Search PubMed⌕ Search

Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 1,261 records · Page 70Linked to original sources
PubMed1986

[Therapy of primary resistant or recurrent small cell bronchial carcinoma with vindesine and ifosfamide].

A combination of vindesine (3 mg/m2, day 1) and ifosfamide (60 mg/kg, days 1-5 + Mesna) was administered every three weeks to 11 patients with primary resistant and 23 with recurrent small-cell bronchial carcinoma. All patients had been pre-treated with chemotherapy, 16 in addition with radiotherapy. At the onset of the vindesine-ifosfamide treatment the cancer was in a localized regional stage in ten patients, while in 24 it was in a more widely spread stage. In 29 patients whose treatment results could be evaluated the remission rate was 38%, with two complete and nine partial remissions. In a further eight patients the cancer was arrested. The patients with complete remission (for 46 and 53 weeks, respectively), those with partial remission (median of 39 weeks) and those with stationary disease (median of 31 weeks) survived significantly longer than those with progressing disease (13 weeks). There was no correlation between treatment result and pre-treatment. On recurrence after complete remission or in the localized regional stage the remission rate was 70% and 60%, respectively, and the survival time was extended in 90% of cases. In addition to nausea, alopecia and myelosuppression, side-effects included vomiting, reversible CNS symptoms, polyneuropathy and urotoxicity. On the basis of acceptable toxicity, combined vindesine and ifosfamide constitute an effective treatment of otherwise treatment-refractory cases of small-cell bronchial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Quantification of ATP-producing and consuming processes of Ehrlich ascites tumour cells.

ATP production of Ehrlich ascites tumour cells was estimated on the basis of their coupled respiration and lactate formation. ATP-consuming processes were assessed from the effects of selective inhibitors of RNA synthesis, protein synthesis and proteolysis, Na+/K+-ATPase on respiration. The extent of protein synthesis and proteolysis were also determined directly. From these values and those of the inhibition of respiration by selective inhibitors, a P/O ratio of 2.2 was calculated. About 75% of the total ATP consumption could be assigned to specific processes. The major ATP-consuming processes of tumour cells in an amino-acid-enriched medium, in which they are in an approximate steady state, are protein synthesis with about 30% of total ATP consumption, and Na+/K+-ATPase with about 20%, while RNA synthesis, ATP-dependent proteolysis and Ca2+-ATPase contribute about 10% each. In an amino-acid-free glucose medium, protein synthesis is reduced to a third, with a corresponding decrease of respiration, whereas the rate of the other ATP-consuming processes is unchanged.

Adenosine Triphosphatases↗
PubMed1986

Iodinated photoreactive vasopressin antagonists: labelling of hepatic vasopressin receptor subunits.

To identify and characterize V1 vasopressin receptors, photoreactive antagonists of the glycogenolytic and vasoconstrictor activity of vasopressin have been synthesized. The following analogues with 3-mercapto-3,3-cyclopentamethylene-propionic acid (Mca) and N-methylalanine (MeAla) in position 1 and 7 of vasopressin (VP) were effective V1 antagonists: [Mca1, D-Tyr2, MeAla7, Lys8]VP (1), [Mca1, MeAla7, Arg8, Lys9]VP (2), [Mca1, MeAla7, Arg8, D-Lys9]VP (3). Introduction of the photoreactive 4-azidophenylamidino group into the side-chain of Lys8 in analogue 1 or into Lys9 in analogues 2 and 3 increased the potency (for analogue 1 a tenfold increase in the antiglycogenolytic effect and a fivefold increase in the antivasopressor effect) and binding affinity for the rat hepatic V1 receptor. Mono-iodination at Tyr2 with 125I resulted in photoreactive antagonists of high specific radioactivity, which had roughly the same binding affinity as vasopressin for the rat hepatic V1 receptor (Kd = 0.9-1.8 nM). In photoaffinity labelling experiments with purified rat liver membranes, containing 2--3 pmol V1 receptor/mg protein, the analogues labelled specifically two proteins with the relative molecular masses (Mr) of 30,000 and 38,000. These results and the results of a recent study using 3H-labelled photoreactive vasopressin agonists [Boer, R. and Fahrenholz, F. (1985) J. Biol. Chem. 260, 15051-15054] provide evidence that both vasopressin agonists and antagonists can interact with the same two subunits of the heterodimeric hepatic V1 receptor. Furthermore the radioiodinated photoreactive V1 antagonists should be helpful to identify V1 receptor proteins in membranes of other cell types.

Affinity Labels↗
PubMed1986

[Thyrotropin-displacing antibodies in thyroid gland diseases].

Thyroid-stimulating antibodies were assayed in 798 patients with thyroid diseases and 122 controls by means of a heterologous radioreceptor assay as thyrotropin displacement activity (TDA). With an intraassay variance of 5-6% and an interassay variance of 8-13% in higher TDA values, test results were well reproducible. Thus, TDA assay is suitable for routine testing and follow-up of titers in the upper range. With only few exceptions TDA values of F greater than or equal to 11% are found exclusively in Graves' disease (sensitivity 39.2%; specificity vs other thyroid diseases 99.7%). In patients with functional autonomy in nodular goitre (Plummer's disease) TDA is consistently negative. TDA measurement is a valuable means for the detection of Graves' disease and for differential diagnosis of hyperthyroidism of undetermined pathogenesis.

Antibodies↗
PubMed1986

Spontaneous vesiculation of aqueous lipid dispersions.

The swelling properties of lipid mixtures consisting of phosphatidylcholine and a charged single-chain detergent have been studied. The work presented here is confined to lipid mixtures forming smectic lamellar phases in H2O. These mixtures exhibit continuous swelling with increasing water content, provided the surface charge density exceeds a threshold value of about 1-2 microC/cm2. In excess H2O, such mixtures undergo spontaneous vesiculation: unilamellar vesicles form spontaneously when excess H2O or salt solutions of moderate ionic strength (I less than 0.2) are added to the dried film of such lipid mixtures. The resulting dispersion of unilamellar vesicles is usually polydisperse. Its average size depends on the detergent/phospholipid mole ratio, decreasing with increasing detergent content. It is shown that in the phase diagram of three-component systems consisting of phosphatidylcholine, a charged single-chain detergent, and excess H2O there is a compositional range, though narrow, within which the small unilamellar vesicle (diameter less than 100 nm) is the thermodynamically most stable structure. This behavior is characteristic of charged, single-chain detergents of 14 and more C atoms. Many pharmacologically active compounds are amphiphilic and surface-active, and as such, they will orient at phospholipid-water interfaces, imparting a net surface charge to neutral lipid surfaces. It is shown that such drugs exhibit detergent-like action. Mixed films of phosphatidylcholine and a pharmacologically active compound behave similarly to phosphatidylcholine-detergent mixtures: they undergo spontaneous vesiculation when excess H2O or salt solutions of moderate ionic strength are added. In this case, the drug itself induces vesiculation; possible pharmacological implications of this finding are discussed.

Lipid Bilayers↗
PubMed1986

Kinetics of 125I-ubiquitin conjugation with and liberation from rabbit reticulocyte stroma.

The breakdown of mitochondria-containing stroma of rabbit reticulocytes is an ATP- and ubiquitin-dependent process and there is no evidence for an ATP-dependent but ubiquitin-independent proteolysis in these cells. The ubiquitin conjugate formation with heat-denatured stroma proteins is about one-fifth of that with native stroma. In reticulocytes there exist two mechanisms of ubiquitin liberation from its conjugates with stroma proteins: an ATP-dependent and hemin-resistant release of ubiquitin, which is assumed to be the first step in the degradation of ubiquitin conjugates by the protease system, and a release of ubiquitin catalyzed by an isopeptidase activity.

Adenosine Triphosphate↗
PubMed1986

Lectin binding sites in Paramecium tetraurelia cells. I. Labeling analysis predominantly of secretory components.

Though all three lectins tested (ConA, RCA II, WGA) bound to the entire cell membrane, none bound selectively to the docking site of secretory organelles (trichocysts); the same results were achieved with FITC-conjugates, or, on the EM level, with peroxidase- or gold-labeling. Only WGA triggered the release of trichocysts and none of the lectins tested inhibited AED-induced synchronous exocytosis. When exocytosis was triggered synchronously in the presence of any of these three lectins (FITC-conjugates), the resulting ghosts trapped the FITC-lectins and the cell surface was immediately afterwards studded with regularly spaced dots (corresponding to the ghosts located on the regularly spaced exocytosis sites). These disappeared within about 10 min from the cell surface (thus reflecting ghost internalization with a half life of 3 min) and fluorescent label was then found in approximately 6-10 vacuoles, which are several microns in diameter, stain for acid phosphatase and, on the EM level, contain numerous membrane fragments (otherwise not found in this form in digesting vacuoles). We conclude that synchronous massive exocytosis involves lysosomal breakdown rather than reutilization of internalized trichocyst membranes and that these contain lectin binding sites (given the fact free fluorescent probes did not efficiently stain ghosts). Trichocyst contents were analyzed for their lectin binding capacity in situ and on polyacrylamide gels. RCA II yielded intense staining (particularly of "tips"), while ConA (fluorescence concentrated over "bodies") and WGA yielded less staining of trichocyst contents on the light and electron microscopic level. Only ConA- and WGA-staining was inhibitable by an excess of specific sugars, while RCA II binding was not. ConA binding was also confirmed on polyacrylamide gels which also allowed us to assess the rather low degree of glycosylation (approximately 1% by comparison with known glycoprotein standards) of the main trichocyst proteins contained in their expandable "matrix". Since RCA II binding could be due to its own glycosylation residues we looked for an endogenous lectin. The conjecture was substantiated by the binding of FITC-lactose-albumin (inhibitable by a mixture of glucose-galactose). This preliminary new finding may be important for the elucidation of trichocyst function.

Animals↗
PubMed1986

Disintegration of nucleoskeletal elements by metrizamide/2 M salt isopyknic centrifugation.

Supramolecular structures that remain bound to chromosomal DNA under high salt conditions are believed to anchor DNA in the interphase nuclear skeleton. In order to identify these anchorage structures, the non-DNA materials that remain firmly bound to chromosomal DNA under conditions that disintegrate the high salt-stable architecture of nuclei were investigated. Nuclei of Ehrlich ascites cells were histone-depleted by treatment with 2 M salt. The residual halo structures were gently sheared and subjected to metrizamide isopyknic centrifugation in the presence of 2 M salt. By this combined treatment the high salt stable nuclear skeleton becomes disintegrated and three main fractions are resolved. A light fraction comprises the DNA which appears to be essentially depleted of other nuclear components. The only non-DNA material that could be identified in the DNA band is a fraction of (nascent) RNP. No other materials which could reflect nucleoskeletal elements (e.g. lamina proteins) were found together with DNA. A peak of intermediate density comprises RNA/RNP dissociated from DNA. The heavy fraction contains the proteins that become dissociated from DNA by high-salt and/or centrifugal forces, e.g. histones and the major nuclear lamina proteins. The results indicate that nascent RNP is more tightly bound to chromosomal DNA than other components that may be involved in nuclear skeletons. This suggest that transcription complexes represent at least one type of anchorage structure of DNA, which is consistent with results indicating that nascent RNA and actively transcribed DNA sequences are preferentially retained in high-salt-treated nuclei.

Animals↗
PubMed1986

A human lymphokine released by mononuclear blood cells upon contact with CEA.

As revealed by the macrophage electrophoretic mobility (MEM) technique mononuclear blood cells from certain cancer patients respond to carcinoembryonic antigen (CEA). This phenomenon appeared to be due to a specific lymphokine release. In this study, the lymphokine activity of supernatant pools was stepwise enriched by gel filtration on Sephadex. The mediator activity was recovered within a molecular mass region less than 47 kDA. The lymphokine was highly enriched during further gel filtration steps and showed a single activity peak in the molecular mass region of 23.5 kDa. Gel filtrations of appropriate control supernatants resulted in biologically inactive fractions. The lymphokine was heat-labile at 56 degrees C, showed a clear-cut, dose-dependent effect on macrophages, and could be blocked by fucose. Preparative gel electrophoresis of radiolabeled and unlabeled lymphokine resulted in two corresponding peaks of biological activity and radioactivity.

Carcinoembryonic Antigen↗
PubMed1986

Glycerol, a metabolic end product of Trichomonas vaginalis and Tritrichomonas foetus.

Glycerol was demonstrated as an end product of anaerobic glucose metabolism in Trichomonas vaginalis and Tritrichomonas foetus, produced in addition to acetate, H2, CO2, and lactate or succinate. In T. vaginalis strain C-1, glycerol amounted to 16% of the fermentation products and was formed at an average rate of 38 nmol min-1 (mg protein)-1. Corresponding figures for T. foetus strain KV1 were 7% and 4.8 nmol min-1 (mg protein)-1. The amounts of glycerol detected compensated almost exactly for the deficits in fermentation products recognized earlier, thus complete redox balances can now be provided for both organisms. The metronidazole-resistant T. foetus strain KV1-1MR-100 excreted only negligible amounts of glycerol and carried out an ethanol-CO2 fermentation. Aerobiosis hardly affected glycerol formation in T. vaginalis strains C-1 and NYH 286, but almost completely abolished it in T. foetus strain KV1. An NADP-dependent glycerol 3-phosphate dehydrogenase and a Mg2+-dependent glycerol 3-phosphatase were detected in the cytosol of both species. The phosphatase is distinct from the particle-bound nonspecific acid phosphatase. Glycerol kinase activity was not detected in either organism. Enhanced pCO2 did not affect the ratio of fermentation products in T. vaginalis strain C-1, but significantly increased the amount of succinate, and decreased the amounts of acetate, H2, and CO2, formed by T. foetus.

Aerobiosis↗
PubMed1986

Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes.

Hydrogenosomes isolated from Tritrichomonas foetus and Trichomonas vaginalis fermented pyruvate to acetate, malate, H2, and CO2 in an anaerobic process dependent on ADP, Pi, Mg2+, and succinate. The extent to which pyruvate was carboxylated to malate by malate dehydrogenase (decarboxylating) rather than decarboxylated to acetate by pyruvate/ferredoxin oxidoreductase was dependent on pCO2. The processes observed showed carbon and redox balances. The presence of an NADH/ferredoxin oxidoreductase activity was demonstrated. This enzyme is likely to be involved in the transfer of electrons from the ferredoxin reduced in pyruvate oxidation to NAD+ needed for the reductive carboxylation of pyruvate. Disruption of hydrogenosomes with Triton X-100 led to cessation of pyruvate-dependent H2 formation which could be restored by addition of coenzyme A and methyl viologen or ferredoxin. The formation of acetate and H2 by undisrupted hydrogenosomes proceeded at approximately half maximal rates in the presence of 25 microM succinate for T. foetus and 5 microM succinate for T. vaginalis. The apparent Km value of the acetate/succinate CoA transferase from T. foetus for succinate was approximately 45 microM, thus the stimulating effect of succinate might be due to the requirement of this enzyme for succinate. The exact mechanism of this effect remains to be elucidated, however.

Acetates↗
PubMed1986

The heterogeneity of the nucleus raphes dorsalis in albino rats. A fluorescence histochemical and microelectrophoretic study.

In albino rats, the nucleus raphes dorsalis (NRD) of the midbrain was investigated using a sensitive fluorochroming procedure to detect indolamines in combination with a microelectrophoretic method to demonstrate the isoenzyme pattern of acetylcholinesterase (AChE). Based on the fluorescence histochemical appearance, 3 types of indolaminergic cells were identified in the various areas of the NRD. According to data of the literature and in agreement with our own results, the morphological heterogeneity of the NRD was shown. Significant differences of AChE specific zymograms of NRD regions (subgroups) demonstrate that organization of NRD is heterogeneously proved not only by morphological results but also in respect of enzyme constitution.

Acetylcholinesterase↗
PubMed1986

On the surface lattice of microtubules: helix starts, protofilament number, seam, and handedness.

The tubulin monomers of brain microtubules reassembled in vitro are arranged on a 3-start helix, irrespective of whether the number of protofilaments is 13 or 14. The dimer packing is that of the B-lattice described for flagellar microtubules. This implies that the tubulin core of microtubules contains at least one helical discontinuity. Neither 5-start nor 8-start helices have a physical significance and thus cannot be implicated in models of microtubule elongation, but the structure is compatible with elongation of protofilaments by dimers or protofilamentous oligomers. The inner and outer surfaces of the microtubule wall can be visualized by propane jet freezing, freeze fracturing, and metal replication, at a resolution of at least 4 nm. The 3-start helix is left-handed, in contrast to a previous study based on negative staining and shadowing. The reasons for this discrepancy are discussed.

Cytoskeleton↗
PubMed1986

In vitro drug susceptibility and doses of metronidazole required for cure in cases of refractory vaginal trichomoniasis.

There are currently no laboratory or clinical guidelines for the identification and treatment of disease caused by metronidazole-resistant strains of Trichomonas vaginalis. Fifty-three isolates of T. vaginalis from cases of refractory vaginitis in the United States (26 states) and Canada were tested for aerobic and anaerobic metronidazole susceptibility, and after various dosages of metronidazole, the therapeutic outcomes were evaluated for 31 of these cases. The mean aerobic metronidazole susceptibility of these isolates was 195.5 micrograms/ml (range, 12.5-greater than 1,000), which was about eightfold higher than that seen in isolates that were not resistant to metronidazole. The mean anaerobic susceptibility was 5 micrograms/ml (range, 1.6-25), which was about threefold higher than that of isolates from nonresistant strains. The average aerobic-to-anaerobic ratio of metronidazole susceptibility in the highly resistant isolates was more than 3.5-fold greater than that seen in the nonresistant isolates. White women accounted for 88% of the resistant infections. Of 31 cases that were re-treated and monitored, the highest average dose that failed to achieve a cure was 2.1 g of metronidazole/day given over an eight-day period; 27 (87%) of 31 cases were ultimately cured with an average dosage of 2.6 g of metronidazole/day given over a mean period of nine days. Resistance to treatment with metronidazole varied from mild to severe, and the resistance was occasionally more severe than the susceptibility values indicate.

Adolescent↗