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U Reuter

Publications and source records attributed to U Reuter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Differential surface expression of HLA-DRB1 and HLA-DRB4 among peripheral blood cells of DR4 positive individuals.

Increasing interest in the functional consequences of differential expression of MHC class II molecules prompted us to examine the surface expression of HLA class II molecules on fresh peripheral blood mononuclear cells. Differential regulation of DR4 and DRB4 was shown for peripheral blood monocytes. In addition, DR4 expression is upregulated on B cells of patients suffering from chronic inflammation and is reduced under prednisolone-treatment. The expression levels of total DR molecules on a given cell type are almost identical comparing different haplotypes among non-RA controls, suggesting that the alpha-chain determines the level of surface expression. The present findings fit the hypothesis that the differential expression of HLA class II molecules is involved in regulation of the immune response and may thus contribute to determining susceptibility to immunological diseases.

Arthritis, Rheumatoid↗
PubMed1998

Cortical spreading depression-associated hyperemia in rats: involvement of serotonin.

We investigated whether the vasoactive neurotransmitter serotonin (5-HT) is involved in cortical spreading depression (CSD)-associated hyperemia in the rat. We focused on the 5-HT2 receptor, which is engaged in 5-HT induced small arteriolar relaxation in cats, as well as on the 5-HT1D/1B receptor, the binding site of the potent antimigraine drug sumatriptan. In male barbiturate anaesthetized Wistar rats (n=25) CSDs were elicited by brain topical application of 1 M KCl, and the DC-potential and regional cerebral blood flow (rCBF, by Laser Doppler flowmetry) were measured over the same hemisphere through dura and thinned bone, respectively. Intravenous application of 8 mg/kg of the 5-HT2A/2C receptor antagonist ritanserin (group I; n=8) significantly reduced the hyperperfusion amplitude during CSD by approximately 44% (p<0.05, from 342+/-124 to 194+/-97%, baseline before CSD=100%), and prolonged its duration by approx. 30%. Vehicle alone (group II; n=4) did not affect CSD hyperperfusion. The highly selective 5-HT1D/1B receptor agonist 311C90 was given in two doses: 100 micrograms/kg i.v. (n=5) had no effect on CSD hyperperfusion, while 800 micrograms/kg (n=5) increased hyperperfusion significantly (p<0.05, from 224+/-86 to 310+/-148%). We conclude that serotonin is, probably via 5-HT2 receptors, involved in the modulation of the regional cerebral blood flow increase during CSD. Novel highly selective receptor antagonists may help to discriminate the differential contribution of various 5-HT receptor subspecies.

Animals↗
PubMed1998

Changes in the classification of carcinogenic chemicals in the work area. Section III of the German List of MAK and BAT Values.

Carcinogenic chemicals in the work area are currently classified into three categories in section III of the German List of MAK and BAT Values (list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these categories - IIIA1, IIIA2, IIIB - be retained as Categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics, and for which risk at low doses can be assessed are classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented.

Animals↗
PubMed1998

Changes in the classification of carcinogenic chemicals in the work area. (Section III of the German List of MAK and BAT values).

Carcinogenic chemicals in the work area were previously classified into three categories in section III of the German List of MAK and BAT values (the list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification was based on qualitative criteria and reflected essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. In the new classification scheme the former sections IIIA1, IIIA2, and IIIB are retained as categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to the risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by non-genotoxic mechanisms, and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose/response relationships and toxicokinetics and for which risk at low doses can be assessed are classified in category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for category 4 (1,4-dioxane) and category 5 (styrene) are presented.

Animals↗
PubMed1998

Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats.

We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.

Animals↗
PubMed1998

Maximum workplace concentration values and carcinogenicity classification for mixtures.

In Germany, the Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) generally sets maximum workplace concentration values (i.e., a proposed occupational exposure level [OEL]) for single substances, not for mixtures. For mixtures containing substances with a genotoxic and carcinogenic potential, the commission considered it scientifically inappropriate to establish a safe threshold. This approach is currently under discussion. Carcinogenic mixtures are categorized according to either the carcinogenicity of the mixture or the classification of the carcinogenic substances included. In regulating exposure to mixtures, an approach similar to that used by the American Conference of Governmental Hygienists is proposed: For components with the same target organ and mode of action or interfering metabolism, synergistic effects must be expected and the respective OELs must be lowered. However, if there is proof that the components act independently, the OELs of the individual compounds are not considered to be modified. In the view of the commission, calculating OELs for solvent mixtures according to their liquid phase composition is not justified, and the setting of scientifically based OELs for complex mixtures is not possible.

Carcinogens↗
PubMed1997

Proposed changes in the classification of carcinogenic chemicals in the work area.

Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

Animals↗
PubMed1997

Noninvasive near infrared spectroscopy monitoring of regional cerebral blood oxygenation changes during peri-infarct depolarizations in focal cerebral ischemia in the rat.

Intermittent peri-infarct depolarizations (PID), which spread from the vicinity of the infarction over the cortex, have been reported in focal ischemia. These depolarizations resemble cortical spreading depression except that they damage the cortex and enlarge the infarct volume possibly because of compromised oxygen delivery. The main purpose of this study was to evaluate the noninvasive technique of near-infrared spectroscopy (NIRS) for the identification of PID and to evaluate its capability for further pathophysiological studies. We used male barbiturate-anesthetized Wistar rats (n = 10) in which middle cerebral artery occlusion had been performed with a surgical thread. Middle cerebral artery occlusion resulted in a drop in parietally measured regional cerebral blood flow (laser Doppler flowmetry) to 31 +/- 8% of baseline flow. Six +/- 4 minutes after the induction of focal ischemia, 5 +/- 2 direct current deflections were recorded during a one-hour measurement period which may be regarded as PID. Measuring regional cerebral blood oxygenation changes with a NIRO 500 revealed dynamic concentration changes in the three chromophores oxyhemoglobin [HbO2], deoxyhemoglobin [Hb], and the oxidized form of cytochrome aa3 [CytO] during PID. Typically, an initial slight decrease of [HbO2] (-6.1 +/- 1.7 arbitrary units [AU] and an increase of [Hb] (+11.5 +/- 7.7 AU) were followed by an increase of [HbO2] (+10.8 +/- 4.7 AU) and a decrease of [Hb] (-4.7 +/- 5.5 AU); [CytO] decreased during the depolarizations (-2.0 +/- 1.2 AU). We conclude that NIRS can detect typical PID-associated changes in blood oxygenation. We hypothesize that during the course of PID, unlike "normal" spreading depression, hypoxygenation precedes hyperoxygenation of the microcirculation in a given cortex volume as the depolarization wave propagates through hemodynamically compromised to intact tissue. This would accord with the known damaging effect of PID. The NIRS "fingerprint" of PID encourages the search for PID during early stroke in patients.

Animals↗
PubMed1997

Importance of psychological well being and disease activity in termination of an initial DMARD therapy.

OBJECTIVE: To estimate the frequency of and to identify possible risk factors involved with terminating an initial disease modifying antirheumatic drug (DMARD) therapy. We hypothesized that treatment termination depends not only on side effects and inefficacy but also on the therapeutic setting and the health beliefs of the patient. METHODS: We observed an inception cohort of 302 patients with early rheumatoid arthritis (< 2 years) and first prescription of DMARD for 3 years. Survival analysis was used to estimate treatment continuation under rheumatological care. The study group comprised 4 rheumatological outpatient clinics and 7 private practices in Berlin. RESULTS: Of the initial cohort 80% continued the same drug or were in remission after one year, 70% after 2 years. Within the first 2 years, methotrexate therapy was terminated in 15% of the cases and sulfasalazine therapy in 40%, respectively. In both forms of therapy, the discontinuation rate was dependent on initial disease activity. However, the influence of the patient's psychological status at baseline was equally strong. DMARD treatment was terminated earlier and more frequently in patients with poor psychological well being. These findings hold true after controlling for disease activity or severity. CONCLUSION: Patient psychological well being and disease activity at start of initial DMARD therapy are important predictors of early drug discontinuation. By influencing psychological well being (e.g., by patient education programs), continuation of DMARD therapy might be further improved.

Adult↗
PubMed1996

[Complications of preventive cryoretinopexy in retinal foramina and degeneration in 1,000 eyes].

INTRODUCTION: Prophylactic treatment of full-thickness retinal breaks is widely accepted. The side effects and benefits of prophylactic treatment, however, have to be considered critically. The complication rates of prophylactic procedures must be compared. The aim of our study was to find out the complication rate of cryopexy in prophylactic retinal surgery. PATIENTS: Retrospectively we analyzed 1000 eyes of 746 patients who were prophylactically treated by cryopexy for different reasons. We included eyes with round holes, horse shoe tears and peripheral degenerations. Follow-up time ranged from 6 months to 7 years (average 30 months). RESULTS: Further surgical treatment was necessary in 3.4% of the patients (1.8% had a second cryopexy, 0.1% needed laser coagulation, and in 1.5% a subsequent scleral buckling procedure was necessary. In 17.6% of these cases (0.6% of all cases) the retinal detachment occurred in the periphery of the primary cryopexy after more than 1 year. In all our patients we did not find postoperative macular pucker or cystoid macular edema. CONCLUSIONS: The complication rate of cryopexy performed for the treatment of retinal holes and degeneration is low. This method has to be regarded as a therapeutic tool in the prophylactic treatment of (dangerous) retinal areas.

Adolescent↗
PubMed1996

Brachial and digital artery pulse pressures in hypertensive and normotensive subjects.

OBJECTIVES AND PATIENTS: To determine whether or not the pulsatile component of blood pressure (BP) measured centrally and peripherally allows a separation between hypertensive and normal subjects, as well as within hypertensive and normal subjects, as well as within hypertensive patients. We tested the hypothesis that the difference in central and peripheral pulse pressures is increased in hypertensive, compared to normotensive persons, and that this component is influenced by genetic variance. We studied 46 hypertensive patients and 56 age-matched normal subjects, as well as 10 hypertensive families with 74 members of the same age range. DESIGN: Pulse pressure was measured at the brachial artery and the digital artery in the standing and supine position. The difference in the pulse pressures between these sites was calculated. Further, digital volume-pulse amplitude and stroke volume measurements were determined with impedance plethysmography. RESULTS: The differences between central and peripheral pulse pressures were similar in hypertensive patients compared to normal subjects, regardless of posture. However, in the standing position the frequency distribution of this variable in hypertensive patients was bimodal and split into two significantly different distributions (P < 0.05) with peaks at -24 mm Hg and -1 mm Hg, compared to a single peak at -11 mm Hg in normal subjects. Furthermore, these two subgroups of hypertensive patients differed in their brachial systolic BP (127 +/- 10 vs 134 +/- 12 mm Hg; P < 0.05), their brachial pulse pressures (32 +/- 8 vs 42 +/- 8 mm Hg; P < 0.05), and in their peripheral compliance (1.59 +/- 0.92 vs 2.21 +/- 1.00 microliter/mm Hg per 100 ml tissue; P < 0.05). The frequency distribution of pulse pressure differences was also bimodal in members of hypertensive families, even though most (46 out of 74) were normotensive. CONCLUSION: The difference between the digital and brachial pulsatile component may be a useful intermediary phenotype in essential hypertension. Furthermore, the nonuniform decreases in arterial compliance exhibited by our patients may be of pathogenic significance.

Adult↗
PubMed1996

[Optic nerve involvement in chronic lymphatic leukemia of the B-cell series].

BACKGROUND: Malignant Non-Hodgkin lymphomas rarely manifest with ocular symptoms. We report on a patient with a low grade malignant lymphoma of the b-cell type with optic nerve involvement. PATIENT: In 1990 a 38-year old patient presented with typical symptoms of optic neuritis in the left eye. Magnetic resonance imaging (MRI) revealed a signal enhancement in the left optic nerve. Hematologically a well differentiated Non Hodgkin's lymphoma of the b-cell type was diagnosed. Neurological signs and symptoms in the following years were regarded as manifestations of multiple sclerosis (MS). In 1994 the patient presented with an acute visual loss in the right eye. MRI this time revealed a signal enhancement in the right optic nerve and a big CNS lesion. Gradually a bilateral partial optic nerve atrophy developed. The cerebrospinal fluid contained atypical lymphocytes, matching with the cells in the peripheral blood, morphologically and in the fluorescence-activated cell sorter (FACS). These findings suggest an intracerebral manifestation of a well differentiated Non-Hodgkin's lymphoma. CONCLUSION: Low grade malignant well-differentiated Non-Hodgkin lymphomas infiltrate the optic nerve. The clinical course in our case mimicked multiple sclerosis.

Adult↗
PubMed1995

Release of lysosomal protease from retinal pigment epithelium and fibroblasts during mechanical stresses.

BACKGROUND: Mechanical expansion in tissues or in cells may occur under physiological and pathological conditions and is accompanied by increased activity of proteolytic enzymes. In traction detachment, retinal cells are subjected to mechanical strain. The purpose of this study was to ascertain whether retinal pigment epithelium (RPE) cells and fibroblasts in tissue culture release proteases due to mechanical stress and to investigate the importance of the cytoskeleton for mechanotransduction to the lysosomes during cellular stress reactions. METHODS: Cell layers were grown on silicone-rubber membranes and subjected to mechanical stresses by expansion of the membrane. Concentrations of N-acetyl-beta-glucosaminidase (NAG), acid phosphatase (AP), and lactate dehydrogenase (LDH) were determined in extracellular fluid. Colchicine 0.5 x 10(-5) M was used to disrupt the cytoskeleton prior to expansion. RESULTS: RPE cells and fibroblasts separated during mechanical expansion, which was accompanied by extracellular release of proteolytic activity of NAG (RPE 37.50%; fibroblasts 23.22% above control value), but not of AP. LDH activity did not increase, indicating preserved integrity of the cell membranes during stretching. Colchicine caused immediate detachment of fibroblasts, and RPE did not release significant activity of NAG under subsequent extension. CONCLUSION: In traction detachment, RPE may release in vivo proteases to cut intercellular adhesions in order to escape mechanical strain. Our results indicate that release of proteases from RPE may be involved in the pathophysiology of traction detachment, facilitating by their degradative action the disconnection between RPE and outer segments. Similarly, fibroblasts may respond to changes in tension of scleral or corneal tissue. Release of proteases following mechanical stress seems to require an intact cytoskeleton.

Acetylglucosaminidase↗
PubMed1995

Transdifferentiation of human monocytes into fibroblast-like cells in vitro.

Proliferative vitreoretinopathy is a process of uncontrolled cell proliferation in the vitreous. There is some evidence that monocytes and macrophages play an essential role during the pathogenesis. The purpose of this study was to investigate whether human monocytes derived from the peripheral blood can transform into fibroblast-like cells under in vitro conditions. To provide similar environmental conditions in vitro, human monocytes were brought onto fresh calf vitreous and kept for 17 days. Monocytes differentiated into macrophages and assumed a fibroblast-like morphology. During transdifferentiation, expression of CD11c was present for only 3 days and that of CD18, for only 7 days. The longest presence was found for CD68 expression, which lasted for 15 days. The present results indicate that human monocytes from the peripheral blood are capable of transforming into fibroblast-like cells under in vitro conditions. Blood-borne monocytes could therefore represent a major source for the fibroblast-like cells found in proliferative vitreoretinopathy.

Antibodies, Monoclonal↗
PubMed1995

Compliance of the digital artery is decreased in patients with essential hypertension.

The compliance of the arterial vascular system is decreased in hypertensive subjects. On the other hand, the vessel wall properties such as compliance depend on blood pressure (BP). The aim of the present study was to determine the compliance of the digital arteries and to test the hypothesis that decreased compliance is either caused by a downward shift of the compliance-pressure relation or, alternatively, by a change in the compliance-pressure relation itself. We used impedance plethysmography and a finger BP measuring device to determine beat-to-beat the pressure-pulse amplitude (delta P), the volume-pulse amplitude (delta V) and the compliance from digital arteries of 10 hypertensive patients and 10 similarly aged normal subjects. The mean local blood pressure (MLBP) in the digital arteries was changed by vertically varying the position of the right hand in relation to the heart. The compliance of the digital arteries in hypertensive patients (2.76 microliters/mm Hg per 100 ml tissue) is significantly (P < 0.05) decreased compared with that in normal subjects (4.03 microliters/mm Hg per 100 ml tissue). A reduction of MLBP by 50 mm Hg leads to an increase of compliance in normotensive subjects from 4.03 to 12.68 microliters/mm Hg per 100 ml tissue but in hypertensive patients only from 2.76 to 6.16 microliters/mm Hg per 100 ml tissue. The slope of the curve in the low pressure range was also markedly decreased in hypertensive patients compared with controls. We conclude, that the compliance-pressure relation is not merely shifted but also extensively alterated in hypertensive patients.

Adult↗
PubMed1993

Osmotic stress in an in vitro model of the outer blood-retinal barrier.

Because of the difficulty involved in in vivo experimental manipulations of the outer blood-retinal barrier, we developed an in vitro model. Retinal pigment epithelium (RPE) from bovine eyes was grown on semipermeable membranes. A continuous monolayer of RPE developed a measurable transepithelial electrical resistance (TER). TER was used as a parameter of barrier function. The tightness of the cellular monolayer was also tested with fluorescein. The TER increased in confluent cultures by 60-70 ohms-cm2, and there was no fluorescein leakage. After exposure of the cultures to 0.2% trypsin or 1% ethylenediaminetetraacetic acid (ETDA), we detected a reversible breakdown of the epithelial barrier function. Under transmission electron microscopy, we detected no disassembly of the junctional components after breakdown of the barrier function with trypsin or EDTA. A hyperosmotic NaCl solution in the basal medium as well as a hypoosmotic NaCl solution in the apical medium induced a breakdown in the TER, whereas a hyperosmotic NaCl solution in the apical medium induced only a slight decrease in the TER. Under transmission electron microscopy, we detected an intracellular blistering and large intercellular widening. A hypo-osmolar NaCl solution in the basal medium induced a rise in the TER. With regard to these experiments, it seems, at least in vitro, that the function of occluding junctions in bovine RPE as permeability barriers depends on extracellular calcium. Furthermore, our results were such as if the outer blood-retinal barrier were designed to prevent subretinal inflow of free water.

Animals↗