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Biomedical subjects

K Goerttler

Publications and source records attributed to K Goerttler.

At least 37 records · Page 2Linked to original sources
PubMed1984

[DNA measurement of malignant tumors by impulse cytophotometry. The principles and importance for assessing growth behavior and the degree of abnormality].

Monometric DNA impulse cytophotometry of ploidism state (diploid or aneuploid tumors with stemmline shift, polyploidism ) and proportion of DNA-synthesized cells (S-phase proportion) were determined on over 500, mostly malignant, tumors of different sites. The results were compared with histopathological findings (TNM stage and degree of differentiation). Large diploid carcinomas of the oral cavity have lower S-phase activity than aneuploid tumors. Carcinomas of the breast, stomach and ovary are frequently diploid. Aneuploid carcinomas of these regions generally have high synthesizing activity. Mucoid signet-ring carcinomas of the stomach have lower S-phase activity than non-mucoid carcinomas. In the colorectal region aneuploid carcinoma predominates, in the colon more than in the rectum. Tumor metastases from colon and rectum into the liver predominantly are from aneuploid primary tumors. For tumors of the breast, corpus uteri and ovary with high and moderate differentiation there is a direct correlation between histological grade of differentiation and the S-phase proportions. Aneuploid tumors vary from low to high synthesizing activity. Diploid meningioma and glioma have a low S-phase proportion, aneuploidism correlates with an increase in growth. Supplementation of histopathological diagnosis by determining ploidism and S-phase activity makes an important contribution in the assessment of the degree of malignancy, as well as for therapeutic purposes.

Aneuploidy↗
PubMed1984

Spontaneous tumors and lifespan of female NMRI mice of the outbred stock Sut:NMRT during a lifetime study.

A group of 150 female NMRI mice of the outbred stock Sut:NMRT was kept until they died naturally, at which time they were necropsied and examined histologically for spontaneous tumors. The natural life expectancy (median) was 782 days. Life expectancy was markedly reduced by mammary and pulmonary adenocarcinoma, and by tumors of the hypophysis. The spontaneous tumor rate was 58%. That is to say, 87 of the 150 mice had spontaneous tumors: 57 animals each had one tumor, 20 animals each had two tumors, and 10 animals each had three tumors. The organs most commonly affected by tumors were those of the lymphoreticular and haematopoietic systems, followed by the respiratory tract in second place and the breast in third place. Data reported in the literature generally show the same organ distribution, but the total tumor rate given is generally somewhat lower as the animals are seldom left alive until they die naturally (spontaneously).

Aging↗
PubMed1984

A spontaneous transplantable lymphosarcoma of the Syrian golden hamster (Mesocricetus auratus): Experimental induction of metastases after subcutaneous and intravenous inoculation.

A spontaneously occurring lymphosarcoma of the Syrian golden hamster was both subcutaneously and intravenously inoculated into 300 female and male animals each. Tumor growth was observed at a 100% rate. Using both types of inoculations, metastases occurred in 50% of the inoculated animals, preferentially in lungs, liver, pancreatic lymph nodes, spleen and kidney. The participation of different lymph node groups was more frequent after subcutaneous application. The transplantable tumor described might serve as a mode for additional studies on experimentally induced metastasis.

Animals↗
PubMed1984

The proliferative index (PI) of human breast cancer as obtained by flow cytometry.

As known from previous reports, the DNA synthesis fraction of mammary carcinoma cells is correlated with the course of the disease and response to adjuvant therapy. Quantitative parameters of the proliferative activity can be determined by the classic 3HTdR-labelling technique as well as by the more rapid flow cytometric (FCM) DNA analysis. The values of DNA-cytometric S-phase fractions in breast cancers reported up to now were consistently higher than those obtained by the 3HTdR labelling index (LI). This discrepancy was surmounted in the present study by corrections for systemic errors of the method. The fractions of cells in stages of the cell cycle as well as the DNA indices (DI) in 155 cases of primary resectable breast cancers were analyzed by DNA flow cytometry. The patients were aged between 24 and 88 years. As indicated by a bimodal age distribution with a decrease at age 60, the patient population was a representative of the generally known breast cancer incidence. 54% of the patients had aneuploid tumor cells with preferences of DNA indices 1.6 and 2.0. In the remaining 46%, no cell populations with deviating DNA content could be detected, in part possibly due to very small differences beyond the limits of detection. No correlations were found between age, menopausal status, histologic type of tumors, tumor size, fractions in stages of the cell cycle and proliferative index (PI = S + G2 + M in %), except a significant correlation between the S-phase fractions and the (G2 + M)-phase fractions in a ratio of approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Suppression of the first stage of phorbol 12-tetradecanoate 13-acetate-effected tumor promotion in mouse skin by nontoxic inhibition of DNA synthesis.

In order to evaluate the significance of epidermal cell proliferation for the first stage of skin tumor promotion, the effect of hydroxyurea (HU), an inhibitor of DNA synthesis, on tumor formation was studied. Mice initiated with 7,12-dimethylbenz[a]anthracene received a single dose of phorbol 12-myristate 13-acetate (PMA) in stage I of promotion, followed by twice weekly application of the irritant skin mitogen phorbol 12-retinoate 13-acetate in stage II. A single dose of HU given intraperitoneally at different times before or after treatment with PMA was found to interfere with tumor formation, exhibiting an almost complete inhibition if administered 18 hr after PMA--i.e., at the time of maximal DNA synthesis. The inhibition of tumor formation by HU in the two-stage promotion experiment did not prevent a subsequent promotion of cells by repetitive PMA treatment. This indicates that the inhibitory effect of HU was due neither to cytotoxicity (killing of initiated cells) nor to an interference with initiation. The data indicate that epidermal DNA synthesis is obligatory for PMA-induced first-stage promotion. The causal relationship between both events remains to be established.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Skin tumor formation in the European hamster (Cricetus cricetus L.) after topical initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA).

Initiation with the carcinogen 7,12-dimethylbenz[a]anthracene followed by promotion with the hyperplasiogenic phorbol ester 12-O-tetradecanoylphorbol-13-acetate carried out on the dorsal skin of European hamsters (Cricetus cricetus L.) led to the formation of a broad spectrum of skin tumors in terms of a two-stage principle. Tumor formation involved the epidermis and its appendages, the connective tissue, and the vascular and pigmentary system. With regard to the sensitivity to initiation with DMBA alone and initiation with DMBA and promotion with TPA the European hamster occupies a special position since all of the DMBA-TPA sensitive two-stage target organs known from the mouse, rabbit, Syrian golden hamster and rat are combined in this animal.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Cytostatic and cytotoxic response of Ehrlich ascites tumor cells in vivo on chronic treatment with cytarabine, bleomycin, and peplomycin.

The cytokinetic response of Ehrlich ascites tumor (EAT) cells in vivo upon chronic treatment at low dosage levels with cytarabine (1-beta-D-arabinofuranosylcytosine, ara-c) bleomycin (BLM) and peplomycin (PEP) was estimated. Bivariate DNA histograms allow the simultaneous evaluation of the cell cycle status of living and killed cells. It could be confirmed that ara-C is cytostatic on cells in S phase. Pronounced cytotoxicity was observed in G1 and G2+M phase. BLM and PEP showed no (or neglectable ) accumulation of vital cells in any cycle phase. Both drugs, however, are cytotoxic on cells, regardless their position within the cell cycle. A successive application of ara-C and BLM (or PEP) in a cell kinetics-directed therapy schedule may be taken into account.

Animals↗
PubMed1984

Interaction of phorbol derivatives with replicating cells.

The significance of the interaction of phorbol derivatives with replicating cells has been studied in HeLa cells and in tumour promotion experiments. Dose-response relationships for the radiomimetic activity of phorbol derivatives in HeLa cells (Kinzel et al., 1980) were obtained by analysis of the degree of transient blockage in G2 phase of the cell cycle. HeLa cells are shown to be one order of magnitude more sensitive to 12-O-tetradecanoylphorbol-13-acetate (TPA) than to equally mitogenic and irritant but much less promoting derivatives. The susceptibility of HeLa cells reflects the promoting capacity of these compounds. Studies on effects of modifiers on TPA-induced G2 blockage indicate that the influence of TPA, even in a single cell cycle phase, may be the result of a 'multiple site' attack. The significance of the interaction of TPA with replicating mouse epidermal cells in tumour promotion has been demonstrated in animal experiments after initiation with 7-12-dimethylbenz[a]anthracene by using a two-stage protocol which effects promotion with a single dose of TPA followed by repeated treatment with 12-O-retinoylphorbol-13-acetate (Fürstenberger et al., 1981). A single dose of the inhibitor of DNA synthesis, hydroxyurea, given to groups of mice at different times before and after treatment with TPA interferes with tumour formation; almost complete inhibition is observed after 18 h. The interaction of TPA and DNA-synthesizing cells seems to be of crucial importance to the first stage of tumour promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Keratin polypeptide composition as a biochemical tool for the discrimination of benign and malignant epithelial lesions in man.

An investigation was undertaken of the keratin polypeptides of various benign and malignant tumors of the human skin and vaginal epithelium by one and two dimensional gel electrophoresis. The keratin patterns of benign tumors were found to be similar to the patterns of normal epithelium or stratum corneum. The relative proportion of stratum-corneum associated keratin polypeptides to those polypeptides characteristic for the living layers corresponds to morphological features (e.g., hyperkeratosis, acanthosis). In contrast to benign tumors, epithelial carcinomas totally lack the group of high-molecular-weight keratins. This finding may be helpful in the diagnostic discrimination between benign and malignant epithelial lesions.

Electrophoresis↗
PubMed1983

Electrolyte and glucose metabolism in VX-2 carcinoma of the rabbit.

Biochemical and other parameters in VX-2 carcinoma in rabbits were evaluated. VX-2 carcinoma not only produced hypercalcemia but also hypophosphatemia and 25-OH-vitamin D deficiency. An increased turnover of 25-OH-vitamin D seems likely. Serum parathyroid hormone and urinary cyclic AMP did not increase. Hypokalemia occurred in association with hypophosphatemia and lowered blood glucose within 1 week after tumor transplantation. At the end of the experiment glucose and insulin were both below the control range. It is concluded that VX-2 carcinoma in rabbits yields much more complex biochemical alterations than reported before on calcium metabolism.

Animals↗
PubMed1983

On the persistence of tumor initiation in two-stage carcinogenesis on mouse skin.

The persistence of the initiated state during two-step carcinogenesis in mouse epidermis is a generally accepted phenomenon, however, conflicting results exist with regard to the degree of irreversibility relative to the age of the animals. Several factors such as age-dependent alterations in the response of the epidermis to the promoter and skin damage following the initiation step have been proposed to account for the observed discrepancies. In the present investigation we have tried to circumvent skin-damaging effects of topically applied 7,12-dimethylbenz[a]anthracene by intragastric administration of the drug. Tumor production by topical promotion with 12-O-tetradecanoylphorbol-13-acetate was subsequently determined in 600 female NMRI mice using intervals of 4, 8, 16, 24, 32 and 40 weeks between initiation and promotion. Independent of the delay between the initiating and promoting step, we observed a similar time course and extent of tumor production in the different experimental groups. This indirectly proves that the promoting capacity of 12-O-tetradecanoylphorbol-13-acetate is age-independent and that during aging no substantial loss of initiated cells occurs in mouse epidermis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Multistage tumor development in the human esophagus - the first identification of cocarcinogens of the tumor promoter type as principal carcinogenic risk factors in a local life style cancer.

An experimental analysis is described which demonstrates that the epidemiologically established high rate of esophageal cancer among blacks and creoles in Curacao most likely is the result of a multistage process involving initiators and promoters. As part of local lifestyle, the group at risk utilizes for various purposes plant parts of an indigenous bush Croton flavens L. ("Welensali"). Moreover they consume, as an everyday beverage, a "bush tea" made from the leaves of the bush. The roots, leaves and tea are shown to contain a multitude of irritant croton factors which are characterized as diterpene esters of the tigliane type. In mouse skin these exhibit strong promoting activity comparable to that of TPA. As the latter, also the croton factors isolated, show no solitary carcinogenic activity. One cup of Welensali tea contains the equivalent of about 12-times the irritant dose of croton factor F1; in addition, the equivalent of about 1.4-times the irritant dose 50 of the corresponding "cryptic" promoter F1-20-decanoate is present. These amounts are considered sufficient to maintain chronic irritation of the esophagus as an important element of co-carcinogenesis, especially of tumor promotion. Also, persons at risk in Curacao have been exposed at times previously to certain initiators. Mice treated by an initiation/promotion protocol with DMBA (or other initiators) and TPA develop tumors of the forestomach. Therefore, esophageal cancer on Curacao may be considered the first case for cocarcinogens of the tumor promoter type being principal risk factors in a life style cancer.

Animals↗
PubMed1983

Age-related nuclear size variability of thyreocytes in thyroid aspirates.

Variations in nuclear areas in thyroid aspirates may be caused by many different pathologic conditions of the thyroid gland. Our experience in routine thyroid cytology has suggested that the age of the patient could also be a factor that can influence the nuclear size of thyroid epithelial cells. Planimetric measurements of nuclear areas of cytologically normal thyroid nuclei from patients with normal thyroid glands and from those with cold thyroid nodules, with each category containing two different age groups, revealed both a significant increase in nuclear areas in normal thyroid tissue from older patients and a significant increase in nuclear size variability among older patients with nodular goiters. This finding seems to indicate that patient age is another factor that exercises an influence upon the variability of nuclear areas, even in histologically normal thyroid glands.

Adolescent↗
PubMed1982

Assignment of snRNA gene sequences to the large chromosomes of rat kangaroo and chinese hamster isolated by flow cytometric sorting.

Chromosomes from a rat kangaroo (Potorous tridactylus) cell line (PtK2) and from a Chinese hamster (Cricetulus griseus) cell line (CHV79) were isolated by means of fluorescence activated flow cytometric sorting. DAPI (4'-6-diamino-2-phenylindole) was used as the DNA specific fluorescent dye. The karyotype of the PtK2 cells which exhibits 13 chromosomes was separated into 6, and the 22 chromosomes of the CHV79 cells were resolved into 11 fractions. DNA extracted from these chromosomal fractions was used for restriction enzyme digestion and blotting on nitrocellulose filters. The blots were challenged with gene probes corresponding to ribosomal RNA (18S and 28S) and small nuclear RNA (U1-snRNA) genes. The rRNA genes were exclusively assigned to chromosomes containing the nucleolus organizing region (in PtK2: X chromosome; in CHV79: chromosomes 4, 5, 6, and 11). - Solely the largest chromosomes in both cell lines hybridized with U1-snRNA indicating that these gene sequences are located on those chromosomes only. Further possible genetic and biochemical applications of this experimental system are discussed.

Animals↗
PubMed1982

Fatal nitrosamine poisoning.

A case is reported in which progressive liver symptoms with rise in bilirubin concentration, hemorrhagic diathesis, and signs of portal hypertension developed three years before death in liver coma. The pathologic and neuropathologic findings are described. The case was clarified after dimethylnitrosamine was demonstrated in food intended for the patient and after it was established that small amounts of nitrosamine could have been repeatedly ingested by the patient over a period of years. Comparable cases of human dimethylnitrosamine poisonings published in the literature are presented. The relatively typical morphologic alterations in the liver are described. Problems involved in the histological interpretation of such liver changes as well as the forensic conclusions to be drawn are discussed.

Adult↗