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Biomedical subjects

J Nielsen

Publications and source records attributed to J Nielsen.

At least 217 records · Page 12Linked to original sources

Evidence of facilitation of soleus-coupled Renshaw cells during voluntary co-contraction of antagonistic ankle muscles in man.

1. The amount of recurrent inhibition onto soleus motoneurones was compared during plantar flexion and co-contraction of antagonistic ankle plantar and dorsiflexors at matched levels of background activity in the soleus muscle. 2. During weak plantar flexion and co-contraction (less than 10% of maximal voluntary plantar flexion effort) a test reflex discharge (H' reflex), which was conditioned by a previous reflex discharge, was found to be significantly more depressed in relation to rest than an unconditioned reference H reflex. During strong plantar flexion (more than 50% of maximal voluntary plantar flexion effort) the H' reflex either increased more or to the same extent as the reference H reflex in relation to rest. In contrast to this, the H' reflex was strongly depressed during co-contraction, whereas the reference H reflex was not significantly different from its resting value. 3. At the end of the ramp phase of a phasic contraction, large variations of the H' reflex were observed during plantar flexion (large increase in relation to rest) and during co-contraction (marked decrease), whereas the reference H reflex was facilitated in the two situations. 4. These observations provide evidence that soleus-coupled Renshaw cells are differently regulated during co-contraction and plantar flexion. It is suggested that the Renshaw cells are inhibited during strong plantar flexion but not during strong co-contraction. The functional significance of the findings is discussed.

Adult↗

[Ultrasonically guided gastroscopically assisted percutaneous internal drainage of pancreatic pseudocysts].

Non-surgical procedures are increasingly being used for drainage of pancreatic pseudocysts. We describe the results of placement of a double pigtail cystogastric stent under ultrasonographic and gastroscopic guidance. The stent was placed in 22 of 25 pseudocysts. There was no mortality associated with the procedure and the total complication rate was 20%. The cysts resolved in all patients and 87% reported reduction of abdominal pain. The median stent-time was 347 days and there were no cyst recurrences or complications during that time. After removal of the stent four out of 19 patients had recurrences. After placement of a second stent in these four patients there were no recurrences. Treatment with a cystogastric stent is comparable to surgical cystogastrostomy as regards to results and has fewer complications.

Adult↗

Growth energetics and metabolic fluxes in continuous cultures of Penicillium chrysogenum.

Continuous cultures of the penicillin producing fungus Penicillium chrysogenum have been analyzed with respect to the macromolecular composition of the mycelium. All cultivations were carried out using a chemically defined medium with glucose as the growth limiting component. Biomass was harvested at steady state and analyzed for proteins, lipids, RNA, DNA, and carbohydrates. Carbohydrates present in the cell wall, i.e., glucans and chitin, and carbohydrates serving as storage materials, i.e., glycogen, were measured. It was observed that the levels of DNA and lipids are relative constant, whereas the proteins and stable RNA levels increase with the specific growth rate and the total amount of carbohydrates decreases with the specific growth rate. Glycogen is only present in small amounts, decreasing with the specific growth rate. As an average the measured macromolecules account for 77 +/- 2% (w/w) of the biomass. On the basis of estimations of the metabolic costs for biosynthesis and polymerization of the different macromolecules the total ATP and NADPH requirements for cell biosynthesis from glucose and inorganic salts, i.e., YxATP,growth and YxNADPH, have been quantified. The biosynthesis of 1 g biomass was calculated to require 39.9 mmol of ATP and 7.5 mmol of NADPH when cytosolic acetyl-CoA is formed from citrate by citrate lyase and oxaloacetate is recycled back into the TCA cycle. Other pathways of acetyl-CoA biosynthesis have been considered. The calculations show that the different biosynthetic routes for generating cytosolic acetyl-CoA have a significant influence on the theoretical value of ATP and NADPH requirements for cell biosynthesis. Combining a detailed stoichiometric model for growth and product formation of P. chrysogenum with experimental data on the macromolecular composition of P. chrysogenum and precise measurements of substrate uptake and product formation the intracellular flux distribution was calculated for different cultivation conditions.

Adenosine Triphosphate↗

[Infections related to central venous catheters].

Central venous catheters (CVC) are a major source of nosocomial bacteraemia. The majority of cases are due to Staphylococcus aureus and coagulase-negative staphylococci. Severe complications, in particular septic shock, develop in 30% of all CVC-associated septicaemia cases and are usually caused by S. aureus. Some patients develop metastatic suppurative complications. Risk factors include prolonged catheterization, localization of catheter to the groin, the number of times the system is entered, use for parenteral nutrition and for dialysis, immunosuppresion and loss of skin integrity especially in burns. Important measures to decrease the rate of CVC-related infections include aseptic technique during insertion, changing transparent semipermeable dressing at least every 48 hours and replacement of the entire delivery system every 72 h. Technological advances such as bonding antimicrobial agents to the intravascular device may reduce the risk of infection. Treatment of CVC-related infections usually requires catheter removal.

Bacterial Infections↗

On the mechanism of the post-activation depression of the H-reflex in human subjects.

It was demonstrated that the soleus H-reflex was depressed for more than 10 s following a preceding passive dorsiflexion of the ankle joint. This depression was caused by activation of large-diameter afferents with receptors located in the leg muscles, as an ischaemic block of large-diameter fibres just below the knee joint abolished the depression, whereas a similar block just proximal to the ankle joint was ineffective. The depression of the H-reflex was not caused by changes in motoneuronal excitability, as motor-evoked potentials by magnetic brain stimulation were not depressed by the same passive dorsiflexion. Therefore it was concluded that the long-lasting depression is due to mechanisms acting at presynaptic level. The transmission of the monosynaptic Ia excitation from the femoral nerve to soleus motoneurones was not depressed by the ankle dorsiflexion. The depression thus seems to be confined to those afferents that were activated by the conditioning dorsiflexion. In parallel experiments on decerebrate cats, more invasive methods have complemented the indirect techniques used in the experiments on human subjects. A similar long-lasting depression of triceps surae monosynaptic reflexes was evoked by a preceding conditioning stimulation of the triceps surae Ia afferents. This depression was accompanied by a reduction of the monosynaptic Ia excitatory postsynaptic potential recorded intracellularly in triceps surae motoneurones, but not by changes in the input resistance or membrane potential in the motoneurones. Stimulation of separate branches within the triceps surae nerve demonstrated that the depression is confined to those afferents that were activated by the conditioning stimulus. This long-lasting depression was not accompanied by a dorsal root potential. It is concluded that the long-lasting depression is probably caused by a presynaptic effect, but different from the "classical" GABAergic presynaptic inhibition which is widely distributed among afferent fibres and accompanied by dorsal root potentials. It is more probably related to the phenomenon of a reduced transmitter release from previously activated fibres, i.e. a homosynaptic post-activation depression. The consequences of this post-activation depression for the interpretation of results on spinal mechanisms during voluntary movements in man are discussed.

Adult↗

Work load during floor cleaning. The effect of cleaning methods and work technique.

Cardiovascular and muscle load levels were evaluated during floor cleaning. A group of 12 experienced female cleaners participated in the study. Of the subjects 6 used a mopping method and 6 a traditional scrub and cloth method. Heart rate, oxygen consumption, rating of perceived exertion, electromyography from the trapezius muscle and video recordings were obtained during floor cleaning. With respect to relative heart rate and oxygen consumption the two groups did not differ. The results revealed a high cardiovascular load corresponding on average to 53 percent of the individual maximal oxygen uptake. In addition 65 percent of the observed period was spent with the back in a position forward flexed more than 20 degrees C. The time spent in extreme forward back flexion was shorter for the mopping group. Both groups exhibited high static, median and peak shoulder muscle load levels of 10 percent, 25 percent and 54 percent maximal voluntary contraction, respectively. At the same time, however, the mopping group tended to have a higher shoulder load than the group using the scrub and cloth method. Furthermore, electromyographic signs of fatigue in the trapezius muscle indicated a more stereotype activation of the shoulder muscles during mopping than during scrubbing. Based on these results, it was concluded that mopping cannot be recommended as less strenuous than scrubbing.

Adult↗

NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride.

Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral neuropathic pain participated in a double-blind placebo-controlled study where ketamine or magnesium chloride were administered by a 10 min bolus infusion (ketamine: 0.84 mumol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a continuous infusion (ketamine: 1.3 mumol/kg/h = 0.3 mg/kg/h, magnesium: 0.16 mmol/kg/h). Ongoing pain determined by VAS score, area of touch-evoked allodynia, detection and pain thresholds to mechanical and thermal stimuli were measured before and during drug infusion. Ketamine produced a significant reduction of spontaneous pain (57%) and of the area of allodynia (33%). Magnesium chloride reduced pain (29%) and area of allodynia (18%) insignificantly. Following ketamine there was a significant correlation between the reduction in ongoing pain and reduction in area of touch-evoked allodynia. Detection and pain thresholds to mechanical and thermal stimuli were not significantly changed by the drugs. These findings suggest that both ongoing pain and touch-evoked pain (allodynia) in neuropathic pain are inter-related phenomena, which may be mediated by the same mechanism and involving a N-methyl-D-aspartate receptor.

Adult↗

A convergent solid-phase synthesis of actinomycin analogues--towards implementation of double-combinatorial chemistry.

The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our search for a novel class of nucleic acid binders. A highly convergent, solid-phase synthetic strategy has been developed for a class of peptide-aryl-peptide conjugates modeled upon natural actinomycins. The features of this method include the use of Fmoc solid-phase peptide synthesis, side-chain to side-chain cyclization on the solid phase, a chemoselective cleavage step and segment condensation. The synthetic scheme is consistent with the requirements for combinatorial synthesis and furthermore, the final segment condensation allows, for the first time, double-combinatorial chemistry to be performed where two combinatorial libraries can be reacted with each other.

Amino Acids↗

Occurrence of cancer in women with Turner syndrome.

A study of cancer incidence in a cohort of 597 women with Turner syndrome (TS) and a virtually complete follow-up is presented. The cohort was established from the Danish Cytogenetic Register. Information on cancer incidence was obtained from the Danish Cancer Registry and compared with the expected number calculated from the age-, period- and site-specific cancer rates for Danish women. A total of 21 neoplasms was observed, of which 13 occurred more than 1 year after diagnosis of TS, corresponding to a relative risk of cancer of 1.1. Wilms' tumour was the only identified childhood cancer. No case of gonadoblastoma or dysgerminoma was identified in the 29 women with a Y chromosome or in the women in whom no Y chromosome material was detected by standard cytogenetic methods, suggesting that the risk of ovarian germ cell tumours may be lower than previously estimated. Colon cancer was observed in five patients (relative risk 6.9, 95% confidence interval 2.2-16.2). Further studies are needed to assess whether colon cancer in TS is related to Turner-associated genes on the sex chromosome(s).

Adolescent↗

Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain.

We have compared the analgesic efficacy of the racemic mixture and the stereoisomer (S+) of the NMDA antagonist ketamine. In a double-blind, three-way crossover, placebo-controlled study, we assessed the following: pain evoked by small/large area pressure stimuli, pain detection threshold and pain ratings to small/large area of heat stimuli, pain detection threshold and pain rating to heat stimuli of brief/long duration, summation pain threshold and pain ratings to repeated heat/electrical stimuli, side effects and reaction time. Plasma concentrations of 350 ng ml-1 for ketamine (racemic) and 180 ng ml-1 for ketamine (S+) were tried. We found that ketamine (racemic) prolonged the reaction time more than ketamine (S+). Both drugs affected pain caused by repeated stimuli or stimuli of long duration equally or more than a single stimulus of short duration. They also affected pain evoked from large areas equally or more than pain evoked from small areas. The (S+)-isomer was approximately twice as potent as the racemic mixture of ketamine in inhibiting central summation.

Adult↗

Physiological effects of nitrogen starvation in an anaerobic batch culture of Saccharomyces cerevisiae.

The effects of nitrogen starvation on the anaerobic physiology of Saccharomyces cerevisiae were studied in cells cultivated in a bioreactor. The composition of the mineral medium was designed such that the nitrogen source became depleted while there was still ample glucose left in the medium. The culture was characterized by acoustic gas analysis, flow injection analysis and HPLC analysis of extracellular substrates and metabolites. During the cultivation, the macromolecular composition of the cells was analysed with respect to the cellular content of RNA, protein, trehalose and glycogen. During exponential growth under anaerobic conditions, the maximum specific growth rate conditions. Depletion of ammonium in the medium led to an abrupt decrease (mumax) of S. cerevisiae CBS 8066 (0.46 h-1) was identical to the mumax determined under aerobic in the flux through glycolysis. Subsequently, a continuous decrease in the carbon dioxide evolution rate, caused by catabolite inactivation of the hexose-transport system, was observed. The apparent half-life of the transport system under nitrogen starvation was 13 h. During the exponential growth phase, the cellular content of RNA and protein was 15% (w/w) and 60% (w/w), respectively. At the end of the cultivation where the cells had been starved of nitrogen for 18 h, the cellular content of RNA and protein had decreased to 4% (w/w) and 22% (w/w), respectively. The intracellular carbohydrate content increased dramatically as trehalose and glycogen accumulated to final concentrations of 7% (w/w) and 25% (w/w), respectively. Glycerol formation during nitrogen starvation was higher than that accounted for by the formation of organic acids, suggesting a protein turnover of approximately 6% h-1. The growth energetics of S. cerevisiae CBS 8066 also changed as a result of nitrogen starvation, and YxATP was observed to increase from 80 mmol g-1 during the exponential growth phase to more than 130 mmol g-1 towards the end of the cultivation. The presented results illustrate the effect of nitrogen starvation on glycerol formation, protein turnover, catabolite inactivation of the sugar-transport system, the cellular composition, the cell cycle and growth energetics.

Ammonia↗

The occurrence and course of skin symptoms on the hands among female cleaners.

Skin symptoms on the hands were studied in questionnaire-based studies conducted in 1989 and 1991 among female cleaners employed at Danish nursing homes, schools and offices. A total of 1166 participated in 1989, and 1011 of them participated in 1991. The average age was 45 years and the average of seniority was 10 years. 1/5 of the cleaners reported problems with cleaning agents. A total of 81% had wet hands more than 1/4 of their working hours. A total of 43% reported having at least 1 out of 4 skin symptoms during a 1-year period. Among them, 70% reported improvement during weekends and holidays. A positive correlation was found between hours per week spent with wet hands and skin symptoms. During the 2-year follow-up period, the risk of developing skin symptoms was higher in the group that remained cleaners than in the group that left their cleaning jobs. Accordingly, the prognosis was better in the group that left their cleaning jobs compared to the group that remained cleaners. Retirement occurred more often among cleaners with skin symptoms than among the others. There is a future need to develop and implement new work organisation and cleaning methods to reduce the time spent with wet hands.

Adolescent↗

Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae.

The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in the corresponding wild-type strain. In contrast, the polyploid delta mig1 strain exhibited an even more stringent glucose control of maltose metabolism than the corresponding wild-type strain, which could be explained by a more rigid catabolite inactivation of maltose permease, affecting the uptake of maltose. Growth on the glucose-sucrose mixture showed that the polypoid delta mig1 strain was relieved of glucose repression of the SUC genes. The disruption of MIG1 was shown to bring about pleiotropic effects, manifested in changes in the pattern of secreted metabolites and in the specific growth rate.

DNA-Binding Proteins↗

Isolation of a gene involved in 1,3-beta-glucan synthesis in Aspergillus nidulans and purification of the corresponding protein.

Saccharomyces cerevisiae has two highly homologous genes, FKS1 and FKS2, which encode interchangeable putative catalytic subunits of 1,3-beta-glucan synthase (GS), an enzyme that synthesizes an essential polymer of the fungal cell wall. To determine if GS in Aspergillus species is similar, an FKS homolog, fksA, was cloned from Aspergillus nidulans by cross-hybridization, and the corresponding protein was purified. Sequence analysis revealed a 5,716-nucleotide coding region interrupted by two 56-bp introns. The fksA gene encodes a predicted peptide of 229 kDa, FksAp, that shows a remarkable degree of conservation in size, charge, amino acid identity, and predicted membrane topology with the S. cerevisiae FKS proteins (Fksps). FksAp exhibits 64 and 65% identity to Fks1p and Fks2p, respectively, and 79% similarity. Hydropathy analysis of FksAp suggests an integral membrane protein with 16 transmembrane helices that coincide with the transmembrane helices of the Saccharomyces Fksps. The sizes of the nontransmembrane domains are strikingly similar to those of Fks1p. The region of FksAp most homologous to the Saccharomyces FKS polypeptides is a large hydrophilic domain of 578 amino acids that is predicted to be cytoplasmic. This domain is 86% identical to the corresponding region of Fks1p and is a good candidate for the location of the catalytic site. Antibodies raised against a peptide derived from the FksAp sequence recognize a protein of approximately 200 kDa in crude membranes and detergent-solubilized active extracts. This protein is enriched approximately 300-fold in GS purified by product entrapment. Purified anti-FksAp immunoglobulin G immunodepletes nearly all of the GS activity in crude or purified extracts when Staphylococcus aureus cells are used to precipitate the antibodies, although it does not inhibit enzymatic activity when added to extracts. The purified GS is inhibited by echinocandins with a sensitivity equal to that displayed by whole cells. Thus, the product of fksA is important for the activity of highly purified preparations of GS, either as the catalytic subunit itself or as an associated copurifying subunit that mediates susceptibility of enzymatic activity to echinocandin inhibition.

Amino Acid Sequence↗

Population balance models of autonomous microbial oscillations.

Autonomous oscillations in continuous microbial cultures is well documented for the case of baker's yeast, Saccharomyces cerevisiae, for which it has been observed under a range of operating conditions. We have found that autonomous microbial oscillations can be modeled by unstructured population balance models in which a key cell cycle parameter is a function of the environmental conditions, e.g., the concentration of a substrate or product. Although these models are remarkably simple, they can display a wide range of dynamic behaviors. These behaviors include, for binary fission organisms, solutions containing a single synchronous population and, for budding yeasts, two synchronized subpopulations with a period of oscillation similar to that of the cell cycle length, a pattern that has been observed experimentally in S. cerevisiae. Numerical simulations of the model equations also show that complex periodic solutions with periods very different from the cell cycle length are possible. The ability of the population balance approach to accurately describe the available data of yeast culture dynamics will be discussed.

Cell Cycle↗

Continuous cultivation of Penicillium chrysogenum. Growth on glucose and penicillin production.

A series of constant-mass, continuous cultivations of the penicillin producing mold Penicillium chrysogenum was carried out using a chemically defined medium with glucose as the growth-limiting component. The stoichiometry for growth of P. chrysogenum on glucose was characterized in terms of mass-yield and maintenance coefficients. Saturation kinetics with respect to glucose was used to describe the glucose consumption rate at steady-state conditions. Transient data indicate that the maximum rate of glucose consumption at a particular set of operating conditions is correlated to the metabolic 'capacity' of the mold as reflected by its intracellular RNA content. A progressive loss in the penicillin productivity in glucose limited chemostat cultures was correlated to the formation of two mutants. The two mutants were characterized by their sporulation when grown as surface cultures and by Southern dot-tests for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin-N synthase (IPNS) and acyl-CoA:6-APA acyltransferase (AT). The loss of penicillin productivity was caused by an increasing fraction of mutants which had lost the genes encoding for all three enzymes needed in the penicillin synthesizing pathway.

Culture Media↗