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Biomedical subjects

W Gehring

Publications and source records attributed to W Gehring.

At least 37 records · Page 2Linked to original sources
PubMed1993

Nuclear magnetic resonance spectroscopy of a DNA complex with the uniformly 13C-labeled Antennapedia homeodomain and structure determination of the DNA-bound homeodomain.

A 1:1 complex formed by the mutant Antennapedia(C39S) homeodomain and a 14 base-pair DNA duplex (molecular weight approximately 18,000) was prepared in which the protein was uniformly 13C-labeled. Using two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy with 13C(omega 1, omega 2)-double-half-filter and three-dimensional 13C-correlated NOE spectroscopy, nearly complete sequence-specific resonance assignments were obtained for both the protein and the DNA in the complex. On this basis conformational constraints needed for a three-dimensional structure determination were collected. Using 855 intramolecular distance constraints as input, the structure of the DNA-bound Antp(C39S) homeodomain was calculated with the program DIANA, followed by restrained energy minimization with the program OPAL. A group of 20 conformers characterizes a well-defined structure for residues 8 to 56, with an average of 0.5 A of the pairwise root-mean-square deviations calculated for the backbone atoms of the individual conformers relative to the mean coordinates. The quality of the resulting structure is comparable to the one for the free protein, and the global fold of the free Antp(C39S) homeodomain was found to be conserved in the DNA complex. The structure of the DNA-bound protein was the starting point for the subsequent structure determination of the complete Antp(C39S) homeodomain-DNA complex in solution.

Amino Acid Sequence↗
PubMed1993

Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex.

The nuclear magnetic resonance (NMR) solution structure of a complex formed by the mutant Antennapedia homeodomain with Cys39 replaced by Ser, Antp(C39S), and a 14 base-pair DNA duplex containing the BS2 operator sequence was determined using uniform 13C and 15N-labeling of the protein. Two-dimensional nuclear Overhauser enhancement spectroscopy ([1H,1H]NOESY) with 15N(omega 2)-half-filter and 13C(omega 1, omega 2)-double-half-filter, and three-dimensional heteronuclear-correlated [1H,1H]NOESY yielded a total of 855 intramolecular NOE upper distance constraints in the homeodomain, 151 upper distance constraints within the DNA duplex, and 39 intermolecular protein-DNA upper distance constraints. These data were used as the input for the structure calculation with simulated annealing followed by molecular dynamics in a water bath and energy refinement. A group of 16 conformers was thus generated which represent the solution structure of the Antp(C39S) homeodomain-DNA complex. The new structure determination confirms the salient features reported previously from a preliminary investigation of the same complex, in particular the location of the recognition helix in the major groove with the turn of the helix-turn-helix motif outside the contact area with the DNA, and the N-terminal arm of the homeodomain contacting the minor groove of the DNA. In addition, distinct amino acid side-chain-DNA contacts could be identified, and evidence was found that the invariant residue Asn51 (and possibly also Gln50) is in a slow dynamic equilibrium between two or several different DNA contact sites. The molecular dynamics calculations in a water bath yielded structures with hydration water molecules in the protein-DNA interface, which coincides with direct NMR observations of hydration waters. In the Appendix the experimental data obtained with the Antp(C39S) homeodomain-DNA complex and the techniques used for the structure calculation are evaluated using a simulated input data set derived from the X-ray crystal structure of a DNA complex with a homologous homeodomain. This study indicates that a nearly complete set of NOE upper distance constraints for the Antp(C39S) homeodomain and the protein-DNA interface was presently obtained. It further shows that the structure calculation used here yields a precise reproduction of the crystal structure from the simulated input data, and also results in hydration of the protein-DNA interface in the recalculated complex.

Animals↗
PubMed1992

Enhancement of the penetration of dithranol and increase of effect of dithranol on the skin by liposomes.

An assessment was made in healthy skin of dithranol erythema caused by a 10-min occlusive application of 0.5% dithranol (CAS 1143-38-0) in liposomal gel (Natipide II) with and without the addition of 3% salicylic acid, and of 0.5% dithranol in vaseline and in a removable standard ointment base, both with 3% salicylic acid. Both liposomal preparations led to a significant potentiation of the dithranol erythema. The results indicate a strong promotion of the penetration of dithranol by the liposomal gel.

Adult↗
PubMed1991

Structure determination of the Antp (C39----S) homeodomain from nuclear magnetic resonance data in solution using a novel strategy for the structure calculation with the programs DIANA, CALIBA, HABAS and GLOMSA.

The structure of a mutant Antennapedia homeodomain, Antp(C39----S), from Drosophila melanogaster was determined using a set of new programs introduced in the accompanying paper. An input dataset of 957 distance constraints and 171 dihedral angle constraints was collected using two-dimensional n.m.r. experiments with the 15N-labeled protein. The resulting high quality structure for Antp(C39----S), with an average root-mean-square deviation of 0.53 A between the backbone atoms of residues 7 to 59 in 20 energy-refined distance geometry structures and the mean structure, is nearly identical to the previously reported structure of the wild-type Antp homeodomain. The only significant difference is in the connection between helices III and IV, which was found to be less kinked than was indicated by the structure determination for Antp. The main emphasis of the presentation in this paper is on a detailed account of the practical use of a novel strategy for the computation of nuclear magnetic resonance structures of proteins with the combined use of the programs DIANA, CALIBA, HABAS and GLOMSA.

Algorithms↗
PubMed1990

Results of a combination treatment with natamycin and butylscopolamine in cases of intestinal Candida colonization.

The findings described show that Candida species can be found in the feces of approximately half a population of nonselected test persons and in the mouths of approximately a third. Intestinal Candida colonization was found in most of these persons after one feces examination, and in practically all of them after a second examination. 10 d of therapy with 400 mg natamycin per day in sugar-coated tablet form and 40 mg natamycin in the form of tablets for sucking produced a negative fungus test for the feces in only 20% of the cases. Although a combination of this therapy with 3 x 10 mg butylscopolamine per day improved short-term results significantly, the long-term results were hardly influenced at all. Typifying results according to the Warnock method showed that we are dealing with recurrences in practically all cases and not with new infections. Minimal inhibition concentrations (MIC) of natamycin showed no marked changes as a consequence of the natamycin treatment.

Adult↗
PubMed1990

Significance of empty liposomes alone and as drug carriers in dermatotherapy.

The influence of three different liposome formulations (NAT 106, NAT 50, NAT 89), as empty liposomes and loaded with 0.05% betamethasone, on blood circulation in the corium was investigated by means of laser Doppler flowmetry. All three empty liposomes brought about a decrease in circulation. The maximum effect was reached 90 min after a 30-min occlusive application of the test preparations. Loading with betamethasone resulted in a significant increase in circulation after only 15 min. This increase in interpreted as a steroid effect. No comparable symptoms appeared with the application of base cream DAC (an O/W emulsion) or of betamethasone in base cream under identical experimental conditions.

Betamethasone↗
PubMed1990

[The effect of selected output parameters on the flushing results of MOET (Multiple Ovulation and Embryo Transfer)].

Superovulation responses from 299 Hessian donors were used to analyse the influence of selected traits and ovulation-parameters. The effects of the age of life were similar to those of other authors. Fat yield (phenotypic) showed a small positive influence on the number of collected embryos. Genetic value of the sire had no effect and using sperm of one or two bulls made no difference. A prediction of an individual MOET-response by a selected parameter is not possible.

Age Factors↗
PubMed1990

[Comparative study of the effect of various antiseptics and ozone gas on pathogens of ulcus cruris].

The germicidal influence of various antiseptics on the bacterial and fungal flora of leg ulcers was studied in vitro. Best effects were achieved by the triphenylmethane dyes brilliant green and methylrosaniline chloride. Chloramine and povidone iodine yielded average results, whereas the germicidal effects of potassium permanganate and eosin were not satisfactory. On the other hand, treatment with ozone resulted in sufficient inactivation of germs--with the only exceptions of Serratia and Klebsiella species.

Anti-Infective Agents, Local↗
PubMed1989

[Cardiospermum--a new phytogenic drug in dermatology?].

In a double blind study on persons with healthy skin, we tested the efficacy of cardiospermum ointment against the ointment base only. There were no significant differences between placebo and active substance regarding clinical evaluation, light reflection photometry, and transepidermal water loss. By means of doppler laser flowmetry, we found a decrease in corial blood supply after 16 hours' application of cardiospermum, which suggests a possible antiphlogistic effect.

Adult↗
PubMed1989

[Hairdressers' eczema--results of expert assessment 1984-1987].

The following study is based on the evaluation of 116 expert opinions obtained between 1984 and 1987 regarding patients working as hairdressers and suffering from eczemas. The most frequent allergen was nickel sulfate (57.7%). Exclusive nickel allergy without sensitization to substances professionally used, however, was only found in 6.9% of the female patients tested. Nickel allergy associated with sensitization to such substances was observed in 50.5% of the patients. 90 out of the 116 persons tested showed positive reactions to the indicator substance used in the hairdressers' trade and/or to the substances actually used during their work. Exclusive sensitization to one or more substances of the indicator group (occupationally used substances negative) was found in 13.3% of the patients; exclusive sensitization to substances actually used (indicator group negative) was seen in 16.7%.

Adult↗
PubMed1989

Hox-7, a mouse homeobox gene with a novel pattern of expression during embryogenesis.

A new mouse Hox locus, Hox-7, is defined on chromosome 5 by a gene homologous to the Drosophila gene msh, which contains a homeobox sequence distantly related to that of Antennapedia. By in situ hybridization, expression of Hox-7 is detected in the neural fold of embryos, and also in cephalic neural crest. In addition, expression takes place in the developing valves of the embryonic heart. Mandibular and hyoid arches are strongly labelled, expression becoming restricted to the most distal part of mouth and face processes as development proceeds. Intense labelling is also observed in developing limb buds, in the distal region which has been shown to be essential for limb morphogenesis. The pronounced accumulation and regional localization of Hox-7 transcripts in mandibular and limb processes point to a specific morphogenetic role for this mouse homeobox gene.

Amino Acid Sequence↗
PubMed1989

[Practical aspects of local steroid treatment].

Dermatocorticosteroids, the extent of whose effects show extraordinary differences, are principally applied in the case of skin inflammations and hyperproliferative skin diseases. Side effects, especially a dermally atrophizing effect, but also the provocation of rosacea, rosacea-like dermatitis and steroid acne, make it necessary to apply a treatment with as few side-effects as possible. Here in particular, therapy in steps and, to a lesser extent, interval therapy have proved themselves as being valuable. It is best to restrict oneself to a few dermatocorticosteroids, contained as far as possible in the same hypoallergenic base at varying concentrations. Thus the risk of sensitization and the different penetration levels depending on localization and dermatosis are taken into full account. A combined therapy with antibiotics is not indicated as a rule, and a combination with antimycotics should be restricted to a short period of time only.

Administration, Topical↗
PubMed1989

[Familial circumscribed plantar keratosis with sensorineural hearing loss and sporadic CHILD syndrome].

The authors report a case of siblings in whom circumscribed plantar keratoderma developed during early childhood. The keratotic areas increased with age and also affected the dorsal aspects of the digital joints. In addition, a markedly progressive disturbance in sound perception occurred in both children from age 4 onwards. This observation confirms the concept proposed by Blanchet-Bardon et al. that focal palmoplantar keratoderma with sensorineural hearing loss constitutes a distinct entity. In addition, the younger sister was affected with the CHILD syndrome. She suffered from linear ichthyosiform nevus with ipsilateral ectrodactyly. The simultaneous occurrence of the two syndromes is probably purely coincidental.

Child↗