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Biomedical subjects

J Nielsen

Publications and source records attributed to J Nielsen.

At least 145 records · Page 8Linked to original sources

Pain produced by electric stimulation of the rectum in patients with irritable bowel syndrome: further evidence of visceral hyperalgesia.

BACKGROUND: Visceral hyperalgesia is most likely a phenomenon of substantial clinical importance and may also play a role in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the manifestation of visceral hyperalgesia in IBS patients by nociceptive electric stimulation of the rectosigmoid junction and rectum. METHODS: Twelve IBS patients fulfilling the Rome criteria and 9 healthy controls were studied. Visceral single and repeated electric burst stimuli were applied with a bipolar electric stimulator inserted through the sigmoidoscope. The sensation (ST) and pain detection (PDT) thresholds were determined in response to single and repeated stimuli at the rectosigmoid junction, and PDT to repeated stimuli at four different positions in the rectum. Cutaneous single and repeated electric stimuli were applied to the lateral aspect of the foot, determining ST and PDT. RESULTS: Cutaneous stimulation showed no significant differences for ST and PDT between patients and controls. The rectosigmoid junction showed significantly lower ST for single stimuli (P<0.01) and a significantly lower PDT for single and for repeated stimuli (P<0.05 and P<0.02) in IBS patients. In the rectum the IBS patients had a significantly lower PDT than controls (P<0.001). CONCLUSIONS: For cutaneous electric stimulation no differences in the pain thresholds between the two groups were found, showing that there is no generalized hyperalgesia in IBS patients. The IBS patients had a specific decrease of the pain thresholds in the rectum and rectosigmoid junction, indicating visceral hyperalgesia. These results point to central visceral hyperexcitability as an important factor in the pathophysiology of IBS.

Abdominal Pain↗

An experimental pain model based on electric stimulations of the colon mucosa.

BACKGROUND: Pain intensity and distribution related to diseases of the gut are important diagnostic indicators in gastroenterology. Experimental pain models provide a unique possibility for standardized activation of the nociceptive system, but only few human models exist. METHODS: An experimental pain model based on electric stimuli in the human colon was developed and applied. Eleven patients who were referred for surveillance colonoscopy due to earlier polyps in the colon were included. None had any abdominal pain complaints. The following areas were stimulated with 'single', 'repeated', or 'continuous' electric current: the cecum, the hepatic and splenic flexures, and the rectosigmoid junction. RESULTS: All subjects felt deep, diffuse pain during the stimulation, with referral to localized somatic structures. The pain detection thresholds after repeated stimuli were similar in the four areas. The threshold for single stimulation was higher than the threshold for repeated stimulation. Most reported pain in the lower and left site of the abdominal wall during stimuli at the splenic flexure and rectosigmoid junction. Stimuli at the right colon, however, resulted mostly in pain at the contralateral site of the abdomen. CONCLUSIONS: The presented model was robust and suitable for eliciting pain in different regions of the large intestine. The importance of temporal summation in visceral pain was shown. Mapping of the referred pain areas mimics clinical observations and has ontogenetic and anatomic consistency. The model may therefore improve the evaluation of pain in patients with diseases of the colon.

Abdominal Pain↗

Chorea in juvenile primary antiphospholipid syndrome. Reversible decreased circulation in the basal ganglia visualised by single photon emission computed tomography.

Chorea was observed in a 12-year-old girl with primary antiphospholipid syndrome (APS). She developed severe chorea in a few weeks. On immunosuppressive treatment, including high doses of glucocorticoids and cyclophosphamide, she had a rapid clinical recovery. Single photon emission computed tomography (SPECT) of the brain showed decreased circulation in the basal ganglia and in the medial parts of both temporal lobes. One month after treatment, SPECT was completely normalised. APS in children has a variety of clinical manifestations, and should be suspected in cases of unexplained thromboembolic disease or obscure neurological symptoms.

Antiphospholipid Syndrome↗

Factors Intrinsic to the Axillary Bud Determine Topophysic Effects on Bud and Shoot Growth and Flower Development in Rosa hybrida.

Topophysis (the influence of the position of axillary buds along the shoot on bud and shoot growth, fresh biomass accumulation, and flower development) were studied in Rosa hybrida L. Single-node cuttings with five-leaflet leaves were excised from nine stem positions and grown as single-stemmed rose plants. Plants were grown at 20-h photoperiods, 22 degrees C average air temperature, and an average photosynthetic photon flux density of 228 µmol m-2 s-1. Generally, onset of axillary bud growth and initial shoot growth were promoted, and flower height and bloom quality were reduced in plants from apical bud positions. Stem diameter, stem growth rate, and biomass buildup were greatest from medial bud positions; the plastochron was greater, and stems and internodes were longer, from basal bud positions. Flower diameter and cut flower vase life were not significantly influenced by topophysis. The results demonstrate that topophysis can determine the potential for plant development and flowering in R. hybrida and that this knowledge may be used to regulate plant growth. Results also indicate intrinsic mechanisms determining axillary bud growth, but the physiology of topophysis is presently unclear. A probable role of cytokinins in the topophysic prevention of growth observed is discussed.

Journal Article↗

Work-related eye symptoms and respiratory symptoms in female cleaners.

A prospective study was conducted in order to describe the incidence of eye symptoms, nose or throat symptoms, asthma and bronchitis among cleaners compared with former cleaners and according to the 'use of sprayers'. In 1989 and in 1991 questionnaire-based studies were conducted among female cleaners employed at Danish nursing homes, schools and offices. A cohort of 1,011 females was followed over two years. At baseline in 1989, the average age was 45 years and the average of seniority was 10 years. Overall, the cleaners tended to have the same or higher risk of developing respiratory symptoms compared to former cleaners. The 'use of sprayers' during the follow-up period was associated with an increased risk of eye and respiratory symptoms.

Aerosols↗

Identification of enzymes and quantification of metabolic fluxes in the wild type and in a recombinant aspergillus oryzae strain

Two alpha-amylase-producing strains of Aspergillus oryzae, a wild-type strain and a recombinant containing additional copies of the alpha-amylase gene, were characterized with respect to enzyme activities, localization of enzymes to the mitochondria or cytosol, macromolecular composition, and metabolic fluxes through the central metabolism during glucose-limited chemostat cultivations. Citrate synthase and isocitrate dehydrogenase (NAD) activities were found only in the mitochondria, glucose-6-phosphate dehydrogenase and glutamate dehydrogenase (NADP) activities were found only in the cytosol, and isocitrate dehydrogenase (NADP), glutamate oxaloacetate transaminase, malate dehydrogenase, and glutamate dehydrogenase (NAD) activities were found in both the mitochondria and the cytosol. The measured biomass components and ash could account for 95% (wt/wt) of the biomass. The protein and RNA contents increased linearly with increasing specific growth rate, but the carbohydrate and chitin contents decreased. A metabolic model consisting of 69 fluxes and 59 intracellular metabolites was used to calculate the metabolic fluxes through the central metabolism at several specific growth rates, with ammonia or nitrate as the nitrogen source. The flux through the pentose phosphate pathway increased with increasing specific growth rate. The fluxes through the pentose phosphate pathway were 15 to 26% higher for the recombinant strain than for the wild-type strain.

Journal Article↗

Expression of the Escherichia coli pntA and pntB genes, encoding nicotinamide nucleotide transhydrogenase, in Saccharomyces cerevisiae and its effect on product formation during anaerobic glucose fermentation.

We studied the physiological effect of the interconversion between the NAD(H) and NADP(H) coenzyme systems in recombinant Saccharomyces cerevisiae expressing the membrane-bound transhydrogenase from Escherichia coli. Our objective was to determine if the membrane-bound transhydrogenase could work in reoxidation of NADH to NAD+ in S. cerevisiae and thereby reduce glycerol formation during anaerobic fermentation. Membranes isolated from the recombinant strains exhibited reduction of 3-acetylpyridine-NAD+ by NADPH and by NADH in the presence of NADP+, which demonstrated that an active enzyme was present. Unlike the situation in E. coli, however, most of the transhydrogenase activity was not present in the yeast plasma membrane; rather, the enzyme appeared to remain localized in the membrane of the endoplasmic reticulum. During anaerobic glucose fermentation we observed an increase in the formation of 2-oxoglutarate, glycerol, and acetic acid in a strain expressing a high level of transhydrogenase, which indicated that increased NADPH consumption and NADH production occurred. The intracellular concentrations of NADH, NAD+, NADPH, and NADP+ were measured in cells expressing transhydrogenase. The reduction of the NADPH pool indicated that the transhydrogenase transferred reducing equivalents from NADPH to NAD+.

Anaerobiosis↗

A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development.

Insulin-like growth factor II (IGF-II) is a major fetal growth factor. The IGF-II gene generates multiple mRNAs with different 5' untranslated regions (5' UTRs) that are translated in a differential manner during development. We have identified a human family of three IGF-II mRNA-binding proteins (IMPs) that exhibit multiple attachments to the 5' UTR from the translationally regulated IGF-II leader 3 mRNA but are unable to bind to the 5' UTR from the constitutively translated IGF-II leader 4 mRNA. IMPs contain the unique combination of two RNA recognition motifs and four hnRNP K homology domains and are homologous to the Xenopus Vera and chicken zipcode-binding proteins. IMP localizes to subcytoplasmic domains in a growth-dependent and cell-specific manner and causes a dose-dependent translational repression of IGF-II leader 3 -luciferase mRNA. Mouse IMPs are produced in a burst at embryonic day 12.5 followed by a decline towards birth, and, similar to IGF-II, IMPs are especially expressed in developing epithelia, muscle, and placenta in both mouse and human embryos. The results imply that cytoplasmic 5' UTR-binding proteins control IGF-II biosynthesis during late mammalian development.

3T3 Cells↗

Efficacy of measures of hygiene in workers sensitised to acid anhydrides and the influence of selection bias on the results.

OBJECTIVES: Organic acid anhydrides are potential sensitisers and cause occupational airway diseases. In an intervention study the efficacy of measures of hygiene at the workplace and possible selection bias were investigated. METHODS: A first investigation with 110 workers exposed to hexahydrophthalic acid anhydride (HHPA) and methyltetrahydrophthalic acid anhydride (MTHPA) was carried out in July 1991. The results (skin prick test, specific serum IgE) showed that 20 people were sensitised, and in a challenge test the clinical relevance of the sensitisation was confirmed in six subjects. In December 1991, the hygiene conditions at the plant were improved. In November 1995 a second investigation of 84 people was performed (anamnesis, skin prick test, specific IgE, spirometry, and ambient and biological monitoring). The 27 people who had left the plant in the meantime were asked their reasons for leaving. RESULTS: The relative risk of people sensitised in 1991 of leaving the plant between 1991 and 1995 was 2.6 (95% confidence interval (95% CI) 1.4 to 4.9) compared with people without any sign of sensitisation. The percentage of people identified as sensitised in 1991, who were still working at the plant and came to the second investigation, was higher than for people without evidence of sensitisation (10/10 v 47/73; p < 0.05). In all the 10 sensitised people in 1991 the findings of the first investigation were confirmed in 1995. The rate of sensitisation in 1995 was 21%. None of the six people employed after 1991 showed evidence of sensitisation. Of the six people with clinically relevant sensitisation confirmed by a challenge test in 1991, five were still at their workplace. From 1991 they were only exposed to MTHPA at a reduced concentration (< 0.5-36 micrograms/m3 in 1995). All of them reported fewer symptoms than in 1991. No signs of bronchial obstruction were detected by spirometry at the workplace. CONCLUSIONS: In cross sectional studies there is a selection bias with a risk of underestimating the incidence of allergic diseases. The results further suggest that the improved hygiene conditions probably had a positive effect on the symptoms in sensitised people.

Adult↗

Growth and production kinetics of a teicoplanin producing strain of Actinoplanes teichomyceticus.

The growth and production kinetics of a teicoplanin producing strain of Actinoplanes teichomyceticus (ATCC 31121) was investigated during batch cultivations on defined media. The growth was characterised by two exponential growth phases (EGPs), with a higher specific growth rate in the first than in the second phase. Also the specific rate of formation of teicoplanin was significantly lower in the second phase than in the first phase. This two-phased growth pattern was suggested to be caused by inhibition of growth by teicoplanin accumulated. Furthermore high concentrations of ammonia or phosphate reduced both the specific growth rate in the first EGP and the total production of teicoplanin.

Actinomycetales↗

Experimental corticosteroid induction of Pneumocystis carinii pneumonia in piglets.

Animal models of Pneumocystis carinii (Pc) pneumonia (PCP) play a central role in research on the Pc microorganism itself and the disease, especially the pathogenesis and the host defence. The classic rat model with corticosteroid-induced reactivation of a latent infection has been most widely used. In our search for alternative non-rodent models, six 31/2-week-old piglets were injected intramuscularly with methylprednisolone acetate, at 18 mg/kg body weight, once a week for 6 weeks. Six littermate piglets constituted the control group. The principals showed a markedly lower growth rate than the controls. Furthermore, they developed "moon face" and "pot belly", snoring sounds while eating, and pronounced respiratory distress during handling. Significant changes in haematological parameters, including lymphopenia, were observed in the principal group. The Pc antibody titres of the controls increased to high levels, whereas the principals were all low-titred or seronegative for Pc at the last blood sampling. At necropsy, the mean body weight of the principals was about half that of the controls. In addition, they had an extreme reduction of the thymus together with dark red consolidations of the frontal lung lobes and/or atelectatic looking diaphragmatic lobes. Histopathologically, there was a focal interstitial pneumonia. Alveolar walls and interstitia had mononuclear cell infiltrations and the alveolar lumina were occluded by foamy acidophilic honeycomb material with a varying number of Pc cysts. The reduced body weight, the thymus involution, and the lymphopenia, together with the reduced levels of specific Pc antibodies and the histomorphology of the PCP, were consistent parameters of the principal group and comparable to the findings of the classic rat model. Thus, the present study is the first to describe that prolonged administration of high doses of methylprednisolone acetate can induce PCP in piglets.

Animals↗

Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane potential of Penicillium chrysogenum.

Physiological effects of phenoxyacetic acid, the penicillin V side-chain precursor, on steady-state continuous cultures of Penicillium chrysogenum have been studied both theoretically and experimentally. Theoretical calculations show that at an extracellular pH of 6.50, phenoxyacetic acid has negligible influence on the growth energetics due to protonophoric uncoupling of membrane potentials by passive diffusive uptake. On the other hand, when the extracellular pH is lowered to 5.00, a severe maintenance-related uncoupling effect of phenoxyacetic acid is calculated. These findings were confirmed experimentally by steady-state continuous cultivations with a high-yielding penicillin strain of P. chrysogenum performed on a chemically defined and glucose-limited medium at pH 6.50 and pH 5.00, both with and without phenoxyacetic acid present. The yield and maintenance coefficients were determined from steady-state measurements of the specific uptake rates of glucose and oxygen and the specific production rate of carbon dioxide as functions of the specific growth rate. Combining these data with a simple stoichiometric model for the primary metabolism of P. chrysogenum allows quantitative information to be extracted on the growth energetics in terms of ATP spent in maintenance- and growth-related processes, i.e. mATP and YxATP. The increased maintenance-related ATP consumption when adding phenoxyacetic acid at pH 5.00 agrees with the theoretical calculations on the uncoupling effect of phenoxyacetic acid. When YxATP is compared with earlier reported values for the theoretical ATP requirement for biosynthesis of P. chrysogenum, i.e. YxATP, growth, it is found that YxATP,growth is only 40-50% of YxATP, which stresses that a large amount of ATP is wasted in turnover of macromolecules, leaks, and futile cycles.

Adenosine Triphosphate↗

The effect of transcranial magnetic stimulation on the soleus H reflex during human walking.

1. The effect of transcranial magnetic stimulation (TMS) on the soleus H reflex was investigated in the stance phase of walking in seventeen human subjects. For comparison, measurements were also made during quiet standing, matched tonic plantar flexion and matched dynamic plantar flexion. 2. During walking and dynamic plantar flexion subliminal (0.95 times threshold for a motor response in the soleus muscle) TMS evoked a large short-latency facilitation (onset at conditioning-test interval: -5 to -1 ms) of the H reflex followed by a later (onset at conditioning-test interval: 3-16 ms) long-lasting inhibition. In contrast, during standing and tonic plantar flexion the short-latency facilitation was either absent or small and the late inhibition was replaced by a long-lasting facilitation. 3. When grading the intensity of TMS it was found that the short-latency facilitation had a lower threshold during walking than during standing and tonic plantar flexion. Regardless of the stimulus intensity the late facilitation was never seen during walking and dynamic plantar flexion and the late inhibition was not seen, except for one subject, during standing and tonic plantar flexion. 4. A similar difference in the threshold of the short-latency facilitation between walking and standing was not observed when the magnetic stimulation was replaced by transcranial electrical stimulation. 5. The lower threshold of the short-latency facilitation evoked by magnetic but not electrical transcranial stimulation during walking compared with standing suggests that cortical cells with direct motoneuronal connections increase their excitability in relation to human walking. The significance of the differences in the late facilitatory and inhibitory effects during the different tasks is unclear.

Cerebral Cortex↗

Evaluation of reciprocal inhibition of the soleus H-reflex during tonic plantar flexion in man.

Changes in reciprocal inhibition from ankle dorsiflexors to ankle plantar flexors were evaluated at increasing levels of tonic plantar flexion in 11 healthy subjects. Stimulation of the common peroneal nerve (CPN) evoked a short-latency depression of the rectified and averaged soleus electromyogram (average latency of depression: 40 ms) and a short-latency inhibition of the soleus H-reflex (conditioning-test interval: 2-3 ms). When the intensity of the CPN stimulation was below approximately 1.2 x motor threshold (x MT) the inhibition of both the soleus EMG (expressed as the amount of EMG during the inhibition as percentage of the background EMG) and the soleus H-reflex (expressed as the size of the conditioned reflex as percentage of the control H-reflex size) were seen to decrease with increasing levels of plantar flexion. At intensities of stimulation higher than approximately 1.2 x MT the inhibition of the EMG and the H-reflex was very strong and was not modulated with contraction. It is suggested that the decrease of reciprocal inhibition with increasing levels of plantar flexion is due to a decreased excitability of the Ia inhibitory interneurones which are responsible for the inhibition. It is emphasized that submaximal stimulation is necessary to demonstrate this modulation of inhibition and that the functional contribution of reciprocal inhibition to motor performance cannot be revealed from the amount of inhibition evoked by artificial electrical stimulation of a peripheral nerve.

Adult↗

Evidence that a transcortical pathway contributes to stretch reflexes in the tibialis anterior muscle in man.

1. In human subjects, stretch applied to ankle dorsiflexors elicited three bursts of reflex activity in the tibialis anterior (TA) muscle (labelled M1, M2 and M3) at mean onset latencies of 44, 69 and 95 ms, respectively. The possibility that the later of these reflex bursts is mediated by a transcortical pathway was investigated. 2. The stretch evoked a cerebral potential recorded from the somatosensory cortex at a mean onset latency of 47 ms in nine subjects. In the same subjects a compound motor-evoked potential (MEP) in the TA muscle, evoked by magnetic stimulation of the motor cortex, had a mean onset latency of 32 ms. The M1 and the M2 reflexes thus had too short a latency to be caused by a transcortical pathway (minimum latency, 79 ms (47 + 32)), whereas the later part of the M2 and all of the M3 reflex had a sufficiently long latency. 3. When the transcranial magnetic stimulation was timed so that the MEP arrived in the TA muscle at the same time as the M1 or M2 reflexes, no extra increase in the potential was observed. However, when the MEP arrived at the same time as the M3 reflex a significant (P < 0.01) extra-facilitation was observed in all twelve subjects investigated. 4. Peaks evoked by transcranial magnetic stimulation in the post-stimulus time histogram of the discharge probability of single TA motor units (n = 28) were strongly facilitated when they occurred at the same time as the M3 response. This was not the case for the first peaks evoked by electrical transcranial stimulation in any of nine units investigated. 5. We suggest that these findings are explained by an increased cortical excitability following TA stretch and that this supports the hypothesis that the M3 response in the TA muscle is - at least partly - mediated by a transcortical reflex.

Adult↗