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Biomedical subjects

C Koch

Publications and source records attributed to C Koch.

At least 127 records · Page 7Linked to original sources
PubMed1999

Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA).

BACKGROUND: IgG and IgG subclass antibodies to Aspergillus fumigatus (A fumigatus) were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic bronchopulmonary aspergillosis (ABPA). METHODS: An ELISA technique using water soluble somatic hyphal (WSSH) A fumigatus antigens and subclass specific monoclonal antibodies was used for cross sectional quantification of IgG and IgG1-4 subclass antibody levels in the serum of 238 patients with cystic fibrosis and 107 healthy controls. RESULTS: In patients with cystic fibrosis persistently colonised with A fumigatus the subclass antibody levels were significantly increased compared with patients with cystic fibrosis never or rarely colonised (p < 0.001). The group of patients persistently colonised with A fumigatus with ABPA (+Af+ABPA) had significantly increased levels of IgG antibodies to A fumigatus (Af-IgG) (median 69 ELISA units (EU) versus 31) and of subclasses Af-IgG1 (91 versus 27), Af-IgG2 (143 versus 56), and Af-IgG4 antibodies (72 versus 20), but not of IgG3 (17 versus 15), compared with the colonised patients without ABPA (+Af-ABPA). Patients with cystic fibrosis with no or only rare isolates of A fumigatus without ABPA (-Af-ABPA) also had significantly increased subclass antibody levels (Af-IgG1 9 versus 3, Af-IgG2 28 versus 5, Af-IgG4 16 versus 4; p < 0.001) compared with healthy controls. Low, although detectable, levels of antibodies were demonstrated in healthy controls. ABPA seemed to occur independently of Pseudomonas aeruginosa infection. Using diagnostic cut off levels for ABPA, sensitivity and specificity were calculated. The highest specificity was found for IgG4 (88%); sensitivity was between 65% and 73%. The positive predictive values (PPV) were moderate, whereas the negative predictive values (NPV) were high (96% in all subclasses except IgG3 with 94%). PPV increased to 50% if IgG1 as well as IgG2 and IgG4 were included. CONCLUSIONS: In a large number of unselected patients with cystic fibrosis significantly increased levels of Af-specific antibodies belonging to total IgG and all four subclasses were found in all groups of patients compared with healthy controls. In patients persistently colonised with A fumigatus these levels were significantly higher than in non-colonised patients, and the significantly highest levels (with the exception of IgG3) were found in patients with ABPA. Using a sensitive ELISA technique, measurements of IgG and IgG subclass antibodies to A fumigatus might be of importance in the management of ABPA, especially as a screening test to exclude the presence of ABPA; other tests are needed to confirm the diagnosis.

Adolescent↗
PubMed1999

An analog VLSI implementation of a visual interneuron: enhanced sensory processing through biophysical modeling.

Flies are capable of rapid, coordinated flight through unstructured environments. This flight is guided by visual motion information that is extracted from photoreceptors in a robust manner. One feature of the fly's visual processing that adds to this robustness is the saturation of wide-field motion-sensitive neuron responses with increasing pattern size. This makes the cell's responses less dependent on the sparseness of the optical flow field while retaining motion information. By implementing a compartmental neuronal model in silicon, we add this "gain control" to an existing analog VLSI model of fly vision. This results in enhanced performance in a compact, low-power CMOS motion sensor. Our silicon system also demonstrates that modern, biophysically-detailed models of neural sensory processing systems can be instantiated in VLSI hardware.

Algorithms↗
PubMed1999

Encoding of visual information by LGN bursts.

Encoding of visual information by LGN bursts. Thalamic relay cells respond to visual stimuli either in burst mode, as a result of activation of a low-threshold Ca2+ conductance, or in tonic mode, when this conductance is inactive. We investigated the role of these two response modes for the encoding of the time course of dynamic visual stimuli, based on extracellular recordings of 35 relay cells from the lateral geniculate nucleus of anesthetized cats. We presented a spatially optimized visual stimulus whose contrast fluctuated randomly in time with frequencies of up to 32 Hz. We estimated the visual information in the neural responses using a linear stimulus reconstruction method. Both burst and tonic spikes carried information about stimulus contrast, exceeding one bit per action potential for the highest variance stimuli. The "meaning" of an action potential, i.e., the optimal estimate of the stimulus at times preceding a spike, was similar for burst and tonic spikes. In within-trial comparisons, tonic spikes carried about twice as much information per action potential as bursts, but bursts as unitary events encoded about three times more information per event than tonic spikes. The coding efficiency of a neuron for a particular stimulus is defined as the fraction of the neural coding capacity that carries stimulus information. Based on a lower bound estimate of coding efficiency, bursts had approximately 1.5-fold higher efficiency than tonic spikes, or 3-fold if bursts were considered unitary events. Our main conclusion is that both bursts and tonic spikes encode stimulus information efficiently, which rules out the hypothesis that bursts are nonvisual responses.

Action Potentials↗
PubMed1999

Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

Adolescent↗
PubMed1999

Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae.

A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.

Adolescent↗
PubMed1999

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients.

OBJECTIVE: The aim of the present study was to investigate whether patients with cystic fibrosis (CF) are GH resistant with increased GH release and decreased concentrations of IGF-I as a result of malabsorption, increased catabolism and impaired glucose tolerance. DESIGN: Twenty CF patients were included, ten with normal glucose tolerance (five male, five female, median age 25.5 years (range 20-31)) and ten with diabetes mellitus (five male, five female, median age 25.3 years (range 17-45). Twenty healthy individuals served as controls (ten male, ten female, median age 28.4 years (range 18-36)). METHODS: GH status was evaluated by 12h spontaneous GH release during the night time, arginine-stimulated GH release and the basal concentrations of IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3). Twelve hour spontaneous GH profiles were estimated using a constant blood withdrawal technique with sampling every 30min and the Pulsar method was used for the analysis of profiles. RESULTS: No significant differences were found in spontaneous and stimulated GH release in CF patients compared with healthy controls, whereas IGF-I and IGFBP-3 were significantly decreased in CF patients compared with healthy controls. The combination of reduced IGF-I and IGFBP-3 with normal GH release points to a relative GH resistance or a disturbance in the pituitary axis in patients with CF. The spontaneous GH release, the stimulated GH release and the basal concentrations of IGF-I and IGFBP-3 were not significantly different in diabetic CF patients compared with CF patients with normal glucose tolerance and the presence of diabetes mellitus was not consistent with increased GH resistance in CF patients. CONCLUSION: CF patients with normal glucose tolerance and diabetic CF patients had normal GH release and decreased concentrations of IGF-I indicating a relative GH resistance.

Adolescent↗
PubMed1999

Role of geons in object recognition across ages.

Little research has been conducted regarding the developmental implications of Biederman's 1987 Recognition by Components theory. The present study compared objects fragmented according to this theory, i.e., vertices were left intact and midsegments were deleted, with objects that were randomly fragmented. A total of 169 students from three age groups (first grade, fourth grade, and college) participated. Approximately half of the participants viewed pictures with intact vertices and half viewed the randomly fragmented pictures. Analysis showed that participants recognized more pictures across groups; however, there were no significant differences between the two sets of pictures. This finding suggests that vertices are important but are not necessary for object recognition. The role of midsegments in object recognition is also discussed.

Adolescent↗
PubMed1999

Attentional capacity is undifferentiated: concurrent discrimination of form, color, and motion.

We report a series of experiments on the concurrent discrimination of form, color, and motion attributes. All tasks involved joint discrimination of attributes, and positions and were highly demanding of attention. We quantified interference between concurrent discriminations by establishing the attention-operating characteristic. Interference was indistinguishable for similar and dissimilar task combinations (form-form, color-color, motion-motion, and color-form, color-motion, motion-color, and motion-form, respectively). These results suggest strongly that different visual discriminations draw on the same attentional capacity--in other words, that the capacity of visual attention is undifferentiated.

Attention↗
PubMed1999

A hypertext-based tutorial with links to the Web for teaching statistics and research methods.

An online tutorial for research design and statistics is described. This tutorial provides a way for students to learn how scales of measure, research design, statistics, and graphing data are related. The tutorial also helps students determine what statistical analysis is appropriate for a given design and how the results of the analysis should be plotted in order to effectively communicate the results of a study. Initial research suggests that students using the tutorial are more accurate in their decisions about the design and statistics associated with a study. Students are also more confident in the decisions and find them easier to make when using the tutorial. Furthermore, practice with the tutorial appears to improve problem-solving ability in subsequent design and statistics scenarios. Implications for teaching statistics and research design are discussed.

Computer-Assisted Instruction↗
PubMed1999

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. III. New DNA-binding metabolites.

Based on the chemical screening technique, biomolecular-chemical screening has been developed which makes use of two-dimensional TLC analysis of microbial extracts and combines thin-layer chromatography (RP-18) with binding studies towards DNA. In the first dimension the metabolites of the crude microbial extract are separated, and in the second dimension binding properties towards DNA are analysed. An initial screening program with 500 microbial extracts prepared by solid-phase extraction with XAD-16 resin resulted in 17 samples which contained metabolites with significant DNA-binding behavior. Fermentation, isolation and structural characterization led to already known metabolites [phenazine-1,6-dicarboxylate (1), phencomycin (2), 11-carboxy-menoxymycin B (3), soyasaponine I (4), and (8S)-3-(2-hydroxypropyl)-cyclohexanone (5)], as well as to new secondary metabolites. Fermentation of the producing organisms of the new DNA-binding metabolites, ent-8,8adihydro-ramulosin (6). (2R,4R)-4-hydroxy-2-(1,3-pentadienyl)-piperidine (7), (5R)-dihydro-5-pentyl-4'-methyl-4'-hydroxy-2(3H)-furanone (8), and seco-4,23-hydroxyoleane-12-en-22-one-3-carboxylic acid (9), as well as isolation, structural characterization, and physico-chemical properties are reported.

Chromatography, Thin Layer↗
PubMed1998

Affinity chromatography of serine proteases on the triazine dye ligand Cibacron Blue F3G-A.

The interaction between complement component factor B and the triazine dye ligand Cibacron Blue F3G-A coupled to a cross-linked agarose matrix (Blue Sepharose) was found to involve the Bb part of the molecule, and to be inhibited by benzamidine. Human, chicken and rainbow trout factor B which had bound to Blue Sepharose could, subsequently be eluted with benzamidine. Other serine proteases (C2, factor II, factor IX, trypsin, chymotrypsin, proteinase 3) also bound to Blue Sepharose but only those belonging to the trypsin family could be eluted with benzamidine. Trypsin treated with the active-site inhibitor phenylmethylsulfonyl fluoride did not bind to Blue Sepharose and pretreatment of Blue Sepharose with benzamidine did not influence binding of proteases. We conclude that trypsin-like serine proteases can be purified on Blue Sepharose and that the interaction of these serine proteases with Blue Sepharose involves the active site of the enzyme.

Animals↗
PubMed1998

A human T-cell leukemia virus Tax variant incapable of activating NF-kappaB retains its immortalizing potential for primary T-lymphocytes.

The human T-cell leukemia virus type 1 (HTLV-1) transactivator (Tax) has been shown to interfere with regulated cellular proliferation. Many studies have focused on the ability of Tax to transform rodent fibroblasts; however, none has defined the molecular requirements for Tax transformation of human lymphoid cells. We show here that tax induces permanent growth of human primary T-lymphocytes by using a transformation/immortalization defective rhadinovirus vector. The cells phenotypically resemble HTLV-immortalized lymphocytes and contain episomally persisting recombinant rhadinoviral sequences, which stably express functional Tax protein. As Tax can activate major cellular signal transducing pathways including NF-kappaB and cAMP-responsive element binding protein (CREB), we asked for the relevance of these routes in the immortalization of human lymphocytes. By using Tax mutants that either activate exclusively CREB/activating transcription factor or are defective in activating this signaling pathway, we delineated that Tax can induce immortalization of primary human T-lymphocytes through a mechanism independent of NF-kappaB activation.

Cell Line, Transformed↗
PubMed1998

Feature extraction by burst-like spike patterns in multiple sensory maps.

In most sensory systems, higher order central neurons extract those stimulus features from the sensory periphery that are behaviorally relevant (e.g.,Marr, 1982; Heiligenberg, 1991). Recent studies have quantified the time-varying information carried by spike trains of sensory neurons in various systems using stimulus estimation methods (Bialek et al., 1991; Wessel et al., 1996). Here, we address the question of how this information is transferred from the sensory neuron level to higher order neurons across multiple sensory maps by using the electrosensory system in weakly electric fish as a model. To determine how electric field amplitude modulations are temporally encoded and processed at two subsequent stages of the amplitude coding pathway, we recorded the responses of P-type afferents and E- and I-type pyramidal cells in the electrosensory lateral line lobe (ELL) to random distortions of a mimic of the fish's own electric field. Cells in two of the three somatotopically organized ELL maps were studied (centromedial and lateral) (Maler, 1979; Carr and Maler, 1986). Linear and second order nonlinear stimulus estimation methods indicated that in contrast to P-receptor afferents, pyramidal cells did not reliably encode time-varying information about any function of the stimulus obtained by linear filtering and half-wave rectification. Two pattern classifiers were applied to discriminate stimulus waveforms preceding the occurrence or nonoccurrence of pyramidal cell spikes in response to the stimulus. These signal-detection methods revealed that pyramidal cells reliably encoded the presence of upstrokes and downstrokes in random amplitude modulations by short bursts of spikes. Furthermore, among the different cell types in the ELL, I-type pyramidal cells in the centromedial map performed a better pattern-recognition task than those in the lateral map and than E-type pyramidal cells in either map.

Action Potentials↗
PubMed1998

Constraints on cortical and thalamic projections: the no-strong-loops hypothesis.

The many distinct cortical areas of the macaque monkey visual system can be arranged hierarchically, but not in a unique way. We suggest that the connections between these cortical areas never form strong, directed loops. For connections between the visual cortex and particular thalamic nuclei, we predict that certain types of connections will not be found. If strong, directed loops were to exist, we suggest that the cortex would go into uncontrolled oscillations.

Animals↗
PubMed1998

Pseudomonas aeruginosa and Burkholderia cepacia infection in cystic fibrosis patients treated in Toronto and Copenhagen.

Differences in the course of pulmonary disease in cystic fibrosis (CF) may be altered by different treatment strategies in different CF centers. The Copenhagen clinic uses scheduled, regular and very aggressive treatment of lung infection. The Toronto clinic treats pulmonary infection with oral, inhaled, or intravenous antibiotics, and has emphasized aggressive nutritional therapy. This study compared the clinical status of CF patients treated in the two centers (Toronto, Canada, n=302, and Copenhagen, Denmark, n=214) using a cross-sectional design in terms of Pseudomonas aeruginosa (PA) and Burkholderia cepacia (BC) lung infections, pulmonary function, and levels of PA and BC precipitating antibodies (precipitins). Median ages were similar, but the age distribution was significantly different, with a higher proportion of patients under 10 and > or = 25 years in Toronto, and higher proportion of patients 11-24 years of age in Copenhagen. A higher number of female patients was observed in Copenhagen than in Toronto. Seventy-nine percent of Copenhagen patients, and 52% of Toronto patients were deltaF508 homozygous. Of all the patients, 20.1% of Copenhagen patients and 38% of Toronto patients were deltaF508 heterozygous. Ten percent of Toronto patients had two uncommon mutations. Pulmonary function and nutritional status in both groups were similar despite varying treatment strategies. The prevalence of PA was lower in Danish children and higher in Danish adults than in Canada. These differences are probably due to cohort isolation, which was introduced in Copenhagen in 1981. The prevalence of BC was higher in Toronto than in Copenhagen patients at all ages. In both centers, the number of PA and BC precipitins increased with age in patients chronically infected with PA and BC, respectively, and the number of both PA and BC precipitins rose with declining lung function. This study suggests that the clinic populations had similar pulmonary and nutritional statuses despite differing clinic antibiotic treatment strategies. Microbial colonization seemed to differ, at least in part, because of differences in cohort isolation strategies. Early, aggressive anti-pseudomonal chemotherapy may have reduced pseudomonal colonization among younger patients in Copenhagen. Future studies will be required to assess the impact of this on this cohort's outcome.

Adolescent↗
PubMed1998

[Congestive myelopathy caused by spinal dural arteriovenous fistulas. Anamnesis, clinical aspects, diagnosis, therapy and prognosis].

Congestive myelopathy, formerly referred to as varicosis spinalis or Foix-Alajouanine syndrome, is caused by a spinal dural arteriovenous fistula (SDAVF). So far, the blood supply from the meningeal arteries draining through the fistula into the medullary venous system can only be verified by spinal angiography. Patients predominantly male and over the age of 60 are afflicted. Initially reversible functional disorders caused by the congestion of the spinal cord veins eventually become irreversible, the most common symptom being an increasingly paretic gait disorder, the signs of which generally begin symmetrically and progress from distal to proximal signs. Simultaneously, predominantly transverse sensory dysfunctions develop, as well as bladder and bowel dysfunctions, most often leading to incontinence. MRI typically shows a central medullary signal enhancement with slight swelling of the afflicted region, initially indicative of a reversible congestive edema and later of an irreversible infarction, and extended perimedullar vessels. Thus, if the clinical course and the characteristic MRI findings suggest the possibility of disease related to congestive myelopathy, spinal angiography becomes indispensable. Since ensuing the success of therapy and prognosis depends on rapid determination of the extent of the illness, a speedy diagnostic reaction is mandatory to institute the treatment necessary to prevent paraplegia.

Adult↗
PubMed1998

Periparturient rise in fecal egg counts associated with prolactin concentration increase in French Alpine dairy goats.

Previous data on periparturient relaxation of immunity during gastrointestinal nematode infection in goats are scarce and conflicting; one study carried out in fiber (Angora) goats showed a positive association of fecal egg counts with prolactin concentrations around parturition, whereas the two other available studies dealing with dairy goats, gave divergent results. The objectives of the study were thus to assess the occurrence of a periparturient rise in fecal egg counts in dairy goats and to examine a possible relationship between the level of milk production and the intensity of the periparturient rise. A total of 28 French Alpine grazing dairy goats naturally infected with Teladorsagia, Trichostrongylus, and Oesophagostomum were allocated into two groups according to their reproductive status; group 1 (n = 7) consisted of nonpregnant lactating animals in the 3rd month of lactation, whereas group 2 (n = 21) was composed of dry goats at 6 weeks before term. Fecal egg counts, pepsinogen and phosphate blood concentrations, blood eosinophil counts, and prolactin concentrations were individually monitored at weekly intervals for 12 weeks (from midwinter to early spring). The mean fecal egg counts were significantly higher in pregnant goats during the 2 weeks before (668 versus 242 eggs per gram of feces (epg), P < 0.05) and the 2 weeks after (962 versus 279 epg, P < 0.01) parturition as compared with nonpregnant lactating animals. No significant difference was seen in the composition of larval cultures between the two groups of animals, with Oesophagostomum infective larvae being found predominantly, particularly at the time of parturition. Pepsinogen and phosphate concentrations as well as blood eosinophil counts were similar between the two groups throughout the survey and indicated a moderate larval challenge. The mean prolactin concentration measured in pregnant goats was significantly higher (P < 0.01) at the time of parturition (298 versus 130 ng ml(-1)) and at 4 weeks after parturition (387 versus 193 ng ml(-1)) than that determined in nonpregnant animals. Furthermore, a significant correlation (rs = 0.30, df = 79; P < 0.01) between fecal egg counts and prolactin concentrations was recorded for the pregnant goats during the 4-weeks period around parturition.

Animals↗