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Biomedical subjects

G Eder

Publications and source records attributed to G Eder.

At least 19 recordsLinked to original sources
PubMed2003

Antigen dependent adverse reactions and seroconversion of a tick-borne encephalitis vaccine in children.

Two randomized, double blind dose comparison studies were conducted in 595 children in Austria and Germany with an albumin-free and thiomersal-free tick-borne encephalitis (TBE) vaccine. Vaccinated subjects of an age between 6 months and 12 years randomly assigned received either the full adult dose or half the adult dose. Results from vaccinated children under 1 year of age at the time of the first vaccination (159 subjects) showed an age dependent immune response. There were significantly fewer adverse systemic events (e.g. fever reactions). In children who received only half the adult dose, while seroconversion was not significantly different (93% versus 98%) after the second vaccination, and 100% for both groups after the third vaccination. Based on these results, it is recommended to vaccinate children between the ages of 1 and 12 years with half the adult dose.

Aging↗
PubMed2002

Respiratory mechanics in mice: strain and sex specific differences.

To assess the contribution of genetic background to respiratory mechanics, we developed a ventilator unit to measure lung function parameters in the mouse. We studied two commonly used inbred mice strains originating from Mus musculus domesticus (C57BL/6 and C3HeB/FeJ) and a third strain derived from Mus musculus molossinus [Japanese fancy mouse 1 (JF1)]. The ventilator allows for accurate performance of the different breathing manoeuvres required for measuring in- and expiratory reserve capacity, quasi-static and dynamic compliance, and airway resistance. In combination with a mass spectrometer for monitoring gas concentrations, single-breath manoeuvres were performed and He-expirograms obtained, from which dead space volume and slope of phase III were determined. From each strain and each sex, 10, 2-month old animals were studied immediately after being killed by an intraperitoneal overdose of xylazine and ketamine. C3HeB/FeJ and C57BL/6 exhibited comparable lung volumes. In male C3HeB/FeJ mice, e.g. vital capacity (VC) was 1072 +/- 79 microL, inspiratory reserve capacity 782 +/- 88 microL, and dead space volume at total lung inflation 216 +/- 18 microL. Lung volumes of JF1 were significantly lower (e.g. VC 611 +/- 53 microL, P < 0.01) even when normalized to body weight. In all three strains, specific lung volumes were significantly higher in females than in males, possibly explained by a higher oxygen demand during pregnancy and lactation, both of which fill most of their life times. Static compliance in C3HeB/FeJ was 64.3 +/- 5.4 microL cmH2O-1. It was smaller in C57BL/6 and JF1 mice, even when related to the lung volume. Analysis of the degree of genetic vs. non-genetic components of the phenotypic variation revealed that at least 80% of the total variation of lung volumes and static compliance in the mixed population is attributable to genetic differences between individuals. These differences will be verified in further studies by segregation and genetic linkage analysis.

Animals↗
PubMed2001

[Development of a novel influenza vaccine derived from a continuous cell line].

Influenza viruses for production are presently produced in embryonated hen"s eggs. This conventional standard methodology is extremely cumbersome; it requires millions of eggs and an extensive purification to reduce the amount of contaminating egg proteins and to minimise the risk of allergies against egg albumin. The shortage of eggs in a pandemic situation, the selection of egg-adapted variants and the presence of adventitious viruses has emphasised the necessity for production of Influenza vaccines on a well characterised stable cell line. Our established serum and protein free Vero cell technology has been successfully adapted to large scale production of a huge variety of Influenza virus strains. The production in 1200 liter fermenter cultures under serum free conditions gave antigen yields comparable to the conventional embryonated egg technology. The development of a rapid and efficient purification scheme resulted in a safe high purity vaccine which was at least as immunogenic as conventional egg-derived vaccines in a mouse model. Clinical trials in the UK, Poland and Austria demonstrated that the Vero cell derived influenza vaccine is well tolerated, safe and highly immunogenic in humans.

Animals↗
PubMed2000

Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus (HCV) envelope E2 protein modified the infection after challenge with homologous monoclonal HCV.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Development of vaccines to prevent HCV infection, or at least prevent progression to chronicity, is a major goal. In mice and rhesus macaques, a DNA vaccine encoding cell-surface HCV-envelope 2 (E2) glycoprotein stimulated stronger immune responses than a vaccine encoding intracellular E2. Therefore, we used DNA encoding surface-expressed E2 to immunize chimpanzees 2768 and 3001. Chimpanzee 3001 developed anti-E2 after the second immunization and antibodies to hypervariable region 1 (HVR1) after the third immunization. Although chimpanzee 2768 had only low levels of anti-E2 after the third immunization, an anamnestic response occurred after HCV challenge. CTL responses to E2 were not detected before challenge, but a strong response was detected after HCV challenge in chimpanzee 2768. An E2-specific CD4+ response was detected in chimpanzee 2768 before challenge and in both chimpanzees postchallenge. Three weeks after the last immunization, animals were challenged with 100 50% chimpanzee-infectious doses (CID(50)) of homologous monoclonal HCV. As a control, a naive chimpanzee was inoculated with 3 CID(50) of the challenge virus. The vaccine did not generate sterilizing immunity because both vaccinated chimpanzees were infected. However, both vaccinated chimpanzees resolved the infection early whereas the control animal became chronically infected. Compared with the control animal, hepatitis appeared earlier in the course of the infection in both vaccinated chimpanzees. Therefore, DNA vaccine encoding cell surface-expressed E2 did not elicit sterilizing immunity in chimpanzees against challenge with a monoclonal homologous virus, but did appear to modify the infection and might have prevented progression to chronicity.

Animals↗
PubMed1999

Evidence for extracellular processing of pro-von Willebrand factor after infusion in animals with and without severe von Willebrand disease.

Although proteolytic processing of pro-von Willebrand factor (pro-vWF) resulting in free propeptide and mature vWF is known to be initiated intracellularly, vWF released from endothelial cells may contain a high proportion of incompletely processed pro-vWF. Because pro-vWF is only rarely detectable in normal human plasma, we investigated whether extracellular processing of pro-vWF is possible. A recombinant preparation (rpvWF) containing both pro-vWF and mature vWF subunits was infused into 2 pigs and 1 dog with severe von Willebrand disease, 2 mice with a targeted disruption of the vWF gene, and 2 healthy baboons. Total vWF antigen (vWF:Ag), free propeptide, and pro-vWF were measured using enzyme-linked immunosorbent assay techniques in blood samples drawn before and after infusion. vWF:Ag increased promptly. No pro-vWF could be detected when the first postinfusion sample was drawn after 30 minutes (pigs) or 60 minutes (mice), but pro-vWF was detectable for short periods when postinfusion samples were drawn after 15 minutes (dog) or 5 minutes (baboons). In contrast, free propeptide was increased at the first timepoint measured, suggesting that it was generated from the pro-vWF in the rpvWF preparation. vWF multimers were analyzed in the rpvWF preparation and in plasma samples drawn before and after infusion of rpvWF using ultra-high resolution 3% agarose gels to allow separation of homo- and hetero-forms of the vWF polymers. Within 30 minutes after infusion in the pigs, 1 hour in the dog and the mice, and within 2 hours in the baboons, the multimer pattern had changed to that typically seen in mature vWF. These data indicate that propeptide cleavage from unprocessed vWF can occur extracellularly in the circulation. The enzyme or enzymes responsible for this cleavage in plasma remain to be identified.

Animals↗
PubMed1999

A novel mammalian cell (Vero) derived influenza virus vaccine: development, characterization and industrial scale production.

Influenza virus for vaccine production are presently produced in embryonated chicken eggs. This conventional standard methodology is extremely cumbersome; it requires a huge amount of eggs and an extensive purification to reduce the amount of contaminating egg proteins and to minimize the risk of allergies against egg albumin. The shortage of eggs in a pandemic situation, the selection of egg-adapted variants and the presence of adventitious viruses has emphasized the necessity for production of influenza vaccines on a well characterized stable cell line. Our established Vero cell technology has been successfully adapted to large scale production of a variety of influenza virus strains. The production in 1200 litre fermenter cultures under serum-free conditions gave antigen yields comparable to the conventional embryonated egg technology. The development of a rapid and efficient purification scheme resulted in a safe high purity vaccine which was at least as immunogenic as conventional egg-derived vaccines in a mouse model. This vaccine has been shown to be safe and highly immunogenic in chimpanzees and to be capable of protecting ferrets against challenge with live virus. Clinical trials have now been initiated in the UK and Austria.

Animals↗
PubMed1999

Association of GB virus C (GBV-C)/hepatitis G virus (HGV) with haematological diseases of different malignant potential.

Among risk groups for GB virus C (GBV-C)/HGV infection, patients with haematological diseases are particularly exposed due to the combination of transfusional support and immunodeficiency status. To examine any association between GBV-C/HGV positivity and different malignancy potential of hematological diseases, we investigated two groups of patients, one with clonal stem cell disease with long latency period (myelodysplasia, myeloproliferative disease) and one with malignant haematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with the data from cytogenetic analysis at first diagnosis. The frequency of GBV-C/HGV infection in these patients was studied using reverse transcription-polymerase chain reaction (RT-PCR) and E2 antibody assay. Serum GBV-C RNA was found in 29/47 (62%) patients. The prevalence of GBV-C RNA in the group of oncological cases (72%) was significantly higher (P= .02) than in the patients with clonal stem cell diseases (28%). Among the GBV-C negative cases, only 25% had malignant haematological diseases. The data from GBV-C/ HGV tested cases for which cytogenetic analysis was carried out indicated an association of GBV-C/HGV positivity with genomic destabilization in general. Of the cases with numerical and structural aberrations, 64% were GBV-C positive. A correlation could not be confirmed between GBV-C/HGV and liver enzyme levels, blood transfusions, chemotherapy treatment, or viral coinfection. These findings suggest a high risk of GBV-C/HGV infection in patients with haematological disorders especially in the group of malignant diseases. These observations may indicate that the persistence of GBV-C/HGV in these patients could be associated with susceptibility to genomic destabilisation.

Flaviviridae↗
PubMed1999

Health effects of sulfur-related environmental air pollution. IV. Respiratory lung function.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1-microm neutral sulfite aerosol with a particle-associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1-microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Before and at the end of exposure, respiratory lung function was evaluated in both groups in anesthetized and mechanically ventilated animals. Lung volumes as well as static and dynamic lung compliances were measured. Series dead-space volumes and slopes of the alveolar plateau for respiratory (O2, CO2) and inert test gases (He, SF6) were determined from single-breath washout tracings. Monodisperse 0.9-microm DEHS droplets were used to assess convective mixing in the lungs and to evaluate airway dimensions in vivo. Gas exchange across the alveolar-capillary layer was characterized by membrane diffusing capacity for carbon monoxide and alveolar-arterial pressure differences for respiratory gases. A bronchial challenge with carbachol was used to assess airway responsiveness. In comparison to the control group, dogs exposed to sulfur(IV) and acidic aerosol exhibited no significant changes in any respiratory lung function parameter. Also the responsiveness of the bronchial airways to carbachol was not affected. In view of the results obtained in this and previous studies, we conclude that anticipated synergistic effects of the two air pollutants on pulmonary lung function were not observed. It is hypothesized that antagonistic effects of the air pollutants on the activity of phospholipase A2 play an important role and account for counteracting physiological compensatory mechanisms. The results emphasize the complexity of health effects on lung function in response to the complex mixtures of ambient air pollutants and witness the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1999

Effects of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on in vitro activities of secreted aspartyl proteinases of Candida albicans isolates from HIV-infected patients.

The effects of therapeutically relevant concentrations of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on the in vitro proteinase activity of Candida albicans were investigated with isolates from HIV-infected and uninfected patients with oral candidiasis. After exposure to the HIV proteinase inhibitors, proteinase activity was significantly reduced in a dose-dependent manner. These inhibitory effects, which were similar to that of pepstatin A, and the reduced virulence phenotype in experimental candidiasis after application of saquinavir indicate the usefulness of these HIV proteinase inhibitors as potential anticandidal agents.

AIDS-Related Opportunistic Infections↗
PubMed1999

Factor Xa and prothrombin: mechanism of action of FEIBA.

A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high-titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)-deficient dog and controlled bleeding in rabbits with antibody-induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.

Animals↗
PubMed1999

Development of a Vero cell-derived influenza whole virus vaccine.

Influenza vaccine production is dependent on the availability of embryonated hen eggs for virus growth. This is an extremely cumbersome system with many disadvantages with respect to selection of virus variants and the presence of adventitious viruses. We have developed an alternative cell culture system which allows rapid production of large volumes of vaccine. The WHO-approved Vero cell line was used in serum-free culture to grow many influenza strains to high titre. This system could be scaled-up to allow vaccine production with a 1200 litre fermenter. A purification scheme was developed which resulted in a high purity whole virus vaccine. This was demonstrated to be at least as immunogenic as a conventional egg-derived preparation.

Animals↗
PubMed1998

A randomized, controlled trial to study the efficacy and safety of C1 inhibitor concentrate in treating hereditary angioedema.

BACKGROUND: No effective treatment exists in the United States for acute attacks of hereditary angioedema (HAE). STUDY DESIGN AND METHODS: To evaluate the efficacy and safety of C1 inhibitor concentrate in treating HAE, a large primary care and referral center hospital conducted a randomized, placebo-controlled, double-blind trial with intent-to-treat analysis. Of the 36 patients enrolled in the study, 23 received treatment, and 22 completed the trial. C1 inhibitor concentrate or albumin (placebo) infusions were administered in a blind fashion to HAE patients who came to the hospital for treatment no later than 5 hours after an attack began. RESULTS: Relief was almost twice as fast in persons receiving C1 inhibitor concentrate than in the controls: 7.62 hours (mean; SD 7.08) versus 15.35 hours (mean; SD 8.31), respectively. The difference for time-to-relief was highly significant (p = 0.007, Mann-Whitney U test). The median time-to-relief was 6.17 hours (interquartile range 0.33-15.35) in the treatment group and 15.35 hours (interquartile range 14.00-22.83) in the control group. Resolution of symptoms was one-third faster in the C1 inhibitor concentrate group than in the placebo group: 23.98 hours (mean; SD 14.81) and 34.58 hours (mean; SD 13.56), respectively (p = 0.09, Mann-Whitney U test). Recovery of functional C1 inhibitor was 119.65 percent (mean; SD 50.80), and half-life was 37.87 hours (mean; SD 19.75). Recovery of antigenic C1 inhibitor was 147.75 percent (mean; SD 97.68), and half-life was 24.01 hours (mean; SD 9.70). There were no viral infections or serious adverse effects from the drug after 70 attacks in the treatment group and 96 attacks in the control group. CONCLUSIONS: C1 inhibitor concentrate is a safe, effective treatment for acute attacks of HAE.

Acute Disease↗
PubMed1997

Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets.

There is now abundant evidence to substantiate an important role of hepatitis C virus (HCV) core protein in cellular gene expression as well as in the viral cycle. Thus the subcellular localization of this protein has important implications. However, several studies have shown controversial results: the HCV core has been, indeed, described as cytoplasmic or nuclear depending on the size of the protein or on the genotype analyzed. We have studied the localization of the HCV core protein in two different cell lines, one nonhepatic (CHO) and the other hepatic (HepG2). Double immunofluorescence staining using a nuclear membrane marker and confocal analysis showed the core protein pattern to be cytoplasmic and globular. This pattern is not cell cycle-regulated. Electron microscopy analysis revealed the nature of the globular staining observed in immunofluorescence. The HCV core protein accumulated at the surface of lipid droplets that were also the unique morphological feature of nonhepatic core transfected cells. The lipid droplets were isolated by sequential ultracentrifugation on the basis of their density; biochemical analysis revealed a prevalence of triglycerides. In addition the core protein colocalized with apolipoprotein AII at the surface of the lipid droplets as revealed by confocal microscopy. Moreover analysis of liver biopsies from chronically HCV-infected chimpanzees revealed that HCV core is cytoplasmic and localized on the endoplasmic reticulum and on lipid droplets. These results clearly define the subcellular localization of the HCV core protein and suggest a relationship between the expression of the HCV core protein and cellular lipid metabolism.

Animals↗
PubMed1996

Ultrasound guided spleen biopsy in chimpanzees (pan troglodytes).

To the best of our knowledge, this is the first published investigation of the size and position of chimpanzee spleens as measured by ultrasound, and that a fine-needle biopsy of the chimpanzee spleen, guided by ultrasound, has been performed. In general, the chimpanzee spleen is smaller than the human spleen (mean length of 8.9 cm, SD 1.17 cm; mean thickness 2.4 cm, SD 0.35 cm; n = 14) and its position may be different due to different numbers of thoracic vertebrae. Fine-needle biopsy is a safe and simple method to obtain lymphoid tissue sufficient for PCR testing of HIV-1.

Animals↗
PubMed1996

A longitudinal study of the kidney function of the chimpanzee (Pan troglodytes) in comparison with humans.

A prospective study of the kidney function of chimpanzees (Pan troglodytes) kept at the Hans Popper Primate Centre has been performed within the last 10 years. The aim of the study was to analyse urine samples for specific gravity, to determine serum creatinine, serum urea, and urinary creatinine, and to calculate creatinine clearance and reference values for healthy chimpanzees. From 1750 urine specimens of adolescent and 568 of infant chimpanzees a mean specific gravity value of 1.013 +/- 0.006 (standard deviation) kg/l and 1.007 +/- 0.003 (standard deviation) kg/l, respectively, was calculated. Serum creatinine was determined in 1864 single samples from 52 chimpanzees; a median value of 101.8 mumol/l (P (5%) 79.6 mumol/l, P (95%) 139.7 mumol/l) was calculated, which is higher than that in humans. Serum urea tests (n = 1831) in the same 52 chimpanzees resulted in a median value of 2.01 mmol/l (P (5%) 0.86 mmol/l, P (95%) 4.78 mmol/l). The calculated median creatinine clearance value of 23.9 ml/min (P (5%) 4.4 ml/min, P (95%) 65.3 ml/min) is lower in chimpanzees than in man. A correction of the creatinine clearance values to the body surface area of 1.73 m2, as routinely performed in humans, gave unusually high results, as there was no proper equation to calculate the surface area of chimpanzees. The use of estimation equations for creatinine clearance values of chimpanzees as developed for humans is therefore not recommended.

Animals↗
PubMed1995

Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans.

Foamy viruses (FVs) persist in healthy individuals of various mammalian species, including nonhuman primates. Laboratory markers of FV infection are (1) virus in throat epithelium or peripheral blood lymphocytes (PBLs), (2) proviral DNA sequences in PBLs and various solid organs, and (3) antibodies reactive to viral antigens on Western blots, in radioimmunoprecipitation tests, and in immunofluorescence assays. Using PCR and serological tests, we readily detected FV markers in naturally infected African green monkeys, rhesus monkeys, and chimpanzees, as well as in accidentally infected humans. Transmission of simian foamy viruses to humans (by bite or inadvertent laboratory infection) leads to viral markers, without affecting the recipient. Reports on FV-associated clinical disorders (e.g., thyroid or neurological) have remained controversial. In this study we failed to detect, by PCR, viral sequences in the samples from 223 patients, including 16 HIV-infected Africans, 46 Graves' disease patients, and 28 patients with the de Quervain's thyroiditis. Evaluation of 2688 sera from suspected high-risk areas (e.g., Central and East Africa, or high-risk groups such as HIV-infected individuals and patients with AIDS, thyroid, and neurological disorders) did not reveal FV-specific antibodies in a single case. Previously reported FV seroprevalence in various populations has never been verified by appropriate confirmatory tests. The strain of "human foamy virus" has remained a unique isolate. In conclusion, FVs are unlikely--at present--to circulate in human populations.

Africa↗