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A Walther

Publications and source records attributed to A Walther.

At least 37 records · Page 2Linked to original sources

A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR.

The glucocorticoid-regulated protein annexin I (lipocortin I) has been shown to mediate antiinflammatory activities of glucocorticoids, but the molecular basis of its action has remained elusive. Here we show that annexin I acts through the formyl peptide receptor (FPR) on human neutrophils. Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. Lower peptide concentrations possibly found in inflammatory situations elicit Ca2+ transients without fully activating the MAP kinase pathway. This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. These findings identify annexin I peptides as novel, endogenous FPR ligands and establish a mechanistic basis of annexin I-mediated antiinflammatory effects.

Amino Acid Sequence↗

Leukocyte-independent plasma extravasation during endotoxemia.

OBJECTIVES: To determine the meaning of leukocyte-endothelial interactions for the development of endotoxin-induced vascular leakage. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-four male Wistar rats. INTERVENTIONS: After application of fucoidin to prevent leukocyte rolling and adherence (25 mg/kg; n = 8; fucoidin/LPS group) or saline 0.9% (n = 8; LPS group), animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 8) received an equivalent volume of saline 0.9%. MEASUREMENTS AND MAIN RESULTS: Leukocyte rolling and leukocyte adherence, red cell velocity, vessel diameters, venular wall shear rate, volumetric blood flow, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline, 60 mins, and 120 mins after start of a continuous endotoxin infusion. Fucoidin prevented leukocyte rolling (baseline, 3+/-2 rollers; 120 mins, 3+/-1 rollers; not significant vs. baseline; p < .01 vs. LPS group) and reduced the adherence of leukocytes at baseline and during endotoxemia and showed only a slight increase in adherent leukocytes (baseline, 100+/-38 cells/mm2; 120 mins, 244+/-68 cells/mm2; p < .05 vs. baseline; p < .01 vs. LPS group). In the LPS group, endotoxin exposure induced a marked increase in adherent leukocytes (baseline, 248+/-24 cells/mm2; 120 mins, 560+/-57 cells/mm2; p < .01). Leukocyte adherence in control animals (control group) did not increase significantly. Macromolecular leakage, expressed as the ratio of perivenular to intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.16+/-0.03 to 0.49+/-0.04 (p < .01 vs. baseline; p < .05 vs. control) during the infusion of endotoxin in the LPS group. Fucoidin application did not diminish the extravasation of albumin (baseline, 0.09+/-0.03; 120 mins, 0.61+/-0.10; p < .01 vs. baseline; p < .01 vs. control). CONCLUSIONS: These results demonstrate that despite a significant reduction of adherent leukocytes to the endothelium by fucoidin, there is no reduction in macromolecular leakage, indicating that leukocyte-endothelial interactions only play a minor role for the development of macromolecular leakage and microvascular damage in the early phase of endotoxemia.

Animals↗

Plasma levels of eicosanoids after transfusion of intraoperatively salvaged blood.

BACKGROUND: The interest in autologous red blood cell salvage is increasing rapidly, but it is well known that platelets and white cells are activated during cell washing. Therefore, we aimed to determine whether or not eicosanoids transfused together with the salvaged blood are responsible for nonhemolytic immunological transfusion reactions. MATERIALS AND METHODS: In 11 patients who underwent radical prostatectomy we studied the release of eicosanoids, prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TxB(2)), in association with reinfusion of intraoperatively salvaged blood. Blood samples were taken before operation, on days 1 and 3 after operation and before and after cell washing. RESULTS: There was a twofold increase in PGE(2) and a twentyfold increase in TxB(2) in the unwashed salvaged blood. Washing caused a reduction in eicosanoid plasma levels of up to 95%, but a significantly lower level in relation to its corresponding preoperative value was only found for PGE(2). After transfusion of an average of 420 ml RBC sediment from washed blood, the patients' plasma concentrations of PGE(2) and TxB(2) on the 1st and 3rd postoperative day did not significantly differ compared to baseline values. CONCLUSION: Our data support the notion that RBC sediment from 'salvaged' and washed autologous blood contains increased amounts of PGE(2) and TxB(2). It remains, however, questionable if these passively infused eicosanoids become biologically active. According to our study, the PGE(2) and TxB(2) transfused are apparently not responsible for nonhemolytic immunological transfusion reactions.

Aged↗

Influence of C1-esterase inhibitor on tissue oxygenation of jejunal mucosa during endotoxemia.

BACKGROUND: The complement system has been shown to play an important role in the pathogenesis of microcirculatory disturbances in trauma and sepsis. The intestinal mucosa is the most susceptible portion of the gut to impaired perfusion and oxygen delivery. The objective of this study was to investigate the effects of C1-esterase inhibitor (C1-INH) on arterial oxygenation (PaO2) and tissue oxygenation (PtiO2) of jejunal mucosa during endotoxemia. METHODS: Eighteen anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark type microcatheter PO2 probe and a micro thermocouple were placed on the mucosa in order to measure PtiO2. The animals were randomly assigned to receive one of the three treatments: infusion of Escherichia coli lipopolysaccharides (LPS) without C1-INH pretreatment (LPS group); or infusion of LPS with C1-INH pretreatment (C1-INH group); the control group (n = 6) without treatment of either C1-INH or LPS. The mean arterial pressure (MAP), heart rate (HR), PaO2 and PtiO2 were measured at baseline, 60 and 120 min after induction of endotoxemia. RESULTS: Hemodynamic parameters (MAP, HR) in all the three groups showed no significant changes during the study period. PaO2 significantly decreased in the LPS group. This decrease could be attenuated by pretreatment with C1-INH. The mucosal PtiO2 of the jejunum in the control group remained stable. It significantly decreased in the LPS and in the C1-INH groups without showing a significant difference after 120 min of endotoxemia. CONCLUSIONS: Pretreatment with C1-INH was able to diminish a decrease in PaO2 during endotoxemia, indicating that pulmonary injury was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa could not be prevented suggesting a minor involvement of complement activation in this pathophysiological process.

Animals↗

Influence of N-acetylcysteine treatment on endotoxin-induced microcirculatory disturbances.

OBJECTIVES: To determine the influence of N-acetylcysteine (NAC) in a treatment model, its effects on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 40 male Wistar rats. INTERVENTIONS: The rats randomly received one of four treatments: infusion of saline (SAL) or Escherichia coli lipopolysaccharides (LPS) followed by treatment with saline (SAL) or NAC (150 mg.kg-1 body weight) 30 min after induction of endotoxemia. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were evaluated every 30 min over a period of 120 min using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from red cell velocity, and vessel diameter. NAC in rats without endotoxemia (SAL + NAC group) compared to the control group (SAL + SAL) did not change microcirculatory parameters in postcapillary venules of rat mesentery. In both LPS-treated groups (LPS + SAL and LPS + NAC), leukocyte adherence increased after just 30 min. NAC treatment prevented a further increase in leukocyte adherence and attenuated the extravasation of fluorescence-labeled albumin during endotoxemia. Venular diameters remained unchanged, while erythrocyte velocity decreased in the LPS + SAL group. This led to a lower venular wall shear rate in this group. CONCLUSIONS: Treatment with NAC attenuates endotoxin-induced leukocyte adherence and macromolecular leakage in postcapillary venules of rat mesentery, showing that NAC is also effective after the onset of endotoxemia.

Acetylcysteine↗

Assignment of the auxin binding abilities of ABP44 in gel.

Several approaches were successfully performed to directly assign and characterize auxin binding of ABP44 in gel. The 44 kDa high affinity auxin binding protein ABP44 from pea was tested for its ability to bind 5-azido-[7-3H]-IAA in photoaffinity labeling experiments. Competition experiments with several auxin analogues confirm data published previously (Reinard and Jacobsen 1995). Critical reflections of the limitations of the method are also discussed. Immunostaining using the antibody D16 (Napier and Venis 1992), which is directed against the putative binding site of ABP1, revealed that ABP44's auxin binding site is at least partially related to the corresponding site of ABP1. Nevertheless, both proteins do not share any further immunological relationships. Our results with D16 recommend a careful reconsideration of data published by other authors. Furthermore, a 80 kDa, dimeric glutathione dependent formaldehyde dehydrogenase (FDH) from mung bean, described recently, was found to be different from ABP44. In contrast to the described FDH, ABP44 exhibited no FDH activity.

Gels↗

[Advantages and limitations of intraoperative mechanical autotransfusion in al prostatectomies].

UNLABELLED: Intraoperative autotransfusion (MAT), preoperative autologous blood donation, and preoperative normovolaemic haemodilution are three different methods to avoid homologous blood transfusion during surgical procedures. The controversial use of MAT via cell saver in tumour surgery as well as contamination of the operative field with urine illustrate the particular difficulties of autologous blood transfusion in connection with radical prostatectomy. We investigated changes in the osmotic resistance of the retransfused red blood cells (RBC), bacterial contamination, changes in coagulation parameters, and the presence of tumour cells. PATIENTS AND METHODS: After written informed consent, 24 patients who presented for radical prostatectomy were randomly allocated to either a group that used MAT or a group that used homologous transfusion. The patients received "balanced anaesthesia" with midazolam, fentanyl, atracurium, and nitrous oxide/oxygen. The analysed parameters from the preoperative period to the 3rd postoperative day are shown in Table 1. The Haemonetics 3 Plus Cell Saver was used for autotransfusion. RESULTS: Our results showed that the haematologic parameters, coagulation factors, and serum chemistry did not differ between the two groups (Tables 2-4). However, there were significant differences during the investigated period. The osmotic resistance of the salvaged RBCs was higher than that preoperatively. Furthermore, there were no tumour cells in the autologous salvaged RBCs. CONCLUSION: Our results showed no decrease in the quality of the autotransfused RBCs, urine was not retransfused; and there were no significant differences between the groups postoperatively. Although there were no tumour cells in the salvaged blood, the possibility of blood irradiation is discussed. We concluded that because of the risk of infection of homologous blood products, MAT is a safe possibility to reduce the amount of homologous blood transfusion required in connection with radical prostatectomy.

Aged↗

Interaction of auxin-binding protein 1 with maize coleoptile plasma membranes in vitro.

In a search for membrane "docking proteins" interacting with Zea mays auxin-binding protein (ABP1) the binding of purified ABP1 to maize coleoptile plasma-membrane vesicles was investigated. Concentration-dependent, saturable binding of ABP1 to the membrane vesicles was observed in binding assays using 10(-8)-10(-6) M ABP1. Biotinylated ABP1 was displaced from the membrane binding sites by competition with unlabeled ABP1, demonstrating specific binding. The association step proved to be pH-dependent with maximum binding at pH 5.0 or lower. Auxins did not influence the ABP1 binding to plasma-membrane vesicles, but ABP1 associated with plasma-membrane vesicles was still able to specifically bind [3H]naphthalene-1-acetic acid. The rather stable interaction of ABP1 with plasma-membrane vesicles was only affected by strong alkaline buffers or detergents. The binding capacity was calculated to be in the range of 0.2 pmol ABP1 per g coleoptile fresh weight.

Cell Membrane↗

[Heparin-induced thrombopenia and thrombosis].

Heparin-induced thrombocytopenia (HIT) with thrombosis is a rare, but important complication of heparin therapy. We describe the case of a 53-year-old patient hospitalized with complicated pelvic fracture. Intravenous infusion of unfractionated heparin (15'000 IU/24 h) was given for thrombosis prevention. After 11 days' treatment the patient developed deep venous thrombosis of the left calf, complicated 2 days later by massive bilateral pulmonary embolism. Simultaneous with these thromboembolic events, thrombocytopenia, signs of activated coagulation, and antibodies to heparin occurred. In the context of this case the diagnostic and therapeutic possibilities of HIT, and in particular treatment with the heparinoid danaproid (Orgaran), are discussed.

Chondroitin Sulfates↗

Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial.

Recent findings have indicated that lithium treatment markedly reduces suicide risk in major affective disorders. To compare the effect of lithium with carbamazepine and amitriptyline, suicidal behavior was analyzed during the randomized prospective long-term MAP study (N = 378; duration 2.5 years). Of the nine suicides and five attempted suicides, none took place during lithium treatment. The findings support the view that lithium has a specific antisuicidal effect over and above its prophylactic benefit.

Adolescent↗

Laser blood-flow measurements in malignant tumors during photodynamic therapy (PDT)--an experimental study.

Laser blood-flow measurements were made on the tumor surface of 18 human oral cancer tumors growing on the shank of nude mice during and up to 6 h after photodynamic therapy (PDT) to detect changes in microcirculation. In eight animals, the same procedure was done without PDT. Simultaneously, the skin microcirculation in the contralateral leg was measured to detect systemically caused changes in microcirculation. Two days later, specimens of the tumor region were taken and analyzed histologically. Our results suggest a mainly direct effect of PDT on the tumor cells rather than tumor necrosis caused by decreased microcirculation.

Animals↗

Development of late congenital hip dysplasia: significance of ultrasound screening.

Ultrasound for detecting congenital hip dysplasia was performed in 5970 infants, 2121 of whom were reinvestigated. Of those reinvestigated 726 belonged to the screened group not at risk examined as newborns, 70 were infants at risk first investigated as newborns and 363 were infants at risk first examined after the newborn period; the remainder were infants not at risk first investigated after the newborn period. Pathological findings were obtained in 7.7% of the entire group, in 3.9% of children at no risk, and in 5% of patients at risk. Deterioration of Graf's classification of types was seen in 3.2%. 13 children, 3 of the screened group and 10 of the nonscreened group developed hip dysplasia. None of them would have been missed since they were borderline type IIA on at least one side, which warranted mandatory follow-up.

Age Factors↗

Computerized ordering of experimental animals and test authorization.

The authorization procedure required by law in Switzerland and the internal set-up at Roche for acquiring experimental animals has made a computerized system for monitoring authorizations and animal deliveries essential. The INQUIRE software program, which can be run on the central computer, was used to set-up databases with information on all personnel who place orders and perform experiments (PERI), authorization matters (BEWI), orders (ORDR), deliveries (SPED), animal species (SPEC), animal strains (STRE), populations (POPU) and the management of various data (BARA). The authorizations database (BEWI) permits sequential searches on specific questions. The animals ordered in the ORDR database are constantly updated in BEWI, thus ensuring that the authorized animal quotas are not exceeded. Expiry of an authorization or an unregistered experimenter will come to light in the course of the plausibility study. Through ORDR the experimenter has a good overview of the animals that he has ordered or have been ordered for him, and he can select the most appropriate strain or population for his studies in STRE or POPU, which contain data on the genetic and physiological characteristics as well as the breeding and keeping of all sublines and stocks. Realization of the IFIS project has made it a simple matter to keep a check on the legal requirements pertaining to animal experimentation and to update the information and evaluate the entire stock of data at any time.

Animals↗

[Friedrich August von Ammon (1799-1861) and Dresden ophthalmology in the 1st half of the 19th century].

Friedrich August von Ammon of Dresden took a considerable part in shaping ophthalmology into a scientifically and clinically independent part of medicine, thus inserting himself into the great development of the specialty during the first half of the 19th century. In particular, he investigated the ontogeny of the human eye as well as its pathological anatomy. He edited journals, published monographs, created a school of his own and gained in this way far-reaching influence. As a practitioner, a teacher and a physician-in-ordinary to the King of Saxony, he maintained the tradition of an earlier ophthalmologist of Dresden: Georg Bartisch.

Germany↗

[Phototherapy of parapsoriasis].

The effectiveness of photo(chemo)therapy was tested on 69 patients with different forms of parapsoriasis (parapsoriasis guttata, n = 14; pityriasis lichenoides et varioliformis acuta, n = 6; and parapsoriasis en plaques, n = 49). The forms of parapsoriasis differed in their response to phototherapy and in their relapse rates. Whereas parapsoriasis guttata can be regarded as a definite indication for UVA therapy, much higher UVA doses are required for pityriasis lichenoides et varioliformis and the probability of relapses is higher. It was not possible to interrupt the relapsing course of parapsoriasis en plaqes in the majority of patients. Relapses occurred within 7 months in 63.2% of the cases. A healing effect that lasted for more than one year was achieved only in 18 patients.

Adolescent↗

[Open tuberculosis with radiologically negative cavity findings].

Non-cavernous bacillary tuberculosis is observed with relatively increasing frequency nowadays. Most patients affected have very few or no symptoms, and radiographs usually show circumscribed lesions. The essential feature is the low infection risk due to the small number of bacilli excreted.

Female↗