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Biomedical subjects

Matthias Schmidt

Publications and source records attributed to Matthias Schmidt.

At least 19 recordsLinked to original sources

Wetting, drying, and layering of colloid-polymer mixtures at porous interfaces.

The influence of interface porosity on the wetting properties of colloid-polymer mixtures is studied within density functional theory for the Asakura-Oosawa-Vrij model at the surface of a quenched hard-sphere matrix. While the porosity hardly changes the location of the transition from partial to complete wetting at colloidal bulk gas-liquid coexistence, the onset of wetting, as signaled by the first discontinuous layering transition, can be efficiently controlled by tailoring the porosity. We furthermore find that the penetrability of the porous interface induces complete drying into the matrix upon approaching capillary coexistence.

Journal Article↗

Entropic interfaces in hard-core model amphiphilic mixtures.

We investigate bulk and interfacial properties of a recently proposed hard-body model for a ternary mixture of amphiphilic particles, spheres and needles using density functional theory. The simple model amphiphiles are formed by bonding a vanishingly thin needle tail radially to a hard-sphere head group. Such particles provide a natural amphiphile when added to a binary mixture of spheres and needles. As all interactions are hard, we seek to find whether amphiphilic effects can be driven by entropy without the need to invoke attractive interactions. In order to assess the amphiphilic character of the model we first examine the spatial and orientational distribution of the amphiphiles at the free interface between demixed needle-rich and amphiphile-rich fluid phases of the binary amphiphile-needle subsystem. We then consider the free interface between sphere-rich and needle-rich phases upon adding amphiphiles with low concentration to the demixed system. In both cases the orientational distribution of the particles in the interface provides strong evidence that amphiphilic properties can arise purely from geometrical packing effects.

Journal Article↗

GABA receptor rho subunit expression in the developing rat brain.

Ionotropic GABA(C) receptors are composed of rho1, rho2 and rho3 subunits. Although the distribution of rho subunit mRNAs in the adult brain has been studied, information on the developmental regulation of different rho subunits in the brain is scattered and incomplete. Here, GABA(C) receptor rho subunit expression was studied in the developing rat brain. In situ hybridization on postnatal brain slices showed rho2 mRNA expression from newborn in superficial gray layer (SGL) of superior colliculus (SuC), and from the first postnatal week in the hippocampal CA1 region and pretectal nucleus of the optic tract. rho2 mRNA was also expressed in the adult dorsal lateral geniculate nucleus. Quantitative RT-PCR revealed expression of all three rho subunits in the hippocampus and superior colliculus from the first postnatal day. In the hippocampus, rho2 mRNA expression clearly dominated over rho1 and rho3, whereas in the superior colliculus, rho1 mRNA expression levels were similar to rho2. In both areas, a clear up-modulation of rho2 and rho3 mRNA during the first postnatal week was detected. GABA(C) receptor protein expression was confirmed in adult hippocampus, superior colliculus and dorsal lateral geniculate nucleus by immunohistochemistry. Our results demonstrate for the first time the expression of all three rho subunit mRNAs in several regions of the developing and adult rat brain. Our quantitative data allows assessment of putative subunit combinations in the superior colliculus and hippocampus. From the selective distribution of rho subunits, it may be hypothesized that GABA(C) receptors are specifically involved in aspects of visual image motion processing in the rat brain.

Animals↗

Differences between cation-chloride co-transporter functions in the visual cortex of pigmented and albino rats.

Albinism in mammals is accompanied by specific morphological and functional alterations of the visual system. To understand their cellular basis we studied the physiological characteristics and transmembrane currents of pyramidal neurons in 350-microm-thick slices of visual cortex from pigmented and albino rats using whole-cell and gramicidin perforated patch-clamp recordings. The resting membrane potential was significantly more positive and the rheobase was significantly lower in neurons of layers II/III and V in albinos as compared with pigmented rats. No significant differences were found in the input resistance, time constant and chronaxy. Whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated currents were not significantly different, the maximum gamma-aminobutyric acid (GABA)(A) receptor (GABA(A)R)-mediated currents and miniature inhibitory postsynaptic currents showed significantly lower amplitudes in neurons of layer V in visual cortex of albinos as compared with pigmented rats. The reversal potential of the GABA(A)R-mediated currents (E(GABA)) was significantly shifted to more positive values in albinos. Pharmacological experiments showed that this shift could be caused by an increased action of the inward chloride co-transporter NKCC1 and reduced action of the outward chloride co-transporter KCC2 in albino rats. This difference seems to be restricted to the visual cortex because in pyramidal neurons from frontal cortex E(GABA) was not significantly different in albinos as compared with pigmented rats. These results are discussed in relation to functional alterations in the albino visual system.

Animals↗

Quality control in urinary stone analysis: results of 44 ring trials (1980-2001).

Urinary stone analysis is the most important diagnostic step after stone removal from the body. The methods employed for these analyses are based on diverse analytical principles. Chemical methods are used for detecting individual ions. Infrared spectroscopy is used for examining molecular structures, and X-ray diffraction for determination of the crystalline structure of a substance. Since 1980, a twice-yearly ring trials quality control survey has been on offer to examine the quality of urinary stone analyses. A summary of the results of 44 ring trials (1980-2001) has been compiled for individual pure substances and binary (two-component) mixtures. On average, 100 laboratories have participated in these ring trials. Initially, over 80% of the participants carried out their analyses using chemical methods. In 2001, this figure decreased to a mere 13%. In contrast, a progressive increase in the use of infrared spectroscopy was observed, up to 79% of all participants employed this method. X-Ray diffraction was only employed in a small number of specialised laboratories (5-9%). The chemical methods produced a very high proportion of errors (6.5-94%) with both the pure substances and binary mixtures, whereas high error rates for infrared spectroscopy and X-ray diffraction were confined to individual substances only. Due to the poor results in the ring trials, the majority of laboratories stopped using chemical analysis, which is now considered to be obsolete. Regarding mixtures, error rates of over 10% also occurred with infrared spectroscopy and X-ray diffraction. Ring trials are indispensable for the quality management of urinary stone analysis.

Diagnostic Errors↗

Isotropic-nematic transition of hard rods immersed in random sphere matrices.

Using replica density functional theory and Monte Carlo computer simulations we investigate a system of annealed hard spherocylinders adsorbed in a matrix of quenched hard spheres. Theoretical predictions for the partition coefficient, defined as the ratio of density of rods in the matrix and that in a reservoir, agree well with simulation results. Theory predicts the isotropic-nematic transition to remain first order upon increasing sphere packing fraction, and to shift towards lower rod densities. This scenario is consistent with our simulation results that clearly show a jump in the nematic order parameter upon increasing the rod density at constant matrix packing fraction, corresponding to the isotropic-nematic transition, even for sphere matrix packing fractions < or approximately equal to 0.3.

Journal Article↗

Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow.

Myofibroblasts play a key role in wound closure but their origin is poorly understood. To investigate whether fibrocytes contribute to myofibroblast population, we examined the phenotype of fibrocytes and myofibroblasts present in the wounded skin of BALB/c mice. During wound healing, there was a marked increase in the number of cells expressing the myofibroblast marker alpha-smooth muscle actin in the granulation tissue. Between 4 and 7 days post-wounding, more than 50% of these cells also expressed the CD13 antigen. CD13(+)/collagen I+ fibrocytes could be isolated at an early stage of the healing process from digested fragments of wounded tissue by fluorescence-activated cell sorting. Like authentic fibrocytes, these cells were also CD45(+)/CD34(+)/CD14-. Between 4 and 7 days post-injury, 61.4% of the isolated fibrocytes were found to express alpha-smooth muscle actin gene and protein. We repeated similar experiments in female mice that had received a male whole bone marrow transplant after total body irradiation. By in situ hybridization, we identified the Y chromosome in the nuclei of the majority of fibrocytes isolated from the wounded tissue of these animals. Our data indicate that circulating fibrocytes contribute to the myofibroblast population in the wounded skin and that they originate from the bone marrow.

Animals↗

Spontaneous activity of rat pretectal nuclear complex neurons in vitro.

BACKGROUND: Neurons in the mammalian pretectum are involved in the control of various visual and oculomotor tasks. Because functionally independent pretectal cell populations show a wide variation of response types to visual stimulation in vivo, they may also differ in their intrinsic properties when recorded in vitro. We therefore performed whole-cell patch clamp recordings from neurons in the caudal third of the pretectal nuclear complex in frontal brain slices obtained from 3 to 6 week old hooded rats and tried to classify pretectal neurons electrophysiologically. RESULTS: Pretectal neurons showed various response types to intracellular depolarizations, including bursting and regular firing behavior. One population of pretectal nuclear complex neurons could be particularly distinguished from others because they displayed spontaneous activity in vitro. These cells had more positive resting potentials and higher input resistances than cells that were not spontaneously active. The maintained firing of spontaneously active pretectal cells was characterized by only small variances in interspike intervals and thus showed a regular temporal patterning. The firing rate was directly correlated to the membrane potential. Removing excitatory inputs by blockade of AMPA and/or NMDA receptors did not change the spontaneous activity. Simultaneous blockade of excitatory and inhibitory synaptic input by a substitution of extracellular calcium with cobalt neither changed the firing rate nor its temporal patterning. Each action potential was preceeded by a depolarizing inward current which was insensitive to calcium removal but which disappeared in the presence of tetrodotoxin. CONCLUSIONS: Our results indicate that a specific subpopulation of pretectal neurons is capable of generating maintained activity in the absence of any external synaptic input. This maintained activity depends on a sodium conductance and is independent from calcium currents.

Action Potentials↗

Floating liquid phase in sedimenting colloid-polymer mixtures.

Density functional theory and computer simulation are used to investigate sedimentation equilibria of colloid-polymer mixtures within the Asakura-Oosawa-Vrij model of hard sphere colloids and ideal polymers. When the ratio of buoyant masses of the two species is comparable to the ratio of differences in density of the coexisting bulk (colloid) gas and liquid phases, a stable "floating liquid" phase is found, i.e., a thin layer of liquid sandwiched between upper and lower gas phases. The full phase diagram of the mixture under gravity shows coexistence of this floating liquid phase with a single gas phase or a phase involving liquid-gas equilibrium; the phase coexistence lines meet at a triple point. This scenario remains valid for general asymmetric binary mixtures undergoing bulk phase separation.

Adsorption↗

Density functional theory for sphere-needle mixtures: toward finite rod thickness.

For mixtures of hard spheres and hard spherocylinders of large aspect ratio a recently proposed density functional theory is extended to incorporate effects due to nonvanishing rod thickness. This is accomplished by introducing several new geometric weight functions into the framework. We demonstrate explicitly how these weight functions recover the sphere-rod Mayer bond.

Journal Article↗

Direct visual observation of thermal capillary waves.

We studied the free fluid-fluid interface in a phase-separated colloid-polymer dispersion with laser scanning confocal microscopy and directly observed thermally induced capillary waves at the interface in real space. Experimental results for static and dynamic correlation functions validate the capillary wave model down to almost the particle level. The ultralow interfacial tension, the capillary length, and the capillary time are found to be in agreement with independent measurements. Furthermore, we show that capillary waves induce the spontaneous breakup of thin liquid films and thus are of key importance in the process of droplet coalescence.

Journal Article↗

GABAC receptor mediated inhibition in acutely isolated neurons of the rat dorsal lateral geniculate nucleus.

In the dorsal lateral geniculate nucleus (dLGN), GABA(C) receptors seems to be specifically expressed by local GABAergic interneurons. Although the presence of GABA(C) receptors has been demonstrated, a quantitative estimation of their contribution to inhibition in dLGN is lacking. Because the amount of inhibition mediated by these receptors might reflect their functional importance we performed whole-cell patch clamp recordings from dLGN cells acutely dissociated from brain slices. We focally applied the GABA receptor agonist muscimol and quantified effects mediated through either GABA(C) or GABA(A) receptors. Because their basic dendritic morphology was preserved, we tried to morphologically differentiate between thalamocortical cells and local interneurons. In the majority of multipolar cells, representing thalamocortical projection neurons, the specific GABA(A) receptor antagonist bicuculline completely blocked muscimol induced currents. In contrast, in most of the bipolar cells, representing interneurons, bicuculline blocked only 70-80% of the muscimol induced currents. The remaining currents were blocked by co-application of TPMPA, a specific GABA(C) receptor antagonist, or picrotoxin, an unspecific GABA(A) and GABA(C) receptor blocker. The latter neurons were also sensitive to the selective GABA(C) receptor agonist cis-aminocrotonic acid. These results indicate that in those dLGN neurons that express GABA(C) receptors, these receptors contribute considerably to GABAergic inhibitory inputs.

Animals↗

F-18-FDG uptake is a reliable predictory of functional recovery of akinetic but viable infarct regions as defined by magnetic resonance imaging before and after revascularization.

Identification of akinetic but viable myocardium is important for the selection of patients for coronary revascularization. In order to assess predictive values of end-diastolic wall thickness and dobutamine induced wall thickening obtained by magnetic resonance imaging (MRI) and [18F]Fluorodeoxyglucose uptake assessed by positron emission tomography (F-18-FDG-PET), these parameters were compared to recovery of left ventricular function after successful revascularization. Forty patients with chronic myocardial infarction and regional a- or dyskinesia by ventriculography underwent rest- and dobutamine-MRI studies (10 microg dobutamine/kg body weight/min) and F-18-FDG-PET. Viability of the infarct region was considered to be present if; 1) end-diastolic wall thickness was > or =5.5 mm; 2) dobutamine induced wall thickening > or =2 mm could be measured; and 3) normalized F-18-FDG-uptake was > or =50% in > or =50% of akinetic segments. Preserved end-diastolic wall thickness was found in 32/40 patients, functional improvement during dobutamine infusion in 26/40 patients and preserved F-18-FDG-uptake in 29/40 patients. After revascularization regional left ventricular function improved in 25/40 patients. Positive and negative predictive values and diagnostic accuracy were 78%, 100%, and 83% for preserved end-diastolic wall thickness, 92%, 93%, and 93% for dobutamine inducible contraction reserve and 86%, 100%, and 90% for preserved F-18-FDG-uptake. Quantitative assessment of dobutamine induced systolic wall thickening by MRI and F-18-FDG-uptake by PET are highly accurate techniques for the identification of viable myocardium and prediction of functional recovery after successful revascularization. Preserved end-diastolic wall thickness results in an overestimation of viable myocardium compared to functional improvement, but wall thickness <5.5 mm excludes recovery of regional function.

Adult↗

Determination of the calcium oxalate crystallization risk from urine samples: the BONN Risk Index in comparison to other risk formulas.

PURPOSE: Regular risk evaluation and risk monitoring during stone therapy are recommended measures to ensure reduction of recurrence of crystal formation. This strategy optimizes the patient treatment by a more individual approach and decreases expensive over treatment. We evaluated the BONN Risk Index (BRI) through data actualization and evaluation refinement. The BRI was compared with the most common methods of risk evaluation, namely calculation of relative urinary calcium oxalate (CaOx) supersaturation (RS) and of the urine activity product (AP)CaOx index to estimate the urine AP with respect to CaOx. MATERIALS AND METHODS: A total of 201, 12 and 24-hour urine samples were collected from 95 healthy volunteers and from 106 CaOx stone formers. Crystallization experiments following the BRI method were performed. RS and APCaOx were calculated from urinalysis. Data were indexed and individually grouped into 8 classes, and frequency distributions were plotted. A calculation scheme for the BRI based estimation of the statistical probability of a clinically healthy person being a (still nondetected) CaOx stone former is provided. RESULTS: Logarithmically arranged BRI groups from healthy subject and patient data showed Gaussian frequency distributions. Compared with RS and APCaOx BRI allowed optimum distinction between healthy subjects and stone formers. The healthy subject probability of already being a CaOx stone former strongly increased with increasing BRI. CONCLUSIONS: The BRI for evaluating CaOx crystallization risk allows reliable distinction between healthy subjects and CaOx stone formers. Although RS and APCaOx require much more analytical efforts for determination, their results do not show higher reliability.

Calcium Oxalate↗

Inhibition of superior colliculus neurons by a GABAergic input from the pretectal nuclear complex in the rat.

The mammalian pretectal nuclear complex (PNC) is a visual and visuomotor control structure which is strongly connected to other subcortical visual structures. This indicates that the PNC also controls subcortical visual information flow during the execution of various oculomotor programs. A prominent, presumably GABAergic, projection from the PNC targets the superficial grey layer of the superior colliculus (SC), which itself is a central structure for visual information processing necessary for the generation of saccadic eye movements. In order to characterize the pretectotectal projection in vitro, we performed whole-cell patch-clamp recordings from SC and PNC neurons in slices obtained from 3-6-week-old pigmented rats. Focal glutamate injections into the PNC and electrical PNC stimulation were used to induce postsynaptic responses in SC neurons. Electrical stimulation of the SC allowed electrophysiological identification of PNC neurons that provide the inhibitory pretectotectal input. Only inhibitory postsynaptic currents could be elicited in SC neurons both by pharmacological and by electrical activation of the ipsilateral PNC. Concomitantly, a small number of PNC neurons could be antidromically activated from the ipsilateral SC. Most SC cells postsynaptic to the prectectal input showed the dendritic morphology of wide-field and narrow-field cells and are therefore regarded as projection neurons. All inhibitory currents evoked by PNC activation could be completely blocked by bath application of the selective GABA(A) receptor antagonist bicuculline. Together these results indicate that SC projection neurons receive a direct inhibitory input from the ipsilateral PNC and that this input is mediated by GABA(A) receptors.

Animals↗

Capillary condensation and interface structure of a model colloid-polymer mixture in a porous medium.

We consider the Asakura-Oosawa model of hard sphere colloids and ideal polymers in contact with a porous matrix modeled by immobilized configurations of hard spheres. For this ternary mixture a fundamental measure density functional theory is employed, where the matrix particles are quenched and the colloids and polymers are annealed, i.e., allowed to equilibrate. We study capillary condensation of the mixture in a small sample of matrix as well as demixing and the fluid-fluid interface inside a bulk matrix. Density profiles normal to the interface and surface tensions are calculated and compared to the case without matrix. Two kinds of matrices are considered: (i) colloid-sized matrix particles at low packing fractions and (ii) large matrix particles at high packing fractions. These two cases show fundamentally different behavior and should both be experimentally realizable. Furthermore, we argue that capillary condensation of a colloidal suspension could be experimentally accessible. We find that in case (ii), even at high packing fractions, the main effect of the matrix is to exclude volume and, to high accuracy, the results can be mapped onto those of the same system without matrix via a simple rescaling.

Biophysics↗