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Biomedical subjects

T Christensen

Publications and source records attributed to T Christensen.

At least 19 recordsLinked to original sources

Characterization of tertiary interactions in a folded protein by NMR methods: studies of pH-induced structural changes in human growth hormone.

The pH-induced conformational changes in human growth hormone (hGH) have been studied, using a new quantitative NMR approach that combines 13C labeling of specific backbone carbonyl carbons with a complete spectral analysis of the corresponding 13C resonances. Thus, a complete analysis of the carbonyl resonances of the 26 Leu residues of hGH and their variation with pH provided detailed information about the equilibrium folding processes of the protein, including information about the kinetics of the folding. By combining this information with the pH dependence of readily identifiable 1H resonances, the pH-induced changes observed in the carbonyl carbon spectra can be associated with specific regions in the protein and can be ascribed to a series of localized adjustments in the tertiary structure, brought about by changes in the hydrogen bond interactions or electrostatic interactions between different residues in the globular folded protein. The preexchange lifetimes of these adjustments range from a fraction of a millisecond to a few milliseconds.

Amino Acid Sequence

[Monosymptomatic pneumoperitoneum is not an indication for surgery].

UNLABELLED: Pneumoperitoneum results from a perforation of the gastrointestinal tract in the majority of instances and the necessity for surgery is involved. In some cases with monosymptomatic pneumoperitoneum, surgery is unnecessary. A case of a man aged 64 with great amount of free intraperitoneal air is presented. The patient was clinically unaffected and had neither fever nor signs of peritoneal affection. The intraperitoneal air decreased slowly and disappeared after about 60 days. A self-sealing perforation of a duodenal ulcer was the cause of pneumoperitoneum. The most common causes of non-surgical pneumoperitoneum (PP) are discussed. IN CONCLUSION: Monosymptomatic PP is not an indication for emergency surgery. If the patient has no signs of peritoneal reactions conservative treatment can be considered.

Humans

Chemical and radiological risk factors associated with waste from energy production.

We have tried to estimate the toxic potential of waste from nuclear power plants and from power plants burning fossil fuels. The potential risks have been expressed as 'risk potentials' or 'person equivalents.' These are purely theoretical units and represent only an attempt to quantify the potential impact of different sources and substances on human health. Existing concentration limits for effects on human health are used. The philosophy behind establishing limits for several carcinogenic chemicals is based on a linear dose-effect curve. That is, no lower concentration of no effect exists and one has to accept a certain small risk by accepting the concentration limit. This is in line with the establishment of limits for radiation. Waste products from coal combustion have the highest potential risk among the fossil fuel alternatives. The highest risk is caused by metals, and the fly ash represents the effluent stream giving the largest contribution to the potential risk. The waste from nuclear power production has a lower potential risk than coal if today's limit values re used. If one adjusts the limits for radiation dose and the concentration limit values so that a similar risk is accepted by the limits, nuclear waste seems to have a much higher potential risk than waste from fossil fuel. The possibility that such risk estimates may be used as arguments for safe storage of the different types of waste is discussed. In order to obtain the actual risk from the potential risk, the dispersion of the waste in the environment and its uptake and effects in man have to be taken into account.

Environmental Pollution

Natural radiation--a perspective to radiological risk factors of nuclear energy production.

Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nodic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92,000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23,000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases of radionuclides from a final repository of spent nuclear fuel to the consequences of natural radionuclides in different environments. The danger index of natural radiological environments will not be significantly increased by future releases of nuclear fuel radionuclides.

Hot Temperature

Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin.

The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24%. These alterations may be related to cerebral osmoregulation. Also, the levels of tyrosine and phenylalanine increased 15% and 35%, respectively, during administration of vasopressin. No changes of other amino acids were observed.

Amino Acids

Neurocysticercosis: a short review and presentation of a Scandinavian case.

Cysticercosis is a disease entity caused by the larval form (Cysticercus cellulosae) of the pork tapeworm (Taenia solium). When man becomes the intermediate host, cysticercal cysts can develop in various organs. Neurocysticercosis, i.e. cysticercosis of the central nervous system, can lead to a broad range of neurological disturbances. The disease is usually confined to geographical regions where sanitation is poor but can occur among immigrants or travellers from such regions. Due to increased travel and immigration the disease may appear in non-endemic areas. We describe a recent case of neurocysticercosis in a 28-year-old Danish woman, who had been travelling in the Far East. She was successfully treated with praziquantel. A short review of the literature is given as the knowledge of the diagnosis and treatment of the disease has increased greatly in the last decade.

Adult

Specific carbon-13 labelling of leucine residues in human growth hormone.

Biosynthetic human growth hormone specifically 13C-labelled in the carbonyl positions of all 26 leucine residues has been obtained by recombinant DNA techniques using 13C-labelled leucine and an E. coli strain that requires leucine. It is shown that, on the whole, the labelling is specific with no significant mislabelling as would have been the case had the 13C-labelled leucine been metabolized.

Carbon Isotopes

Effect of phenylsuccinate on potassium- and ischemia-induced release of glutamate in rat hippocampus monitored by microdialysis.

The extracellular concentration of glutamate in rat hippocampus during physiological conditions, elevated extracellular K+ and global ischemia was followed by microdialysis and subsequent determination of glutamate by HPLC. The effect of phenylsuccinate, an inhibitor of the mitochondrial dicarboxylate carrier, was studied. It was found that while phenylsuccinate had no effect on the extracellular glutamate concentration during perfusion under physiological and ischemic conditions, the potassium-induced increase in the extracellular glutamate concentration was totally blocked by phenylsuccinate. Ischemia led to a pronounced glutamate overflow. The finding that phenylsuccinate could inhibit potassium-induced glutamate release into the extracellular space but not that induced by ischemia suggests that glutamate released under these conditions originates from different pools. Since glutamate released by a depolarizing concentration of potassium is likely to originate primarily from the transmitter pool, the ischemia-induced glutamate overflow may primarily be released from both the transmitter and the metabolic pool. This is compatible with the previous finding that phenylsuccinate specifically prevents biosynthesis of transmitter glutamate leaving the metabolic glutamate pool unaffected.

Animals

[Cerebral cysticercosis].

A Danish woman aged 28 years who had travelled in the Far East developed cerebral symptoms with headache and visual disturbances. Migraine was suspected. Subsequent CT scanning revealed multiple processes and metastases were suspected. As the patient had travelled in the Far East 1 1/2 years previously, she was examined for neurocysticercosis. This diagnosis was established and the patient was successfully treated with praziquantel. On account of increased travelling activity, the possibility of neurocysticercosis should be borne in mind when dealing with patients with cerebral symptoms and relevant travelling histories.

Adult

Functional cloning of BUD5, a CDC25-related gene from S. cerevisiae that can suppress a dominant-negative RAS2 mutant.

By searching for genes that behave like CDC25 of S. cerevisiae in their ability to counteract a dominant-negative RAS2 mutant in a wild-type RAS-dependent manner, we have isolated a CDC25-like homolog, BUD5. BUD5 is tightly linked to the MAT locus. Although overexpressed BUD5 cannot substitute for CDC25 function, we present evidence that its gene product can bind to the guanine nucleotide binding-deficient RAS2val19ala22 gene product and thereby counteract its dominant-negative effect. We propose that BUD5 is a member of a family of CDC25-related genes that encode activators of RAS and RAS-like proteins.

Amino Acid Sequence

Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials.

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.

Animals

Reversible pancreatic elastase-induced bronchial secretory cell metaplasia in the rat.

Porcine pancreatic elastase (PPE) causes irreversible secretory cell metaplasia (SCM) in the intrapulmonary bronchi of hamsters. To determine whether this lesion can be induced in another rodent species, PPE was transorally instilled into the lungs of anesthetized rats. Saline-treated rats served as controls. Animals were killed 1 week, 3 weeks and 3 months after enzyme treatment and the lungs were inflation-fixed with 4% formalin/1% glutaraldehyde in 0.1 M Na cacodylate buffer at pH 7.4. Transverse sections from 3 intrapulmonary airway levels were embedded in paraffin and in glycol methacrylate. The secretory cell index (SCI) was determined from PAS-stained paraffin sections using a standardized scale of 0 to 4. There were no significant differences between SCI values of PPE-treated rats and saline-treated controls at any time point. Secretory cells in methacrylate sections were subclassified into S1, S2 and S3 cells on the basis of increasing amounts of PAS-positive intracellular granules. At one week, there was no effect of PPE on airway level I secretory cells, but significant increases in numbers of S2 and S3 cells were seen in level II and in S3 cells in level III. At 3 weeks, the number of S1 cells were increased in level I and S2 and S3 cells were increased in level III; level II secretory cells were unaffected. Level III secretory cells had returned to normal by 3 months. There were no significant differences between treatment groups in the total number of secretory cells (S1 + S2 + S3) at any airway level or time point examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Immunoglobulin and complement studies in children with Schönlein-Henoch Syndrome and other vasculitic diseases.

In 35 children with Schönlein-Henoch Syndrome (SHS) serum IgG, IgM, and IgA concentrations were increased in 15%, 21%, and 44% of cases, respectively. Seven children with other vasculitic syndromes (VS) had normal serum Ig concentrations. Serum concentration of IgG subclass IgG1 was increased in 72% of children with SHS and 57% with VS. In SHS this was related to the presence of arthritis, but inversely related to nephritic symptoms. Only a few children had IgG subclasses IgG2, IgG3, or IgG4 concentrations outside the normal ranges. Platelet associated Ig (PAIg) was found in 75% of children with SHS or VS. In SHS the identification of increased amounts of PAIgG was related to the presence of nephritis. The serum concentration of properdin, a component of the alternative complement system, was reduced in 21% of children with SHS. This was related to the presence of abdominal symptoms or nephritis. No cases of retinal vasculitis was observed, but 4 of 22 children with SHS had punctuate retinal haemorrhages. SHS and VS may be clinical variations of the same syndrome. The immunological aspects indicate a close relationship with autoimmune diseases.

Adolescent

Effect of different phototherapy lights on retinal and choroidal blood flow.

The response of retinal (RBF) and choroidal (ChBF) blood flow to illumination with light with different spectra was investigated in spontaneously breathing newborn piglets. After 1 h in complete darkness, the animals were exposed to blue, white or green light in such a manner that equal energy was delivered to the eye. RBF and ChBF showed different flow responses. After 60 min exposure to blue light, RBF increased from 0.22 +/- 0.01 ml/min/g at baseline to 0.32 +/- 0.03 ml/min/g (+/- SEM) (p less than 0.03). Apart from this increase, RBF did not change significantly during any of the experimental settings. ChBF, on the other hand, was significantly affected by illumination. Thus, at 120 min of light exposure all three types of light decreased ChBF significantly from baseline (darkness) levels. Blue light decreased ChBF (mean +/- SEM) from 13.78 +/- 0.84 to 7.61 +/- 0.67 ml/min/g (p less than 0.01), white light from 17.43 +/- 1.86 to 9.86 +/- 1.07 ml/min/g (p less than 0.01), and green light from 14.13 +/- 1.64 to 8.31 +/- 1.30 ml/min/g (p less than 0.02). The results indicate that light is an important modulator of ChBF and to a certain extent also RBF. Further, the results suggest that ChBF and RBF are regulated differently.

Animals

Acupuncture in the treatment of Graves' ophthalmopathy. A blinded randomized study.

Seventeen patients with Graves' ophthalmopathy, all euthyroid for at least one year, were included in a blinded trial to test the effect of acupuncture twice a week during two months on the eye disease, assessed by an ophthalmologist and computed tomography of the eye muscle volume. No significant change was found in eye muscle volume, Hertel measure, palpebral aperture, intraocular pressure, Hess chart, nor was there any statistically significant improvement of the irritative conjunctival symptoms.

Acupuncture Therapy