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Biomedical subjects

J Blümel

Publications and source records attributed to J Blümel.

At least 19 recordsLinked to original sources
PubMed2004

Immobilization of phosphines on silica: identification of byproducts via 31P CP/MAS studies of model alkyl-, aryl-, and ethoxyphosphonium salts.

Immobilizing bifunctional phosphines with ethoxysilane groups on silica often leads predominantly, and sometimes quantitatively, to P(V) side products that occupy space on the surface but cannot bind metal complexes. Although this side reaction is well-known, and dreaded because it leads to leaching of adsorbed catalysts that are not bound covalently, the exact nature of the surface-bound side product was not yet known. With the help of polycrystalline model compounds of the types [R3PEt]+X- and [R3POEt]+X- (R=alkyl, aryl; X=Cl-, Br-, I-, BF4-) and their solid-state NMR characteristics [delta(31P), CSA], it is demonstrated that the side product is an ethylphosphonium salt bound to the surface by a siloxide anion, [R3PEt]+[Si-O]-.

Journal Article↗
PubMed2004

Cell culture-based assay of parvovirus B19 and the relevance of animal model viruses.

One of the most challenging problems with the interpretation of virus validation studies is the relevance of the model viruses investigated. There are cases where model viruses have been shown to predict the inactivation/removal of a specific virus while unexpected results were obtained in other cases such as inactivation of parvovirus B19 by pasteurisation or treatment with guanidinium hydrochloride. The understanding of the mechanism underlying virus inactivation/removal might be helpful for the selection of model viruses and for the assessment of validation data on its relevance for a specific virus in question.

Albumins↗
PubMed2003

Quantitative trait loci mapping of functional traits in the German Holstein cattle population.

A whole-genome scan to detect quantitative trait loci (QTL) for functional traits was performed in the German Holstein cattle population. For this purpose, 263 genetic markers across all autosomes and the pseudoautosomal region of the sex chromosomes were genotyped in 16 granddaughter-design families with 872 sons. The traits investigated were deregressed breedingvalues for maternal and direct effects on dystocia (DYSm, DYSd) and stillbirth (STIm, STId) as well as maternal and paternal effects on nonreturn rates of 90 d (NR90m, NR90p). Furthermore, deregressed breeding values for functional herd life (FHL) and daughter yield deviation for somatic cell count (SCC) were investigated. Weighted multimarker regression analyses across families and permutation tests were applied for the detection of QTL and the calculation of statistical significance. A ten percent genomewise significant QTL was localized for DYSm on chromosome 8 and for SCC on chromosome 18. A further 24 putative QTL exceeding the 5% chromosomewise threshold were detected. On chromosomes 7, 8, 10, 18, and X/Yps, coincidence of QTL for several traits was observed. Our results suggest that loci with influence on udder health may also contribute to genetic variance of longevity. Prior to implementation of these QTL in marker assisted selection programs for functional traits, information about direct and correlated effects of these QTL as well as fine mapping of their chromosomal positions is required.

Animals↗
PubMed2002

Mapping of the bovine blood group systems J, N', R', and Z show evidence for oligo-genetic inheritance.

Genes determining the bovine erythrocyte antigens were mapped by linkage analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a grand-daughter design were elucidated for the genes determining the erythrocyte antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ according to standard paternity testing procedures in the blood typing laboratories. Linkage analyses were performed with 248 microsatellite markers, eight SSCP markers and four polymorphic proteins and enzymes covering the 29 autosomes and the pseudoautosomal region of the sex chromosomes. The number of informative meioses for the blood group systems ranged from 76 to 947. Blood group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen loci showed significant linkage to a single chromosome and were mapped unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to chromosome 17. However, the EAN' system previously known as part of the EAF system could be mapped to chromosome 5. In addition, the blood group systems EAJ, the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers on various chromosomes and also to other blood groups. The appearance of a single blood group system might be therefore either dependent on the existence of other blood group systems or because of an interaction between different loci on various chromosomes as is known in humans and in pigs.

Animals↗
PubMed2001

A whole genome scan for differences in recombination rates among three Bos taurus breeds.

Twenty paternal half-sib families of a granddaughter design were genotyped for 265 genetic markers, most of them microsatellites. These were 16 Holstein families, 3 Simmental families, and 1 Brown Swiss family. The number of sires per breed was 872, 170, and 32, respectively. Two-point recombination rates were estimated both jointly for all breeds and each single breed separately. Of 1168 marker intervals, 865 provided estimates for at least two breeds. Differences between breeds were tested by likelihood ratio tests. Four marker intervals, representing three genomic regions on BTA19, BTA24, and BTA27, show a significant impact of the breed at a false discovery rate of 0.23 and indicate a genetic component of observed heterogeneity of recombination. The variability of recombination rates between cattle breeds might not be a common feature of the whole genome, but rather might be restricted to certain chromosomal segments. Thus, attention should be paid to heterogeneities when pooling data of such regions from different breeds.

Animals↗
PubMed2001

Parvovirus B19 DNA in plasma pools and plasma derivatives.

BACKGROUND AND OBJECTIVES: Human parvovirus B19 (B19) has been transmitted by various plasma-derived medicinal products. The aim of this study was to determine the frequency and the level of B19 DNA contamination in plasma pools destined for fractionation and in a broad range of plasma derivatives. In addition, removal of B19 DNA by the manufacturing process was investigated in cases where corresponding samples from plasma pool and product were available. MATERIALS AND METHODS: Plasma pool samples and blood products were tested for B19 DNA by nested polymerase chain reaction (PCR), and the viral DNA content was determined by TaqMan quantitative PCR. RESULTS: Two-hundred and twenty two of 372 plasma pools for fractionation contained B19 DNA at concentrations of 10(2)-10(8) genome equivalents/ml (geq/ml). While approximately 65% of the DNA-positive plasma pools were only moderately contaminated (< 10(5) geq/ml), 35% contained > 10(6) geq/ml. High frequencies of contamination were detected in Factor VIII (79 of 91), prothrombin complex concentrates (38 of 43) and Factor IX (41 of 62), where the concentration of B19 DNA ranged between 102 and 107 geq/ml. A lower level of B19 DNA contamination was found in antithrombin III (five of 26 samples), in anti-D immunoglobulins (three of 37 samples) and in albumin (four of 51 samples), with levels ranging between 10(2) and 10(3) geq/ml. Furthermore, investigation of plasma pools for solvent/detergent plasma (S/D plasma), from two manufacturers, revealed B19 DNA in 15 of 66 batches at concentrations of 10(2)-10(8) geq/ml. Similar concentrations were detected in the corresponding final S/D plasma products. Anti-B19 immunoglobulin G (IgG) was found in plasma pools and S/D plasma at concentrations of approximately 40 IU/ml. CONCLUSION: Although positive PCR results do not necessarily reflect infectivity, these data show that B19 is a common contaminant in plasma pools and in plasma-derived medicinal products. Considering the resistance of animal parvoviruses to inactivation by heat and chemical agents, and the absence of specific information for B19, the risk of B19 transmission by plasma products should be considered. Physicians should be aware of this problem when treating patients of B19-related risk groups. The plasma fractionation industry should continue their efforts to avoid B19 contamination of plasma derivatives and develop methods which are effective in removing/inactivating parvovirus B19.

Blood↗
PubMed2000

Structure of simian virus 40 DNA replicated by herpes simplex virus type 1.

Replicating herpes simplex virus type 1 (HSV-1) DNA is known to form large branched structures. The aim of this study was to define whether HSV-1-specific DNA elements in cis play a critical role in formation of this structure. We did this by investigating the structure of heterologous simian virus 40 (SV40) DNA, which is replicated in HSV-infected cells by SV40 large T-antigen and defined HSV-encoded replication factors (e.g., DNA polymerase, single-stranded DNA-binding protein, and helicase-primase). During this process, extrachromosomal concatemeric DNA replication products are formed, indicating a herpesvirus-specific replication mode. In this study, we found that the replicating SV40 DNA consisted of a complex branched structure indistinguishable from that of replicating HSV DNA. Thus, no HSV-specific DNA element is necessary in cis for the formation of the large branched structure during HSV DNA replication. The trans-acting HSV DNA replication proteins seem to be sufficient to generate these complex structures. Moreover, replicating SV40 DNA showed a high frequency of homologous recombination events, which is typical for HSV DNA replication. However, in contrast to HSV origin-bearing amplicon plasmids, SV40 plasmids bearing the HSV cleavage-packaging signal were not efficiently processed to linear 150-kb DNA packaged into HSV capsids. This indicates that initiation of DNA synthesis on HSV-ori determines some, yet undefined, property of replicating HSV DNA, which is crucial for regular processing of the replication intermediates to daughter genomes.

Animals↗
PubMed2000

An intra-laboratory validation of the Integrated Model for the Differentiation of Skin Reactions (IMDS): discrimination between (photo)allergic and (photo)irritant skin reactions in mice.

We recently presented a modified local lymph node test which made it possible to quickly and reliably differentiate between irritative and allergic skin reactions with extremely simple parameters. The Integrated Model for the Differentiation of Skin Reactions (IMDS) test combines measurement of cell proliferation in draining lymph nodes with measurement of primary ear swelling after topical application of the test substance on three consecutive days. In contrast to the 'classic' skin sensitisation test in guinea-pigs the IMDS test is considerably faster and is based on objective measured data, not subjective skin evaluations. Like the Local Lymph Node Assay (LLNA), measurement of allergic potential in the IMDS test is based on the underlying immunological mechanisms, but also considers the behaviour of immune competent cells following non-specific activation by irritants. In addition, the IMDS test can employ UV radiation after application of the substance and, therefore, make differentiation possible between different types of skin photoreaction (photoallergy and photoirritation) after both topical and systemic administration. Attempts to achieve this kind of discrimination with the LLNA necessitate considerably greater expenditure, as proliferation in the draining lymph nodes can also be induced by moderate to extreme (photo)irritants. In a previous paper in which we presented the IMDS test, we examined each type of reaction in reference to one single standard; the next logical step was therefore a broad-based intra-laboratory validation. An important factor in the validation was the use of standards that had been thoroughly examined in both guinea pig and mouse systems and were also relevant with regard to estimation of the risk for humans. The data presented here show that the IMDS is a simple and reliable tool for obtaining fast and reproducible assessments of potential (photo)allergic and (photo)irritant skin reactions to substances.

Administration, Cutaneous↗
PubMed2000

Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions.

Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.

Administration, Oral↗
PubMed1999

Primary immune response in skin and skin-associated lymphoid tissue of interleukin-4 transgenic mice.

The interleukin-4 transgenic mice investigated here exhibit a ubiquitous expression of interleukin-4 in all organs, including the skin. In this study, the induction phase of oxazolone-induced local primary contact hypersensitivity and croton oil-induced irritant contact dermatitis in transgenic and wild-type mice was analysed. Compared to wild-type mice, the transgenic mice showed a decreased activation of the skin-draining lymph nodes but a strong hyperreactivity in the skin after topical sensitisation. In contrast to this, both the transgenic and the wild-type mice developed a strong and comparable inflammatory skin reaction after topical irritation. A striking increased expression level of tumour necrosis factor-alpha and macrophage inflammatory protein-2 genes were found in the skin of the transgenic mice during primary local contact hypersensitivity, while both the transgenic and the wild-type mice developed comparable expression levels of these cytokines during irritant contact dermatitis. Compared to wild-type mice, a strongly enhanced expression level of interleukin-6 transcripts derived from epidermal antigen presenting cells were detected in the skin of IL-4 transgenic mice, whereas in the skin-draining lymph nodes of transgenic mice significantly lower levels were detected. We conclude that the migration of epidermal antigen-presenting cells towards the skin-draining lymph nodes is reduced in transgenic mice, which could be due to the different cytokine balance in these mice strains. The atypical irritant-like reaction observed in transgenic mice after topical sensitisation is a phenomenon comparable to atopic diseases and therefore this transgenic strain might be a helpful model for investigating the immunopathophysiological features of these diseases.

Animals↗
PubMed1998

An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions.

Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack of in vitro and in vivo assays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+ cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.

Animals↗
PubMed1998

Typing of Nocardia farcinica by pulsed-field gel electrophoresis reveals an endemic strain as source of hospital infections.

Severe postoperative wound infections caused by Nocardia farcinica were repeatedly observed in a German hospital surgical ward. A pulsed-field gel electrophoresis (PFGE) protocol was established to characterize the genetic relatedness of the bacterial isolates from these infections. All 18 isolates from postoperative infections that have occurred since 1985 belong to a common endemic genotype; organisms of this genotype were also detected in the air of two rooms of the department where these postoperative infections occurred. In contrast, two environmental isolates from another building on the same campus showed a distinct genotype. Three cases of pulmonary infections, at a department which is located in proximity to the surgical department, were also caused by the endemic type, which suggests aerogenic spread of the endemic strain to these patients. Controls consisting of epidemiologically unrelated isolates from sporadic infections in other towns belonged in each case to a different genotype. PFGE was well suited to differentiate various types of N. farcinica and revealed an endemic strain causing postoperative wound infections possibly after aerogenic transmission.

Bacterial Typing Techniques↗
PubMed1997

Adenovirus-induced liver necrosis in a case of AIDS.

Adenovirus-induced liver necrosis is rare. Because the era of AIDS (acquired immunodeficiency syndrome) this entity was seen predominantly in infants suffering from inborn immunodeficiency syndromes or from iatrogenic immunosuppression because of bone marrow or liver transplantation. Here, we report a case of a 30-year-old woman with AIDS who developed fever and rapidly progressing liver failure. A frozen section from a needle biopsy of the liver allowed a quick diagnosis of viral liver necrosis. The light-microscopic and electron microscopic aspects were typical of adenovirus infection and should be known to the surgical pathologist. The diagnosis was confirmed by immunohistochemistry and DNA hybridization analysis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Study on simian virus 40 DNA synthesis in herpes simplex virus-infected cells.

Replication of simian virus 40 (SV40) DNA occurs in SV40 nonpermissive hamster cells upon infection with herpes simplex virus (HSV), leading to concatemeric replication products characteristic for HSV DNA replication. This SV40 origin (ori)-dependent process is governed by SV40 large T antigen and HSV-encoded DNA replication factors; e.g., DNA polymerase, single-strand binding protein (SSB), and helicase-primase. In this study, we show that specific interaction of SV40 T antigen with SV40 ori is crucial for HSV-directed SV40 DNA synthesis and that the property of T antigen to bind and unwind the ori is not sufficient for this process. A T antigen with the mutation T217S, affecting a hypothetical novel DNA replication subfunction, is able to support DNA synthesis in vitro but not in cultured primate cells. This subfunction is also necessary in HSV-infected hamster cells. Using temperature-sensitive mutants, we demonstrate that the T antigen acts at early stages of DNA synthesis while HSV helicase is required continuously as has been shown for HSV DNA polymerase. HSV SSB is also continuously involved in heterologous SV40 DNA synthesis. However, a HSV mutant, temperature-sensitive in SSB function, showed residual synthesis of SV40 DNA but not of HSV DNA at the nonpermissive temperature. The nature of this dichotomy between HSV SSB function on SV40 DNA and HSV DNA will be discussed.

Animals↗
PubMed1995

Thermosensitive UL9 gene function is required for early stages of herpes simplex virus type 1 DNA synthesis.

DNA replication of herpes simplex virus type 1 (HSV-1) is dependent on a virus-encoded sequence-specific origin-binding protein, the product of the UL9 reading frame. We have identified the mutations in the UL9 gene of three temperature-sensitive (ts) mutants of HSV-1 which are responsible for the ts phenotype (A90T in mutant tsS and V220M in tsR and tsX). The mutations are located in two different conserved helicase sequence motifs of UL9. Two further alterations (I204T and E280D) compared to the published sequence were found in the mutant, revertant and parental wild-type strain 17syn+ sequences and therefore seemed to be irrelevant for the ts phenotype. The ts function of the UL9 protein was required at early times during DNA synthesis whereas upward temperature shifts at later times did not considerably inhibit DNA synthesis.

Amino Acid Sequence↗
PubMed1978

[Surgical technic in the treatment of mandibular osteomyelitis].

Our experience with operative treatment of 70 patients with osteomyelitis of the mandible showed that the incision and drainage of soft-tissue abcesses combined with antibiotic therapy led to healing in 22 patients. More extensive measures, such as sequestectomy, decortication, resection of whole areas of the mandible, and transplantation of autologous cancellous bone, however were necessary with 48 of the patients. A detailed description of the various operative techniques was presented; the respective indications were mentioned.

Abscess↗