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This prospective study characterizes T1-T2 breast carcinomas (N = 114) and fibroadenomas (N = 16) by cell kinetic parameters derived from flow cytometrically recorded DNA/protein histograms. Ploidy level, cell cycle distribution and the number of cell subpopulations (SP) characterized by correlating DNA and protein values were assessed. The subpopulations were derived from the three-dimensional plot. The estrogen receptor (ER) status was determined biochemically (N = 61). Within the G1/0 cell peak 1-6 SP were evident in principle. Depending on the number of SP, two subsets were established: subset 1 with < or = 2 SP, subset 2 with > or = 3 SP. They differed significantly in proliferative activity expressed in the percentage of cells in the G2M phase. Subset 2 showed the higher activity. Analysis of subset distributions revealed that subset 1 prevails in favourable prognostic cases as ER positive cases (P < 0.03), lobular carcinomas (P < 0.01) and LN- cases (P < 0.03), whereas subset 2 prevails in the unfavourable counterparts. Analysis of variance showed that the main effect on proliferative activity indicated by G2M% is due to subpopulation composition rather than histologic type, nodal status or ER status (P < 0.01, P < 0.002, P < 0.05), not even due to ploidy level (P < 0.0001). The rationale for subset stratification may be cytogenetic variability connected with protein content heterogeneity accounting for kinetic SP.

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Previous investigations in human precancerous and cancerous tissues identified subsets of cells that were different in respect to a heparin-induced increase in fluorescence intensity (IFI) monitored by flow cytometry. We suggested that differences in IFI were due to different chromatin types in the cells and related to different transcriptional capacities. This study is to prove our suggestion. Heparin-induced IFI was measured in the human breast cell line H184A1N4 cultured under different, defined growth conditions. Cells in quiescence obtained from a culture deprived of serum and other supplements essential for growth or from the confluent state revealed a higher IFI than cells restimulated to proliferation by addition of complete medium; here a reduced IFI was found. Changes in the magnitude of heparin-induced IFI precede changes in cell-cycle stage distribution by at least 6.5 h. We conclude that the heparin-induced effects, as revealed by flow cytometry, reflect changes in the accessibility of chromatin to transcription in different stages of proliferative activity. The results confirm our conclusions from previous findings with clinical material.

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The international literature shows that the constitutional tall stature of girls has so far been treated with high estrogen doses after the onset of puberty. But nowadays it is felt however, that the potential risks of high-dose estrogen therapy are considerable. While the hazards of persisting gonadotropine suppression were found to be less important, thrombo-embolic complications or severe changes in the liver cannot be excluded in young people. Epidemiological findings and animal experiments suggest that these complications are dose-dependent. In search of an alternative to high-dose treatment, we--from 1966-1980 and basing on Whitelaw--administered approximately physiologic estrogen doses (80 micrograms of mestranol per day for 21 days, plus 2 mg of chlormadinonacetate per day for 10 days, cyclically) to a total of 86 tall girls ranging in age from 9 to 13 years. Only the group of the 20 girls with a skeletal age of 9-10 years, who were still prepubertal at the beginning of therapy, revealed a satisfactory mean height reduction of 7.6 cm. Serious side-effects of therapy did not occur. The possible drastic reduction of the estrogen dose to about 1/4 of the daily dose or about 1/3 of the overall dose as compared to the conventional method allows us to conclude that the early start of treatment offers a true alternative to the high-dose estrogen therapy of the female tall stature.

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From the pharmacology of the therapeutically available androgen preparations and the clinical experience results that a highly dosed androgen long-term therapy is effectively possible only by testosterone esters which are to be injected intramuscularly (e.g. testosterone oenanthate). It is indicated in all forms of endocrine hypogonadism, certain aplastic anaemias and if necessary in extreme male high growth. In partial androgen deficiency (pubertas tarda, Klinefelter's syndrome, climacterium virile and others) orally applicable androgens such as testosterone-undecanoate (Andriol) and mesterolone (Vistimon) can be used. The latter is to be preferred when a hyperoestrogenism is present, e.g. in liver cirrhosis. When 17-alpha-alkylated oral androgens are used, their often not sufficiently confirmed anabolic effect and their potential liver toxicity should more be taken into consideration.

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The morphological effects of biotin and L-arginine on fruiting body formation of the ascomycete Sordaria macrospora are investigated by scanning electron and light microscopy. Biotin is recognized as an elongation factor and arginine as a branching factor in vegetative and reproductive hyphae. In the absence of exogenous biotin, development is blocked after the ascogonium-core hypha stage of protoperithecial morphogenesis, whereas linear growth of the myceliar front is maintained. The addition of exogenous arginine to a biotin deficient culture induces the formation of numerous side branches even in the older mycelium. Fruiting body formation, however, remains blocked at the protoperithecial stage as before, because of the inability of the side branches to elongate. When biotin and arginine are administered simultaneously, a most vigorous branching and growth are induced in the older mycelium, accompanied by a rapid and maximal formation of fruiting bodies. The results are summarized in a model of the exogenous control of hyphal morphogenesis. The model is designed to explain the relationship between fruiting and hyphal density as well as the edge effect on fruiting body formation.

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Also at present hypothyroidism is frequently not recognised, especially its discrete forms of the course should be more included in differential-diagnostic considerations. Decisive is the clinical anamnestic suspicion which, after exhaustion of the laboratory-diagnostic possibilities, will justify the application of probatory therapy, even on a relatively large scale. This disease deserves secial regard, taking into consideration its beneficial and well practicable therapeutic influencibility and, on the other hand, its sever prognostic consequences to the subject in case of therapeutic neglect. The problems of therapy are not so much consisting in the occurrence of side-effects or in a non-optimal choice of drugs, but the more in a delayed onset, low dosage or interruption of the therapy.

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