PubMed Health⌕ Search

Biomedical subjects

J Krüger

Publications and source records attributed to J Krüger.

At least 37 records · Page 2Linked to original sources

Immunocompetence of T lymphocytes during whole-blood storage.

In WB stored for 28 days at 4 degrees C the pattern of peripheral T-cell CD25 (IL-2R) expression after polyclonal in vitro stimulation was examined. Flow cytrometic analysis was performed with lymphocytes after 72 h in culture with and without ConA using antibody against CD3 and CD25. In culture supernatants IL-2 was determined. T-cells bearing the CD25 marker decreased with storage time, the mean fluorescence (i.e., number of IL-2R molecules per cell) remained rather stable. IL-2 concentrations peaked with stimulated cells which have been stored for 6 days. The low detectable levels of IL-2 in cultures of T-cells which have not been stored may reflect a much more efficient interplay of IL-2/IL-2R. Thus, even after longer periods of blood storage there are sufficient numbers of T-cells which can be stimulated to excite preprogrammed effector functions, i.e. also a GVHD.

Blood Preservation↗

Coordinate system matching for neuromagnetic and morphological reconstruction overlay.

The overlay of functional and morphological images is an essential tool for advanced and improved functional diagnosis showing the correlation between spatial structures or lesions and functional areas. We present an improved coordinate system matching technique. The well known method of three orthogonal coils combined in one coilset for an angular-independent measure is validated for the use of first- or higher order gradiometers instead of magnetometers. The coilset localization procedure was modified with lock-in detection and current feedback for better long range sensitivity. Real measurements with the 31-channel Philips-MEG system have been carried out. A very good localization accuracy below the measuring area with deviations below 2 mm was found. For coordinate system matching, a 3-D cursor with surface images from segmented MR-data was implemented and an optimized, weighted least squares fit transformation algorithm between functional and morphological systems was developed. The resulting transformations consist of weighted shifts and best-fit rotations and lead to deviations of marker positions in the mm range, depending mainly on the spatial accuracy of the marker fixation.

Algorithms↗

The impact of polymorphonuclear neutrophils on the quality of stored cellular blood products.

BACKGROUND: Storage of blood affects all blood components. Polymorphonuclear neutrophils (PMNs) are considered the main culprits of the storage lesion. Their prestorage removal improves the quality of blood components. Therefore, they are considered of no use in blood transfusion. However, their reduction may remove important antibacterial defense mechanisms. METHODS: The phagocytic activity of PMNs in whole blood was therefore determined together with additional, sequential changes of granula-specific and cytosolic constituents which they release. Blood from 12 volunteer donors was analyzed for plasma Na+ and K+, pH, LDH, lysozyme, PMN elastase, leukocytes, neutrophils, and neutrophil phagocytosis with Phagotest. RESULTS: Leukocytes decreased from (5.0 +/- 1.4) x 10(3) to (3.3 +/- 1.3) x 10(3) cells/microliter (mean +/- SD), most of them being PMNs. Their phagocytic capacity when rewarmed did not change significantly during the first 24 h of storage, after 3 days it came to a halt. At the same time an increasing fall in plasma sodium and pH became apparent, while plasma potassium, LDH, lysozyme, and elastase all rose by 427%, 235%, 87% respectively 1,479% at day 11. Together with these marker enzymes an armamentarium of antibiotic proteins, other proteolytic enzymes, and immunoregulatory molecules is released. CONCLUSION: At present, it seems that the bactericidal activity in blood, due to the removal of phagocytic PMNs, does not outweight the clinical benefits of an improved component preparation where storage lesions are minimized and a number of transfusion-associated adverse reactions are avoided.

Adult↗

Analysis of cytokine profiles of stored CPDA-1 whole blood.

BACKGROUND: The pathophysiologic mechanisms of symptoms of nonhemolytic febrile transfusion reactions (NHFTR) are complex and sometimes poorly understood. The prevalence of these reactions especially with platelet transfusions has been attributed more recently to storage-dependent cytokine levels. Until now cytokine concentrations in whole blood (WB) have found very little attention though WB is still relevant to autologous blood and a systematic evaluation of the storage lesion of WB remains of general interest. METHODS: Concentrations of interleukins (IL-1beta, IL-6, IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factors (TNF-alpha, TNF-beta) were analyzed in blood samples drawn from 7 units of WB over a storage period of 35 days. All cytokine concentrations were determined by enzyme immunoassays. RESULTS: IL-1beta, IL-8 increased steadily in all units and TNF-beta in 3 out of 7 from undetectable levels to concentrations of the lower standard ranges. IL-6 and TNF-alpha showed a mean low level plateau. On GM-CSF release storage seemed to have a minor transient effect. CONCLUSIONS: It seems questionable that on storage the presence of cytokines in WB reaches concentrations sufficient to explain NHFTR. At present the depletion of leukocytes as the main source of cytokines may not be necessary to be carried to the extreme.

Adult↗

[Alanine aminotransferase (ALAT, GPT): a reevaluation of exclusion limits for blood donors].

BACKGROUND: The screening policy of alanine aminotransferase (ALT) testing in blood donors was reassessed. The cutoff value for ALT levels according to German guidelines has always been controversial. In this study the activity and distribution of ALT in a blood donor population were reevaluated and new exclusion levels were defined. METHODS: 5,706 blood donors were tested for ALT activities with the Reflotron system at 37 degrees C. Donors with ALT levels > 51 IU/l were deferred, a detailed physical examination and additional serologic and biochemical testing were done. RESULTS: ALT values of blood donors were transformed in logarithmic values in order to get a Gaussian distribution. The mean transformed value +/- SD was calculated with 1.24 +/- 0.14 for females and with 1.35 +/- 0.16 for males, corresponding to mean values of ALT activity of 17.6 and 22.5 IU/l, respectively. Exclusion levels of > 33.4 IU/l for female and > 46.7 IU/l for male blood donors (geometric mean +2.0 SD) predict a loss of donations of 2.8 and 2.7%, respectively, cutoff values of > 39.1 or > 56.1 IU/l (geometric mean +2.5 SD) a loss of 1.8 and 1.4%, respectively. The most likely causes of elevated ALT levels in 166 of our donors included daily alcohol use (82), infections with/without antibiotic medication (29), therapy with hepatotoxic drugs (8), strenuous exercises (5), bodybuilding complemented by anabolic steroids (2), acute infections with HCV (1), HBV (1) and CMV (1), alcohol/drug abuse and detection of HCV antibodies (1). CONCLUSIONS: ALT screening is still considered a useful indicator of risk donors despite its nonspecificity and limited predictive value. The selection of the appropriate cutoff value has always been disputed. The present exclusion level of > 45 IU/l (25 degrees C), analogous to > 81.8 IU/l (37 degrees C), does not even take into account such a variable as sex. The cutoff value above 4.5 SD of the geometric mean for females and above 3.5 SD for males seems to be of limited medical and practical value.

Alanine Transaminase↗

Analysis, classification, and coding of multielectrode spike trains with hidden Markov models.

It is shown that hidden Markov models (HMMs) are a powerful tool in the analysis of multielectrode data. This is demonstrated for a 30-electrode measurement of neuronal spike activity in the monkey's visual cortex during the application of different visual stimuli. HMMs with optimized parameters code the information contained in the spatiotemporal discharge patterns as a probabilistic function of a Markov process and thus provide abstract dynamical models of the pattern-generating process. We compare HMMs obtained from vector-quantized data with models in which parametrized output processes such as multivariate Poisson or binomial distributions are assumed. In the latter cases the visual stimuli are recognized at rates of more than 90% from the neuronal spike patterns. An analysis of the models obtained reveals important aspects of the coding of information in the brain. For example, we identify relevant time scales and characterize the degree and nature of the spatiotemporal variations on these scales.

Animals↗

Exposure of bus and taxi drivers to urban air pollutants as measured by DNA and protein adducts.

Urinary 1-hydroxypyrene, lymphocyte DNA adducts, serum protein-bound PAH and hemoglobin-bound alkene adducts were analysed from 4 groups of non-smoking men: urban and suburban bus drivers, taxi drivers and suburban controls. The only differences between the groups were in DNA adducts between suburban bus drivers and controls, and in DNA adduct and plasma protein PAH-adducts between taxi drivers and controls.

Air Pollutants↗

Photochemically induced experimental ischemic neuropathy: a clinical, electrophysiological and immunohistochemical study.

A new experimental model of focal peripheral nerve infarction is presented. Ischemia was produced in 12 rats by intravascular thrombosis induced by the photochemical reaction of systemically injected rose bengal to the local application of light from a cold light source. Clinical, electrophysiological and immunohistochemical techniques were used to monitor the pathology and the time course of experimental ischemic neuropathy (EIN) of the sciatic nerve. Primary axonal neurofilament disintegration was detectable 4-24 h after illumination and was followed by wallerian degeneration within the first week. At 7 days, there was a secondary disruption of myelin sheaths accompanied by massive infiltration of macrophages and phagocytosis of the necrotic debris. The majority of detected macrophages were derived from circulating blood monocytes which had invaded the nerve. Two weeks after the initial lesions, degeneration had advanced without any signs of regeneration or remyelination. Electrophysiological recordings corroborate the findings of primary axonal degeneration and failure of regeneration up to 2 weeks after the lesion.

Action Potentials↗

Rhythmic and patterned neuronal firing in visual cortex.

We present evidence from multi-electrode recordings that the stimulus driven activity in a region of monkey visual cortex displays synchronous, oscillatory behaviour with temporally changing patterns of firing. The spatial-temporal patterns are dependent on cortical layer and on visual stimulus, 'build up and die down' with a period of 70-100 msec, and cannot be factorized into separate spatial and temporal components. This finding supports neural network models which explicitly incorporate spatial-temporal structure, ruling against a purely spatial code for information processing. The new type of analysis presented here is also suitable for direct on-line interactive analysis during multi-electrode recording experiments. Further, it could be modified for use in human EEG or evoked response recordings.

Action Potentials↗

Characterization of centromere arrangements and test for random distribution in G0, G1, S, G2, G1, and early S' phase in human lymphocytes.

The arrangement of centromeres, cluster formation and association with the nucleolus and the nuclear membrane were characterized in human lymphocytes during the course of interphase in a cell-phase-dependent manner. We evaluated 3,893 cell nuclei categorized by five parameters. The centromeres were visualized by means of indirect immunofluorescent labeling with anti-centromere antibodies (ACA) contained in serum of patients with CREST syndrome. The cell nuclei were classified as G0, G1, S, G2, G1' and early S' phase by comparing microscopically identified groups of cell nuclei with flow cytometric determination of cell cycle stage of synchronized and unsynchronized lymphocyte cell cultures. Based on a discrimination analysis, a program was devised that calculated the probability for any cell nucleus belonging to the G0, G1, S, G2, G1' and early S' phase using only two microscopic parameters. Various characteristics were determined in the G0, S, and G2 stages. A transition stage to S phase within G1 was detected. This stage shows centromere arrangements not repeated in later cell cycles and which develop from the dissolution of centromere clusters in the periphery of the nucleus during G0 and G1. S phase exhibits various non-random centromere arrangements and associations of centromeres with the nucleolus. G1' and early S' phase of the second cell cycle display no characteristic centromere arrangement. The duplication of centromeres in G2 is asynchronous in two phases. For all cell phases a test for random distribution of the centromeres in the cell nucleus was performed. There is a distinct tendency for centromeres to be in a peripheral position during G0 and G1; this tendency becomes weaker in S phase. Although the visual impression is a seemingly random distribution of centromeres in G2 and G1', statistical analysis still demonstrates a significant deviation from random distribution in favor of a peripheral location. Only the early S phase of the second cell cycle shows no significant deviation from a random distribution.

Cell Cycle↗

[Lymphocytograms in relation to storage time of CPDA1 whole blood concentrates].

Immunocompetent cells have been shown to be effective in immunosuppression after blood transfusion. The analysis of leukocytes by electronic cell counter and of lymphocyte subsets by flow cytometry in stored whole blood revealed a decay of granulocytes within the first day of storage. T-lymphocyte subpopulations and natural killer cells continuously decrease over the time of storage, whereas B lymphocytes are very stable during the first 2 weeks. After 4 weeks lymphocyte subsets had decreased by the following values: total lymphocytes 46.0%, CD3+ 78.3%, CD4+ 80.1%, CD8+ 81.3%, CD19+ 65.9%, CD16/56+ 74.8% and CD3/DR+ 89.5%. Therefore leukocyte removal should be achieved as soon as possible after collection.

Antigens, CD↗

[Leukocyte depletion, a comparison of the "Leukotrap in-line" filter system with a sterile added 4-bag Speacell-R-500-A filter system].

Leukocytes in RBC preparations have a variety of immunologic effects in transfused patients. Not only their elimination at time of transfusion but before storage seems to be advantageous. Filtration with the Leukotrap system at the day of preparation led to an overall reduction of leukocytes of 82.2%, i.e. an average of 5.4 x 10(8) leukocytes/RBC concentrate. Filtration with a Sepacell R 500 A eliminated 99.0% of leukocytes, 3.4 x 10(7) cells remained per blood unit. The determination of lymphocyte subpopulations by flow cytometry after filtration with the Leukotrap system showed a more effective adsorption of B cells than of T and natural killer cells.

Adsorption↗

[Distribution of the incidence of SGPT activity in blood donors].

Predonation SGPT (ALT) testing was performed in 5,706 blood donors (3,944 male, 1,762 female) with the Reflotron system. The values of SGPT activities (IU/l; 25 degrees C) are not normally distributed, whereas the log10 SGPT distribution is largely Gaussian (the arithmetic mean log10 +/- SD for female donors is 0.98 +/- 0.14 and for male donors 1.08 +/- 0.16, the antilog of the mean log10 9.5 and 12.1 IU/l, respectively). In the following the impact of SGPT testing at various exclusion levels on the percentage of deferred donors is shown: (1) female: cutoff level > 18.0 IU/l (mean log10 +2.0 SD) 2.8%, > 19.5 IU/l (+2.25 SD) 2.1%, > 21.1 IU/l (+2.5 SD) 1.8% and > 24.8 IU/l (+3.0 SD) 1.2% deferment. (2) male: cutoff level > 25.2 IU/l (mean log10 +2.0 SD) 2.7%, > 27.6 IU/l (+2.25 SD) 2.3%, > 30.3 IU/l (+2.5 SD) 1.4% and > 36.4 IU/l (+3.0 SD) 0.8% deferment. Using the current cutoff value of > 45 IU/l (according to German regulations, 1987) only 0.2% female (with SGPT > mean log10 +4.5 SD) and 0.3% male (with SGPT > mean log10 +3.5 SD) donors would be excluded. These findings demonstrate that different SGPT exclusion levels for men and women are necessary and that the current cutoff value of > 45 IU/l does not exclude donors who should better be rejected.

Alanine Transaminase↗

[Etiology of increased SGPT activity in blood donors].

From all blood donors screened within a given period of 6 months for SGPT (ALT) immediately before donation, 166 (141 male, 25 female) were found to have SGPT activities above our cutoff value of > 28 IU/l (25 degrees C). In order to define the characteristics of these blood donors they were asked for detailed medical history followed by a thorough physical examination and further serologic and biochemical testing. Factors associated with elevated SGPT activity included daily alcohol consumption (82 donors), infections associated with abnormal DCs (23), therapy with hepatotoxic drugs (8), infections that had been treated with antibiotics (6), strenuous physical exercises (5), body building supported by anabolics (2), acute HBV infection (1), acute HCV infection (1), alcohol/drug abuse and positive test for anti-HCV antibodies (1), anti-CMV positivity with absolute and relative lymphocytosis (1). In 36 cases factors that could have been associated with an increased SGPT activity were not verified. A critical valuation of the presently accepted cutoff value of 45 IU/l (25 degrees C) is given.

Alanine Transaminase↗