Biomedical subjects
Publications and source records attributed to W Müller.
This paper describes the result of the interdisciplinary cooperation of traumatologists of the Berufsgenossenschaftliche Unfallklinik (BGU) in Frankfurt am Main and a team of computer graphics scientists of the Franunhofer Institute for Computer Graphics in Darmstadt. We have developed a highly interactive training simulator system by means of computer graphics and virtual reality techniques.
The strength of receptor-mediated cell adhesion is directly controlled by the mechanism of cohesive failure between the cell surface and underlying substrate. Unbinding can occur either at the locus of the specific bond or within the bilayer, which results in tearing the hydrophobic anchors from the membrane interior. In this work, the surface force apparatus has been used to investigate the relationship between the receptor-ligand bond affinities and the dominant mechanism of receptor-coupled membrane detachment. The receptors and ligands used in this study were membrane-bound streptavidin and biotin analogs, respectively, with solution affinities ranging over 10 orders of magnitude. With the optical technique of the surface force apparatus, the occurrence of membrane rupture was directly visualized in situ. The latter observations together with measurements of the corresponding intermembrane adhesive strengths were used to identify the dominant failure pathway for each streptavidin-analog pair. Even in cases where the membrane pull-out energy exceeded the equilibrium bond energy, cohesive failure occurred within the membrane interior at nearly all bond affinities considered. These results are consistent with previous findings and provide direct support for the commonly held view that, under nonequilibrium conditions of applied external stress, the gradient of the bond energy, not the equilibrium bond energy alone, determines the adhesive strength. Furthermore, our findings directly demonstrate that, in the presence of competing failure mechanisms, the preferred detachment mechanism- hence, the adhesive strength-will be determined by the bond that exhibits the weakest tensile strength. Because the tensile strength is determined by the gradient of the unbinding energy, the critical detachment force will be determined by both the bond energy and the effective bond length.
Grasscutter serum antibodies against Clostridium perfringens beta-toxin were titrated in an enzyme immunoassay. The procedure that is currently used for vaccinating domesticated grasscutters is discussed.
In 1985, in a colony of domesticated grasscutters in Cotonou/Benin (West Africa), an endemic disease that caused severe losses of up to 50 percent of the population was found. The animals regularly showed a necrotic small intestine and strongly reddened and granulated (like a raspberry) Peyer's plaques of the whole small intestine protruding into the intestinal lumen; the latter has never been described in other necrotic enteriditis caused by C. perfringens. In further investigations (Schrägle and Müller, 1989), C. perfringens strains were typed and isolated from the faeces of healthy animals, and 81.6% belonging to the type C were found, a type that causes severe necrotic enteritis in pigs. Two figures show the pathologic-anatomic findings. Meanwhile, the disease was eradicated by the use of a prophylactic vaccination.
The common cytokine receptor gamma chain (gamma c) plays a critical role in lymphoid development through its participation in the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Absence of gamma c results in abnormal lymphopoiesis and immunodeficiency, as evidence by X-linked severe combined immunodeficiency (SCIDX1) in man, and in the corresponding canine and murine models of SCIDX1. Comparison of the phenotypes of mutant mice made deficient for gamma c-dependent cytokines by gene targeting, allows us to define a hierarchy of gamma c-dependent cytokine function in lymphoid development. The participation of distinct cytokine/receptor interactions in the generation, maintenance and regulation of the immune system suggests that developmental steps may be controlled by individual cytokines. The mechanisms by which different cytokine signaling pathways achieve this process remain to be elucidated.
Antiviral immune responses of mice lacking interleukin-2 (IL-2) or IL-4 or both IL-2 and IL-4 (IL-2/4) were compared by using different viruses. Primary cytotoxic T-lymphocyte (CTL) responses against lymphocytic choriomeningitis virus (LCMV) were only moderately reduced in mice lacking IL-2 and were normal in mice lacking IL-4. Mice deficient in both interleukins exhibited variable and more strongly reduced but nevertheless in vivo protective LCMV-specific CTL responses. Similar results were obtained with vaccinia virus. Upon virus-specific restimulation in vitro, spleen cells from IL-2- and IL-2/4-deficient mice failed to generate CTL responses against virus-infected target cells, whereas the response of mice deficient in only IL-4 was comparable to that of control mice. The addition of IL-2 during in vitro restimulation completely restored the responses of both IL-2 and IL-2/4-deficient mice. T-helper-cell-independent immunoglobulin M and T-helper-cell-dependent immunoglobulin G antibody responses against vesicular stomatitis virus glycoprotein were within normal ranges for the various mutant mice. After LCMV infection, specific antibody responses against LCMV nucleoprotein were reduced four- to eightfold. These results show that mice lacking IL-2/4 have an overall tendency to exhibit more severely reduced CTL responses than IL-2- or IL-4-deficient mice. Nevertheless, and surprisingly, in vivo protective immune responses were mounted in the absence of IL-2/4, suggesting that besides a minor contribution from IL-4, other interleukins compensate in vivo for the lack of IL-2 in IL-2-deficient mice.
1. Dissociated neurons from embryonic rat hypothalamus form synaptically coupled networks when cultured for several weeks. When synaptic inhibition is suppressed by the gamma-aminobutyric acid-A (GABAA) antagonist picrotoxin, neurons exhibit "rhythmic" burst activity that is blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 2. We have examined whether this type of activity is generated by pacemaker cells driving follower cells synaptically or whether it is generated by a neuronal network through feedback excitation by Ca2+ imaging of Fura-2/AM-loaded neurons and single-cell recording. 3. IN the presence of the GABAA antagonist picrotoxin (20 microM), a large majority of neurons (> 85%) displayed quasirhythmic increases in intracellular concentration of Ca2+ ([Ca2+]i). Single-cell recording revealed that these increases in [Ca2+]i correspond to burst discharges in individual neurons. When excitatory synaptic transmission was blocked by CNQX (20 microM), none of the imaged neurons exhibited significant oscillations in [Ca2+]i. 4. Investigation of the intervals between bursts from single-cell recording revealed a random distribution over a range of 400% from the minimum interval. Poincaré maps of burst intervals, i.e., graphs of all burst intervals versus their preceding burst interval, revealed that a burst interval is unpredictable from its predecessor. 5. When synaptic coupling was attenuated by low concentrations of CNQX (50-500 nM), the mean burst interval was considerably increased without a change in the random character of burst activity. 4-Aminopyridine (1 mM), known to increase synaptic efficiency, reduced the mean burst interval.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND AND PURPOSE: Previous work has shown that rates of cerebral microemboli downstream of high-grade internal carotid artery stenosis are higher in recently symptomatic compared with asymptomatic patients. In addition, microembolic rates decline after carotid endarterectomy. We conducted a prospective investigation of 40 consecutive asymptomatic or recently symptomatic patients undergoing carotid endarterectomy for 70% to 95% internal carotid artery stenosis to determine the relationship between microembolic rate and pathoanatomic features of the carotid plaque. METHODS: Transcranial Doppler monitoring including automated emboli detection was performed preoperatively to assess the rate of cerebral microemboli of the ipsilateral middle cerebral artery. The corresponding endarterectomy specimens were evaluated histologically with respect to the occurrence of plaque fissuring, intraplaque hemorrhage, plaque ulceration, or intraluminal thrombosis. RESULTS: There were strong associations between plaque ulceration, intraluminal thrombosis, and downstream cerebral microemboli (P < or = .005, respectively). There were no correlations of microembolism with plaque fissuring or intraplaque hemorrhage (P = .82 and P = .28, respectively). CONCLUSIONS: We conclude that ulceration and luminal thrombosis of the atheromatous plaque are the main sources of downstream cerebral microemboli in patients with high-grade internal carotid artery stenosis. Our data support the view that these pathoanatomic features may also play a key role in symptom development.
Previous studies in vivo have shown that IL-10 infusion can prevent lethal endotoxic shock. Mice deficient in the production of IL-10 (IL10T) were used to investigate the regulatory role of IL-10 in the responses to LPS in three experimental systems. In a model of acute endotoxic shock, it was found that the lethal dose of LPS for IL10T mice was 20-fold lower than that for wild type (wt) mice suggesting that endogenous IL-10 determines the amount of LPS which can be tolerated without death. The high mortality rate of IL10T mice challenged with modest doses of LPS was correlated to the uncontrolled production of TNF as treatment with anti-TNF antibody (Ab) resulted in 70% survival. Additional studies suggested that IL-10 mediates protection by controlling the early effectors of endotoxic shock (e.g., TNF alpha) and that it is incapable of directly antagonizing the production and/or actions of late appearing effector molecules (e.g., nitric oxide). We also found that IL10T mice were extremely vulnerable to a generalized Shwartzman reaction where prior exposure to a small amount of LPS primes the host for a lethal response to a subsequent sublethal dose. The priming LPS dose for IL10T mice was 100-fold lower than that required to prime wt mice implying that IL-10 is important for suppressing sensitization. In agreement with this assumption, IL-10 infusion was found to block the sensitization step. Interestingly, IL-10 was not the main effector of endotoxin tolerance as IL10T mice could be tolerized to LPS. Furthermore, IL-10 infusion could not substitute for the desensitizing dose of LPS. These results show that IL-10 is a critical component of the host's natural defense against the development of pathologic responses to LPS although it is not responsible for LPS-induced tolerance.
In a retrospective study, the outcome of the chronic low back pain syndrome was investigated in a group of 53 patients. Average time since the diagnosis was established was 18 years. 25% of the patients--all female but one--developed fibromyalgia. The criteria of Yunus and Wolfe, modified by Müller and Lautenschläger, were applied to establish the diagnosis of fibromyalgia. In 60% of the patients chronic low back pain persisted at the time of final examination, while 8 patients were asymptomatic. Predictive parameters for the chance of getting fibromyalgia were sex and postural disorders such as scoliosis. Other radiological findings, for example degenerative changes of the spine, did not coincide with the group of patients who developed fibromyalgia. The predictive value of pain localisation, number of tender points, presence and severity of functional and vegetative symptoms, and the psychosocial situation is uncertain and should be investigated in further long term prospective studies.
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Measuring and evaluating locally generated VECP present a chance to overcome methodical restriction in conventional subjective perimetry. To achieve this, stimuli are required which ensure the generation of detectable responses under controlled scattered light influence. The suitability of LED for this task was studied. LED stimuli (lambda = 560 nm) were moved in steps of 3 degrees from 0 degree to 30 degrees on the horizontal meridian within a perimeter sphere. The stimuli were 0.8 degree and 1.7 degrees in size, 20 ms in duration and 0.5 Hz in frequency. The background illumination was 10 cd/m2. A total 467 responses recorded from 20 volunteers (age 26 +/- 2) known to be free of any visual field defect have been evaluated. Using only one LED (size 0.8 degree) VECPs are detectable in the visual field < 9 degrees exclusively. An increase of stimuli size to 1.7 degrees made the generation of detectable VECP within the peripheral visual field possible. Statistical evaluation (sign test) proved significantly that VECP can be reliably elicited under LED stimulation. LED (lambda = 560 nm) are suitable for the generation of localized VECP in the visual field up to an eccentricity of 30 degrees.
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