PubMed Health⌕ Search

Biomedical subjects

T Wirth

Publications and source records attributed to T Wirth.

At least 19 recordsLinked to original sources
PubMed1992

Functional analysis of defined mutations in the immunoglobulin heavy-chain enhancer in transgenic mice.

We have analyzed the effect of defined mutations in the mouse immunoglobulin heavy-chain enhancer after introduction into the germline of transgenic mice. We have tested a mutation of the enhancer octamer motif, a double mutation of the octamer motif and the microB-site, and a triple mutation in the microE2, microE3 and microE4-sites. All constructs are expressed in the spleen of transgenic mice. Furthermore, expression is exclusively detectable in lymphoid organs and not in several nonlymphoid tissues. Whereas mutations in the microE-sites have a more pronounced effect on transgene activity in thymocytes as compared to bone marrow and spleen cells, the octamer/microB double mutation shows significantly reduced expression levels only in B-cells. Finally, our results demonstrate that the intronic heavy-chain enhancer element does not contribute to the increase steady state levels of heavy-chain mRNA after stimulation of spleen cells with LPS.

Animals↗
PubMed1992

Synovial haemangioma of the knee joint.

Synovial haemangioma of joints are rare, but usually affect the knee joints of children and adolescents. Recurrent swelling, usually due to haemarthrosis, and intermittent pain may be present for a long time before the diagnosis is made. In this case report the common features of the condition are described, with emphasis on the occurrence of atraumatic haemarthrosis in children. The value of arthroscopy in diagnosis is discussed.

Arthroscopy↗
PubMed1992

Ultrasonography in Legg-Calvé-Perthes disease.

Ultrasonography was found to be a valuable investigation in the assessment and management of Legg-Calvé-Perthes disease (LCPD). It was used to assess 23 patients with LCPD in 25 affected hips and was compared with radiographs obtained at the same time. A chronological five-part staging of LCPD is proposed, expressing the degree of flattening and fragmentation as well as reconstitution of the femoral head as seen on ultrasound examination. Thickening of articular cartilage was documented, and associated findings of synovitis and lateral extrusion of the femoral head were evaluated. An intraarticular hip effusion was present in 74% of cases in stages I-II. Lateral extrusion increased from stage II onwards until the healing stage. The phase of reconstitution (stage IV) demonstrated both resorption of the necrotic bone and formation of new immature osteoid tissue. Lateral extrusion and the start of the healing phase can be shown earlier by ultrasonography than by radiography.

Child↗
PubMed1992

Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity.

Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif. Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however. We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line. Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells. This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2-mediated enhancer activation. Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation. Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position. The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position.

Animals↗
PubMed1992

[Participation refusal by probands in an epidemiologic long-term study--sociodemographic, clinical and psychometric findings].

Usually little is known about probands who participated in an epidemiological longitudinal field survey but refused participation in follow-up investigations. For reasons of data protection and on account of the fact that investigative instruments used in longterm field surveys or panel studies are more focused on well defined issues (opinions, attitudes, assessment of behaviors) and less on personality variables, differentiated statements on probands who explicitly refused cooperation can hardly be made. In our epidemiological longitudinal field study on prevalence and course of psychogenic disorders we have a different situation. Within the limits of our study we had the unique opportunity to gain far-reaching information on probands who refused to participate in preceding investigations in regard to sociodemographic, psychometric and clinical variables. The clientele of refusers we present in our paper mainly comprises elderly, married, rather obsessive-compulsive structured, lower-class females. According to our data interactive aspects are equally responsible for reduced cooperativeness. The significance of our findings for the planning and carrying out of epidemiological longitudinal field surveys is discussed.

Adult↗
PubMed1991

Anti-IgM antibodies down modulate mu-enhancer activity and OTF2 levels in LPS-stimulated mouse splenic B-cells.

Stimulation of small, resting, splenic B cells with bacterial lipopolysaccharide (LPS) induces proliferation, differentiation to plasma cell formation, and the expression of immunoglobulin heavy chain (IgH). When this is combined with agents which crosslink surface Ig, differentiation and the induction of surface immunoglobulin are suppressed even though proliferation proceeds. We find that anti-mu antibodies suppresses Ig gene expression of transfected mu constructs, even if either the membrane or secretory segments have been deleted. We examined the effects of anti-mu treatment on the IgH enhancer (IgHE) attached to a heterologous test gene (CAT). Indeed the IgH enhancer alone was subject to anti-mu suppression, while the SV40 enhancer was insensitive. To determine what was responsible for suppression of enhancer function by anti-mu we examined nuclear extracts from stimulated splenic B cells for the presence of sequence-specific DNA binding activities to various sites within the enhancer. We found two specific differences--an induction in mu E5 binding activity, and a reduction in octamer transcription factor 2 (OTF2) binding activity, after anti-mu treatment. Analysis of these cells by in situ immunofluorescence with anti-OTF2 antibodies suggests that the nuclear localization of OTF2 in anti-mu treated cells may change, as well as its absolute level.

Animals↗
PubMed1991

Multiple Oct2 isoforms are generated by alternative splicing.

The interaction of the Oct2 transcription factor with the cognate octamer motif ATGCAAAT is a critical determinant of the lymphoid-specific expression of immunoglobulin genes. Ectopic expression of cloned Oct2 cDNA was shown to be sufficient to reconstitute at least some aspects of this regulation in non-lymphoid cells. We describe the isolation and characterization of multiple cDNAs encoding mouse Oct2 from a mature B-cell line and we show that a variety of isoforms of this transcription factor is generated from a single gene by an alternative splicing mechanism. All the isoforms retain the previously characterized POU-domain and are therefore able to bind to the octamer motif. Different amounts of the various isoforms are present within the same B-cell regardless of the developmental stage of B-cell differentiation and at least some of the isoforms are conserved between mouse and humans. In cotransfection experiments we show that all the isoforms are able to activate an octamer containing promoter element in fibroblasts revealing an unexpected functional redundancy. Finally, we show that one of the isoforms encodes the previously described lymphoid-specific Oct2B protein which has been suggested to be involved in the function of the octamer motif in the context of the immunoglobulin heavy-chain (IgH) enhancer.

Amino Acid Sequence↗
PubMed1991

[Wound secretions in standard orthopedic surgery interventions using a new kind of closed vacuum drainage. A report of experiences].

One year's experience with 400 closed Redyrob drainage systems in 267 male and female patients has yielded encouraging results, which led to the replacement of the drainage system formerly used in the orthopaedic university clinic in Marburg by the new system. This makes it possible to regulate the suction strength between 0 and 900 mbar and to couple two suction tubes with one container. Drainage without suction and changing of the containers, which may be necessary in the case of large wound surfaces, can be performed without opening the system, which would endanger both patients and clinic personnel. Additional containers were only needed in 2.3%, because of the better filling volume. Thus, the new drainage system also proved to be superior with respect to cost efficiency and disposal. The total amount of wound secretion never exceeded 1620 ml, depending on the type of surgery performed, and there were no cases of infection or bleeding complications. The suction was regulated in 74% of all systems, and after most of the operations for insertion of endoprostheses. The handling of the systems was classed by the staff on the ward as "very good" or "good" in 96% of all cases. These results are discussed in the light of important aspects of wound drainage already mentioned by other authors.

Adult↗
PubMed1988

Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function.

Enhancers and promoters, cis-acting regulators of mammalian gene expression, are modular units containing multiple short binding sites for specific trans-acting transcription factors. To investigate if factors binding to enhancer sequences are functionally different from promoter-binding factors, we asked if a short DNA sequence element in the immunoglobulin kappa (kappa) light chain enhancer that binds to the nuclear factor NF-kappa B could also serve as a functional promoter element. A synthetic oligonucleotide containing this binding site was placed in either orientation upstream of the beta-globin TATA-element. In myeloma cells, the NF-kappa B binding site efficiently directed transcription. The promoter activity was directly correlated with the presence of the nuclear factor NF-kappa B: there was no transcription in fibroblasts or in unstimulated pre-B cells where the factor was absent. Transcription could be stimulated in pre-B cells by treatments known to activate NF-kappa B. Thus, the same nuclear factor can act as a positive activator of both enhancer and promoter function, suggesting that the two functions involve similar events in the transcription process.

Animals↗
PubMed1985

Structure and genomic organization of a new family of murine retrovirus-related DNA sequences (MuRRS).

A new class of murine retrovirus-related sequences (MuRRS) is described. These 5.7 kb long transposon-like DNA-elements start and end with approximately 600 bp long repeats identical to previously identified solitary LTR-like elements (LTR-IS). There are about 50 - 100 5.7 kb elements and about 500 - 1000 solo LTR-IS elements per mouse haploid genome. Sequence analysis of one cloned MuRRS element revealed several possible open reading frames with partial sequence homologies to retroviral gag, pol and env genes.

Animals↗
PubMed1977

[Feminizing adrenal cortex carcinoma in a 66-year-old man].

Feminizing tumors of the adrenal cortex in man are very rare. The case is reported of a 66-year-old man who had a carcinoma of the right adrenal cortex which produced various steroid fractions. In the primary tumor and in the second reccurrence the estrogens were dominant. In electron microscopy the tumor cells are poorly differentiated. They may be attributed to the fasciculo-reticular layer and show no signs specific for their secretory activity. The patient died 2 1/2 years after onset of the disease. The case is discussed in the light of the pertinent literature.

Adrenal Cortex Hormones↗
PubMed1975

[The effect of asbestos cement, UICC asbestos samples and quartz on the peritoneum of the mouse].

Aqueous suspensions of asbestos cement powder injected experimentally into the peritoneal cavity of mice act as a fibrogenic agent, as do chrysotile asbestos or chrysotile asbestos-containing soil samples. The fibrotic nodules caused by the dust resemble morphologically silicosis granulomas. In addition, asbestos cement has a characteristically strong cytotoxic effect during the first 2 weeks of the experiment. It is suggested that this is due to the chrysotile asbestos and/or the calcite component of the powder. Amosite and crocidolite, on the other hand, induce a diffuse peritoneal fibrosis with the appearance of numerous foreign body giant cells and asbestos bodies. Dust particles displaced to the regional lymph nodes are frequent in the animals treated with quartz, asbestos cement and asbestos-containing soil samples. A spindle cell type sarcoma arising from the visceral peritoneum is observed in animals injected with crocidolite or asbestos cement. In addition, dusts containing chrysotile asbestos induce considerable amyloidosis of the liver and spleen.

Amyloidosis↗
PubMedDate not supplied

A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes.

Immunoglobulin gene promoters are active only in lymphoid cells and this tissue-specific activity requires an octamer sequence, ATTTGCAT. Paradoxically, this same octamer motif seems to be a transcriptional control element in promoters which are active in all tissues. Using an electrophoretic mobility shift assay to identify DNA binding proteins, we have now detected two species of nuclear proteins which bind specifically to this octamer. One previously characterized form (NF-A1) was found in all cell lines tested while the other form (NF-A2) was restricted to lymphoid cell lines. NF-A2 was found in cell lines representing all stages of B-cell differentiation and in half of the T-lymphoma cell lines tested. The identification of a lymphoid-specific octamer binding protein may account for the lymphoid-specific activity of immunoglobulin promoters.

Animals↗
PubMedDate not supplied

An octamer oligonucleotide upstream of a TATA motif is sufficient for lymphoid-specific promoter activity.

The octamer sequence ATGCAAAT or its inverse complement ATTTGCAT is well-conserved in all immunoglobulin gene promoters and has been implicated in promoter function by deletion analysis. Although immunoglobulin promoters are tissue-specific, the octamer is also a functional element in non-tissue-specific upstream regions--like those controlling U1 and U2 small nuclear RNA and histone H2B genes--where it is associated with additional canonical elements. Specific interactions occur between the octamer motif and both lymphoid-specific and ubiquitous proteins. By using a synthetic octamer oligonucleotide inserted upstream of the beta-globin TATA box we show here that the octamer element by itself is sufficient for directing lymphocyte-specific RNA synthesis when within 70 base pairs of the start site of transcription. We also demonstrate that mutations in any position of the conserved motif interfere with this function.

Animals↗
PubMedDate not supplied

[Autologous cartilage-bone transplantation in the therapy of osteochondrosis dissecans of the knee joint].

This study presents the results of twelve patients, treated by an autologous bone and cartilage transplant for an advanced stage (stage IV and V referring to Rodegerdts and Gleissner, 14) of osteochondritis dissecans of the knee. In a follow up examination after an average time of 3.7 years all patients could be reviewed clinically and radiologically. The clinical results have been very satisfying in all but one patient. Radiologically all patients showed early signs of gonarthrosis, but only in 4 of 12 patients more advanced signs of arthrosis were found. In their own opinion all patients were satisfied with the outcome of the operation, and two of them regarded the result as excellent. Besides the operative technique the indications practising autologous bone-cartilage-transplantation in large osteochondral defects of osteochondritis dissecans are described as well. Furthermore the advantages of autologous against homologous bone-cartilage-transplants are discussed.

Adolescent↗