Search PubMed⌕ Search

Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 1,153 records · Page 64Linked to original sources

CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties.

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.

Alkylation↗

Osteogenesis imperfecta in childhood: cardiac and renal manifestations.

We examined 58 children aged 1-16 years with various forms of osteogenesis imperfecta (OI). Congenital cardiac malformations were diagnosed in 4 children (valvular aortic stenosis, 2 with atrial septal defect II, Fallot Tetralogy). Two additional children developed holosystolic mitral valve prolapse and regurgitation. Children suffering from a severe clinical course (type III according to the Sillence classification) showed aortic root dilatation (28%) and increased septal (40%) and posterior left ventricular wall thickening (68%) on initial evaluation. All three parameters were significantly correlated to body surface area. Kidney stones and renal papillary calcifications were detected in 4 children. Cardiovascular abnormalities and nephrolithiasis may be important extraskeletal manifestations of childhood OI.

Adolescent↗

Presence of a fructose-2,6-bisphosphate-insensitive pyrophosphate: fructose-6-phosphate phosphotransferase in the anaerobic protozoa Tritrichomonas foetus, Trichomonas vaginalis and Isotricha prostoma.

Extracts of the anaerobic protozoa Tritrichomonas foetus, Trichomonas vaginalis and Isotricha prostoma contained a high activity (0.5-1 mumol min-1 (mg protein)-1) of pyrophosphate:fructose-6-phosphate phosphotransferase (PPi-PFK), but no detectable ATP: fructose-6-phosphate phosphotransferase. PPi-PFK from I. prostoma was purified close to homogeneity by adsorption on phospho-Ultrogel and elution with fructose-1,6-bisphosphate, and subsequent anion-exchange chromatography. The enzyme had an Mr of 95,000 as determined by gel filtration and consisted of subunits of Mr 48,000. PPi-PFK from I. prostoma and from T. foetus displayed hyperbolic kinetics with respect to their substrates and were not affected by fructose-2,6-bisphosphate. In sharp contrast with what has been found in other eukaryotes, no evidence could be found for the presence of fructose-2,6-bisphosphate in the two trichomonads, in I. prostoma and in Entamoeba histolytica.

Animals↗

Differences in response of acetylcholinesterase to diisopropylfluorophosphate in the mesencephalic raphe region. A microelectrophoretic, histochemical, and biochemical study in albino rats.

To demonstrate the DFP-effects on the AChE of the mesencephalic raphe region albino rats were investigated using the pharmaco-histochemical method of Butcher et al. (1975). At several times after 1 mg DFP/kg body weight, the histochemical reactions in certain AChE-containing neurons were measured semiquantitatively and compared with biochemical data. Additionally, the multiple forms of water-soluble AChE were separated by microelectrophoresis. Only the electrophoretical results indicate changes of the structural AChE composition 5 d after DFP administration.

Acetylcholinesterase↗

Eicosanoids produced during interactions between Pseudomonas aeruginosa and alveolar macrophages are species-dependent.

Eicosanoid production during phagocytosis of pyogenic bacteria by rabbit alveolar macrophages was studied as a model of early events in the pathogenesis of pneumonia. Adherent alveolar macrophages, prelabelled with [3H]-arachidonic acid (AA), were incubated with live, opsonized Staphylococcus aureus or Pseudomonas aeruginosa (bacteria:macrophage ratio of 50:1) at 37 degrees C for 90 min. Supernatant eicosanoids were extracted and separated by reverse phase high performance liquid chromatography (RP-HPLC). While the amounts of labelled PGE2, TXB2, and PGD2 produced in response to the two organisms were equal, the amount of PGF2 alpha elicited by S. aureus amounted to three times that released during macrophage challenge with P. aeruginosa. Overall, preferential release of cyclooxygenase products occurred during phagocytosis of S. aureus. In contrast, eicosanoids identified presumptively as oxygenated metabolites of AA predominated in cultures challenged with opsonized P. aeruginosa. Live, non-opsonized P. aeruginosa elicited the same profile of eicosanoids, but in reduced amounts. Inhibitor studies indicated that these AA derivatives were not synthesized via the macrophage lipoxygenase pathway. Their production was dependent on the viability of P. aeruginosa. Macrophages challenged with opsonized, heat-killed P. aeruginosa resulted in production of an eicosanoid profile similar to that elicited by S. aureus. Secondary metabolism by P. aeruginosa of eicosanoids released from the macrophage did not contribute to the unique profile produced during the interaction of this organism with labelled macrophages. Our data indicate that during binding to macrophages, the primary human pathogen, P. aeruginosa, specifically modulates the profile of eicosanoids produced. This effect on inflammatory mediators may be of biological significance in the pathogenesis of pneumonia.

Animals↗

[SPECT-3-D reconstructions of lung perfusion in patients with thoracic space-occupying lesions].

The present study deals with 3-dimensional reconstruction of lung perfusion examinations in 20 patients with thoracic masses. The images were obtained by single photon emission tomography (SPECT) and were compared with conventional scintigraphic images and with the CT findings. 3-D reconstructions proved superior to 2-dimensional images for the topographic demonstration of the affected lung segments. No additional information could be obtained concerning the extent of the mass. Use of this method is valuable for the preoperative estimation of pulmonary perfusion.

Adult↗

In vitro membrane assembly of a polytopic, transmembrane protein results in an enzymatically active conformation.

In vitro integration of the polytopic, transmembrane lactose permease into membrane vesicles from Escherichia coli is demonstrated. To this end the enzyme was synthesized in a homologous, cell-free transcription-translation system. In this system, synthesis occurred in an essentially membrane-free environment leading to the formation of lactose permease aggregates, which were resistant to protease digestion and detergent solubilization. However, if inverted membrane vesicles from E. coli were included in the synthesis reaction, most de novo-synthesized lactose permease could be recovered from a membrane-containing subfraction (enriched in leader [signal] peptidase activity). This membrane association of lactose permease was Na2CO3 resistant, detergent sensitive, and yielded a distinct pattern of proteolytic cleavage peptides. Moreover, membrane vesicles when present cotranslationally during synthesis of lactose permease, acquired the capability to accumulate lactose, strongly suggesting a correct in vitro assembly of the enzyme. Because of the extensive aggregation of lactose permease synthesized in the absence of membranes, only low amounts originating from the soluble enzyme pool integrated posttranslationally into the membrane vesicles. Unlike the translocation of the outer membrane protein LamB into membrane vesicles, integration of lactose permease was found to be independent of the H+-motive force.

Alkylation↗

Human papillomavirus type 48.

The cloning and partial characterization of the genome of human papillomavirus (HPV) type 48 is presented. Hybridization and short DNA sequence analyses permitted the alignment of the genome to the HPV genetic map.

Carcinoma, Squamous Cell↗

Human papillomavirus type 53.

The cloning and partial characterization of the genome of human papillomavirus type 53 is presented. The virus is a distinct type and is most closely related to human papillomavirus type 30.

Cervix Uteri↗

The stability of the circadian rhythm of green finches (Carduelis chloris) under the influence of a weak electrical field.

Free-running activity rhythms of nine green finches (Carduelis chloris) were studied under the influence of a 10-Hz square-wave electrical field. With a field strength of magnitude of E = 2.5 V/m in the empty cage, the population had a mean period of 23.64 +/- 0.77 hr. In the same experiment, but without the electrical field, the period was 23.66 +/- 0.80 hr. These results are in contradiction to Wever's description of a field-induced shortening of the period. A series of experiments with 10-Hz pulses of the same square-wave form, yet with various field strengths (8.7 and 65.2 V/m), also gave no effects.

Animals↗

[Focusing water shock waves for lithotripsy by various ellipsoid reflectors].

A spherical shock wave generated in the first focus of an ellipsoid is focused in the second focus after reflection. Shadowgraphs provide an impression of the converging process, while the pressure field ist measured with speciality designed pressure probes having a high temporal and spatial resolution. Two different types of reflectors have been investigated. The first is like a spherical mirror with a short focal length, the second is a deep reflector "surrounding" the generation point. Variation of the parameters, size of the reflector, and incident shock energy reveal their influence on the focusing process and the point of maximal pressure, which in the case of deep ellipsoids can deviate from the geometrical focus. Here, non-linear propagation effects on the long distances to the focus lead to an increase in the size of the focal region. Although these reflectors utilize much more of the primary shock front, their peak pressure of 400 bar is low compared with the "shallow" reflectors with 1200 bar and their small focus. The effect of the deep type on kidney stones is however greater. The desintegration process and the reaction of the generated cavitation bubbles have been studied with a high speed camera. It can be shown that stone splinters do not injure the kidney tissue, but liquid jets generated by oscillating cavitation bubbles lead to tissue damage.

Humans↗

Rioprostil, a new prostaglandin E1, prevents cyclosporin A-induced damage to endocrine and exocrine pancreas.

The possibility that rioprostil can prevent cyclosporin A-induced damage to the pancreas is investigated. Cyclosporin A is given to rats once daily intragastrically in doses of 5, 10 and 20 mg/kg body weight. These doses cause dose dependent significant reduction of insulin release and enzyme secretion from the arterially perfused isolated pancreas. The subcutaneous injection of rioprostil, 15 micrograms/kg twice daily, could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could also afford significant protection from the effects of 10 and 20 mg/kg cyclosporin A on both insulin release and enzyme secretion. The cytoprotective action of rioprostil on the pancreas may have therapeutic implications.

Animals↗

[Surgical therapy and results in stomach cancer at an Austrian regional hospital].

The resection rate of 216 gastric carcinomas, which were treated between January 1984 and October 1988, was 81.5%. Total gastrectomies were performed in 65.3%, distal resections in 33% and proximal resections in 1.7%. 68.1% of the operations were performed with curative intention, 13.4% were palliative, 18.5% were bypass operations and explorative laparotomies. In 52% the operations were extended to other organs. The total lethality of gastrectomies was 6.3% (for operations with curative intention 3.1%, for palliative ones 21%). None of the patients died of insufficiency of the anastomosis. The total lethality of distal and proximal resections was 3.7% (for operations with curative intention 0%, for palliative ones 20%). Explorative laparotomies and bypass operations had a lethality of 10%. According to the histo-pathological classification of the WHO 6% were well, 31% moderately and 46.8% poorly differentiated adenocarcinomas. Signet ring cell carcinomas were diagnosed in 9.3% of the cases. A histological classification of metastasis only was done in 3.2%. 3.7% of the cases were not examined histologically. 55.7% corresponded to the intestinal, 29.6% to the diffuse and 7% to the mixed type of Lauren. A Lauren classification was not possible in 7.8%. According to the UICC-criteria 13% were stage IA, 14.35% IB, 10.2% II, 14.35% IIIA, 10.2% IIIB and 6% IV(RO). In 31.9% a residual tumor (R1/R2) had to be left behind. The percentage of early cancer was 16%. 14 of the 34 early cancers corresponded to the mucosa and 20 to the submucosa type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Staining of carious dentin with Kariesdetektor].

In a histological study of the staining effect of the staining solution Kariesdetektor 60 human teeth with carious lesions of varying sizes were separated into one control half and one test half each immediately following their extraction. Non-decalcified thin ground sections were prepared with the aid of the saw-cut-and-grind technique. The test halves were stained with Kariesdetektor, the control preparations with toluidine blue. The staining effect of the disclosing dye was evaluated under the light microscope and compared with the control preparations. In enamel the disclosing dye stained all carious areas except the dark and the more peripheral transparent zones. In dentinal caries the zones of necrosis and penetration were safely stained. Zones of demineralization, dead tracts, and transparency zones were not stained. Kariesdetektor is a reliable optical aid in removing infected carious hard tooth structures.

Dental Caries↗

Bioequivalence and pharmacodynamics of a modified glibenclamide formulation in healthy volunteers.

A glibenclamide preparation (Glycolande N) with a modified galenic formulation was compared with a marketed standard preparation for bioequivalence and hypoglycaemic action after single oral administration of 3.5 mg. Twelve healthy male volunteers participated in this open two-way cross-over study. The confidence intervals around the mean values of the standard preparation were all in the range of +/- 20%. No significant differences were found between both formulations for Cmax, Tmax, AUC1 and AUC3. The glucose profiles were virtually equal. Both preparations are regarded as bioequivalent and therapeutically equivalent.

Adult↗