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Biomedical subjects

C Koch

Publications and source records attributed to C Koch.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effects of the initial level of milk production and of the dietary protein intake on the course of natural nematode infection in dairy goats.

The level of dietary protein is known to alter the establishment and the pathophysiology of gastrointestinal nematodes in sheep. On the other hand, high-producing dairy goats are less resistant and/or resilient than low-producing ones to experimental nematode infection. During a 2-year study, we have investigated the course of a natural nematode infection (mainly T. colubriformis) in a high-producing dairy goat flock. In year 1, 50 grazing goats divided in high (HP) or low producer (LP) were compared from April to October for parasitological and milk parameters. In year 2, the 25 HP goats were only considered and were allocated to two levels of dietary protein, high level (HPr) with a protein coverage of 125% or normal level (NPr) with a protein coverage of 106%. They were monitored as above. In year 1, HP goats showed a greater nematode egg output (1856 vs. 1000epg) associated with higher values in T. colubriformis IgG in autumn than LP ones whereas the decrease in serum phosphate concentration was similar in both groups. In year 2, HPr goats exhibited lower egg output in autumn (2219 vs. 2817) vs. NPr ones. Moreover, milk yield and fat content were significantly higher in HPr vs. NPr in the 2nd part of the study. HP goats are less resistant to nematode infection in natural conditions. Resistance and resilience of HP goats may partially be improved by a protein supplementation in the diet.

Animal Feed↗
PubMed2000

Gender differences in the functional organization of the brain for working memory.

Gender differences in brain activation during working memory tasks were examined with fMRI. Seventeen right-handed subjects (nine males, eight females) were studied with four different verbal working memory tasks of varying difficulty using whole brain echo-planar fMRI. Consistent with prior studies, we observed activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC), and additionally, caudate activation in both sexes. The volume of activated brain tissue increased with increasing task difficulty. For all four tasks, the male subjects showed bilateral activation or right-sided dominance (LPFC, PC and caudate), whereas females showed activation predominantly in the left hemisphere. The task performance data demonstrated higher accuracy and slightly slower reaction times for the female subjects. Our results show a highly significant (p < 0.001) gender differences in the functional organization of the brain for working memory. These gender-specific differences in functional organization of the brain may be due to gender-differences in problem solving strategies or the neurodevelopment. Therefore, gender matching or stratification is required for studies of brain function using imaging techniques.

Adult↗
PubMed2000

A quantitative enzyme-linked immunoassay for the detection of 2, 6-dichlorobenzamide (BAM), a degradation product of the herbicide dichlobenil.

2,6-Dichlorobenzamide (BAM) is the dominant degradation product in soil of the widely used herbicide dichlobenil. To detect BAM in water, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) was developed. As an alternative to conventional coating of ELISA plates, the assay is based on direct covalent immobilisation. We achieved a surface which requires a short time for the immobilisation of ligand, is stable under dry storage, and which permits assays with a low CV. The performance of the assay was demonstrated by an inter-well CV that was generally less than 6%, a detection limit (DL(15)) of 0.02 microg/l and an IC(50) of 0.19 microg/l. Cross-reactivity was measured against nine analytes with structural homology to BAM. The highest degree of cross-reactivity (10.8%) was seen with 2,6-dichlorothiobenzamide (Chlorthiamid). Considering an EU-limit of 0.1 microg/l as the permissible maximum for the presence of pesticides in drinking water, this ELISA-procedure is suitable for large-scale screening of water samples suspected of being contaminated with BAM.

Animals↗
PubMed2000

Localization of lung surfactant protein D on mucosal surfaces in human tissues.

Lung surfactant protein-D (SP-D), a collectin mainly produced by alveolar type II cells, initiates the effector mechanisms of innate immunity on binding to microbial carbohydrates. A panel of mRNAs from human tissues was screened for SP-D mRNA by RT-PCR. The lung was the main site of synthesis, but transcripts were readily amplified from trachea, brain, testis, salivary gland, heart, prostate gland, kidney, and pancreas. Minor sites of synthesis were uterus, small intestine, placenta, mammary gland, and stomach. The sequence of SP-D derived from parotid gland mRNA was identical with that of pulmonary SP-D. mAbs were raised against SP-D, and one was used to locate SP-D in cells and tissues by immunohistochemistry. SP-D immunoreactivity was found in alveolar type II cells, Clara cells, on and within alveolar macrophages, in epithelial cells of large and small ducts of the parotid gland, sweat glands, and lachrymal glands, in epithelial cells of the gall bladder and intrahepatic bile ducts, and in exocrine pancreatic ducts. SP-D was also present in epithelial cells of the skin, esophagus, small intestine, and urinary tract, as well as in the collecting ducts of the kidney. SP-D is generally present on mucosal surfaces and not restricted to a subset of cells in the lung. The localization and functions of SP-D indicate that this collectin is the counterpart in the innate immune system of IgA in the adaptive immune system.

Antibodies, Monoclonal↗
PubMed2000

L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase.

The adhesion molecules known as selectins mediate the capture of neutrophils from the bloodstream. We have previously reported that ligation and cross-linking of L-selectin on the neutrophil surface enhances the adhesive function of beta(2)-integrins in a synergistic manner with chemotactic agonists. In this work, we examined degranulation and adhesion of neutrophils in response to cross-linking of L-selectin and addition of interleukin-8. Cross-linking of L-selectin induced priming of degranulation that was similar to that observed with the alkaloid cytochalasin B. Activation mediated by L-selectin of neutrophil shape change and adhesion through CD11b/CD18 were strongly blocked by Merck C, an imidazole-based inhibitor of p38 mitogen-activated protein kinase (MAPK), but not by a structurally similar non-binding regioisomer. Priming by L-selectin of the release of secondary, tertiary, and secretory, but not primary, granules was blocked by inhibition of p38 MAPK. Peak phosphorylation of p38 MAPK was observed within 1 min of cross-linking L-selectin, whereas phosphorylation of ERK1/2 was highest at 10 min. Phosphorylation of p38 MAPK, but not ERK1/2, was inhibited by Merck C. These data suggest that signal transduction as a result of clustering L-selectin utilizes p38 MAPK to effect neutrophil shape change, integrin activation, and the release of secondary, tertiary, and secretory granules.

Cell Adhesion↗
PubMed2000

Effect of Salts on the Micellization, Clouding, and Solubilization Behavior of Pluronic F127 Solutions.

We have examined the effect of NaCl, Na(2)SO(4), Na(3)PO(4), and NaSCN on F127 solutions; properties examined were critical micellization temperature (cmt), cloud point, and solubilization of a model hydrophobic drug, propyl paraben. Static light scattering showed that the first three salts lower the cmt of F127 in the order Na(3)PO(4)>Na(2)SO(4)>NaCl. The extent of lowering depends on the salt concentration and can be ascribed to the water structure-making properties of these salts. NaSCN, a water structure breaker, was found to increase cmt. Pyrene fluorescence was used to study the changes in micellar interior in the presence of salts. We found that the micellar micropolarity is not significantly changed by salts, evidenced by a constant I(1)/I(3) ratio of pyrene. However, the I(e)/I(3) ratio changes significantly with salts, being lower for NaCl, Na(2)SO(4), and Na(3)PO(4) and higher for NaSCN. This is consistent with an increase in the total hydrophobic micellar domain, in micellar microviscosity, or both. Solubilization of propylparaben increases in the presence of Na(3)PO(4), consistent with a larger hydrophobic domain for solubilization. The thermodynamics of micellization continue to be entropically driven in the presence of salts, evidenced by a positive entropy overcoming an unfavorable enthalpy. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Candidate genes for the hypoxic tumor phenotype.

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma-derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.

Animals↗
PubMed2000

Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.

The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.

Animals↗
PubMed2000

The homologue of mannose-binding lectin in the carp family Cyprinidae is expressed at high level in spleen, and the deduced primary structure predicts affinity for galactose.

Mannose-binding lectin (MBL) participates in the innate immune system as an activator of the complement system and as an opsonin after binding to certain carbohydrate structures on microorganisms. We isolated and characterized cDNA transcripts encoding an MBL homologue from three members of the carp family Cyprinidae, the zebrafish Danio rerio, the goldfish Carassius auratus, and the carp Cyprinus carpio. The carp and zebrafish transcripts contain two polyadenylation sites and RT-PCR on mRNA from carp tissues revealed the carp transcript to be most prominently expressed in the spleen. The deduced mature proteins contain 228 or 233 amino acids with a short N-terminal segment containing a single conserved cysteine expected to form interchain disulfide bridges, a collagen domain interrupted by four amino acids between two glycine residues, a neck region predicted to form an alpha-helical coiled-coil structure, and a C-terminal carbohydrate recognition domain (CRD). Several of the structurally important residues in the CRD are conserved, but the residues known to interact with the calcium ion and hydroxyl groups of the carbohydrate ligand are different. The amino acid motif EPN, important for mannose specificity, was QPD in the Cyprinidae homologue, suggesting specificity for galactose instead. The identity between the deduced amino acid sequences is more than 90% between the carp and the goldfish and 68% and 65% between these two species, respectively, and the zebrafish. The identity with bird and mammalian MBLs ranges from 28 to 33%.

Amino Acid Sequence↗
PubMed2000

Attentional effects on contrast detection in the presence of surround masks.

We studied how attention affects contrast detection performance when the target is surrounded by mask elements. In each display quadrant we presented a hexagon of six vertical Gabor patches (the 'surround'). Only one of the hexagons contained a central Gabor patch (the 'target') and the task was to report that quadrant (spatial four-alternative-forced choice). Attention was manipulated by means of a double-task paradigm: in one condition observers had to perform concurrently a central letter-discrimination task, and the contrast-detection task was then only poorly attended, while attention was fully available in the other condition. We find that under poorly attended conditions targets can be detected only when the target contrast exceeds the surround contrast (contrast popout) or when the target orientation differs from the surround orientation by more than 10-15 degrees (orientation popout). When the target orientation is similar to the surround orientation, attention can reduce the contrast detection thresholds in some cases more than four-fold, demonstrating a very strong attentional effect.

Attention↗
PubMed2000

A saliency-based search mechanism for overt and covert shifts of visual attention.

Most models of visual search, whether involving overt eye movements or covert shifts of attention, are based on the concept of a saliency map, that is, an explicit two-dimensional map that encodes the saliency or conspicuity of objects in the visual environment. Competition among neurons in this map gives rise to a single winning location that corresponds to the next attended target. Inhibiting this location automatically allows the system to attend to the next most salient location. We describe a detailed computer implementation of such a scheme, focusing on the problem of combining information across modalities, here orientation, intensity and color information, in a purely stimulus-driven manner. The model is applied to common psychophysical stimuli as well as to a very demanding visual search task. Its successful performance is used to address the extent to which the primate visual system carries out visual search via one or more such saliency maps and how this can be tested.

Adolescent↗
PubMed2000

Control of the classical and the MBL pathway of complement activation.

The activation of complement via the mannan-binding lectin (MBL) pathway is initiated by the MBL complex consisting of the carbohydrate binding molecule, MBL, two associated serine proteases, MASP-1 and MASP-2, and a third protein, MAp19. In the present report we used an assay of complement activation specifically reflecting the physiological activity of the MBL complex to identify biological and synthetic inhibitors. Inhibitor activity towards the MBL complex was compared to the inhibition of the classical pathway C1 complex and to a complex of MBL and recombinant MASP-2. A number of synthetic inhibitors were found to differ in their activities towards complement activation via the MBL pathway and the classical pathway. C1 inhibitor inhibited both pathways whereas alpha2-macroglobulin (alpha2M) inhibited neither. C1 inhibitor and alpha2M were found to be associated with the MBL complex. Upon incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand, impaired control of complement activation may lead to severe and often chronically disabling diseases. The results in the present report suggests the possibility of specifically inhibiting of the MBL pathway of complement activation.

Animals↗
PubMed2000

Efficacy of copper oxide needles for the control of nematode parasites in dairy goats.

The spread of benzimidazole-resistant nematodes in dairy goat farms is of a great concern as probably more than 70% of the flocks are involved. As there are very few other anthelmintic options during the lactating period, we have evaluated the efficacy of copper oxide needles (CON, Copinox, Bayer, UK) in both experimental and natural infections in goats. The curative effect of CON (2-4 g) on existing worm burdens was assessed in goats experimentally infected with Teladorsagia circumcincta, Haemonchus contortus and Trichostrongyus colubriformis, compared to controls. The preventive effect of CON (4 g) on worm establishment was monitored for 2 months in animals experimentally infected with H. contortus and for 3 months in naturally infected animals on a farm exhibiting predominant infections with T. circumcincta and Oesophagostomum venulosum. In both experimental and natural conditions, the efficacy of CON was nil against Teladorsagia, Trichostrongylus and Oesophagostomum infections. In contrast, the efficacy of CON against Haemonchus was clearly established in reducing the worm burden (75%) as well as in lowering the egg output (37-95%) in relation to the establishment of new infections over several weeks. Copper oxide needles may represent an alternative to conventional anthelmintics in the control of Haemonchus infection in some goat farms.

Administration, Oral↗
PubMed2000

Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis.

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. METHODS: Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group. RESULTS: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System). CONCLUSIONS: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.

Adolescent↗
PubMed2000

Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from a hypersensitivity response to Aspergillus fumigatus, although the pathogenesis of the disease is unknown and its prevalence in cystic fibrosis (CF) is still poorly defined. Data from the Epidemiologic Registry of Cystic Fibrosis (ERCF) on 12,447 CF patients gathered from 224 CF centres in nine European countries were analysed. The ERCF definition of ABPA diagnosis is a positive skin test and serum precipitins to A. fumigatus, together with serum immunoglobulin (Ig)E levels >1,000 U x mL(-1) and additional clinical or laboratory parameters. The overall prevalence of ABPA in the ERCF population was 7.8% (range: 2.1% in Sweden to 13.6% in Belgium). Prevalence was low <6 yrs of age but was almost constant approximately 10% thereafter. No sex differences were observed. ABPA affected 8.0% of patients with a deltaF508/deltaF508 genotype and 5-6% with deltaF508/G551D, deltaF508/G542X and deltaF508/N1303K genotypes. ABPA patients presented a lower forced expiratory volume in one second (FEV1) than those without ABPA at any age and the prevalence ranged from 6.6% in patients with FEV1 > or =20-12.9% in those with FEV1 <40%. ABPA was associated with higher rates of microbial colonization, pneumothorax and massive haemoptysis, and with higher IgG serum levels and poorer nutritional status. A mixed model regression analysis of lung function showed that FEVI decline during the follow-up period was not substantially different in ABPA patients compared with non-ABPA patients for any subgroups based on age or disease severity at enrollment. To conclude, allergic bronchopulmonary aspergillosis is a frequent complication in cystic fibrosis patients, particularly after the age of 6 yrs, and it is generally associated with a poorer clinical condition. However, any clear independent influence of allergic bronchopulmonary aspergillosis on the rate of lung function decline in the short term was not shown.

Adolescent↗
PubMed2000

The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type.

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF -P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN-gamma (p<0.05) and higher IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore, a positive correlation between IFN-gamma production and lung function was found (FVC: Rho = 0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.

Adult↗