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Biomedical subjects

M Kollmann

Publications and source records attributed to M Kollmann.

At least 19 recordsLinked to original sources

Quantitative data generation for systems biology: the impact of randomisation, calibrators and normalisers.

Systems biology is an approach to the analysis and prediction of the dynamic behaviour of biological networks through mathematical modelling based on experimental data. The current lack of reliable quantitative data, especially in the field of signal transduction, means that new methodologies in data acquisition and processing are needed. Here, we present methods to advance the established techniques of immunoprecipitation and immunoblotting to more accurate and quantitative procedures. We propose randomisation of sample loading to disrupt lane correlations and the use of normalisers and calibrators for data correction. To predict the impact of each method on improving the data quality we used simulations. These studies showed that randomisation reduces the standard deviation of a smoothed signal by 55% +/- 10%, independently from most experimental settings. Normalisation with appropriate endogenous or external proteins further reduces the deviation from the true values. As the improvement strongly depends on the quality of the normaliser measurement, a criteria-based normalisation procedure was developed. Our approach was experimentally verified by application of the proposed methods to time course data obtained by the immunoblotting technique. This analysis showed that the procedure is robust and can significantly improve the quality of experimental data.

Algorithms↗

Variations in substitution rate in human and mouse genomes.

We present a method to quantify spatial fluctuations of the substitution rate on different length scales throughout genomes of eukaryotes. The fluctuations on large length scales are found to be predominantly a consequence of a coarse-graining effect of fluctuations on shorter length scales. This is verified for both the mouse and the human genome. We also found that the relative standard deviation of fluctuations in substitution rate is about a factor three smaller in mouse than in human. The method allows furthermore to determine time-resolved substitution rate maps of the genomes, where the corresponding autocorrelation functions quantify the velocity of spatial chromosomal reorganization.

Animals↗

Dynamic scaling and freezing criteria in quasi-two-dimensional dispersions.

We report on a Brownian dynamics simulation study of quasi-two-dimensional dispersions of colloidal spheres interacting by long-range electrostatic and dipolar magnetic forces. The calculated dynamic correlation functions are shown to obey dynamic scaling in terms of a characteristic relaxation time related to the mean particle distance and, due to hydrodynamic interactions, to the particle size. The dynamical freezing criterion of Löwen [Phys. Rev. E 53, R29 (1996)] is shown to be equivalent to a two-dimensional static freezing criterion.

Journal Article↗

Caging of a d-dimensional sphere and its relevance for the random dense sphere packing.

We analyze the caging of a hard sphere (i.e., the complete arrest of all translational motions) by randomly distributed static contact points on the sphere surface for arbitrary dimension d>/=1, and prove that the average number of uncorrelated contacts required to cage a sphere is (d)=2d+1. Computer simulations, which confirm this analytical result, are also used to model the effect of correlations between contacts that occur in real hard-sphere systems. Our analysis predicts an average coordination number of 4.79 (+/-0.02) for caged spheres, which agrees surprisingly well with the experimental coordination number for random sphere packings reported by Mason [Nature 217, 733 (1968)]. This result supports the physical picture that the coordination number in random dense sphere packings is primarily determined by caging effects. It also suggests that it should be possible to construct such packings from a local caging rule.

Journal Article↗

Molybdenum balance studies in premature male infants.

UNLABELLED: Despite the fact that the trace element molybdenum (Mo) is essential, there is insufficient knowledge about the demands in infancy. Mo balances were therefore assessed under consideration of formula Mo concentrations ranging from 0.125 to 2.704 micromol/l. Sixteen premature male infants participated in the investigation. Their birth weights were between 1,500 and 1,990 g, the median (range) gestational age was 34 (32-36) weeks and the post-conceptual age at the time of study 37.4 (34.1-40.6) weeks. Twenty-four balance studies were performed and the materials analysed by atomic absorption spectroscopy. Infants with a "low" Mo intake received 0.024 (0.020-0.035) micromol/ kg per day, had a urinary excretion of 0.02 (0.008-0.045) and a retention of 0.0006 (-0.03 to 0.008) micromol/kg per day. Infants with a "high" intake received 0.284 (0.227-0.487) micromol/kg per day, had a urinary excretion of 0.243 (0.118-0.378) and a retention of 0.022 (-71.1 to 141.44) micromol/kg per day. Since the median urinary excretion exceeded 60% of the Mo intake at low and high intakes, sufficient resorption but minimal retention was assessed at low intakes of Mo. CONCLUSION: In view of the limited knowledge of long-term exposure to an elevated molybdenum intake and the substantial retention observed at higher intakes, upper limits should be set for molybdenum concentrations in preterm infant formulas.

Humans↗

Breathers and multibreathers in a periodically driven damped discrete nonlinear Schrödinger equation.

We study an integrable discretization of the nonlinear Schrödinger equation (NLS) under the effects of damping and periodic driving, from the point of view of spatially localized solutions oscillating in time with the driver's frequency. We locate the equilibrium states of the discretized (DNLS) system in the plane of its dissipation gamma and forcing amplitude H parameters and use a shooting algorithm to construct the desired solutions psi(n)(t)=phi(n) exp(it) as homoclinic orbits of a four-dimensional symplectic map in the complex phi(n),phi(n+1) space, for -infinity<n<infinity. We derive, in the gamma=0 case, closed form expressions for two fundamental such solutions having a single hump in n, psi(n)+, and psi(n)-, and determine analytically their threshold of existence in the (gamma,H) plane using Mel'nikov's theory. Then, we demonstrate numerically that above this threshold a remarkable variety of multihump structures appear, whose complexity in terms of their spatial extrema grows with increasing H. All these solutions are numerically found to be unstable in time, except for psi(n)-, which is seen to be stable over a certain region in the (gamma,H) plane. In the continuum limit our results are in close agreement with recent studies on the NLS equation. From a more general perspective, we view these DNLS multihump solutions as homoclinic orbits of a higher-dimensional map thereby providing a possible mechanism for explaining the occurrence of similar structures called discrete (multi-) breathers found in a wide variety of one-dimensional nonlinear lattices.

Journal Article↗

The hyperkeratotic variant of porokeratosis Mibelli is a distinct entity: clinical and ultrastructural evidence.

An isolated case with the hyperkeratotic variant of porokeratosis Mibelli (PM) is reported. The 62-year-old woman developed multiple brown macules with well demarcated large keratotic nodules on both legs. Histopathological studies revealed the presence of a cornoid lamella characteristic of porokeratosis. Ultrastructural investigations revealed dyskeratotic as well as edematous, swollen keratinocytes; autophagocytotic vacuoles were visible. The clinical and ultrastructural peculiarities of the hyperkeratotic variant of PM suggest the possibility of a separate entity.

Administration, Topical↗

Unusual coexistence of systemic lupus erythematosus and primary biliary cirrhosis.

Systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are distinct clinical disorders which rarely occur in the same patient. We report on a 65-year-old woman with coexistence of both conditions. Diagnosis of SLE was ascertained by the presence of seven ACR criteria (cutaneous lesions, photosensitivity, antinuclear and anti-double-stranded-DNA antibodies, pancytopenia, arthritis, oral lesions). PBC was disclosed by clinical investigation, liver histology and highly positive antimitochondrial M2 antibodies. The most important differential diagnoses of lupus hepatitis are PBC and autoimmune hepatitis. Diagnostic criteria for these conditions are discussed, and previous reports on overlap between SLE and PBC are reviewed.

Aged↗

[Endophthalmitis. Importance of microbiologic studies for therapy and prognosis].

The fast and precise identification of infectious agents and their characterization is of upmost importance for the diagnosis and therapy of infectious endophthalmitis. A preliminary estimate of the most probable predominant agents may improve the choice of an adequate antimicrobial therapy prior to definitive microbiological analysis in culture media. A prospective study was performed in 46 patients with endophthalmitis. During surgery mostly undiluted samples were inoculated in 10 different culture media. Microscopic investigation and laboratory processing were performed within the next 10-120 min. A presumptive classification based on immediate direct microscopy and a preliminary recommendation on treatment were achieved in 25 cases. Culture yielded positive results in 38 cases (83%). In 8 cases the inoculates remained negative. Most of the positive cultures (92%) contained only gram-positive bacteria, including 10 cases of mixed gram-positive infections. In 2 samples bacteria and fungi were present, while 2 contained fungi only. Of 8 posttraumatic eyes, 4 were infected with Bacillus spp. The results show that specific therapeutic approaches are required. Direct inoculation of surgical culture media combined with immediate microscopic investigation permits a fast and precise microbiological diagnosis.

Adolescent↗

Lack of immunoglobulin A1 protease production by Haemophilus ducreyi.

A collection of 20 strains of Haemophilus ducreyi including freshly isolated, low-passage and multi-passage reference strains was examined for immunoglobulin A1 protease production by SDS-PAGE and immunoblotting. None of the strains demonstrated IgA1 protease activity despite the fact that different culture media were used. By direct immunofluorescence testing, binding of IgA to Haemophilus ducreyi organisms could be demonstrated.

Blotting, Western↗

Absence of extracellular enzyme activity and cytotoxicity in cell-free culture filtrates of Haemophilus ducreyi.

Ten isolates of Haemophilus ducreyi, including seven clinical isolates and three laboratory reference strains, were assessed for their ability to produce extracellular enzymes which might contribute to their pathogenicity. Protease, elastase, lecithinase, lipase or collagenase enzyme activity were not detected in culture filtrates from any of the isolates tested using either plate or spectrophotometrical assays. Furthermore, cell-free culture filtrates did not exhibit cytotoxic activity in vitro when tested using either an established tissue culture cell line (Vero) or a primary cell culture of human keratinocytes. These results suggest that extracellular products do not play a role in host invasion or production of tissue damage by H. ducreyi.

Cell-Free System↗

[Quitting--reentering].

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Education, Professional, Retraining↗

[Fundus hemorrhage in malaria tropica].

The case is presented of a 20-year-old tourist with mild falciparum malaria and bilateral preretinal and intraretinal hemorrhage, including a macular hemorrhage with reversible visual loss, which developed during his return flight from West Africa. The diagnosis was initiated by the university eye hospital originally consulted. Possible pathogenic mechanisms, ocular findings in malaria, and the increasing problems of imported malaria are summarized and reviewed.

Adult↗

Selenium-75-labeled sucralfate: comparison with other radiolabels and initial clinical studies.

Sucralfate was synthesized to include a 75Se label, then compared with 111In-sucralfate and 99mTc-Human serum albumin (HSA)-sucralfate in vitro and in an animal ulcer model. The 75Se label was the only one of the three that was stable in both human gastric juice and simulated intestinal fluid in vitro. In rats with gastric ulcers, ulcer:nonulcer ratios of bound radioactivity averaged 15.4, 6.3, and 5.6 for 75Se, 111In, and 99mTc-HSA labels, respectively. Biodistribution studies of 75Se-sucralfate indicated that little is absorbed from the gastrointestinal tract, and the distribution is similar to that of 14C-sucralfate. Selective binding of 75Se sucralfate was successfully imaged in patients with esophagitis (esophageal mean T1/2 binding = 65 +/- 32 min), gastritis (gastric mean T 1/2 binding = 118 +/- 34 min), and gastric ulcers (ulcer mean T 1/2 binding = 135 +/- 59 min). Duodenal ulcers were not successfully imaged. Normal subjects showed no abnormal localization of sucralfate, and esophageal and gastric clearances were rapid.

Adult↗

Binding properties of 111In-diethylenetriaminepentaacetic acid (DTPA)-fragment E1,2, a fibrin-specific probe, are dependent on use of protecting complex during attachment of DTPA groups.

Fragments E1 and E2, plasmic degradation products of crosslinked fibrin, bind specifically to polymers of fibrin. A mixture of these fragments, denoted as fragment E1,2, was radiolabeled with 111In after covalently attaching metal chelating groups (diethylenetriaminepentaacetic acid, DTPA) to the fragment, using two approaches. In the first approach, DTPA groups were attached directly to purified fragment E1,2. In the second approach, attachment sites of DTPA groups were directed away from the active region of the molecule by having fragment E1,2 bound in complex, with its active sites protected during the derivatization. Direct attachment of DTPA groups to fragment E1,2 resulted in complete loss of binding to fibrin in vitro. When derivatized in complex, 111In-DTPA-fragment E1,2 retained a higher degree of binding to human fragment DD and human plasma clots in vitro than did radioiodinated fragment E1, even when up to eight DTPA groups were attached per molecule of fragment E1,2.

Fibrin Fibrinogen Degradation Products↗

[The long path to psychotherapy. On the "patient career" of psychoneurotic and psychosomatic patients].

Among other factors the prognosis of psychoneurotic and psychosomatic disorders depends upon how soon after the onset of the symptoms a specific psychotherapeutic treatment is initiated. A group of one hundred test subjects, selected at random from among the patients admitted for treatment at a special clinic, was used to determine the factors responsible for the duration of the so-called careers of these patients. Contrary to what was expected it turned out that particularly three factors correlate positively with a speedy admission to psychotherapy. Thus younger psychoneurotic or psychosomatic patients, patients who in their own conception consider their disorder to be psychogenic, and patients in whom psychic or psychosomatic complaints have caused an impairment of their function at work, are the ones who are admitted to psychotherapy relatively soon after the first manifestation of their complaints. It must be noted that none of these three factors is explanatory for any of the others.

Adolescent↗