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Biomedical subjects

G Knoll

Publications and source records attributed to G Knoll.

At least 19 recordsLinked to original sources

Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression.

We reviewed any study where 10 or more healthy adults donated a kidney, and proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year later. Bibliographic databases were searched until November 2005. 31 primary authors provided additional information. Forty-eight studies from 27 countries followed a total of 5048 donors. An average of 7 years after donation (range 1-25 years), the average 24 h urine protein was 154 mg/day and the average GFR was 86 ml/min. In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0-28%), and 0.2% a GFR less than 30 ml/min (range 0-2.2%). In controlled studies urinary protein was higher in donors and became more pronounced with time (three studies totaling 59 controls and 129 donors; controls 83 mg/day, donors 147 mg/day, weighted mean difference 66 mg/day, 95% confidence interval (CI) 24-108). An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6-15; difference not associated with time after donation (P=0.2)). Kidney donation results in small increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years. Future studies will provide better estimates, and identify those donors at least risk of long-term morbidity.

Adolescent↗

Use of the embedded peritoneal dialysis catheter: experience and results from a North American Center.

Since 2000, the Ottawa Hospital Home Dialysis Program has used a variation on the embedded peritoneal dialysis catheter technique described by Moncrief et al. In this paper, we describe our approach to placement of peritoneal access and report our experience with 304 embedded catheters placed between January 2000 and December 2003. We review the advantages and disadvantages of this technique and describe factors that have been important to the success of our program.

Catheterization↗

Factors associated with publication following presentation at a transplantation meeting.

Full publication of abstracts presented at scientific meetings ranges from 25-74%. To determine the rate and factors associated with publication in organ transplantation, we examined abstracts presented at the American Transplant Congress in May 2000. Of 1147 abstracts, 607 (53%) achieved full publication at 4.5 years (mean 1.32 +/- 0.88 years). Fifty-nine percent (357/607) were published in three transplantation journals. For randomized trials, the proportion published was 61%. On multivariate analysis, industry sponsorship (OR 1.78; 95% CI 1.04-3.06), basic science research (OR 1.68; 95% CI 1.32-2.14), non-American center (OR 1.67; 95% CI 1.28-2.20) and oral presentation (OR 1.36; 95% CI 1.07-1.73) were independent predictors of full publication. Nearly half of all abstracts presented at a transplantation meeting remain unpublished. This finding needs to be considered when interpreting systematic reviews in the field of transplantation.

Congresses as Topic↗

Phosphorus removal and recovery from wastewater by tobermorite-seeded crystallisation of calcium phosphate.

Investigations were focused on the development of a technology for phosphorus (P) recovery straight from wastewater. Facing the finiteness of the natural resources of this essential nutrient, the declared goal must be the sustainable use of available phosphorus sinks such as wastewater treatment plants (WWTP) for the generation of P rock substitutes. A feasible method for simultaneous elimination and recovery of phosphorus from wastewater proved to be the P-RoC process - the phosphorus recovery from wastewater by induced crystallisation of calcium phosphate, applying tobermorite-rich waste compounds of the construction industry. The experiments were performed in fixed bed-, stirred- and expanded bed reactors in laboratory--as well as in pilot-scale experiments. The efficiency and longevity of the P-RoC process was determined by the supply of Ca ions and the initial P concentration. Total P (P-tot) contents in the generated crystallisation products of up to 13% P-tot (30% P2O5) were achieved. Mineralogical investigations proved the formation of a hydroxy-apatite-(HAP)-like coating onto the seed material's surface. Reuse options for the generated crystallisation products, such as substitute for phosphate rock or as new fertiliser, were assessed.

Calcium Compounds↗

Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPA, myfortic).

AIM: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population. METHODS: All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented. RESULTS: Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups. CONCLUSIONS: These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.

Adult↗

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study.

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

Adult↗

Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy.

Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with alpha-actinin or other Z-line components. These results suggest that Cypher functions as a linker-strut to maintain cytoskeletal structure during contraction.

Actinin↗

Spatio-temporal current density reconstruction (stCDR) from EEG/MEG-data.

Among the different approaches to the bioelectromagnetic inverse problem, the current-density reconstruction methods (CDR) provide the most general solutions. Since the inverse problem does not have a unique solution, model assumptions have to be taken into account. Multi-channel measurements contain not only spatial, but also temporal information about the sources, so a naturally extension to existing methods leads to spatio-temporal model constraints. Spatio-temporal CDR's (stCDR) have been tested in simplified volume conductor models, assuming different spatial model constraints and a smooth temporal activation model. Comparison to existing spatial model constraints showed a significant improvement of spatial and temporal resolution of the reconstructed sources for the spatio-temporal models especial in noisy data.

Algorithms↗

Calcium stores in differentiated Dictyostelium discoideum: prespore cells sequester calcium more efficiently than prestalk cells.

Dictyostelium discoideum pseudoplasmodia exhibit a gradient of the cytosolic free Ca2+-concentration ([Ca2+]i) along their anterior-posterior axis involved in cell-type specific differentiation. [Ca2+]i is high in prestalk and low in prespore cells. We determined the content and localization of calcium and other elements in cryosectioned cells of pseudoplasmodia and fruiting bodies by X-ray microanalysis. Granular stores rich in Ca, Mg and P were identified. Average Ca was higher in prespore than prestalk granules (225vs 111 mmol/kg dry weight). Total Ca stored in granules was also higher in prespore than prestalk cells. The amount of P and S in granules differed between the two cell types indicating different store composition. In spores mean granular Ca was 120 mmol/kg dry weight. Stalk cells had smaller granules with 360 mmol Ca/kg dry weight. Complementary to microanalysis, vesicular Ca2+-fluxes were studied in fractionated cell homogenates. The rate of Ca2+-uptake was higher in pellet fractions of prespore than prestalk amoebae (4.7 vs 3.4 nmol/min x mg). Ca2+-release was greater in supernatant fractions from prestalk than prespore cells (16.5vs 7.7 nmol/10(8)cells). In summary, prestalk and prespore cells possess qualitatively different, high-capacity stores containing distinct amounts of Ca and probably being involved in regulation of the anterior-posterior [Ca2+]i-gradient.

Animals↗

The influence of skull-conductivity misspecification on inverse source localization in realistically shaped finite element head models.

The electric conductivities of different tissues are important parameters of the head model and their precise knowledge appears to be a prerequisite for the localization of electric sources within the brain. To estimate the error in source localization due to errors in assumed conductivity values, parameter variations on skull conductivities are examined. The skull conductivity was varied in a wide range and, in a second part of this paper, the effect of a nonhomogeneous skull conductivity was examined. An error in conductivity of lower than 20% appears to be acceptable for fine finite element head models with average discretization errors down to 3 mm. Nonhomogeneous skull conductivities, e.g., sutures, yield important mislocalizations especially in the vincinty of electrodes and should be modeled.

Brain↗

Inverse localization of electric dipole current sources in finite element models of the human head.

The paper describes finite element related procedures for inverse localization of multiple sources in realistically shaped head models. Dipole sources are modeled by placing proper monopole sources on neighboring nodes. Lead field operators are established for dipole sources. Two different strategies for the solution of inverse problems, namely combinatorial optimization techniques and regularization methods are discussed and applied to visually evoked potentials, for which exemplary results are shown. Most of the procedures described are fully automatic and require only proper input preparation. The overall work for the example presented (from EEG recording to visual inspection of the results) can be performed in roughly a week, most of which is waiting time for the computation of the lead field matrix or inverse calculations on a standard and affordable engineering workstation.

Cerebral Cortex↗

cAMP-induced changes in the cytosolic free Ca2+ concentration in Dictyostelium discoideum are light sensitive.

The cytosolic free calcium concentration ([Ca2+]i) of the social amoeba Dictyostelium discoideum was analyzed after challenge with the chemoattractant cAMP. [Ca2+]i was measured by digital imaging in single cells loaded with the Ca2+ indicator Fura-2-dextran. Global stimulation with low concentrations of cAMP (0.1-1 microM) led to a global transient [Ca2+]i increase. This increase was abolished when cells were illuminated with high doses of light. However, after a short recovery period of several minutes, the cells again displayed the normal response. Inhibition of the [Ca2+]i elevation depended on the wavelength of illumination light. We compared the required recovery period of cells irradiated with either 340, 380, 405, 450 or 490 nm at defined intensities. Light of 405 nm had a pronounced effect; 340 nm alone or in combination with 380 nm was also effective, but to a lesser extent, whereas neither 450 nm nor 490 nm inhibited the [Ca2+]i increase, even at very high irradiance. The wavelength dependence matched the absorption spectrum of amoebae grown in darkness that contain a photopigment which seems to be responsible for phototaxis of single cells. Cells grown in darkness exhibited an increased sensitivity of the cAMP-induced [Ca2+]i transient towards light compared to light-grown cells. From these data we conclude that phototactic signaling could interfere with chemotactic signaling at the level of [Ca2+]i changes.

Animals↗

Calcium-sequestering organelles of Dictyostelium discoideum: changes in element content during early development as measured by electron probe X-ray microanalysis.

Starving Dictyostelium discoideum amoebae aggregate within a few hours by chemotaxis towards the attractant cAMP to form a multicellular organism. The differentiating cells possess rapid and efficient calcium buffering and sequestration systems which enable them to restrict changes in the cytosolic free calcium concentration temporally and spatially during their chemotactic reaction and allow the continuous accumulation of Ca2+ during development. In order to identify and to characterize calcium storage compartments, we analyzed the element content of amoebae at three consecutive stages of differentiation. Determination of the element distribution was done using energy-dispersive X-ray microanalysis of freeze-dried cryosections of rapid-frozen cells. Amoebae were frozen in the vegetative and aggregation-competent state and after formation of aggregates. Aggregation-competent as well as aggregated cells contained mass dense granules with large amounts of calcium together with phosphorous and either potassium or magnesium: in aggregation-competent cells calcium was colocalized with potassium, whereas in aggregated cells the mass dense granules contained calcium and magnesium. Although mass dense granules were also present in undifferentiated, vegetative cells, they contained only low amounts of phosphorous and potassium together with little Ca and Mg. We conclude that during their differentiation D. discoideum cells use an intracellular storage compartment to sequester Ca and other cations constantly throughout development.

Animals↗

Challenge with high concentrations of cyclic AMP induces transient changes in the cytosolic free calcium concentration in Dictyostelium discoideum.

Dictyostelium discoideum cells use cyclic AMP (cAMP) for chemotactic signaling as well as for differentiation. The precise regulation of the cytosolic Ca2+ concentration ([Ca2+]i) seems to play a key role for both processes. We performed single cell measurements of [Ca2+]i in amoebae that were starved in suspension for various times and scrape-loaded with the Ca2+ indicator fura-2. Stimulation of cells with cAMP at the concentration required to induce gene expression (> or = 100 microM) elicited a global transient increase in [Ca2+]i that depended on the presence of external Ca2+. Both vegetative and aggregation-competent cells displayed a rise in [Ca2+]i, with aggregation-competent cells responding more often than vegetative cells. Basal [Ca2+]i in the presence of Ca2+ was high in vegetative cells and declined during development; the cAMP-induced rise in [Ca2+]i was higher and lasted longer in vegetative cells than in aggregative cells. The addition of 2'-deoxy-cAMP, which binds to the cAMP receptor, induced an increase in [Ca2+]i, whereas the membrane-permeant analogue 8-bromo-cAMP that has a low affinity for the receptor but activates cAMP-dependent protein kinase had no effect. This indicates that the change in [Ca2+]i is mediated by the cell surface cAMP receptor. Since HC85 mutant cells, which lack the G alpha 2 subunit of the G-protein that couples the receptor to phospholipase C, also responded to stimulation with cAMP, the Ca2+ influx does not seem to be triggered by the phosphoinositide signaling cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

A calcium influx is neither strictly associated with nor necessary for exocytotic membrane fusion in Paramecium cells.

Exocytosis of trichocysts in Paramecium cells was generally believed to depend on extracellular Ca, since it is accompanied by a Ca influx and not seen in the absence of Ca. However, by short term removal of Ca we showed recently that only extrusion of secretory contents, but not membrane fusion after stimulation with aminoethyldextran (AED), depends on extracellular Ca. We have now extended these studies to longer times and shown that membrane fusion is stimulated by AED even after 1 min at low Ca (< or = 30 nM). At prolonged times membrane fusion was induced by sole removal of Ca. In the presence of AED, trichocyst contents were slowly extruded followed by resealing of the fused membranes, indicating independency of endocytotic membrane fusion from extracellular Ca (though we observed aberrant resealing). Later on, Ca removal is followed by cell death. By using videomicroscopy, we further provide the first evidence that exocytosis is not necessarily accompanied by an influx of Ca in the presence of the usual high concentrations (1 mM), since local exocytosis at the rear end of the cells is not followed by ciliary reversal which is triggered by Ca influx. We conclude that a Ca influx is neither regularly associated with, nor necessary for, induction of exocytotic membrane fusion in Paramecium cells. As a source for a possible alternative intracellular liberation of calcium during exocytosis, we analyzed the subplasmalemmal alveolar sac system by electron spectroscopic imaging and found indications for Ca redistributions shortly after stimulation.

Animals↗

Antiglomerular basement membrane antibody-mediated nephritis with normal pulmonary and renal function. A case report and review of the literature.

Antiglomerular basement membrane (anti-GBM) antibody-mediated disease is usually characterized by a rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. We report a case of anti-GBM-mediated nephritis that presented with hematuria and proteinuria. There was no evidence of renal insufficiency or pulmonary hemorrhage. Clinicians should be aware of this rare presentation of anti-GBM-mediated nephritis.

Adult↗

A cortical phosphoprotein ('PP63') sensitive to exocytosis triggering in Paramecium cells. Immunolocalization and quenched-flow correlation of time course of dephosphorylation with membrane fusion.

We had previously shown that a phosphoprotein of 63 kDa ('PP63') is rapidly and selectively dephosphorylated during synchronous (less than or equal to 1 s) trichocyst exocytosis in Paramecium cells and then rephosphorylated within less than or equal to 1 min [Zieseniss & Plattner (1985) J. Cell Biol. 101, 2028-2035]. Using a new quenched-flow device, we now find a strict correlation between PP63 dephosphorylation and the process of membrane fusion, both occurring within 80 ms. Uptake of 32P over 90 min, followed by exocytosis and rephosphorylation for 1 min, results in a rather selective phosphorylation of the dephosphorylated form, P63, to PP63. Solubilization by repeated freezing and thawing allows isolations of P63 and PP63. On isoelectric focusing autoradiograms they have pI values of 6.05, 5.95 (major spots), 5.85 and 5.75. All spots are sensitive to alkaline, but not to acidic, hydrolysis (except for the pI-6.05 spot). On two-dimensional-gel autoradiograms the most prominent spot, of pI 5.95, is most extensively de- and re-phosphorylated. This spot, from de- and re-phosphorylated samples, was used to produce monospecific antibodies. A cortical localization of PP63 was revealed by producing Western blots from isolated cell-surface fragments ('cortices') and by immunofluorescence labelling. We assume that both P63 and PP63 are attached to cortical structures, e.g. around trichocysts, though they are partly soluble. This localization and the strict correlation of PP63 dephosphorylation with exocytotic membrane fusion suggests a role in fusion regulation.

Animals↗