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1.
J Phys Condens Matter ; 30(4): 045901, 2018 Jan 31.
Article in English | MEDLINE | ID: mdl-29214983

ABSTRACT

The formation of a localized surface plasmon resonance (SPR) spectrum of randomly distributed gold nanoparticles in the surface layer of silicate float glass, generated and implanted by UV ArF-excimer laser irradiation of a thin gold layer sputter-coated on the glass surface, was studied by the T-matrix method, which enables particle agglomeration to be taken into account. The experimental technique used is promising for the production of submicron patterns of plasmonic nanoparticles (given by laser masks or gratings) without damage to the glass surface. Analysis of the applicability of the multi-spheres T-matrix (MSTM) method to the studied material was performed through calculations of SPR characteristics for differently arranged and structured gold nanoparticles (gold nanoparticles in solution, particles pairs, and core-shell silver-gold nanoparticles) for which either experimental data or results of the modeling by other methods are available. For the studied gold nanoparticles in glass, it was revealed that the theoretical description of their SPR spectrum requires consideration of the plasmon coupling between particles, which can be done effectively by MSTM calculations. The obtained statistical distributions over particle sizes and over interparticle distances demonstrated the saturation behavior with respect to the number of particles under consideration, which enabled us to determine the effective aggregate of particles, sufficient to form the SPR spectrum. The suggested technique for the fitting of an experimental SPR spectrum of gold nanoparticles in glass by varying the geometrical parameters of the particles aggregate in the recurring calculations of spectrum by MSTM method enabled us to determine statistical characteristics of the aggregate: the average distance between particles, average size, and size distribution of the particles. The fitting strategy of the SPR spectrum presented here can be applied to nanoparticles of any nature and in various substances, and, in principle, can be extended for particles with non-spherical shapes, like ellipsoids, rod-like and other T-matrix-solvable shapes.

2.
Leukemia ; 31(5): 1117-1122, 2017 05.
Article in English | MEDLINE | ID: mdl-27909342

ABSTRACT

Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0.0001). RIPA was impaired in patients receiving concomitant antiplatelet therapy or anticoagulation (14 vs 25 U, P=0.005). A gradual decline of median RIPA values was observed with increasing bleeding severity. Importantly, no CTC grade 2 or 3 bleeding were observed with RIPA values of >36 U. Sequential monitoring indicated a decrease of RIPA values from a median of 17 to 9 U within 2 weeks after initiation of treatment as well as an increase above the critical threshold of 36 U within 7 days when ibrutinib was paused. Low RIPA values were similar during treatment with another BTK inhibitor, CC292. Quantitative assessment of platelet function is a practical tool to monitor bleeding tendency under BTK-inhibitor therapy.


Subject(s)
Hemorrhage/chemically induced , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Platelet Aggregation/drug effects , Pyrazoles/adverse effects , Pyrimidines/adverse effects , Ristocetin/pharmacology , Adenine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Drug Monitoring/methods , Female , Hemorrhage/drug therapy , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Middle Aged , Piperidines , Protein Kinase Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage
4.
J Thromb Haemost ; 12(6): 948-57, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24702774

ABSTRACT

BACKGROUND: Urokinase-type plasminogen activator (u-PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. Interleukin (IL)-33 is a member of the IL-1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL-33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells. OBJECTIVE: We investigated the impact of IL-33 on u-PA in endothelial cells as a new possible function for IL-33. METHODS AND RESULTS: We could demonstrate that IL-33 upregulated u-PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time- and concentration-dependent manner via interaction with its receptor ST2 and activation of the nuclear factor-κB pathway but independent of autocrine IL-1-induced effects. The hydroxymethylglutaryl-coenzyme A reductase inhibitor simvastatin abrogated the IL-33-induced increase in u-PA, thus providing further evidence for pleiotropic effects of statins. IL-33 induced u-PA-dependent capillary-like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u-PA mRNA positively correlated with IL-33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL-33 and u-PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry. CONCLUSIONS: We hypothesize that IL-33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u-PA-driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies.


Subject(s)
Angiogenesis Inducing Agents/pharmacology , Endothelial Cells/drug effects , Interleukins/pharmacology , Neovascularization, Physiologic/drug effects , Urokinase-Type Plasminogen Activator/metabolism , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/genetics , Carotid Artery Diseases/metabolism , Carotid Artery Diseases/pathology , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/enzymology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/enzymology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Interleukin-1 Receptor-Like 1 Protein , Interleukin-33 , Interleukins/genetics , Interleukins/metabolism , NF-kappa B/metabolism , Plaque, Atherosclerotic , RNA Interference , RNA, Messenger/metabolism , Receptors, Cell Surface/agonists , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Recombinant Proteins/pharmacology , Signal Transduction/drug effects , Simvastatin/pharmacology , Time Factors , Transfection , Up-Regulation , Urokinase-Type Plasminogen Activator/genetics
5.
Liver Transpl ; 18(6): 671-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22298465

ABSTRACT

There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL-28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL-28B genotyping for identifying HCV recipients at risk for severe HCV recurrence.


Subject(s)
Hepatitis C, Chronic/genetics , Interleukins/genetics , Interleukins/immunology , Liver Transplantation/immunology , Postoperative Complications/genetics , Viral Load/immunology , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Disease Progression , Female , Genotype , Graft Survival/immunology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/mortality , Humans , Interferons , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/virology , Predictive Value of Tests , Recurrence , Retrospective Studies , Risk Factors , Survival Analysis , Young Adult
6.
J Magn Reson ; 208(1): 156-62, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21106419

ABSTRACT

Residual second moment of dipolar interactions M(2) and correlation time segmental dynamics distributions were measured by Hahn-echo decays in combination with inverse Laplace transform for a series of unfilled and filled EPDM samples as functions of carbon-black N683 filler content. The fillers-polymer chain interactions which dramatically restrict the mobility of bound rubber modify the dynamics of mobile chains. These changes depend on the filler content and can be evaluated from distributions of M(2). A dipolar filter was applied to eliminate the contribution of bound rubber. In the first approach the Hahn-echo decays were fitted with a theoretical relationship to obtain the average values of the (1)H residual second moment and correlation time <τ(c)>. For the mobile EPDM segments the power-law distribution of correlation function was compared to the exponential correlation function and found inadequate in the long-time regime. In the second approach a log-Gauss distribution for the correlation time was assumed. Furthermore, using an averaged value of the correlation time, the distributions of the residual second moment were determined using an inverse Laplace transform for the entire series of measured samples. The unfilled EPDM sample shows a bimodal distribution of residual second moments, which can be associated to the mobile polymer sub-chains (M(2) ≅ 6.1 rad (2) s(-2)) and the second one associated to the dangling chains M(2) ≅ 5.4 rad(2) s(-2)). By restraining the mobility of bound rubber, the carbon-black fillers induce diversity in the segmental dynamics like the apparition of a distinct mobile component and changes in the distribution of mobile and free-end polymer segments.


Subject(s)
Algorithms , Magnetic Resonance Spectroscopy/methods , Models, Chemical , Soot/analysis , Soot/chemistry , Computer Simulation , Protons
7.
Biometals ; 19(5): 513-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16937257

ABSTRACT

Structural identity between a recombinant transferrin mutant (N413Q, N611Q) secreted from Saccharomyces cerevisiae and the native protein was shown by CD analysis and immunodiffusion assays against anti-hSTf. The ability of the recombinant protein to bind iron was confirmed by urea-PAGE and EPR analysis of the iron-saturated protein revealed the characteristic holo-transferrin spectrum, indicating conservation of both iron-binding sites. The integrity of the unglycosylated recombinant protein indicates that such protein could be a valuable tool not only for structure-function characterisation but also crystallisation assays. In addition, the recombinant transferrin was found to be as effective as native transferrin as a growth factor in cell culture medium.


Subject(s)
Transferrin/metabolism , Cell Proliferation , Electron Spin Resonance Spectroscopy , Glycosylation , Humans , Precipitin Tests , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/genetics , Spectrum Analysis , Transferrin/chemistry , Transferrin/genetics
8.
Kidney Int ; 68(6): 2497-507, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16316326

ABSTRACT

BACKGROUND: Unilateral loss of kidney function is followed by compensatory contralateral growth. The early, genome-wide transcriptional response of the untouched kidney to unilateral ureteral obstruction (UUO) or unilateral nephrectomy is unknown. METHODS: Twelve adult male Sprague-Dawley rats were subjected to UUO and twelve rats to unilateral nephrectomy. At time points 12, 24, and 72 hours after insult four rats each were sacrificed and the contralateral kidney harvested for genome-wide gene expression analysis, transcription factor analysis, and histomorphology. RESULTS: Microarray studies revealed that the majority of differentially expressed transcripts were suppressed in UUO and unilateral nephrectomy compared to control kidneys. The function of these suppressed genes is predominantly growth inhibition and apoptosis suggesting a net pro-hypertrophic response. Insulin-like growth factor-2 (IGF-2)-binding protein was one of the few activated genes. We observed a distinctly different molecular signature between UUO and unilateral nephrectomy at the three time points investigated. The early response in UUO rats suggests a counterbalance to the nonfiltering kidney by activation of transport pathways such as the aquaporins. Unilateral nephrectomy kidneys, on the other hand, respond immediately to contralateral nephrectomy by activation of cell cycle regulators such as the cyclin family. Several genes with weakly defined function were found to be associated with either UUO or unilateral nephrectomy. Transcription factor analysis of the identified transcripts suggests common regulation at least of some of these genes. All kidneys showed normal histology. CONCLUSION: Release of growth inhibition by nephrectomy leads to immediate cell cycle activation after unilateral nephrectomy, whereas UUO kidneys counterbalance filtration failure by activation of several transporters.


Subject(s)
Hydronephrosis/genetics , Hydronephrosis/physiopathology , Kidney/physiology , Oligonucleotide Array Sequence Analysis , Transcriptional Activation/physiology , Animals , Carrier Proteins/genetics , Insulin-Like Growth Factor II/genetics , Kidney/surgery , Male , Nephrectomy , Rats , Rats, Sprague-Dawley , Transcription Factors/genetics , Ureteral Obstruction/genetics , Ureteral Obstruction/physiopathology
9.
Z Orthop Ihre Grenzgeb ; 143(6): 660-8, 2005.
Article in German | MEDLINE | ID: mdl-16380899

ABSTRACT

INTRODUCTION: Repair of large skeletal defects using bone allografts has become a routine procedure in orthopaedic and trauma surgery. Different procedures of sterilisation (82.5 degrees C disinfection; 121 degrees C autoclaving; PES; Tutoplast; 25 kGy gamma irradiation) are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone allografts. The efficiency of these procedures has been proven. However, the effects on the cellular response are rarely investigated. This present in vitro study investigates the immunological answer of human bone marrow cells to human allogenous and autologous bone platelets which were sterilised by different methods. MATERIALS AND METHODS: Human bone marrow cells and the bone platelets were harvested from patients undergoing a total hip replacement. All patients provided informed consent. Human bone platelets, 10 mm in diameter, 3 mm in height, were produced from femoral heads which were removed within the scope of total hip replacements. They were sterilised by different procedures or were disinfected (gamma radiotherapy, PES/ethanol treatment, Tutoplast procedure, 121 degrees C autoclaving, > 82.5 degrees C thermodisinfection). In addition, an autologous in vitro bone donation was simulated and compared with the allogenous bone grafts. Endobon was evaluated as a bovine hydroxyapatite ceramic. As control a human bone marrow cell culture without bone platelets was used. Over a period of four weeks the changes of the immunogenic cell populations were analysed in vitro (FACS analysis). Light and scanning microscopy were done to reveal morphological differences. As a vitality test the trypan-blue staining was performed. RESULTS: Light and scanning microscopy demonstrated large differences between the various sterilisation and disinfection methods. After 4 weeks the autologous bone platelets were completely covered with homogenously distributed human osteoblast like cells. The heat-sterilised/disinfected transplants demonstrated similar effects compared to the autologous bone grafts while the irradiated bone platelets demonstrated less cell coverage. 2/3 of the cells were vital on average after four weeks, with the exception of the irradiated bone platelets. The FACS analysis revealed in comparison to the control group provable differences in the immunological answer for the autologous bone donation as well as for the differently sterilised or disinfected allogenous bone grafts. The heat sterilisation or, respectively, disinfection methods compared to the autologous bone donation demonstrated almost similar in vitro effects. By far the worst results, characterised by an excessively increased portion of cytotoxic T-cells and a decreased amount of viable cells, were seen in the 25 kGy gamma irradiation samples. CONCLUSIONS: The results demonstrate the influence of the different sterilisation and disinfection procedures on the differentiation of human marrow cells (host). Similar in vitro effects were seen for the autologous and heat-treated bone platelets. The treatment of allogenous bone grafts with PES/ethanol and the Tutoplast procedures showed, just as Endobon, only low differences in comparison with the control cultures. The worse results in the case of the irradiated bone platelets may be explained by the production of free radicals which led to an excessive cell death.


Subject(s)
Blood Platelets/immunology , Bone Marrow Cells/immunology , Bone Transplantation/immunology , Sterilization/methods , Transplantation, Autologous/immunology , Transplantation, Homologous/immunology , Blood Platelets/pathology , Bone Marrow Cells/pathology , Bone Marrow Transplantation/immunology , Cell Communication/immunology , Cell Differentiation , Cells, Cultured , Disinfection , Humans , Immunologic Factors/immunology
10.
Am J Transplant ; 4(10): 1595-604, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15367214

ABSTRACT

Recipients of live donor transplant kidneys (LIV) exhibit a significantly longer allograft half-life compared with cadaveric donor organs (CADs). The reasons are incompletely understood. Therefore this study sought to elucidate the genome-wide gene expression profiles in microdissected transplant kidney biopsies obtained from five cadaveric and five matched live donors before transplantation. cDNA microarrays were used to determine the transcripts in isolated glomeruli (G) and the tubulointerstitial (TI) compartment. Data were subjected to hierarchical clustering, maxT adjustment and a jackknife procedure to ensure robustness of reported findings; validation was performed by independent analysis of split biopsies and TaqMan-PCR. One hundred and thirteen sequences representing 62 unique genes (17 redundant features), and 34 ESTs separated G from TI. No difference in gene expression was found in G between LIV and CAD kidneys, but nine genes (two represented twice) and three ESTs were abundantly expressed in the CAD TI compared with LIV. The main biological function of these genes is counter regulation of oxidative stress. Promoter analysis of significant features suggested coregulated gene groups. These data suggest that CAD kidneys exhibit a distinctly different set of transcripts in the TI compartment but not in the G compartment when compared with LIV kidneys.


Subject(s)
Gene Expression/physiology , Kidney Transplantation , Kidney/physiology , Oxidative Stress , Transplants , Cadaver , Gene Expression Profiling , Humans , Kidney Glomerulus/physiology , Living Donors , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic
11.
Lab Invest ; 84(3): 353-61, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14704720

ABSTRACT

Roughly 25% of cadaveric, but rarely living donor renal transplant recipients, develop postischemic acute renal failure, which is a main risk factor for reduced long-term allograft survival. An accurate prediction of recipients at risk for ARF is not possible on the basis of donor kidney morphology or donor/recipient demographics. We determined the genome-wide gene-expression pattern using cDNA microarrays in three groups of 36 donor kidney wedge biopsies: living donor kidneys with primary function, cadaveric donor kidneys with primary function and cadaveric donor kidneys with biopsy proven acute renal failure. The descriptive genes were characterized in gene ontology terms to determine their functional role. The validation of microarray experiments was performed by real-time PCR. We retrieved 132 genes after maxT adjustment for multiple testing that significantly separated living from cadaveric kidneys, and 48 genes that classified the donor kidneys according to their post-transplant course. The main functional roles of these genes are cell communication, apoptosis and inflammation. In particular, members of the complement cascade were activated in cadaveric, but not in living donor kidneys. Thus, suppression of inflammation in the cadaveric donor might be a cheap and promising intervention for postischemic acute renal failure.


Subject(s)
Kidney Transplantation/physiology , Acute Kidney Injury/prevention & control , Adult , Aged , Biopsy , Cadaver , Gene Expression Profiling , Graft Survival/genetics , Humans , Inflammation/prevention & control , Living Donors , Middle Aged , Oligonucleotide Array Sequence Analysis , Tissue Donors
12.
Eur J Vasc Endovasc Surg ; 27(2): 167-71, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14718899

ABSTRACT

OBJECTIVES: Neurological deficit defines the outcome of Carotid Endarterectomy (CEA) that is mainly caused by cerebral ischemia. Diffusion-weighted imaging (DWI) is a sensitive method for demonstrating even small ischemic lesions. The aim of this study was to evaluate the frequency, clinical significance and course of ischemic lesions after CEA using serial DWI. METHODS: DWI was performed within 1 day before and after CEA in 88 patients. Postoperative lesions were analyzed by their quantity, volume and distribution. To differentiate temporary ischemia from definite cerebral infarction (blood brain barrier disruption) all patients with a positive postoperative DWI were reexamined with contrast-enhanced T1-MRI 7-10 days after the procedure. All patients were examined by a neurologist within 2 days before and after CEA. RESULTS: Two patients showed a postoperative neurological deficit. Postoperative DWI revealed ipsilateral ischemic lesions in 15 patients. In seven of these patients a brain infarction was diagnosed on the T1-MRI during follow-up. A significant correlation between the number of DWI lesions (p=0.031) as well as the volume of DWI lesions (p=0.023) and definite infarction was found. Symptomatic patients preoperatively showed significantly more DWI lesions (p=0.036) and cerebral infarcts (p=0.003). CONCLUSION: DWI is a sensitive method of demonstrating ischemic events after CEA. The number and volume of DWI lesions after CEA are highly predictive of brain infarction.


Subject(s)
Cerebral Infarction/diagnosis , Diffusion Magnetic Resonance Imaging , Endarterectomy, Carotid , Ischemic Attack, Transient/diagnosis , Postoperative Complications/diagnosis , Aged , Brain/pathology , Female , Humans , Male
13.
Transplantation ; 76(4): 715-20, 2003 Aug 27.
Article in English | MEDLINE | ID: mdl-12973116

ABSTRACT

BACKGROUND: About 30% of cadaveric renal allografts, but almost never living-donor kidneys, develop postischemic acute renal-transplant failure (ARF). We therefore quantified the expression of essential reperfusion regulators in different compartments of cadaveric and living-donor kidney biopsies. METHODS: Specimens were obtained from donor kidneys at the end of the cold ischemia time before implantation and categorized into three groups according to donor source and early posttransplant function. Ten living-donor biopsies (LIV) were compared with nine cadaveric kidney biopsies (CAD) with primary posttransplant function (CAD-PF) and to nine with ARF (CAD-ARF). Laser capture microdissection was used to isolate glomeruli from tubulointerstitium. The gene expression of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1beta, endothelin (ET)-1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) was quantified in glomeruli and tubulointerstitium by real-time polymerase chain reaction (TaqMan). RESULTS: Tubulointerstitial areas of all CAD kidneys revealed significantly lower mRNA levels of all investigated genes compared with LIV. Tubulointerstitial ET-1, iNOS, and eNOS in CAD-ARF averaged only half of the expression in CAD-PF kidneys. ICAM-1 and IL-1beta mRNA concentrations were equal in CAD-PF and CAD-ARF. Glomerular expression of the investigated genes was equal in CAD and LIV kidneys with the exception of ICAM-1 and ET-1, which were two times higher in CAD-PF compared with LIV and CAD-ARF. CONCLUSION: These data suggest that CAD compared with LIV kidneys have an impaired expression of immune and vasoregulatory genes in the tubulointerstitium, which may represent reduced cellular vitality and capacity to adaptation. The observed further reduction of ET-1, iNOS, and eNOS expression in CAD-ARF might contribute to reperfusion injury and delayed allograft function.


Subject(s)
Acute Kidney Injury/metabolism , Endothelin-1/genetics , Ischemia/metabolism , Kidney/blood supply , Nitric Oxide Synthase/genetics , Tissue Donors , Adult , Biopsy , Gene Expression , Humans , Intercellular Adhesion Molecule-1/genetics , Interleukin-1/genetics , Kidney/metabolism , Middle Aged , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , RNA, Messenger/analysis , Transplantation, Homologous
14.
J Speech Lang Hear Res ; 45(6): 1285-96, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12546494

ABSTRACT

Classical temporal integration (TI) is often viewed as a frequency-dependent, energy-based detection process. Detection thresholds for brief sinusoidal increments in either a fixed-level or a random-level broadband pedestal are reported that refute this traditional perspective of TI, Instead, evidence is presented that indicates (a) detection of absolute energy is not necessary for the TI effect and (b) the frequency dependence of TI is consistent with variations across frequency in peripheral auditory tuning, rather than the integration process per se. When peripheral frequency selectivity is controlled, TI can be explained by a frequency-invariant integration process over at least the frequency range from 500 to 4,000 Hz. This process is characterized by threshold improvements of 8-9 dB per decade increase in duration for increment durations between 10 and 300 ms.


Subject(s)
Cues , Hearing/physiology , Adult , Audiometry, Pure-Tone/methods , Auditory Threshold/physiology , Humans , Models, Biological , Perceptual Masking/physiology
15.
J Acoust Soc Am ; 110(4): 2065-84, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11681385

ABSTRACT

The perceptual significance of the cochlear amplifier was evaluated by predicting level-discrimination performance based on stochastic auditory-nerve (AN) activity. Performance was calculated for three models of processing: the optimal all-information processor (based on discharge times), the optimal rate-place processor (based on discharge counts), and a monaural coincidence-based processor that uses a non-optimal combination of rate and temporal information. An analytical AN model included compressive magnitude and level-dependent-phase responses associated with the cochlear amplifier, and high-, medium-, and low-spontaneous-rate (SR) fibers with characteristic frequencies (CFs) spanning the AN population. The relative contributions of nonlinear magnitude and nonlinear phase responses to level encoding were compared by using four versions of the model, which included and excluded the nonlinear gain and phase responses in all possible combinations. Nonlinear basilar-membrane (BM) phase responses are robustly encoded in near-CF AN fibers at low frequencies. Strongly compressive BM responses at high frequencies near CF interact with the high thresholds of low-SR AN fibers to produce large dynamic ranges. Coincidence performance based on a narrow range of AN CFs was robust across a wide dynamic range at both low and high frequencies, and matched human performance levels. Coincidence performance based on all CFs demonstrated the "near-miss" to Weber's law at low frequencies and the high-frequency "mid-level bump." Monaural coincidence detection is a physiologically realistic mechanism that is extremely general in that it can utilize AN information (average-rate, synchrony, and nonlinear-phase cues) from all SR groups.


Subject(s)
Basilar Membrane/physiology , Cochlea/physiology , Cochlear Nerve/physiology , Loudness Perception/physiology , Nerve Fibers/physiology , Pitch Discrimination/physiology , Audiometry, Pure-Tone , Dominance, Cerebral/physiology , Evoked Potentials, Auditory/physiology , Humans , Nonlinear Dynamics , Psychoacoustics
16.
Neural Comput ; 13(10): 2273-316, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11570999

ABSTRACT

A method for calculating psychophysical performance limits based on stochastic neural responses is introduced and compared to previous analytical methods for evaluating auditory discrimination of tone frequency and level. The method uses signal detection theory and a computational model for a population of auditory nerve (AN) fiber responses. The use of computational models allows predictions to be made over a wider parameter range and with more complete descriptions of AN responses than in analytical models. Performance based on AN discharge times (all-information) is compared to performance based only on discharge counts (rate-place). After the method is verified over the range of parameters for which previous analytical models are applicable, the parameter space is then extended. For example, a computational model of AN activity that extends to high frequencies is used to explore the common belief that rate-place information is responsible for frequency encoding at high frequencies due to the rolloff in AN phase locking above 2 kHz. This rolloff is thought to eliminate temporal information at high frequencies. Contrary to this belief, results of this analysis show that rate-place predictions for frequency discrimination are inconsistent with human performance in the dependence on frequency for high frequencies and that there is significant temporal information in the AN up to at least 10 kHz. In fact, the all-information predictions match the functional dependence of human performance on frequency, although optimal performance is much better than human performance. The use of computational AN models in this study provides new constraints on hypotheses of neural encoding of frequency in the auditory system; however, the method is limited to simple tasks with deterministic stimuli. A companion article in this issue ("Evaluating Auditory Performance Limits: II") describes an extension of this approach to more complex tasks that include random variation of one parameter, for example, random-level variation, which is often used in psychophysics to test neural encoding hypotheses.


Subject(s)
Cochlear Nerve/physiology , Hearing/physiology , Models, Neurological , Pitch Discrimination/physiology , Animals , Humans , Psychophysics
17.
Neural Comput ; 13(10): 2317-38, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11571000

ABSTRACT

Previous studies have combined analytical models of stochastic neural responses with signal detection theory (SDT) to predict psychophysical performance limits; however, these studies have typically been limited to simple models and simple psychophysical tasks. A companion article in this issue ("Evaluating Auditory Performance Limits: I") describes an extension of the SDT approach to allow the use of computational models that provide more accurate descriptions of neural responses. This article describes an extension to more complex psychophysical tasks. A general method is presented for evaluating psychophysical performance limits for discrimination tasks in which one stimulus parameter is randomly varied. Psychophysical experiments often randomly vary a single parameter in order to restrict the cues that are available to the subject. The method is demonstrated for the auditory task of random-level frequency discrimination using a computational auditory nerve (AN) model. Performance limits based on AN discharge times (all-information) are compared to performance limits based only on discharge counts (rate place). Both decision models are successful in predicting that random-level variation has no effect on performance in quiet, which is the typical result in psychophysical tasks with random-level variation. The distribution of information across the AN population provides insight into how different types of AN information can be used to avoid the influence of random-level variation. The rate-place model relies on comparisons between fibers above and below the tone frequency (i.e., the population response), while the all-information model does not require such across-fiber comparisons. Frequency discrimination with random-level variation in the presence of high-frequency noise is also simulated. No effect is predicted for all-information, consistent with the small effect in human performance; however, a large effect is predicted for rate-place in noise with random-level variation.


Subject(s)
Cochlear Nerve/physiology , Hearing/physiology , Models, Neurological , Pitch Discrimination/physiology , Animals , Humans
18.
Am J Physiol Regul Integr Comp Physiol ; 281(1): R346-51, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11404311

ABSTRACT

This study was designed to further examine the role of plasma ANG II in the excretion of sodium in the Pekin duck, a bird with salt glands. Renal and extrarenal (salt gland) excretion of an intravenously administered isotonic saline load was monitored over a 4-h period in a group of eight birds under two conditions: the control condition, in which isotonic saline infusion decreased endogenous plasma ANG II from 102.6 to 16.5 pg/ml, and the experimental condition, in which ANG II suppression was prevented by intravenous infusion of a 3.5 ng. kg(-1). min(-1) dose of synthetic ANG II. ANG II infusion significantly decreased the total sodium excretion (by 15%), primarily via an inhibition of salt gland output. The results suggest that ANG II suppression facilitates the excretion of an administered sodium load in birds with salt glands.


Subject(s)
Angiotensin II/blood , Kidney/physiology , Salt Gland/physiology , Sodium/blood , Sodium/urine , Vasoconstrictor Agents/blood , Angiotensin II/pharmacology , Animals , Ducks , Female , Male , Natriuresis/drug effects , Natriuresis/physiology , Osmolar Concentration , Urine , Vasoconstrictor Agents/pharmacology
19.
J Acoust Soc Am ; 109(2): 648-70, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11248971

ABSTRACT

A phenomenological model was developed to describe responses of high-spontaneous-rate auditory-nerve (AN) fibers, including several nonlinear response properties. Level-dependent gain (compression), bandwidth, and phase properties were implemented with a control path that varied the gain and bandwidth of tuning in the signal-path filter. By making the bandwidth of the control path broad with respect to the signal path, the wide frequency range of two-tone suppression was included. By making the control-path filter level dependent and tuned to a frequency slightly higher than the signal-path filter, other properties of two-tone suppression were also included. These properties included the asymmetrical growth of suppression above and below the characteristic frequency and the frequency offset of the suppression tuning curve with respect to the excitatory tuning curve. The implementation of this model represents a relatively simple phenomenological description of a single mechanism that underlies several important nonlinear response properties of AN fibers. The model provides a tool for studying the roles of these nonlinearities in the encoding of simple and complex sounds in the responses of populations of AN fibers.


Subject(s)
Cochlear Nerve/physiology , Nerve Fibers/physiology , Nonlinear Dynamics , Audiometry, Pure-Tone , Auditory Pathways/physiology , Basilar Membrane/physiology , Humans , Models, Biological , Sound , Synaptic Transmission/physiology
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