[Rhythmic circulatory dysregulation in stiff man syndrome]. / Rhythmische Kreislaufdysregulation bei Stiff-man-Syndrom.

A woman with severe stiff-man syndrome showed periodic cardiovascular dysregulation. The blood pressure changed spontaneously every 5-10 min. This rhythm was also maintained after relaxation. However, the vegetative and motoric disturbances disappeared after intrathecal application of baclofen. It is speculated that spinal GABAergic mechanisms are responsible for the tonic regulation of the cardiovascular system.

Distribution of epidermal growth factor receptor gene amplification in brain tumours and correlation to prognosis.

In 75 gliomas and 31 meningiomas, mutations at the epidermal growth factor receptor (EGFR) gene locus were restricted to gliomas. The ligands of this receptor, epidermal growth factor and transforming growth factor alpha, lacked quantitative changes at their loci in gliomas and meningiomas. EGFR gene amplification occurred in astrocytomas, oligodendrogliomas, ependymomas and glioblastomas. The frequency of this mutation significantly increased with the malignancy grade and the patient's age. Especially in glioblastomas of individuals aged over 64 years, EGFR gene mutations were observed without chromosome-10-specific allele losses. This finding contradicts the hypothesis that deletion of one entire chromosome 10 regularly precedes EGFR gene amplification in primary glioblastomas of patients aged over 50 years. It was found that most individuals whose gliomas carry an EGFR gene mutation have a poor prognosis, comparable to that of glioblastoma patients even when the tumour is graded as benign.

Loss of alleles in brain tumours: distribution and correlations with clinical course.

Gliomas (n = 44) and meningiomas (n = 24) of different grades of malignancy were analysed for allele losses at loci on chromosomes 10, 13, 17 and 22. Deletions of genetic material on these chromosomes occurred in gliomas without being restricted to any histological entity. The frequency of chromosome-10-specific allele losses increased significantly with the age of the patients and with the grade of malignancy of the tumours. Deletions of chromosome 10 material were associated with a poor prognosis. The glioblastomas of patients aged over 70 years lacked the loss of the entire chromosome 10, even in tumours with EGFR gene amplification. Deletions at loci of chromosomes 13, 17 and 22 were observed in 18-32% of all gliomas, independent of grade of malignancy, patients' age, EGFR gene amplification and clinical course. Only chromosome-22-specific allele losses were found preferentially in gliomas of female patients. Loss of chromosome 22 alleles in 44% was the only mutation detected in meningiomas. This occurred independently of grade of malignancy and biological factors.

Amplification and expression of the epidermal growth factor receptor gene during the progression of neuroepithelial tumours in vivo.

The epidermal growth factor receptor (EGFR) gene is homologous to the oncogene c-erbB. The occurrence of amplification and rearrangements at the EGFR gene locus is associated with malignancy in neuroepithelial tumours. Sixteen neuroepithelial tumours from eight patients with recurrence of their neoplasms were analysed for changes at the EGFR gene locus and for expression of EGFR. Ten tumours from five patients lacked changes at the EGFR gene locus. Three of eight individuals showed EGFR gene amplifications in both tumours with a higher grade of amplification in the second tumour. In addition to amplification, a rearrangement was found in both tumours of the first patient. In the second case an amplification of chromosome-7-specific c-met sequences was found in the regrown tumour, suggesting that a polysomy 7 was at least partly responsible for the higher copy number of the EGFR sequences. In both tumours of the third patient with EGFR gene amplification different alleles were amplified. In contrast to the findings at the DNA level the EGFR expression, analysed by immunohistochemical techniques, showed a more heterogeneous pattern after tumour progression.

[Function of oncogenes in neuroepithelial tumors]. / Der Einfluss von Onkogenen in neuroepithelialen Tumoren.

The human genome contains so-called protooncogenes which can be activated to oncogenes by mutations. Oncogenes contribute to the development of tumours of the nervous system. Some of the oncogenes are related to growth factors or to cytogenetic changes in tumours. A survey is given of current research on oncogene loci in neuroepithelial tumours by recombinant DNA techniques. In neuroblastomas the amplification of the oncogene N-myc is associated with a poorer prognosis. In neuroepithelial tumours the amplification of c-erbB, which is in part homologous to the epidermal growth factor receptor gene, is restricted to malignant neoplasias. An enhanced expression of the oncogene c-sis, which codes for the platelet-derived growth factor, is found in 85% of malignant gliomas. Many studies of relatively fewer cases suggest the influence of other, further oncogenes in the group of neuroepithelial tumours.

Amplification of the c-erbB oncogene is associated with malignancy in primary tumours of neuroepithelial tissue.

In various primary brain tumours of neuroepithelial tissue recombinant DNA techniques were used to demonstrate changes of the epidermal growth factor receptor gene, which is homologous to the c-erbB oncogene. Twenty-one of 40 grade III/IV tumours, but only 1 of 16 grade I/II tumours were found to contain amplified and/or rearranged c-erbB sequences. This highly significant difference suggest that c-erbB amplification, rearrangement, or both, are important steps in malignant transformation in a subset of patients with neuroepithelial tumours.

Rare Ha-ras and c-mos alleles in patients with intracranial tumors.

The occurrence of rare hypervariable Ha-ras alleles or of a rare c-mos allele in white blood cell DNA is claimed to be associated with susceptibility to cancer. We analyzed a group of patients with intracranial tumors to determine whether the occurrence of rare alleles at the Ha-ras locus and at the c-mos locus was increased in comparison with normal individuals. We found a higher incidence of rare hypervariable Ha-ras alleles (9.5% to 3%) and a 5 kilobase EcoRI c-mos allele (2.5% to 0%) in the patients. These results are consistent with the opinion that such unusual alleles are associated with a predisposition to intracranial tumors.

A familial X-autosome translocation with the breakpoint in the "critical region".

We report a case of an X-autosome translocation t(X;4)(q13;p16) found in both sexes in three generations. The anomaly was diagnosed in a couple referred for cytogenetic investigation as a result of three spontaneous abortions. With the exception of the miscarriages there are no particularities in the gynecologic data of the woman or in the pedigree. In all 50 lymphocytes and in 66 of 68 fibroblasts investigated the normal X chromosome was the late replicating one.

[Diagnosis of fetal sex from trophoblast DNA]. / Fetale Geschlechtsdiagnose aus Trophoblast-DNA.

By using recombinant DNA technology fetal sex determination was performed with 13 different trophoblast samples. In all cases trophoblast and fetal sex were identical. The importance of first trimester trophoblast biopsy for the prenatal diagnosis of inherited disease is being discussed.

Chromosome anomalies in 136 couples with a history of recurrent abortions.

Cytogenetic studies were performed on 136 couples with a history of two or more abortions referred to us after gynaecological causes of the abortions had been excluded. Fifteen (11%) of the couples were found to have a chromosome anomaly, and when the couples were subdivided according to number of abortions, surprisingly 6 (10%) of the 59 couples with a history of only two abortions had a chromosome anomaly. An increased frequency of mosaicism for X-chromosome aneuploidy (2.2%) in the women from the 136 couples was also found. A review of the literature shows that translocations of some chromosomes (e.g. nos. 1, 7 or 22) preferentially lead to fetal wastage, while those involving, for example, chromosome nos. 5, 9, 14 or 21 are more likely to result in the birth of a handicapped child. Couples with a history of two abortions should be investigated cytogenetically. Other causes of miscarriages must, however, be excluded first.

Contrasting DNA sequence organisation patterns in sauropsidian genomes.

The genomic DNA organisation patterns of four sauropsidian species, namely Python reticularis, Caiman crocodilus, Terrapene carolina triungius and Columba livia domestica were investigated by reassociation of short and long DNA fragments, by hyperchromicity measurements of reannealed fragments and by length estimations of S1-nuclease resistant repetitive duplexes. While the genomic DNA of the three reptilian species shows a short period interspersion pattern, the genome of the avian species is organised in a long period interspersion pattern apparently typical for birds. These findings are discussed in view of the close phylogenetic relationships of birds and reptiles, and also with regard to a possible relationship between the extent of sequence interspersion and genome size.