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In hematological malignancies, gene expression profiling using DNA-microarrays led to the discovery of novel lymphoma and leukemia subgroups. The heterogeneous entity of diffuse large B-cell lymphoma could be subdivided into the germinal center B-cell-like and the activated B-cell-like subtype which differ in pathogenesis and clinical behavior. In leukemia, existing entities defined by morphological, cytogenetic, molecular and immunophenotypic criteria were confirmed on the global gene expression level; in addition, new important molecular subgroups could be identified. In retrospective clinical lymphoma and leukemia studies, robust gene expression signatures were discovered that predict the clinical course at the time of diagnosis. Given the huge potential of the DNA-microarray technology, application in the routine diagnostic setting appears possible.

The determination of steroid hormone receptors obtained an increasing significance in the last years. It has contributed to the explanation of the mechanism of hormone regulation in the organism. The test allows an additional indication, exceeding the histological differentiation, both in breast and endometrial cancer with regard to prognosis of the patient and of success of an adjuvant or curative hormone therapy, especially in progredient cases. The receptor test can be decisive for the strategy of therapy. The test allows a better indication of the expected success of therapy for different types of leukemia and malignant lymphoma, too. But the success of a pure glucocorticoid therapy is often temporarily restricted because of the spontaneous occurrence of steroid resistant receptor mutants.

By means of the silicagel thin layer chromatography and spectrophotometry the qualitative differences of the polymeric dipyrryl methenes in the bile and in the urine in normal and pathological conditions were demonstrated. The differences between the polymeric dipyrryl methenes of fresh hepatic bile and the polymeric dipyrryl methenes of the older hepatic and fresh duodenal bile were found. The same differences were found in the urine between the normal urinary polymeric dipyrryl methenes and the polymeric dipyrryl methenes in the hyperhemolytic state and in the bile duct obstruction. An entirely different quality of the polymeric dipyrryl methenes in the urine is to be admitted in the liver diseases.

This study aimed to evaluate the molecular weight distribution patterns and the quantitative expression of surface glycoproteins (S-GP) of various differentiation stages of human leucocytes. S-GP were first exposed by treatment with neuraminidase; subsequently they were labelled by galactose-oxidase treatment followed by reduction with 3H-sodium borohydride. Labelled S-GP were separated on polyacrylamide gels in the presence of SDS and were visualized by means of fluorography. A total of 8 major S-GP bands with apparent molecular weights of 230 000, 215 000, 200 000, 185 000, 175 000, 150 000, 125 000 and 110 000 daltons were identified. All of these S-GP were already expressed at the level of pluripotent myelopoietic stem cells but different in their relative expression during further cellular maturation.

Acridine dyes inhibit the incorporation of 3H-thymidine and 3H-uridine in intact cells to the same extent as Actinomycin D. In contrast to Actinomycin D, RNA synthesis by DNA - dependent RNA polymerase in a cell-free system is inhibited at lo2 higher concentrations of acridine dyes, only. Possible differential effects on the cell membrane resulting in decreased intracellular pools of uridine and thymidine are discussed.

Studies on purine de novo-synthesis and cyclic AMP in normal and pathologic leukocytes. The destruction of neoplastic cells by cytostatic agents depends on the existence of metabolic reactions within the cells which can be specifically blocked by these agents. Concerning the action of purine antagonists there is, as yet, no clear evidence whether de novo synthesis of purines takes place in normal as well as in leukemic leukocytes. Therefore studies were performed to evaluate the capacity of these cells to incorporate the purine precursor, glycine, into their acid-soluble adenine nucleotides. The results demonstrate that "resting" human lymphocytes are not capable of building purines de novo. However, stimulation of the cells with a mitogen (Phytohemagglutinin) leads to the induction of de novo purine synthesis. Leukemic cells do not show uniform behaviour. In order to get more information about the mechanisms by which synthesis of purines as well as the morphologic transformation of lymphocytes may be induced, the metabolism of cyclic AMP was investigated. According to our results the nucleotide does not play an essential role in initiating the transformation process, but it seems to have regulating function in the further development of cell transformation. The studies furthermore indicate an important role of cyclic AMP during proliferation of leukemic cells.

The 24 h-whole-body retention (WBR), determined by a whole-body counter, may be used to quantify exactly bone seeking properties of a radiopharmaceutical. The 24h-WBR of 99mTc-methylene-diphosphonate was determined in 200 patients and was found to be independent of kidney function if this function was normal or only slightly diminished. The 24h-WBR was slightly dependent on age since it decreased up to 20 years of age, reaching a minimum at 20-25 years, and then increased with increasing age. Normal values of 24h-WBR for individuals of more than 20 years of age were 31.8 +/- 5% of injected dose. Not more than two focal accumulations, i.e. skeletal metastases, failed to elevate the 24h-WBR significantly (p less than 0.1). However, a highly significant (p less than 0.001) difference to normals was found in patients with multiple metastases (24h-WBR: 38.2 +/- 7%), with diffuse osseous involvement as in primary hyperparathyroidism (24h-WBR: 49 +/- 11.7%, p less than 0.001) or with osteoporosis (24h-WBR: 45%). The 24h-WBR was found to be very sensitive in grading diffuse osseous involvement. This was shown in single-tumor patients by follow-up as the 24h-WBR in addition to bone scans was useful to describe progression or remission. Moreover, the 24h-WBR correlated closely with results of bone marrow biopsies in a small group of patients with malignancies of the lymphoreticular system.