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C Koch

Publications and source records attributed to C Koch.

At least 109 records · Page 6Linked to original sources
PubMed1999

A Study of the Temperature-Dependent Micellization of Pluronic F127.

We have examined the temperature-dependent micellization of the pharmaceutically important PEO-PPO-PEO copolymer, Pluronic F127, using static light scattering and various aspects of the pyrene fluorescence spectrum (monomer intensity, excimer formation and the I1/I3 ratio). All techniques gave essentially the same value for the critical micellization temperatures (cmt) of various F127 solutions, and our results agreed with those reported in the literature. Cmt values decrease with increasing F127 concentration. We observed significant solubilization of pyrene in F127 solutions below the cmt, which was also reflected in the measured I1/I3 ratios. The thermodynamics of the micellization process were studied and gave different results at low and high F127 concentrations. In the low F127 concentration range (up to approximately 50 mg/mL), we obtain DeltaH = 312 kJ mol-1 and DeltaS = 1.14 kJ mol-1 K-1. Above 50 mg/mL we obtain DeltaH = 136 kJ mol-1 and a DeltaS = 0.54 kJ mol-1 K-1. This discontinuity in thermodynamic behavior can be due to a change in aggregation number with temperature and/or a change in the micellization process at higher concentrations. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

A comparison in individual murine tumors of techniques for measuring oxygen levels.

PURPOSE: To investigate the relationship between different techniques for measuring oxygen levels in a murine tumor model. METHODS AND MATERIALS: Using the murine fibrosarcoma line KHT-C, five techniques of measuring oxygen levels-the Eppendorf pO2 Histograph, EF5 binding, the comet assay, a paired survival assay, and an in vivo growth delay assay-were assessed. In these experiments, three or more techniques were applied in different combinations to measure the oxygen levels in individual tumors. RESULTS: Statistically significant correlations were observed between the hypoxic proportions calculated from the paired survival assay with those from EF5 binding. The comet assay was found to have a statistically significant correlation with the paired survival analysis and the growth delay analysis. No statistically significant correlation was found between the Eppendorf pO2 Histograph measurements and those from the other techniques, although there were weak correlations with the paired survival assay and EF5 binding. For technical reasons, a comparison was not made between EF5 binding and the growth delay assay. CONCLUSIONS: The correlations found between EF5 binding and the comet assay with the radiobiological assays suggest that these techniques have potential for predicting outcome following radiation treatment. The lack of correlation seen between the pO2 Histograph data and the radiobiological assays is in contrast to results from early clinical trials.

Animals↗
PubMed1999

A role for Ctr9p and Paf1p in the regulation G1 cyclin expression in yeast.

Entry into the cell cycle in budding yeast involves transcriptional activation of G1cyclin genes and DNA synthesis genes when cells reach a critical size in late G1. Expression of G1cyclins CLN1 and CLN2 is regulated by the transcription factor SBF (composed of Swi4p and Swi6p) and depends on the cyclin-dependent Cdc28 protein kinase and cyclin Cln3p. To identify novel regulators of SBF-dependent gene expression we screened for mutants that fail to activate transcription of G1cyclins. We found mutations in a gene called CTR9. ctr9 mutants are inviable at 37 degrees C and accumulate large cells. CTR9 is identical to CDP1. CTR9 encodes a conserved nuclear protein of 125 kDa containing several TPR repeats implicated in protein-protein interactions. We show that Ctr9p is a component of a high molecular weight protein complex. Using immuno-affinity chromatography we found that Ctr9p associates with polypeptides of 50 and 65 kDa. By mass spectrometry these were identified as Cdc73p and Paf1p. We show that Paf1p, like Ctr9p, is required for efficient CLN2 transcription, whereas Cdc73p is not. Paf1p and Cdc73p were previously reported to be RNA poly-merase II-associated proteins, suggesting that the Ctr9p complex may interact with the general transcription apparatus.

Cell Cycle↗
PubMed1999

Complexity and the nervous system.

Advances in the neurosciences have revealed the staggering complexity of even "simple" nervous systems. This is reflected in their function, their evolutionary history, their structure, and the coding schemes they use to represent information. These four viewpoints need all play a role in any future science of "brain complexity."

Animals↗
PubMed1999

Analog VLSI-based modeling of the primate oculomotor system.

One way to understand a neurobiological system is by building a simulacrum that replicates its behavior in real time using similar constraints. Analog very large-scale integrated (VLSI) electronic circuit technology provides such an enabling technology. We here describe a neuromorphic system that is part of a long-term effort to understand the primate oculomotor system. It requires both fast sensory processing and fast motor control to interact with the world. A one-dimensional hardware model of the primate eye has been built that simulates the physical dynamics of the biological system. It is driven by two different analog VLSI chips, one mimicking cortical visual processing for target selection and tracking and another modeling brain stem circuits that drive the eye muscles. Our oculomotor plant demonstrates both smooth pursuit movements, driven by a retinal velocity error signal, and saccadic eye movements, controlled by retinal position error, and can reproduce several behavioral, stimulation, lesion, and adaptation experiments performed on primates.

Adaptation, Physiological↗
PubMed1999

Increased antigen-specific Th-2 response in allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis.

The majority of patients with cystic fibrosis (CF) become colonized with Aspergillus fumigatus (A. fumigatus) in the lower respiratory tract, the prevalence being up to 60%. Between 1-11% of CF patients develop allergic bronchopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected patients suffering from cystic fibrosis or atopic asthma have suggested a pathogenic role for antigen-specific "Th2-like" T lymphocytes. The aim of this study was to evaluate the quantitative importance of such Th2 cells, using improved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF patients with ABPA and from a control group without ABPA. Thus, 20 patients with CF, heavily colonized with A. fumigatus in the lower respiratory tract, were studied: 10 patients with ABPA, and 10 without. Unseparated PBMC were stimulated in vitro by A. fumigatus antigen and by an unrelated antigen (tetanus toxoid) as a control. After 6 days of stimulation, IL-4 and IL-5 (markers for Th2 cell activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were quantified in the supernatants by enzyme-linked immunosorbent assay. PBMC from ABPA patients secreted significantly higher amounts of IL-4, i.e., 0.48 (0.15-0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/mL, compared to secretions obtained in non-ABPA CF controls of 0.07 (0.04-0.16) ng/mL and 3.00 (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN-gamma secretion was similar in the two groups, amounting to 21.5 (2.05-72.5) ng/mL in ABPA patients vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant differences were obtained in the cytokine secretion induced by tetanus toxoid stimulation between the two groups. We conclude that ABPA in CF patients is associated with an antigen-specific, Th2-like T-cell immune response, as indicated by excessive secretion of IL-4 and IL-5.

Adolescent↗
PubMed1999

Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974-1995).

Recurrent and chronic lower airway infection with Pseudomonas aeruginosa (PA) is an important component of cystic fibrosis (CF) pulmonary disease. Different modes of treatment and control of CF patients have been introduced at the Copenhagen CF Centre over the past 20 years and have been associated with improved survival. Treatment consisted of: 1) elective antibiotics for 14 days every 3 months to patients with chronic PA infection (started in 1976), 2) cohort isolation to prevent cross-infection (patients with PA were separated from patients without PA, starting in 1981); and 3) early intensive treatment with inhaled colistin and oral ciprofloxacin from time of initial PA colonization (started in 1989). The aim of the present study was to evaluate the impact of each of these interventions on the changes in the epidemiology of PA. Based on monthly cultures of lower airway secretions in each CF patient seen during 1974-1995, significant changes in the incidence and prevalence of the PA infection were found. The monthly prevalence of chronic PA increased significantly (P < 0.0001) from below 40% before 1976 to above 60% in 1980, which was found to be due to cross-infection among the CF patients after introduction of elective antibiotic courses in 1976. To deal with this problem, cohort isolation was introduced in 1981, and since then the monthly point prevalence of chronic PA decreased slowly until 1989 (P < 0.0001), when early intensive treatment from initial PA colonization was introduced; this was associated with a further decrease in point prevalence to 45% in 1995 (P < 0.005). The annual incidence of chronic PA infection also decreased significantly (P < 0.01) from 16% to below 2% after introduction of cohort isolation and early intensive treatment from initial PA isolation. Furthermore, the time from acquisition of first PA to development of chronic PA infection increased significantly, from approximately 1 year to almost 4 years after introduction of cohort isolation (P < 0.0001). After introduction of early intensive treatment, the probability of still not having developed chronic PA infection 7 years after the first isolation of PA was above 80% (P < 0.0001). In conclusion, the introduction of cohort isolation and early intensive treatment following the initial isolation of PA resulted in a reduced incidence and prevalence of chronic PA infection. We are not aware of other studies showing a decreasing prevalence of chronic PA infection, as survival of CF patients has increased.

Adolescent↗
PubMed1999

Immunoblockade of endogenous glucagon-like peptide-1 by monoclonal antibodies in conscious rats: effect on the insulin response to intragastric glucose.

The physiological action of endogenous active forms of glucagon-like peptide-1 (GLP-1) on the insulin response to intragastric glucose was studied in conscious male Wistar rats by immunoblockade with two monoclonal antibodies directed against different epitopes of GLP-1(7-36)amide. Plasma concentrations of intraperitoneally injected monoclonal antibodies were determined before and during each experiment by an enzyme-linked immunosorbent assay (ELISA) specific for GLP-1-binding antibodies. Three hours after injection of the two monoclonal antibodies, the plasma insulin response (area under the curve) following intragastric glucose 1 g/kg was reduced to a mean level (mean +/- SEM) of 60%+/-8% (n = 11) of control responses previously determined in the same rats, and the time course of the response showed almost no increase in insulin during the first 10 minutes, reaching a maximum of 45.1+/-4.6 microU/mL at 30 minutes, in contrast to the rapid increase of the control response to a maximum of 64.5+/-5.1 microU/mL at 15 minutes. Total C-terminally amidated GLP-1 measured by radioimmunoassay (RIA) of acid ethanol-extracted plasma increased from a mean basal level of 10+/-2 pmol/Lto a peak of 31+/-5 pmol/L at 15 minutes in the control experiments, while basal and response levels greater than 100 pmol/L were recorded after antibody treatment. The increase of plasma glucose was reduced in the presence of the antibodies, peaking at a mean of 9.7+/-0.3 mmol/L at 30 minutes, compared with 11.8+/-0.5 mmol/L at 30 minutes in the control experiments. The action of GLP-1 appears particularly important for the early insulin response to ingested glucose, and the unexpected effect of the antibodies on the glucose response may point to a net promoting effect of GLP-1 on intestinal glucose absorption.

Animals↗
PubMed1999

Attention activates winner-take-all competition among visual filters.

Shifting attention away from a visual stimulus reduces, but does not abolish, visual discrimination performance. This residual vision with 'poor' attention can be compared to normal vision with 'full' attention to reveal how attention alters visual perception. We report large differences between residual and normal visual thresholds for discriminating the orientation or spatial frequency of simple patterns, and smaller differences for discriminating contrast. A computational model, in which attention activates a winner-take-all competition among overlapping visual filters, quantitatively accounts for all observations. Our model predicts that the effects of attention on visual cortical neurons include increased contrast gain as well as sharper tuning to orientation and spatial frequency.

Attention↗
PubMed1999

How voltage-dependent conductances can adapt to maximize the information encoded by neuronal firing rate.

Information from the senses must be compressed into the limited range of responses that spiking neurons can generate. For optimal compression, the neuron's response should match the statistics of stimuli encountered in nature. Given a maximum firing rate, a nerve cell should learn to use each available firing rate equally often. Given a set mean firing rate, it should self-organize to respond with high firing rates only to comparatively rare events. Here we derive an unsupervised learning rule that continuously adapts membrane conductances of a Hodgkin-Huxley model neuron to optimize the representation of sensory information in the firing rate. Maximizing information transfer between the stimulus and the cell's firing rate can be interpreted as a non-Hebbian developmental mechanism.

Electric Conductivity↗
PubMed1999

Secular changes in anthropometric data in cystic fibrosis patients.

The aim of this study was to study the secular changes in anthropometric data over calendar time in patients with cystic fibrosis (CF). Growth curves were constructed for 270 patients based on height and weight registrations from the medical files. Height, body mass index (BMI), magnitude of pubertal peak height velocity (PHV) and age at PHV were analysed for possible secular changes from the 1960s to the 1990s. There was a significant change in height over calendar time in only 1 of 12 age groups. BMI showed a significant increase in 10- and 15-y-old boys and girls and in 5-y-old girls. The magnitude of PHV changed significantly over time, whereas age at PHV was constant. No significant changes in height and age at PHV over calendar time were observed; this was probably due to a selection bias since the oldest patients, who survived to be part of the present investigation, represented milder forms of the disease. The increase in BMI and change in magnitude of PHV over calendar time may reflect the improvement in treatment leading to a better survival and clinical status through puberty. The increase in BMI and change in magnitude of PHV were sufficient to overcome the selection bias from older patients with milder disease.

Adolescent↗
PubMed1999

T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density.

CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is up-regulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb. Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 10(8) and 7 x 10(9) M-1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity (KA > 7 x 10(9) M-1) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of 'activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.

Animals↗
PubMed1999

Management of spinal dural arteriovenous fistulae using an interdisciplinary neuroradiological/neurosurgical approach: experience with 47 cases.

OBJECTIVE: Spinal dural arteriovenous fistulae (SDAVFs) are frequently diagnosed after unacceptable delays and are therefore treated at a disadvantageously advanced stage. There is controversy regarding their treatment and the respective roles of interventional neuroradiologists and neurosurgeons. We present our series of 47 patients to illustrate the necessity for early treatment and the value of an interdisciplinary approach. METHODS: All patients exhibited suspicious magnetic resonance imaging and/or myelographic findings. Subsequent spinal angiography revealed the SDAVFs. Twelve patients were treated primarily by surgical interruption of the arterialized intradural draining vein, and eight patients underwent surgery after unsuccessful embolization. Twelve patients were surgically treated several months after embolization because of the recruitment of collateral vessels. Definitive embolization was achieved for 15 patients. All patients were monitored with magnetic resonance imaging and at least one control angiographic examination. Follow-up periods ranged from 2 months to 8 years. RESULTS: There was an obvious male prevalence, with 35 male and 12 female patients. Only six of the patients were less than 50 years of age. The SDAVFs were found twice as often on the left side, compared with the right. A total of 85% of the SDAVFs were located between T2 and L2. Presenting signs were most often progressive paraparesis, with 66% of the patients exhibiting progression to a condition in which they could not walk without support or were confined to a wheelchair. For 50% of the patients, the time at which the correct diagnosis was established was more than 15 months after the onset of the first symptoms. After treatment, 18 patients showed improvement (38%), the conditions of 26 patients (55%) were unchanged (without further deterioration), and the conditions of three patients (6%) had deteriorated. CONCLUSION: Attempts at embolization should be made at the time of angiography, because no adverse effects were recorded in our series and there was a 30% chance of the patients being cured by that modality alone. Even if recanalization occurs, the internal labeling of a feeding vessel with radio-opaque embolization material allows exact intraoperative fluorographic localization of the origin of the draining vein, facilitating minimally invasive surgical exposure.

Adult↗
PubMed1999

Constitutive activation of the human bradykinin B2 receptor induced by mutations in transmembrane helices III and VI.

We report that mutation of specific residues in the human B2 bradykinin (BK) receptor induces its marked constitutive activation, evaluated through inositol phosphate production in COS-7 cells expressing the wild-type or mutant receptors. We provide evidence for a strikingly high constitutive activation of the B2 receptor induced by alanine substitution of the Asn113 residue, located in the third transmembrane domain. These results are reminiscent of our previous finding that mutation of the homologous Asn111 residue induces constitutive activation of the AT1 angiotensin II receptor. BK overstimulation of the constitutively activated mutant N113A receptor was also observed. Phe replacement of the Trp256 residue, fairly conserved in transmembrane domain VI of G protein-coupled receptors, also induced a less prominent but significant constitutive activation. Interestingly, the peptidic HOE 140 compound and an original nonpeptidic compound LF 16 0335, which both behaved as inverse agonists of the wild-type receptor expressed in COS-7 cells, became potent and efficient agonists of the two constitutively activated mutant N113A and W256F receptors. These parallel changes observed for two chemically unrelated series can serve as a basis for future studies of structure-function relationships and modeling of activation processes, based on a detailed analysis of the network of helix-helix interactions, which stabilize the inactive receptor conformation and undergo rearrangements on transition to activated states.

Animals↗
PubMed1999

Vibrio anguillarum resistance to rainbow trout (Oncorhynchus mykiss) serum: role of O-antigen structure of lipopolysaccharide.

The sensitivity of Vibrio anguillarum to the bactericidal effect of rainbow trout serum was investigated with different strains of serogroups O1 and O2a, which are the most frequently found serogroups in clinical outbreaks of vibriosis. All of the V. anguillarum strains were able to activate complement in rainbow trout serum, but smooth strains of V. anguillarum serogroup O1 were resistant to complement-mediated killing in the absence of specific antibodies. In the case of V. anguillarum serogroup O2a strains, 80% of the analyzed strains were resistant to rainbow trout serum even when specific antibodies were present. Analysis of the lipopolysaccharide structures of the tested V. anguillarum strains showed a positive correlation between the O-antigen size of the lipopolysaccharide and resistance to serum killing. The classical complement pathway was responsible for the antibody-dependent serum killing of susceptible V. anguillarum strains. When serum-resistant V. anguillarum serogroup O2a strains were grown in glucose-enriched Lennox L broth, they produced lipopolysaccharide molecules with fewer high-molecular-weight O-antigen units than did strains grown in broth without the addition of glucose. Strains grown in glucose-enriched medium became sensitive to rainbow trout serum killing, indicating that the high-molecular-weight O-antigen side chains prevented the activated complement from damaging the bacterium.

Animals↗
PubMed1999

Bone mineral status in 134 patients with cystic fibrosis.

AIM: To investigate bone mineral status in patients with cystic fibrosis (CF). PATIENTS AND METHODS: Whole body bone mineral content (BMC), projected bone area, and bone mineral density (BMD) were determined by dual energy x ray absorptiometry in 134 patients with CF and compared with 396 healthy controls. RESULTS: In patients </= 19 years of age, BMD for age was normal in boys and marginally reduced in girls, whereas BMC for age was significantly reduced in both sexes. Height for age and bone area for height were significantly reduced, indicating "short" and "narrow" bones, whereas BMC for bone area was increased, indicating increased size corrected BMC. In patients > 19 years of age, BMD and BMC for age were significantly reduced. CONCLUSION: Short and narrow bones were the main reasons for reduced BMC for age in patients </= 19 years of age, indicating that treatment to prevent osteoporosis in younger patients should be directed at increasing bone size, whereas conventional treatment with calcium and vitamin D supplementation alone might not be as effective. Because of the significant decrease in BMD and BMC in adult patients, we fear that these patients may develop osteoporotic fractures prematurely.

Absorptiometry, Photon↗