[A program of preventive and health monitoring examinations for children and adolescents in East Germany].
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Biomedical subjects
Publications and source records attributed to D Müller.
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On the basis of an extensive data material it was demonstrated that the early recognition of a glomerulonephritis is dependent on the proof of a proteinuria and indeed it is independently of its size and reproducibility. Extensive serological examinations are without diagnostic significance, especially the estimation of the serum complement and the immunoglobulins. Patients with proteinuria should be included in a kidney dispensaire system. The diagnostik programm, including percutaneous renal biopsy, is dependent on the size and constancy of proteinuria and other urinary findings like microscopic hematuria.
A 302 bp DNA fragment and a 113 bp subfragment of the former, both containing the fd gene VIII promoter (P VIII), were found to exhibit temperature-dependent differential behaviour in RNA chain initiation from P VIII. At 37 degrees C no significant differences were observed, while at 17 degrees C chain initiation was strongly suppressed only with the 113 bp fragment. This phenomenon depended on the presence of the (blunt) DNA terminus upstream from P VIII (position -70). Footprinting revealed that at 17 degrees C RNA polymerase was bound to this DNA fragment in a different mode. Contacts were observed only upstream from position -25. On the contrary, at 37 degrees C only the promoter complex footprint was visible. These results indicate that at 17 degrees C formation of the non-initiating complex is more favourable than formation of the promoter complex (which is closed at 17 degrees C; Hofer, B., Müller, D. and Köster, H. (1985) Nucleic Acids Res. 13, 5995-6013) and that formation of both complexes is mutually exclusive. No footprints of RNA polymerase were observed at other DNA termini. This indicates a sequence-specificity for the interaction at the terminus of the 113 bp fragment. The footprint pattern, together with features of the DNA sequence, suggests that the contacts involved in this interaction are similar to those promoter contacts formed upstream from position -20 and that DNA without a -10 region can be specifically recognized by RNA polymerase.
SV40 large T antigen is phosphorylated at up to ten different amino acids clustered in an N-terminal and a C-terminal part of the polypeptide chain. The N-terminal phosphorylated residues include Ser 123 and Thr 124. We have analyzed the oligomerization, the complex formation with the cellular oncoprotein p53 and the DNA-binding properties of T antigen from two different SV40 transformed cell lines which have either an amino acid exchange at Ser 123 to Phe (W7) or Thr 124 to Ile (D29). In comparison to wild-type T antigen both mutant T antigens have a slightly reduced binding affinity for both binding sites, I and II, of SV40 DNA. Phosphorylation at both residues of T antigen is not essential for formation of the complex with p53. Only the phosphorylation at Thr 124 seems to be critical for the formation of high molecular mass oligomers. Our data support the hypothesis that the oligomerization of T antigen seems to be implicated in viral DNA replication.
In Germany, the relative frequency of pineal region tumours seems to be much higher than hitherto assumed. At the University Hospital Hamburg, from 1980-1985 17 children with pineal region tumours were encountered amongst 102 children with CNS tumours. Two-cell-type germinoma is the most frequent pineal region tumour. Cerebrospinal fluid cytology is highly successful in identifying this germ cell tumour. Surgical removal has become a reasonably safe procedure in the treatment of pineal region tumours and was successful in all 10 cases so treated. In addition, our patients with two-cell-type germinomas received craniospinal axis radiation. All children, treated by both surgical removal and craniospinal axis radiation are so far relapse-free and are functioning on a pretreatment level.
Three cases of intramedullary spinal hemangioblastoma are presented. Since the tissue adjacent to the neoplasm often shows a gliosis resembling an astrocytoma, a misinterpretation in the intraoperative histological diagnosis may lead to an unnecessary extirpation of the reactive tissue. It is recommended that biopsies be performed in cases in which a hemangioblastoma being considered. This is necessary in order to get specimen from the hemangioblastoma itself for the intraoperative histological evaluation.
During lytic infection SV40 T antigen binds specifically to three different regions of the SV40 DNA to initiate DNA replication and to regulate early and late transcription. We constructed plasmids containing either 23-bp synthetic oligonucleotides representing site I or II or SV40 DNA fragments with combinations of binding sites II and III with or without SV40 specific flanking regions. These plasmids were used to determine which sequences are sufficient for specific binding to isolated regions II and III. Under identical conditions T antigen bound in a sensitive in vitro binding assay efficiently to site I but not to the corresponding oligonucleotide of site II. Binding to site II could only be observed in the presence of the adjacent 17-bp AT-rich region of the SV40 DNA. On account of the markedly low affinity for binding site II, T antigen concentrations were required which exceeded those necessary to achieve saturation of binding to site I. The very low affinity for isolated site III could be slightly raised by the same AT-rich region. An increased binding to site II at 37 degrees compared to 0 degree in the presence of this region points to an indirect influence on the DNA structure of the binding site.
The results of an evaluation of the perfusion scintigraphy findings of 350 hospitalised neurological patients and 55 more strictly selected neurosurgical patients with cerebrovascular complaints, revealed an accuraty of 83%, a sensitivity of 89%, and a specificity of 83%. The selection of the patients had no influence on the results as a whole. Compared with contrast-medium angiography, incorrect diagnosis must be expected in 17% of the cases. This includes erroneous negative findings in 10% of the cases. Grounds for misinterpretations are suggested, and the biological and methodological limitations of the method are set forth.
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Early T cell differentiation is described in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis, supporting multi-lineage differentiation potential of CML precursor cells. In the absence of myeloid markers, strong positivity for terminal deoxynucleotidyl transferase (TdT) and reactivity with T cell antibody 3A1, but lack of more mature T cell antigens, provided evidence for immature T cell differentiation. Molecular analysis of the breakpoint cluster region (bcr) in chromosome 22 revealed a rearrangement and thus confirmed the CML origin of the early T cell blasts. T cell receptor beta chain sequences were found in germline configuration and therefore suggest a very immature stage of T cell differentiation in the CML blasts.
We have studied the biosynthesis and biochemical properties of the c-fos gene product and its associated protein (p39) in growth factor-stimulated fibroblasts. c-fos is a markedly acidic protein that is extensively post-translationally modified by phosphorylation and another type of modification not changing its relative molecular mass (Mr). More than 10 different forms of c-fos protein can be identified by two-dimensional gel analysis. In c-fos-transformed cells, however, most of the highly modified forms are missing. The affinity for DNA of less phosphorylated c-fos-protein complexes is higher than that of the highly modified ones. The transforming potential of c-fos protein and its affinity for DNA thus seems to be inversely correlated with the extent of its phosphorylation. In contrast to c-fos, p39 is a basic protein that is rendered even more basic by post-translational modification. Two other forms of p39 differing in specific domains of the protein (p41 and p43) were also found to be complexed with c-fos.
The authors re-examine cases of complete peripheral nerve injury of the upper extremity. Motor activity and sensibility assessment make use of Highet's scale. Some general principles of surgical treatment of peripheral nerve injuries are presented and individual factors which influence its results are worked out, e.g. moment of diagnosis, kind of nerve suture, moment of operation, age of patient, grade of injury, concomitant injuries, and length of graft. Conclusions are drawn for the concept of treatment.
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Various nerve conduction velocities, the terminal latency (TL) of facial nerve, the trigeminofacial reflex and fast auditory evoked potentials (FAEP) were investigated in 26 patients with peroneal muscular atrophy (22 with HMSN I and 4 with HMSN II). With the brain nerve status revealing no clinical abnormalities, 85.7% of HMSN I patients showed a longer-than-normal TL of the facial nerve, 66.6% had a prolonged early reflex component of trigeminofacial reflex and 22.7% pathological FAEPs. Normal neurophysiologic findings were obtained for brain nerves of HMSN II subjects. Subclinical involvement of the mid-group of brain nerves did not at all correlate with the impairment of extremity nerves and the duration of the disease. The present results reflect the heterogeneity of HMSN.
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