[Local therapy of chronic synovitis].
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Chronic Disease↗
Biomedical subjects
W Müller
Publications and source records attributed to W Müller.
T helper cell membranes promote IL-4-independent expression of germ-line C gamma 1 transcripts in B cells.
Studies using plasma membranes from activated Th cell clones (Th membranes) to stimulate B cells have shown that both a contact-mediated activation signal plus Th-derived cytokines are required for antibody production. In order to clearly separate and define the role of these two signals in isotype switching, B cells were stimulated with Th membranes in the presence or absence of cytokines, and the transcriptional activity of the unrearranged H chain loci was determined. In the presence of Th membranes, two known switch factors were shown to specifically induce germ-line transcription of the same H chain loci as in LPS-stimulated B cells (IL-4 induced C gamma 1 and C epsilon transcription, transforming growth factor-beta induced C alpha transcription). The contact-mediated activation signal provided by the Th membranes, in the absence of any added cytokines, resulted in the specific induction of C gamma 1 germ-line transcription, and thus functioned as a switch signal for IgG1. These findings provide a mechanism for previously observed IL-4-independent isotype switching to IgG1.
Animals↗
Expression of transforming growth factor-alpha in gastric carcinoma and normal gastric mucosa cells.
The presence of transforming growth factor-alpha (TGF-alpha) was studied in a total of 120 consecutive patients with gastric carcinomas. This immunohistochemical study found TGF-alpha expression in 60% (n = 72) of carcinomas. It also was detected in normal gastric epithelial mucosa in 36% (n = 43) of specimens. There was no significant statistical correlation between TGF-alpha expression and clinical features (e.g., patient age and sex) or pathologic features (e.g., tumor stage, grade, and localization or growth pattern according to an earlier histologic classification). Expression of TGF-alpha by these tumor cells had no influence on prognosis. It was neither a histopathologic marker of high malignancy nor a useful prognostic tool. It had no influence on the invasive growth pattern of gastric carcinoma.
Female↗
A critical role of lambda 5 protein in B cell development.
The lambda 5 gene is a homolog of immunoglobulin J lambda-C lambda genes, expressed specifically in immature B-lineage cells. Lambda 5-encoded molecules form membrane complexes with mu or D mu proteins in association with an additional protein specifically expressed in immature B cells that is encoded by the Vpre-B gene. We have generated mice in which the lambda 5 gene is inactivated by targeted gene disruption in embryonic stem cells. In these mice, B cell development in the bone marrow is blocked at the pre-B cell stage. However, the blockade is leaky, allowing B cells to populate the peripheral immune system at a low rate. These cells are allelically excluded and able to respond to antigen.
Animals↗
[Gallstone ileus--still a current disease].
Two cases of gall-stone ileus during the past months have encouraged us to discuss the epidemiology, pathogenesis, diagnosis and therapy. This pathology is not as rare as one thinks and represents 23% of cases of mechanical ileus of the small intestine in patients over 65 years of age, thus being the third cause after stenosis due to carcinoma and incarcerated hernia. The importance of this illness is due to two factors: the diagnostic difficulties because of a periodic symptomatology with often a lack of typical radiologic signs and the still important mortality of 5 to 10% today. We present the casuistic of seven cases which have occurred over the last 15 years in our hospital and compare our experience with those of the literature. We discuss the therapeutic problem of enterolithotomy or one-stage repair. The main point for a reduction in mortality is an early diagnosis with the consequent reduction of the time from the appearance of the ileus to the operation.
Aged↗
Complete nucleotide sequence of band 3 related anion transport protein AE2 from human kidney.
The cDNA coding for the complete human band 3 related anion exchange protein AE2 has been cloned from human kidney mRNA. The protein is encoded by a mRNA of approx. 3885 nucleotides containing an open reading frame of 3720 nucleotides. The AE2 protein consists of 1240 amino acid residues and has a molecular mass of 136,805 Da.
Amino Acid Sequence↗
[Interleukin-6 (IL-6), soluble interleukin-2-receptor (sIL-2R) and microheterogeneity of alpha-! acid glycoprotein (AGP): new markers of the acute-phase reaction?].
Cytokines and the different glycosylation profiles of some acute phase proteins appear to be of great value in investigating the activity of inflammatory rheumatic diseases. Using an ELISA to measure the serum concentration of sIL-2R and IL-6 and an affinity electrophoresis with Concanavalin A as a lectin to determine the microheterogenity of the alpha-1-acid-glycoprotein (AGP), we tested the sera of 63 patients with various rheumatic and infectious diseases and 17 healthy persons and compared the results with the usual markers of inflammation, e.g. erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and with the clinical activity of the disease. ESR, CRP and sIL-2R were significantly elevated (p less than 0.001) in seropositive rheumatoid arthritis (RA) and in acute bacterial infection. ESR and CRP showed a better correlation with the clinical activity of RA than sIL-2R. Marked elevation of IL-6 was found only in 30% of RA patients in the early stage of the acute phase reaction (APR). The AGP reactivity coefficient (AGP-RC) was significantly decreased in RA (p less than 0.01) but increased in bacterial infections (p less than 0.001). Our results show that there is no advantage in measuring sIL-2R in the routine diagnosis of rheumatic diseases. Raised IL-6 levels seem to indicate an early stage of APR. If ESR and CRP are elevated, the AGP-RC helps to differentiate between infection and chronic inflammatory rheumatic diseases.
Acute-Phase Reaction↗
Analysis of cytokine mRNA levels in interleukin-4-transgenic mice by quantitative polymerase chain reaction.
Interleukin (IL)-4-transgenic mice were used as a model system to study the consequences of low levels of IL-4 expression for the expression of other cytokines examined by quantitative polymerase chain reaction (PCR). For this purpose, a plasmid was constructed which contains, in tandem array, 5' and 3' primer sequences specific for the cytokine genes IL-1 to IL-6, tumor necrosis factor (TNF), lymphotoxin (LT), interferon (IFN)-gamma and beta-actin. During co-amplification, target and control DNA compete for the primers and the amount of PCR product is proportional to the amount of input DNA. Competitive PCR was performed first to adjust the cDNA to be compared to identical concentrations of beta-actin cDNA and subsequently to determine cytokine mRNA levels from spleen cells of normal and IL-4-transgenic animals. The sensitivity of this approach was demonstrated by the capability to detect a twofold difference in IL-4 mRNA levels between IL-4-transgenic heterozygous and homozygous animals. Upon lipopolysaccharide activation, the IL-4 transgene which is expressed essentially in B lymphocytes was induced approximately 50-fold. Several cytokine mRNA such as those coding for IL-5, IL-6, IFN-gamma and also the IL-4 receptor were found to be up-regulated in IL-4-transgenic mice, whereas IL-1, IL-2, IL-3, TNF and LT mRNA levels did not seemed to be influenced by IL-4. A possible functional significance of the elevated IFN-gamma mRNA was demonstrated by showing that (a) CD23 expression was not increased, and (b) Mac-1+ cells were markedly increased in the spleen of transgenic mice.
Animals↗
Evaluation of the genotoxic potential of sorbic acid and potassium sorbate.
The genotoxic potential of sorbic acid and potassium sorbate was investigated in vivo and in vitro. Oral administration of sorbic acid (up to 5000 mg/kg body weight) did not induce sister chromatid exchanges or the formation of micronuclei in bone marrow cells of mice. Intraperitoneal treatment of rats with 400-1200 mg potassium sorbate/kg body weight did not alter the elution profile of DNA from isolated liver cells in the in vivo alkaline elution assay. Sorbic acid did not induce DNA repair in cultured human A549 cells in the unscheduled DNA synthesis (UDS) assay. In vitro incubation of the cells with 1-1000 micrograms potassium sorbate/ml, in the absence or presence of rat liver homogenate, did not result in the formation of DNA single-strand breaks in the alkaline elution assay. These results demonstrate that sorbic acid and its potassium salt are not genotoxic in vivo or in vitro. In contrast to sorbic acid and potassium sorbate, sodium sorbate is very sensitive to oxidative degradation; the main oxidation product was identified to be 4,5-oxohexenoate, which was mutagenic in the Ames test.
Administration, Oral↗
Collaborative study of mutagenicity with Salmonella typhimurium TA102.
Thirty compounds of various chemical classes were investigated for mutagenicity in a collaborative study (3 laboratories) using Salmonella typhimurium TA102. With 5 compounds, namely hydrazine sulfate, phenylhydrazine, hydralazine, glutardialdehyde and glyoxal, mutagenicity was detected by all laboratories. Formaldehyde was assessed as weakly mutagenic in only 1 of 3 laboratories. The remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite of the overall good qualitative agreement in the mutagenicity results between the 3 laboratories some quantitative discrepancies occurred in the dose response of the mutagenic compounds. Varying inter- and intra-laboratory differences in the spontaneous rate of revertants were obtained. The usefulness of the tester strain TA102 in routine mutagenicity testing is discussed.
Evaluation Studies as Topic↗
Ca2+ signalling in postsynaptic dendrites and spines of mammalian neurons in brain slice.
Postsynaptic Ca2+ changes are involved in control of cellular excitability and induction of synaptic long-term changes. We monitored Ca2+ changes in dendrites and spines during synaptic and direct stimulation using high resolution microfluorometry of fura-2 injected into CA3 pyramidal neurons in guinea pig hippocampal slice. When driven by current injection from an intracellular electrode or with synaptic stimulation, postsynaptic Ca2+ accumulations were highest in the proximal dendrites with a pronounced fall-off towards the soma and some fall-off towards more distal dendrites. Muscarinic activation by low concentrations of carbachol strongly increased intradendritic Ca2+ accumulation during directly-evoked repetitive firing. This enhancement occurred in large part because muscarinic activation suppressed the normal Ca(2+)-dependent activation of K-channels that mediates adaptation of firing. Repetitive firing of cholinergic fibers in the slice reproduced the effects of carbachol. Inhibition of acetylcholine-esterase activity by eserine enhanced the effects of repetitive stimulation of chlolinergic fibers. All effects were reversible and were blocked by the muscarinic antagonist atropine. Ca2+ accumulations in postsynaptic spines might be the basis of specificity of synaptic plasticity. With selective stimulation of few associative/comissural fibers, Ca2+ accumulated in single postsynaptic spines but not in the parent dendrite. With strong stimulation, dendrite levels also increased but spine levels were considerably higher. The NMDA-receptor antagonist AP-5 blocked Ca(2+)-peaks in spines, but left Ca2+ changes in dendrite shafts largely unaffected. Sustained steep Ca2+ gradients between single spines and the parent dendrite, often lasting several minutes, developed with repeated stimulation. Our results demonstrate a spine entity that can act independent from the dendrite with respect to Ca(2+)-dependent processes. Muscarinic augmentation of dendritic Ca2+ levels might reduce diffusional loss of Ca2+ from hot spines into the parent dendrite, thus supporting cooperativity and associativity of synaptic plasticity.
Animals↗
Differentiation of oxytalan fibres from elastic fibres with reagents for detection of magnesium.
Elastic fibres in various human and animal tissues revealed positive results with reagents for the detection of magnesium. By contrast, no Mg could be detected in oxytalan fibres or in zonular fibres of the ciliary body, which are composed of microfibrils not containing elastin. Mg is therefore concluded to be associated with the elastin core of elastic fibres. Its antagonism to calcium is speculated to play a protective role in maintaining the extensibility of elastin.
Animals↗
[Muscle relaxation with no effect on oxygen uptake during isoflurane anesthesia?].
To determine the effects of vecuronium neuromuscular blockade on O2 consumption (VO2) during isoflurane anaesthesia 12 patients were studied. 12 patients (ASA-PS I-II, 37.1 +/- 12.1 yr, 173 +/- 8 cm, 70.1 +/- 8.6 kg), scheduled for urological lower abdominal surgery, received isoflurane-N2O-O2-anaesthesia under steady-state conditions (1.3 MAC). Duration of anaesthesia was 169 +/- 32 min and 0.057 +/- 0.016 mg/kg/h vecuronium were needed. The desired level of neuromuscular transmission was set to 10% of control. This level of neuromuscular blockade was kept constant for 60 min by a negative feedback controlled infusion of vecuronium. VO2 was measured by an indirect calorimetry device (MMC Horizon, STPD). During and after recovery of neuromuscular function anaesthesia was maintained and oxygen measurements were continued. Preanaesthetic values of VO2 were in the predicted range for basal metabolism. Steady-state general anaesthesia lead to an 26-28% reduction of VO2 (Range: 144-232 ml/min) compared to the preanaesthetic values (202-288 ml/min, p < 0.01). Neuromuscular blockade showed no significant effect on O2 uptake. We conclude that in patients with adequate depth of anaesthesia vecuronium-induced neuromuscular blockade does not lead to a further reduction of oxygen consumption, since muscular tone is already reduced by general anaesthesia.
Abdomen↗
[Instruments and treatment principle of ultrasound osteotomy in mouth, jaw and facial surgery].
Ultrasonic instruments, technical principles and characteristics of ultrasonic osteotomy are presented. The clinical value is assessed. A software for 3D-reconstruction of tomographic pictures on personal computers is used for better planning of surgical operations.
Animals↗
Long-term consequences of interleukin-6 overexpression in transgenic mice.
With the aim of using interleukin-6 (IL-6)-inducible promoters to express transgenes, we investigated the long-term consequences of high levels of IL-6 in mice. As a first step, we generated transgenic mice constitutively expressing the murine IL-6 at a level sufficient to induce IL-6-responsive genes. These mice were analyzed with respect to the indirect and direct consequences of elevated IL-6 expression over a time period of about 2 years. Although biologically active IL-6 was expressed from the transgene and different alterations could be documented (less immature B cells in bone marrow, expression of IL-6-inducible liver genes), the mice appeared healthy and could easily be used for breeding. Only in mice older than 18 months did we find a high incidence of lymphomas associated with different tissues. These results indicate that the side effects of long-term treatment with IL-6 are relatively moderate, and that IL-6 might be used to mediate the expression of heterologous genes in the context of functional studies.
Acute-Phase Proteins↗
Extracorporeal membrane oxygenation without ligation of the carotid artery: use in two neonates.
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Bacterial Infections↗
Specific involvement of Ca(2+)-calmodulin kinase II in cholinergic modulation of neuronal responsiveness.
1. Muscarinic agonists when applied in the hippocampus at low concentrations suppress intrinsic controls on neuronal excitability through the block of Ca(2+)-activated K conductance(s), gK (Ca), underlying the adaptation of firing and slow afterhyperpolarization (sAHP) in CA1 and CA3 neurons. Carbachol, for example, is effective at 0.1-0.3 microM suggesting activation of a relatively high-affinity receptor. 2. We have examined the mechanism of this action by using a new, highly specific, peptide inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) as well as other kinase inhibitors and show that the muscarinic block of gK (Ca) relies on CaMKII activation in both CA1 and CA3 neurons. Thus phosphorylation of these channels or of an intermediary protein causes the channels to remain closed in the presence of Ca2+ and depolarization. 3. The very similar electrophysiological effects of serotonergic and glutamatergic agonists are mediated either through other kinases or by entirely different processes. 4. Block of intrinsic phosphatase activity by okadaic acid also reduced adaptation and sAHP, and muscarinic agonists had no further effect on these quantities. 5. The removal of presynaptic cholinergic inputs to the hippocampus in animals has a deleterious effect on the performance of tasks requiring spatial memory and is also implicated as a cause of cognitive disorders in humans. By increasing Ca2+ accumulation during electrical activity and promoting CaMKII activity, muscarinic input provides parallel reinforcing pathways for the induction of long-term potentiation, an important cellular memory mechanism. This suggests a possible link between behavioral and cellular approaches to the analysis of learning and memory.
Adaptation, Physiological↗
Soluble interleukin-2 receptors in children with juvenile chronic arthritis.
Concentrations of interleukin-2 receptors were studied in sera of 81 patients with pauciarticular-, polyarticular-, and systemic-onset juvenile chronic arthritis using a double antibody "sandwich" enzyme-linked immunosorbent technique. Serum concentrations were significantly increased in all subgroups when compared with the healthy controls. Higher concentrations were found in systemic onset disease than in pauci- or polyarticular onset disease. Serum levels were found to be increased in both inactive and active disease, showing maximal values in patients with systemic features. A correlation to C-reactive protein, alpha 1-acid glycoprotein, and erythrocyte sedimentation was observed. Increased sIL-2R values suggest disease activity despite the absence of clinical symptoms.
Acute-Phase Proteins↗