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M Meyer

Publications and source records attributed to M Meyer.

At least 559 records · Page 31Linked to original sources
PubMed1986

Evaluation of the effect of agar on the results obtained in the L5178Y mouse lymphoma assay.

The L5178Y TK+/- mouse lymphoma assay is widely used in mutagenicity testing. Trifluorothymidine-resistant (TFTr) mutants are quantitated following growth in agar-supplemented cloning medium. In an attempt to evaluate the effect of agar on plating efficiency, we have tested several lots of Difco Noble agar (cat. No. 0142-01-8; normally used in this assay) and compared it with Baltimore Biological Laboratory (BBL) agar (cat No. 11849). We find that BBL agar gives a higher and less variable plating efficiency than any of the Noble lots tested. Colonies plated in BBL agar tend to appear significantly earlier on the plates than those cloned in Noble agar. The absolute mutant number and the induced mutant frequency quantitated from a treated culture is generally higher in BBL compared to Noble agar. To determine if this higher frequency is due to increased mutant recovery rather than "sneak through" of nonmutant cells, we isolated 97 mutants from treated cultures (44 large colonies and 53 small colonies) and 69 mutants from untreated cultures (24 large colonies and 45 small colonies) and tested them for TFT resistance. All but one (a large colony from an untreated culture) were found to be TFTr, indicating that the mutant frequency is due to an increased mutant recovery. The spontaneous mutant frequency was quantitated for 122 untreated cultures. Showing little variation within and between experiments, the spontaneous mutant frequency yielded a mean of 57.7, with a standard deviation of 14.4. Under our laboratory conditions, BBL agar gave reliable results, and we prefer it for use in cloning L5178Y mouse lymphoma cells.

Agar↗
PubMed1986

Gas exchange efficacy of high-frequency oscillatory ventilation studied by helium washout from dog lungs.

The gas exchange efficacy of high-frequency oscillatory ventilation (HFOV) was assessed from an analysis of helium washout from lungs in anesthetized paralyzed supine dogs. Piston stroke volumes (Vs) were varied from 20 to 40 ml, frequencies (f), from 10 to 40 Hz and mean airway opening pressures from 2 to 10 cm H2O. The time course of washout could be described as the sum of three exponential components. Based on a series model comprising a proximal and a distal lung compartment, two component conductances, a 'distal' conductance (Gd) and a 'proximal' conductance (Gp) and an overall conductance of the lung (Gl) could be calculated. Gd, Gp and Gl increased with f up to a maximum value remaining constant or decreasing at higher f; the frequency at which the maximum occurred depending on Vs and on the diameter of the endotracheal tube (ET). With increasing Vs generally the G values increased, but decreased at higher f with the smaller ET. The insoluble inert gas washout is shown to be a useful method for assessing the ventilatory gas exchange conductance of lungs during HFOV.

Airway Resistance↗
PubMed1986

Nalmefene: intravenous safety and kinetics of a new opioid antagonist.

In a placebo-controlled, double-blind study we evaluated the safety and kinetics of a new narcotic antagonist, nalmefene, after 2, 6, 12, and 24 mg intravenous doses to healthy men. At each dose level four subjects received active drug and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness. The plasma concentration-time data were best fit with a triexponential equation, and the terminal elimination phase had a harmonic mean t1/2 of 8 to 9 hours. Only about 5% of the dose was excreted in the urine as intact nalmefene, with up to 60% excreted as nalmefene glucuronide. Although intersubject differences were noted, mean or dose-normalized mean kinetic parameters such as clearance, steady-state volume of distribution, terminal t1/2, and AUC showed no consistent trends related to increasing doses, indicating that nalmefene has linear pharmacokinetics.

Adult↗
PubMed1986

[Use of botulinum toxin in ophthalmology].

Botulin toxin A was introduced as a treatment in ophthalmology by Dr. Scott of San Francisco. One important application is in cases of blepharospasm, where the toxin is injected into the lateral parts of the lower and upper lid and, if necessary, over the eyebrows in a single dose of 1-2 nanograms, preferably using a needle under electromyographic control. The effect on the blepharospasm is visible after a few days and lasts for several months. The procedure can be repeated several times. The second application is in cases of strabismus. In paralytic strabismus, contracture of the antagonist of the paralyzed muscle can be weakened by local injection of botulin toxin with a coaxial electrode under electromyographic control. Good results were observed in cases of eye muscle disorders in endocrine ophthalmopathy. In concomitant strabismus (exotropia or esotropia) administration of botulin toxin is also possible although a certain paresis of the injected muscle has to be taken into account. The doses for strabismus vary between 1/2 and 2 nanograms of the toxin. The administration of botulin toxin either in blepharospasm or strabismus has no systemic side effects and is a safe procedure if performed under careful electromyographic control. First personal experiences in the treatment both of blepharospasmus as well paralytic strabismus and concomitant strabismus are reported.

Blepharospasm↗
PubMed1986

Pulmonary diffusing capacity for carbon monoxide by rebreathing in awake dogs.

In order to reduce the effects of functional inhomogeneities on the determination of pulmonary diffusing capacity (transfer factor) for CO (DLCO), DLCO was measured by a rebreathing method in 5 awake chronically tracheostomized dogs (mean body weight 28 kg) during high ventilation (15-25 times above normal) induced by hypoxia, hypercapnia, exercise, or their combinations. The animals rebreathed for 15 s a mixture containing 1% He, 0.1% C18O, with CO2 and O2 concentrations adjusted to maintain end-tidal PCO2 and PO2 close to their prerebreathing values. Gas partial pressures in the trachea were continuously monitored by mass spectrometry. DLCO was calculated from C18O equilibration kinetics, effective ventilation (obtained from He mixing kinetics) and lung volume (obtained from He dilution). Each of the factors, hypoxia, hypercapnia and exercise, contributed to increasing DLCO. During exercise in combined hypoxia and hypercapnia, DLCO (mean +/- SE) was 71.7 +/- 1.8 ml/(min X Torr). The mechanisms for increases in DLCO might have involved improvement of diffusion conditions, decrease of functional inhomogeneities and reduction of the effects of functional inhomogeneities. The highest DLCO values were close to values derived from morphometry.

Animals↗
PubMed1986

Phase I-II evaluation of intra-arterial diaziquone for recurrent malignant astrocytomas.

Diaziquone (AZQ) is a lypophilic alkylating agent that crosses the blood-brain barrier and has shown broad activity in animal tumor models. Five of 12 patients with malignant astrocytoma treated with iv AZQ had clinical and/or radiographic improvement (Schold, Neurology 34:615, 1984). Intra-arterial administration of AZQ to patients with brain tumors should produce higher peak levels of drug in the tumor and should reduce systemic toxicity. Twenty-one patients with astrocytoma (grade II, four; grade III, 11; and grade IV, six), in all of whom irradiation and intra-arterial carmustine chemotherapy failed, received intra-arterial AZQ as a single dose every 28 days. Two of 20 evaluable patients experienced partial responses of 5 and 8+ months, respectively. Four patients had disease stabilization of 3, 4, 5, and 8 months' duration, respectively, and one of these patients had tumor shrinkage (partial response) after seven courses of AZQ. The initial dose in the first three patients was 10 mg/m2, and doses in subsequent groups of three patients were begun at increases of 5 mg/m2. The within-group dose escalation was 5 mg/m2 per course if there was no hematologic toxicity. Dose-limiting toxicity was myelosuppression, which occurred at doses greater than 15 mg/m2. The maximum tolerated dose was 25 mg/m2. Intra-arterial AZQ appears to be of marginal effectiveness in patients refractory to carmustine and offers no advantage over iv AZQ in efficacy or toxicity.

Adult↗
PubMed1986

[Contribution of electron microscopy of cultures of fibroblasts in the diagnosis of hereditary metabolic diseases].

This work is an electron microscopic study of fibroblast culture of patients with metabolic diseases. In all cases, except for Niemann-Pick disease, primary lysosomes or secondary lysosomes containing lamellar, rectilinear or curvilinear material are accumulated in cytoplasm of fibroblasts. Though clinical consequences of metabolic diseases are diverse, cellular injuries are relatively uniform. Then electron microscopic study would'nt allow the diagnostic of a metabolic disease but it can provide an orientation. In one case, the enzymatic defect is not determined with biochemical analyses though clinical observation is characteristic of a metabolic disease; only the electron microscopic study shows a lysosomal accumulation.

Adolescent↗
PubMed1985

Proton nuclear magnetic resonance spectroscopy of horseradish peroxidase isoenzymes: correlation of distinctive spectra with isoenzyme specific activities.

High-resolution proton NMR spectra are reported for the paramagnetic ferric native and cyano complexes of the five major horseradish root peroxidase (HRP) isoenzymes (A1, A2, A3, B, and C). Axial imidazole resonances are observed in the native and cyano-complex spectra of all the isoenzymes, thus indicating the presence of a common axial histidine ligand. Proton NMR spectra outside the usual diamagnetic region are identical for sets of A1 and A2 isoenzymes and for the B and C isoenzyme set. Variation in heme residue chemical shift positions may be controlled in part by porphyrin vinyl side chain-protein interactions. Diverse upfield spectra among the isoenzymes reflect amino acid substitutions and/or conformational differences near the prosthetic group, as signals in this region must result from amino acid residues in proximity to the heme center. Acid-base dependence studies reveal an "alkaline" transition that converts the native high-spin iron (III) porphyrin to the low-spin state. The transition occurs at pH 9.3, 9.4, 9.8, and 10.9 for respective HRP A1, A2, A3, and C isoenzymes, respectively. Significantly, this ordering also reflects specific activities for the isoenzymes in the order A1 = A2 greater than A3 greater than B = C. Identical proton NMR spectra for A1/A2 and B/C isoenzyme sets parallel equivalent specific activities for members of a particular set. Proton NMR spectra thus appear to be highly sensitive to protein modifications that affect catalytic activity.

Amino Acids↗
PubMed1985

Diversity of glycoprotein deficiencies in Glanzmann's thrombasthenia.

The platelet proteins of 9 thrombasthenic patients from 7 families were analysed by high resolution two-dimensional gel electrophoresis (HR-2DE) and crossed immunoelectrophoresis (CIE). In 7 patients both glycoproteins (GPs) IIb and IIIa were absent or reduced to roughly the same extent. In two related patients only a trace of GP IIb-IIIa complex was detected in CIE, but HR-2DE revealed a glycopeptide in the position of GP IIIa in an amount comparable to type II thrombasthenia. This GP IIIa-like component was neither recognized normally by anti-GP IIb-IIIa antibodies nor labeled by surface iodination. In unreduced-reduced two-dimensional gel electrophoresis two components were observed in the region of GP IIIa. The assumption of a structural variant of GP IIIa in the two related patients is discussed.

Blood Platelet Disorders↗