Search PubMed⌕ Search

Biomedical subjects

Matthias Schmidt

Publications and source records attributed to Matthias Schmidt.

52 records · Page 3Linked to original sources

Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma.

The mechanisms contributing to airway wall remodeling in asthma are under investigation to identify appropriate therapeutic targets. Bronchial myofibroblasts would represent an important target because they play a crucial role in the genesis of subepithelial fibrosis, a characteristic feature of the remodeling process, but their origin is poorly understood. We hypothesized that they originate from fibrocytes, circulating cells with the unique characteristic of expressing the hemopoietic stem cell Ag CD34 and collagen I. In this study we show that allergen exposure induces the accumulation of fibrocyte-like cells in the bronchial mucosa of patients with allergic asthma. These cells are CD34-positive; express collagen I and alpha-smooth muscle actin, a marker of myofibroblasts; and localize to areas of collagen deposition below the epithelium. By tracking labeled circulating fibrocytes in a mouse model of allergic asthma, we provide evidence that fibrocytes are indeed recruited into the bronchial tissue following allergen exposure and differentiate into myofibroblasts. We also show that human circulating fibrocytes acquire the myofibroblast phenotype under in vitro stimulation with fibrogenic cytokines that are produced in exaggerated quantities in asthmatic airways. These results indicate that circulating fibrocytes may function as myofibroblast precursors and may contribute to the genesis of subepithelial fibrosis in asthma.

Allergens↗

Depth of olfactory sulcus and olfactory function.

The aim of this study was to identify whether the depth of the olfactory sulcus relates to olfactory function in healthy subjects. Forty-four healthy, male volunteers (age range 22-45 years, mean age 28.3 years) were included in this study. Olfactory function was measured for phenyl ethyl alcohol odor thresholds, odor discrimination, and odor identification. Magnetic resonance imaging of the olfactory sulcus was performed immediately following olfactometry. Based on previous investigations the depth of the olfactory sulcus was measured in the plane of the posterior tangent through the eyeballs. Olfactory function correlated significantly with left-sided depth of the olfactory sulcus (r(44)=0.33, P=0.03); no such correlation was seen for the right side. In addition, olfactory sulcus depth was found to be significantly deeper on the right compared to the left side (t=5.61, P<0.001). The present results suggest that there is small, but significant relation between morphological brain structures and measures of olfactory function. Further, lateralization of olfactory sulcus depth may correlate to functional lateralization in the olfactory system. Thus, it may be carefully speculated that sensory input in the olfactory system results in cortical growth in the area of the olfactory sulcus, at least at some developmental stage.

Adult↗

The alteration of urine composition due to stone material present in the urinary tract.

OBJECTIVES: Based on a recently introduced mathematical model approach we show that uroliths located in the urinary tract (UT) can substantially deplete the urinary concentrations of lithogenic constituents by continuous growth. METHODS: To illustrate the influence of the urinary depletion effect on urinalysis, a "typical" calcium oxalate (CaOx) stone former, presently not stone-free, was investigated. Serum and urine samples were analyzed. Several metabolic tests were performed. Crystallization risk according to the BONN-Risk-Index (BRI) and the relative supersaturation in respect to CaOx (RS(CaOx)) were determined. X-ray films taken before and after a period of six months were evaluated in order to estimate stone size and average stone growth rate taken place within that period. RESULTS: Regarding CaOx urolithiasis the urine samples show a pathologically altered pH, a low 24h-citric acid excretion, and a low 24h-urine volume. Neither calcium nor oxalate excretion data reflect values indicating these substances as risk factors. However, BRI and RS(CaOx) reflect a high crystallization risk. The patient's intestinal oxalate absorption is high. Applying the depletion model, the patient's 24h-urine composition shifts from normooxaluric to hyperoxaluric. CONCLUSION: In the patient, a hitherto undetected hyperoxaluria is diagnosed when in-vivo stone growth is taken into account. This is a clear indication that the metabolic status can only be evaluated correctly in "stone-free" patients. Any stone material present in the UT must be considered in urinalysis interpretation as the stone-related urinary depletion effect is of high clinical relevance. A helpful nomogram is presented, allowing the estimation of the extent of urinary depletion caused by CaOx uroliths.

Adult↗

Voriconazole treatment of presumptive disseminated Aspergillus infection in a child with acute leukemia.

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.

Acute Disease↗

GABAC receptors in the rat superior colliculus and pretectum participate in synaptic neurotransmission.

In mammals, GABA(C) receptors seem to be specifically expressed in the retina and the subcortical visual system, with highest extraretinal expression levels in the superior colliculus (SC). Although its presence in the superficial SC has been demonstrated physiologically, a direct involvement of this receptor type in fast synaptic neurotransmission still awaits verification. We addressed the question of a possible synaptic localization of GABA(C) receptors by performing in vitro whole-cell patch-clamp recordings of inhibitory postsynaptic currents (IPSCs) in single neurons of the rat SC and the neighboring pretectal nuclear complex, where GABA(C) receptors are also expressed at significant levels. To increase the likelihood to record IPSCs we induced spontaneous activity by application of the potassium channel blocker 4-aminopyridine (4-AP) and blocked glutamate-mediated excitatory neurotransmission with kynurenic acid. All 4-AP-induced postsynaptic currents were of synaptic origin because they were completely suppressed by lidocaine or by substitution of extracellular calcium with cobalt. In 40% of the SC cells and in 60% of the pretectal neurons, IPSCs in the presence of 4-AP and kynurenic acid were only partly blocked by the selective GABA(A) receptor antagonist bicuculline. Inhibitory currents that were insensitive to bicuculline, however, could be blocked by coapplication of either the specific GABA(C) receptor antagonist 1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid or picrotoxin, an unselective GABA(A) and GABA(C) receptor antagonist. We conclude that GABA(C) receptors are, at least partially, located synaptically in SC and pretectal neurons in the rat, which indicates a direct function of this receptor type for synaptic processing in both structures.

4-Aminopyridine↗

Increased capacity for synthesis of the D1 protein and of catalase at low temperature in leaves of cold-hardened winter rye (Secale cereale L.).

The effect of low temperature on protein synthesis, particularly the synthesis of the photolabile proteins D1 of photosystem II and catalase (EC 1.11.1.6), was compared in non-hardened leaves (NHL) and cold-hardened leaves (CHL) of winter rye (Secale cereale L.). At 4 degrees C, both the uptake of L-[(35)S]methionine into leaf sections and its incorporation into proteins were reduced, relative to 25 degrees C. However, much lower reductions were observed in CHL than in NHL. In particular, the proportion of the L-[(35)S]methionine uptake incorporated into membrane proteins at 4 degrees C was considerably higher in CHL than in NHL. At 25 degrees C, the incorporation of L-[(35)S]methionine into both the D1 protein and catalase was lower in CHL than in NHL, in accord with a slower light-induced turnover in CHL. At 4 degrees C, the incorporation into the D1 protein and catalase was, however, much higher in CHL than in NHL, indicating that their de novo synthesis was less suppressed by the low temperature. The results indicate that cold-acclimated leaves had an improved ability to repair the photolabile proteins D1 and catalase at low temperature, relative to NHL. mRNAs for the D1 protein and for leaf catalase were not increased in CHL, relative to NHL. The superior capacity of CHL for repair at low temperature must result from posttranscriptional mechanisms. The translational efficiency of the catalase mRNA was similarly increased in both NHL and CHL during 7-h exposures to high light at 4 degrees C, while the amounts of the catalase transcript declined under these conditions. However, during a recovery period at 22 degrees C, subsequent to an exposure of NHL to 4 degrees C and high light, transient increases of the D1 and catalase mRNAs were observed.

Adaptation, Physiological↗

Density-functional theory for fluids in porous media.

As models for substances adsorbed within amorphous solid matrices, we consider mixtures of spheres with either hard or ideal interactions where several (matrix) components are quenched and the remaining (adsorbate) components are equilibrated. We propose a density-functional theory, based on the exact zero-dimensional limit, which treats both matrix and adsorbate components on the level of the respective one-body density profiles. As a test, we calculate pair correlation functions for hard spheres adsorbed in either a hard sphere or an ideal sphere matrix, and find good agreement with our computer simulation results.

Journal Article↗

Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas.

Paragangliomas or glomus tumours of the head and neck region are rare somatostatin receptor-expressing neuroendocrine tumours. Precise preoperative diagnosis is of special importance in order to adequately weigh the potential benefit of the operation against the inherent risks of the procedure. In this study, the clinical value of somatostatin receptor imaging was assessed in 19 patients who underwent somatostatin receptor scintigraphy because of known or suspected paraganglioma of the head and neck region. The results were compared with the results of computed tomography and/or magnetic resonance imaging, histology and clinical follow-up. [(111)In-DTPA- D-Phe(1)]-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 140-220 MBq (111)In-octreotide. Whole-body and planar images as well as single-photon emission tomography images were acquired and lesions were graded according to qualitative tracer uptake. Somatostatin receptor imaging was positive in nine patients, identifying paragangliomas for the first time in three patients and recurrent disease in six patients. In one patient, a second, previously unknown paraganglioma site was identified. Negative results were obtained in ten patients. These patients included one suffering from chronic hyperplastic otitis externa, one with granuloma tissue and an organised haematoma, one with an acoustic neuroma, one with an asymmetric internal carotid artery, two with ectasia of the bulbus venae jugularis and one with a jugular vein thrombosis. In two patients with a strong family history of paraganglioma, individual involvement could be excluded. In only one patient did somatostatin receptor imaging and magnetic resonance imaging yield false negative results in respect of recurrent paraganglioma tissue. It is concluded that somatostatin receptor scintigraphy provides important information in patients with suspected paragangliomas of the head and neck region and has a strong impact on further therapeutic management.

Adolescent↗

Colloidal rod-sphere mixtures: fluid-fluid interfaces and the Onsager limit.

Using a geometry-based density functional theory we investigate the free interface between demixed bulk fluid phases of a colloidal mixture of hard spheres and vanishingly thin needles. Results are presented for the spatial and orientational density distributions of the particles, as well as for the interface tension. Density profiles display oscillations on the sphere-rich side of the interface provided the sphere liquid phase is on the oscillatory side of the Fisher-Widom line in the bulk phase diagram. Needles tend to align parallel (perpendicular) to the interface on the needle-rich (sphere-rich) side displaying biaxial (uniaxial) order. Furthermore, we generalize the theory to the Onsager limit for interacting rods, and give explicit expressions for the functional in simple geometries.

Journal Article↗

Demixing of colloid-polymer mixtures in poor solvents.

The influence of poor solvent quality on fluid demixing of a model mixture of colloids and nonadsorbing polymers is investigated using density functional theory. The colloidal particles are modeled as hard spheres and the polymer coils as effective interpenetrating spheres that have hard interactions with the colloids. The solvent is modeled as a two-component mixture of a primary solvent, regarded as a background theta solvent for the polymer, and a cosolvent of point particles that are excluded from both colloids and polymers. Cosolvent exclusion favors overlap of polymers, mimicking the effect of a poor solvent by inducing an effective attraction between polymers. For this model, a geometry-based density functional theory is derived and applied to bulk fluid phase behavior. With increasing cosolvent concentration (worsening solvent quality), the predicted colloid-polymer demixing binodal shifts to lower colloid concentrations, promoting demixing. For sufficiently poor solvent, a reentrant demixing transition is predicted at low colloid concentrations.

Journal Article↗

Do effective interactions depend on the choice of coordinates?

A common approach to complex systems such as colloidal suspensions or polymer solutions describes the mesoscopic behavior using effective interactions. These potentials act between the macromolecular entities and can be derived by integrating out the microscopic degrees of freedom. The remaining macroparticle coordinates need to be chosen a priori. Two obvious choices are (i) the centers of mass and (ii) distinct microscopic entities, such as special "tagged" monomers. Here we compare both in the framework of the Asakura-Oosawa colloid-ideal polymer mixture. Using computer simulations, we find that although the effective pair interaction between colloid and polymer differ markedly, correlation functions are in fair agreement.

Journal Article↗

Colloids, polymers, and needles: demixing phase behavior.

We consider a ternary mixture of hard colloidal spheres, ideal polymer spheres, and rigid vanishingly thin needles, which model stretched polymers or colloidal rods. For this model, we develop a geometry-based density functional theory, apply it to bulk fluid phases, and predict demixing phase behavior. In the case of no polymer-needle interactions, two-phase coexistence between colloid-rich and colloid-poor phases is found. For hard needle-polymer interactions, we predict rich phase diagrams, exhibiting three-phase coexistence, and reentrant demixing behavior.

Journal Article↗

Post-transcriptional mechanisms control catalase synthesis during its light-induced turnover in rye leaves through the availability of the hemin cofactor and reversible changes of the translation efficiency of mRNA.

The enzyme catalase is light-sensitive. In leaves, losses caused by photoinactivation are replaced by new enzyme and the rate of de novo synthesis must be rapidly and flexibly attuned to fluctuating light conditions. In mature rye leaves, post-transcriptional mechanisms were shown to control the rate of catalase synthesis. The amount of the leaf catalase (CAT-1) transcript did not increase with light intensity, but was even higher after dark exposure of light-grown leaves. Initiation was apparently not limiting translation in the dark, as the association of the Cat1 mRNA with polysomes did not change notably under different light conditions. By analysing the translation of catalase polypeptides in cell-free systems with poly(A)+ RNA from leaves or with mRNA transcribed from a Cat1-containing cDNA clone, two mechanisms of post-transcriptional control were identified. First, translation of catalase depended on the presence of hemin. In leaves, the availability of hemin may signal the extent of catalase degradation as the hemin of the inactivated enzyme is recycled. Second, the translation efficiency of the Cat1 transcripts was reversibly modulated in a dose-dependent manner by the light intensity to which leaves were exposed, prior to extraction. The Cat1 mRNA from light-exposed leaves was translated much more efficiently than mRNA from dark-exposed leaves. The increase of its translation activity in vivo was not blocked by cordycepin but was suppressed by methylation inhibitors, indicating a reversible modification of pre-existing mRNA by methylation. Translation of in vitro synthesized Cat1 mRNA required a methylated cap (m7GpppG), but was virtually below detection when it contained an unmethylated cap (GpppG).

Catalase↗

Intranasal volume and olfactory function.

The aim of this exploratory study was to identify the volume intranasal segments as they relate to parameters of olfactory function. Fifty healthy male volunteers (age range 22-59 years, mean age 28.5 years) were included. Olfactory function was measured by lateralized phenyl ethyl alcohol odor thresholds and odor discrimination, and by bilateral odor identification. Magnetic resonance imaging of the nasal cavity was performed immediately following olfactometry. To correlate the results of olfactometry with intranasal volume, each nasal cavity was divided into 11 segments. Significant correlations were found between the odor thresholds and volumes of the anterior part of the lower and upper meatus of the right nasal cavity. These results reveal that two nasal segments are important for inter-individual differences of odor thresholds in healthy subjects: (i) the segment in the upper meatus below the cribriform plate and (ii) the anterior segment of the inferior meatus. The latter finding is of special interest for nasal surgery, which allows modification of this volume through resection of the inferior turbinate and/or septoplasty.

Adult↗

Freezing transition of hard hyperspheres.

We investigate the system of D-dimensional hard spheres in D-dimensional space, where D>3. For the fluid phase of these hyperspheres, we generalize scaled-particle theory to arbitrary D and furthermore use the virial expansion and the Percus-Yevick integral equation. For the crystalline phase, we adopt cell theory based on elementary geometrical assumptions about close-packed lattices. Regardless of the approximation applied, and for dimensions as high as D=50, we find a first-order freezing transition, which preempts the Kirkwood second-order instability of the fluid. The relative density jump increases with D, and a generalized Lindemann rule of melting holds. We have also used ideas from fundamental-measure theory to obtain a free energy density functional for hard hyperspheres. Finally, we have calculated the surface tension of a hypersphere fluid near a hard smooth (hyper-)wall within scaled-particle theory.

Journal Article↗

First case of trisomy 13 plus mosaic trisomy 1q.

OBJECTIVES: In a case with severe sonographic abnormalities followed by missed abortion in week 14 + 5 days, cytogenetic analysis was performed on placental tissue. A mosaic karyotype 47,XY,+13,add(1)(q44)[3]/47,XY, +13[9]/46,XY[36] was detected. The purpose of the present study was to characterize the additional material on chromosome 1q. METHODS: According to GTG banding, the additional material on chromosome 1 was most probably chromosome 1 material. Thus, multicolor banding analysis using a chromosome 1 specific probe set was done to precisely describe the rearranged chromosome 1. RESULTS: Molecular cytogenetic approaches revealed that the derivative chromosome 1 was der(1)(1p36.3-->1q44::1q12-->1q44). CONCLUSIONS: This is the first description of a case with a trisomy 13 plus a partial trisomy 1q presenting with clinical signs of both aberrations. Moreover, the multicolor banding technique is suited to resolve complex karyotypes in the prenatal diagnosis, i.e., chromosome preparations of fibroblasts.

Abortion, Missed↗