Biomedical subjects

T Wirth

Publications and source records attributed to T Wirth.

97 records · Page 6Linked to original sources

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

In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system.

We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cells were transduced by two modified retroviral tet vectors containing the transactivator regulatory unit and the IL-2 gene driven by the tetO/promoter, respectively. In the absence of tet, IL-2 expression in the target cells was stable over several months. IL-2 production was in the range of 40 U/10(6) cells/24 hours. A fine tuning of IL-2 expression could be achieved by culturing the transduced cells with increasing doses of tet, whereby a concentration of 500 ng/mL tet in the culture medium abrogated IL-2 expression. Most importantly for clinical application, IL-2 expression by the transduced melanoma cells could also be regulated in vivo. When nu/nu mice were inoculated with the transduced tumor cells, they failed to develop tumors. Instead, the inhibition of IL-2 expression in the transduced tumor cells by oral administration of tet led to subcutaneous tumor growth; this growth rate was comparable with the growth rate of subcutaneously inoculated untransduced parental cells. The finding demonstrates the applicability of the tet-regulated system in cancer gene therapy.

3T3 Cells↗

PubMedDate not supplied

[Diagnosis and therapy of coxitis fugax with special reference to the value of ultrasonographY-assisted diagnosis and hip joint puncture].

Between 1984 to 1991 55 children (mean age 7.0 years) were observed with a painful effusion of the hip examined by ultrasound. Children with radiologically diagnosed hip diseases were excluded. In 47 cases we found a transient synovitis of the hip which started at an average interval of 4 days in mean before admission. All children were reexamined 6 weeks after the end of treatment sonographically and clinically, 4 of those revealing incipient Perthes diseases. The primary sonographic right/left difference in amount of effusion (mean) was 4.0 +/- 1.7 mm and after aspiration 1.5 +/- 1.4 mm with a significantly correlation with the amount of aspirated synovial fluid. The radiological findings for a diagnosis of an effusion of the hip were not reliable. Beside the diagnostic signs of the appearance of the aspirated fluid the sonographic assisted aspiration of the hip is an important treatment mode to reduce the intracapsular pressure and the pain of a hip effusion in children.

Adolescent↗

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↗

PubMedDate not supplied

[Is conservative treatment of partial or complete anterior cruciate ligament rupture still justified? An analysis of the recent literature and a recommendation for arriving at a decision].

In a review of the recent literature after conservative treatment of the complete anterior cruciate ligament (acl) rupture good results were found in an average (av) of 56% (12-80%) of all cases. In comparison the conservative treatment of partial tears showed in 84% (60-100%) of all cases good results. 79% (32-100%) of the patients with complete acl ruptures and 90% (66-100%) of the cases with partial acl tears were able to continue their sport activities. Secondary acl replacement or meniscus surgery were later necessary in 20% and 14% of the cases (av) with complete acl ruptures and in only 6% and 5% (av) of the cases with partial tears. Most of the patients who were operated later were young and ambitiously engaged in sports. The results of the mostly retrospective studies display a high variability. For this reason it is necessary to perform more prospective, controlled and randomized studies to verify the preventive effect of an early operative treatment to protect the joint form osteoarthritis and progressive instability. Arthrocopy is essential for all cases of acute hemartrosis. Partial acl tears are predominantly treated conservatively, while complete acl ruptures should be treated following an individual decision regimen. A tree for decision making of the treatment of acute acl-injuries is proposed.

Anterior Cruciate Ligament↗

PubMedDate not supplied

[Magnetic resonance tomography in diagnosis and therapy follow-up of patients with congenital hip dysplasia and hip dislocation].

AIM: In patients with congenital dislocation of the hip the assessment of the correct position of the hip joint after closed or open reduction is very difficult to make from the radiograph with the hips in plaster. As the delayed recognition of a recurrent hip dislocation has bad effects on the outcome of the affected hip a safe and reliable imaging method must be employed. METHOD: From 1993 to 1996 6 patients with 8 congenital dislocations of the hip joint were examined by magnetic resonance imaging for evaluation of the position of the hip in plaster after reduction. Magnetic resonance imaging was performed immediately after closed or open reduction. 3 hips had to be treated by open surgery. RESULTS: The investigation confirmed that magnetic resonance imaging allows perfect differentiation between the bony and cartilaginous parts of the hip joint in plaster as well. Interpositioning of soft tissues which prevent reduction could also be visualized clearly. The best sequence in order to differentiate bony from cartilaginous structures was a gradient echo sequence in flash-technique using a flip-angle of 60 degrees. In all cases the correct position of the hip joint after reduction could be demonstrated in plaster. CONCLUSION: Therefore, magnetic resonance imaging is the imaging method of choice for confirmation and documentation of the reduced position of the hip joint in plaster. Radiographs are no longer needed.

Cartilage, Articular↗