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Biomedical subjects

H Meisel

Publications and source records attributed to H Meisel.

At least 19 recordsLinked to original sources
PubMed2005

Detection of human hantavirus infections in Lithuania.

BACKGROUND: In Europe certain hantaviruses are known to cause hemorrhagic fever with renal syndrome of different severity. The objective of the present investigation was to study the presence of hantavirus infections in Lithuania. MATERIAL AND METHODS: Two different serum panels from cancer patients (n = 438) and blood donors (n = 299) from Lithuania were tested by monoclonal antibody capture IgG ELISA using yeast-expressed recombinant nucleocapsid (rN) proteins of Puumala virus (PUUV), Hantaan virus (HTNV) and Dobrava virus (DOBV). The reactivity of ELISA-positive sera was proven in Western blot tests using various hantavirus rN proteins. Selected serum samples were further analyzed by focus reduction neutralization assays. RESULTS: In the IgG ELISA 39 sera from the cancer patients and four sera from blood donors were found to be reactive with at least one of the rN proteins. By immunoblot using the three yeast-expressed rN proteins, the ELISA reactivity of 36 of 39 and two of four serum samples from cancer patients and blood donors, respectively, was confirmed; this corresponds to a seroprevalence of 8.2% and 0.7%, respectively. In ELISA, the majority of the samples reacted exclusively with rN proteins of HTNV and DOBV (31 of 36 and one of two in the two groups). In the group of sera selected for serotyping by focus reduction neutralization assay, this dominance was confirmed by the identification of eight DOBV but only four PUUV infections. No infection by HTNV or another hantavirus besides DOBV and PUUV was verified. Anti-hantavirus-positive human sera were detected in all seven investigated counties of Lithuania. CONCLUSION: In Lithuania at least two hantaviruses, DOBV and PUUV, circulate and cause human infections. Additional investigations are needed to study the seroprevalence more precisely and to search for clinical cases of hantavirus infections.

Antibodies, Viral↗
PubMed2005

Acrylamide-occurrence in mixed concentrate feed for dairy cows and carry-over into milk.

During the preparation of cooked foods acrylamide is formed from asparagine and reducing sugars at high temperatures. By-products of oil, starch and sugar production, which may be found in animal feed, partially result from processing steps using heat treatment that are similarly likely to form acrylamide. Possibly, pelletizing during the processing of mixed concentrates may also be involved in acrylamide formation. Thus the occurrence of acrylamide in animal feed and the potential for carry-over into animal products should be tested. Independently of the feed matrix, 1.5 g per day of acrylamide was fed to a cow for ten days resulting in a mean concentration of 175 microg/kg of acrylamide in the milk. From the data obtained the mean carry-over was found to be 0.24%, and a mean half-life time of 2.8 h was estimated. This means acrylamide was rapidly transformed in the cow. The acrylamide concentrations in three commercial mixed concentrates were respectively 180, 145 and 140 microg/kg feed. To test the possible effect of pelletizing, the peripheral zones were separately analysed. No difference in concentration was observed. Based on the carry-over rate estimated in this study, a maximum concentration of approx. 0.2 microg/kg of acrylamide would be expected in milk from cows fed with such feeds.

Acrylamide↗
PubMed2005

Parvovirus B19 infection associated with unilateral cervical lymphadenopathy, apoptotic sinus histiocytosis, and prolonged fatigue.

This report describes the case of a 16 year old girl with a history of high fever, prolonged fatigue, and cervical lymphadenopathy of the right side. In addition, the patient showed neutropenia, thrombopenia, and pronounced reticulopenia. Cervical ultrasound showed unilateral hypoechoic lymph nodes up to 23 mm in diameter suspicious for malignant lymphoma. Histology of a cervical lymph node specimen revealed massive nodular histiocytic proliferation and prominent apoptosis without necrosis. Parvovirus B19 was detected by polymerase chain reaction and immunohistochemistry in the lymph node. In summary, this case is an unusual presentation of parvovirus B19 infection. The virus was identified as the potential causative agent of unilateral cervical lymphoma and apoptotic sinus histocytosis, thus broadening the clinicopathological spectrum of parvovirus B19 induced diseases.

Adolescent↗
PubMed2004

Caseinophosphopeptides and their cell modulating potential.

In the context of the EU research project FAIR-CT 98-3077, studies were carried out to investigate caseinophosphopeptides (CPP) as potential ingredients for functional food and pharmaceutical applications. CPP preparations were produced by enrichment of CPP from hydrolytic casein digests. Enzyme preparations used for hydrolysis were PTN 3.0 S, Alcalase, Bioprotease P conc, Proteinase DS. Cytochemical studies were carried out to examine the cytotoxic potential or cell modulating activities of CPP using human cancer cell lines (HL-60, Caco-2) and non-malignant polymorphonuclear leukocytes (PML) from oral cavity. PML cells isolated by magnetic cell sorting using CD-15-antibody-labelled paramagnetic beads were used for the first time for testing food-derived peptides. Cell activity was measured by formazan dye formation. Effects on enterocytic differentiation properties of Caco-2 cells were examined by transepithelial membrane resistance of Caco-2 cell monolayers and brush border associated alkaline phosphatase activity. In conclusion, (1) no deleterious cytochemical consequences (apoptotic, antiproliferative or general cytotoxic effects) were observed on presenting a range of CPP preparations to various human cell systems, indicating that these compounds can be rated harmless at a cellular level, (2) stimulation of IgG-secretion into culture supernatant of PBL points to possible immunoenhancing properties of CPP preparations.

B-Lymphocytes↗
PubMed2004

[Prevalence of hantavirus infections in Germany].

Hantaviruses belong to the group of "emerging" viruses. Pathogenic European hantaviruses can cause a human disease designated "hemorrhagic fever with renal syndrome" of varying severity. In general, diagnostics of hantavirus infections are based on immunofluorescence assays using virus-infected cells or enzyme immunoassays and Western blot tests using recombinant nucleocapsid proteins. For highly sensitive detection of hantavirus-specific antibodies in the enzyme immunoassay, a homologous hantavirus nucleocapsid protein is needed as a diagnostic antigen. Serological typing of hantavirus infections can be obtained by neutralization assays, which in certain cases require the use of late convalescent sera. The seroprevalence in the normal German population is about 1%. In professionally exposed risk groups, e. g., forest workers, a seroprevalence higher than that in the normal population was observed. Endemic regions for hantavirus infections are located mainly in Baden-Württemberg. In the years 2001-2003 an annual number of about 200 clinically apparent hantavirus infections were registered in Germany. Neutralization assays detected almost exclusively human infections caused by Puumala and Dobrava viruses, only very rarely by Tula virus. Until this day in Germany mainly mild to moderate courses of human hantavirus infections have been documented. Besides infections caused by "German" hantaviruses, up to 10% of the clinically apparent hantavirus infections registered annually in Germany are caused by infections imported from other countries, mainly from Europe. So far only very limited molecular genetic data about the circulating hantaviruses in Germany are available. Additional investigations are needed to get a more precise picture about the distribution of hantaviruses in Germany and to calculate the resulting risk for the human population.

Communicable Disease Control↗
PubMed2004

In vitro generation and stability of the lactokinin beta-lactoglobulin fragment (142-148).

The objectives of this study were to investigate the generation of beta-lactoglobulin fragment (142-148) (beta-LG f(142-148) during the hydrolysis of whey proteins, and the in vitro stability of this fragment upon incubation with gastrointestinal and serum proteinases and peptidases. An enzyme immunoassay (EIA) protocol was developed for the quantification of beta-LG f(142-148) in whey protein hydrolysates and in human blood serum. The minimum detection limit was 3 ng/mL. The level of the peptide in whey protein hydrolysates was influenced by the degree of hydrolysis (DH). As expected, highest levels of this peptide were found in hydrolysates generated with trypsin. Sequential incubation of hydrolysates at different DH values with pepsin and Corolase PP, to simulate gastrointestinal digestion, generally resulted in the degradation of beta-LG f(142-148) as determined by EIA. Reversed-phase HPLC and angiotensin-I-converting enzyme (ACE) activity assays demonstrated that synthetic beta-LG f(142-148) was rapidly degraded upon incubation with human serum. Furthermore, beta-LG f(142-148) could not be detected by EIA in the sera of 2 human volunteers following its oral ingestion or in sera from these volunteers subsequently spiked with beta-LG f(142-148). These in vitro results indicate that beta-LG f(142-148) is probably not sufficiently stable to gastrointestinal and serum proteinases and peptidases to act as an hypotensive agent in humans following oral ingestion. The in vitro methodology described herein has general application in evaluating the hypotensive potential of food protein-derived ACE inhibitory peptides.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Life-threatening Dobrava hantavirus infection with unusually extended pulmonary involvement.

In Europe, hantavirus infections usually present as hemorrhagic fever with renal syndrome and its mild form nephropathia epidemica, while clinical cases with severe pulmonary affections are extremely rare and appear to be confined to infections by New World hanta viruses in the Americas. We report on a female patient from Northern Germany, who suffered primarily from severe acute respiratory distress syndrome-like pulmonary failure due to Dobrava hantavirus infection that was complicated by acute renal insufficiency.

Female↗
PubMed2003

Detection of caseinophosphopeptides in the distal ileostomy fluid of human subjects.

Caseinophosphopeptides (CPP) were detected for the first time in ileostomy fluid, collected at 2 h intervals for 10 h post milk and CPP ingestion, from human volunteers with an ileostomy. The level of CPP present in ileostomy fluid obtained from milk-fed volunteers was markedly higher than that from volunteers fed with selected CPP preparations. The findings are based on HPLC analysis in combination with peptide-bound P determination, thin-layer electrophoresis and amino acid analysis, together with ELISA studies using polyclonal antibodies raised against a set of CPP to detect immunoreactive CPP in ileostomy fluid. These procedures allowed the detection of nm concentrations of CPP. CPP, which can be released during intestinal digestion, may function as bioactive constituents and carriers for different minerals, especially Ca, and may be used as ingredients in functional foods or pharmaceutical preparations.

Adult↗
PubMed2003

Biofunctional peptides from milk proteins: mineral binding and cytomodulatory effects.

The protein fraction of milk contains many valuable components and biologically active substances. Moreover, milk proteins are precursors of many different biologically active peptides which are inactive within the sequence of the precursor protein but can be released by enzymatic proteolysis. Many milk protein-derived peptides, such as caseinophosphopeptides, reveal multi-functional bioactivities. Caseinophosphopeptides can form soluble organophosphate salts and may function as carriers for different minerals, especially calcium. Furthermore, they have been shown to exert cytomodulatory effects. Cytomodulatory peptides inhibit cancer cell growth or they stimulate the activity of immunocompetent cells and neonatal intestinal cells, respectively. Several bioactive peptides derived from milk proteins are potential modulators of various regulatory processes in the body and thus may exert beneficial physiological effects. Caseinophosphopeptides are already produced on an industrial-scale and as a consequence these peptides have been considered for application as ingredients in both 'functional foods' and pharmaceutical preparations. Although the physiological significance as exogenous regulatory substances is not yet fully understood, both mineral binding and cytomodulatory peptides derived from bovine milk proteins are claimed to be health enhancing components that can be used to reduce the risk of disease or to enhance a certain physiological function.

Adjuvants, Immunologic↗
PubMed2002

Mapping of B-cell epitopes in the nucleocapsid protein of Puumala hantavirus.

Hantavirus nucleocapsid protein (N) has been proven to induce highly protective immune responses in animal models. The knowledge on the mechanisms behind N-induced protection is still limited, although recent data suggest that both cellular and humoral immune responses are of importance. For a detailed B-cell epitope mapping of Puumala hantavirus (PUUV) N, we used recombinant N derivatives of the Russian strain CG18-20 and the Swedish strain Vranica/Hällnäs, as well as overlapping synthetic peptides corresponding to the Finnish prototype strain Sotkamo. The majority of a panel of monoclonal antibodies (mAbs) reacted with proteins derived from all included PUUV strains demonstrating the antigenic similarity of these proteins. In line with previous results, the epitopes of most mAbs were mapped within the 80 N-terminal amino acids of N. The present study further revealed that the epitopes of four mAbs raised against native viral N were located within amino acids 14-45, whereas one mAb raised against recombinant N was mapped to amino acids 14-39. Differences between the reactivity of the PUUV strains Vranica/Hällnäs and CG18-20 N suggested the importance of amino acid position 35 for the integrity of the epitopes. In line with the patterns obtained by the truncated recombinant proteins, mapping by overlapping peptides (PEPSCAN) confirmed a complex recognition pattern for most analyzed mAbs. Together, the results revealed the existence of several, partially overlapping, and discontinuous B-cell epitopes. In addition, based on differences within the same competition group, novel epitopes were defined.

Amino Acid Sequence↗
PubMed2001

DNA vaccination of mice with a plasmid encoding Puumala hantavirus nucleocapsid protein mimics the B-cell response induced by virus infection.

Inoculation of naked DNA has been applied for the development of prophylactic and therapeutic vaccines against different viral infections. To study the humoral immune response induced by DNA vaccination we cloned the entire nucleocapsid protein-encoding sequence of the Puumala hantavirus strain Vranica/Hällnäs into the CMV promoter-driven expression unit of the plasmid pcDNA3, generating pcDNA3-VR1. A single dose injection of 50 microg of plasmid DNA into each M. tibialis anterior of BALB/c mice induced a high-titered antibody response against the nucleocapsid protein as documented 6 and 11 weeks after immunisation. PEPSCAN analysis of a serum pool of the pcDNA3-VR1-vaccinated animals revealed antibodies reacting with epitopes covering the whole nucleocapsid protein. The epitope-specificity of the immune response induced by DNA vaccination seems to reflect the antibody response in experimentally virus-infected bank voles (the natural host of the Puumala virus) and humans. The data suggest that DNA vaccination could be used for the identification of highly immunogenic epitopes in viral proteins.

Animals↗
PubMed2001

First molecular evidence for Puumala hantavirus in Slovakia.

We report on the first Puumala hantavirus nucleotide sequence (strain Opina-916) amplified from a bank vole trapped in Slovakia, central Europe. Phylogenetic analysis of the S-segment sequence grouped the virus within the western/central European sublineage of Puumala virus. In the neighborhood of the rodent trapping site two cases of human infection by the Puumala virus were verified.

Animals↗
PubMed2001

Prevalence of markers for hepatitis A, B and C in the German population. Results of the German National Health Interview and Examination Survey 1998.

The prevalence of serological parameters indicative of infection with hepatitis A, B and C was determined using sera collected from representative population samples in the former East German (new) federal states and the West German (old) federal states during the German National Health and Examination Survey in 1998. Sera were tested for antibodies to hepatitis A virus (HAV), to hepatitis B core antigen (HBc) and to hepatitis B surface antigen (HBsAg), hepatitis C Virus (HCV), as well as for the presence of HBsAg and HCV-RNA. The mean weighted prevalence of anti-HAV was 46.5% (95% CI: 45.3-47.7) and increased markedly with age. The mean weighted prevalence of past infection with hepatitis B was 7.7% (95% CI: 7.0-8.4) in the old federal states and 4.3% (95% CI: 3.2-5.3) in the new federal states, corresponding to an overall prevalence of 7.0% (95% CI: 6.4-7.6). The mean weighted prevalence of HBsAg carriage was 0.6% (95% CI: 0.4-0.8), while the prevalence of HCV antibodies was 0.4% (95% CI: 0.2-0.5).

Cross-Sectional Studies↗
PubMed2001

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species.

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381-935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans.

Adolescent↗
PubMed2001

Clinical characterization of Dobrava hantavirus infections in Germany.

There is increasing evidence that Dobrava (DOBV) but not Hantaan (HTNV) hantavirus is a hemorrhagic fever with renal syndrome (HFRS) causing agent in Central Europe. However, only single clinical cases of HFRS due to acute DOBV infection have been described so far. We report on three male patients from a non-endemic hantavirus focus in Northern Germany who suffered from mild to moderate HFRS strongly resembling nephropathia epidemica. Serotyping by detection of hantavirus species-specific neutralizing antibodies revealed acute infections by the HTNV-related hantavirus DOBV in all three cases. Since DOBV infections in the Balkans frequently present as severe HFRS, our cases suggest that Central-European DOBV infections have a different, less severe clinical outcome. These differences in DOBV virulence towards humans might be due to the existence of different genetic lineages of DOBV.

Acute Disease↗
PubMed2000

Puumala (PUU) hantavirus strain differences and insertion positions in the hepatitis B virus core antigen influence B-cell immunogenicity and protective potential of core-derived particles.

Hepatitis B virus (HBV) core-derived chimeric particles carrying a Puumala (PUU) hantavirus (strain Vranica/Hällnäs) nucleocapsid (N) protein sequence (aa 1-45), alternatively inserted at three distinct positions (N-, C-terminus, or the internal region), and mosaic particles consisting of HBV core as well as core/PUU (Vranica/Hällnäs) N (aa 1-45) readthrough protein were generated. Chimeric particles carrying the insert at the N-terminus or the internal region of core induced some protective immune response in bank voles (Clethrionomys glareolus) against a subsequent PUU virus (strain Kazan) challenge; 40-50% of the animals showed markers of protection. In contrast, internal insertion of PUU strain CG18-20 N (aa 1-45) into the HBV core caused a highly protective immune response in the bank vole model. Immunizations with particles carrying aa 75-119 of PUU (CG18-20) N at the C-terminus of core verified the presence of a second, minor protective region in the N protein. A strong PUU N-specific antibody response was detected not only in bank voles immunized with chimeric particles containing internal and N-terminal fusions of PUU N protein but also in animals immunized with the corresponding mosaic particles. Except for the exclusive occurrence of antibodies directed against aa 231-240 of N in non-protected animals post virus challenge, there was no additional obvious difference in the epitope-specificity of N-specific antibodies from immunized animals prior and post virus challenge.

Amino Acid Sequence↗