Search PubMed⌕ Search

Biomedical subjects

C Koch

Publications and source records attributed to C Koch.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sulphation of the salivary mucin MG1 (MUC-5B) is not correlated to the degree of its sialylation and is unaffected by cystic fibrosis.

Defective acidification of intracellular organelles, particularly the trans-Golgi network, has been proposed to explain the decreased sialylation and increased sulphation of secreted proteins in cystic fibrosis (CF). To test this hypothesis we compared expression of sulphate and sialic acid on three salivary mucins namely MG1 (MUC-5B), MG2 (MUC-7) and GL. Proteins in whole mouth saliva (WMS) from four individuals were separated by fast protein liquid chromatography (FPLC) on a Superdex 200 column and the partially purified mucins slot-blotted and assayed for sulphate content by staining with Alcian Blue. Sulphation varied with the individual and with the mucin: MG1 was the most sulphated and contributed almost the entire sulphate content of WMS. These results allowed us to test small volumes of WMS from 20 CF patients and age- and sex-matched controls for estimates of sulphate content on MG1. Wherever possible sulphate on MG1 was also visualised by staining washed SDS-PAGE gels with Alcian Blue at pH 1.0. To assess the sialic acid content of salivary mucins, electroblots of SDS-PAGE gels were probed with labelled Triticum vulgaris agglutinin. In summary, our results show MG1 to be the main sulphated protein in whole mouth saliva and there are large differences in the expression of sulphate and of sialic acid on this mucin, both in control and CF groups. CF led neither a decrease in sialylation nor an increase in sulphation and direct comparisons of sialic acid content with sulphate in MG1 failed to reveal any obvious link between the two in health or in disease. Our data thus do not support the hypothesis of defective acidification as the underlying cause of altered glycosylation in CF, but point instead to inter-individual differences in expression/functioning of terminal glycosyltransferases for published observations. We thank the European Union Biomed II programme for support.

Acids↗
PubMed2001

Altered sialyl- and fucosyl-linkage on mucins in cystic fibrosis patients promotes formation of the sialyl-Lewis X determinant on salivary MUC-5B and MUC-7.

Destruction of the lungs as a consequence of recurrent infections with microorganisms such as Pseudomonas aeruginosa remains the underlying cause of most morbidity and mortality in cystic fibrosis (CF). We have hypothesized that changes in the glycosylation of key tracheal mucins such as MUC5B and MUC7 might increase the risk of pulmonary disease in CF patients. However, in preference to sputum we have examined the sugar-chains on these mucins in saliva because in the latter not only can the glycoproteins be collected from controls, but they are essentially free from modifications made following bacterial infection in disease. Proteins in ductal or whole-mouth saliva from 20 CF patients with the Delta F-508 CFTR mutation and age-and sex-matched controls were separated by SDS-PAGE and blotted onto nitrocellulose and then probed with labelled lectins of known specificity. Linkage of terminal sialic acid on the blotted mucins was determined using Sambucus nigra agglutinin (detects the 2-->6 linkage) and Maackia amurensis agglutinin (the 2-->3 linkage). Fucose was detected by Ulex europaeus agglutinin-1 (1-->2 linkage) and Aleuria aurantia agglutinin (1-->3 linkage). We found that each mucin shows a characteristic glycosylation pattern and in controls most of the sialic acid is 2-->6 linked on MG1 (MUC 5B) and 2-->3 linked on MG2 (MUC 7). CF is associated with a shift from a 2-->6 linkage to a 2-->3 linkage on MG1 with some patients showing almost no 2-->6 linkage; 2-->3 linkage on MG2 is similarly increased in disease in some individuals. The expression of fucose on these mucins is also raised in CF patients. These shift to a 2-->3 linkage of sialic acid, and with increased fucosylation this promotes the formation of sialyl-Lewis X antigen detected on CF mucins in our study. These changes will be tested for their correlation with the severity of lung disease. We gratefully acknowledge support from the European Union Biomed-II Programme.

Cystic Fibrosis↗
PubMed2001

Neural correlates of attention and working memory deficits in HIV patients.

OBJECTIVES: To evaluate the neural correlates of attention and working memory deficits in patients with HIV-1. METHOD: fMRI was used to evaluate brain activity in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched seronegative subjects, while performing a battery of tasks that required different levels of attention for working memory. RESULTS: Patients with HIV showed greater brain activation (blood oxygenation level dependent signal changes) in some regions compared with control subjects while performing the same tasks. For the simpler tasks, patients with HIV showed greater activation in the parietal regions. However, with more difficult tasks, patients with HIV showed greater activation additionally in the frontal lobes. Reaction times during these tasks were slower but accuracy was similar in the patients with HIV compared with control subjects. CONCLUSION: Injury to the neural substrate caused by HIV infection may necessitate greater attentional modulation of the neural circuits, hence a greater use of the brain reserve; additional activation of the frontal lobes is required to perform the more complex tasks. The task-dependent increased frontal activation in patients with HIV suggests that the neural correlate of attentional deficits may be excessive attentional modulation as a result of frontostriatal brain injury.

AIDS Dementia Complex↗
PubMed2001

Association between deficiency of mannose-binding lectin and severe infections after chemotherapy.

The plasma protein mannose-binding lectin (MBL) activates the complement system by binding to carbohydrate structures presented by microorganisms and thus could be an important component of the innate immune defence system. We measured MBL in patients with leukaemia who were scheduled to undergo chemotherapy (ie, a population especially susceptible to infection) and related the results to severity of infection after chemotherapy. We showed a significant association between low concentrations of MBL and serious infections related to chemotherapy (p<0.0001). These results suggest that increasing concentrations of MBL in patients having chemotherapy could reduce susceptibility to infection.

Adult↗
PubMed2001

Neurotransmitters and apoptosis in the developing brain.

In the immature mammalian brain during a period of rapid growth (brain growth spurt/synaptogenesis period), neuronal apoptosis can be triggered by the transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the excessive activation of gamma-aminobutyric acid (GABA(A)) receptors. Apoptogenic agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol, halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period starts in the sixth month of pregnancy and extends to the third year after birth. Ethanol, which has both NMDA antagonist and GABA(A) agonist properties, is particularly effective in triggering widespread apoptotic neurodegeneration during this vulnerable period. Thus, maternal ingestion of ethanol during the third trimester of pregnancy can readily explain the dysmorphogenic changes in the fetal brain and consequent neurobehavioral disturbances that characterize the human fetal alcohol syndrome. In addition, there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain.

Animals↗
PubMed2001

Atomic string holography.

A new diffraction-channeling effect has been discovered, in which Kikuchi or channeling line patterns formed by high energy electrons, neutrons, and positrons are shown to break up into a series of annular disks if the crystal thickness traversed by the beam is small. The disks may be interpreted as Gabor in-line holograms of strings of atoms projected along the beam path. For electrons or positrons the patterns may be detected with little background by detecting characteristic x-ray emission from a thin film as a function of the diffraction conditions of a collimated, ionizing, high energy beam. Uses of the effect for structure determination and atomic-resolution lensless imaging are suggested.

Journal Article↗
PubMed2001

Seeing properties of an invisible object: feature inheritance and shine-through.

We characterize a class of spatio-temporal illusions with two complementary properties. Firstly, if a vernier stimulus is flashed for a short time on a monitor and is followed immediately by a grating, the latter can express features of the vernier, such as its offset, its orientation, or its motion (feature inheritance). Yet the vernier stimulus itself remains perceptually invisible. Secondly, the vernier can be rendered visible by presenting gratings with a larger number of elements (shine-through). Under these conditions, subjects perceive two independent "objects" each carrying their own features. Transition between these two domains can be effected by subtle changes in the spatio-temporal layout of the grating. This should allow psychophysicists and electrophysiologists to investigate feature binding in a precise and quantitative manner.

Attention↗
PubMed2001

European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations.

SUMMARY. By August 1997, 11,749 patients with cystic fibrosis had been enrolled in the European Epidemiologic Registry of Cystic Fibrosis (ERCF). Genotype analysis had been performed on 8,963 (76%) of these patients, and the majority had one or two identifiable mutations. Patients with known mutations were classified according to the type of mutation (Classes I-V), and were grouped according to the class of mutation on both chromosomes. This resulted in six subgroups, including all patients homozygous for Class I (I/I, n = 72), for Class II (II/II, n = 5,020), and for Class III mutations, (III/III, n = 23). Since there were only 23 patients homozygous for Class III mutations, a fourth group was made up of patients who were compound heterozygous for a Class II and III mutation (II/III, n = 265). There were only five patients homozygous for Class IV mutations, and consequently a fifth group was made up of all patients carrying at least one Class IV mutation, regardless of the nature of the mutation on the other chromosome (IV/any, n = 187). None were homozygous for Class V mutations; consequently, a sixth group consisted of patients carrying at least one Class V mutation (V/any, n = 22). Mean age was highest in groups III/III, IV/any, and V/any (15.6, 16, and 17 years, respectively) as opposed to 12.4 years in group II/II and 13.4 in group II/III, but both group III/III and V/any were small, and the confidence interval of the mean was large. The percentage of patients receiving pancreatic enzymes was lower in groups IV/any and V/any than in any of the other groups, i.e., approximately 50% of patients 18 years or older in both groups as opposed to between 90-100% of all other patients regardless of age. The prevalence of diabetes mellitus increased with age from 2.6% in patients < 18 years to 22.1% in patients 18 years or older in the large group II/II, but was only 1.5% in patients 18 years or older in group IV/any. Disregarding the small group III/III, abnormally elevated liver enzymes and/or bilirubin (1.5 x upper normal limit) was much less frequent in group IV/any than in any of the other groups, both overall and in patients aged 18 years or more. The course of lung disease appeared to be less dependent on genotype than pancreatic function, with only minor differences between groups; however, the mean values of both FVC % and FEV(1) % were slightly higher in group IV/any than all other groups in both younger and older patients. The same was found for the prevalence of some major clinical signs of severe lung disease, such as clubbing, hyperinflation, and crepitations. Overall mean weight expressed as an age percentile was markedly higher in group IV/any than in any other group, which may be related to the finding of a much lower prevalence of chronic P. aeruginosa infection in patients 18 years or older belonging to group IV/any (and V/any) than in any other group. In conclusion, the presence of a class IV mutation appears to offer some degree of protection against pancreatic insufficiency, diabetes mellitus, and liver disease. We confirmed that lung disease follows a milder clinical course in patients with a class IV mutation and that the presence of a class IV mutation (and possibly class V) is associated with a delay in the onset of P. aeruginosa infection.

Adolescent↗
PubMed2001

Presence of cystic fibrosis-related diabetes mellitus is tightly linked to poor lung function in patients with cystic fibrosis: data from the European Epidemiologic Registry of Cystic Fibrosis.

Data derived from a cross-sectional analysis of 7,566 patients stratified into six age groups were used to compare lung function, body mass index (BMI), and weight for age in patients with and without cystic fibrosis-related diabetes mellitus (CFDM). The presence of CFDM was tightly linked to poor lung function, regardless of age. The mean value of FEV(1) % predicted in the age groups < 10, 10-< 15, 15-< 20, 20-< 25, 25-< 30, and 30 years or older were 87%, 77%, 69%, 58%, 55%, and 53% in the nondiabetic cystic fibrosis (CF) patients as compared to 79%, 66%, 55%, 49%, 46%, and 44% in the diabetic CF patients. BMI and weight for age were also lower in diabetic than nondiabetic CF patients in all age groups, except for BMI in the youngest patients. The difference in lung function and in nutritional parameters between diabetic and nondiabetic CF patients was not linked to presence or absence of any specific pathogen in the lower respiratory tract. These results confirm and extend those of earlier studies in smaller numbers of patients, and they clearly identify CFDM as a powerful determinant of severe lung disease and reduced survival in patients with CF and diabetes mellitus.

Adolescent↗
PubMed2001

Rainbow trout offspring with different resistance to viral haemorrhagic septicaemia.

To study immunological and immunogenetical parameters related to resistance against viral haemorrhagic septicaemia (VHS), attempts to make gynogenetic strains of rainbow trout selected for high and low resistance to VHS were initiated in 1988. The first gynogenetic generation of inbreeding resulted in the more resistant offspring E8 and the low resistance offspring K3; the K3 offspring having the same high mortality as the susceptible reference strain of outbred trout in infection trials. A second gynogenetic generation derived from the E8 strain resulted in some low resistance offspring, and two gynogenetic families in which all, or nearly all, fish survived challenge with VHS virus. In this study, an attempt to associate the distribution of different MHC class II genotypes with low and high resistance gynogenetic offspring was performed. Two different MHC haplotypes could be distinguished, and in both low and high resistance families all three genotypes were found, which could be explained by the fact that the mother fish carried the heterozygous genotype. Although no significant differences in MHC II genotypes were found between the high and low resistance offspring, a significantly different distribution of haplotypes in the low resistance offspring was observed, that could not be explained by a one- or two-locus model.

Animals↗
PubMed2001

[Development of a standardized instrument for quantitative and reproducible rehabilitation data assessment after polytrauma (HASPOC)].

INTRODUCTION: Previous scoring systems for measurement of the quality of outcome are based on scores regarding injuries to individual body regions. Known scores which describe several organ regions are of no importance for trauma patients. Therefore a new rehabilitation outcome evaluation score was developed at our hospital. METHODS: Based on a prospective reinvestigation, a score system was developed that allows a quantitative appraisal of the subjective and objective outcome. A complete physical examination was performed, including ROM, neurologic examination and strength analysis. Part I (113 questions) is to be filled out by the patient; part II (191 questions) focusses on different body regions, physical examination and functional scoring. Included are the MFA, FIM, GCO and Frankel score. A final score (HASPOC) was developed to give a quantitative result of the outcome. RESULTS: The new score has a range from 5 to 411 points. One hundred and fifty patients were re-examined. The mean follow-up time was 2.2 +/- 0.1 years. The SF 12 indicated an outcome more than satisfactory in 63% of cases. The MFA demonstrated moderate or severe restrictions in 41%, in the case of injuries of the lower extremity in 52% of patients. The HASPOC indicated a mean of 44.5 points. CONCLUSION: This paper describes the development, structure, and the quantitative outcome of rehabilitation in polytrauma patients. This standardized rehabilitation instrument deals with a very heterogeneous patient population and shows the rehabilitation deficits accurately. Implemented recognized evaluations allow comparison of these results with those of other scoring systems.

Data Collection↗
PubMed2001

Spatial aspects of object formation revealed by a new illusion, shine-through.

When a vernier stimulus is presented for a short time and followed by a grating comprising five straight lines, the vernier remains invisible but may bequeath its offset to the grating (feature inheritance). For more than seven grating elements, the vernier is rendered visible as a shine-through element. However, shine-through depends strongly on the spatio-temporal layout of the grating. Here, we show that spatially inhomogeneous gratings diminish shine-through and vernier discrimination. Even subtle deviations, in the range of a few minutes of arc, matter. However, longer presentation times of the vernier regenerate shine-through. Feature inheritance and shine-through may become a useful tool in investigating such different topics as time course of information processing, feature binding, attention, and masking.

Adult↗
PubMed2001

Shine-through: temporal aspects.

If a vernier stimulus precedes a grating for a very short time, the vernier either remains invisible, but may bequeath some of its properties to the grating (feature inheritance), or might shine through keeping its features - depending on the number of grating elements [Herzog, M. H. & Koch, C., 2001. Seeing properties of an invisible element: feature inheritance and shine-through. Proceedings of the National Academy of Science USA 98, 4271-4275]. Feature inheritance and shine-through represent two different states of feature binding [Herzog, M. H., Koch, C., & Fahle, M., Switching binding states. Visual Cognition (in press)], whereas shine-through depends in subtle ways on the spatial layout of the grating [Herzog, M. H., Fahle, M., & Koch, C., (2001). Spatial aspects of object formation revealed by a new illusion, shine-through Vision Research]. Here, we show that also temporal parameters of the grating influence shine-through. For example, a delayed presentation of certain grating elements can deteriorate performance dramatically.

Afterimage↗
PubMed2001

Flanker effects in peripheral contrast discrimination--psychophysics and modeling.

We studied lateral interactions in the periphery by measuring how contrast discrimination of a peripheral Gabor patch is affected by flankers. In the psychophysical experiments, two Gabor targets appeared simultaneously to the left and right of fixation (4 degrees eccentricity). Observers reported which contrast was higher (spatial 2-alternative-forced-choice). In different conditions, Gabor flankers of different orientation, phase, and contrast were present above and below the two targets, at a distance of three times the spatial Gabor period. The data show that collinear flanks impair discrimination performance for low pedestal contrasts but have no effect for high pedestal contrasts. The transition between these two result patterns occurs typically at a pedestal contrast which is similar to the flanker contrast. For orthogonal flanks, we find facilitation at low pedestal contrasts, and suppression at intermediate contrasts. We account for this complex interaction pattern by a model that assumes that flankers can provide additive input to the target unit, and that they further contribute to the target's gain control, but only in a limited range of pedestal contrasts; once the target contrast exceeds a critical value, inhibition becomes subtractive rather than divisive. We further make specific propositions on how this model could be implemented at the neuronal level and show that a simple integrate and fire unit that receives time-modulated inhibition behaves in a fashion strikingly similar to the model inferred from the psychophysical data.

Contrast Sensitivity↗
PubMed2001

Computational modelling of visual attention.

Five important trends have emerged from recent work on computational models of focal visual attention that emphasize the bottom-up, image-based control of attentional deployment. First, the perceptual saliency of stimuli critically depends on the surrounding context. Second, a unique 'saliency map' that topographically encodes for stimulus conspicuity over the visual scene has proved to be an efficient and plausible bottom-up control strategy. Third, inhibition of return, the process by which the currently attended location is prevented from being attended again, is a crucial element of attentional deployment. Fourth, attention and eye movements tightly interplay, posing computational challenges with respect to the coordinate system used to control attention. And last, scene understanding and object recognition strongly constrain the selection of attended locations. Insights from these five key areas provide a framework for a computational and neurobiological understanding of visual attention.

Animals↗
PubMed2001

[Thermal effects of ultrasound].

AIM: Diagnostic ultrasound is a powerful, versatile and safe investigation tool in modern medicine. Methods are described, and conclusions are drawn and recommendations given for a responsible use of diagnostic ultrasound. METHOD AND RESULTS: Because of the increasing ultrasonic power penetrating the body, diagnostic techniques cannot always be applied without risk. The increase in temperature induced by ultrasound absorption should be considered a potential hazard in certain applications. The paper presents the physical basis for a quantitative estimation of the risk of a specific treatment plan. Mathematical models and the thermal index are described. CONCLUSION: Our findings and recommendations form a viable basis for the responsible use of diagnostic ultrasound.

Animals↗