[A model system in cell culture shows pathogenic processes. Biochemical diagnosis in Alzheimer dementia].
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Alzheimer Disease↗
Biomedical subjects
M Jensen
Publications and source records attributed to M Jensen.
[Nutritional and fluid supplementation for neonates. Types and use of supplementation in maternity wards].
The objective of the study was to evaluate the practice of giving supplementary feeding to newborns on maternity wards according to type of supplement, use and choice of supplement in different clinical settings, recommended frequency of breast-feeding, recommended types of infant formula and finally the influence of paediatric department and geographic site on the use of different types and use of supplements at the wards. Sixty maternity wards (95%) in Denmark filled in and returned the questionnaire. The maternity wards offered six different kinds of supplements and 36% of the maternity wards offered human milk. The study gave the impression of a large consumption of supplements on the maternity wards. Most of the maternity wards (83%) would recommend hydrolysed infant formula for infants with a family history of allergy, and almost the same number (88%) would recommend traditional infant formula for infants without a family history of allergy. Mothers' request for hydrolysed infant formula for infants without a family history of allergy was refused in 20% of the maternity wards. There were no differences between the recommended frequencies of breast-feeding. Maternity wards in hospitals with paediatric departments would significantly more frequently offer the infants supplements than maternity wards in hospitals without paediatric departments. The same maternity wards would significantly more often use water and human milk and more rarely water with glucose than maternity wards in hospitals without paediatric departments. In the western part of Denmark the maternity wards significantly more often used traditional infant formula and water with glucose than in the eastern part of Denmark. In conclusion, the investigation showed a considerable variation in the different types of supplements used in the maternity wards. The variation was influenced by the presence of a paediatric department in the hospital as well as by the geographic site. To ensure a higher and more uniform quality in this area it would be desirable if The National Board of Health in collaboration with the Allergy committee in the Danish Society of Paediatricians would publish recommendations to all who work professionally with mothers and infants.
Denmark↗
Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.
To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0001), PS2N1411 (P = 0.009), APPK670N,M671L (P < 0.0001), and APPV7171 (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.
Alzheimer Disease↗
[Spiral computed tomography for treatment planning and quality assurance in radiotherapy].
BACKGROUND: The possibilities of spiral CT for radiotherapeutic treatment planning and quality assurance have been systematically investigated. PATIENTS AND METHODS: The influence of parameters such as slice thickness, table speed and increment on geometric accuracy was studied. Ring-, spheric-, PMMA- and humanoid Alderson phantoms were used. Furthermore, patients with infradiaphragmatic irradiation of Hodgkin's disease or with mediastinal irradiation were studied using CT-angiography. Patients with carcinomas of the head and neck before HDR- and PDR-brachytherapy were examined as well. RESULTS: Spiral CT offers 3D volume data information with excellent reduction of breath and motion artefacts for virtual simulation. 2D multiplanar reconstructions with excellent local resolution may be obtained. 3D MIP (Maximum Intensity Projection), based on CT-angiographic imaging, is a good tool for infradiaphragmatic treatment planning of Hodgkin's disease, if small numbers for slice thickness, table speed and increment are used. SSD (Surface Shaded Display) offers good 3D visualization and good geometric control of intracavitary and interstitial brachytherapy applicators. High qualitative multiplanar reconstructions are useful for CT-based brachytherapy planning. CONCLUSIONS: Spiral CT is a precious tool for 3D treatment planning and virtual simulation in radiotherapy and superior to conventional CT data acquisition. Quality assurance is improved for dose-volume-histograms and for brachytherapy.
Angiography↗
[Daylight processing system in radiotherapy. Technical changes and cost benefit analysis].
BACKGROUND: In radiotherapy portal and verification imaging take an important place in daily quality assurance procedures. Different types of films and cassettes have to be used to gain an optimal result for photon and electron beams. MATERIALS AND METHODS: We describe a modification of a machine for daylight processing, which has been technically enabled not only to process all X-rays from simulator, brachytherapy, CT and MRI but all film materials from portal and verification imaging as well without changing system's configuration. Using a light gap, verification films are automatically differentiated from portal films or from film material from simulation and the cassettes are automatically loaded with the new verification film. Furtheron, we took some attention on cost effectivity. RESULTS: The daylight processing machine is sufficiently integrated into daily routine work load and spares a lot of staff time. Higher primary costs are overbalanced within a few years by lower supporting costs (Table 1). This is especially due to lower film material costs (Table 2), but also a result of staff time reduction. CONCLUSIONS: Radiotherapeutic departments may gain much comfort using a daylight processing machine as development unit.
Brachytherapy↗
Increased cerebrospinal fluid tau in patients with Alzheimer's disease.
One of the pathological features in Alzheimer's disease (AD) is neurofibrillary tangles in the brain. The main constituent of tangles is the microtubuli-associated protein tau in a hyperphosphorylated state. Tau is also released into cerebrospinal fluid (CSF), and in this study we have used an enzyme linked immunosorbent assay to measure tau in CSF from AD and control cases. Our findings show that tau levels in AD cases are significantly elevated compared to healthy control individuals. We suggest that tau may serve as a biochemical marker of Alzheimer's disease.
Aged↗
Spinal nomenclature.
There has been a proliferation of differing terms, even among practicing surgeons. A morphologically based nomenclature may be needed for radiologic purposes, whereas a more histopathologic terminology would be desirable for surgical descriptors. Whichever approach is undertaken, the true radiologic-surgical correlation of disc abnormalities within the spine is doomed to failure without agreement on some type of standard nomenclature. A review of the problem and potential solutions are suggested.
Humans↗
Zinc absorption estimated by fecal monitoring of zinc stable isotopes validated by comparison with whole-body retention of zinc radioisotopes in humans.
Knowledge about zinc availability from human diets is limited due to methodological difficulties. Recently developed stable isotope techniques for estimating dietary zinc absorption were compared with radioisotope techniques in five men and three women. Stable and radioactive zinc isotopes were simultaneously administered. Fecal excretion of the isotopes as well as whole-body retention of the radioactive zinc isotope was monitored. Concentration of stable zinc isotope label in fecal samples was determined by inductively coupled plasma mass spectrometry by fully quantitative measurements and from inductively coupled plasma mass spectrometry isotope ratios combined with analysis of total zinc content using atomic absorption spectrometry. Zinc absorption estimated from whole-body retention was 27 +/- 6% (mean +/- SD), estimated zinc absorption obtained by fecal monitoring of radioisotope was 26 +/- 9%, and the two stable zinc measurements resulted in values of 29 +/- 12 and 33 +/- 12%, respectively. There was no significant difference in zinc absorption estimated from whole-body retention and with the fecal monitoring methods. Recovered stable zinc isotope label was significantly lower than recovered radioisotope. For individual fecal samples, systematic differences of 16% and 12%, respectively (P < 0.05), between the radioisotope recovery and the recovery of stable isotopes with the two methods for measurement was observed. The stable zinc isotope technique for measurement of zinc absorption resulted in mean results similar to those of the radioisotope technique, but with a larger variation in the measurements.
Adult↗
Circulating interleukin-1 receptor antagonist concentrations are increased in adult patients with thermal injury.
OBJECTIVE: To investigate the balance between circulating concentrations of interleukin (IL)-1 and its natural inhibitor interleukin-1 receptor antagonist (IL-1Ra) in human inflammation. DESIGN: Prospective case-control study. SETTING: University hospital burn care unit. PATIENTS: Fifteen patients with second- or third-degree thermal injuries of 7% to 78% of total body surface and 15 healthy age- and sex-matched control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median plasma IL-1Ra, but not IL-1 beta or tumor necrosis factor-alpha (TNF-alpha) concentrations were markedly increased on the day of admission in patients with thermal injuries compared with controls (1615 [range 426 to 23,800] vs. 494 [range 196 to 1093] pg/mL; p < .001). In survivors, the median IL-1Ra concentration normalized 12 to 21 days after admission. The concentration of IL-1Ra on the day of admission was weakly positively correlated to the extent and degree of thermal injury (r2 = .46; p < .05). IL-1Ra on days 1 to 3 was highest in three nonsurvivors with inhalation injuries compared with survivors (2166 [range 1362 to 36,624] vs. 1344 [range 665 to 13,085] pg/mL; p < .05). IL-1Ra increased significantly after debridement and skin transplantation (preoperatively 742 [range 488 to 1506] vs. postoperatively 1431 [range 1286 to 2107] pg/mL; p < .01). In nonsurvivors, median IL-1Ra was 3.6-fold higher than IL-1 beta on days 1 to 2 and 36-fold higher than IL-1 beta in three patients with bacteremia. IL-1Ra was studied for its relationship to previously reported parameters of the acute-phase response determined in the same samples from these patients. The increased concentrations of IL-1Ra coincided with a decrease in serum albumin concentration and increases in rectal temperature. However, IL-1Ra did not correlate with rectal temperature, plasma concentrations of endotoxin, IL-1 beta, or TNF-alpha either at admission or in follow-up samples. CONCLUSIONS: Thermal injury causes an increase of circulating IL-1Ra, especially in patients with inhalation injuries. With the current plasma assays for IL-1 beta, IL-1Ra may be a more sensitive marker of human inflammation than IL-1 beta or TNF-alpha.
Adult↗
The metabolic pathway generating p3, an A beta-peptide fragment, is probably non-amyloidogenic.
The Alzheimer a beta amyloid precursor protein is metabolized by at least two secretory pathways. One generates the A beta peptide and the other a N-terminally truncated A beta fragment termed p3 that is considered non-amyloidogenic. However, direct evidence is missing. We have undertaken to synthesize and purify p3. Pure p3 polymerizes in vitro, forming a lattice with an ultrastructure distinct from the linear fibrils of A beta. In contrast to amyloid, polymerized p3 does not bind thioflavine T. It is therefore concluded that amino acids in the N-terminal part of the A beta molecule are required for formation of typical amyloid fibrils and that the metabolic pathway generating p3 probably is non-amyloidogenic
Amino Acid Sequence↗
[Positron emission tomography. A new measurement method for imaging of regional and biochemical parameters].
Positron emission tomography (PET) is a method for quantitative imaging of regional physiological and biochemical parameters. Positron emitting radioactive isotopes can be produced by a cyclotron, eg. the biologically important carbon (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle of the PET scanner the quantitative distribution of the administered isotopes can be determined and images can be provided as well as dynamic information on blood flow, metabolism and receptor function. In neurology PET has been used for investigations on numerous physiological processes in the brain: circulation, metabolism and receptor studies. In Parkinson's disease PET studies have been able to localize the pathology specifically, and in early stroke PET technique can outline focal areas with living but non-functioning cells, and this could make it possible to intervene in this early state. With positron emission tomography a quantitative evaluation of myocardial blood flow, glucose and fatty acid metabolism can be made as well as combined assessments of blood flow and metabolism. Combined studies of blood flow and metabolism can determine whether myocardial segments with abnormal motility consist of necrotic or viable tissue, thereby delineating effects of revascularisation. In the future it will probably be possible to characterize the myocardial receptor status in different cardiac diseases. The PET technique is used in oncology for clinical as well as more basic research on tumor perfusion and metabolism. Further, tumor uptake of positron labelled cytotoxic drugs might predict the clinical benefit of treatment.
Brain↗
Properties of the scrapie prion protein: quantitative analysis of protease resistance.
The disease-specific isoform of the prion protein (PrPSc) is an essential part of the infectious particle which causes spongiform degeneration in various mammalian species. PrPSc differs from PrP of normal animals (PrPc) by its relative protease resistance. The physical nature of this difference is still unknown. We analyzed the protease resistance of PrPSc quantitatively using an enzyme-linked immunofiltration assay. PrPSc was rendered completely protease-sensitive at alkaline pH or in > 1.5 M guanidinium thiocyanate (GdnSCN). Denaturation in 4 M GdnSCN completely abolished the protease resistance of PrPSc within 15 min, while denaturation in 7.2 M urea showed a slower time course. In the presence of ethanol, PrPSc was protected from denaturation by GdnSCN or alkaline pH. Denaturation curves were used to calculate the free energy (delta GD) as a function of different denaturant concentrations. Linear regression of delta GD values was used to extrapolate the free energy in the absence of denaturants (delta GH2O), yielding similar values (delta GH2O,GdnSCN = -2.3 kcal/mol; delta GH2O,urea = -3.1 kcal/mol). The linear relationship between delta GD and the denaturant concentration is suggestive of a two-state model involving the conformational change of a single protein domain. This is also reflected in the small number of side chains (11.6) additionally exposed to the solvent upon conversion of PrPSc to its protease-sensitive isoform. Our results suggest that only minor rearrangements of the structure of PrP are needed to abolish the protease resistance of PrPSc.
Animals↗
Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy.
Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy.
Antigens, Viral↗
Quantification of liver fat using magnetic resonance spectroscopy.
Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.
Adult↗
Assessment of insulin action in NIDDM in the presence of dynamic changes in insulin and glucose concentration.
Both glucose and insulin are important regulators of glucose uptake and hepatic glucose release. Because insulin concentrations rarely if ever increase under daily living conditions, unless glucose concentrations also increase, we sought to determine whether hepatic and extrahepatic responses to changes in insulin and glucose concentration are impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). To address this question, glucose metabolism was measured in diabetic and nondiabetic subjects. A computer-driven infusion system was used to produce a nondiabetic postprandial insulin profile in both groups while sufficient exogenous glucose was infused to mimic nondiabetic postprandial glucose concentrations. Although NIDDM was associated with greater (P < 0.05) hepatic glucose release both before and during the prandial insulin infusion, suppression did not differ in the diabetic and nondiabetic subjects (-1.06 +/- 0.20 vs. -0.86 +/- 0.15 mmol/kg every 4 h). In contrast, stimulation of both glucose disappearance (0.77 +/- 0.27 vs. 1.68 +/- 0.27 mmol/kg every 4 h) and forearm glucose uptake (187 +/- 81 vs. 550 +/- 149 mumol/dl every 4 h) was lower (P < 0.05) in diabetic than in nondiabetic subjects. Thus, despite increased basal rates of glucose production, obese individuals with NIDDM had decreased stimulation of glucose disappearance but normal suppression of hepatic glucose release in response to nondiabetic prandial glucose and insulin concentrations. These data indicate that the increase in glucose that occurs with carbohydrate ingestion is likely to compensate for hepatic but not extrahepatic insulin resistance.
Blood Glucose↗
[Pressure sores--a black heel].
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Female↗
Toxicokinetics of nickel in mice studied with the gamma-emitting isotope 57Ni.
The gamma-emitting isotope 57Ni was generated in a cyclotron to allow whole-body counting of laboratory animals dosed with nickel. 57NiCl2 was administered either orally by gastric intubation or by intraperitoneal injection to groups of mice in doses equivalent to the average human daily dietary nickel intake per mass unit. When given orally, the whole-body retention (WBR) was 0.02-0.36% of the administered dose at 45-75 hr. When given intraperitoneally, the WBR was 1-6% at 20-50 hr. After adjustment for the rapid excretion of systemic nickel, the intestinal absorption could be estimated to be 1.7-10%. The relative WBR did not vary with the magnitude of the dose within 0.05-5 mumol Ni/kg given orally or 0.005-0.5 mumol/kg given intraperitoneally. At 8 hr, the tissue concentration was highest in the kidneys, followed by the carcass, lungs, testicles, liver, and the spleen. After 20 hr, the highest concentrations were still found in the kidneys followed by the lungs, the liver, and the carcass. At 20 hr after oral administration, 50-70% of 57Ni retained in the body was within the carcass. The second highest nickel content was found in the kidneys, followed by the liver and lungs. Whereas nickel in the kidneys was rapidly excreted, the elimination from the lungs and liver was relatively slow, thereby, after 40 hr, resulting in a higher nickel content in the liver than that in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Pancreatic beta-cell function and interleukin-1 beta in plasma during the acute phase response in patients with major burn injuries.
Animal experiments demonstrate that interleukin-1 beta (IL-1 beta) is beta-cell cytotoxic in vitro and inhibits insulin secretion in vivo. However, it is unknown if IL-1 beta affects beta-cell function in man. Since IL-1 beta and other cytokines are main mediators of the acute phase response, the objectives of the present study were to examine beta-cell function in patients with major burn injuries, and to test if changes in beta-cell function correlated to systemic levels of IL-1 beta and tumour necrosis factor alpha (TNF alpha). We established and validated an IL-1 beta assay measuring free and protein bound IL-1 beta; protein bound IL-1 beta was detached from the IL-1 beta specific binding protein by acidification, rendering it accessible for the employed antibody. The IL-1 beta specific binding protein (43-60 kDa) was found in serum and plasma from all tested patients and normal subjects. Survivors of burn injuries had a stimulated beta-cell function, whereas non-survivors had an impaired beta-cell function as indicated by an increased plasma concentration of proinsulin, and an increased proinsulin/insulin ratio. In addition, non-survivors had significantly increased plasma levels of IL-1 beta. However, we could not demonstrate any correlation between C-peptide, proinsulin, insulin or proinsulin/insulin ratio and plasma concentration of IL-1 beta. In conclusion, beta-cell function abnormalities are evident in patients with major burn injuries, and a high plasma level of IL-1 beta correlates with a fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute-Phase Reaction↗