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Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 289 records · Page 16Linked to original sources

[Antiproliferative activity of a highly purified coal tar preparation in comparison with clobetasol-17-propionate].

Coal tar and glucocorticosteroids are among the preparations used for the treatment of hyperproliferative inflammatory dermatosis. Coal tar generally seems to have a better effect on psoriasis capillitii than betamethasone-17-valerate. This finding is confirmed by investigations with human skin fibroblasts. The coal tar preparation Berniter has a strongly inhibitory effect on cell proliferation. The action of the preparation with tar can be clearly distinguished from the effect of the vehicle. At the ED50 concentration of the substance with tar, the vehicle without tar causes no inhibition. Based on weight equivalents Berniter has a greater inhibitory effect on proliferation of human skin fibroblasts than clobetasol-17-propionate. In the case of both substances protein biosynthesis is only affected at concentrations higher than those needed for the inhibition of proliferation. Berniter and the vehicle without tar have an equally strong effect on protein synthesis. Berniter affects the nucleoside triphosphatase bound to the nuclear membrane, and thus influences the nucleocytoplasmic transport of mRNA. The effect of the vehicle and the preparation containing tar on this parameter are very similar. Berniter has a positive effect on cell mobility. In preconfluent cultures the mobility of the cell is slightly increased and in confluent cultures significantly. Our results show that Berniter inhibits proliferation in cell cultures of human skin fibroblasts to a higher degree than clobetasol-17-propionate. It is to be assumed that neither the inhibition of protein synthesis nor the inhibition of mRNA transport play a causal role in the antiproliferative effect of coal tar. Inhibition of proliferation as a result of general damage to the cell can also be practically ruled out.

Adenosine Triphosphatases↗

[Cystadenoma of the pancreas].

We report on a patient with a microcystic adenoma of the head of the pancreas. Cystic neoplasms of the pancreas comprise only about 2% of all exocrine tumours. They can be divided into two distinct groups with different prognoses: the microcystic glycogen containing tumours, which are always benign and the mucinous cystic tumours, the majority of which shows malignant dysplasia. Clinically they manifest as a palpable abdominal mass with unspecific upper abdominal pain. Preoperative diagnosis is difficult to achieve. Computer-tomography and ultrasound are the main radiological facilities that allow some degree of differentiation. During operation a frozen section is mandatory to differentiate between a pseudocyst and a real cyst with epithelial wall. Resection of the tumour is the therapy of choice. The prognosis of the microcystic adenoma is good, the prognosis of the mucinous cystadenoma-cystadenocarcinoma is much better than the prognosis of the adenocarcinoma of the pancreas.

Cystadenoma↗

[Retro- and prospective studies on the value of clinical and laboratory chemical data in acute appendicitis].

In a retrospective study 536 appendicectomized patients were analyzed, in order to identify anamnestic, clinical and laboratory findings which allow the differentiation between acute and non-acute appendicitis. 150 consecutive patients were studied prospectively, which were referred to our department with a presumptive diagnosis of acute appendicitis. Eight single criteria were found, which exhibited a significantly different frequency in acute and non-acute appendicitis. Each criterion showed a low sensitivity and specificity; a score, which was created by combination of these single criteria also had low sensitivity and specificity. We conclude that the correct indication for appendicectomy highly depends on clinical experience of the surgeon.

Acute Disease↗

[Perioperative management of thoracic surgery patients].

Immediate postoperative extubation of patients submitted to chest surgery is possible in almost all cases. The intensive care unit responsible for these patients should have good facilities for bronchoscopy, and the indication for this procedure should be made, postoperatively, on a broad basis. The introduction of peri-operative antibiotic prophylaxis has led to a substantial decline in disturbances of wound healing. Due to the use of autologous blood transfusion, the need for homologous blood transfusions has been reduced significantly.

Aged↗

Tumor promotion and depletion of protein kinase C in epidermal JB6 cells.

Promotion of JB6 epidermal cells to anchorage-independent growth requires exposure to TPA for greater than 4 days. Over a similar time span, a practically complete loss of enzymic and immunoreactive proteinkinase C (PKC) equivalents was observed at greater than 10 nM TPA. Promotion did not appear to require (transient) activation of PKC since PKC inhibitors H7 and HA1004 did not prevent but enhanced colony formation in soft agar at concentrations greater than IC50-values. The efficacy of the inhibitors in vivo was shown by their ability to suppress PKC-induced transcription of c-fos gen. PKC inhibitors that interfered with cell proliferation at lower concentrations than those required for PKC inhibition (sphingosine, staurosporin, sangivamycin, trifluoperazine) did not stimulate anchorage-independent growth. As H7 as well as HA1004 were able to promote JB6 cells in the complete absence of TPA, and induced neither depletion nor processing of PKC we postulate that depletion/inactivation rather than activation of PKC correlates with the promotion of epidermal JB6 cells to anchorage-independent growth.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The construction of new proteins: V. A template-assembled synthetic protein (TASP) containing both a 4-helix bundle and beta-barrel-like structure.

The construction of a template-assembled synthetic protein (TASP) designed to contain both a 4-helix bundle and a beta-barrel as two folding "domains" is described. For the de novo design of proteins, amphiphilic helices (alpha) and beta-sheets (beta) are covalently attached to a template peptide (T) carrying functional side chains suitably oriented to promote intramolecular folding of the secondary structure blocks into a characteristic packing arrangement, i.e., T8-(4 alpha)(4 beta). The design of this new macromolecule was assisted by computer modeling, which suggested a low-energy conformation with tight hydrophobic packing of the secondary structure subunits. Solid-phase synthesis of the "two-domain" TASP molecule was achieved using orthogonal protection techniques. The solution properties as well as circular dichroism (CD) and infrared spectroscopy (IR) data under various experimental conditions are consistent with the folded conformation suggested by modeling.

Chemical Phenomena↗

Animal experiments for the determination of an optimal wavelength for retinal coagulations.

The retina of rabbits was coagulated with different wave-lengths (570-630 nm) using a tunable dye laser with Rhodamin 6G. To achieve comparable ophthalmoscopic appearance the intensity of the laser beam was varied with neutral filters of varying absorption. Histologic examination of fresh coagulation effects and 3-week-old coagulation scars showed no difference in relation to the wave-length used. Theoretically, 577 nm seems to be a particularly useful wavelength for the treatment of a wide variety of retinal lesions because it is not absorbed in xanthophyll and penetrates opacities of the optic media better than argon blue green. Furthermore, it is absorbed maximally in hemoglobin, making it particularly suitable for the coagulation of blood vessels.

Animals↗

Chromatin-bound histone 1 kinase activity in synchronized HeLa S3 cells.

The chromatin-bound H1 kinase activity of HeLa S3 cells that had been synchronized with 2.7 mM thymidine for 24 h has been followed during their progression into mitosis. They were arrested at this stage of the cell cycle by adding 0.13 microM nocodazole 8 h after the removal of thymidine. The kinase was partially purified by extracting chromatin proteins with 0.4 M NaCl and fractionation with ammonium sulfate (17.5-35%), a procedure in which a significant amount of in vivo histone 1 phosphorylating activity was retained. H1 kinase activity increased as the cells entered mitosis, rising to a maximum level sevenfold higher than interphase as the mitotic index reached about 50%. A rapid decrease in activity followed this maximum approximately 2 h after cells started to accumulate in mitosis. At this time, the mitotic index was still increasing, although at a lower rate than during the increase of the kinase activity. Other protein kinase activities measured by using core histones, casein, and protamine as substrates remained fairly constant at a comparatively low level. HeLa H1 kinase activity was further distinguished from several known protein kinase activities by the lack of stimulation or inhibition with known modulators of protein phosphorylating activities.

Calcium↗

Myasthenia gravis associated with multiple sclerosis. Epidemiological survey and immunological findings.

Patient registers on myasthenia gravis (94 patients) and multiple sclerosis (991 patients) from a population of 1.5 million were reviewed to find patients with both diseases. Seven potential candidates were found, but both diagnoses were confirmed in 2 women only. The first patient had also iritis, the second patient had, besides MG and MS, bronchial asthma and polyarthritis. Both neurological diseases had a relatively mild clinical course. Thymectomy relieved MG symptoms in both patients. Cerebrospinal fluid studies during the follow-up indicated immunoactivation within the central nervous system. Changes in cellular immunity were also noted. The HLA types were different. The combination of these two diseases appears to be more common than expected.

Adolescent↗

Motor control in childhood onset dopa-responsive dystonia (Segawa syndrome).

To elucidate the pathophysiological features of childhood onset dopa-responsive dystonia (DRD) we used a variety of quantitative analysis techniques to evaluate aspects of reflex- and voluntary motor control in two brothers with this disorder. The observed patterns were compared with those obtained in patients with adult onset Parkinson's disease (PD) and Huntington's disease (HD). In both brothers onset of the disease was in the first decade. Both responded either to treatment with L-Dopa or a combination of L-Dopa with trihexiphenidyl. Neurophysiological studies revealed slowing of different upper extremity voluntary motor activities and a low frequency postural tremor similar to results in other basal ganglia disorders including PD. In contrast to adult onset PD, fastest isometric voluntary index finger contractions did not show the typical kinetic tremor oscillations superimposed on the force trajectories. Also, different to adult PD, no impairment of stance regulating reflexes or saccadic and smooth pursuit eye movements was found in DRD. Magnetoelectrical stimulation of motor cortex showed normal efferent cortical spinal activity. Data indicate that like in other basal ganglia diseases slowing of voluntary motor activity is also a constant feature in DRD. DRD patients show, however, a clear difference to the pattern of motor abnormalities obtainable in PD. Both the pattern of motor control abnormalities is different, and the longlasting effect. In contrast to PD the pathophysiological mechanism in DRD possibly involves a lack of maturation of dopaminergic substantia nigra neurons rather than a degenerative process.

Adolescent↗

Differential phosphorylation of the nucleoprotein of influenza A viruses.

An analysis of the nucleoprotein (NP) of 29 different influenza A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting of six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent significant changes, indicating subtle phosphorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced in vivo by the specific stimulation of cellular protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7.H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West Nile). Therefore the correct phosphorylation of the NP of influenza viruses appears to be essential for influenza virus replication.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Halothane-induced variability in the neuromuscular transmission of patients with myasthenia gravis.

The purpose of the present clinical study was to explore the skeletal muscle mechano (MMG)- and electromyographic (EMG) responses during halothane/oxygen/air anaesthesia in patients with myasthenia gravis (MG) compared with patients with normal neuromuscular transmission. The majority of MG-patients had a significant decremental response of the evoked muscle action potentials to a train-of-four (TOF) stimulation during halothane exposure (mean decrease of train-of-four ratio was 33% during the highest mean halothane concentration of 1.9 MAC). An excellent correlation was found between MMG- and EMG-measurements (r2 = 0.878, P less than 0.001). However, marked individual variations in the neuromuscular response to halothane were seen. Neither preoperative muscle fatigability nor acetylcholine receptor antibodies predicted the decremental muscle responses produced by halothane among MG-patients. The increased presence of HLA-B8 among myasthenics with halothane-suppressed muscle responses after TOF stimulation could be demonstrated (P less than 0.01).

Adolescent↗

Circulating IgA- and IgM-rheumatoid factors in patients with primary Sjögren syndrome. Correlation to extraglandular manifestations.

IgM- and IgA-rheumatoid factors (RF) were determined by ELISA technique in 40 consecutive patients with primary Sjögren syndrome (primary SS), all fulfilling the Copenhagen diagnostic criteria. Increased concentrations of IgM-RF were found in 25 patients (63%) (median concentration: 85 IU/ml, range 11-302 IU/ml). Increased concentrations of IgA-RF were found in 22 of the patients (55%) (median concentration: 100 AU/ml, range 25-255 AU/ml). The levels of IgM- and IgA-RF were closely correlated (r = 0.82, p less than 0.001). IgM-RF (p = 0.037), but not IgA-RF (p = 0.17), was significantly correlated to the presence of antinuclear antibodies (ANA). In contrast, IgA-RF (p = 0.002), but not IgM RF (p = 0.068), was significantly correlated to the presence of hypergammaglobulinemia. The most common extraglandular manifestations were: arthralgia/synovitis (60%), myalgia/myositis (28%), Raynaud's phenomenon (20%) and pulmonary manifestations (15%). Concentrations of both IgM-RF (r = 0.43, p less than 0.01) and IgA-RF (r = 0.57, p less than 0.001) were correlated to the number of extraglandular manifestations present in each patient.

Adult↗