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Biomedical subjects

R Ulrich

Publications and source records attributed to R Ulrich.

At least 19 recordsLinked to original sources
PubMed2006

A new Puumala hantavirus subtype in rodents associated with an outbreak of Nephropathia epidemica in South-East Germany in 2004.

A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East Germany, starting in April 2004. While only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by June 2005. To determine the reservoir responsible for the infections, a total of 43 rodents were trapped in Lower Bavaria. Serological and genetic investigations revealed that Puumala virus (PUUV) is dominant in the local population of bank voles. Partial PUUV S segment nucleotide sequences originating from bank voles at four different trapping sites in Lower Bavaria showed a low divergence (up to 3.1%). This is contrasted by a nucleotide sequence divergence of 14-16% to PUUV strains detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be responsible for the observed increase of human hantavirus infections in 2004-2005.

Animals↗
PubMed2006

Size and position of truncations in the carboxy-terminal region of major capsid protein VP1 of hamster polyomavirus expressed in yeast determine its assembly capacity.

The hamster polyomavirus major capsid protein VP1 was modified in its carboxy-terminal region by consecutive truncations and single amino acid exchanges. The ability of yeast-expressed VP1 variants to form virus-like particles (VLPs) strongly depended on the size and position of the truncation. VP1 variants lacking 21, 69, and 79 amino acid (aa) residues in their carboxy-terminal region efficiently formed VLPs similar to those formed by the unmodified VP1 (diameter 40-45 nm). In contrast, VP1 derivatives with carboxy-terminal truncations of 35 to 56 aa residues failed to form VLPs. VP1 mutants with a single A336G aa exchange or internal deletions of aa 335 to aa 346 and aa 335 to aa 363 resulted in the formation of VLPs of a smaller size (diameter 20 nm). These data indicate that certain parts of the carboxy-terminal region of VP1 are not essential for pentamer-pentamer interactions in the capsid, at least in the yeast expression system used.

Amino Acid Sequence↗
PubMed2006

Generation of monoclonal antibodies of desired specificity using chimeric polyomavirus-derived virus-like particles.

Foreign protein sequences presented on hamster polyomavirus (HaPyV) major capsid protein VP1-derived virus-like particles (VLPs) have been demonstrated to be highly immunogenic. The current study was aimed to evaluate VP1-derived chimeric VLPs as tools for hybridoma technology to generate monoclonal antibodies (mAbs) of desired specificity. Chimeric VLPs containing inserts of different size and origin were used as immunogens. Chimeric VLPs carrying a 9 amino acid (aa)-long cytotoxic T-cell epitope (STAPPVHNV) of human mucin 1 (MUC1) elicited a strong epitope-specific humoral immune response in mice and promoted the production of MUC1-specific mAbs. From a total of seven mAbs of IgG isotype generated against the chimeric VLPs, two mAbs were directed against the MUC1 epitope and five mAbs against the VP1-carrier. Two out of five anti-VP1 mAbs recognized epitopes located at the previously defined insertion site #2 (aa 223/224), which confirms its surface-exposed localization. Chimeric VLPs carrying a 120-aa long sequence of Puumala hantavirus (PUUV) nucleocapsid protein (NP) promoted the generation of five mAbs of IgG isotype specific to PUUV NP. All mAbs recognized the full-length NP of different PUUV strains. In contrast, no VP1-specific mAbs were obtained. The ability of chimeric VLPs to activate antigen-presenting cells was evaluated by studying the uptake of chimeric VLPs by murine spleen cell-derived dendritic cells (DCs). Efficient uptake of VLPs and activation of murine DCs were demonstrated, which may represent the basis of the strong immunogenicity of chimeric VLPs. In conclusion, chimeric VLPs effectively stimulated the production of IgG antibodies specific for foreign epitopes presented at surface-exposed regions. Thus, chimeric HaPyV VP1-derived VLPs represent efficient immunogens for hybridoma technology and provide a promising alternative to chemical coupling of synthetic peptides to carrier proteins.

Animals↗
PubMed2006

The use of nutritional supplements among master athletes.

We assessed the use of nutritional supplements among master athletes focusing on their source of information and source of supply of nutritional supplements. 1560 standardized, anonymous questionnaires were distributed among participants of the World Masters Athletics Championships Indoors 2004. These questions were related to biometric parameters, social indicators, training parameters, illicit drugs, and nutritional supplements. Chi2-tests were computed to reveal meaningful associations between basic information (age, gender, family status, children, education, country of origin, disciplines, training years, smoking, and the use of alcohol, illicit drugs, and doping) and the intake of nutritional supplements. Descriptive information on the history of their use of nutritional supplements was also provided. 60.5 % of all participants reported the actual use of nutritional supplements. We found no significant differences between nutritional supplement users and non-users with regard to basic information. The substances predominantly used were vitamins (35.4 %) and minerals (29.9 %). In contrast to elite athletes who use nutritional supplements to increase their athletic performance, master athletes use these substances predominantly for health reasons and, thus, have a closer contact to the health care system. Physicians are their preferred source of information about nutritional supplements. More than half of the interviewed athletes obtain their nutritional supplements from pharmacies or physicians. The results of this study indicate that nutritional supplement users in master athletics show no specific user profile. Since it is not rare for nutritional supplements to contain trace contaminations of anabolic androgenic steroids or pro-hormones, physicians should also inform master competitive athletes of the dangers of testing positive for doping substances due to their intake of nutritional supplements and advise them accordingly.

Adult↗
PubMed2006

Cerebellar hypoplasia in three sibling cats after intrauterine or early postnatal parvovirus infection.

The present report describes the case of an intrauterine or early postnatal parvovirus infection with subsequent cerebellar hypoplasia in three kittens from the same litter. Clinical examination of affected cats revealed neurologic signs indicative of cerebellar ataxia. Due to poor prognosis, animals were euthanised and submitted for necropsy. Post mortem examination demonstrated variable degrees of cerebellar hypoplasia. Histologically, brain lesions were characterised by segmental loss of the external and internal granular layer and decreased numbers of Purkinje cells. Reactive proliferation of astrocytes in the central nervous system was verified by the detection of GFAP-expressing glial cells in affected areas using immunohistochemistry. Furthermore, parvovirus antigen was detected immunohistochemically in neuronal cells of the cerebellum, but not in other parts of the brain and spinal cord or non-neuronal tissues. The present report demonstrates the usefulness of post mortem examination and detection of viral antigen by immunohistochemistry for the discrimination of neurologic disorders in feline species. Neurologic deficiencies due to cerebellar hypoplasia caused by in utero or perinatal feline parvovirus infection should be taken into consideration as differential diagnoses for ataxia in neonatal and juvenile cats.

Animals↗
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

Acoustics and psychosocial environment in intensive coronary care.

BACKGROUND: Stress, strain, and fatigue at the workplace have previously not been studied in relation to acoustic conditions. AIMS: To examine the influence of different acoustic conditions on the work environment and the staff in a coronary critical care unit (CCU). METHOD: Psychosocial work environment data from start and end of each individual shift were obtained from three shifts (morning, afternoon, and night) for a one-week baseline period and for two four-week periods during which either sound reflecting or sound absorbing tiles were installed. RESULTS: Reverberation times and speech intelligibility improved during the study period when the ceiling tiles were changed from sound reflecting tiles to sound absorbing ones of identical appearance. Improved acoustics positively affected the work environment; the afternoon shift staff experienced significantly lower work demands and reported less pressure and strain. CONCLUSIONS: Important gains in the psychosocial work environment of healthcare can be achieved by improving room acoustics. The study points to the importance of further research on possible effects of acoustics in healthcare on staff turnover, quality of patient care, and medical errors.

Acoustics↗
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

Yeast-expressed hantavirus Dobrava nucleocapsid protein induces a strong, long-lasting, and highly cross-reactive immune response in mice.

In Europe, Dobrava virus (DOBV) carried by the yellow-necked field mouse Apodemus flavicollis is one of the hantaviruses that can cause severe hemorrhagic fever with renal syndrome in humans. For several hantaviruses, the nucleocapsid (N) protein has proven to be very immunogenic in humans and rodents and even can protect rodents against a virus challenge. To investigate the immunogenicity of DOBV N protein, BALB/c and C57BL/6 mice were immunized three times with a DOBV recombinant N (rN) protein expressed in yeast Saccharomyces cerevisiae together with complete Freund's, with incomplete Freund's, and without adjuvant, respectively. Mice of both strains elicited N-specific antibodies with end-point titers being as high as 1:1,000,000 in C57BL/6 mice. The antibodies induced by DOBV rN protein were highly cross-reactive to the rN proteins of hantaviruses Puumala and Hantaan. In both mice strains, DOBV rN protein induced N-specific antibodies of all IgG subclasses (IgG1, IgG2a, IgG2b, and IgG3), suggesting a mixed Th1/Th2 immune response. Taken together, yeast-expressed DOBV rN protein represents a promising vaccine candidate.

Animals↗
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↗
PubMed2002

Polyomavirus infection in hamsters and trichoepitheliomas/cutaneous adnexal tumours.

Multiple skin nodules, with histological features of adnexal tumours consistent with trichoepithelioma, were observed on the head and trunk of Syrian hamsters. Skin biopsies from 20 hamsters from five different colonies were affected, and two of the affected hamsters also had lymphoma. Two owners reported that 16 of 70 hamsters and 50 of 100 hamsters in their colonies had similar skin lesions. These tumours have previously been associated in laboratory colonies with hamster polyomavirus (HaPV) infection. Examination of skin tissues by electron microscopy failed to reveal intranuclear virus particles. Using recombinant major capsid protein VP1 of HaPV, VP1-specific antibodies were detected in sera from 12 of 12 affected hamsters and in four of four unaffected in-contact hamsters, by ELISA. The ELISA data were verified by immunoblot analysis. Eleven of 13 serum samples contained antibodies which reacted with at least one recombinant structural HaPV protein (VP2), including samples from three in-contact unaffected hamsters. Nine of the 11 anti-VP2-positive samples also reacted with recombinant VP3 of HaPV, and six reacted with VP1. Amplification by PCR and sequencing detected VP1 -encoding sequences showing a high degree of homology with HaPV. The findings suggest a possible infection by HaPV or a HaPV-like virus and it is likely that such an infection was enzootic within the affected colonies.

Animals↗
PubMed2002

Clozapine: its impact on aggressive behavior among patients in a state psychiatric hospital.

Clozapine has shown consistent efficacy against positive symptoms of psychoses, and emerging reports indicate improvements in aggression and suicidality. This study evaluated the impact of clozapine aggression in a psychiatric hospital. Over a three year period, 137 subjects with schizophrenia or schizoaffective disorder received clozapine, of whom nearly 50% (n=69) experienced seclusion or restraint. Using a mirror-image study design, seclusion and restraint rates were computed per patient-month pre-clozapine and compared during clozapine treatment to a maximum of 12 months in either direction. The rest of the hospital not receiving clozapine served as a comparator group. Statistically significant reductions occurred in both seclusion (0.44+/-0.46 vs. 0.16+/-0.32, z=-3.91, p=0.0003) and restraint (0.34+/-0.47 vs. 0.08+/-0.23, z=-2.27, p=0.032) during clozapine treatment as compared with the pre-clozapine period. The comparator group experienced a low rate of seclusion and restraint throughout. While there are limitations to a mirror-image design, this study supports the emerging data on the benefits of clozapine for aggressive and violent patients with psychoses. Preliminary data suggests other second generation antipsychotic agents may have similar effects.

Adult↗
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↗
PubMed2002

Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae.

OBJECTIVES: Non-viral methods of gene transfer have been preferred in gene therapy approaches for several reasons, particularly for their safety, simplicity and convenience in introducing heterologous DNA into cells. Polyomavirus virus-like particles (VLPs) represent a promising carrier for encapsidation of foreign nucleic acids for gene therapy. For the development of such gene delivery systems as well as for providing reagents for improving virus diagnostics, an efficient yeast expression system for the generation of different polyomavirus VLPs was established. METHODS: A galactose-inducible Saccharomyces cerevisiae yeast expression system was used. Formation of empty VLPs was confirmed by cesium chloride ultracentrifugation, agarose gel electrophoresis and electron microscopy. Cross-reactivity of the major capsid proteins (VP1) of different polyomaviruses was analyzed by Western blot using rabbit and mice sera raised against the VP1 proteins. RESULTS: VP1 of polyomaviruses from humans (JC polyomavirus and serotypes AS and SB of BK polyomavirus), rhesus monkeys (simian virus 40), hamsters (hamster polyomavirus), mice (murine polyomavirus) and birds (budgerigar fledgling disease virus) were expressed at high levels in yeast. Empty VLPs formed by all yeast-expressed VP1 proteins were dissociated into pentamers and reassociated into VLPs by defined ion and pH conditions. Different patterns of cross-reactivity of the VP1 proteins with heterologous mice and rabbit sera were observed. CONCLUSION: The developed heterologous yeast expression system is suitable for high-level production of polyomavirus VLPs. Yeast-derived VLPs are generally free of toxins, host cell DNA and proteins. These VLPs might be useful for the generation of new diagnostical tools, gene delivery systems and antiviral vaccines.

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

A chemiluminescence detection method of hantaviral antigens in neutralisation assays and inhibitor studies.

A protocol for chemiluminescence detection of hantaviral antigens in infected cell foci is described. This focus detection is based on the conversion of a substrate into a luminescent product by peroxidase-antibody conjugates; the emitted light of infected cell foci can easily be recorded by autoradiography or video imaging providing a hard copy for documentation. The main advantage of this method as compared to conventional immunochemical staining is a higher detection sensitivity due to the inherent magnification effect of luminescence causing an obvious boost in focal image and intensity. This enables reduction of (i) incubation time of virus-infected cells and (ii) amount of needed antibody for antigen detection in foci. This method is applied to a chemiluminescence focus reduction assay for the serotyping of hantavirus-specific neutralising antibodies in infected persons and for the determination of activity of antiviral agents against hantavirus.

Animals↗
PubMed2001

Hantavirus infections and their prevention.

Hantaviruses are rodent-borne bunyaviruses which cause haemorrhagic fever with renal syndrome and Hantavirus pulmonary syndrome in humans. This review covers the host interactions of the viruses, including the rodent reservoirs, the clinical outcome of human infections as well as the pathogenesis and laboratory diagnosis of infections. The current stage in prophylaxis and therapy of hantaviral diseases is described and different approaches in vaccine development are discussed.

Animals↗