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Biomedical subjects

R Wagner

Publications and source records attributed to R Wagner.

At least 109 records · Page 6Linked to original sources
PubMed1999

Accelerated clearance of SHIV in rhesus monkeys by virus-like particle vaccines is dependent on induction of neutralizing antibodies.

Recombinant, insect cell derived SIV Pr56(gag) virus-like particles (VLPs) have been modified either by inserting HIV-1 Gp160 derived peptides into the Pr56(gag) precursor or by integrating the complete HIV-1 gp120 in the particle membrane. To investigate the protective efficacy of these particulate antigens, rhesus macaques were immunized with VLPs both adjuvant-free or adsorbed to alum. In addition, recombinant Semliki Forest viruses (SFV) expressing proteins corresponding to the VLP constructs were established and administered as live vaccines in combination with particulate antigens. Vaccination induced specific humoral responses irrespective of the immunization regimen. However, in contrast to Pr56(gag)-specific antibodies, Env-specific antibody titers could not be increased by booster immunizations in this study. Cell-mediated immune responses were detected following vaccination with VLP-preparations as well as recombinant SFVs. A tendency towards stimulating both enhanced cell mediated as well as humoral immune responses was observed following priming with recombinant SFVs. Upon challenge with SHIV-4 all vaccinated monkeys became infected. However, animals, that were vaccinated with VLPs presenting the complete gp120, managed to clear virus faster than nonimmunized controls. The observed virus elimination significantly correlated with an anamnestic antibody response and an accelerated appearance of neutralizing antibodies postchallenge.

AIDS Vaccines↗
PubMed1999

Improvement of myocardial blood flow to ischemic regions by angiotensin-converting enzyme inhibition with quinaprilat IV: a study using [15O] water dobutamine stress positron emission tomography.

OBJECTIVES: This study was designed to analyze the effects of acute angiotensin-converting enzyme (ACE) inhibition on myocardial blood flow (MBF) in control and ischemic regions. BACKGROUND: Although animal studies indicate an improvement of MBF to ischemic regions after ACE inhibition, this effect has not been conclusively demonstrated in patients with coronary artery disease. METHODS: Myocardial blood flow was analyzed in ischemic and nonischemic regions of 10 symptomatic patients with coronary artery disease using repetitive [15O] water positron emission tomography at rest and during maximal dobutamine stress before and after ACE inhibition with quinaprilat 10 mg i.v. To exclude the possibility that repetitive ischemia may cause an increase in MBF, eight patients underwent the same protocol without quinaprilat (placebo patients). RESULTS: Rate pressure product in control and quinaprilat patients was comparable. In placebo patients, repetitive dobutamine stress did not change MBF to ischemic regions (1.41 +/- 0.17 during the first stress vs. 1.39 +/- 0.19 ml/min/g during the second stress, p = 0.93). In contrast, MBF in ischemic regions increased significantly after acute ACE inhibition with quinaprilat during repetitive dobutamine stress (1.10 +/- 0.13 vs. 1.69 +/- 0.17 ml/min/g, p < 0.015). Dobutamine coronary reserve in ischemic regions remained unchanged in placebo patients (1.07 +/- 0.11 vs. 1.10 +/- 0.16, p = 0.92), but increased significantly after quinaprilat (0.97 +/- 0.10 vs. 1.44 +/- 0.14, p < 0.002). Total coronary resistance decreased after ACE inhibition (123 +/- 19 vs. 71 +/- 10 mm Hg x min x g/ml, p < 0.02). CONCLUSIONS: Angiotensin-converting enzyme inhibition by quinaprilat significantly improves MBF to ischemic regions in patients with coronary artery disease.

Adult↗
PubMed1999

Local variations of the chemistry in as-cast gamma-TiAl (TiBx) alloys and its consequence for thermomechanical treatments

The first part of the paper presents an accompanying investigation to a thermomechanical processing route of gamma-TiAl turbine blades. By means of scanning electron microscopy and energy dispersive X-ray (EDX) analysis, the chemical homogeneity and the microstructures of gamma-TiAl as-cast ingots, work pieces and the final turbine blades are determined. We find that the local Al-content in as-cast ingots can vary by more than 1.5 at.%. Large chemical inhomogeneities present in as-cast ingots can only be eliminated to a certain degree by subsequent thermomechanical processing. An additional aim of the study is to assess the influence of a thermomechanical processing on the morphology of titanium boride precipitates and the alpha2-Ti3Al-phase. The second part of the paper contains a detailed analytical study devoted to homogenization of a range of gamma-TiAl cast alloys. Different microstructures are generated in a laboratory-scale argon-arc furnace by both rapid and slow solidification rates and an additional homogenization treatment, respectively. Quantitative EDX analysis shows that only rapid solidification of ingots with a subsequent homogenization treatment leads to a nearly chemically homogeneous microstructure.

Journal Article↗
PubMed1999

Parental representations associated with adult separation anxiety and panic disorder--agoraphobia.

OBJECTIVE: Early bonding abnormalities have been associated with a range of anxiety and depressive disorders in adulthood, but no specific parental patterns have emerged for particular disorders. The present study investigated the possibility that parental overprotectiveness may be linked to a risk of separation anxiety (SA) in adulthood. METHOD: Two samples were recruited: volunteers (n = 34) whose major anxieties focused on separation concerns, and adult anxiety clinic patients (n = 37) who were diagnosed with panic disorder. Parental characteristics and early SA were assessed by dichotomising the combined sample first according to adult SA categorisation and then by panic disorder status. RESULTS: Subjects assigned to the adult SA category reported high levels of juvenile SA and exposure to maternal overprotectiveness, whereas patients diagnosed with panic disorder reported few differences in their bonding histories compared to residual anxious patients. CONCLUSIONS: The findings of this study suggest that early SA and parental overprotectiveness may not be associated with panic disorder per se, but rather with persisting SA symptoms in adulthood. The overlapping samples and retrospectivity of some measures are important limitations of the study.

Adult↗
PubMed1999

[Prophylaxis against obstetric acid aspiration syndrome in the German Federal Republic in 1997. A review based on results of a federal survey].

A survey of all German hospitals providing obstetric anesthesia was performed in 1997 (n = 1061, recovery rate 82%; comprising about 700,000 deliveries and 115,000 cesareans, resp.) concerning the routine prophylactic measures for acid aspiration syndrome (AAS) in pregnant patients and before obstetric procedures (i.e., prevention of aspiration by positioning, Sellick's manoeuvre, reduction of intragastric volume, or reduction of gastric content acidity). In pregnant patients, any prophylaxis of AAS is performed in 36%. Of the patients expecting delivery in the labour ward, only 7% receive pharmacological AAS treatment. Before scheduled (urgent, non-emergency) cesarean section in general anesthesia, 93% (94%) of patients receive prophylactic treatment, either pharmacological or non-pharmacological. Before regional anesthesia, the corresponding numbers are 52% for both scheduled or urgent CS.

Adult↗
PubMed1999

Bleomycin versus OH-radical-induced malonaldehydic-product formation in DNA.

PURPOSE: To compare the actions of bleomycin and ionizing radiation on DNA regarding the formation of malonaldehyde-like products. MATERIALS AND METHODS: Calf thymus DNA was treated with iron/bleomycin or gamma-radiation at pH 7. Products were analysed by HPLC. The thiobarbituric-acid reactivity of the samples was determined directly or after HPLC by post-column derivatization. ESI mass spectra were taken on-line following HPLC. RESULTS: Malonaldehyde and malonaldehyde-like products as detected by the sensitive 2-thiobarbituric acid (TBA) assay are formed in gamma-irradiated DNA and thymidine solutions as well as upon treatment of DNA with bleomycin/iron. In gamma-irradiated DNA solutions in the presence of oxygen, no base propenals were detected, and the major TBA-active product was malonaldehyde. In the gamma-radiolysis of thymidine, thymine propenal was formed only in traces (not more than 0.07 per cent of the OH-radical yield). Malonaldehyde was practically absent after treatment with bleomycin; three other TBA-active products were seen by HPLC which have been identified as the cytosine, thymine, and adenine propenals. Guanine propenal was not detected under our conditions. CONCLUSIONS: The absence of these base propenals upon gamma-radiolysis implies that although the initiating step of OH-radical and bleomycin action [i.e. H-abstraction at C(4')] may be the same, the bleomycin-iron complex must participate in subsequent steps en route to the base propenals. It is proposed that the bleomycin pathway may involve the interaction of the C(4')-peroxyl radical with the 'spent' bleomycin-iron complex by ligand exchange, under formation of a bleomycin-iron-peroxyl-radical complex, Blm(Fe4+,*OOR), which then decomposes by heterolysis into the alkoxy cation precursor +OR of the base propenal and reconstitution of the bleomycin-iron complex Blm(Fe,O)3+, i.e. gives rise to base propenal formation without the involvement of a C(4')-hydroperoxide.

Animals↗
PubMed1999

Anesthesia for cesarean section and acid aspiration prophylaxis: a German survey.

UNLABELLED: We surveyed routine anesthetic practice and measures to prevent acid aspiration syndrome (AAS) in patients undergoing cesarean section (CS) throughout Germany. Of 1061 questionnaires, 81.9% were returned. For scheduled CS, general anesthesia was used in 63% of cases, and for urgent CS, it was used in 82% of cases. Regional anesthesia was used less often for both scheduled and urgent CS in smaller (< or =500 deliveries/yr; 28% and 16%, respectively) than in medium-sized (500-1000 deliveries/yr; 42% and 19%, respectively) or major obstetric departments (>1000 deliveries/yr; 45% and 21%, respectively). Among the regional techniques, epidural anesthesia (59%) was preferred more than spinal anesthesia (40%) in scheduled CS. In urgent CS, spinal anesthesia predominated (56% vs 42%). Pharmacological AAS prophylaxis is routinely used in 69% (68%) of departments before elective (urgent) CS under general anesthesia and in 52% under regional anesthesia. H2-blocking drugs are preferred for AAS prophylaxis over H2-blocker plus sodium citrate and sodium citrate alone. Both the incidence of and the mortality from AAS at CS are very low in Germany (<1 fatality per year). Nevertheless, AAS prophylaxis deserves more widespread use in obstetric anesthesia and in other patients at risk (e.g., children, outpatients). IMPLICATIONS: According to a countrywide survey, the use of regional anesthesia for cesarean section and pharmacological prophylaxis of acid aspiration syndrome is considerably less common in Germany than in the United States, United Kingdom, or other European countries.

Anesthesia, Conduction↗
PubMed1999

Reduced postoperative infections with an immune-enhancing nutritional supplement.

OBJECTIVES/HYPOTHESIS: Malnutrition is a significant risk factor for postoperative infections in patients undergoing oncologic surgery. This study was undertaken to determine if perioperative nutritional supplementation with an immune-enhancing formula is superior to standard formula in the prevention of postoperative infectious complications. STUDY DESIGN: This was a prospective, randomized, double-blind trial comparing perioperative nutritional supplementation with Impact and standard nutritional formulas. METHODS: Following stratification, 136 patients undergoing oncologic head and neck surgery were randomly assigned to one of four treatment groups: preoperative/postoperative Impact, postoperative Impact, preoperative/postoperative standard formula, and postoperative standard formula. Outcome measures included laboratory evaluations of nutritional status, infectious and wound healing complications, and duration of hospitalization. Statistical analysis was performed using chi2 or two-tailed Fisher Exact Tests, when appropriate. RESULTS: Intent-to-treat (P = .02) and actual therapy (P = .04) analyses revealed a significant decrease in the incidence of postoperative infectious complications (all sites) in patients who received Impact. There was no significant difference in wound healing problems or duration of hospitalization. Postoperative measures of nutrition status demonstrated a higher serum albumin (P = .05) in patients who received Impact compared with standard formula. CONCLUSIONS: Compared with standard formula, perioperative nutritional supplementation with Impact significantly reduced the incidence of infectious complications. The length of hospitalization was significantly prolonged in patients with postoperative infections, suggesting potential cost savings with the use of immune-enhancing formulas such as Impact.

Aged↗
PubMed1999

Self-focusing, channel formation, and high-energy ion generation in interaction of an intense short laser pulse with a He jet.

Using interferometry, we investigate the dynamics of interaction of a relativistically intense 4-TW, 400-fs laser pulse with a He gas jet. We observe a stable plasma channel 1 mm long and less than 30 microm in diameter, with a radial gradient of electron density approximately 5 x 10(22) cm(-4) and with an on-axis electron density approximately ten times less than its maximum value of 8 x 10(19) cm(-3). A high radial velocity of the surrounding gas ionization of approximately 3.8 x 10(8) cm/s has been observed after the channel formation, and it is attributed to the fast ions expelled from the laser channel and propagating radially outward. We developed a kinetic model which describes the plasma channel formation and the subsequent ambient gas excitation and ionization. Comparing the model predictions with the interferometric data, we reconstructed the axial profile of laser channel and on-axis laser intensity. The estimated maximum energy of accelerated ions is about 500 keV, and the total energy of the fast ions is 5% of the laser pulse energy.

Journal Article↗
PubMed1999

Consumer perceptions of involuntary outpatient commitment.

This study examined beliefs about the provisions of outpatient commitment and their effects among 306 people with severe and persistent mental illness who were awaiting a period of outpatient commitment. More than 80 percent of the respondents perceived that the court order for outpatient commitment required them to keep their appointments at the mental health center and to take medication as prescribed. More than three-quarters believed that the outpatient commitment order made it more likely that people would keep their mental health appointments, take their medication, and stay out of the hospital.

Adult↗
PubMed1999

Construction and characterization of recombinant VLPs and Semliki-Forest virus live vectors for comparative evaluation in the SHIV monkey model.

For testing of recombinant virus-like particles (VLPs) in the SHIV monkey model, SIVmac239 Pr56gag precursor-based pseudovirions were modified by HIV-1 gp160 derived peptides. First, well-characterized epitopes from the HIV-1 envelope glycoprotein were inserted into the Pr56gag precursor by replacing defined regions that were shown to be dispensable for virus particle formation. Expression of these chimeric proteins in a baculovirus expression system resulted in efficient assembly and release of non-infectious, hybrid VLPs. In a second approach the HIV-1IIIB external glycoprotein gp120 was covalently linked to an Epstein-Barr virus derived transmembrane domain. Coexpression of the hybrid envelope derivative with the Pr56gag precursor yielded recombinant SIV derived Pr56gag particles with the HIV-1 gp120 firmly anchored on the VLP surface. Immunization of rhesus monkeys with either naked VLPs or VLPs adsorbed to alum induced substantial serum antibody titers and promoted both T helper cell and cytotoxic T lymphocyte responses. Furthermore, priming macaques with the corresponding set of recombinant Semliki-Forest viruses tended to enhance the immunological outcome. Challenge of the immunized monkeys with chimeric SHIV resulted in a clearly accelerated reduction of the plasma viremia as compared to control animals.

Amino Acid Sequence↗
PubMed1999

Immunostimulatory CpG motifs trigger a T helper-1 immune response to human immunodeficiency virus type-1 (HIV-1) gp 160 envelope proteins.

Bacterial DNA sequences containing unmethylated CpG motifs have recently been proposed to exhibit immunostimulatory effects on B-, T- and NK cells, leading to the induction of humoral and cell-mediated immune responses. In the present study we investigated the immunomodulatory effects of a CpG-containing oligodeoxynucleotide (CpG ODN) to the HIV-1 gp 160 envelope (Env) protein in the BALB/c mouse model. Priming and boosting of mice with gp 160 adsorbed to aluminium hydroxide (Alum) induced a typical T helper-2 (Th2)-dominated immune response with high titers of gp 160-specific immunoglobulin (Ig)G1 isotypes but a weak IgG2a response. Specifically re-stimulated splenocytes from these mice predominantly secreted interleukin (IL)-5 but only minute amounts of interferon-gamma (IFN-gamma) upon specific re-stimulation. In contrast, a boost immunisation of gp 160/Alum primed mice with a gp 160/Alum/CpG combination resulted in a seven times higher production of IgG2a antibodies, without affecting the titers of IgG1 isotypes. Furthermore, approximately 10-fold increased levels of IFN-gamma, but significantly reduced amounts of IL-5, were secreted from gp 160-restimulated splenic cells. A further greater than 30-fold increase in the levels of specific IgG2a responses and a substantially elevated secretion of IFN-gamma were observed when the mice received gp160/Alum/CpG combinations for priming and boost injections. Thus, CpG ODNs are useful as an adjuvant to induce a typical Th0/Th1 response to HIV gp 160 proteins. However, despite the induction of a more Th1-like immune response, gp 16O/Alum/CpG combinations were not sufficient to prime an Env-specific cytotoxic T-cell (CTL) response.

AIDS Vaccines↗
PubMed1999

[Reconstruction of the venous outflow in liver transplantation using the "piggyback" technique].

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Between November 1994 and November 1997 this technique was used in 29 patients in our institute. Most of the patients were operated on without veno-venous bypass and we observed no complications concerning venous outflow tract reconstruction and no renal failure. Hemodynamic measurements during the operation showed only an insignificant decrease in cardiac index during the partial clamp on the inferior vena cava. The piggyback technique proved to be a convenient and safe approach to the venous outflow tract reconstruction in a majority of liver transplantations and has been used routinely in our institute.

Adolescent↗
PubMed1999

[F-18-FDG PET in autonomous goiter].

AIM: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients. METHODS: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism. CONCLUSION: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated.

Adenoma↗
PubMed1998

Origin of a chloroplast protein importer.

During evolution, chloroplasts have relinquished the majority of their genes to the nucleus. The products of transferred genes are imported into the organelle with the help of an import machinery that is distributed across the inner and outer plastid membranes. The evolutionary origin of this machinery is puzzling because, in the putative predecessors, the cyanobacteria, the outer two membranes, the plasma membrane, and the lipopolysaccharide layer lack a functionally similar protein import system. A 75-kDa protein-conducting channel in the outer envelope of pea chloroplasts, Toc75, shares approximately 22% amino acid identity to a similarly sized protein, designated SynToc75, encoded in the Synechocystis PCC6803 genome. Here we show that SynToc75 is located in the outer membrane (lipopolysaccharide layer) of Synechocystis PCC6803 and that SynToc75 forms a voltage-gated, high conductance channel with a high affinity for polyamines and peptides in reconstituted liposomes. These findings suggest that a component of the chloroplast protein import system, Toc75, was recruited from a preexisting channel-forming protein of the cyanobacterial outer membrane. Furthermore, the presence of a protein in the chloroplastic outer envelope homologous to a cyanobacterial protein provides support for the prokaryotic nature of this chloroplastic membrane.

Amino Acid Sequence↗
PubMed1998

Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual.

HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/microl. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77-85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was recognized by HLA-A11-restricted CTL. Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the A11-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation.

Amino Acid Sequence↗
PubMed1998

Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment].

The mitochondrial outer membrane contains machinery for the import of preproteins encoded by nuclear genes. Eight different Tom (translocase of outer membrane) proteins have been identified that function as receptors and/or are related to a hypothetical general import pore. Many mitochondrial membrane channel activities have been described, including one related to Tim23 of the inner-membrane protein-import system; however, the pore-forming subunit(s) of the Tom machinery have not been identified until now. Here we describe the expression and functional reconstitution of Tom40, an integral membrane protein with mainly beta-sheet structure. Tom40 forms a cation-selective high-conductance channel that specifically binds to and transports mitochondrial-targeting sequences added to the cis side of the membrane. We conclude that Tom40 is the pore-forming subunit of the mitochondrial general import pore and that it constitutes a hydrophilic, approximately 22 A wide channel for the import of preproteins.

Amino Acid Sequence↗