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Biomedical subjects

J Wenzel

Publications and source records attributed to J Wenzel.

At least 19 recordsLinked to original sources

The value of lymphocytopenia as a marker of systemic involvement in cutaneous lupus erythematosus.

BACKGROUND: Some patients suffering from cutaneous lupus erythematosus (CLE) develop extracutaneous manifestations during the course of the disease: up to 5% of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE) patients show systemic involvement. Recent studies revealed some markers indicating systemic manifestations of CLE patients. However, the significance of diminished peripheral lymphocyte numbers as a marker of systemic involvement in CLE has not been investigated before. OBJECTIVES: To determine the value of lymphocytopenia (< 1500 cells microL(-1)) as a marker of extracutaneous manifestations in CLE patients. : Methods The records of 72 CLE patients (44 DLE; 28 SCLE) were investigated. Systemic involvement was defined in accordance with the criteria of the European Academy of Dermatology and Venereology. Analyses of peripheral lymphocyte numbers were done by fluorescence-activated cell sorter analysis. RESULTS: Five CLE patients developed extracutaneous manifestations during the course of disease. All these patients were lymphocytopenic. Differences between peripheral lymphocyte numbers of CLE patients with and without additional systemic involvement were highly significant (P < 0.01). CONCLUSIONS: Our results suggest that lymphocytopenia in patients with CLE is a high sensitive but low specific marker of systemic involvement.

Adult↗

Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor.

The CD95/Fas/Apo-1 ligand is expressed on activated lymphocytes, NK cells, platelets, certain immune-privileged cells and some tumor cells and induces apoptosis through the death receptor CD95/Fas/Apo-1. In murine T cells, membrane-bound CD95L (Fas ligand) also acts as a costimulatory receptor to coordinate activation and function in vivo. The molecular basis for this reverse signal transduction is yet unknown. In the present report, we identify individual interaction domains of enzymes and adapter molecules that selectively interact with full-length CD95L from transfectants and human T cells. These results may help to explain the costimulatory capacity of CD95L.

Amino Acid Sequence↗

Association of inclusion body myositis with subacute cutaneous lupus erythematosus.

We present the case of a 71-year-old man with inclusion body myositis combined with subacute cutaneous lupus erythematosus and dysphagia. Although inclusion body myositis is usually resistant to immunosuppressive therapy, this patient improved under treatment with corticosteroids. The presented case is discussed in the context of earlier reports of inclusion body myositis and lupus erythematosus.

Aged↗

A comparison of physical examination and clinicopathologic parameters between sheared and nonsheared alpacas (Lama pacos).

The purpose of this study was to determine the physiological changes associated with chronic heat stress in sheared versus nonsheared alpacas. Fourteen intact male adult alpacas were randomly assigned to one of the two groups: Group S alpacas were sheared to within 2cm of their skin; Group NS alpacas were not sheared. These animals were maintained from June through August in east central Alabama. Data collected in the morning, every two weeks, included vital signs, body weight, body condition score, complete blood counts, serum chemistries and electrolytes, whole blood selenium, and plasma cortisol. S and NS groups were contrasted using the repeated measures analysis of variance, and pertinent correlations with weather parameters were calculated. Clinical heat stress was not evident in any animals during the study. Significant differences between treatment groups were seen in rectal temperature (P=0.0095), sodium concentration (P=0.0219), and blood urea nitrogen (BUN) (P=0.0189). The mean rectal temperature of the NS group was above the normal range on five sampling times compared to only once for the S group. However, mean sodium and serum urea nitrogen levels were within normal limits in both groups at all sampling times. Rectal temperature of only the S group was positively correlated to weather parameters. Sodium of both S and NS groups and BUN of the NS group were negatively correlated with weather parameters. This study indicates that there are differences between sheared and nonsheared alpacas in physical examination and clinicopathologic parameters that can be correlated with changes in ambient conditions. These differences suggest that nonsheared alpacas are less heat tolerant than sheared alpacas. Therefore, shearing is recommended for animals exposed to similar conditions.

Journal Article↗

Early and late morphological effects of experimental HPNS--animal model of psychosis?

The high pressure neurological syndrome (HPNS), a neurological condition during elevated pressure especially in deep diving, has been simulated with experimental animals. Rats were subjected to 61 bars with slow pressure increase and one or two hours constant high pressure; subsequently the pressure was released to sea level within 20 seconds--leading to immediate oxygen depletion and death of animals--or with slow decompression rates allowing survival. In all animals, brains and partly other organs were investigated morphologically. In animals sacrificed immediately, subtle changes in different brain regions were found: symmetrical occurrence of dark neurons in the hippocampus formation, cortex and brain stem, reduced expression of tyrosin hydroxylase in the substantia nigra and enhanced expression of Bax protein in some of these regions. The dark neurons were only observed after aldehyde fixation, otherwise the brains were unaltered despite ultrarapid decrease of highly elevated pressure. In animals that were allowed to survive for different time periods, some of these subtle changes were equally noted by light and electron microscopy. Furthermore, the ventricles were enlarged, the astrocytic reaction in the hippocampus increased and some signs of the destruction of the adrenal gland were visible. We conclude, that HPNS leads to minimal changes within the nervous system. The behaviour of animals during pressure was slightly altered, the weights after the experiments reduced, but no lasting sequelae were noted. Since both in human and experimental deep diving conditions signs of psychosis were reported, this HPNS model must be considered as a tentative animal model of human psychosis.

Adrenal Glands↗

Flame figures in urticarial lesions accompanying systemic lupus erythematosus.

We present the case of a 38-year-old female patient with systemic lupus erythematosus and atypical urticarial skin lesions with an alteration in shape, but not complete disappearance, within 24 hours. Hematoxylin-eosin-stained sections revealed flame figures. We review urticarial lesions in lupus erythematosus and discuss the possible pathomechanisms.

Adult↗

Functional specialization and topographic segregation of hippocampal astrocytes.

Astrocytes have been suggested to play several roles in the complex control of brain microenvironment. However, they have been generally considered to constitute a homogeneous population of cells. Here we show that at least three electrophysiologically distinct types of astrocytes can be found in the mature hippocampus. These subpopulations of glia were characterized by expression of different ion currents. In astrocytes exposed to elevated K+, Cs+ prevented influx of K+ only in cells with inwardly rectifying currents (IIR). The topographic distribution of glia with Cs+-sensitive inward rectifying currents (involved in K+ buffering) was nonuniform. Cs+-sensitive astrocytes were predominantly found in CA3 radiatum, whereas most CA1 astrocytes were Cs+-insensitive. Functional significance of the spatial segregation of glial cells with inward rectification was addressed in slices that were bathed in Cs+-containing media. Under these conditions, neuronal stimulation induced spontaneous epileptiform activity, which first appeared in CA3 and was then synaptically propagated to CA1. Intracellular labeling of astrocytes with biocytin revealed that CA1 astrocytes are characterized by a high degree of cell-to-cell coupling; in contrast, cell labeling in CA3 revealed smaller groups and occasionally individual cells. Three individual biocytin-labeled cells had electrophysiological properties indistinguishable from Cs+-sensitive astrocytes but had morphology typical of oligodendroglia. These results provide evidence for a role of K+ uptake via IIR into astrocytes. The segregated expression of potassium channels in a subpopulation of astrocytes suggests that functionally specialized cell types are involved in K+ homeostasis.

Animals↗

The influence of CO2 in a space-like environment: study design.

For the operation of manned spacecraft, the removal of CO2 from the cabin atmosphere, produced by its inhabitants, is essential. This is accomplished by chemical absorption in a gas processing unit, a process which requires energy and consumables. Therefore, in terms of resource management, the CO2-level should be kept as high as possible. Otherwise, considering crew health and performance and also the interference with life science experiments, the CO2 load should be as on Earth, close to zero. In order to obtain more information about the permissible CO2 level for future space missions and also to clarify Space Station design criteria, NASA-ESA-DARA have initiated a ground-based simulation study with two different CO2 levels: 0.7% (first campaign) and 1.2% CO2 (second campaign). For this study the deep diving facility of DLR was used to provide atmospheric control and long-term habitation for the test subjects in studying the effect of increased CO2 on physiological and psychological functions. A number of experiments were implemented, which tested selected effects of raised CO2 on humans. Four male subjects stayed in the chamber for 26 d in each campaign, in order to perform the different tests in repeated trials, with the aim of evaluating possible long-term effects. CO2 was controlled by absorption with soda lime, flushing with fresh air and the addition of CO2, if necessary. Essentially, the CO2 produced by the subjects was used to maintain the level at 0.7 and 1.2%, respectively. Basic control of CO2 was carried out in the soda lime container of the Life Support System. In order to maintain the required level, the amount of gas flowing through the soda lime could be adjusted by a remote controlled bypass. With this set-up it was possible to keep CO2 at an average level between 0.67 and 0.73% in the first campaign and between 1.17 and 1.23% in the second campaign. The results of the experiments support the current CO2 limits for space operations, insofar as values around 1% do not impose any severe restrictions to human habitation for at least several weeks, whereas life sciences experiments especially sensitive to CO2 influences have to be carefully evaluated for possible interferences.

Adult↗

Effects of chronically increased ambient CO2 concentrations on aerobic capacity.

As part of a joint NASA-ESA-DARA study on the effects of chronically increased CO2 concentrations in ambient air, changes in parameters indicating aerobic capacity were investigated by cycle ergometry. Two potential sources for reductions of aerobic capacities were hypothesized: 1) the adaptations to CO2 such as reduction in H(+)-buffer capacities which may influence muscle metabolism; 2) the reduced physical activities which may lead to a detraining effect. Four subjects were exposed to 0.7% and 1.2% CO2 concentration in a confined compartment for 23 d each with 3 mo in between the two campaigns. A combined exercise test was applied before, during (on days 5, 11, and 22) and after CO2 exposure. Comparing steady-states at 30 W and 80 W power, elevated ventilation was found increased during CO2 exposure with significant differences between the two campaigns. Peak oxygen uptake decreased over the period of CO2 exposure, but was found not significantly different on day 5 compared to pre-exposure measurements. This decrease was not dependent on the CO2 concentration. The lactate concentration at low exercise intensities was found elevated during CO2 exposure. A shift in reverse direction was observed after the CO2 exposure. Since peak oxygen uptake did not differ on day 5 and the lactate concentration was found increased, it was concluded that the potential changes in muscle metabolism by adaptation to elevated CO2 concentrations did not influence the aerobic capacities. Therefore, it was concluded that the changes in aerobic capacities are the result of the reduced physical activities of the subjects while living in the confined compartment.

Adaptation, Physiological↗

Joint NASA-ESA-DARA Study. Part three: circadian rhythms and activity-rest cycle under different CO2 concentrations.

BACKGROUND: During manned space missions, the actual concentration of carbon dioxide (CO2) is frequently elevated to a degree that may affect human functioning and productivity. Therefore, a ground-based international study was performed that tested various psychological and physiological functions under the condition of two different levels of CO2. Thus, a specific experiment aimed at the influence of enhanced CO2-concentrations on the sleep-wake cycle and the circadian system. METHODS: Four volunteers were subjected to a CO2 concentration of 0.7% and 1.2%, respectively, for 24 consecutive days under each condition. Before they were exposed to these elevated levels, baseline measurements were conducted during 5 d under ambient CO2 concentrations (<0.1%). Circadian parameters were assessed by continuous recording of body temperature and by the determination of excretion rates of cortisol, 6-hydroximelatoninsulfate and catecholamines at 3-h intervals during wake. These measurements were conducted on 3 consecutive days 4 times during the two campaigns. Nondominant wrist activity and subjective fatigue was monitored throughout both study phases. RESULTS: Daily means of activity showed significant differences between the two study conditions (with lower values during the 1.2% condition), but these differences only occurred during day-time, whereas during sleep activity levels remained the same. Diurnal mean and circadian amplitude of the temperature rhythm was also significantly lower during the 1.2% condition. CONCLUSIONS: The lower daily mean and circadian amplitudes of temperature during the higher CO2 level can be explained by lower physical activity that was monitored under this level, i.e., a masking effect. We hesitate to explain the lower activity (and hence temperature) as a response to the changed CO2 concentration. More probably, subjects became so acquainted with the procedures of the study protocol during the second study phase (1.2% CO2) that they did not need similar effort to conduct the tasks as during the first phase. The activity level during sleep which was the same during the two phases may support this conclusions. Thus, we conclude that CO2 levels up to 1.2% do not impair the circadian rhythm of healthy men.

Adult↗

Early morphological findings in experimental high pressure neurological syndrome.

HPNS (high pressure neurological syndrome) is considered to be reversible condition of the nervous system caused by elevated (atmospheric) pressure. Clinical observations and experimental findings gave rise to the belief that this syndrome at least partly functions as a model of a dopamin dependent psychosis. Morphological alterations during or after HPNS in man and animals have not been reported so far. We treated rats for three hours with an increasing pressure of helium-oxygen mixture up to 61 ATA in a pressure chamber. This pressure was subsequently maintained for one hour and then released to zero within twenty seconds. The rats died within the first three seconds of pressure release due to complete deoxygenation. Brains were immediately removed and either cooled in liquid nitrogen or fixed in formalin. In both instances the central nervous tissue was excellently preserved. In paraffin embedded formalin fixed specimens, dark neurons in different brain regions were found, especially within parts of the dentate gyrus, the CA 4 subfield of the ammons horn, in dopaminergic brainstem nuclei and in some cortical pyramidal cells. In dopaminergic cells, tyrosine hydroxylase was found to be absent in cells transformed into dark neurons. These dark neurons which have long been recognized in neuropathology, probably represent reversibly damaged neurons transformed into the dark configuration by aldehyde fixation. They may correspond to early apoptosis or they may be the consequence of cytoskeletal disruption.

Animals↗

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine.

AIMS: Objective of this study was to investigate whether adenosine modulates renal erythropoietin production. METHODS: In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000 m in a low pressure chamber for 5.5 h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo. RESULTS: Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations. CONCLUSIONS: The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.

Adenosine↗