Changes in the proliferation characteristics of a solid transplantable tumour of the mouse with time after transplantation.

The aim of the present investigation was to study changes in cell proliferation kinetics with time after transplantation in a solid transplantable mammary carcinoma of the C3H mouse. From growth curves and tumour doubling times, three different experimental times were chosen; the exponential phase of growth on the 7th day post-transplantation, during the phase of retardation on the 21st day after transplantation and in the stationary phase of growth on the 30th day after transplantation. It was found that the cell loss factor contributed primarily to the retardation of volume growth. The lowering of the growth fraction played a minor part in the delay of growth while the duration of cell cycle was not prolonged before the plateau phase of growth on the 30th day after transplantation was reached.

[Kaposi's sarcoma (author's transl)]. / Kaposi-Sarkom Zufälliges Zusammentreffen mit einem aplastischen Syndrom bei einem Patienten?

Kaposi's sarcoma of the skin and an aplastic syndrome occurred together in a 51-year-old patient. Macroscopically livid papules and nodules were observed. Histomorphologically endotheliomatous cell proliferation with signs of infiltrative growth was found. Because of the aplastic pancytopenia cytostatic treatment of the Kaposi sarcoma was contraindicated. The patient finally died of vascular failure with haemorrhagic diathesis being manifest. Syntropy of Kaposi's sarcoma with malignant haematological diseases is known. However, association with aplastic anaemia has not been observed so far. The pathogenesis of Kaposi's sarcoma is unknown.

Experimental investigations on a sequential combination chemotherapy protocol.

This paper deals with experimental investigations concerning the composition of a cytostatic three-drug-protocol in diploid Ehrlich-Ascites-Tumor (EAT) cells in vivo at a far advanced stage of the disease. Hydroxyurea (HU) and vincristine (VCR) were used in very low doses to induce a modification of the growth pattern of tumor cells alike partial synchronization. Adriamycin (ADM) was selected as cytocidal drug during DNA synthesis of the partially synchronized cells. It was found that the sequential combination of HU and VCR (first HU and 12 h thereafter VCR) caused the greatest alteration of growth pattern compared with other combination protocols. A further statistically significant increase of the degree of synchrony was observed after a second VCR administration -- 22 h after HU. By means of this protocol the EAT was subdivided into two proliferating subpopulations, a diploid and tetraploid one. The tetraploid population resulted from surviving cells being not able to perform dytokinesis correctly, so that polynuclear cells and cells with a large single nucleus containing tetraploid DNA values were created. With respect to therapy, the administation of ADM at the time of DNA synthesis of the partially synchronized cells resulted in a statistically significant prolongation of the mean survival time and in 30% of cures of the animals. The dosage of ADM was 2.6 mg/kg, i.e., a nonlethal dose (50% of the LD10). Other combinations, i.e., simultaneous or reversed sequential combinations, did not show any therapeutic improvement compared to single drug therapy of ADM.

[Tracheal transplantation in inbred strains of rats.--IV. Histologic and histoautoradiographic findings in the epithelium (author's transl)]. / Die Trachealtransplantation im Tierexperiment. Versuche an isohistogenen Rattenstämmen: IV. Histologische und histoautoradiographische Befunde am Epithel.

In the first ten days after transplantation isogeneic and allogeneic tracheal transplants keep their epithelium, showing metaplasia as a sign of distinct regenerative activity in this time. In various degrees dependent on the constellation of experiments there are only signs of a weak chronic rejection. After more than 280 days again a stratified epithelium can be seen. In exeptional cases mucosa of second-set-transplants only show an obvious rejection reaction.

Age-dependent change of the effect of a cytostatic drug on the proliferation kinetics of a solid tumor of the mouse.

The aim of the present investigations was to study the effectiveness of a cytostatic drug (VCR) during different phases of tumor growth (1st, 7th, 14th days a.t.) and at the periphery and at the centre of the tumor (on the 14th day a.t.). Furthermore the inducement of a partial synchronization in the proliferation of tumor cells was attempted. It was found that the intensity of the cytostatic effect significantly decreased both with the passage of time after transplantation and within the tumor from the periphery to the centre. The changing cytostatic sensitivity probably is due to the diminishing vascular supply and the decreased rate of cell proliferation; especially the decline of the growth fraction. A partial synchronization of the proliferation of tumor cells could not be demonstrated.

[In-vitro-technique for autoradiographic investigations of cell proliferation in benign and malignant alterations of the human urinary bladder mucosa from biopsy specimens (author' transl)]. / Zur Zellkinetik von Urotheltumoren. In-vitro-Verfahren zur autoradiographischen Untersuchung der Zellproliferation von gut- und bösartigen Veränderungen der menschlichen Harnblasenschleimhaut am Biopsiegewebe.

An in-vitro double labelling technique with 3H- AND 14C-Thymidine was applied to biopsy specimens of the human urinary bladder mucosa in order to determine proliferation kinetics of normal bladder epithelium as well as its benign and malignant alterations. Application of above mentioned technique led to evaluable autoradiographs. The mean 3H-Thymidine labelling-index in bladder cancer was remarkably higher than in normal bladder epithelium and in benign papillomas. There was a good correlation between histologic grading of malignancy and increase of the mean 3H-Thymidine labelling index. Addition of 5-Fluorodesoxyuridine to the incubation medium had no influence on the labelling of the incubated tissue.

[Nephroblastoma, partly appearing as a sarcoma botryoides of the renal pelvis (author's transl)]. / Nephroblastom, teils unter dem Bild eines Sarcoma botryoides des Nierenbeckens.

A renal tumour in a 4-year old girl morphologically appeared as both a nephroblastoma and, in parts, as a sarcoma botryoides of the renal pelvis. The histogenesis of this dysontogenetic tumour is most probably due to a disturbance of growth and differentiation both of the metanephrogenic blastema as well as partly of the urethral bud. This type of dysontogenetic tumour is extremely rare. Problems of diagnosis and operative therapy and the possibility of postoperative radiation therapy and cystostatic treatment are discussed.

The presence and significance of the Thomsen-Friedenreich antigen in mammary gland. II. Its topochemistry in normal, hyperplastic and carcinoma tissue of the breast.

Normal tissue as well as various benign and malignant lesions of the breast were histochemically examined for the presence of the Thomsen-Friedenreich (TF)-antigen. Fluorescein- or 3H-labelled peanut agglutinin was used for this purpose, a lectin that is known to have a high affinity for the TF-antigen. The occurrence of this TF-antigen seemed in all cases, even in the carcinoma lobulare in situ that is regarded as being derived from myoepithelial cells by some authors, to be associated with a secretory condition. Its presence (free and neuraminic acid covered) in normal, hyperplastic and malignant breast tissue, however, cannot be considered a specific tumour associated antigen as has been previously assumed. Furthermore the investigations have shown that the intensity of fluorescence for peanut agglutinin (PNA)-receptors was generally stronger in differentiated carcinomas than in undifferentiated carcinomas of the breast. The histochemical findings are discussed with regard to diagnostical and immunotherapeutical aspects.

Histochemical methods for the demonstration of Thomsen-Friedenreich antigen in cell suspensions and tissue sections.

1. Three different methods are described for the visualisation of the Thomsen-Friedenreich (TF) antigen on cell suspensions, formalin-fixed and paraffin embedded or frozen tissue sections: a) Rosette formation with chicken and sheep erythrocytes. b) Fluorescence-microscopy with fluorescein labelled peanut agglutinin. c) Autoradiography with 3H-labelled peanut agglutinin. 2. The TF antigen was shown, as far as presently investigated, to be exposed on various blood cells, glomerula of the kidney and normal mammary gland after neuraminidase treatment. Mammary gland was also shown to possess TF receptors without prior treatment with neuraminidase. 3. The exposure of this cryptantigen can be brought about by bacterial or viral neuraminidase and is followed by an antigen/antibody reaction, which can lead to possible pathological consequences.

[Measurement of post-irradiation population kinetics using single-cell cytophotometry combined with double-labeling autoradiography: model investigations into a diploid Ehrlich ascites tumor after 475 rd X-irradiation (author's transl)]. / Die Messung der Populationskinetik nach Bestrahlung durch Kombination von Einzelzellzytophotometrie und zweizeitiger Markierungsautoradiographie. Modelluntersuchungen an einem diploiden Ehrlich-Aszites-Tumor nach 475 rd Röntgenbestrahlung.

A technique for in vivo determination of the population kinetics in tumors following irradiation is reported in this paper. Using the model of a diploid Ehrlich ascites tumor (EAT-dipl), the migration of cells from different subpopulations was followed up through the generation cycle. The measurability of post-irradiation growth kinetics in different subpopulations is emphasized with regard to its importance for practical application with combination treatments or possibility for the problem of dose-time relations. The individual results obtained after 475 rd are presented in detail.

Disturbance of DNA-Synthesis in early psoriasis.

In earlier studies we have shown that there is a significant prolongation of DNA-synthesis time (ts) in the epidermal cells of fully developed psoriatic lesions. The present study shows that this prolongation is to be observed even in very early plaques. The prolongation of ts precedes the development of acanthosis. A dermal infiltrate with increased proliferative activity seems to be a stimulus, in the sense of a Koebner-phenomenon. There is no pronounced prolongation of ts in other acute or chronic inflammatory processes of the skin. The behaviour of the infiltrate in psoriasis is similar to that in allergic patch test reaction. However, the abnormal psoriatic epidermis, with disturbed DNA-synthesis, does not react to the above mentioned infiltrate with a limited hyperproliferation but with the development of a psoriatic plaque. There is obviously congenital disturbances of metabolism within the epidermal cells in psoriasis.

[Treatment of cardiogenic shock after acute myocardial infarction with intra-aortic balloon counterpulsation (author's transl)]. / Die Behandlung des kardiogenen Schocks bei akutem Herzinfarkt mit der intraaortalen Ballon pulsation

Intra-aortic balloon counterpulsation (IABP) was used in 20 patients with acute myocardial infarction and cardiogenic shock, after four hours of drug treatment. In all instances the abnormal haemodynamic state had been demonstrated. Four patients were successfully treated and finally discharged home. In two with post-infarction ventricular septal defect and cardiogenic shock, IABP also successfully reversed the shock state, while in seven the shock state was reversed but they died 2-8 days after IABP had been stopped. IABP failed in seven patients who died during its application. In those in whom IABP failed there had been no significant fall in pulmonary-artery pressure and no significant increase in stroke volume. The post-mortem examinations demonstrated that cardiogenic shock was irreversible where more than 50% of the left ventricular myocardium had been infarcted.

Effect of different sex of tumour bearing mice and of ovariectomy on the proliferation kinetics of a solid, transplantable mammary carcinoma (C3H-mouse).

The aim of the present investigation was to study the influence of sex of tumour bearing mice and of ovariectomy on the proliferation kinetics of a solid, transplantable mammary carcinoma (C3H-mouse). According to the growth curves the tumour growth was delayed in spayed female and in male mice compared with normal female animals. This was due to a longer cell cycle time of tumour cells in the former, mainly caused by a prolonged presynthetic gap (TG1). Concerning the growth fraction and the cell loss factor, essential differences could not be detected. Thus, the solid tumour displayed a distinct though partial disengagement of growth from hormonal dependence.

[A case of sarcoma of the talus giving the radiographic appearance of a "cyst" (author's transl)]. / Sarkom im Talus unter dem röntgenologischen Bild einer "Zyste"

A case of sarcoma in the talus with the radiographic appearance of a cyst is reported. In spite of local excision of a part of the talus there were local recurrence and metastases. The histologic diagnosis is discussed.

[Kinetics of cell proliferation in normal epidermis before and after application of 1 per cent vitamin A-acid solution (author's transl)]. / Die Proliferationskinetik normaler Epidermis vor und nach äusserlicher Anwendung einer 1 per cent igen Vitamin A-Säure-Lösung

A 1 per cent Vitamin A-acid solution was applied externally for 2 weeks on normal epidermis. The result was an acute dermatitis, characterized by hyperproliferation and shortened phases of cell cycle. There was no increase in the proliferative activity of lymphoid cells in the moderate dermal infiltrate.