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Biomedical subjects

H J Thiel

Publications and source records attributed to H J Thiel.

At least 19 recordsLinked to original sources

[Tick-borne encephalitis (TBE) with special emphasis on infection in horses].

The tick-borne encephalitis (TBE), also known as early summer meningo-encephalitis, is a geographically limited virus infection transmitted mainly by ticks. The importance of TBE is largely underestimated. The causative agent TBE-Virus (TBEV) is grouped into the genus Flavivirus of the virus family Flaviviridae. Clinical disease including fatal outcomes has been described for men and dogs. With regard to horses only a limited number of case reports is available. In a study performed at the Institute of Virology, Justus-Liebig-University Giessen serum samples from the German endemic region of Marburg-Biedenkopf were tested for antibodies against TBEV. From 240 sera tested 7 (2.9%) were regarded as positive in a serum neutralization test (SNT). In an ELISA, performed in parallel to confirm the SNT results, 5 out of 7 positive sera from the SNT were also positive. The remaining two samples with low SNT-titres and all sera from horses negative in the SNT were also negative in the ELISA. This article is focussed on TBE of horses. In this context different aspects of TBE are included such as properties of the causative agent, interactions between causative agent, host animals and environment, spread of TBEV, pathogenesis, clinical symptoms, diagnosis and control.

Animals↗

[Noroviruses and sapoviruses in man and farm animals].

Noro- and Sapoviruses belong to the virus family Caliciviridae and are important causative agents of acute epidemic gastroenteritis in man. In many cases transmission of Noro- and Sapoviruses occurs via contaminated food or water and the respective diseases are therefore designated as food borne. Recently, the presence of Noro- and Sapoviruses in farm animals has attracted increasing attention. Clinical symptoms were observed after experimental infection of cattle and swine with members of the two virus groups. Thus far it is not known, whether virus transmission from animals to man does occur.

Acute Disease↗

Evidence for the presence of two novel pestivirus species.

The genus Pestivirus of the family Flaviviridae comprises four species, namely Bovine viral diarrhea virus-1 (BVDV-1), BVDV-2, Border disease virus (BDV), and Classical swine fever virus (CSFV). Comparative analyses of partial sequences have suggested that pestivirus isolates from giraffe (Giraffe-1) and reindeer (Reindeer-1) are distinct from the established species (Becher et al., Virology 262, 64--71, 1999). In this study, we report the complete genomic sequences of pestivirus strains Giraffe-1 and Reindeer-1. Comparative sequence analyses revealed considerable differences among Giraffe-1, Reindeer-1, and the currently recognized pestivirus species. Phylogenetic analysis of the complete coding sequences of these two strains, along with 13 other sequences representing the four established species, indicated that CSFV, BDV, and Reindeer-1 have bifurcated from one common branch and BVDV-1 and BVDV-2 from another. In the former branch BDV and the pestivirus from reindeer are more similar to each other than to CSFV. The giraffe pestivirus is equally distinct from both major branches. In addition, the antigenic relatedness of pestivirus isolates covering the observed major genetic groups was studied by cross-neutralization assays. A clustering procedure on the basis of antigenic differences indicated the presence of six major groups corresponding to the genetically defined groups. Taken together, the results of our analyses addressing both nucleotide sequence relatedness and serological relatedness argue for the inclusion of Giraffe-1 and Reindeer-1 as the first members of two separate novel species within the genus Pestivirus.

Amino Acid Sequence↗

[Recall dermatitis caused by re-exposure to docetaxel following irradiation of the brain. Case report and review of the literature].

BACKGROUND: Together with radiation therapy the taxanes Paclitaxel and Docetaxel are more and more integrated into multimodal therapy regimens concerning breast- and lung cancer as well as squamous cell carcinoma of the head and neck. Especially in palliative situations we have to be aware of increasing side effects caused by interaction of the different treatment components. Therefore we report on a severe recall dermatitis that occurred in two breast-cancer patients following irradiation of the brain and reexposition to Docetaxel. PATIENTS AND METHOD: From January until March 1999 two female patients suffering from metastatic breast cancer and newly diagnosed cerebral metastases respectively carcinomatous meningitis underwent irradiation of the whole brain (2 Gy 5 days/week up to a reference dose of 50 Gy) in our department. Both patients had several courses of Docetaxel (Taxotere) 30 mg/m2 BSA weekly respectively 100 mg/m2 BSA/month since October and November 1998. After completion of radiotherapy chemotherapy with Docetaxel was continued. RESULTS: Both patients tolerated Docetaxel well before and during radiotherapy. However, after having finished irradiation of the brain and receiving Docetaxel again a severe erythema of the irradiated skin and large areas of moist epitheliolysis with crust occurred (CTC grade IV). CONCLUSION: The dermatitis related to irradiation and reexposition to Docetaxel observed in our two cases is interpreted as a recall reaction. The basic initiating pathologic mechanism has not been solved completely. Further investigation is needed to find out how the taxanes can be used in combination radiochemotherapy regimens without causing severe toxicity to the irradiated skin or mucosa.

Aged↗

Beam-deflection method of diagnosing impaired vision.

We describe a simple method to assign a diagnosis of cataract to patients with obscurely impaired vision as well as to those with mild lens opacities. When the narrowest slit is used in a slitlamp examination, a small beam of light appears on the macula. Routine fundoscopy with the 78.0 diopter lens or a 3-mirror glass is appropriate. If a cataract is present, the beam of light is scattered into several straight lines, distorted lines, or both. This has proved a useful diagnostic tool when the lens appears clear but the patient's vision is impaired, and extensive examinations such as computer tomography or nuclear magnetic resonance tomography for impaired vision may be avoided. The beam-deflection method uses devices that are generally available and can detect cataract in the early stages of development.

Adolescent↗

Efficacy and safety of contact transscleral diode laser cyclophotocoagulation for advanced glaucoma.

BACKGROUND: This prospective study was conducted to evaluate the efficacy and safety of transscleral diode laser cyclophotocoagulation in refractory, advanced glaucoma. PATIENTS AND METHODS: One hundred eyes of 100 patients with advanced glaucoma refractory to medical treatment were consecutively treated by transscleral diode laser cyclophotocoagulation. Success was defined as a final intraocular pressure between 5 and 21 mm Hg in eyes with a visual acuity of more than hard movements, relief of pain in eyes with a visual acuity of hand movements or less including blind eyes, and reduction of carbonic anhydrase inhibitor use in all eyes. RESULTS: Ninety-three patients were followed up for 1 year after initial treatment. The overall success rate was 74.2%. Of 60 eyes with a visual acuity of more than hand movements, intraocular pressure between 5 and 21 mm Hg was achieved in 41 (68.3%) eyes. Relief of pain was achieved in 28 (84.8%) of 33 eyes. Reduction of systemic carbonic anhydrase inhibitor use was highly significant (P < 0.0001). Within 1 year, 173 laser procedures (mean, 1.9 per patient) were performed. The probability of success increased significantly (P = 0.004) with the age of the patients, from 55% for patients younger than the age of 50 years to 83% for patients older than the age of 50 years. Previous ocular surgery decreased the success probability from 95% to 68% (P = 0.02). A high success rate was achieved in inflammatory glaucoma (75%), primary open-angle glaucoma (89.5%), and neovascular glaucoma (86.7%). The results were relatively poor in traumatic glaucoma (57.1%), aphakic glaucoma (57.1%), and congenital or juvenile glaucoma (62.5%). No significant relationship between loss of visual acuity and failure of treatment (P = 0.3) could be detected. No phthisis bulbi or persistent hypotonia developed. CONCLUSIONS: Transscleral diode laser cyclophotocoagulation is an effective and safe method for the treatment of advanced, refractory glaucoma. However, repeated treatments are often necessary. Success of treatment depends on the age of patients, previous surgery, and the type of glaucoma.

Adolescent↗

RNA recombination between persisting pestivirus and a vaccine strain: generation of cytopathogenic virus and induction of lethal disease.

Molecular analysis of a cytopathogenic (cp) bovine viral diarrhea virus (BVDV) isolate (1741) obtained from a case of mucosal disease (MD) led to the identification of five different viral subgenomic RNAs in addition to a noncytopathogenic (noncp) strain (NCP 1741). For each of the subgenomes, a large internal deletion was found together with an inserted sequence encoding part of ribosomal protein S27a fused to an N-terminally truncated ubiquitin monomer. Surprisingly, the two cellular insertions together with flanking viral sequences encoding parts of NS3 and NS4B are >99% identical to the previously described sequence of BVDV vaccine strain RIT (P. Becher, M. Orlich, and H.-J. Thiel, J. Virol. 72:8697-8704, 1998), while the remainder of the subgenomes is derived from the genome of NCP 1741. Further analyses including molecular cloning and nucleotide sequencing of the recombination partners revealed that both homologous and nonhomologous RNA recombination contributed to the generation of the viral subgenomes. Interestingly, for another cp BVDV isolate (CP 4584) from an independent case of MD, again an insertion of a RIT-derived sequence element was detected. In contrast to CP 1741, for CP 4584 a duplication of the genomic region encoding NS3 and parts of NS4A and NS4B was found. Transfection of bovine cells with RNA transcribed from a chimeric cDNA construct showed that the RIT-derived insertion together with the CP 4584-specific duplication of viral sequences represents the genetic basis of cytopathogenicity of CP 4584. Remarkably, passages of the recovered cp virus in cell culture led to emergence of noncp BVDV and a number of viral subgenomes whose genome organization was similar to that in BVDV 1741.

Animals↗

A cellular J-domain protein modulates polyprotein processing and cytopathogenicity of a pestivirus.

Pestiviruses are positive-strand RNA viruses closely related to human hepatitis C virus. Gene expression of these viruses occurs via translation of a polyprotein, which is further processed by cellular and viral proteases. Here we report the formation of a stable complex between an as-yet-undescribed cellular J-domain protein, a member of the DnaJ-chaperone family, and pestiviral nonstructural protein NS2. Accordingly, we termed the cellular protein Jiv, for J-domain protein interacting with viral protein. Jiv has the potential to induce in trans one specific processing step in the viral polyprotein, namely, cleavage of NS2-3. Efficient generation of its cleavage product NS3 has previously been shown to be obligatory for the cytopathogenicity of the pestiviruses. Regulated expression of Jiv in cells infected with noncytopathogenic bovine viral diarrhea virus disclosed a direct correlation between the intracellular level of Jiv, the extent of NS2-3 cleavage, and pestiviral cytopathogenicity.

Amino Acid Sequence↗

[Vaccination against foot and mouth disease: current state and perspectives].

Foot-and-mouth disease (FMD) is endemic in many parts of the world and poses a permanent threat for cloven-hoofed animals in all countries. The available vaccines against FMD are safe and efficacious. Combat of FMD by vaccination is controversial in currently FMD-free countries including the ones of the European Union. The article summarizes our knowledge concerning production and use of vaccines, virus persistence, differentiation between vaccinated and infected animals, vaccination programs and perspectives of vaccine development.

Animals↗

Insertion of cellular NEDD8 coding sequences in a pestivirus.

For the cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strain CP 821, a duplication of the genomic region encoding part of NS2, NS3, NS4A, and part of NS4B together with a nonviral insertion was detected. Further analyses including molecular cloning and sequencing of the putative cellular recombination partner showed that the insertion in CP 821 originated from a bovine mRNA encoding the cellular protein NEDD8, which is 58% identical to ubiquitin. To our knowledge the genome of CP 821 represents the first viral RNA with a NEDD8 coding insertion. Remarkably, the insertion site differs from that described for insertions of ubiquitin. The NEDD8 sequence allows an additional cleavage of the viral polyprotein, whereby an NS3 with an unusual N-terminus is generated. Furthermore, the CP 821-specific genomic alterations were introduced into an infectious noncytopathogenic (noncp) BVDV cDNA clone. After transfection of bovine cells with the respective RNA, a cp virus was recovered. This showed that the NEDD8 coding insertion together with the duplicated viral sequences represents the genetic basis for cytopathogenicity of CP 821. In addition to the recovered cp virus, noncp BVDV rapidly evolved after transfection. This is the first time that a change from the cp to the noncp phenotype was demonstrated in the course of replication in tissue culture cells.

Amino Acid Sequence↗

Translation from the internal ribosome entry site of bovine viral diarrhea virus is independent of the interaction with polypyrimidine tract-binding protein.

Translation of the pestiviral polyprotein is initiated cap independently at an internal site of the viral RNA, the internal ribosome entry site (IRES). We investigated the translation from the IRES of bovine viral diarrhea virus (BVDV) and the possible interaction of the unconventional cellular RNA-binding proteins, particularly of polypyrimidine tract-binding protein (PTB). The BVDV IRES is translationally active in rabbit reticulocyte lysate (RRL), and it is translated most efficiently at low concentrations of Mg(2+)- and K(+)-ions. In the UV cross-link assay, several proteins from RRL bind to the BVDV IRES, including proteins of 50, 65 and 72kDa, but no protein of 57kDa possibly corresponding to PTB, although PTB is endogenously present in RRL. However, the BVDV IRES can bind PTB weakly under certain conditions. Interestingly, in a functional depletion and add-back translation system, PTB does not enhance translation of BVDV, although PTB enhances translation of a picornavirus in this translation stimulation assay. These results indicate that PTB can bind the BVDV IRES RNA, but translation is independent of the action of PTB.

Animals↗

Rabbit hemorrhagic disease virus: genome organization and polyprotein processing of a calicivirus studied after transient expression of cDNA constructs.

Rabbit hemorrhagic disease virus (RHDV) belongs to the family Caliciviridae. Studies on this virus are hampered by the lack of a convenient cell culture system. To study viral protein expression a cDNA construct containing the entire protein-coding region of the virus was established and used for transient expression studies. After metabolic labeling of transfected cells and immunoprecipitation with a set of RHDV-specific antisera a variety of polypeptides were identified and assigned to defined regions of the viral genome. The consensus sequences of already identified or putative proteolytic cleavage sites in the viral polyprotein were changed by the introduction of mutations into the expression construct. Expression of these mutated constructs and analysis of the protein patterns allowed us to identify novel cleavage sites in the polyprotein and revealed the first details regarding the order of polyprotein processing.

Chromosome Mapping↗

NS3 serine protease of bovine viral diarrhea virus: characterization of active site residues, NS4A cofactor domain, and protease-cofactor interactions.

The gene expression of bovine viral diarrhea virus (BVDV), a pestivirus, occurs via translation of a hypothetical polyprotein that is processed cotranslationally and posttranslationally by viral and cellular enzymes. A protease located in the N-terminal region of nonstructural (NS) protein NS3 catalyzes the cleavages, leading to the release of NS4A, NS4B, NS5A, and NS5B. Our study provides experimental evidence that histidine at position 1658 and aspartic acid at position 1686 constitute together with the previously identified serine at position 1752 (S1752) the catalytic triad of the pestiviral NS3 serine protease. Interestingly, a mutant protease encompassing an exchange of the active site S1752 to threonine still showed residual activity. This finding links the NS3 protease of pestiviruses to the capsid protease of Sindbis virus. Furthermore, we observed that the minimal protease domain of NS3 encompasses about 209 amino acids. The NS3 protease was found to be sensitive to N-terminal truncation because a deletion of 6 amino acids significantly reduced the cleavage efficiency at the NS4A/4B site. Larger N-terminal deletions also impaired the activity of the enzyme with respect to the other cleavage sites but to a different degree at each site. The NS3 protease of BVDV has previously been shown to depend on NS4A as cofactor. We demonstrate here that the central region of NS4A represents the cofactor domain. Furthermore, coprecipitation studies strongly suggest an interaction between NS4A and the N-terminal region of NS3. Besides the remarkable similarities observed between the pestiviral NS3 protease and the corresponding enzyme of hepatitis C virus (HCV), our results suggest a common ancestry between these enzymes and the capsid protease of Sindbis virus.

Animals↗

[Prevention of radiation-induced diarrhea by smectite. Results of a double-blind randomized, placebo-controlled multicenter study].

PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6 g smectite daily and 91 patients received 2 x 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (> or = 3 pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. CONCLUSION: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.

Abdomen↗

[Are filtering interventions in glaucoma patients with extensive visual field defects associated with a higher functional risk?].

BACKGROUND: We evaluated the prevalence of the loss of visual acuity due to loss of the central portion of the visual field and foveolar fixation in the first week after glaucoma filtering surgery. PATIENTS AND METHODS: We included 408 patients, in whom glaucoma filtering surgery was performed between January 1993 and April 1997 at the University Eye Clinic in Tübingen and who had completed 1-year follow-up examinations. The retrospective evaluation included preoperative, intraoperative and postoperative data. We excluded all patients who did not complete 1-year follow-up examinations (12 +/- 3 months), who have died during the 1-year follow-up, who had combined glaucoma and cataract surgery or in whom the Molteno implant procedure was performed. RESULTS: A total of 404 patients (99.3%) did not suffer loss of the central visual field and foveolar fixation in the first week after glaucoma filtering surgery. In 11 cases, loss of visual acuity > 2 dB was due to progressive lens opacification. One patient suffered from postoperative progression of his age-related maculopathy. In one patient (0.2%) progression of a preexisting relative central scotoma occurred immediately after the operation. Two patients (0.5%) suffered from loss of fixation and the central visual field immediately after glaucoma filtering surgery. CONCLUSIONS: Loss of the central visual field and central fixation immediately after glaucoma filtering surgery is a rare complication. Therefore, glaucoma filtering surgery can also be recommended for patients with advanced visual field defects.

Filtering Surgery↗

[Evaluating the Pro Ton applanation tonometer in rabbits].

PURPOSE: To assess use of the tonometer ProTon for measuring intraocular pressure in rabbits. MATERIALS AND METHODS: Eleven chinchilla-bastard rabbits were measured under standardized conditions with the applanation tonometer ProTon for 62 +/- 15 days. One rabbit was excluded because of intensively defensive reactions. RESULTS: Intraocular pressure in the ten rabbits was 12.15 +/- 3.63 mmHg in the right eye and 12.11 +/- 3.52 mmHg in the left eye. CONCLUSION: Intraocular pressure can be measured reliably over a long period with the applanation tonometer ProTon. It is therefore suitable for determining intraocular pressure in experimentally induced glaucoma in rabbits.

Animals↗

Ultrasonic transmission in viscoelastic substances.

PURPOSE: To study the propagation of ultrasonic shock waves in viscoelastic agents and the resulting corneal load. SETTING: University Siegen, Institute for Mechanics and Control Engineering, Siegen, Germany. METHODS: The anterior chamber of a manufactured artificial eye was constructed according to anatomic dimensions. Three openings were drilled--for the phaco tip, for the exchange of a viscoelastic agent or water, and for the shock-wave sensor. The sensor was fixed to the area corresponding to the corneal apex. The sensor signal was analyzed using a direct oscilloscope that measured the amplitude reaching the corneal apex. Shock-wave propagation in several viscoelastic agents was compared with that in balanced salt solution. RESULTS: In hydroxypropyl methylcellulose, the shock wave was amplified or influenced slightly. In hyaluronic-acid preparations, acoustic dampening occurred. CONCLUSION: Removal of hyaluronic-acid derivatives prior to phacoemulsification is not necessary.

Anterior Chamber↗

[Manifestation of Creutzfeldt-Jakob disease 30 years after corneal transplantation].

BACKGROUND: Creutzfeldt-Jakob disease, currently viewed as one of the prionic diseases, occurs in by far the majority of cases sporadically, sometimes in families, and in rare instances as a transmissible disease with every conceivable interval of latency. HISTORY AND SIGNS: This report of a 45-year-old female concerns a spongiform encephalopathy which appeared almost 30 years after penetrating keratoplasty. The corneal material came from a 63-year-old donor with Creutzfeldt-Jakob disease; the keratoplasty was performed at a time when the transmissibility of certain diseases was still unknown. CONCLUSION: The risk of transmission of the disease is very low but cannot be ruled out.

Creutzfeldt-Jakob Syndrome↗