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Biomedical subjects

G Wille

Publications and source records attributed to G Wille.

At least 19 recordsLinked to original sources

Recanalization after thrombolysis in stroke patients: predictors and prognostic implications.

OBJECTIVE: To estimate rates, predictors, and prognostic importance of recanalization in an unselected series of patients with stroke treated with IV thrombolysis. METHODS: We performed a CT angiography or transcranial Doppler (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with documented occlusion of the intracranial internal carotid or middle cerebral artery (MCA). Complete recanalization was defined by a rating of 3 on the Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain Ischemia grading scales. Information about risk factors, clinical features, and outcome was prospectively collected by standardized procedures. RESULTS: Complete recanalization was achieved in 36 of the 64 patients (56.3%). There was a nonsignificant trend of recanalization rates to decline with a more proximal site of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in subjects with additional extracranial carotid occlusion (p = 0.03). Finally, complete recanalization predicted a favorable stroke outcome at day 90 independently of the information provided by age, NIH Stroke Scale, and onset-to-needle time. CONCLUSIONS: We found a high rate of vessel recanalization after IV thrombolysis occlusion. However, recanalization was infrequent in patients with diabetes and extracranial carotid occlusion. Information on recanalization was a powerful, early predictor for clinical outcome.

Aged↗

Incarcerated vermiform appendix in a left-sided inguinal hernia.

We report here of a patient with an incarcerated vermiform appendix occurring in a left-sided indirect inguinal hernia. Occasionally, appendices are found in a hernial sac; however, the finding of an incarcerated vermiform appendix in an inguinal hernia on the left side is very unusual and has only been previously described once. The patient suffering this rare entity underwent appendectomy and repair of the hernia and experienced an uneventful postoperative recovery. The possibility of the presence of a situs inversus, or malrotation, as an underlying cause for the observed pathology was excluded by x-ray examination.

Aged↗

Malassezin--A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50 = 1.57 microM) in rat hepatocytes.

Animals↗

[Synthesis of fluorochromes and pigments in Malassezia furfur by using tryptophan as the single source of nitrogen].

A new minimal medium consisting only of L-tryptophan (L-trp) and a lipid source induced formation of brown pigmentation only in the species Malassezia furfur. Strains of the species M. sympodialis and M. pachydermatis failed to grow on this medium. Pigmentogenesis was already induced in M. furfur by 0.01 g% tryptophan, the pH optimum was pH = 5. Alternative amino nitrogen sources given concurrently with trp suppressed pigmentogenesis. The extract of the culture exhibited remarkable fluorescence, and several indole derivatives with a broad spectrum of colors were detected by means of mass spectroscopy and NMR. This finding may have an impact on the clinical appearance of pityriasis versicolor, a very common skin disease caused by lipophilic yeasts of the genus Malassezia. We hypothesize that in pityriasis versicolor metabolic adaptation of Malassezia yeasts to altered nitrogen conditions on superficial skin might be of pathophysiological importance. Tryptophan as inductor of pigmentogenesis probably cumulates during excessive sweating, a well known manifestation factor of pityriasis versicolor.

Dermatomycoses↗

Keratins as molecular markers of epithelial differentiation: differential expression in crypt epithelium of human palatine tonsils.

The expression of keratins in the stratified squamous nonkeratinizing epithelium lining the surface and the crypts of human palatine tonsils was analyzed by high-resolution gel electrophoresis, immunoblotting, and immunohistochemical techniques. In contrast to the superficial epithelium, which showed a fairly constant keratin composition consisting of the neutral-to-basic keratins K4, K5, K6, and K8 and the acidic keratins K13, K14, K16, and K19, the keratin profiles of tonsillar crypt epithelial cells were found to be more variable, particularly with respect to the expression levels of K4 and K13. These were identical to those of surface epithelium, reduced, or abolished. Since K4 and K13 characterize the mature stage of differentiation in squamous nonkeratinizing epithelia, their decrease is indicative of an incomplete epithelial differentiation. Immunohistochemical analyses confirmed this hypothesis and allowed us, furthermore, to correlate the expression of K13 with the morphologic alterations of tonsillar crypt epithelium in the course of reticulation.

Adolescent↗

Allele frequencies and segregation of human polymorphic keratins K4 and K5.

Two electrophoretic variants for each of the human keratins K4 and K5 that are expressed in squamous nonkeratinizing epithelia lining the upper digestive tract could be distinguished on SDS-PAGE. Based on a sampling size of 1,299 unrelated individuals, calculation of allele frequencies showed the alleles to be in Hardy-Weinberg equilibrium. The genetic basis of this variation was confirmed by both quantitative gene dosage dependence and the transmission of the variants as Mendelian traits in two families. Thus the human keratin genes K4 and K5 are polymorphic, and each presents with two codominant alleles (a and b).

Alleles↗

Conformational characteristics of the hexanucleoside pentaphosphate AUAUAU: a 2D NMR study at 500 MHz.

All 36 ribose proton resonances and most of the base proton resonances of the hexanucleoside pentaphosphate AUAUAU have been assigned unequivocally using 2D J-resolved spectroscopy, spin echo correlated spectroscopy (SECSY) and 2D NOE spectroscopy (NOESY). The NMR parameters of AUAUAU are compared with those of smaller fragments that contain methylated adenine bases: m62AU, m62AUm62A, m62AUm62AU and m62AUm62AUm62A. Previous studies on this series of compounds have shown that in all these cases purine-pyrimidine-purine sequences prefer to adopt a mixture of states which have as common feature that the interior pyrimidine residues are bulged out, whereas the purine residues stack upon each other. Chemical shift data, proton-proton coupling constants, as well as the observation of imino-proton resonances for AUAUAU show unambiguously that upon lowering the temperature the high-temperature "bulged out" situation reverts to a normal A-RNA-like double helix.

Computers↗

Interaction of platinum compounds with short oligodeoxynucleotides containing guanine and cytosine.

The products resulting from reaction of cis-Pt(NH3)2Cl2 with d(CpCpGpG), d(GpCpG), d(pCpGpCpG), d(pGpCpGpC) and d(CpGpCpG) and from reaction of [Pt(dien)Cl]Cl with d(CpCpGpG) and d(GpCpG) have been characterized with the aid of proton NMR spectroscopy, circular dichroic spectroscopy and Pt analysis. The binding sites of the Pt compounds were determined by pH-dependent NMR spectroscopy. Binding of the two Pt compounds invariably occurs at the guanine N7 atoms. In all compounds containing [cis-Pt(NH3)2]2+ chelates are formed by coordination of platinum to two guanines of the same oligonucleotide. The resulting intrastrand-cross-linked oligonucleotides contain either d(GpG) . cisPt units, or d(GpCpG) . cisPt units. In the latter case the middle cytosine is not coordinated to platinum. As a result the conformational changes originating from these two chelates are different from each other. In the case of [Pt(dien)Cl]Cl as a starting product, two types of oligonucleotide adducts are formed, i.e. those with one Pt atom/molecule and those with two Pt atoms/molecule. The NMR spectra of the adducts containing only one Pt(dien)2+ show that only one adduct is formed, although two guanine bases are present. This indicates a preference for one of the N7 atoms in the molecule.

Binding Sites↗

Proton NMR studies on the covalently linked RNA-DNA hybrid r(GCG)d(TATACGC). Assignment of proton resonances by application of the nuclear Overhauser effect.

Proton NMR spectra of a covalently linked self-complementary RNA X DNA hybrid, r(GCG)-d(TATACGC), are recorded in H2O and D2O. Imino proton resonances as well as the non-exchangeable base and H-1' resonances are unambiguously assigned by means of nuclear. Overhauser effect measurements. Additional information was obtained by 31P NMR and circular dichroism spectra. The RNA parts in the duplex attain full conformational purity and adopt the usual A-RNA conformation. The DNA residues opposite the RNA tract do not adopt an A-type structure completely. Their respective sugar rings still appear to possess a certain conformational freedom. The same holds true for the central d(-TATA-) sequence which forms a DNA X DNA duplex. There appears to be a structural break in this part: the first two residues, T(4) and A(5), are clearly influenced by the adjacent RNA structure, whereas residues T(6) and A(7) behave quite similar to what usually is found in DNA duplexes in aqueous solution.

Base Sequence↗

Assignment of non-exchangeable base proton and H1' resonances of a deoxyoctanucleoside heptaphosphate d(G-G-C*-C*-G-G-C-C) by using the nuclear Overhauser effect.

The resonances of the non-exchangeable base protons and 1' protons of the octamer d(G-G-C*-C*-G-G-C-C), C* = m5dC, have been assigned by means of NOE difference NMR spectroscopy at 500 MHz. From the measured J1'2' and J1'2" it follows that the octamer at low temperature prefers to adopt a B-DNA double-helical conformation in solution, however, some residual conformational freedom is detected at the 3' terminus. From the chemical shift versus temperature profiles it is concluded that no major conformational change occurs below 60-65 degrees C where the duplex formation for residues (2) to (6) is essentially completed under the conditions used.

Base Sequence↗

Conformational analysis of a ribopentanucleoside tetraphosphate in aqueous solution. A two-dimensional NMR study at 500 MHz.

The 30 ribose proton resonances of the pentaribonucleoside tetraphosphate m6(2)AUm6(2)AUm6(2)A have been assigned unequivocally by means of spin-echo-correlated spectroscopy, 2D J-resolved spectroscopy and Nuclear Overhauser difference spectroscopy, carried out at 500 MHz. A detailed comparison of the conformational properties of the title compound with its constituent fragments m6(2)AUm6(2)AU, m6(2)AUm6(2)A, m6(2)AU and the relevant monomers is given. Chemical shift data indicate the existence of a doubly "bulged out" conformer, in which the two interior U-fragments are not involved in regular nearest neighbour stacking interactions. The coupling constants of the ribose-ring are interpreted in terms of the N/S equilibrium, and population distributions along the backbone angles beta and gamma are presented. The combined data suggest a strong similarity between the 5'-terminal triplets in m6(2)AUm6(2)AUm6(2)A, m6(2)AUm6(2)AU and m6(2)AUm6(2)A2.

Adenine↗

A general method for the synthesis of 5'-monophosphates of DNA fragments via phosphotriester intermediates.

A new and attractive phosphorylation procedure which allows the introduction, via phosphotriester intermediates, of 5'-phosphate functions of DNA fragments is described. The method is based on the activation of bifunctional phosphorylating agents with 1-hydroxybenzotriazole. The approach will be exemplified by the synthesis of pACGC using four different 5'-phosphotriester intermediates.

Chemical Phenomena↗

Chemical synthesis of a messenger ribonucleic acid fragment: AUGUUCUUCUUCUUCUUC.

The synthesis via a phosphotriester method of the octadecaribonucleotide AUG(UUC)5 (19) is reported. The octadecanucleotide is meant to serve as a synthetic messenger in a ribosomal protein synthesizing system. A fully protected octadecamer intermediate (18a) was prepared by a block coupling procedure. For the introduction of the desired 3'-5'-internucleotide bonds a 3'-O-(2,2,2-trichloroethyl 2-chlorophenyl phosphate) function was incorporated into the monomeric building blocks which were applied in the synthesis of 18a. Monomeric and oligomeric compounds with a thus protected 3'-O-phosphotriester function can be selectively deblocked to give 3'-O-phosphodiester derivatives suitable for condensation with 5'-hydroxyl (oligo)nucleotides. Conversion of fully protected oligomers to 5'-hydroxyl derivatives, suitable for further coupling at the 5' end, was effected by selective removal of the levulinyl function at the 5' end. The fully protected octadecanucleotide 18a was deblocked with fluoride ions, followed by ammonia and acid to give the required octadecamer 19. The condensing agent 1-(2,4,6-triisopropyl-phenylsulfonyl)-3-nitro-1,2,4-triazole, which was applied to effect the formation of fully protected 3'-5'-internucleotide phosphotriester functions, may give rise to side reactions with the heterocylic bases uracil and guanine. The consequences of these side reactions for the synthesis of octadecamer 19 are reported.

Base Sequence↗

[Ascertainment of physical fitness for work in persons applying for annuities in the Federal Republic of Germany (author's transl)].

Annuities granted because of unfitness for work in general or unfitness to perform particular professional work are being paid in Germany by a state insurance agency. Unfitness for work has to be ascertained in each individual case as has been ruled by jurisdiction of the Highest German Court. It is the task of the medical expert in the course of this procedure to register the clinical status of the applicants and to reach a medical judgment in regard to fitness for work. This judgment does not rely upon the diagnosis or prognosis of a particular disease; a decreased fitness for work because of a particular disease can only be assumed if the disease has led to long-term irreversible deficient organ functions. Annuities for a limited time period may be granted if there is a chance for improvement of health. Problems of finding expert judgement are reported.

Disability Evaluation↗

Synthesis of oligonucleotides with sequences identical with or analogous to the 3'-end of 16S ribosomal RNA of Escherichia coli: preparation of m-6-2-A-C-C-U-C-C and A-C-C-U-C-m-4-2C via phosphotriester intermediates.

The synthesis of two fully-protected hexanucleotides (11a and 11b) via a phosphotriester approach, which is based on the use of two types of protecting groups for the internucleotide linkages, i.e. one 2,2,2-tribromo-ethyl at the 5'-terminus and four 2-chlorophenyl groups for the remaining linkages, is reported. The hexanucleotides 11a and 11b, assembled via a block-wise two-step phosphotriester method, can be deblocked conveniently to give the two hexamers 12a and 12b containing only 3'leads to5' internucleotide linkages.

Adenine Nucleotides↗

Synthesis of oligonucleotides with sequences identical with or analogous to the 3'-end of 16S ribosomal RNA of Escherichia coli: preparation of A-C-C-U-C-C via the modified phosphotriester method.

A combination of two different methods for the synthesis of oligoribonucleotides, i.e. the two-step phosphotriester method with 2-chlorophenyl phosphate as bifunctional phosphate source and the modified triester method with 2,2,2-trichloroethyl 2-chlorophenyl phosphorochloridate as monofunctional phosphate source, is applied for the synthesis of the fully-protected hexaribonucleotide A-C-C-U-C-C. The two-step method is used for the synthesis of the required dinucleotide monophosphates 9, 10 and 11. Application of the modified triester method for the coupling of the oligonucleotide blocks results in the formation of the fully-protected hexamer 15. Furthermore, attention is paid to 2,4,6-triisopropylbenzenesulphonyl 4-nitroimidazolide as a new condensing agent for the coupling of larger oligonucleotide blocks.

Adenine Nucleotides↗