Biomedical subjects
Publications and source records attributed to G Keller.
Forty-one histologically verified endometrial carcinomas were examined to reveal relationship, if any, between cytoplasmic receptor content and tumour differentiation, cytologic diagnosis and mean nuclear surface area. The latter in itself was found to be a reliable prognostic sign of the estrogen receptor positivity of the tumour.
Results of combined treatment with two different drug combinations were compared in 82 patients with advanced ovarian carcinoma (stages III-IV). 41 patients received cyclophosphamide, methotrexate, vincristine (CMV) and the other 41 patients were treated with cyclophosphamide, adriamycin and cisplatin (CAP). 34 patients (82.9%) treated with the CAP-regimen and 20 patients (48.8%) treated with CMV had remissions following treatment. The average duration of remission was longer in the CAP group (18.1 months) compared to CMV treatment (11.6 months). The mean survival time 24.3 and 14.7 months respectively. It is concluded that three drug therapy is optimal in advanced ovarian carcinoma.
A new short-term suspension culture system is described in which pluripotential hematopoietic precursors from mouse bone marrow increase 8 to 12 times in number over a 4-day period. The increase is shown to derive from myeloid precursors undergoing repeated cell divisions prior to definitive lineage restriction. The response, which occurs in the absence of any pre-formed feeder layer, depends on dual stimulation by both IL-1 and IL-3, and the maximum effect depends on the presence of both factors together from the initiation of the cultures. The observations extend the known range of targets of IL-1 and IL-3 to include primitive pluripotential precursors capable of some degree of self-renewal, and provide a specific and relatively simple assay both for the precursors and the soluble factors which regulate them.
A recombinant retrovirus, N-TK-src, was used to introduce the v-src oncogene into mouse hematopoietic cells. This vector efficiently expresses both the neo and v-src genes in different hematopoietic lineages in culture as well as in mice reconstituted with infected bone marrow cells. Expression of v-src had no dramatic effect on the proliferative and differentiative capacity of hematopoietic precursors when assayed in methyl cellulose cultures. However, in mice reconstituted with N-TK-src-infected bone marrow cells, expression of v-src leads to the rapid development of a severe myeloproliferative disease, characterized by splenomegaly, anemia, and a shift of hematopoiesis from the bone marrow to the spleen.
Authors compared the results of 242 cytologic examinations of patients suffering from endometrial carcinoma with the histologic picture of the tumour. Conventional methods of cytodiagnostic screening in case of less differentiated tumours were found to give better results. Results of hormonal cytologic examinations demonstrate that there is an inverse relation between differentiation of tumour and maturity of vaginal epithelium. The authors analyze this observation with regard to the receptor theory of the malignant transformation of the endometrium.
Marrow cells from 5-fluorouracil (5-FU)-treated mice formed few or no mixed erythroid colonies when plated in semisolid medium with interleukin 3 (IL 3) and erythropoietin (Ep) alone. When conditioned medium (CM) from plastic-adherent marrow or thymus cells was also included, however, growth of mixed erythroid colonies was strongly stimulated. Both IL 3 and the accessory activity (AA) had to be present at the initiation of the cultures for growth to occur. AA was also produced by a cloned immortalized line (95/1.7) of fibroblastoid marrow cells that lacked macrophage-specific cell surface markers. Colony-stimulating factor-1 (CSF-1) was also released, but not granulocyte colony-stimulating activity. When 95/1.7 CM was analyzed by gel filtration, AA eluted with an apparent size of 35 kd and separated completely from the CSF-1. Biologic assays failed to detect IL 1 or IL 3 activity in 95/1.7 CM. Growth of mixed erythroid colonies from 5-FU-treated marrow is thus stimulated by adherent marrow cell-derived factors that appear distinct not only from the known CSFs including IL 3, but also from IL 1.
Multiple organ failure continues as the main cause of death after burns, trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a setting of clinical organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once in the organ failure syndrome, most treatment modalities become progressively ineffective, including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention with rapid control of the source and restoration of oxygen transport. The response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimulus. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is currently hypothesized that this liver failure represents a state of regulatory dysfunction induced by the activated hepatic macrophage, the Kupffer cell. This same process may also influence metabolic failure in other organs where this cell-cell regulation can occur, e.g. kidney, lung. The activation of these macrophages is hypothesized to represent the final stage of a series of continuous stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized. Treatment consists of the modalities outlined above and the employment of aggressive metabolic (nutritional) support.
30 patients with ovarian dysgerminoma are reported. Whenever possible the patients were operated radically. In cases when dissemination occurred, exploration was performed. 28 patients were irradiated. Applying adequate therapy, complete growths have proved to have poor prognosis.
The clonal make-up of the haematopoietic system of mice reconstituted with retrovirus-infected bone marrow cells was analysed at two different points in time following reconstitution. We have found that under these conditions, the haematopoietic system consists of clones that persist throughout the 5 month course of the experiment as well as those which undergo temporal changes. The various changes that we have observed included the appearance of a new clone(s) in all lineages, the loss of a clone from some lineages and the shift in the appearance of a clone from one lineage to another. In addition, we provide evidence which suggests that the clonal make-up of the thymus changes with time; early after reconstitution it consists of many clones, whereas at the later time-points it contains a limited number of predominant clones. These studies document the dramatic clonal changes which occur within the various lineages for a long time following reconstitution and highlight the difficulty in demonstrating lineage-specific stem cells.
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The inhibition of monoamine oxidase (MAO) in rat liver and brain by the short-acting MAO-A inhibitors moclobemide (Ro 11-1163 = p-chloro-N-[2-morpholinoethyl]benzamide) and brofaremine and by the short-acting MAO-B inhibitors Ro 16-6491 (N-[2-aminoethyl]-p-chloro-benzamide) and almoxatone, administered p.o. at roughly equieffective doses 2 h before decapitation, was investigated for its reversibility under various in vitro conditions. MAO A activity in liver homogenates, inhibited by moclobemide (300 mumol/kg) to approx. 15% of control, time dependently recovered during 0.5 to 2 h of incubation at 37 degrees C, irrespective of whether the homogenates were prepared and incubated in distilled water or Krebs-Ringer buffer (KRB). Dialysis of such homogenates for 4 h in distilled water at 37 degrees C (but not at 13 degrees C) led to a complete return of the MAO activity. In liver homogenates from rats pretreated with brofaremine (30 mumol/kg), dialysis for 4 h at 37 degrees C against distilled water caused only little recovery of the MAO activity. Likewise, MAO-B inhibited by Ro 16-6491 (30 mumol/kg) to approx. 4% of control returned to almost control activity after 4 h of dialysis at 37 degrees C, while inhibition induced by almoxatone (30 mumol/kg) was little or not reversed at all. In brain homogenates prepared in, and dialysed against, distilled water or KRB at 37 degrees C (but not at 13 degrees C), MAO-A inhibited by moclobemide (100-300 mumol/kg) to approx. 15% of control, partially (KRB) or almost completely (dist. water) returned to control activity after 4 h of dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper discusses different possibilities of deriving reference values for the natural radioactivity concentrations in building materials to estimate possible additional radiation exposure for the population. Based on comprehensive experimental and theoretical investigations the consequences of the resulting hypothetical reference activity concentrations in building materials, applying different dose limits, were examined. The calculation of the activity concentration standards was performed for standard conditions obtained by earlier studies on exhalation of Radon-222 and Radon-220 from building materials.
Relations between ethanol consumption and variations of dopaminergic activity expressed by altered apomorphine induced stereotypy behaviour in the rat were investigated. The results of this study show an increase of the stimulating effect of 1 mg/kg apomorphine in nonpreferent ethanol pretreated animals. These changes are present until 72 h after ethanol withdrawal. Ethanol preferent rats do not differ significantly in their stereotypy behaviour from ethanol untreated animals. The observed behavioural alterations will be discussed as an expression of dopaminergic supersensitivity in nigrostriatal structures in nonpreferent rats after chronic ethanol treatment.
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A recombinant retroviral vector with an inserted bacterial neomycin resistance (neo) gene was used to transfer in vitro neomycin resistance (neoR) into murine cytotoxic lymphocyte precursors (CLP). The infection protocol involved co-cultivation of mitogen-activated splenic T-blasts with irradiated cells that produced either the recombinant retrovirus plus a helper virus, or exclusively the recombinant retrovirus. Infected T-blasts were subsequently cultured under limiting dilution (LD) conditions that supported clonal in vitro development of a large fraction of murine CLP. In infected T-blast populations, frequency estimates were obtained for CLP that developed into functional cytotoxic T-lymphocyte (CTL) populations under G418-selected or non-selected conditions; from these frequency estimates, an efficiency of transduction of the neoR phenotype into murine CLP of 2-8% was calculated. Some conditions were defined that influenced transduction efficiency, i.e., the density of the infecting monolayer cells; the presence of interleukin 2-containing conditioned medium and mitogenic lectins during the co-culture period; a delayed onset of G418 selection after infection. It was demonstrated that the neoR phenotype of functional CTL populations derived from infected CLP resulted from expressed recombinant retrovirus.
The human gamma- and beta-globin genes are expressed during the fetal and adult developmental periods, respectively. Differences in the sequences of their promoters may be relevant to their developmental regulation. The gamma globin gene promoter was found to be stronger than that of the beta gene. In HeLa cells co-transfected with plasmids containing the two genes, transcripts arising from the gamma promoter accumulated to a level 3-fold higher than those initiated from the beta-promoter. We have recently shown that deletion of the most distal of the conserved elements of the promoter (CACCC) reduces function to 25% of the wild-type, whereas the removal of the proximal of the two duplicated (CCAAT) elements increases promoter function 2- to 4-fold in HeLa cells during transient gene expression. Both the wild-type promoter and the truncation and linker-scanning mutants from which one of the two duplicated "CCAAT' elements had been removed, exhibited regulated expression when stably integrated into chromosomes of mouse erythroleukemia (MEL) cells. Thus, duplication of the "CCAAT' element, the feature by which the gamma promoter differs most strikingly from the beta, is not essential for function in erythroid cells.
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The results of our investigations in the Federal Republic of Germany on the indoor and outdoor exposure to natural radiation from gamma rays and radon and thoron daughters are presented. Indoor the median Rn-222 concentration was approximately four times higher than outdoors. A correlation analysis of the data obtained showed that indoors the equilibrium factor F is almost independent of ventilation, Rn-222 concentration and other parameters. The mean equilibrium factor was measured to be F = 0.3 in dwellings and approximately F = 0.4 outdoors. The results of our investigations on diffusion coefficients and exhalation rates showed, that the activity concentration in dwellings and in cellars can generally be explained by the radon exhalation from the building materials. Only in areas of high radon concentrations, the exhalation from the soil was a decisive factor. The mean effective dose equivalent by residence in dwellings amounted to 0.2 - 0.8 mSv/a for Rn-222 daughters and approximately 0.1 mSv/a for Rn-220 daughters. A relationship has been derived which permits the calculation of the expected average radiation exposure in dwellings by gamma radiation and by radon inhalation as function of the radionuclide concentration in building materials.