Search PubMed⌕ Search

Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 217 records · Page 12Linked to original sources
PubMed1995

[Acute renal failure in neuroleptic malignant syndrome].

The neuroleptic malignant syndrome is characterized by hyperpyrexia, muscle rigidity, extrapyramidal motion disorder, vegetative symptoms and mental disorientation. This group of symptoms develops abruptly and may lead to serious complications. One of these complications is the acute renal failure. Permanent muscle rigidity causes the damage of muscle cells which result in myoglobinaemia, myoglobinuria and elevations in muscle related creatine phosphokinase. The authors report the case of a young man who underwent neuroleptic medication because of hebephrenia. During the medication the following symptoms were developed: extrapyramidal symptoms, restlessness, muscle rigidity, high fever. These symptoms eventually lead to acute renal failure caused by rhabdomyolysis (characteristic urine finding, significant elevations in serum creatine phosphokinase). With regards to the neuroleptic malignant syndrome dantrolenum and bromocriptin treatment were applied with the discontinuation of neuroleptic medication. As a part of the complex therapy a massive volumen-supplementing and alkalizing treatment was used but haemodialysis had also become necessary. During the above mentioned treatment symptoms referring to the neuroleptic malignant syndrome resolved and the acute renal failure was cured. The case report calls attention to a specific group of symptoms and the possibilities for prevention and treatment. The above case report is the first observation in Hungary.

Acute Kidney Injury↗
PubMed1995

Conformation and function of the N-linked glycan in the adhesion domain of human CD2.

The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)2-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.

Acetylglucosamine↗
PubMed1995

Detection of long-lived bound water molecules in complexes of human dihydrofolate reductase with methotrexate and NADPH.

The locations of long-lived bound water molecules in the binary complex of human dihydrofolate reductase (hDHFR) with methotrexate (MTX) and the ternary complex of hDHFR with MTX and NADPH have been investigated using 15N-resolved, three-dimensional ROESY-HMQC and NOESY-HSQC spectra acquired at 25 degrees C and 8 degrees C. NOEs with NH groups of the protein are detected for five bound water molecules in the binary complex and six bound water molecules in the ternary complex. Inspection of crystal structures of hDHFR reveals that the bound water molecules perform structural and functional roles in the complexes. Two water molecules located outside the active site, WatA and WatB, have similar NOEs in the binary and ternary complexes. These water molecules from multiple hydrogen bonds bridging loops and/or secondary structural elements in crystal structures of hDHFR and so stabilize the tertiary fold of the enzyme. Two water molecules in the active site, WatC and WatD, also have similar NOEs in both complexes. In crystal structures of hDHFR, WatC is involved in MTX binding by forming hydrogen bonds to the ligand and protein, while WatD stabilizes WatC by hydrogen bonding to it and the protein. A third active-site water molecule, WatE, has a markedly stronger NOE in the ternary complex than in the binary complex. Differences in the binding of WatE in the binary and ternary complexes are important for understanding the mechanism of DHFR, since this water molecule is believed to be involved in substrate protonation. Although the increased NOE intensity for WatE could be caused by a change in the position of water molecule, it may also be caused by an increase in its lifetime, since structural fluctuations in the active site are decreased upon cofactor binding. NOEs for one other water molecule, WatF, may be observed in the ternary complex but not the binary complex. WatF forms hydrogen bonds bridging the cofactor and the protein in crystal structures of hDHFR.

Amino Acid Sequence↗
PubMed1995

Contributions of tryptophan 24 and glutamate 30 to binding long-lived water molecules in the ternary complex of human dihydrofolate reductase with methotrexate and NADPH studied by site-directed mutagenesis and nuclear magnetic resonance spectroscopy.

Previous NMR studies on the ternary complex of human dihydrofolate reductase (hDHFR) with methotrexate (MTX) and NADPH detected six long-lived bound water molecules. Two of the water molecules, WatA and WatB, stabilize the structure of the protein while the other four, WatC, WatD, WatE and WatF, are involved in substrate binding and specificity. WatE may also act as a proton shuttle during catalysis. Here, the contributions of individual residues to the binding of these water molecules are investigated by performing NMR experiments on ternary complexes of mutant enzymes, W24F, E30A and E30Q. W24 and E30 are conserved residues that form hydrogen bonds with WatE in crystal structures of DHFR. Nuclear Overhauser effects (NOEs) are detected between WatE and the protein in all the mutant complexes, hence WatE still has a long lifetime bound to the complex when one of its hydrogen-bonding partners is deleted or altered by mutagenesis. The NOEs for WatE are much weaker, however, in the mutants than in wild-type. The NOEs for the other water molecules in and near the active site, WatA, WatC, WatD and WatF, also tend to be weaker in the mutant complexes. Little or no change is apparent in the NOEs for WatB, which is located outside the active site, farthest from the mutated residues. The decreased NOE intensities for the bound water molecules could be caused by changes in the positions and/or lifetimes of the water molecules. Chemical shift and NOE data indicate that the mutants have structures very similar to that of wild-type hDHFR, with possible conformational changes occurring only near the mutated residues. Based on the lack of structural change in the protein and evidence for increased structural fluctuations in the active sites of the mutant enzymes, it is likely that the NOE changes are caused, at least in part, by decreases in the lifetimes of the bound water molecules.

Amino Acid Sequence↗
PubMed1995

Composition and sequence specific resonance assignments of the heterogeneous N-linked glycan in the 13.6 kDa adhesion domain of human CD2 as determined by NMR on the intact glycoprotein.

CD2, a T cell specific surface adhesion receptor, is critically important for T lymphocytes to mediate their regulatory and effector functions. The amino terminal domain of human CD2 is responsible for cell adhesion, binding to CD58 on antigen-presenting cells or target cells. This adhesion domain in human CD2 contains a single high-mannose N-glycan. This carbohydrate or part of it appears to be required to maintain the native conformation of the polypeptide and its ability to bind CD58. To better understand the structural aspects that regulate human CD2 adhesion functions, we had previously determined the solution structure of the protein part of the N-glycosylated adhesion domain of human CD2 (hu-sCD2(105); MW approximately 13.6 kDa) by NMR spectroscopy. Here, we have identified protein--carbohydrate and carbohydrate--carbohydrate interactions and, in combination with previous knowledge from electrospray ionization mass spectrometry, have determined the composition of the heterogeneous high-mannose glycan in hu-sCD2(105). These contacts clearly define the carbohydrate's orientation with respect to the protein. The NMR data further suggest that one arm of the glycan is folded toward the trisaccharide core consisting of GlcNAc1-GlcNAc2-Man3. A detailed comparison between chemical shift data of free model oligosaccharides with those of the glycomers present in our hu-sCD2(105) sample reveals that only the resonances of the two GlcNAc residues are significantly different from those of free high-mannose glycans. This work was based on a new strategy to achieve sequential assignments of the 1H and 13C resonances of the heterogeneous high-mannose carbohydrate [(Man)nGlcNAc2, n = 5-8] in hu-sCD2(105) on the intact glycoprotein using a combination of homonuclear 1H-1H and heteronuclear 1H-13C NMR experiments at natural abundance.

CD2 Antigens↗
PubMed1995

Illness stage, concurrent medications, and other correlates of low testosterone in men with HIV illness.

Our objective was to assess whether illness stage, markers of illness progression, and use of medications believed to lower testosterone are associated with low serum testosterone in HIV+ men. Data were available for 234 HIV+ men screened for eligibility for a study of testosterone replacement therapy and/or an antidepressant trial. A screening interview was used to elicit demographic and medical information. Blood was drawn to measure markers of immunodeficiency and serum testosterone. Thirty-eight percent of the sample had testosterone levels below the normal range. Low testosterone was associated with lower CD4 cell count, later stage of illness, use of megestrol, and older age. Regression analysis showed that only age and use of such medications as megestrol were significant predictors of low testosterone. Given the prevalence of low testosterone in HIV+ men and its link to sexual dysfunction, more research is needed on treatments aimed at correcting or compensating for this hormonal deficiency as well as the study of the impact of such medications as megestrol on testosterone levels in older men.

Adult↗
PubMed1995

Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry.

The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta-sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions.

Amino Acid Sequence↗
PubMed1995

alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm.

Endplate preparations of the rat left hemidiaphragm were incubated with [3H]choline to label neuronal transmitter stores. Nerve evoked release of newly-synthesized [3H]acetylcholine was measured in the absence of cholinesterase inhibitors to investigate whether snake venom neurotoxins by blocking presynaptic nicotinic autoreceptors affect evoked transmitter release. Contractions of the indirectly stimulated hemidiaphragm were recorded to characterize the blocking effect of alpha-neurotoxins at the post-synaptic nicotinic receptors. Neither the long chain neurotoxins alpha-cobratoxin (1 microgram ml-1) and alpha-bungarotoxin (5 microgram ml-1) nor the short chain neurotoxin erabutoxin-b (0.1, 1 and 10 micrograms ml-1) affected the nerve-evoked release of [3H]acetylcholine. kappa-Bungarotoxin (1 and 5 micrograms ml-1), a toxin preferentially blocking neuronal nicotinic receptors, did also not affect evoked [3H]acetylcholine release, whereas (+)-tubocurarine (1 microM) under identical conditions reduced the release by about 50%. alpha-Bungarotoxin, alpha-cobratoxin and erabutoxin-b concentration-dependently (0.01-0.6 micrograms ml-1) inhibited nerve-evoked contractions of the hemidiaphragm. All neurotoxins except erabutoxin-b enhanced the basal tritium efflux immediately when applied to the endplate preparation or to a non-innervated muscle strip labelled with [3H]choline. This effect was attributed to an enhanced efflux of [3H]phosphorylcholine, whereas the efflux of [3H]choline and [3H]acetylcholine was not affected. It is concluded that the alpha-neurotoxins and kappa-bungarotoxin do not block presynaptic nicotinic receptors of motor nerves. These nicotinic autoreceptors differ from nicotinic receptors localized at the muscle membrane and at autonomic ganglia.

Acetylcholine↗
PubMed1995

Testosterone replacement therapy in HIV illness.

The purpose of this study was to determine whether testosterone replacement therapy ameliorates sexual dysfunction and associated problems of mood, energy, and appetite in HIV+ men with immune suppression (CD4 < 400 cells/cu mm) and low levels of serum testosterone. Assessments at study baseline and endpoint included psychiatric evaluation using the Structured Clinical Interview for DSM-III-R, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, the Karnofsky Performance Index, and a side-effects rating scale. Eighty-one men entered treatment and 72 completed at least 8 weeks. At study entry, 84% had an AIDS-defining condition (1993 CDC Criteria). In terms of sexual interest and function, 85% of study completers were clearcut responders at week 8. Mood response was also good: of the 44 study completers who had mood problems at baseline, 28 (64%) were rated as much improved. Mean change in CD4 cell count after treatment was not statistically significant. These findings suggest that testosterone replacement therapy should be considered for men with immune suppression and low testosterone levels who complain of diminished sexual desire and/or dysfunction. Replication with a placebo component is indicated.

Adult↗
PubMed1995

Analysis of high-resolution ECG changes during percutaneous transluminal coronary angioplasty.

The authors have hypothesized that low-level, electrocardiographic changes may accompany transient ischemia induced by percutaneous transluminal coronary angioplasty. Altered repolarization may manifest as subclinical changes in ST-T morphology. Changes in depolarization may manifest as low-amplitude notches and slurs, a phenomenon the authors term abnormal intra-QRS potentials. The initial aim of this study was to characterize changes in high-resolution electrocardiograph signals that might be linked to ischemic involvement of the ventricular myocardium.

Angioplasty, Balloon, Coronary↗
PubMed1995

Intimacy and sexual risk behaviour in serodiscordant male couples.

Several studies have demonstrated individual-level determinants of HIV sexual risk behaviour. Very little research has been conducted to identify couple-level factors associated with unsafe sexual behaviour. As part of a three-year study of more than 100 serodiscordant male couples, we conducted an in-depth qualitative study of 15 Latino and non-Latino male couples via focus groups and a follow-up telephone survey. We identified the sexual risk behaviour that occurs in these male couples, their perceptions of susceptibility for HIV transmission, and numerous couple-level and intrapsychic factors associated with their risk behaviour. We also describe the challenges confronted by these couples and barriers to emotional intimacy and couple satisfaction. Finally, we provide suggestions for ways of intervening to facilitate improved couple functioning, pleasure, satisfaction, and communication, and ways of reducing sexual risk behaviour without loss of emotional intimacy.

Adaptation, Psychological↗
PubMed1995

Isolation and characterization of a calmodulin-like protein from Halobacterium salinarium.

The first evidence for a calmodulin-like protein in an archaeon, Halobacterium salinarium, is reported here. The calmodulin-like protein, with a molecular mass of 24 kDa and an estimated pI of 4.8, stimulated cyclic nucleotide phosphodiesterase in a calcium-dependent manner. This stimulation could be suppressed by calmodulin inhibitors. The Ca(2+)-binding ability was verified by 45Ca autoradiography.

Bacterial Proteins↗