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Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 73 records · Page 4Linked to original sources
PubMed2003

Identification of low-density platelet populations with increased reactivity and elevated alpha-granule content.

The present study examines biochemical and functional characteristics of platelet density subpopulations together with their ability to mobilise intracellular fibrinogen when activated. Platelets from three healthy volunteers were investigated. The total platelet population was separated according to density in a linear Percoll gradient in a plasma-free milieu containing EDTA that binds soluble Ca(2+). Subsequently, platelets from each individual were divided according to density into 11 or 12 aliquots. In all fractions, we determined platelet count, intracellular P-selectin and the ADP-evoked platelet fibrinogen binding as a measure of platelet reactivity together with the platelet dense body content. The work demonstrates that platelets use stored intracellular fibrinogen when activated. It also shows that the platelet-fibrinogen binding can be initiated in a surrounding depleted of Ca(2+) and fibrinogen. Moreover, the study demonstrates subpopulations of light platelets having increased reactivity and more alpha-granules but less dense bodies. The biological significance of the findings needs to be elucidated.

Adenosine Diphosphate↗
PubMed2003

The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma.

BACKGROUND: The extent of epithelial injury in asthma is reflected by expression of the epidermal growth factor receptor (EGFR), which is increased in proportion to disease severity and is corticosteroid refractory. Although the EGFR is involved in epithelial growth and differentiation, it is unknown whether it also contributes to the inflammatory response in asthma. OBJECTIVES: Because severe asthma is characterized by neutrophilic inflammation, we investigated the relationship between EGFR activation and production of IL-8 and macrophage inhibitory protein-1 alpha (MIP-1alpha) using in vitro culture models and examined the association between epithelial expression of IL-8 and EGFR in bronchial biopsies from asthmatic subjects. METHODS: H292 or primary bronchial epithelial cells were exposed to EGF or H2O2 to achieve ligand-dependent and ligand-independent EGFR activation; IL-8 mRNA was measured by real-time PCR and IL-8 and MIP-1alpha protein measured by enzyme-linked immunosorbent assay (ELISA). Epithelial IL-8 and EGFR expression in bronchial biopsies from asthmatic subjects was examined by immunohistochemistry and quantified by image analysis. RESULTS: Using H292 cells, EGF and H2O2 increased IL-8 gene expression and release and this was completely suppressed by the EGFR-selective tyrosine kinase inhibitor, AG1478, but only partially by dexamethasone. MIP-1alpha release was not stimulated by EGF, whereas H2O2 caused a 1.8-fold increase and this was insensitive to AG1478. EGF also significantly stimulated IL-8 release from asthmatic or normal primary epithelial cell cultures established from bronchial brushings. In bronchial biopsies, epithelial IL-8, MIP-1alpha, EGFR and submucosal neutrophils were all significantly increased in severe compared to mild disease and there was a strong correlation between EGFR and IL-8 expression (r = 0.70, P < 0.001). CONCLUSIONS: These results suggest that in severe asthma, epithelial damage has the potential to contribute to neutrophilic inflammation through enhanced production of IL-8 via EGFR- dependent mechanisms.

Adult↗
PubMed2003

Improving planning procedure in brain biopsy: coupling frame-based stereotaxy with navigational device STP 4.0.

37 consecutive patients with space-occupying intracerebral lesions were operated via frame-based stereotaxy. After CT-localizing of suspect lesions and computer-supported definition of entry and target coordinates a serial stereotactic biopsy was performed. Biopsy specimens allowed a satisfactory neuropathological examination and diagnostic result in 36 cases (97 %). Only three patients (8.1 %) showed an intraoperative bleeding, which was not associated with any postoperative CT-detectable hematoma, neurosurgical intervention nor with any neurological deficits. In summary we described the method of a computerized planning technique for stereotactic biopsy with the use of a special stereotactic planning program. High percentage of satisfactory neuropathological diagnoses and comfortable and accurate definition of target and entry coordinates justify computer support as a routine method.

Adolescent↗
PubMed2003

[Gangliocytic paraganglioma of the ampulla of Vater].

A case of a bleeding duodenal gangliocytic paraganglioma (GPG) of the Papilla Vateri is reported. The 47 year old patient was treated successfully by partial pancreaticoduodenectomy. Histologically the GPG is characterized by three types of cells: epitheloid cells, ganglion-like cells and spindle cells. So far 81 cases are reported in the literature. Most cases of GPGs are benign, metastasis or recurrence is possible. This case showed an infiltrative growth pattern indicating the true neoplastic nature of this tumor.

Ampulla of Vater↗
PubMed2003

[Functions of circulating and intra-abdominal polymorphonuclear leukocytes during human secondary peritonitis].

INTRODUCTION: Aim of the study was to characterize different functions of circulating and emigrated, intra-abdominal polymorphonuclear leukocytes (cPMNs, ePMNs) during human secondary peritonitis. METHODS: In patients (n=25) with diffuse secondary peritonitis circulating and emigrated PMNs were characterized intra- and until 96 h postoperatively. Patients were allocated to two different groups, e. g. patients with septic complications (shock, organ failure, n=11) and patients without complications (n=14) during peritonitis. In addition a control group of patients (n=10) with abdominal surgery but without peritonitis was investigated. The lucigenin- and luminol-enhanced chemiluminescence was used to determine extra- and intracellular oxygen radical generation of PMNs. Besides spontaneous oxygen radical generation of PMNs, stimulated radical production was investigated after the addition of ionophores A23 187 and C3-coated zymosan. Phagocytosis by PMNs was characterized with opsonized E. coli bacteria and fluorescence-activated cell analysis. RESULTS: Especially patients with complicated peritonitis had strong and long-lasting changes of PMNs functions. The toxic and tissue-destroying production of extracellular oxygen radicals by circulating PMNs was enhanced (e. g., A23 187 - stimulated oxygen radical generation 433 +/- 89 cpm/cPMNs (peritonitis with complications) versus 90 +/- 30 cpm/cPMNs (peritonitis without complications) versus 110 +/- 44 cpm/cPMNs (controls), p < 0.05). Phagocytosis (58 +/- 9 % (ePMNs, peritonitis with complications) versus 81 +/- 6 % (ePMNs, peritonitis without complications) versus 82.2 +/- 1.6 % (ePMNs, controls), p < 0.05) and phagocytosis-associated intracellular oxygen radical generation (8.23 +/- 1.6 x 10(3) cpm/ePMNs (peritonitis with complications) versus 25.2 +/- 5.2 x 10(3) cpm/ePMNs (peritonitis without complications) versus 11.7 +/- 2.8 cpm x 10(3) cpm/ePMNs (controls) p < 0.05) were suppressed. CONCLUSION: Not for all patients with peritonitis does it seem favourable to modulate PMNs-functions. If immunomodulation would be able to down-regulate exaggerated functions of circulating PMNs and to up-regulate the suppressed functions of emigrated PMNs patients with complicated peritonitis might benefit from this therapy.

Colectomy↗
PubMed2003

Molecular characterization of the canine HMGB1.

Due to the close similarities of numerous canine diseases to their human counterparts, the dog could join the mouse as the species of choice to unravel the genetic background of complex diseases as e.g. cancer and metabolic diseases. Accordingly, the role of the dog as a model for therapeutic approaches is strongly increasing. However, prerequisite for such studies is the characterization of the corresponding canine genes. Recently, the human high mobility group protein B1 (HMGB1) has attracted considerable interest of oncologists because of what is called its "double life". Besides its function as an architectural transcription factor HMGB1 can also be secreted by certain cells and then acts as a ligand for the receptor for advanced glycation end products (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways, such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1 in inflammation and tumor metastasis. These results make HMGB1 a very interesting target for therapeutic studies done in model organisms like the dog. In this study we characterized the molecular structure of the canine HMGB1 gene on genomic and cDNA levels, its predicted protein, the gene locus and a basic expression pattern.

Amino Acid Sequence↗
PubMed2003

In vitro simulation of therapeutic plasmatic fibrinolysis.

One type of therapy for thromboembolism is plasmatic thrombolysis. Several plasminogen activators (PA) are clinically available, including urokinase (u-PA), tissue plasminogen activator (t-PA), streptokinase (SK), plasminogen-streptokinase-activator-complex (PSAC), or mutants of t-PA such as reteplase (RP) or tenecteplase (TP). Therapeutic plasmatic fibrinolysis was simulated, using the PA at relevant plasma concentrations, and plasmin (Pli) and PA activities were determined. Normal citrated plasma was supplemented with 31 to 1,000 IU/mL u-PA, 0.31 to 20 microg/mL t-PA, 125 to 4,000 IU/mL SK, 12.5 to 400 U/mL PSAC, 125 to 4,000 U/mL RP, or 0.31 to 10 microg/mL TP. Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (CT), to destroy plasmatic PAI-1 and alpha2-antiplasmin. After 0 to 80 minutes (37 degrees C), 50-microL samples were withdrawn and added to 100 microL 1.5 M arginine, pH 8.7, and oxidized with 50 microL of 20 mM CT. For determination of plasmin activity, 10 microL thereof was incubated with 150 microL 1.5 M arginine, pH 8.7, and 100 microL 20 mM CT preoxidized (15 minutes 37 degrees C) pooled normal citrate buffered EDTA-plasma for 30 minutes (37 degrees C). For determination of [PA+Pli]-activity, arginine was added after this incubation. 25-microL 6 mM Val-Leu-Lys-pNA were added and deltaA/h at room temperature (RT) was monitored, using a microtiterplate reader. [PA+Pli]-Pli = PA. The PA concentration required to induce 25% [ED25] of the maximally inducible Pli-activity in plasma (= 1 U/mL = 45 mg/L = 0.53 micromol/L active Pli; deltaA = 363 +/- 8 mA/h RT) after 10 minutes (37 degrees C) were 320 IU/mL u-PA, 8 microg/mL t-PA, 140 U/mL PSAC, 6,000 IU/mL SK, 720 U/mL RP, and approximately 150 microg/mL TP. The approximate activity half-lives of the PA in plasma were 30 minutes for u-PA, 30 minutes for t-PA, greater than 80 minutes for SK, greater than 80 minutes for PSAC, 50 minutes for RP, and 80 minutes for TP. The present study shows--for the first time--a combined kinetic in vitro simulation of the plasmatic activity of six different PAs. At clinically used concentrations, RP induces the highest plasmatic Pli activity. Due to unselective generation of plasmin in plasma, all PA are of some danger in inducing severe hemorrhagias. Clinical thrombolysis might be improved by usage of more physiologic activators of thrombolysis, such as activators of polymorphonuclear neutrophils.

Fibrinolysin↗
PubMed2003

Adjuvant autologous tumour cell-lysate vaccine versus no adjuvant treatment in patients with M0 renal cell carcinoma after radical nephrectomy: 3-year interim analysis of a German multicentre phase-III trial.

Even M0 RCC is associated with tumour progression in approximately 30% of all patients after radical nephrectomy. Nevertheless, no effective adjuvant treatment after radical nephrectomy has been established. In a multicentre phase-III trial we investigated the impact of an adjuvant autologous tumour cell-lysate vaccination on the progression-free survival of patients with M0 RCC after radical nephrectomy. Between January 1997 and August 1998 a total of 558 patients with a renal tumour were enrolled at 55 different centres (study group) in Germany. Prior to radical nephrectomy all patients were centrally randomized (Quintiles Germany) to either receive an adjuvant autologous tumour cell-lysate vaccine (6 applications at 4-week intervals after radical nephrectomy) or to receive no adjuvant treatment (control group) after radical nephrectomy. All patients were evaluated following standardized diagnostic investigations at 6-month intervals. Following the inclusion criteria (RCC stages pT2-3bpN0-3M0, TNM-classification, UICC 1993), 365 patients were evaluable for the 3-year progression-free survival analysis. There were 240 patients with stage pT2pN0M0 (104 in the vaccine group and 136 patients in the control group) and 89 patients with stage pT3pN0M0 (46 in the vaccine group and 43 patients in the control group). The remaining 36 patients had positive lymph nodes. The trial was performed according to ICH-GCP guidelines. The 3-year progression-free survival rate for all tumour stages was 84.7% in the vaccine group and 80.9% in the control group. Patients with RCC stage pT3pN0-3M0 in the vaccine group demonstrated an advantage (74.4% in the vaccine group vs 65.9% in the control group). For RCC stage pT2pN0-3M0 the 3-year progression-free survival rate in the vaccine group was 89.7% compared to 85.7% in the control group. Follow-up of all patients enrolled in this trial is ongoing. This is the first randomized trial indicating a benefit from an adjuvant vaccination in patients with M0 RCC after radical nephrectomy. The advantage in terms of progression-free survival was more pronounced in patients with T3-tumours. However, it must be emphasized that the results of the final study report (2003) must be awaited before definite recommendations can be made.

Adjuvants, Immunologic↗
PubMed2002

Nature of low-energy dipole strength in nuclei: the case of a resonance at particle threshold in 208Pb.

A high-resolution (gamma,gamma') study of the electric dipole response in 208Pb at the S-DALINAC reveals a resonance structure centered around the neutron emission threshold. Microscopic quasiparticle phonon model calculations in realistic model spaces including the coupling to complex configurations are able to describe the data in great detail. The resonance is shown to result from surface density oscillations of the neutron skin relative to an approximately isospin-saturated core. It also forms an integral part of a toroidal E1 mode representing an example of vortex collective motion in nuclei.

Journal Article↗
PubMed2002

Experimental test of a trace formula for a chaotic three-dimensional microwave cavity.

We have measured resonance spectra in a superconducting microwave cavity with the shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed their spectral fluctuation properties. The experimental length spectrum exhibits contributions from periodic orbits of nongeneric modes and from unstable periodic orbits of the underlying classical system. It is well reproduced by our theoretical calculations based on the trace formula derived by Balian and Duplantier for chaotic electromagnetic cavities.

Journal Article↗
PubMed2002

Deuteron breakup in the 2H(e,e' p) reaction at low momentum transfer and close to threshold.

Deuteron breakup has been studied in a 2H(e,e' p) coincidence experiment at low momentum transfer and for energies close to threshold. The longitudinal-plus-transverse ( L+T) and longitudinal-transverse ( LT) interference cross sections are deduced. Nonrelativistic calculations based on the Bonn potential and including leading order relativistic contributions, meson exchange currents, and isobar configurations describe the ( L+T) data well. Surprisingly, large deviations of 30% to 45% are observed for the LT contribution.

Journal Article↗
PubMed2002

Evidence for a new low-lying resonance state in 7He.

Low-lying resonance states in 7He(6He+n), formed after fragmentation reactions of a 227 MeV/nucleon 8He beam on a carbon target, have been studied. Coincidences between 6He nuclei and neutrons, corresponding to the one-neutron knockout channel in 8He, were selected. The relative energy spectrum in the 6He+n system shows a structure, which is interpreted as the 7He ( Ipi = 3/2(-)) ground state, unbound with 0.43(2) MeV relative to the 6He+n system and a width of Gamma = 0.15(8) MeV overlapping with an excited ( Ipi = 1/2(-)) state observed at 1.0(1) MeV with a width of Gamma = 0.75(8) MeV.

Journal Article↗
PubMed2002

Generation of GW radiation pulses from a VUV free-electron laser operating in the femtosecond regime.

Experimental results are presented from vacuum-ultraviolet free-electron laser (FEL) operating in the self-amplified spontaneous emission (SASE) mode. The generation of ultrashort radiation pulses became possible due to specific tailoring of the bunch charge distribution. A complete characterization of the linear and nonlinear modes of the SASE FEL operation was performed. At saturation the FEL produces ultrashort pulses (30-100 fs FWHM) with a peak radiation power in the GW level and with full transverse coherence. The wavelength was tuned in the range of 95-105 nm.

Journal Article↗
PubMed2002

Changes in AMPA receptor binding in an animal model of inborn paroxysmal dystonia.

Previous pharmacological studies suggested that glutamatergic overactivity contributes to manifestation of dystonic attacks in mutant hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia in which episodes of dystonia occur in response to stress. In the present study, [(3)H]AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor binding was determined by autoradiographic analyses in 41 brain (sub)regions of dt(sz) hamsters under basal conditions, i.e., in the absence of dystonia, and in a group of mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In comparison to nondystonic control hamsters the basal [(3)H]AMPA binding was significantly higher in the ventromedial and ventrolateral caudate putamen, the anterior cingulate cortex, the hippocampus, and the lateral septum of dystonic brains. During dystonic attacks the [(3)H]AMPA binding was significantly lower in the dorsomedial, dorsolateral, and posterior caudate putamen; the ventromedial thalamus; and the frontal cortex of mutant hamsters compared with control animals that were exposed to the same external stimulation. The basal increase in AMPA receptor density within limbic structures may contribute to the susceptibility of stress-inducible dystonic episodes in mutant hamsters. Since AMPA receptor activation is known to cause a fast reduction of the affinity and an internalization of postsynaptic AMPA receptors, the latter finding could reflect a glutamatergic overactivity within the striato-thalamo-cortical circuit during the expression of dystonia, which is in line with previous neurochemical and pharmacological data in dt(sz) hamsters.

Animals↗
PubMed2002

Sodium currents in striatal neurons from dystonic dt(sz) hamsters: altered response to lamotrigine.

Dystonic mutant dt(sz) hamsters are a model for paroxysmal dystonia. Handling/stress provoke the dystonic attacks. This phenomenon subsedes with maturation, but can be reinvoked when these animals receive sodium channel blockers such as lamotrigine, suggesting a dysfunction of striatal sodium channels. Voltage-gated fast sodium currents (I(Na(+))) were studied in acutely isolated striatal neurons from healthy and dt(sz) hamsters in whole-cell voltage clamp recordings. The action of lamotrigine was tested on (a) current/voltage relationship, (b) kinetics, and (c) steady-state inactivation and activation. Under control conditions, properties of I(Na(+)) were not different between healthy and dt(sz) neurons. With lamotrigine, however, (a) peak currents were significantly less depressed by the drug in neurons from dt(sz) hamsters as compared to healthy cells, and (b) the steady-state inactivation curve shift of I(Na(+)) was less pronounced in dt(sz) neurons. The results suggest that in dt(sz) hamsters, fast sodium currents in striatal neurons are more resistant to blockade. This sodium channel alteration might be causal for a functional imbalance between input and output structures of the basal ganglia under conditions of compromised I(+)(Na).

Animals↗
PubMed2002

Microendoscopic lumbar discectomy versus open surgery: an intraoperative EMG study.

This study investigated electromyographic (EMG) activity as a marker of nerve root irritation during two different surgical procedures for lumbar disc herniation. Mechanically elicited EMG activity was recorded during the dynamic stages of surgery in muscle groups innervated by lumbar nerve roots. Confirmation of surgical activity was correlated with the activity of the electromyogram. Fifteen patients with lumbar disc herniations were treated via an endoscopic medial approach, and 15 patients via the open microscopic surgical technique. Results indicated that the endoscopic technique was superior to the open surgical technique and produced less irritation of the nerve root. Significantly less mechanically elicited activity was recorded during both the approach and the root mobilization. The study showed that microendoscopic discectomy allows a smaller incision and less tissue trauma with comparable visualization of the nerve structures than does open surgery.

Adolescent↗