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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 451 records · Page 25Linked to original sources

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↗

[Massive iodine absorption after joint irrigation-suction drainage with PVP-iodine (betadine)].

Iodine is known as a local disinfectant substance for more than 100 years. Its use however was restricted due to strong local irritation. In the last 25 years Polyvinylpyrrolidon-Iodine solutions (Povidone-Iodine, PVP-Iodine, Betadine) has become more and more popular for treating traumatologic, surgical and orthopaedic infections. However several papers have reported changes in the blood chemistry (T3, T4, TSH, PBJ and Iodine excretion in the urine) after utilizing PVP-Iodine, especially in visceral surgery. We report on a patient in whom a massive iodine resorption with clinical signs of hyperthyroidism occurred, with soft tissue necrosis at the site of irrigation.

Adult↗

[Clinical application of biomechanic and functional anatomical findings of the knee joint].

In order to study the functional anatomy of the knee joint, careful anatomical dissections were conducted on over 130 fresh-frozen cadaveric knee specimens. We found no evidence to support the two-bundle and three-bundle theories of cruciate ligament fiber patterns. The longest fibers in the anterior cruciate ligaments (ACL) measured 37 mm, and the longest in the posterior cruciate ligament (PCL), 41 mm. Cruciate ligament insertions follow a transition line on tibia and femur. Usually not all the fibers of the cruciate ligaments are taut at the same time. They are progressively recruited according to the biomechanical demands placed on them. Fibre recruitment in the ACL is from knee flexion to extension and in the PCL from extension to flexion. The concept of fiber recruitment was recently evaluated mathematically. As a working hypothesis, the knee joint can be looked upon as a biological realization of the crossed four-bar linkage, even in three dimensions. In vitro measurements have shown that correct graft placement in cruciate reconstructions is critical for knee biomechanics. Incorrect placement of grafts may lead to decreased range of motion and/or increased laxity. Distance changes of 3 mm between femoral origin and tibial insertion of a graft may lead to a 400% increase of graft preload and will thus easily reach published pull-out forces for some of the graft fixation methods (button = 248 N). Precise drill guides and isometers may be helpful in any operative technique (open, arthroscopic). Using the IKDC evaluation form and the KT-1000 arthrometer, our studies on 25 patients demonstrated a direct correlation between intraoperative graft tracking and the clinical outcome 2 years after operation. Biomechanical studies to investigate in vivo strain patterns of the anterior cruciate ligament and in vitro strain patterns of isometrically placed cruciate graft reconstructions showed that they did not reach critical fixation failure or graft rupture loads. The highest values were measured in Lachman and anterior drawer testing. In the 20-kg Lachman test the maximum load was 96 +/- 6 N. This was twice the maximum loads of any of the quadriceps exercises (40-50 N). With an isometrically placed graft, full active range of motion postoperatively and exercises with isolated or combined contractions of quadriceps and hamstring muscles will result in small graft loads. Postoperative immobilization with plaster and/or protection with braces may therefore become obsolete.

Anterior Cruciate Ligament↗

[Final evaluation of the randomized multicenter study SAKK 40/81: adjuvant portal chemotherapy of curatively resected colorectal cancer].

Between 1981 and 1987, 533 patients from 9 institutions have been entered in a randomized trial to assess the value of adjuvant portal infusion (5-Fluorouracil, Mitomycin C) compared to radical surgery alone. Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group. Estimated 5-year disease-free survival was 52% and 61% respectively (hazard ratio 1:0.75; 95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the control and 69 in the infusion group (p = 0.048). Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate.

Antineoplastic Combined Chemotherapy Protocols↗

[The therapy of swimbladder inflammation (renicola sphaerosporosis) of carp].

In pond experiments the efficiency of different chemotherapy variants against swimbladder inflammation (SBI) was proved. Only by feeding of Fumagillin, specifically affecting Myxosporidians, the infection of kidney with Sphaerospora renicola as well as the force of SBI could be reduced. The chemotherapy with Metronidazole remained inefficacious, whereas the permanent feeding with Methylene blue prevented only the infection with Bothriocephalus acheilognathi and probably lowered insignificantly the breeding-losses on this way. Water-conditioning by means of chloride of lime only lowered the losses caused by gill necrosis, on SBI it had no influence. A relationship between gill necrosis and SBI, that seemed to be possible, could not been corroborated.

Air Sacs↗

[New procedures for resin-metal bonds. A comparative in-vitro study].

Since 1984 it has been possible to create a chemical bond between dental alloys and composite resins resembling the metallo-ceramic bond. Modern systems based on silanization (Rocatec, Silicoater MD, and Spectralink), in connection with the specific resins used in these systems (VisioGem, Dentacolor, and SR-Isosit-N), were tested for their bond strength to 9 common dental alloys (of 7 different types) with regard to shear strength, the topography of the fracture surfaces, and metallographic microstructure transformations. No major structural transformations were observed for any of the systems tested. A notable degree of interdependence was seen in the Silicoater MD system whose bond strength to non-precious alloys (among others) was the lowest in the test. The Rocatec system, on the other hand, showed a superior bond to all types of alloys, especially to pure titanium.

Composite Resins↗

Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation.

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Acute Disease↗

[Judicious use of biological tests in rheumatology].

Among the numerous biologic and immunologic complementary tests the clinician has at his disposal some that document inflammation (ESR, c-reactive protein, complement components, electrophoretic and immunoelectrophoretic profiles) are not specific while others that permit etiologic classification (rheumatoid factor, antinuclear antibodies, genetics of the histocompatibility system, serologic test for microorganisms) are specific but not necessarily related to activity or disease process. None of these tests has absolute diagnostic power. It is therefore important to know their relative clinical significance in order to avoid unnecessary and costly investigations whose interpretation may pose more problems than solve questions.

Antibodies, Antinuclear↗

Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses.

The possibility that postsynaptic spines on neuronal dendrites are discrete biochemical compartments for Ca(2+)-activated processes involved in synaptic plasticity is a widely proposed concept that has eluded experimental demonstration. Using microfluorometry on CA3 neurons in hippocampal slices, we show here that with weak presynaptic stimulation of associative/commissural fibres, Ca2+ accumulates in single postsynaptic spines but not in the parent dendrite. Stronger stimulation also promotes changes in dendrites. The NMDA-receptor antagonist AP-5 blocks changes in Ca2+ in spines. Sustained steep Ca2+ gradients between single spines and the parent dendrite, often lasting several minutes, develop with repeated stimulation. The observed compartmentalization allows for the specificity, cooperativity and associativity displayed by memory models such as long-term potentiation.

2-Amino-5-phosphonovalerate↗

Generation and analysis of interleukin-4 deficient mice.

Interleukin-4 (IL-4) promotes the growth and differentiation of many hematopoietic cells in vitro; in particular, it directs the immunoglobulin (Ig) class switch to IgG1 and IgE. Mice homozygous for a mutation that inactivates the IL-4 gene were generated to test the requirement for IL-4 in vivo. In the mutant mice T and B cell development was normal, but the serum levels of IgG1 and IgE were strongly reduced. The IgG1 dominance in a T cell-dependent immune response was lost, and IgE was not detectable upon nematode infection. Thus, some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo.

Aging↗

[Alpha-1-acid glycoprotein in differential diagnosis of rheumatic diseases].

In recent years, the investigation of acute-phase proteins with the aid of affinity electrophoresis employing lectins as carrier substance, has become ever more important, in particular in the diagnosis of inflammatory rheumatic diseases. In order to investigate the usefulness of a determination of alpha-1 glycoprotein microheterogeneity in the sera as a diagnostic parameter, we evaluated, on a prospective basis, the sera of 85 consecutive patients presenting at our department with various inflammatory rheumatic diseases (chronic rheumatoid arthritis [RA] [n = 22], seronegative spondarthropathies [SpA] [n = 15], polymyalgia rheumatica [PMR] [n = 10], polymyositis dermatomyositis [PM/DM] [n = 8], osteoarthritis [n = 18], and infectious diseases [n = 12]). The results were expressed as reactivity coefficient of the alpha-1 acid glycoproteins (AGP/RC). A significant increase in the AGP/RC was observed in patients with various infections, and in those with RA or SpA with intercurrent infection, as compared with patients with RA or SpA with no intercurrent infection, or in healthy controls. It also proved possible to differentiate between PM/DM and PMR. Determination of the erythrocyte sedimentation rate, and quantification of the C-reactive protein and of alpha-1 glycoprotein, permitted no discrimination between an increase in inflammatory activity related to the basic disease, and an intercurrent bacterial infection. The results show that the determination of qualitative changes in the acute phase proteins, in particular alpha-1 acid glycoproteins, may make it possible to differentiate between inflammatory and infectious diseases. This examination technique may be of future clinical importance.

Adult↗

Most peripheral B cells in mice are ligand selected.

Using amplified cDNA and genomic libraries, we have analyzed the VH gene repertoire of pre-B cells and various B cell subsets of conventional mice at the level of VH genes belonging to the J558 VH gene family. The sequence data were evaluated on the basis of a newly established list of 67 J558 VH genes that comprise approximately two-thirds of the J558 VH genes of the murine IgHb haplotype. The results of the analysis demonstrate that VH gene utilization in pre-B cells, although biased to some extent by B cell autonomous VH gene selection, scatters over the whole range of J558 VH genes present in the germline. In contrast, in mature, peripheral B cells comprising long-lived mu + delta high B cells as well as Ly-1 B cells, small overlapping sets of germline VH genes are dominantly expressed. The data indicate that the recruitment of newly generated B cells into the long-lived peripheral B cell pool is mediated through positive selection by internal and/or external antigens. Because of the absence of immunoglobulin class switching and somatic hypermutation, this process is different from the selection of memory B cells in T cell-dependent immune responses.

Animals↗

Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients.

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.

Antibodies↗