language English
    Publishing date 1996-11-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 185052-0
    ISSN 1873-4200 ; 0301-4622
    ISSN (online) 1873-4200
    ISSN 0301-4622
    DOI 10.1016/s0301-4622(96)02214-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Protein fragments in urine have been considerably underestimated by various protein assays.

    Greive, K A / Balazs, N D / Comper, W D

    Clinical chemistry

    2001  Volume 47, Issue 9, Page(s) 1717–1719

    MeSH term(s) Albumins/analysis ; Albumins/metabolism ; Albuminuria/complications ; Albuminuria/urine ; Biuret Reaction ; Chromatography, High Pressure Liquid ; Diabetes Complications ; Diabetes Mellitus/urine ; Humans ; Nephelometry and Turbidimetry ; Urinalysis/methods
    Chemical Substances Albumins
    Language English
    Publishing date 2001-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
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  10. Article: Charge selectivity in kidney ultrafiltration.

    Comper, W D / Glasgow, E F

    Kidney international

    1995  Volume 47, Issue 5, Page(s) 1242–1251

    MeSH term(s) Animals ; Capillary Permeability/physiology ; Cell Membrane Permeability/physiology ; Ion Transport/physiology ; Kidney Glomerulus/blood supply ; Kidney Glomerulus/cytology ; Kidney Glomerulus/physiology ; Membrane Potentials
    Language English
    Publishing date 1995-05
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1038/ki.1995.178
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