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Biomedical subjects

C Koch

Publications and source records attributed to C Koch.

At least 379 records · Page 21Linked to original sources

The action of the corticofugal pathway on sensory thalamic nuclei: a hypothesis.

The N-methyl-D-aspartate receptor has recently attracted great interest due to its nonlinear current-voltage behavior. In order to evoke a large depolarizing postsynaptic current, the synaptic-induced conductance change must be paired with a postsynaptic depolarization. This temporally tuned AND gate could underlie a number of different operations throughout the nervous system. We propose that the synapses made by the optical nerve onto projection cells in the mammalian dorsal lateral geniculate nucleus are of the N-methyl-D-aspartate type. [In this Commentary, we have pooled data regarding sensory thalamic nuclei from a number of different mammalian species. Unless otherwise mentioned, we have referred to the dorsal division of the cat lateral geniculate nucleus.] About half of all synapses in these cells--located almost exclusively in the peripheral two-thirds of the dendritic tree--are associated with axons originating in layer VI of visual cortex. It then follows that the massive corticogeniculate pathway controls the gain of the retinogeniculate pathway via its action on the N-methyl-D-aspartate receptors. Thus, near-simultaneous activation of the retinal and the cortical input will transiently enhance the geniculate cell response. Generalizing to other thalamic sensory nuclei, afferent information will be routed through the thalamus and on to the cortex as long as cortical activity is congruent with sensory input to the thalamus. Experimental evidence argues for such a mechanism to control the gain of the somatosensory input to the ventrobasal thalamic nucleus.

Animals↗

Combined imipenem/cilastatin and tobramycin therapy of multiresistant Pseudomonas aeruginosa in cystic fibrosis.

Ten patients with cystic fibrosis (CF) and chronic broncho-pulmonary Pseudomonas aeruginosa infection were given imipenem/cilastatin (100 mg/kg/day) in combination with tobramycin (15 mg/kg/day). Forced vital capacity and forced expiratory volume in the first second improved significantly in nine out of ten patients, and most of the patients improved clinically. P. aeruginosa was not eradicated in any patient and resistance against imipenem developed in all patients during treatment. A concomitant increase in MIC of piperacillin and ceftazidime occurred during treatment. In-vitro bactericidal synergy of imipenem and tobramycin was noted in 57% of pretreatment isolates. Seven patients complained of adverse reactions, mainly gastrointestinal, and treatment of three patients was discontinued after 5, 8, and 12 days of therapy, because of rash or nausea and vomiting. The side effects were considered to be due to imipenem/cilastatin. Because of the rapid development of imipenem resistance despite combination therapy, the high proportion of side effects, and the risk of induction of beta-lactam resistance, imipenem/cilastatin cannot be recommended for routine treatment of CF-patients with P. aeruginosa infection.

Adolescent↗

Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospective double-blind placebo-controlled study of colistin inhalation. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.

Administration, Inhalation↗

The efficacy and safety of ciprofloxacin and ofloxacin in chronic Pseudomonas aeruginosa infection in cystic fibrosis.

The clinical efficacy and safety of ciprofloxacin and ofloxacin were compared in a prospective, randomized double blind, placebo combined cross-over study in 26 adult cystic fibrosis patients with chronic broncho-pulmonary Pseudomonas aeruginosa infection. Active treatment consisted of ciprofloxacin 750 mg orally twice daily or ofloxacin 400 mg orally twice daily; both treatments were given for 14 days, with three months between treatment periods; 21 patients completed both treatment periods. Treatment with both ciprofloxacin and ofloxacin was associated with a good clinical response as judged by clinical score, lung function tests and inflammatory parameters; no difference between ciprofloxacin and ofloxacin was found. Adverse reactions were seen in nine of 24 patients who received ciprofloxacin and in six of 23 who received ofloxacin. The majority were dyspeptic reactions or photosensitivity. No serious adverse reactions occurred. Three cases of treatment failure were found, one of which was associated with development of resistant P. aeruginosa during ofloxacin treatment. The mean MIC of both drugs increased during treatment but returned to pretreatment values within three months. Ciprofloxacin and ofloxacin seem to be valuable agents for intermittent treatment of chronic P. aeruginosa lung infection in adult cystic fibrosis patients.

Adolescent↗

Management of Pseudomonas aeruginosa lung infection in Danish cystic fibrosis patients.

The annual mortality rate of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection at the Danish CF-centre ranged from 10 to 20% in the years 1970-1975. In this period the patients received antipseudomonal chemotherapy only during acute exacerbations of infection. From 1976 99 patients acquired chronic P. aeruginosa infection and were given regular and intensive antipseudomonal treatment 3-4 times per year. The patients were followed for 612 patient-years; 7 died and the 10-year survival rate after onset of P. aeruginosa infection was 90% +/- 4%. The annual mortality rate is now 1-2%. Although precipitating antibodies against P. aeruginosa increased significantly, pulmonary function did not deteriorate with duration of infection. Cross-infection between patients caused an increased incidence of chronic P. aeruginosa infection which was reduced by hygienic measures.

Adolescent↗

Double-antibody sandwich enzyme-linked immunosorbent assay for rapid detection of toxin-producing Corynebacterium diphtheriae.

An enzyme-linked immunosorbent assay for determining the toxigenicity of Corynebacterium diphtheriae is presented. The assay uses hyperimmune horse diphtheria antitoxin as a capture antibody and mouse monoclonal diphtheria antitoxin as a detecting antibody. Growth of bacteria and capture of diphtheria toxin by antitoxin are carried out in one step. Toxin produced by as little as 100 toxin-producing corynebacteria is detectable, corresponding to a sensitivity of 10 ng of diphtheria toxin per ml. Demonstration of toxin after incubation of the bacteria for 4.75 h, as well as after 18 h, was in accordance with the modified Elek gel diffusion method and the guinea pig inoculation test. However, heavy inocula incubated overnight produced significantly lower optical density than did diluted inocula; thus, the higher optical density was used as an indicator of toxin production. A decrease in optical density was also seen by shortening the incubation time. For laboratory safety, ethanol was added to the microtiter plate wells before washing out of the bacteria. This resulted in a further decrease in optical density. Using 4.75-h incubation time gave a single false-negative result. No false-positive results were ever seen. Incubation for 18 h is suitable for large-scale screening, and 4.75 h of incubation is suitable for rapid identification of toxin-producing C. diphtheriae.

Corynebacterium diphtheriae↗

Meningococcal disease in congenital absence of the fifth component of complement.

We describe a family in which 2 brothers had meningococcal infection, 1 of them twice. Their parents were first degree cousins. The brothers showed a complete, isolated deficiency of C5, both antigenic and functional. The parents had half-normal values, and the data are compatible with an inherited C5 deficiency where the defect is transmitted as an autosomal codominant trait.

Adult↗

Effect of N-acetylcysteine on the human nasal ciliary activity in vitro.

N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher concentrations. Using a microphoto-oscillographic method combined with microperfusion technique, we studied the direct effect of NAC on human nasal cilia. NAC caused a direct dose- and time-related decrease in ciliary beating frequency, which was detectable at 2 mg/ml and reached statistically significant levels at 20 mg/ml. NAC at 200 mg/ml caused total cessation of movements within 15 s but this effect was completely reversible within 15 min of perfusion with medium alone. At no concentrations of NAC was beating frequency increased over base-line. NAC, however, had no effect on beating pattern. NAC seems to have a selective and fully reversible inhibitory effect on the beating frequency of human cilia in vitro.

Acetylcysteine↗

Purification and properties of the Escherichia coli host factor required for inversion of the G segment in bacteriophage Mu.

G inversion in bacteriophage Mu requires the product of the DNA invertase gene gin and an Escherichia coli host factor termed FIS (factor for inversion stimulation). A recombination substrate must contain two recombination sites, arranged as inverted repeats, and a recombinational enhancer sequence termed sis. FIS has been purified to homogeneity. The purified protein has a relative molecular weight of 12,000 when analyzed under denaturing conditions. The intact protein behaves as a dimer of relative molecular weight 25,000 in gel filtration analysis. The purified protein does not possess any recombinogenic activity when assayed in the absence of the DNA-invertase Gin. In the presence of purified Gin FIS is the only additional protein required for efficient inversion. By performing gel retention assays, we show that FIS is a DNA-binding protein, which specifically binds to DNA fragments containing the recombinational enhancer sis.

Chromatography↗

Regulation of Na+ transport in brown adipose tissue.

In order to test the hypothesis that Na+, K+-ATPase (Na+,K+-dependent ATPase) is involved in the noradrenaline-mediated stimulation of respiration in brown adipose tissue, the effects of noradrenaline on Na+,K+-ATPase in isolated brown-fat-cell membrane vesicles, and on 22Na+ and K+ (86Rb+) fluxes across the membranes of intact isolated cells, were measured. The ouabain-sensitive fraction of the K+-dependent ATPase activity in the isolated membrane-vesicle preparation was small and was not affected by the presence of noradrenaline in the incubation media. The uptake of 86Rb+ into intact hormone-sensitive cells was inhibited by 80% by ouabain, but it was insensitive to the presence of noradrenaline. 22Na+ uptake and efflux measured in the intact cells were 8 times more rapid than the 86Rb+ fluxes and were unaffected by ouabain. This indicated the presence of a separate, more active, transport system for Na+ than the Na+,K+-ATPase. This is likely to be a Na+/Na+ exchange activity under normal aerobic conditions. However, under anaerobic conditions, or conditions simulating anaerobiosis (2 mM-NaCN), the unidirectional uptake of Na+ increased dramatically, while efflux was unaltered.

Adenosine Triphosphatases↗

Regulation of the uncoupling protein in brown adipose tissue.

Presumptive evidence suggests that the brown fat mitochondrial uncoupling protein, thermogenin, is involved in the mechanism of stimulation of respiration by norepinephrine in the intact tissue. Conflicting data have been reported which suggest involvement of either adenine nucleotides, or fatty acids, or long chain acyl-CoA, or protons in the physiological regulation. We measured the electrical potential gradient across the mitochondrial membrane (delta psi m) in control cells and in cells stimulated with norepinephrine, using the accumulation of lipophilic cation, tetraphenylphosphonium, as an indicator of the potential gradient. The value of delta psi m in the cells in the control state is 116 mV, and in the hormonally stimulated state it is 56.6 mV. This supports the view that the protein is involved in the mechanism of hormone action. Other studies were designed to distinguish between the effects of fatty acids and ATP levels on the uncoupling protein in isolated mitochondria and in the adipocytes. ATP levels and fatty acid levels inside intact cells were independently varied using oligomycin or external fatty acids. Their effect on thermogenin was monitored as the capacity of the cells for reverse electron transport from durohydroquinone. The results suggest that ATP modulates the activity of thermogenin, while fatty acids can alter the relationship between ATP and thermogenin activity such that the protein appears to be activated at a higher cellular ATP level in the presence of fatty acids than in their absence.

Adenosine Triphosphate↗

The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus.

In the mammalian visual system, the lateral geniculate nucleus is commonly thought to act merely as a relay for the transmission of visual information from the retina to the visual cortex, a relay without significant elaboration in receptive field properties or signal strength. However, many morphological and electrophysiological observations are at odds with this view. Only 10-20% of the synapses found on geniculate relay neurons are retinal in origin. Roughly half of all synapses derive from cells in layer VI of visual cortex; roughly one third are inhibitory and GABAergic, derived either from interneurons or from cells of the nearby perigeniculate nucleus. Most of the remaining synapses probably derive from cholinergic, noradrenergic, and serotonergic sites within the brainstem reticular formation. Moreover, recent biophysical studies have revealed several ionic currents present in virtually all thalamic neurons. One is a Ca2+-dependent K+ current underlying the afterhyperpolarization (or the IAHP), which may last up to 100-200 ms following an action potential. Activation of the IAHP leads to spike frequency adaptation in response to a sustained, suprathreshold input. Intracellular recordings from other neuronal preparations have shown that the IAHP can be blocked by noradrenaline or acetylcholine, leading to an increased cellular excitability. Another ionic current results from a voltage- and time-dependent Ca2+ conductance that produces a low threshold spike. Activation of this conductance transforms a geniculate neuron from a state of faithful relay of information to one of bursting behavior that bears little relationship to the activity of its retinal afferents. We propose that state-dependent gating of geniculate relay cells, which may represent part of the neuronal substrate involved in certain forms of selective visual attention, can be effected through at least three different mechanisms: conventional GABAergic inhibition, which is largely controlled via brainstem and cortical afferents through interneurons and perigeniculate cells; the IAHP, which is controlled via noradrenergic and cholinergic afferents from the brainstem reticular formation; and the low threshold spike, which may be controlled by GABAergic inputs, cholinergic inputs, and/or the corticogeniculate input, although other possibilities also exist. Furthermore, it seems likely that gating functions involving the corticogeniculate pathway are suited to attentional processes within the visual domain (e.g., saccadic suppression), whereas brainstem inputs seem more likely to have more global effects that switch attention between sensory systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

A genetic polymorphism of the complement component factor B in chickens not linked to the major histocompatibility complex (MHC).

The complement component factor B in chickens exhibits a genetic polymorphism with three common phenotypes, F, F/S, and S. These phenotypes segregate in flocks of chickens homozygous for the MHC (B complex) of the chicken. Furthermore, a genetic analysis has shown that the described factor B polymorphism is not linked to the B complex. It is not known whether the molecular basis for this polymorphism is due to the existence of allelic forms of the structural gene or to some posttranslational modifications, but the finding is discussed in view of the close linkage of factor B polymorphism with the MHC of all mammalian species investigated so far.

Animals↗

A novel polymorphism of human complement component C3 detected by means of a monoclonal antibody.

A mouse monoclonal antibody, HAV 4-1, obtained after immunization of a BALB/c mouse with purified C3F, detected a novel genetic polymorphism of human complement component C3 in a simple immunoblotting system. The frequency of HAV 4-1-positive genes was 20.1%. Reactivity of HAV 4-1 was closely related to C3F, but certain individuals with the C3F allele did not react with HAV 4-1. Conversely, certain C3S homozygous individuals did react with HAV 4-1. The polymorphism detected by this monoclonal antibody is therefore different from the previously described polymorphism based on charge differences.

Alleles↗