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Biomedical subjects

U Schlegel

Publications and source records attributed to U Schlegel.

12 recordsLinked to original sources
PubMed1992

p53 gene mutations in primary lung tumors are conserved in brain metastases.

The p53 product is frequently mutated in human tumors. Both acquired and inherited mutations have been described. These mutations transform p53 from a growth suppressor gene to a transforming oncogene. We examined tissue from 6 patients with primary lung carcinoma and the corresponding brain metastases for the presence of p53 mutations by immunohistochemistry. We then confirmed and characterized the mutations by single strand conformation analysis and by direct sequence analysis. All 6 patients had primary and metastatic tumor expressing a mutant p53. The mutations were all G-T transversions and mapped to exons 5, 6, 7, and 8. The mutations in the primary tumors were precisely conserved in the brain metastases.

Aged↗
PubMed1992

Biomechanical evaluation of the Pinless external fixator.

In open fractures especially in those with severe soft tissue damage, fracture stabilisation is best achieved by using external fixators. There are some intrinsic complications which occur during classical external pin fixation. To overcome the problem of pin track infection and vascular damage from drilling, the Pinless external fixator was developed. It is based on the idea of a forceps with trocar points, which only penetrate the bone cortex superficially. The function of the device was tested in two mechanical trials and two in vitro tests in which one pinless clamp was put under a controlled load of 50 N, 150 cycles/day and studied over a 5 week period in sheep. The loads and time range of the experiment were chosen to simulate a temporary fracture stabilisation in a patient not bearing weight. The main question to be answered was whether the Pinless external fixator would be able to maintain stable fixation. Furthermore, it was to determine the changes at the trocar-to-bone interface. The clamp was found to maintain 72% of the initially applied clamping force after 5 weeks of in vivo application and it was found to be tight at removal. Some decrease of clamping force was found during the first 20 days and then the force tended to level off. There was no slippage nor did the clamp penetrate the cortex. There were no obvious signs of infection around the trocar-holes and in the bacterial tests no pathological cultures were grown. Histology revealed very localised bone reactions, the indentation caused by the trocar tips being only 1.2 mm deep. The study concludes, as far as could be ascertained from these tests, that it is safe to use pinless external fixation for temporary fracture fixation.

Animals↗
PubMed1992

[Chronic schizophreniform psychosis in primary hyperparathyroidism].

We delineate the case history of a 74-year-old female patient. On the occasion of acute physically established psychoses in this case, we were able to detect a primary hyperparathyroidism due to adenoids of the epithelial body. This critical psychopathological condition developed from a psychosyndrome, most likely seeming as senile schizophrenia, and which had previously existed for four years. It will be discussed whether these chronic schizophrenia-like symptoms and signs can be explained by hyperparathyroidism.

Aged↗
PubMed1991

Mutational analysis of the human p53 gene in malignant melanoma.

Nine metastatic melanoma cell lines and two melanocyte cell lines were analyzed for point mutations in highly conserved regions of the p53 gene. No mutations were detected in the two melanocytic cell lines and in eight melanoma cell lines. However, a C----T transition at codon 248, resulting in a substitution of tryptophan for arginine, was found in one melanoma cell line. On immunohistochemical staining, only this cell line showed reactivity for mouse monoclonal antibody 1801, which is immunoreactive with human p53 protein. The original paraffin-embedded specimen from which this mutant cell line was established was obtained, and sequence analysis detected the identical mutation in the p53 gene as that seen in the derived cell line. This is the first report indicating point mutations in the p53 gene in malignant melanocytic tissues.

Base Sequence↗
PubMed1990

The role of human single-stranded DNA binding protein and its individual subunits in simian virus 40 DNA replication.

Human single-stranded DNA binding protein (human SSB) is a multisubunit protein containing polypeptides of 70, 34, and 11 kDa that is required for SV40 DNA replication in vitro. In this report we identify the functions of the SSB and its individual subunits in SV40 DNA replication. The 70 kDa subunit was found to bind to single-stranded DNA, whereas the other subunits did not. Four monoclonal antibodies against human SSB were isolated which inhibited SV40 DNA replication in vitro. The antibodies have been designated alpha SSB70A, alpha SSB70B, alpha SSB70C, and alpha SSB34A to indicate which subunits are recognized. Immunolocalization experiments indicated that human SSB is a nuclear protein. Human SSB is required for the SV40 large tumor antigen-catalyzed unwinding of SV40 DNA and stimulates DNA polymerases (pol) alpha and delta. The DNA unwinding reaction and stimulation of pol delta were blocked by alpha SSB70C, whereas the stimulation of pol alpha by human SSB was unaffected by this antibody. Conversely, alpha SSB70A, -70B, and -34A inhibited the stimulation of pol alpha, but they had no effect on DNA unwinding and pol delta stimulation. None of the antibodies inhibited the binding of SSB to single-stranded DNA. These results suggest that DNA unwinding and stimulation of pol alpha and pol delta are required functions of human SSB in SV40 DNA replication. The human SSB 70-kDa subunit appears to be required for DNA unwinding and pol delta stimulation, whereas both the 70- and 34-kDa subunits may be involved in the stimulation of pol alpha.

Antibodies, Monoclonal↗
PubMed1990

Expression of transforming growth factor alpha in human gliomas.

Expression of transforming growth factor alpha (TGF alpha) is frequently associated with the development of human and animal tumors. Using a sensitive immunohistochemical assay, which can be applied on formalin-fixed, paraffin-embedded tissue, we have examined the expression of TGF alpha in 71 human gliomas (63 untreated and 8 recurrent tumors). Tumors were graded by a 3-grade-system: grade I = low grade gliomas, grade II = anaplastic gliomas and grade III = glioblastomas. A strong positive correlation between tumor grade and extent of TGF alpha expression was found (P less than 0.0001). Polymerase chain reaction (PCR) was used to amplify the fourth exon of the TGF alpha gene of 8 glioma DNA specimens and increasing amounts of normal human DNA, which served as a standard. No amplification of the TGF alpha gene copy number in tumors could be detected.

Base Sequence↗
PubMed1989

Cerebral sarcoidosis presenting as supranuclear gaze palsy with hypokinetic rigid syndrome.

A 31-year-old man with histologically documented pulmonary sarcoidosis developed a severe hypokinetic rigid syndrome with a supranuclear gaze palsy following recurrent lymphocytic meningitis and occlusive hydrocephalus. Magnetic resonance imaging (MRI) showed multiple hyperintense foci in the CNS, not detectable by computed tomography (CT). Long-term steroid therapy led to clinical complete remission.

Adolescent↗
PubMed1987

[Neurosarcoidosis: diagnosis and therapy].

Sarcoidosis is an inflammatory systemic disease with a prevalence of 20 to 50 of 100,000 inhabitants in West-Germany. Caused by an abnormal immune response to a hypothetic inhalative antigen, a granulomatous inflammation in mediastinal lymph nodes occurs, which frequently extends to the lung and sometimes to other tissues. The nervous system is clinically involved in 5% of the cases. The most frequent neurologic symptom is solitary or combined cranial nerve involvement. Cerebral manifestations are nodular or diffuse granulomatous infiltration of the brain and lymphocytic inflammation of the basal meninges. The rarer myelopathies and peripheral neuropathies often cause major neurological deficits. Muscular involvement, which is present in about half of the cases of sarcoidosis, normally causes clinically silent lesions. Chronic sarcoid myopathy or acute polymyositis are rare. Elements of the diagnostic procedure are X-ray of the lung, measurement of serum Angiotensin-Converting Enzyme (ACE)- and serum Lysozyme (LZM)-levels, Bronchoalveolar lavage, Gallium-67-scanning and Kveim-test. The diagnostic value of these investigations and the typical findings in CSF examination, computed tomography, nuclear magnetic resonance, myelography and electrophysiological investigation are presented. Suspected diagnosis of sarcoidosis should be confirmed by biopsy of non-caseating granulomatous lesions in involved tissues. An initially high dosage corticosteroid therapy for many months to several years is often effective. If this is not helpful in cerebral sarcoidosis whole brain irradiation with 1500 to 3000 rd administered in 10 single doses is indicated. Peripheral neuropathy refractory to therapy with orally administered cortisone should be treated with parenteral ultrahigh steroid therapy.

Brain Diseases↗
PubMed1987

Laser Doppler flowmetry for clinical evaluation of femoral head osteonecrosis. Preliminary experience.

Most theories concerning osteonecrosis of the femoral head have as their central focus ischemia of bone. This has been difficult to prove because of lack of a method for direct measurement of bone blood flow. The authors evaluated femoral head blood flow in five patients with established femoral head osteonecrosis using laser Doppler flowmetry. Blood flow within the "avascular" segment was lower than that of the normal cancellous bone of the intertrochanteric region. A surrounding zone of hyperemia was noted in four of the five patients. Laser Doppler flowmetry was easy to use and is a reproducible method for direct estimation of bone-blood flow.

Femur Head↗