Mutational analysis of the PTEN/MMAC1 tumour suppressor gene in primary human malignant mesotheliomas.

Eighteen primary human malignant mesotheliomas obtained from 18 patients were screened for point mutations and microdeletions/insertions in all exons of the tumour suppressor gene PTEN/MMAC1 by SSCP analysis. No mutation could be found. Our preliminary data indicate that disarrangements of PTEN/MMAC1 are at least not frequently involved in mesothelioma formation.

Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas.

Nineteen specimens from primary human malignant mesotheliomas obtained from 19 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 by combined RFLP-PCR/SSCP analysis. In addition, all tumours were screened for deletions and point mutations in the tumour suppressor genes p53, p16INK4a (CDKN2A) and p14ARF (exon-1beta) by combined multiplex-PCR/SSCP analysis. No mutations were found in N-ras, p53 and CDK4. Three tumours displayed homozygous deletion (co-deletion of exons 1, 2 and 3) of p16INK4a. One of them displayed additional homozygous deletion of p14ARF (exon-1beta). Two silent point mutations and 2 polymorphisms were found in p16INK4a in 3 tumours. Our preliminary data indicate that disarrangement of the Rb1 pathway may be involved in mesothelioma formation.

Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi.

Eighteen human congenital melanocytic naevi (CMN) from 17 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 and for sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in the tumour suppressor genes p53 and p16INK4a (CDKN2A) by combined multiplex PCR/SSCP analysis. Positive screening data were specified by sequencing of the corresponding PCR product. Activating point mutations in the N-ras gene (nine CAA (Gln) to AAA (Lys) transversions and one CAA (Gln) to CGA (Arg) transition at codon 61) were detected at high frequency (56%). Furthermore, three missense mutations (V92M) and two silent mutations (CGA (Arg) to CGG (Arg), codon 213, exon 6) were found in the MC1R and p53 genes, respectively. No mutations were found in p16 or CDK4. The activated N-ras oncogene, which is also found in human cutaneous melanomas, may constitute a potential risk factor for melanoma formation within CMN.

[Renal blood flow, diuresis and isotope nephrogram in experimental stenosis of the renal artery (author's transl)]. / Nierendurchblutung, Diurese und Isotopennephrogramm bei experimenteller Stenosierung der Nierenarterie.

After experimental stenosis of the renal artery of the dog, the isotope nephrogram shows a prolongation of the transit-time, when the renal blood flow is reduced to 40--70%. This finding was most significant in low diuresis (0,05--0,2 ml/min), sporadic in moderate diuresis (0,2--2,0 ml/min), no longer demonstrable in forced diuresis (greater than 2,0 ml/min). The diuretic effect of X-ray contrast medium (70% Na-Meglumin-Jotalamat, 0,5 ml/kg i.v.) normalizes a pathologic ING in low diuresis.

[Generic symptoms of Hodgkin's disease in relation to other prognostic criteries (author's transl)]. / Die Allgemeinsymptomatik bei der Hodgkinschen Erkrankung in ihrer Zuordnung zu anderen prognostischen Kriterien.

In 1967-1973, 74 patients with histologic classified Hodgkin's disease were treated in Marburg. We proved the incidence of the most important prognostic criteries: stage, histologic type and clinical symptoms. These criteries are evaluated as equally significant and independent. The B-symptoms, fever, weight loss and night sweats we found in 24 patients, 18 (75%) of them were in stage IV. In the remaining 6 patients in stage II and III, the B-symptoms were followed by relapse or generalisation. We think that the good correlation to the stage means, that clinical symptoms as prognostic signs are not independent.

[The haemodynamic effects of renal artery stenosis (author's transl)]. / Zur hämodynamischen Wirksamkeit der Nierenarterienstenose.

Three reasons are suggested for the difficulty of judging the haemodynamic effects of renal artery stenosis: 1. The flow characteristics in the renal arteries of dogs indicate that, at the critical level of reduction to one third of normal diameter, a further change of only 0.5 mm. will cause a 50% alteration in flow volume. Variations of this order of magnitude cannot be reliably measured on the angiogram. 2. The production of turbulence, which can increase the effect of a stenosis considerably, depends, amongst other things, on the nature of the surface of the stenosis and this cannot be judged. 3. The effect of a stenosis depends on peripheral resistance in the kidney.

[The early urogram in experimental acute stenosis of a renal artery (author's transl)]. / Das Frühurogramm bei experimenteller akuter Stenosierung der Nierenarterie.

1. Renal excretion as seen in the urogram does not parallel changes in blood flow. The significance of the early urogram as a test of function is therefore very limited. 2. Following acute stenosis of one renal artery, there is simultaneous excretion by both kidneys until flow is reduced to 60%; exretion is delayed, with values of 0.5 to 7.5 minutes, following reduction to 30 to 60% of the original; there is no excretion below 30%. 3. Unilateral delay in excretion occurs at about the level of "critical occlusion pressure". 4. Delayed excretion is observed at the level of the so-called "critical stenosis" of the renal artery. A reduction of flow above 20% follows a reduction of the artery in excess of 66%, corresponding with a reduction of the lumen of more than 90%. 5. These findings indicate that delayed excretion in the early urogram is to be expected only as a result of severe stenosis of the renal artery and represents a late feature of renal vascular disease.

[Multiple occlusions and stenoses of the abdominal aortic branches with development of Riolan's collateral and hypertension (author's transl)]. / Mehrfache Verschlüsse und Stenosen der abdominalen Aste der Aorta mitAusbildung einer Riolanschen Kollaterale und eines Hypertonus

One case of multiple occlusions and stenoses of the abdominal aortic archs with development of Riolan's collateral in a young patient with hypertension is described. In the literature some cases are pointet out, which clinically resemble our patient and where the aetiology is not clarified. -- In the discussion about the aetiology of this vascular anomaly a developmental anomaly and mechanical compression by the crura diaphragmatica are named. We think, that an unspecific arteriitis similar to the in Japan well known Tacaysau-Aortitis must also be discussed. This unspecific arteriitis of the abdominal aorta and its branches would explain the occlusion and stenosis of several arteries with development of Riolan's collateral and manifestation of hypertension.

[Calcification in mass lesions in the kidney (author's transl)]. / Verkalkungen in raumfordernden Prozessen der Nieren

In 80 mass lesions of the kidney, we found 11 cases with calcification; six of these occurred amongst 48 tumours and five amongst 32 solitary cysts. In particular, the following were found: 1. The frequency of calcification of 12 to 14% corresponds with that given in the literature. If other radiological signs fail indicate the nature of the space-occupying lesion, then calcification may be of diagnostic value. 2. Calcified cyst walls appear as fine, even, curvi-linear lines, Dense, irregular and extensive calcification indicates a solid tumour. 3. Ring or curvi-linear calcification in not a reliable sign of a cyst. Tumours may also show this type of calcification indicates a solid tumour. 3. Ring or curvi-linear calcification is not a reliable sign of cyst. Tumours may also show this type of calcification. Calcification occurs in solitary cyst with about the same frequency as in tumours. 4. Histologically all calcified tumours were clear cell carcinomas, mostly hypervascular. Only one case showed central necrosis.

[Late recurrences in Hodgkin's disease following radiotherapy]. / Spätrezidive bei M. Hodgkin nach Strahlentherapie

1. From 1950 to 1970, 92 patients with Hodgkin's disease stage I and II were treated by irradiation at the Universitäts-Strahlenklinik Marburg. Staging was performed without diagnostic laparotomy. More than a third might be staged wrong. 2. The over-all survival rates for both, stage I and II, are 65% after five years, 40% after ten years. 15% of the patients are expected to be cured. 3. Three late recurrences after 12 or 13 years are contradictory to the definition of cure in Hodgkin's disease, as a ten years lasting relapse-free interval after primary treatment. In two further cases lymphogranulomatosis developed 7 and 12 years after operation and irradiation of mediastinal tumors, which were histologically classified as lymphadenitis and polymorphcellular sarcoma, but here and there showed the features of lymphogranulomatosis. Two further cases of lymphogranulomatosis were seen with extraordinary long remissions of 11 and 17 years. 4. On the understanding that the primary tumor disease had been cured, we can look at the recurrences as at second tumor disease. Then a tumor-disposition in these patients must be discussed. 5. The occurrence of the prognostically advantageous histologic type of nodular sclerosis, the age of the patients between 27 and 37 years at the first manifestation of the disorder, and the tolerance of peripheral localisation of the tumor disease lead to the conclusion that histologic type and course show the ratio between tumor disease and immunologic situation of the patient. Probably, the histologic features might be the expression of this situation.