The challenge of fibromyalgia: new approaches.
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Fibromyalgia↗
Biomedical subjects
W Müller
Publications and source records attributed to W Müller.
[Cervical necrotizing fasciitis:clinicopathological aspects].
INTRODUCTION: Necrotising fasciitis is a potentially fatal fulminant infection of the subcutaneous tissues. METHODS: Our series comprised 15 patients with severe necrotising fasciitis during a 6-year period (1994-1999) at the surgical and ENT department of the Cantonal Hospital in Lucerne. RESULTS: In 4 cases, the necrotising infection occurred in the head and neck, beginning with a mastoiditis, pharyngitis, tongue swelling and infection of the upper eyelid. The bacteria cultures showed in 3 cases streptococcus of group A, in one case there was a mixed flora. All patients underwent a surgical intervention combined with antibiotics, intensive care was also necessary. All 4 patients with necrotising fasciitis in head and neck survived, 3 of the 11 surgical cases died because of multiorgan failure. DISCUSSION: The high mortality in necrotising fasciitis can only be influenced if diagnosed and treated very early. There often is a difference between the local infection sings and the patient's condition. The treatment includes a sudden surgical intervention combined with antibiotic therapy and intensive care.
Adult↗
Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus.
BACKGROUND: Barrett esophagus (BE) is a condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE is a premalignant lesion because it is the initiating factor in a metaplasia-dysplasia-carcinoma sequence. METHODS: Expression of the proliferation-associated molecule cyclin E was immunohistochemically determined in metaplastic specialized epithelium (SE; n = 24), low grade dysplasia (LGD; n = 21), high grade dysplasia (HGD; n = 17), and invasive adenocarcinoma (CA; n = 35) from 36 esophagectomy specimens. In addition, endoscopically obtained samples of SE with minimal inflammatory changes (n = 11) and SE adjacent to erosions or ulcerations were tested for cyclin E expression. RESULTS: In the surgical specimens, expression of cyclin E was found in 0 of 24 SE (0%), 2 of 21 LGD (9.5%), 3 of 17 HGD (17.6%), and 5 of 35 CA (14. 3%). In the biopsy specimens, expression of cyclin E was found in all samples adjacent to erosions or ulcerations, whereas SE with minimal inflammatory changes was invariably negative for cyclin E. CONCLUSIONS: Accumulation of cyclin E can be found by means of immunohistochemistry in premalignant and malignant lesions in BE as well as in regenerative metaplastic epithelium. The determination of cyclin E expression is therefore not useful in the identification of BE patients with an increased risk for the development of carcinoma.
Adenocarcinoma↗
Muscarinic control of intracortical connections to layer II in rat entorhinal cortex slice.
The cholinergic system is critically involved in oscillatory network activity and synaptic plasticity in the entorhinal cortex (EC) hippocampal formation. Here we demonstrate robust inhibition of field potentials in layer II of the medial EC evoked by stimulation in the deep EC or in the lateral layer II by carbachol (CCh, 0.1-100 microM, K(D) approximately 1 microM). This effect appears not to be mediated by suppression of presynaptic Ca(2+)-signals since paired pulse facilitation was increased by CCh. Blockade of the effect by the muscarinic antagonists atropine and pirenzepine demonstrates mediation by muscarinic receptors, most likely of the M1 subtype. The effect is characterized by absence of desensitization and should be important for laminar shaping of oscillatory activity and synaptic plasticity during acetylcholine-dependent theta-rhythmic activity.
Animals↗
Non-Indian childhood cirrhosis.
Copper is an essential trace element for sustaining life. However, copper in excess is highly toxic and elevated copper concentrations in cells have been associated with several diseases, including non-Indian childhood cirrhosis (NICC) in man and copper toxicosis in Bedlington terriers. NICC and copper toxicosis in Bedlington terriers are phenotypic very similar to Wilson disease and Indian childhood cirrhosis. Recently, the gene underlying Wilson disease (ATP7B) as well as copper transport genes hCTR1, hCTR2 and ATOX1 have been excluded as candidates for NICC in man and copper toxicosis in Bedlington terriers. Currently, a genome wide screen is being carried out to localize the NICC gene. Isolation of the NICC gene and defining its pathophysiology will significantly expand our insight into copper metabolism in man, which, at present, is largely limited. The availability of a dog mutation with phenotypic similarities to NICC will open up new lines of research for studying the disease if it proves to be homologous to NICC but will still represent an important addition to the list of genes determining copper disease in mammals if it doesn t.
Animals↗
Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress.
Biomechanical stress is a major stimulus for cardiac hypertrophy and the transition to heart failure. By generating mice that harbor a ventricular restricted knockout of the gp130 cytokine receptor via Cre-IoxP-mediated recombination, we demonstrate a critical role for a gp130-dependent myocyte survival pathway in the transition to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure overload, these mice display rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis versus the control mice that exhibit compensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure. gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.
Animals↗
Subcellular muscarinic enhancement of excitability and Ca2+-signals in CA1-dendrites in rat hippocampal slice.
The cholinergic system is involved in Ca2+-dependent models of learning. To study subcellular modulation, we evoked 50-100 microm long dendritic Ca2+-responses by focal pressure application of glutamate. These Ca2+-responses were augmented by +70% by focally applied carbachol. This atropine-sensitive augmentation started within 1 s concurrent to an augmentation of the glutamate-evoked somatic depolarization and firing. Tetrodotoxin reduced the Ca2+-response to glutamate by 60-80% while, after having restored the Ca2+-signal by increasing the application of glutamate, its muscarinic augmentation was reduced from +73 to +30%. Lithium (2 mM, >2 h) slowed and reduced augmentation of Ca2+-signals and blocked augmentation of the glutamate-evoked depolarization and firing, but not suppression of the slow after-hyperpolarization following repetitive discharge. Thus, several mechanisms contribute to muscarinic augmentation of Ca2+-signals.
Acetylcholine↗
Rearrangement and expression of immunoglobulin light chain genes can precede heavy chain expression during normal B cell development in mice.
In mouse mutants incapable of expressing mu chains, VkappaJkappa joints are detected in the CD43(+) B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4-7% of CD43(+) B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)kappa genes before the assembly of a productive VHDHJH joint. Thus, mu chain expression is not a prerequisite to Igkappa light chain gene rearrangements in normal development. Overall, approximately 15% of the total CD43(+) B cell progenitor population carry Igkappa gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43(+) progenitors rearrange IgH and Igkappa loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VkappaJkappa joining rapidly initiates kappa chain expression, irrespective of the presence of a mu chain.
Animals↗
IMGT, the international ImMunoGeneTics database.
IMGT, the international ImMunoGeneTics database (http://imgt.cnusc. fr:8104), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr). IMGT comprises three databases: LIGM-DB, a comprehensive database of Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development); a tool, IMGT/DNAPLOT, developed for sequence analysis and alignments; and expertised data based on the IMGT scientific chart, the IMGT repertoire. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc. fr:8104
Animals↗
Lacrimal gland choristoma of the iris.
Intraocular lacrimal gland tissue is an extremely rare choristoma. A newborn girl was seen with a fleshy, vascular tumor arising from the peripheral iris and the anterior chamber angle. The tumor was treated with topical steroids on suspicion of a juvenile xanthogranuloma; later, it grew slightly and a secondary glaucoma developed. Histopathological examination of the resected tumor showed lacrimal gland tissue in the iris. Twelve cases of intraocular lacrimal gland tissue have been reported in the literature.
Anterior Chamber↗
FHIT gene in gastric cancer: association with tumour progression and prognosis.
The FHIT (fragile histidine triad) gene has been recently identified and cloned at chromosome 3p14.2 including FRA3B, the most common fragile site in the human genome. FHIT is suggested to be a candidate tumour suppressor gene in gastrointestinal tract tumours. To elucidate the role of the FHIT gene in gastric cancer, a total of 133 curatively R0-resected gastric carcinomas were investigated for loss of heterozygosity (LOH) at 3p14.2, using four polymorphic microsatellite loci (D3S1300, D3S1313, D3S1481, and D3S1234). LOH of the FHIT gene affecting at least one of the investigated loci was observed in 20 of 123 informative tumours (16.3 per cent). The presence of LOH was correlated neither with major prognostic factors such as pT category, pN category or vascular invasion, nor with histological type or grade of differentiation of the tumours. In addition, there were no differences in the prognosis between patients with gastric carcinomas showing LOH at the FHIT gene and patients with tumours lacking LOH at the FHIT gene. These findings suggest that LOH of the FHIT gene represents an event in the tumourigenesis of only a small subset of gastric carcinomas and does not correlate with tumour progression or prognosis.
Acid Anhydride Hydrolases↗
Expression of cell-cycle regulatory proteins cyclin D1, cyclin E, and their inhibitor p21 WAF1/CIP1 in gastric cancer.
The expression and prognostic role of cyclin D1, cyclin E, and p21 (WAF1/CIP1) were immunohistochemically investigated in 413 curatively resected gastric carcinomas. p21 was expressed in 65.4 per cent (n=270), cyclin D1 in 23.7 per cent (n=98), and cyclin E in 13.6 per cent ( n=56) of the tumours. The expression of p21, cyclin D1, and cyclin E was positively associated with the papillary or tubular type of the WHO classification, as well as with the intestinal type according to the Lauren classification. No significant correlation could be found between the expression of p21, cyclin D1 and cyclin E and the parameters pT category, lymph node involvement, and blood vessel and lymphatic vessel invasion. Concerning survival, no prognostic impact of p21, cyclin D1, and cyclin E expression could be verified, even when different subgroups of patients were analysed separately according to the pT and pN category as well as to the Lauren classification. The present data suggest that neither cyclin D1, cyclin E nor their inhibitor p21 can predict the survival of gastric cancer patients, nor is their immunohistochemical detection a suitable tool for identifying subgroups of patients who may be at higher risk.
Adult↗
Real-time simulation of tissue deformation for the nasal endoscopy simulator (NES).
Endonasal sinus surgery requires a great amount of training before it can be adequately performed. The complicated anatomy involved, the proximity of relevant structures, and the variability of the anatomy due to inborn or iatrogenic variations make several complications possible. Today, cadaver dissections are the "gold standard" for surgical training. To overcome the drawbacks of traditional training methods, the Fraunhofer Institute for Computer Graphics is currently developing a highly interactive medical simulation system for nasal endoscopy and endonasal sinus surgery, in cooperation with the Mainz University Hospital. For the simulation of a rhinoscopic procedure, not only are the realization of the 3D interaction and the geometric representation of the anatomical structures necessary, but also a real-time simulation of the deformation behavior constrained by the instrument collisions. The challenge is to close the gap between a maximal degree of realism and the required real-time conditions.
Cadaver↗
Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody.
In-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.
Animals↗
Familial clustering of infantile cirrhosis in Northern Germany: A clue to the etiology of idiopathic copper toxicosis.
Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet.
Age of Onset↗
Markers of function and proliferation in non-invasive and invasive bi- and plurihormonal adenomas of patients with acromegaly: an immunohistochemical study.
Twenty-seven plurihormonal and 21 growth hormone- prolactin- (GH- PRL-) mixed cell adenomas obtained from patients with acromegaly undergoing transnasal-transsphenoidal surgery were investigated immunohistochemically for expression of Epidermal Growth Factor (EGF), Transforming Growth Factor alpha (TGF alpha), Insulin-like Growth Factor-1 (IGF-1), Estrogen Receptor-Related Protein (ERRP), Multidrug Resistance Marker (MDRM), Protein Kinase C (PKC), Gs alpha,. Cathepsin D and p53. Five plurihormonal adenomas grew invasively. The panel of markers used in this study represents a selection of functional and proliferative markers thought to be associated with the function and development of pituitary adenomas. Our results imply that the growth factors (EGF, TGF alpha, IGF-1), the cell signalling protein Gs alpha and the MDRM are expressed by both types of pituitary adenomas in a similar pattern. Non-invasive GH-PRL-mixed cell adenomas showed an increased expression of IGF-1, TGF alpha and MDRM compared to non-invasive plurihormonal adenomas. No factor was found which would reliably distinguish between invasive and non-invasive adenomas. We failed to confirm the findings of others that p53 and cathepsin D might be indicators of tumor aggressiveness. A participation of ERRP and PKC in the development of bi- and plurihormonal adenomas with acromegaly appears unlikely, as the immunostains were all negative.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Carbachol-induced changes in excitability and [Ca2+]i signalling in projection cells of medial entorhinal cortex layers II and III.
The entorhinal cortex (EC) is a major gateway for sensory information into the hippocampus and receives a cholinergic input from the forebrain. Therefore, we studied muscarinic effects on excitability and intracellular Ca2+ signalling in layer II stellate and layer III pyramidal projection neurons of the EC. In both classes of neurons, local pressure-pulse application of carbachol (1 mM) caused small, atropine-sensitive membrane depolarizations that were not accompanied by any detectable changes in [Ca2+]i. At a higher concentration (10 mM), carbachol induced a larger membrane depolarization associated with synaptic oscillations and epileptiform activity in both classes of neurons. In contrast to the intrinsic theta rhythm in stellate cells with one dominant peak frequency at approximately 7 Hz, the synaptically mediated oscillation induced by carbachol showed three characteristic peaks in the theta and gamma frequency range at approximately 11, 23 and 40 Hz. Although carbachol-induced epileptiform activity was associated with increases in intracellular free Ca2+ in both layer II and III cells, the observed [Ca2+]i accumulation was significantly larger in layer III than in layer II cells. Responses to intracellular current injections showed differences in Ca2+ accumulation in layer II and III cells at the same membrane potentials, suggesting a dominant expression of low- and high-voltage-activated Ca2+ channels in these layer II and III cells, respectively. In conclusion, we present evidence for significant differences in the [Ca2+]i regulation between layer II stellate and layer III pyramidal cells of the medial EC.
2-Amino-5-phosphonovalerate↗
Apnoea of prematurity and changes in cerebral oxygenation and cerebral blood volume.
The aim of this study was to analyse the behaviour of cerebral oxygenation and cerebral blood volume (CBV) in preterm infants during apnoea by means of near-infrared spectroscopy (NIRS). The sum of oxygenated and deoxygenated haemoglobin, the total cerebral haemoglobin (Hbtot) corresponds to CBV, whereas the difference of oxygenated minus deoxygenated haemoglobin (HbD) represents a value for cerebral oxygenation. During 2 hours of daytime sleep, 72 polygraphic tracings (including NIRS) were done in 58 premature infants. The main criteria for study entry were clinically evident episodes of apnoeas and prematurity. According to their length, apnoeas were divided into two groups: apnoeas of 5-14 seconds (Group 1) and apnoeas > or = 15 seconds (Group 2). Periodic breathing was excluded from analysis. A total number of 1345 apnoeas in Group 1 and 74 apnoeas in Group 2 were recorded, 647 (46%) fulfilled criteria for further analysis. We observed different patterns of CBV behaviour, but the majority, namely 94% in Group 1 and 87% in Group 2, showed a decrease of CBV during apnoea. There was always a cerebral deoxygenation (decrease in HbD) in association with apnoeas, which was significantly increased in apnoeas of longer duration.
Analysis of Variance↗