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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 271 records · Page 15Linked to original sources

Muscle damping measured with a modified pendulum test in patients with fibromyalgia, lumbago, and cervical syndrome.

STUDY DESIGN: Muscle tension with tenderness may be localized or generalized as in fibromyalgia. Wartenberg's pendulum test might be appropriate for quantitating muscle damping, at least in generalized cases. OBJECTIVE: Damping values provide a quantitative measure of muscle tension and of the response to various treatments. SUMMARY OF THE BACKGROUND DATA: According to recent anatomic and experimental works, intrafusal muscle fibers are double-innervated by gamma motoneurons and sympathetic fibers. With electromyograph recording, the activity of extrafusal fibers and gamma motoneurons (reflexes) can be assessed and separated from the action of the sympathetic system. METHODS: An electrogoniometer registers the movements of the freely swinging leg. On the oscilloscope, the patient's nodular curve is compared with an ideal calculated dampened curve to find the damping value. Electromyograph surface electrodes from the knee extensors and flexors detect the activity of extrafusal fibers and the occurrence of reflexes. RESULTS: In longstanding severe fibromyalgia, damping values are almost always elevated, at least in one leg. Half or more of patients with chronic lumbago and cervical syndrome present with increased damping. The surface electromyograph remains silent (in contrast to spastic patients). CONCLUSION: The findings support the hypothesis that muscle tension in rheumatic patients results from overactivity of the sympathetic system (or part of it). Even in clinically localized pain syndromes, muscle damping is often increased in the legs. The test is valuable for quantitating muscle tension and the effectiveness of therapeutic methods.

Adult↗

Muscarinic activation reduces changes in [Ca2+]o evoked by stimulation of Schaffer collaterals during blocked synaptic transmission in rat hippocampal slices.

The rat hippocampal slice preparation and blockers of postsynaptic glutamate receptors (6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX) 10 microM; DL-2-amino-5-phosphonovaleric acid (APV) 30 microM) were used to study the effects of muscarinic activation on stimulus-induced decreases in [Ca2+]o presumably due to presynaptic Ca-influx. Perfusion with carbachol (100-200 microM) transiently reduced these changes in [Ca2+]o. Blockade of this muscarinic effect by pirenzepine (200 microM) and prolongation of this effect after prolonged lithium (1 mM) incubation suggest involvement of the muscarinic M1 receptor subtype. These findings suggest, that activation of M1 receptors might contribute to inhibition of excitatory synaptic transmission by inhibiting presynaptic Ca-influx. In this way, the muscarinic enhancement of excitatory input may be limited to non-deleterious levels.

2-Amino-5-phosphonovalerate↗

Effects of glutamate receptor agonists on presumed presynaptic Ca(2+)-signals in juvenile rat hippocampal area CA1.

The physiological role of presynaptic glutamate receptors in controlling presynaptic Ca(2+)-influx and thereby transmitter release is unknown. To test if presynaptic Ca(2+)-uptake in the hippocampus is controlled by glutamate autoreceptors, we created a hippocampal slice preparation for investigation of presumed presynaptic Ca(2+)-signals with ion-sensitive microelectrodes after lesioning of post-synaptic neurons by glucose deprivation. After prolonged glucose deprivation in slices from juvenile animals of postnatal days 13-15 and 20-22, stratum radiatum (SR) and alveus stimulation-induced postsynaptic field potential (fp) components were irreversibly abolished in area CA1, whereas SR stimulation still evoked afferent volleys. Repetitive stimulation of the SR still induced small decreases in the extracellular Ca2+ concentration ([Ca2+]o), but repetitive alveus stimulation no longer induced decreases in [Ca2+]o, suggesting a complete damage of pyramidal cells. In lesioned slices the remaining SR stimulation-induced small decreases in [Ca2+]o presumably reflect presynaptic Ca(2+)-influx. These small decreases in [Ca2+]o were reversibly reduced by kainate, RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and L-glutamic acid (glutamate), without effects on afferent volleys.

Animals↗

Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.

We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.

Aging↗

Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue.

Immune defence against pathogens entering the gut is accomplished by lymphocytes in the gut-associated lymphoid tissue (GALT), a major compartment of the immune system. The GALT, comprising Peyer's patches, lamina propria lymphocytes and intra-epithelial lymphocytes of the intestine, is populated by lymphocytes that migrate there from the vasculature. Here we report that, in mice deficient for the beta7 integrin subfamily of adhesion molecules, the formation of the GALT is severely impaired. This is probably due to a failure of beta7-/- lymphocytes to arrest and adhere to the vasculature at the site of transmigration into the GALT.

Animals↗

In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha.

To examine the function of IL-10 synthesis during early infection with the intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were inoculated with an avirulent parasite strain (ME-49). In contrast to control littermates that displayed 100% survival, the IL-10-deficient animals succumbed within the first 2 wk of the infection, with no evidence of enhanced parasite proliferation. The mortality in the IL-10 KO mice was associated with enhanced liver pathology characterized by increased cellular infiltration and intense necrosis. Levels of IL-12 and IFN-gamma in sera of infected IL-10-deficient animals were four- to sixfold higher than those in sera from control mice, as were mRNA levels for IFN-gamma, IL-1 beta, TNF-alpha, and IL-12 in lung tissue. Similarly, macrophages from IL-10 KO mice activated in vitro or in vivo with T. gondii produced higher levels of TNF-alpha and IL-12 than macrophages from control animals. Moreover, spleen cells from IL-10 KO mice infected with T. gondii secreted more IFN-gamma than splenocytes from nondeficient animals. In vitro depletion experiments indicated that CD4+ lymphocytes are the major source of the latter cytokine in the spleen cell populations, and in vivo depletion with anti-CD4 Abs protected the IL-10 KO mice from parasite-induced mortality. Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology.

Acute Disease↗

T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice.

Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates in the colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis in IL-10-/- mice. We detected an influx of immunoglobulin-positive cells into the colon and the presence of colon-reactive antibodies in the serum of IL-10-/- mice. To assess a pathogenic role for B cells, we generated a B cell-deficient (B-/-) strain of IL-10-/- mice. B-/-IL-10-/- mice acquired a severe colitis analogous to that IL-10-/- mice, implying that B cells were not the primary mediator of IBD in this model. A series of cell transfer experiments was performed to assess a pathogenic role for T cells. When IL-10-/- T cell-enriched lamina propria lymphocytes (LPL) or intraepithelial lymphocytes (IEL) were transferred into immunodeficient recombinase-activating gene (RAG)-2-/- recipients, a mild to severe colitis developed, depending on the cell number transferred. Lymphocytes recovered from the colon of transplanted RAG-2-/- mice with colitis were predominantly alpha beta TCR+CD4+, including a large proportion of CD4+CD8 alpha + cells. These cells were also CD45RB-/low and CD44+, indicative of an activated/memory population. Individual populations of CD4+CD8 alpha-, CD4+CD8 alpha + and CD4-CD8 alpha + T cells were then isolated from the lamina propria compartment of IL-10-/- mice and transferred into RAG-2-/- recipients. Only IL-10-/- CD4-expressing LPL, including both the CD4+CD8 alpha- and CD4+CD8 alpha + populations, induced colitis in recipient mice. Interferon-gamma, but little to no IL-4, was produced by CD4+CD8 alpha- and CD4+CD8 alpha + LPL recovered from the inflamed colons of RAG-2-/- recipients implicating alpha T helper cell 1 (TH1)-mediated response. We thus conclude that colitis in IL-10-/- mice is predominantly mediated by TH1-type alpha beta TCR+ T cells expressing CD4 alone, or in combination with the CD8 alpha molecule.

Animals↗

Magnetometry of evoked fields from human peripheral nerve, brachial plexus and primary somatosensory cortex using a liquid nitrogen cooled superconducting quantum interference device.

Superconducting Quantum Interference Devices (SQUIDs) can be used to detect neuromagnetic fields evoked in the peripheral and central nervous system. Up to now, such measurements had to be based on SQUIDs with a low critical temperature (Tc) requiring liquid helium cooling. Recent improvements in high-Tc SQUID technology relying on liquid nitrogen cooling led to a significant reduction in the system's noise level. Hare, first high-Tc recordings of weak neuromagnetic fields are demonstrated. In particular, along the entire somatosensory afferent pathway including peripheral nerves, brachial plexus and primary somatosensory neocortex evoked neuromagnetic activities were detected using conventional recording parameters for bandwidth and number of averages. This opens up a wide perspective for cost-effective high-Tc magnetometry in clinical neuroscience.

Brachial Plexus↗

Occupational stress and strain of female students: results of physiological, behavioral, and psychological monitoring.

This study of 50 female students (mean age 23) investigated the level of acute and chronic subjective stress, objective strain of everyday university life, and behavior (time budget during a normal day). Physiological parameters, behavioral activities, and psychological parameters were assessed simultaneously both while at the university and at home using a special ambulatory monitoring device capable of storing 23-h records. Comparison between typical study (seminar, lecture) and leisure activities (resting, conversation, etc.) revealed lower heart rate variability during university-related activities, indicative of increased mental load. Physical activity was higher during leisure activities, but heart rate was even higher during study time. Students rated leisure activities to be more enjoyable but less exciting or arousing than studies. Two-factorial MANOVAs with the factors "stay' (at the university, at home) and "chronically stressed by studies', a rating made one week before the monitoring (stressed versus non-stressed students), showed significantly higher heart rates for the chronically stressed students, particularly while at the university as opposed to at home. These students also showed decreased heart rate variability as compared to the non-stressed students, indicating greater mental workload. No differences between the groups were found in socioeconomic variables and personality traits (neuroticism, extraversion, achievement motivation). The results are discussed in the context of the stress concept.

Adult↗

Prognostic influence of p53 expression in gastric cancer.

The presence of the nuclear phosphoprotein p53 was investigated in a series of 120 consecutive gastric carcinomas. This immunohistochemical study on formalin-fixed, paraffin-embedded material found p53 expression in 43 per cent (n = 51) of carcinomas using a monoclonal antibody (DO-1), whereas no immunoreactivity for p53 was present in tumour-associated non-neoplastic gastric mucosa or tumour stroma. There was no statistically significant correlation with known prognostic parameters such as extent of tumour growth (pT state), nodal involvement (pN state), or tumour grade. The same applied for association with patient age and sex or pathological parameters such as tumour size, localization, or growth pattern according to histological classification. Kaplan-Meier analysis revealed marginal statistically significant differences in survival times between patients with p53-positive tumours with more than 35 per cent of p53-positive tumour cells and those with less than 35 per cent of p53-positive tumour cells or p53-negative tumours (P = 0.04). However, by multivariate analysis, p53 immunoreactivity did not turn out as an independent prognostic parameter. p53 expression can easily be detected in a variety of human malignancies including gastric cancer by immunohistochemical methods, but its prognostic significance and possible role as an independent marker of poor prognosis still have to be confirmed by further studies.

Biomarkers, Tumor↗

Plasmodium chabaudi chabaudi: differential susceptibility of gene-targeted mice deficient in IL-10 to an erythrocytic-stage infection.

Female and male mice deficient in IL-10 production by targeted disruption of the IL-10 gene were infected with Plasmodium chabaudi chabaudi (AS) blood-stage parasites. Both male and female mutant mice exhibited more severe signs of disease than did +/+ or heterozygous control mice. Female defective mice also displayed an increased mortality; 56% of mice died within 20 days of infection. Mortality did not appear to be due to a fulminating parasitemia as death occurred at different levels of parasitemia in the individual mice. The acute infection was accompanied by an enhanced Th1 IFN-gamma response. This response was retained in the chronic phase of infection of both male and female mutant mice, whereas in controls the responding CD4+ T cells were predominantly Th2 cells secreting IL-4. The data suggest that IL-10 regulates the inflammatory response to the parasite and that in its absence the combined effects of malaria toxins and the sustained or enhanced IFN-gamma response lead to increased pathology. In the case of female mice absence of IL-10 is sufficient to induce a lethal endotoxin-like reaction.

Anemia↗

Differential p53 protein expression in stomach adenomas of gastric and intestinal phenotypes: possible sequences of p53 alteration in stomach carcinogenesis.

In a comparative study, the expression of p53 protein was investigated in intestinal- and gastric-type adenomas of the stomach. The former is a conventional type, which is well known to be a premalignant lesion of the stomach, but the latter is a rare, more recently noted entity. Of 28 intestinal-type adenomas, 17 (60.7%) contained more than 5% of p53 immunoreactive cells. In these adenomas, the extent of positivity for p53 protein was significantly higher in high-grade dysplasia than in low-grade dysplasia (P < 0.05), suggesting that p53 alteration plays a part in the dysplastic progression of intestinal-type adenomas. Among 18 gastric-type adenomas in which most of the tumour cells displayed gastric-type mucin, substantial expression of p53 protein was found only in the 3 tumours with high-grade dysplasia. Thus, the incidence of p53 expression was significantly higher in intestinal-type adenomas than in gastric-type adenomas (P < 0.01). These results suggest that p53 gene alteration is an earlier event in the gastric carcinogenetic sequence with the intestinal phenotype than in that with the gastric phenotype.

Adenoma↗

Neurodevelopmental outcome of hydrocephalus following intra-/periventricular hemorrhage in preterm infants: short- and long-term results.

Over a 5-year period (1984-1988) intra- and periventricular hemorrhage (IVH/PVH) was observed in 299 preterm infants. Sixty-eight infants developed posthemorrhagic hydrocephalus (PH); of these, 23 infants died and 40 infants could be followed up for assessment of neurological development (5 patients were lost to follow-up). At 1 year of corrected age 15% (25% at 5 year follow-up) of the infants were determined to have developed normally, 35% (25% at 5-year follow-up) showed mild neurological symptoms and/or slight developmental delay, 32.5% (28% at 5-year follow-up) had handicaps and/or moderate mental retardation, and 17.5% (22% at 5-year follow-up) had severe handicaps and/or severe mental retardation. There was a significantly worse outcome in infants with grade 4 IVH/PVH (P < 0.05) and a significantly worse outcome in the group requiring ventriculoperitoneal (VP) shunt (P < 0.05). The results at 1 year of corrected age proved to be a quite realistic predictor of neurological functioning at 5 years of age (80% predicted correctly in the non-shunted-group--one patient lost to follow-up; 95% predicted correctly in the shunted group--four patients lost to follow-up). Cystic periventricular leukomalacia had been diagnosed in 7 (10%) patients and was associated with poor neurodevelopmental outcome. Gestational age, birth weight, time of shunt placement, and peripartum asphyxia had no significant influence on neurodevelopmental outcome. Infants with shunt infections and a high number of shunt revisions were found to have a significantly worse neurodevelopmental outcome (P < 0.01).

Cerebral Hemorrhage↗

Occurrence and distribution of free nerve endings in the distal iliotibial tract system of the knee.

Free nerve endings (FNE) are nociceptive sensory elements transmitting information on pain and inflammation from the connective tissues to the brain. They form an important part of the proprioceptive sensory system of the knee. We present a qualitative and quantitative analysis of FNEs in the distal iliotibial tract (ITT), documenting their occurrence in this structure as well as their specific distribution pattern. FNEs were found in all elements of the distal ITT, with their maximum density in the fixation sites of the distal ITT to the femur and the tibia. This finding correlates well with anatomical and biomechanical studies and stresses the importance of the deep ITT fibre system for lateral knee stability. The relative number of FNEs in the distal ITT ranges from 5 to 10 per 50 mm2 and is comparable to the frequency found in the synovial sheath of the cruciate ligaments. These findings have clinical implications for surgical procedures on the lateral side of the knee. The distinct anatomy of the distal ITT should be respected in all procedures, since extensive operations in this area may cause pain and loss of range-of-motion due to alterations of proprioceptive function.

Adult↗

Deep posterior knee pain caused by a ganglion of the popliteus tendon--a case report.

The most common causes of posterior and posterolateral knee pain (besides referred pain) are knee joint effusions, tendinitis of the hamstring tendons, Baker cyst (semi-membranous cyst), bursitis, meniscal pathologies such as tears and ganglions and lesions of the anterior cruciate ligament. Less common causes include popliteus and gastrocnemius tendinitis, arthrofibrosis after trauma, posterior cruciate ligament sprains, deep venous thrombosis and/or irritations of the common peroneal nerve. We present one patient with posterolateral knee pain after a minor contusion. Magnetic resonance imaging revealed a degenerated posterior horn of the lateral meniscus and a somewhat unclear polypoid structure in the intercondylar region. As the posterior component of the pain persisted even after an arthroscopic partial meniscectomy, an operative revision was performed. A small ganglion of the sheath of the popliteus tendon was found and excised. The patient was immediately relieved of his pain after this procedure. To our knowledge this is the first report concerning a ganglion of the sheath of the popliteus tendon causing posterior knee pain. A similar pathology of the popliteus tendon has been described earlier but at a different localisation (in the hiatus), simulating a parameniscal cyst.

Adult↗