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G Wagner

Publications and source records attributed to G Wagner.

At least 253 records · Page 14Linked to original sources
PubMed1994

An evaluation of least-squares fits to COSY spectra as a means of estimating proton-proton coupling constants. II. Applications to polypeptides.

A new computational method for simultaneously estimating all the proton-proton coupling constants in a molecule from COSY spectra [Yang, J.-X. and Havel, T.F. (1994) J. Biomol. NMR, 4, 807-826] is applied to experimental data from two polypeptides. The first of these is a cyclic hexapeptide denoted as VDA (-D-Ala1-Phe2-Trp3-Lys(Z)4-Val5-Phe6-), in deuterated DMSO, while the second is a 39-residue protein, called decorsin, in aqueous solution. The effect of different data processing strategies and different initial parameter values on the accuracy of the coupling constants was explored. In the case of VDA, most of the coupling constants did not depend strongly on the initial values chosen for the optimization or on how the data were processed. This, together with our previous experience using simulated data, implies strongly that these values are accurate estimates of the coupling constants. They also differ by an average of only 0.36 Hz from the values of the 14 coupling constants that could be measured independently by established methods. In the case of decorsin, many of the coupling constants exhibited a moderate dependence on their initial values and a strong dependence on how the data were processed. With the most successful data processing strategy, the amide-alpha coupling constants differed by an average of 1.11 Hz from the 21 values that could be measured by established methods, while two thirds of the three-bond coupling constants fell within 1.0 Hz of the ranges obtained by applying the Karplus relation to an independently computed ensemble of distance geometry structures. The averages of the coupling constants over multiple optimizations using random initial values were computed in order to obtain the best possible estimates of the coupling constants. Most clearly incorrect averages can be identified by large standard deviations in the coupling constants or the associated line widths and chemical shifts, and can be explained by strong coupling and/or overlap with the water signal, the diagonal peaks or other cross peaks.

Amino Acid Sequence↗
PubMed1994

[Angiography detection and embolization of a hemodynamically significant hemorrhage from the right dorsal penile artery in symphysis rupture].

Pelvic fractures are frequently complicated by concomitant vascular lacerations involving, particularly, branches originating from the internal iliac arteries. Massive hemorrhage may be difficult to be treated surgically. In such cases interventional radiology can be helpful and able to treat definitely extensive hemorrhage caused by pelvic trauma.

Adult↗
PubMed1994

Cell surface adhesion receptors.

Several new structural motifs found in cell surface adhesion receptors have been described in the past few years. Also, several two-domain structures of extracellular portions of cell surface proteins have been reported. Structural models for complexes between receptors and counter-receptors have been proposed. The first reports on carbohydrate conformation in intact glycoprotein domains have recently appeared. These new data are presented within a more general review of the field of cell adhesion receptors.

Amino Acid Sequence↗
PubMed1994

Metal-coordination sphere in the methylated Ada protein-DNA co-complex.

BACKGROUND: The Ada protein of Escherichia coli repairs methyl phosphotriesters in DNA by direct, irreversible methyl transfer to one of its own cysteine residues. This residue, Cys69, is ligated to a tightly bound zinc ion in the protein. After methyl transfer, Ada can bind DNA sequence-specifically, inducing the transcription of genes that confer resistance to the toxic effects of methylating agents. Coordination of zinc via a thioether-S is exceedingly rare. We therefore investigated whether methylation causes ligand exchange of Cys69, replacing the thioether with a new zinc ligand with higher affinity for the metal. RESULTS: We added a 13C-labeled methyl group to Cys69 of Ada and used isotope-edited NMR to observe the behavior of its protons. Comparison of the spectra for the Zn- and 112Cd-bound forms of the methylated protein with that of the 113Cd-bound form provided clear evidence that S-Me-Cys69 is coordinated to the metal in Ada when Ada is bound specifically to DNA. CONCLUSIONS: The transcriptionally competent form of Ada, in which Cys69 is methylated and the protein is bound to DNA, maintains the coordination of S-Me-Cys69 to the metal ion. Thus, ligand exchange is not responsible for switching Ada from a DNA-repair protein to a transcriptional activator. We propose that the lability of the thioether-zinc coordinate bond may provide a mechanism for down-regulation of the adaptive response by inactivation of the Ada DNA-binding domain.

Bacterial Proteins↗
PubMed1994

Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells.

Intracavernous pharmacotherapy relies heavily on the use of vasoactive agents which act by increasing intracellular cAMP levels in human corpus cavernosum smooth muscle. Yet little is known about the cAMP generating system in this tissue, and how it may affect observed patient variability. Thus, the goal of these studies was to better characterize the biochemistry of cAMP formation in human corpus cavernosum smooth muscle, and thus provide more insight into the mechanisms of corporal smooth muscle relaxation in vivo. We studied both receptor and nonreceptor mediated increases in cAMP formation in short-term cultures of human corpus cavernosum smooth muscle cells. Both isoproterenol (ISO) and prostaglandin E1 (PGE1) produced concentration-dependent increases in cAMP, but histamine, serotonin and vasoactive intestinal polypeptide did not. Forskolin, a relatively specific activator of adenylate cyclase, was also a potent stimulant of cAMP formation in these cells. Moreover, there was a direct correlation between the degree of forskolin-induced cAMP accumulation in cultured corporal smooth muscle cells and the magnitude of the forskolin-induced relaxation response of precontracted isolated corporal smooth muscle strips. Prostaglandin E1 and ISO concentration response curves (CRCs) were then assayed in the absence and presence of subthreshold forskolin (0.1 microM.). In the presence of forskolin, the calculated maximal PGE1-induced cAMP accumulation (Emax) was significantly greater than that elicited by PGE1 alone, ISO alone, or ISO + forskolin (p < or = 0.02). In addition, a fixed molar ratio (FMR) (PGE1:ISO) protocol was used to demonstrate that both 80:20 and 70:30 FMRs (but not 95:5 or 90:10), were associated with significantly greater cAMP Emax values than that observed for PGE1 alone (p < or = 0.01). These data provide direct evidence that the degree of cAMP formation in cultured corporal smooth muscle cells is strongly correlated with the magnitude of relaxation of isolated corporal smooth muscle strips. In addition, since simultaneous activation of distinct components of the cAMP generating system produces significant increases in maximal intracellular cAMP accumulation, this suggests that such drug combinations may also augment corporal smooth muscle relaxation in vitro and in vivo.

Alprostadil↗
PubMed1994

Effect of imipramine on mood and enumerative measures of immune status in depressed patients with HIV illness.

OBJECTIVE: The authors' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness. Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate standard doses of imipramine. Second, the authors sought to determine whether imipramine treatment is associated with changes in immune status. METHOD: A double-blind, randomized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic. After 6 weeks of treatment, responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly. All patients were offered 26 weeks of treatment. Of the 97 patients who were randomly assigned to placebo or imipramine, 80 completed the 6-week phase. Main outcome measures included the Clinical Global Impression, the Hamilton Depression Rating Scale, the Brief Symptom Inventory, and CD4 cell count. RESULTS: Among study completers, 31 (39%) had AIDS. The response rate to imipramine was 74% and the response rate to placebo was 26%. There was no difference in depression response between patients with more or less severe immunodeficiency, nor was there a difference in medication dose or side effects. Neither type nor duration of treatment influenced CD4 cell count during the course of treatment. CONCLUSIONS: Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients. Severity of immunosuppression is not associated with imipramine treatment outcome. There is no evidence that imipramine has negative effects on enumerative measures of immune status.

Adolescent↗
PubMed1994

Integration of one's religion and homosexuality: a weapon against internalized homophobia?

Internalized homophobia as a psychological phenomenon has attracted little systematic research despite its destructive impact on the mental health of the gay community. This study looks at the relationship between internalized homophobia and the process of integrating one's religious faith and homosexuality by comparing levels of internalized homophobia among male participants of Dignity, an organization of Catholic gay men and lesbians, with a community sample of gay men with Catholic backgrounds. While many gay men believe they must abandon their religious faith (nearly 50% of this community sample no longer endorse a "formal religion") in order to accept their sexuality, Dignity members are actively integrating their religion and homosexuality--a process which we hypothesized would result in the Dignity participants being less homophobic than the community sample. While results showed no significant differences between the groups with regard to level of internalized homophobia, there are suggestions that involvement in Dignity does foster positive attitudes towards one's homosexuality by helping to overcome a delay in the development of a gay orientation. We also examined how other variables such as HIV status, psychological distress, conservative versus liberal ideology, and integration into the gay community would be associated with internalized homophobia.

Adaptation, Psychological↗
PubMed1994

Detection of varicella zoster virus (VZV) DNA in fetal tissue by polymerase chain reaction.

Primary Varicella Zoster Virus (VZV) infection during pregnancy can be associated with severe fetal malformation. The virological diagnosis of congenital VZV syndrome has not yet been successful, however, as VZV could not be isolated from fetal tissue. We have now applied a polymerase chain reaction (PCR) assay to allow the detection of VZV DNA in fetuses whose mothers had acquired chickenpox in the first trimester of pregnancy. In 2 of 3 fetuses investigated viral DNA was identified by PCR independently in 2 laboratories, thus confirming a direct fetal VZV infection.

Base Sequence↗
PubMed1994

Evaluation of vaginal and perineal area during the use of external sanitary protection throughout the menstrual cycle.

A clinical study evaluated potential external genital effects associated with the use of sanitary protection. The subjects used either a pad with traditional cellulose absorbent core or one containing cellulose and absorbent gelling material. Assessments included objective (transepidermal water loss, vaginal pH) and semi-quantitative subjective--methods (skin irritation grading, gynaecological inspection). No statistical or clinical significant differences for any of the parameters evaluated between the groups using the two pads, or compared to the non-pad control period, were found. The parameters used to study the effects on the genital area of an external sanitary product appear appropriate. No significant changes were observed for either of the two pads during daily use for two menstrual cycles.

Adult↗
PubMed1994

Bacteriorhodopsin crystal growth under microgravity--results of IML-1 and Spacehab-1 experiments.

The results of two crystal-growth experiments in microgravity with the membrane protein bacteriorhodopsin are reported, namely the IML-1 experiment in the Advanced Cryostat which resulted in a significant improvement in the compact crystal morphology of the needles, and the Spacehab-1 experiment in the Advanced Protein Crystallisation Facility which extended the IML-1 results with improved morphology of the triclinic needles. The enhanced diffractional power of these bacteriorhodopsin crystals grown in microgravity has extended the hitherto 8 angstroms resolution limit by 2 angstroms.

Bacteriorhodopsins↗
PubMed1994

Effects of fluoxetine on mood and immune status in depressed patients with HIV illness.

BACKGROUND: When present, depression in the context of human immunodeficiency virus (HIV) illness not only detracts from quality of remaining life but may interfere with motivation to obtain good medical care as well, thus directly influencing life's duration. This study was undertaken to assess the efficacy of fluoxetine in treating depression occurring in the context of HIV illness and to assess effects, if any, of fluoxetine on immune status (T-cell subsets). METHOD: Patients had originally participated in a double-blind, placebo-controlled, 6-week study of imipramine. Imipramine nonresponders or relapsers and side effect dropouts were offered open treatment with fluoxetine for 12 weeks. Adjunctive dextroamphetamine was prescribed if the treating psychiatrist considered it clinically indicated. Eligibility criteria for the original study included a DSM-III-R diagnosis of major depression, dysthymia, or both. Concurrent HIV medications were permitted. RESULTS: Measures included the clinician-rated Hamilton Rating Scale for Depression and Clinical Global Impressions Scale, and patient-rated Brief Symptom Inventory and Beck Hopelessness Scale. Of the 23 patients receiving only fluoxetine, 83% (N = 19) were classified as responders. Of the 7 (30%) who also received adjunctive dextroamphetamine, all responded. Patients with CD4 cell counts under 200/cu mm did as well as others. CD4 cell count was not influenced by duration of treatment with fluoxetine; the average decline was that expected due to the passage of time alone. Side effects were mild and relatively infrequent. CONCLUSION: In this open treatment study, fluoxetine alone and fluoxetine plus dextroamphetamine were found to be effective treatments for patients with HIV illness and Axis I depression, regardless of the initial level of immune deficiency or number or type of HIV medications used concurrently. No negative effects on immune status were observed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effects of sertraline on mood and immune status in patients with major depression and HIV illness: an open trial.

BACKGROUND: To date, the efficacy of sertraline in treating depression in the context of human immunodeficiency virus (HIV) has not been investigated, despite the agent's advantageous side effect profile, low toxicity with overdose, and lack of adverse effect on the cardiovascular system. This 8-week open trial addresses the efficacy of sertraline in the treatment of depressed HIV-infected persons, as well as its toleration and effects on immune status (T cells and natural killer cells). METHOD: Eligibility criteria included a DSM-III-R diagnosis of major depression; among the exclusion criteria were substance abuse, dementia, and severe gastrointestinal complaints. Major outcome variables included the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and laboratory tests measuring T cell subsets and natural killer cells. RESULTS: Twenty-seven gay men and 1 woman entered treatment; 20 completed 8 weeks. Fourteen (70%) of the completers were rated responders. Five of the 8 dropouts (18% of the total sample) discontinued treatment due to side effects. Responders improved significantly on all measures of psychiatric distress as well as quality of life. Those with advanced immunosuppression (CD4 cell count < 200/cu mm) responded as well to treatment as did the others. All T cell subsets, including CD4 cell count, and natural killer cell counts (CD56 and CD57) showed no significant change from baseline to study endpoint, an average of 17 weeks later. CONCLUSION: In this small open trial, sertraline was an effective treatment for depression, displayed no apparent adverse effects on immune status, and was generally well tolerated; however, a randomized placebo-controlled study with a larger, more diverse sample is needed to confirm our results.

1-Naphthylamine↗
PubMed1994

Interaction of albumin-bound ebselen with rat liver glutathione S-transferase and microsomal proteins.

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a selenium-containing heterocyclic compound, transported bound to albumin in blood. In this report, we demonstrate the transfer of ebselen from its albumin complex to rat liver cytosolic glutathione-S-transferase (GST) and microsomal proteins, as compared to papain. Free ebselen binds to the sulfhydryl groups of proteins, such as GST and papain [Nikawa, T., Schuch, G., Wagner, G. & Sies, H. Biochem. Pharmacol. (in press)]. 2-Mercaptoethanol and N-ethylmaleimide interfere with ebselen binding to microsomal proteins, suggesting that ebselen also binds to the sulfhydryl groups of microsomal proteins. Ebselen is transferred from its albumin complex to rat liver cytosolic GST and microsomal proteins, but not to papain. These results suggest the possibility that ebselen is transferred from albumin to other proteins using their sulfhydryl groups in vivo.

Animals↗
PubMed1993

Solution structure of the DNA methyl phosphotriester repair domain of Escherichia coli Ada.

The Escherichia coli Ada protein repairs methyl phosphotriesters in DNA by direct, irreversible methyl transfer to one of its own cysteine residues. The methyl-transfer process appears to be autocatalyzed by coordination of the acceptor residue, Cys-69, to a tightly bound zinc ion. Upon methyl transfer, Ada acquires the ability to bind DNA sequence-specifically and thereby to induce genes that confer resistance to methylating agents. The solution structure of an N-terminal 10-kDa fragment of Ada, which retains zinc binding and DNA methyl phosphotriester repair activities, was determined using multidimensional heteronuclear nuclear magnetic resonance techniques. The structure reveals a zinc-binding motif unlike any observed thus far in transcription factors or zinc-containing enzymes and provides insight into the mechanism of metalloactivated DNA repair.

Bacterial Proteins↗