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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 91 records · Page 5Linked to original sources
PubMed2001

Pattern generation for walking and searching movements of a stick insect leg. II. Control of motoneuronal activity.

In the stick insect, Cuniculina impigra, intracellular recordings from mesothoracic motoneurons that control flexion and extension of the tibia and depression and levation of the trochantero-femur were made while the leg performed walking-like movements on a treadband or stereotyped rhythmic searching movements. We were interested in how synaptic input and intrinsic properties contribute to form the activity pattern of motoneurons during rhythmic leg movements without sensory feedback from other legs. During searching and walking, motoneurons expressed a rhythmic bursting pattern that was formed by a depolarizing input followed by a hyperpolarizing input in the inter-burst interval. This basic pattern was similar in all fast, semi-fast, and slow motoneurons that were recorded. Hyperpolarizations were in synchrony with activity in the antagonistic motoneurons. De- and hyperpolarizations were associated with a decrease in input resistance. All motoneurons showed spike frequency adaptation when depolarized by current injection to a membrane potential similar to that observed during walking. In the hyperpolarizing phase of fast flexor motoneurons, the initial maximum hyperpolarization was followed by a sag in potential toward more depolarized values. Consistent with this observation, only fast flexor motoneurons developed a depolarizing sag potential when hyperpolarized by injection of constant negative current.

Action Potentials↗
PubMed2001

Telomerase activity in cervical smears.

It is well known that almost all carcinoma cells including those of the uterine cervix have re-established their telomerase activity. However, until now there is no conclusive picture on the telomerase activity in cervical dysplasias and about their relationship to HPV infection. To investigate this question, material from 34 patients (15 with normal epithelium, 11 with LGSIL, 8 with HGSIL) obtained by conventional cervical brushing was used and subjected to non-radioactive TRAP-ELISA (Boehringer Mannheim). The HPV analysis was performed by PCR on formalin-fixed, paraffin-embedded biopsy material obtained after cytological investigation. We could show that telomerase activity is detectable in normal cervical epithelium, and that an gradual increase exists for both telomerase activity and HPV positivity from normal epithelium to HGSIL. However, HPV infection and telomerase activity appear to be independent of each other. The high frequency of telomerase positivity in patients with normal cervical epithelium indicates that telomerase activity is not a useful differential diagnostic aid. Whether patients with telomerase-positive dysplasias have a higher probability to progress into an invasive carcinoma remains to be clarified by follow-up studies.

Case-Control Studies↗
PubMed2001

Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study.

OBJECTIVE: The central nervous system representation of social phobia (social anxiety disorder) is largely unknown. The aim of this study was to examine brain activity during symptom provocation in social phobics. METHOD: Positron emission tomography with the use of (15)O water was used to measure regional cerebral blood flow (rCBF) in 18 subjects with DSM-IV-defined social phobia and a nonphobic comparison group while they were speaking in front of an audience and in private. Heart rate and subjective anxiety were also recorded. RESULTS: During public versus private speaking, subjective anxiety increased more in the social phobics than in the comparison group. Increased anxiety was accompanied by enhanced rCBF in the amygdaloid complex in the social phobics relative to the comparison subjects. Cortically, brain blood flow decreased in the social phobics and increased in the comparison subjects more during public than private speaking in the orbitofrontal and insular cortices as well as in the temporal pole and increased less in the social phobics than in the comparison group in the parietal and secondary visual cortices. Furthermore, rCBF increased in the comparison group, but not in the social phobics, in the perirhinal and retrosplenial cortices. CONCLUSIONS: An rCBF pattern of relatively increased cortical rather than subcortical perfusion was observed in the nonphobic subjects, indicating that cortical evaluative processes were taxed by public performance. In contrast, the social phobia symptom profile was associated with increased subcortical activity. Thus, the functional neuroanatomy of social phobia involves the activation of a phylogenetically older danger-recognition system.

Adult↗
PubMed2001

Improvement of strength parameters of a leucite-reinforced glass ceramic by dual-ion exchange.

An innovative dual ion-exchange process can improve the limited strength and the scatter-in-strength of technical glasses. The objective of this study was to prove whether such a two-stage ion-exchange process can also improve the limited strength and the problematic scatter-in-strength of dental ceramic materials. The first exchange was done in KNO3 on a leucite-reinforced glass-ceramic material, the second exchange in 70 mol% KNO3, 30 mol% Na NO3 at different treatment times and temperatures. The dual-exchange process approximately doubled the Weibull strength. Moreover, the Weibull modulus showed a four-fold increase, i.e., the coefficients of variation were reduced from 18.3 to 4.7%. We conclude that the dual-exchange process may help significantly to increase the clinical reliability of glass-ceramic dental restorations, because the strength and the scatter-in-strength will be substantially improved by this treatment.

Aluminum Silicates↗
PubMed2001

The 'innate' host response protects and damages the infected urinary tract.

Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.

Animals↗
PubMed2001

Heat shock protein 70 (HSP70) in gastric adaptation to aspirin in Helicobacter pylori infection.

We have recently shown that adaptation of gastric mucosa to aspirin (ASA) is disturbed in Helicobacter pylori (H. pylori)-infected human stomach, but can be restored by eradication of the bacterium. The aim of this study was 1) to evaluate the influence of H. pylori on expression of heat shock protein 70 (HSP70) during ASA ingestion in these subjects and in mice model and 2) to evaluate, whether altered HSP70 expression might be associated with different adaptation to ASA in H. pylori-positive and eradicated subjects. The gastric mucosal HSP 70 gene expression was determined by quantitative RT-PCR and Western blot and immunohistochemistry during 14 days of ASA ingestion (1 g bid) in the same 8 subjects before and 3 months after successful eradication of H. pylori. In addition, HSP70 mRNA and protein expression were examined in 30 mice without and with H. pylori infection and eradication. During 14 days of ASA treatment, human H. pylori-infected mucosa revealed a decrease of HSP70 expression, while after eradication a higher expression and further increase of HSP70 expression during ASA ingestion were observed. Mice inoculated with H. pylori also exhibited decreased gastric mucosal HSP70 mRNA expression that was restored after eradication therapy. Decreased basal and ASA-induced expression of HSP70 may partly be responsible for impaired gastric adaptation to ASA in H. pylori-positive subjects. We conclude that 1. The HSP70 gene and protein expression is reduced during infection with H. pylori in men and mice and that gastric adaptation to ASA in H. pylori eradicated subjects is accompanied by increased HSP70 expression; 2. It is reasonable to assume that decreased HSP70 expression might contribute to disturbed gastric adaptation in H. pylori infection in humans and 3. The expression of HSP70 plays an important role in the mechanism of gastric adaptation to ASA and that H. pylori infection interferes with this adaptation due to decrease of HSP70 expression in gastric mucosal cells.

Adaptation, Physiological↗
PubMed2001

Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection.

Neutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.

Animals↗
PubMed2000

Caspase-14: analysis of gene structure and mRNA expression during keratinocyte differentiation.

Caspase-14 is expressed in a tissue-specific manner in mouse skin. Here we determined the complete caspase-14 cDNA sequence of human caspase-14 by rapid amplification of cDNA ends. Sequence comparison with a cosmid clone containing genomic DNA revealed that the human caspase-14 gene comprises seven exons. Facultative utilization of a cryptic splice acceptor site within intron 5 leads to the formation of two mRNA species. In situ hybridization of human skin showed that caspase-14 is expressed in the uppermost layer of living epidermal cells, i.e., the granular layer, in hair follicles and sebaceous glands. In vitro caspase-14 transcription was low in subconfluent cultures but strongly increased when keratinocyte differentiation was simulated by maintaining cells at confluence for several days. This transcriptional upregulation was suppressed in the presence of a high extracellular calcium concentration. Our findings show that caspase-14 is regulated at the level of transcription during keratinocyte differentiation in vitro and in vivo.

Amino Acid Sequence↗
PubMed2000

Search for lepton flavor violation in K+ decays into a charged pion and two leptons.

A search for lepton flavor violating decays, K+ --> mu+ mu+ pi-, K+ --> e+ e+ pi-, K+ --> pi+ e+ mu-, K+ --> mu+ e+ pi-, and pi0 --> e+ mu-, was performed using the data collected in Experiment E865 at the Brookhaven Alternating Gradient Synchrotron. No signal was found in any of the decay modes. At the 90% confidence level, the branching ratios are less than 3.0x10(-9), 6.4x10(-10), 5. 2x10(-10), 5.0x10(-10), and 3.4x10(-9), respectively.

Journal Article↗
PubMed2000

Improved limit on the rate of the decay K+ --> pi(+)&mgr;(+)e(-)

We report results of a search for the lepton-family number violating decay K+-->pi(+)&mgr;(+)e(-) from data collected by experiment E865 in 1996 at the Alternating Gradient Synchroton of Brookhaven National Laboratory. We place an upper limit on the branching ratio at 3.9x10(-11) ( 90% C.L.). Together with results based on data collected in 1995 and an earlier experiment, E777, this result establishes a combined 90% confidence level upper limit on the branching ratio at 2.8x10(-11). We also report a new upper limit on the branching ratio for pi(0)-->&mgr;(+)e(-) of 3.8x10(-10) ( 90% C. L.).

Journal Article↗
PubMed2000

Differential response in the human amygdala to racial outgroup vs ingroup face stimuli.

Here we describe response in the human amygdala to the presentation of racial outgroup vs ingroup faces. Functional magnetic resonance imaging (fMRI) measures of brain activity were acquired while subjects who identified themselves as White or Black viewed photographs of both White and Black faces. Across all subjects, we observed significantly greater blood oxygen-level-dependent (BOLD) signal in the amygdala to outgroup vs ingroup faces, but only during later stimulus presentations. A region of interest (ROI)-based analysis of these voxels revealed a significant interaction between amygdala response to outgroup and ingroup faces over time. Specifically, the greater amygdala activation to outgroup faces during later stimulus presentations was the result of amygdala response habituation to repeated presentations of ingroup faces with sustained responses to outgroup faces. The present results suggest that amygdala responses to human face stimuli are affected by the relationship between the perceived race of the stimulus face and that of the subject. Results are discussed as consistent with a role for the amygdala in encoding socially and/or biologically relevant information. We conclude that researchers seeking to study brain responses to face stimuli in human subjects should consider the relationship between the race of subjects and stimuli as a significant potential source of variance. Moreover, these data provide a foundation for future related studies in the neuroscience of social cognition and race.

Adult↗
PubMed2000

New measurement of the rare decay K+ --> pi(+)&mgr;(+)&mgr;(-)

More than 400 K+-->pi(+)&mgr;(+)&mgr;(-) events were observed in a rare K+ decay experiment at the Brookhaven Alternating Gradient Synchrotron. Normalized to the K+-->pi(+)pi(+)pi(-) decay, the branching ratio is determined to be [9.22+/-0.60(stat)+/-0. 49(syst)]x10(-8). This branching ratio and the &mgr;&mgr; mass spectrum is in very good agreement with the measurement of the K+-->pi(+)e(+)e(-) decay, but deviates significantly from the previous measurement.

Journal Article↗
PubMed2000

Brain representation of habituation to repeated complex visual stimulation studied with PET.

To investigate CNS habituation (i.e. response decrement due to stimulus repetition) the present study used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in eight healthy women during two repetitions of complex visual stimuli. Repeated visual stimulation resulted in neural habituation bilaterally in the secondary visual cortex and in the right medial temporal cortex including the amygdala and the hippocampus. Regional CBF in the left thalamus was elevated as a function of repeated stimuli presentations. Thus, repeated presentation of complex visual stimuli result in rCBF habituation in later stages of the visual processing chain. The elevated neural activity in the thalamus might be associated with interruption of further neural transmission related to suppression of non-meaningful behavior.

Adult↗
PubMed2000

Fast functional MRA using time-resolved projection MR angiography with correlation analysis.

Most recently, time-resolved 2D MRA after injection of a contrast agent bolus for various applications has been proposed. Similar to conventional digital subtraction angiography (DSA), 2D MR DSA offers the ability to observe the dilution of the bolus in the vascular system during the passage with a temporal resolution considerably below 1 sec. The purpose of this paper is to present strategies to improve the inherent low signal-to-noise ratio of 2D angiograms while retaining some temporal resolution. This can be achieved by applying algorithms for time series analysis as used in functional MRI. The significantly improved image quality is demonstrated on examples from clinical studies from bronchial MRA as well as cardiovascular MRA. In addition to the increased signal-to-noise ratio, correlation analysis leads to suppression of background signals and to a better discrimination of overlapping vessels. Further improvements in the temporal discrimination of vessels is afforded by the use of consecutive multiple contrast agent boli as demonstrated by numerical simulations and experiments.

Artifacts↗
PubMed2000

Segmental hepatic vein thrombosis associated with heparin-induced thrombocytopenia II.

We report the case of a 55-year-old man who developed heparin-induced thrombocytopenia II after a vertebral fracture. Autopsy revealed segmental hepatic vein thrombosis of the right lobe with subacute congestion and an activation of hepatic stellate cells. This case shows that heparin-induced thrombocytopenia II is a possible cause of the Budd-Chiari syndrome.

Anticoagulants↗
PubMed2000

Improved reliability of leucite reinforced glass by ion exchange.

OBJECTIVES: The aim of this study was to develop an adequate process-, proof- and calculation technique for the chemical strengthening of dental ceramic materials in order to evaluate the efficiency of this method from the engineering point of view. METHODS: Ion exchange examinations below glass temperature have been done for the dental all ceramic system IPS-Empress (Ivoclar). In addition experiments on specimens were undertaken, which were stored in artificial saliva for the period of one month after the ion exchange treatment. The efficiency of the ion-exchange treatments has been evaluated based on the chemical composition of the surface layer, the residual stress distribution, the flexural- and the burst-strength and surface hardness. In addition, Weibull statistical analysis of the four-point bending and burst test data provides new information about the failure mechanisms of chemically strengthened dental ceramics. RESULTS: The ion-exchange process with a potassium salt increases the reliability of the dental ceramic material "IPS-Empress". By the KNO3 or Tuf-Coat ion exchange treatment potassium ions will be implanted as clusters directly into the crystal lattice which results in an increase of the binding energy and hence, in a pronounced increase in the surface hardness. In particular the stress bearing capabilities of dental all ceramic restorations, which are subject to high bending stresses, i.e. dental crowns and dental bridges, are largely improved by the induced residual stresses. This increase of residual stresses did not relax significantly after a one month storage in artificial saliva. SIGNIFICANCE: Enhanced load limits and a more narrow strength distribution spectrum is considered desirable for increasing the clinical longevity of all ceramics.

Algorithms↗
PubMed2000

Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1.

One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate for prevention of acute graft-versus-host disease (GVHD). Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1. Minimum follow-up time was 6 months. Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, respectively. On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5; P = .03) with a single allele mismatch and 2.7 (95% CI, 1.2-6.0; P = .02) with a double allele mismatch. The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6; P = .02) and 5.0 (95% CI, 1.9-12.6; P = .001), respectively. Day 100 treatment-related mortality was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02), but overall survival at day 180 did not differ significantly among the 3 groups. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

Acute Disease↗