Search PubMed⌕ Search

Biomedical subjects

T Maurer

Publications and source records attributed to T Maurer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Homology modelling and 1H NMR studies of human leukaemia inhibitory factor.

Human leukaemia inhibitory factor (LIF) is a glycoprotein with a diverse range of activities on many cell types. A molecular model of LIF has been constructed based mainly on the structure of the related cytokine granulocyte colony-stimulating factor, and refined using simulated annealing and molecular dynamics in water. The model was stable during molecular dynamics refinement and is consistent with known stereochemical data on proteins. It has been assessed by comparison with 1H NMR data on the ionization behaviour of the six histidine residues in LIF, the imidazolium pKa values of which range from 3.6 to 7.4. These pKa values were assigned to individual histidine residues from NMR studies on a series of His-->Ala mutants. The environments of the histidine residues in the model account very well for their observed ionization behaviour. Furthermore, the model is consistent with mutagenesis studies which have defined a group of amino acid residues involved in receptor binding.

Amino Acid Sequence↗
PubMed1994

Solution structure of seminal plasmin in the presence of micelles.

The 47-amino-acid peptide seminal plasmin maintains a random-coil characteristic feature when in aqueous solution, as can be shown by CD and NMR measurements. However, upon binding to a hydrophobic/hydrophilic interface, an increase in the content of secondary structure is observed. This change in conformation can also be induced with the addition of a detergent. The secondary structure segments thus formed were assigned by two-dimensional NMR. The results indicate that hydrophobic interactions are a driving force in the folding of seminal plasmin. The interaction of seminal plasmin with detergent micelles could serve as a model for the binding of this interesting protein with the acrosome membrane of sperm cells.

Amino Acid Sequence↗
PubMed1994

NMR studies of a murine-human chimera of leukaemia inhibitory factor (LIF). Comparison with human LIF.

Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine active on many cell types. We present here 1H NMR studies on the solution properties and stability of MH35, a chimera of murine and human LIF which can be expressed at high levels in Escherichia coli, thus enabling efficient labelling of the protein with the stable isotopes 13C and 15N. MH35 has 85% sequence identity with human LIF and similar activity in biological assays. The 1H chemical shifts of the 12 conserved aromatic residues and the pKa values of the five conserved histidine residues in MH35 and human LIF are very similar. Temperature dependence studies indicate that both proteins are stable, with significant conformational changes occurring only above 70 degrees C. These results show that these proteins have a similar overall structure and stability and that MH35 is therefore a suitable analogue of human LIF for structural studies in solution.

Amino Acid Sequence↗
PubMed1993

A standard protocol for phototoxicity testing. Results from an interlaboratory study.

Based on experience accumulated in a number of laboratories, a standardized protocol for phototoxicity testing in experimental animals by the dermal route is presented. By conducting a limited interlaboratory study, demonstrating a high degree of consistency using 8-methoxypsoralen (8-MOP) and acridine, the sensitivity and reproducibility of the proposed methodology is demonstrated. Important aspects of performing phototoxicity testing are discussed.

Acridines↗
PubMed1993

[Results of a combined surgical procedure in complete Tossy III acromioclavicular joint dislocation].

This paper presents the results of a follow-up examination of 31 patients who had undergone reconstructive surgery for complete acromioclavicular (AC) dislocation between 1 September 1986 and 30 June 1989. The operation performed consisted in suturing of coracoclavicular and acromioclavicular ligaments with a coracoclavicular PDS cord augmentation and a transarticular K-wire left in place for 6 weeks. The follow-up investigation included a questionnaire on subjective assessment and daily problems with the treated shoulder, a clinical examination and a X-ray of both shoulders with 10 kg weight on each side. Good and very good results were found in 93% for clinical patterns, in 90% for subjective opinion, and in 79% for radiological examination. No correlation could be found between clinical results and radiological results, even concerning AC joint arthrosis following the operation.

Acromioclavicular Joint↗
PubMed1992

Radiotherapy of the rhabdomyosarcoma R1H of the rat: recovery from radiation injury in tumour and skin.

The response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation has been reported to be almost independent of the dose per fraction in the range from 0.43 to 10 Gy. To elucidate whether recovery from radiation injury is impaired in fractionated irradiation or not, tumours were exposed on 5 days per week over 6 weeks either to a single daily dose or to two daily fractions separated by an interfraction interval of 2 h. Tumour response was assessed by net growth delay. Skin damage was scored for comparison. A significant reduction in tumour response (p less than 0.009) and skin damage (p less than 0.001) was observed when the daily dose was administered in a twice daily irradiation regimen, indicating that recovery from radiation injury does occur in the course of fractionated irradiation in our tumour system. A tumour response was almost independent of the dose per fraction for time intervals between fractions of at least 8 h, a possible explanation might be that recovery is compensated by improved reoxygenation.

Animals↗
PubMed1992

[Athletic capacity after surgical management of acromioclavicular joint separation].

Acromioclavicular separation is a common injury in sports. This study was done to show the activity and problems of athletes after operative treatment of this kind of injury. Between 1986 and 1989 21 athletes with acromioclavicular separation had been treated by operation. The coracoclavicular ligaments had been sutured and augmented by a PDS cord. The acromioclavicular ligaments had also been reattached and the ac-joint had been transfixed with a Kirschner-wire. The results show 18 athletes doing their sports on the same level as preoperatively. Two athletes with a frequency of sporting activity once a week could not continue their sporting activity. One athlete changed the disciplines to less shoulder stressing kind of sport. The comparison of clinical and radiological results showed no correlation, even patients with an osteoarthrosis of the ac-joint and coracoclavicular ossifications had best clinical results. We recommend therefore operative treatment for acromioclavicular separation in athletes.

Acromioclavicular Joint↗
PubMed1992

[Results of conventional and laparoscopic cholecystectomy].

We report about a retrospective study of 861 conventional and 812 laparoscopic cholecystectomies (including one coelioscopic choledocholithotomy). In the conventionally operated group reoperation was required in 2.7% (1.4% relaparotomy, 1.3% secondary suture), mortality was 0.5%. After laparoscopic treatment the reoperation rate was 2% (10 relaparoscopies, 5 laparotomies, 2 secondary sutures), no mortality. Growing experience and better definition of contraindications for endoscopic cholecystectomy might improve our results in the future.

Adult↗
PubMed1991

Investigation of the membrane-active peptides melittin and glucagon by photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR.

The photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR technique was used to investigate the membrane-active peptides melittin and glucagon. The experiments were performed both in the absence and presence of phospholipid vesicles in order to study the topography of the membrane-bound state. From the results it can be concluded that the melittin peptide chain is oriented in such a way that the single tryptophan residue (Trp19) reaches into the membrane. In the case of glucagon, a binding interaction with vesicle membranes is indicated within the pH range 2-10, whereby the single tryptophan residue (Trp25) is buried in the lipid bilayer and the tyrosine and histidine residues are exposed to the aqueous solvent.

Amino Acid Sequence↗
PubMed1991

Skin sensitization--a critical review of predictive test methods in animals and man.

With the exception of the Draize Test, the guinea-pig test methods currently accepted by regulatory authorities worldwide are well able to predict the potential of a material to cause skin sensitization. Nevertheless, (a) some methods are more sensitive than others (e.g. adjuvant tests are generally more sensitive than non-adjuvant tests); (b) methods cannot be sufficiently standardized to give full reproducibility of results between laboratories; and (c) most methods are based on subjective visual grading of skin reactions--difficulties thus arise when testing coloured or irritant materials. Laboratories must be able to show the sensitivity of the method(s) they use by demonstrating that positive reactions occur with mild/moderate contact allergens rather than the strong/extreme sensitizers currently recommended in certain guidelines, specifically in the EEC Test Method. The sensitivity of the adjuvant tests is such that it is possible to halve the minimum number of animals required by present regulatory guidelines without compromising the capacity of the tests to detect weak/mild sensitizers. A similar review has not yet been made for non-adjuvant tests. Alternative test methods, including some recently developed mouse models, offer several advantages, including more objective endpoints. These tests have not been extensively validated and this precludes their use at present for regulatory purposes other than to confirm the sensitization potential of a material. Two new test methods using mice, the Mouse Ear-swelling Test and the Local Lymph Node Assay, appear promising. They should undergo rigorous interlaboratory testing to determine their sensitivity and specificity. In vitro methods do not represent a viable alternative in the foreseeable future. An approach using quantitative structure-activity relationships is the most likely route to a non-animal model, but this will require considerable research, development and validation. Human sensitization tests have generally not been used for the classification of substances as non-sensitizers. This is because of an absence of internationally agreed test protocols, the lack of positive controls and because the methods for establishing the sensitivity of human tests are less developed than for animal tests. Nevertheless, for products for which direct human contact is intended, predictive tests in human volunteers can be considered. The EEC Directive for the Classification, Packaging and Labelling of Dangerous Substances provides a reasonable approach to the evaluation of skin sensitizers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Draining lymph node cell activation in guinea pigs: comparisons with the murine local lymph node assay.

The local lymph node assay in the mouse is a novel predictive test for the identification of contact sensitizing chemicals. The purpose of the studies described was to determine whether a similar local lymph node assay could be performed successfully in guinea pigs; currently the species of choice for assessment of sensitizing potential for regulatory purposes. Ten sensitizing chemicals (oxazolone, picryl chloride, 2,4-dinitrofluorobenzene, benzocaine, cinnamic aldehyde, 2,4,-dinitrothiocyanobenzene, p-nitrosodimethylaniline, formaldehyde, p-phenylenediamine and cyanuric chloride) and equal concentrations of sodium lauryl sulphate were examined in a guinea pig local lymph node assay. Animals received three consecutive daily applications of various concentrations of the test chemical on the dorsum of both ears. Control animals were untreated. Five days following the initiation of exposure, draining auricular lymph nodes were excised and weighed. Suspensions of lymph node cells (LNC) were prepared and cultured for 24 or 48 h and proliferation measured by incorporation of [3H]thymidine. Exposure to at least one concentration of all sensitizing chemicals, other than benzocaine, induced proliferation by draining LNC. Responses were higher at 24 h rather than 48 h. Evidence is presented that guinea pig LNC proliferation may be enhanced or maintained by addition to culture of an exogenous source of the T cell growth factor interleukin 2 (IL-2). Draining lymph node weight was increased following exposure to some sensitizing chemicals but, compared with LNC proliferation, provided a less sensitive correlate of lymph node activation. Exposure to sodium lauryl sulphate failed to induce changes in either lymph node weight of LNC proliferation. Data are compared with three-day murine local lymph node assays performed concurrently. The available information indicates that the local lymph node assay may be performed in guinea pigs.

Allergens↗
PubMed1990

Flow cytometric determination of the time of metastasis during fractionated radiation therapy of the rat rhabdomyosarcoma R1H.

A technique is presented for determining the time of metastasis during fractionated radiation therapy of the rat rhabdomyosarcoma R1H by flow cytmetric DNA index measurements. The DNA index is the relative DNA content of the tumour cells compared with normal cells. The DNA index of the highly hyperploid R1H tumour decreases linearly during radiation therapy dependent on the total dose applied, with a rate of 0.22% per Gy. Since metastatic cells escape further irradiation, their DNA index should correspond to the DNA index at time of spread. If so, cells disseminated late during a course of fractionated irradiation are expected to produce symptoms later and to have a lower DNA index compared with cells that metastasized at the start of treatment. The results obtained fitted these expectations, showing that timing of metastases by DNA flow cytometry, in principle, is possible. A first application of this method indicates that the risk per clonogenic R1H tumour cell to matastasize increases during fractionated irradiation.

Animals↗
PubMed1989

A differentiated approach to testing skin sensitization. Proposal for a new test guideline skin sensitization.

The present EEC and OECD Guidelines for testing skin sensitization have been reviewed in light of scientific evidence demonstrating that those methods which use Freund's Complete Adjuvant (FCA) are likely to be more accurate in predicting a probable skin-sensitizing effect of a new substance in humans than those methods not employing Freund's Complete Adjuvant. In this new test guideline, therefore, the primary testing of a substance should be carried out using one of the recommended Adjuvant methods. In special cases a non-adjuvant method may be performed in addition. Not all of the seven methods in the EEC Guideline or eight methods in the OECD Guideline have been included, but in a proposal for an updated test protocol two Adjuvant tests (Maximization test by Magnusson and Kligman and Optimization test by Maurer), and two non-Adjuvant tests (Open Epicutaneous test by Klecak and Buehler test) are suggested. The criteria for selecting these methods are based on the fact that they are well validated and widely used on a broad basis by the scientific community. Furthermore, it is considered appropriate to permit the use of a lower number of animals than presently recommended for the testing of skin sensitization. This is also in agreement with aspects of animal welfare.

Animals↗
PubMed1989

The maximization test for skin sensitization potential--updating the standard protocol and validation of a modified protocol.

Since Magnusson and Kligman (1969) first described the maximization test, for assessing skin sensitization potential, the test has been substantially validated and data have been obtained on dose-activity relationships. The original method remains acceptable for qualified risk assessment but several modified protocols have been developed to overcome problems with particular test materials. A modified maximization test is described for compounds that are not soluble in the standard vehicles and, therefore, not injectable, and for formulations, to simulate user exposure conditions. The test compounds 2,4-dinitrochlorobenzene, p-phenylenediamine, 1-(3-chlorophenyl)-3- (4-chlorophenyl)-2-pyrazoline, formaldehyde, benzocain, penicillin G, benzylsalicylate, potassium dichromate and isoeugenol, all gave positive reactions. The incidences of positive reactions varied with the sensitization potentials of the compounds. The results for the first six compounds listed above were compared with those obtained by the standard procedure and were found to be similar. We propose that testing guidelines for skin sensitization should accommodate validated modifications of existing standard procedures.

Administration, Cutaneous↗
PubMed1989

Radiotherapy of the rhabdomyosarcoma R1H of the rat: hyperfractionation--126 fractions applied within 6 weeks.

The effect of a hyperfractionated irradiation treatment on the response of the rhabdomyosarcoma R1H of the rat was studied. Tumors were irradiated under ambient conditions with 126 fractions of X rays, applied in 3 fractions per day with a time interval of 8 +/- 1 hr between fractions on 7 days per week during 6 weeks. The total dose ranged from 54 to 90 Gy, that is the dose per fraction ranged from 0.43 to 0.71 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. The tumor response to the hyperfractionated treatment was found to be slightly more effective compared to the results obtained in a previous study where treatments with 6, 18, 30, and 42 fractions were applied. Since normal tissues are considerably spared with increased numbers of fractions, clinical studies with hyperfractionation seem to be very promising.

Animals↗