Biomedical subjects

T Christensen

Publications and source records attributed to T Christensen.

At least 109 records · Page 6Linked to original sources

PubMed1994

Urokinase receptor. An activation antigen in human T lymphocytes.

The ability of activated T lymphocytes to extravasate and reach inflammatory and malignant foci in the tissues is a basic function of cellular immunity. Recent evidence strongly suggests that the urokinase receptor (uPAR) holds a central position in the development of human two-chain urokinase-mediated pericellular proteolysis and matrix degradation, an important element in cell migration. In this report we establish uPAR as a pan T cell activation Ag. As determined by FACS analysis, CD3+ lymphocytes from healthy donors exhibited no significant uPAR expression. In contrast, patients (e.g., HIV-positive donors) showed distinct uPAR expression, confined to HLA-DR+ cells, in up to 80% of all T cells. In vitro activation by PMA caused a rapid up-regulation of membrane uPAR in all healthy donor T cells and was accompanied by enhanced receptor synthesis and elevated uPAR mRNA levels. A similar induction resulted from activation via the TCR/CD3 complex using mitogens (PHA, and Con A), anti-CD3 antibodies, and alloantigen. Receptor expression at single cell level was also modulated by a number of cytokines. IL-2, IL-4 and IL-7 increased uPAR presentation on 20 to 50% of the T cell population, and combined stimulation of bulk cultures demonstrated an additive effect of IL-2 and IL-7, whereas the response to each of the two was inhibited by IL-4. In addition, TGF-beta 1 substantially reduced the uPAR expression in T cell cultures responding to PHA, IL-2, and IL-7. Irrespective of the activating reagent, the T cells appeared to produce the same molecular uPAR species, but the affinity of uPAR expressed in PMA blasts was decreased, presumably because of a differential location at the cell surface. All activated cultures showed co-expression of uPAR and CD25. The finding that the urokinase receptor is an activation Ag may suggest that cell-associated plasminogen activation is involved in extravasation and migration of activated T cells.

Base Sequence↗

PubMed1994

Tissue restricted gene expression assayed by direct DNA injection into cardiac and skeletal muscle.

We have used direct injection of plasmid DNA into heart and tongue in vivo and transfection into cells in culture to determine (1) whether the pattern of reporter gene expression parallels the cell-type specific expression of endogenous genes, (2) whether the pattern of reporter gene expression approximates that of the same constructs transfected into myocardiocytes and myogenic cells in culture, (3) whether the expression patterns of promoters and enhancers that had been subtly altered by mutations are similar following transfection and direct DNA injection. We utilized reporter gene constructs derived from the two fiber-type specific human troponin C genes: the fast twitch gene (TnCf) and the slow twitch or cardiac gene (cTnC). The endogenous TnCf gene does not express in the heart and the plasmid DNA expresses neither in myocardium after injection nor in transfected cardiomyocytes. However injected TnCf does express vigorously in tongue muscle. Conversely, the endogenous cTnC gene does not express in fast twitch skeletal muscles like tongue and the plasmid DNA does not express in tongue after injection. However, injected cTnC does express in both injected myocardium and in transfected cardiomyocytes. With few discrepancies, various deletions and alterations of the promoters and enhancers of these genes that have previously been defined by transfection into permissive myogenic cells in culture gave parallel expression patterns after injection in myocardium and tongue. Thus we conclude that direct DNA injection appears to provide a method to verify the identities of important cis-acting regulatory regions that have been mapped in cells in culture.

Animals↗

PubMed1994

Evidence for formation of hydroxyl radicals during reperfusion after global cerebral ischaemia in rats using salicylate trapping and microdialysis.

Systemic administration of salicylate (SA) to rats (100 mg kg-1 i.p. ) was used as an in vivo trap of hydroxyl radicals (.OH). In the brain SA reacts with hydroxyl radicals to form the stable adducts 2, 3- and 2,5 dihydroxybenzoic acid (DHBAs) which can thus be taken as an index of .OH formation. The DHBAs were recovered by intracerebral microdialysis in hippocampus or striatum and quantified by high pressure liquid chromatography (HPLC) with electrochemical detection. There were no peaks corresponding to 2,5-DHBA or 2,3-DHBA in the chromatograms from rats not receiving SA. A basal level of 2,5-DHBA was seen in the dialysates from all animals given SA whereas 2, 3-DHBA was not detected. In one group of rats generation of free oxygen radicals was induced in the striatum by adding Fe2+ and ascorbate to the perfusion fluid to test the sensitivity of the system. Addition of Fe2+ ascorbate to the perfusion fluid induced a significant 7-fold increase in 2,5-DHBA that gradually returned to baseline after removal of Fe2+/ascorbate. In two other groups the microdialysis probes were implanted in either the striatum or the hippocampus and the animals were subjected to 20 min of four-vessel occlusion + hypotension (4-VOH). Significant reductions in 2,5-DHBA were detected during ischaemia followed by significant increases of 5-fold and 3-fold in the striatum and hippocampus, respectively, beginning immediately upon reperfusion and lasting for the remainder of the observation period (160 min).

Animals↗

PubMed1994

A retroviral implication in multiple sclerosis?

The etiology of multiple sclerosis (MS) is still unexplained. Epidemiological studies indicate that environmental agents are involved, and MS shares both clinical and histopathological features with retrovirus-mediated neurological diseases in animals and humans. Thus, combining the fields of microbiology and epidemiology may throw new light on the many unanswered questions posed by MS.

HTLV-I Infections↗

PubMed1994

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.

We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration (r2 = 0.98) as well as the serum ferritin concentration (r2 = 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 mumol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration. It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

Bloodletting↗

PubMed1994

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin.

The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r = -0.77, P = 0.009) between the MRI determined liver iron concentration and serum CDT in the patients not on iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.

Adult↗

PubMed1994

Cells, bilirubin and light: formation of bilirubin photoproducts and cellular damage at defined wavelengths.

Cultured cells from one human and one murine cell line were treated with bilirubin and irradiated with visible light of different wavelengths, either from phototherapy lamps or from a Xenon/Mercury lamp equipped with a monochromator. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, the bilirubin and its photoisomers were extracted and analysed with High Pressure Liquid Chromatography. The formation of single strand breaks in the DNA of treated cells was studied using a fluorescence marker. Cytotoxicity in the mouse skin cell line was measured by loss of the ability to form visible colonies in vitro. Green light exposure favours the production of lumirubin, while blue light causes more DNA damage and cytotoxicity. Green light may be more efficient and safer than shorter wavelength exposure when treating jaundiced newborns with phototherapy.

Animals↗

PubMed1994

Quantitative magnetic resonance for assessment of radiation fibrosis after post-mastectomy radiotherapy.

Subcutaneous fibrosis is a serious complication of post-mastectomy radiotherapy with a pronounced influence on skin conditions, shoulder movement and arm oedema. To establish safer radiotherapy schedules, precise evaluation of the tissue damage is required. A feasibility study was performed to assess the value of calculated relaxation times from magnetic resonance (MR) images for quantitative characterization of different degrees of subcutaneous fibrosis after post-mastectomy radiotherapy. A surface coil was applied to the irradiated area, as well as to unirradiated skin, to obtain appropriate MR coronal slices for acquisition of calculated values using a mixed imaging sequence technique. 14 patients with clinically diagnosed subcutaneous fibrosis were examined, 10 of whom had severe fibrosis. The mean T2 values of the treated and untreated side were 53.0 and 56.7, respectively. A statistically significant decrease of the calculated T2 values on the treated side was observed. No correlation was found between the clinically assessed fibrosis and the calculated relaxation times. The findings indicate that despite a general decrease of T2 calculated values, the large variation in the relaxation times restricts the value of MR, as applied in this study, in differentiating between different degrees of fibrosis in normal tissues after radiotherapy.

Aged↗

PubMed1994

Evaluation of lipomatous soft tissue tumors by MR imaging.

Large soft tissue tumors--5 cm or greater--or deep-seated tumors have a greater risk of being malignant than smaller and superficially located tumors (9). In a period of 2 years 43 consecutive patients with lipomatous tumors 5 cm in diameter or greater were examined with MR imaging. The MR findings were correlated to histologic features and diagnosis. Twenty-six tumors were classic lipomas both on MR and at microscopy; 8 lipomas showed other features--some of them raising suspicion of malignancy at MR; all, however, were histologically benign. Nine tumors were considered malignant at MR imaging; all 9 proved to be malignant by microscopy.

Adipose Tissue↗

PubMed1994

Comparison of the safety of standard and triple dose gadodiamide injection in MR imaging of the central nervous system. A double-blind study.

Gadodiamide injection was administered intravenously to 49 patients with known or suspected CNS lesions undergoing MR imaging. Two parallel groups were used to evaluate the efficacy and safety of single doses of 0.1 (25 patients) and 0.3 (24 patients) mmol/kg b.w. The principal measures of efficacy were diagnostic yield of MR and the overall contrast enhancement. Adverse events and serum bilirubin were the main safety parameters. Contrast enhancement of the lesion was observed for 16 patients in each dose group. Thirteen patients in the 0.1 and 17 in the 0.3 mmol/kg group had their diagnosis amended following the postcontrast image, but only one patient in each dose group had their management affected by new information from the postcontrast image. The overall diagnostic utility of gadodiamide injection was good, but there were no differences between the 2 doses studied in this respect. No injection-associated discomfort or other adverse events were reported. No clinically important changes in serum bilirubin, or other parameters of blood chemistry, or hematology were observed. Overall, the safety profile of gadodiamide injection 0.3 mmol/kg b.w. in this study was similar to that of 0.1 mmol/kg b.w.

Adult↗

PubMed1993

MRI mapping of postreconstructive edema following femoropopliteal bypass surgery.

We have used T1 MR images to map the distribution of water contributing to the edema which follows femoropopliteal bypass surgery. Spin-echo images and true parametric T1 images were made at the same time. The spin-echo images were used to identify the tissue anatomy. The extra fluid contributing to the edema distributes in two phases: a volume equivalent to 5% of the leg volume is distributed throughout the leg tissue, while the excess fluid collects in a localized annulus lying adjacent to the fascia. The T1 in the annulus can be as high as 4 sec, indicating build up of free fluid in this region. Although most of this free fluid lies in the subcutaneous fat, there is a component which lies underneath the fascia in the muscle compartment.

Aged↗

PubMed1993

Impairment of Fos protein formation in the rat infarct borderzone by MK-801, but not by NBQX.

In the present immunocytochemical study, we investigated the mechanism of Fos protein induction and the regional distribution of the Fos protein in brains of spontaneously hypertensive rats subjected to 2 h of permanent middle cerebral artery occlusion (MCAO). Rats were administered either saline or a glutamate receptor antagonist; the non-competitive NMDA receptor antagonist MK-801 or the AMPA receptor antagonist NBQX which are known to be able to reduce infarct size in MCA occluded rats. The saline treated rats showed presence of Fos protein in nerve cell nuclei throughout the cortical and striatal infarct borderzone, but no staining in the infarct core or contralateral hemisphere. MK-801 almost totally abolished this expression of Fos protein whereas NBQX had no significant effect on Fos protein expression. It is suggested that the Fos protein induction is due to repeated spreading depressions mediated by NMDA receptors in the infarct borderzone, and that Fos protein due to its persistence in the tissue can be used as a histochemical marker of borderzone tissue at risk for eventually becoming recruited in the infarct.

Animals↗

PubMed1993

Heart transplantation in a case of juvenile hereditary haemochromatosis followed up by MRI and endomyocardial biopsies.

Cardiac involvement in hereditary haemochromatosis (HH) is a poor prognostic sign and is the main cause of death in the juvenile form. The treatment of choice is iron removal therapy by phlebotomy, but treatment by iron chelation (desferrioxamine) has been recommended in cases with severe cardiac symptoms. We describe here the first case of juvenile HH undergoing heart transplantation, which became necessary despite intensive iron removal therapy by phlebotomy and treatment by desferrioxamine. Throughout the course the myocardial iron content was monitored by endomyocardial biopsies and by magnetic resonance imaging (MRI). At the last follow-up, 18 months after transplantation, the myocardial iron content in the transplanted heart was still within reference ranges by biochemical determination and MRI and the patient's condition was completely satisfactory. In conclusion, heart transplantation should be considered in cases of severe juvenile HH. In the follow-up of these patients MRI may be a useful supplement.

Adult↗

PubMed1993

Bilirubin bound to cells does not form photoisomers.

Cultured cells from one human and one murine cell line were incubated with bilirubin by different methods that allowed bilirubin to be bound to cells. The cells were irradiated with visible light of different wavelengths. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, bilirubin and its photoisomers were extracted and analyzed by HPLC. No photoisomers were found in samples of irradiated cells, while the types and amounts of photoisomers that were expected from the literature were found in samples of irradiated bilirubin/albumin mixtures. We conclude that the formation of therapeutically active photoisomers during phototherapy most probably does not take place in skin cells, but most likely in bilirubin bound to albumin in the vessels or in the interstitial space.

Animals↗

PubMed1993

Specific nitrogen-15 labelling of leucine residues in human growth hormone.

Biosynthetic human growth hormone (hGH) specifically 15N labelled in the leucine residues has been obtained by recombinant DNA technology, using 15N-labelled leucine and an E. coli strain that requires leucine. It is shown that, despite the possibility of minor transaminase activity, the labelling on the whole is specific, and that the two-dimensional 1H-15N correlation NMR spectra of hGH can be greatly simplified by this methodology.

Escherichia coli↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

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↗