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Biomedical subjects

E Gebhart

Publications and source records attributed to E Gebhart.

At least 73 records · Page 4Linked to original sources
PubMed1987

Ophthalmic surgical complications in Werner's syndrome: report on 18 eyes of nine patients.

In ten of 18 eyes from nine patients with Werner's syndrome cataract surgery was complicated by wound dehiscence and its consequences: peripheral anterior synechiae (4X), secondary epiretinal gliosis (4X), cystoid macular edema (3X) in the framework of Hruby-Irvine-Gass syndrome, unplanned filtering bleb (2X), and postoperative anterior ischemic optic neuropathy (1X). Additionally, corneal endothelial decompensation occurred in eight eyes. In view of the fibroblasts' reduced growth potential, we suggest small surgical incisions, extracapsular cataract surgery using phacoemulsification, intraocular irrigation solutions protecting corneal endothelium, nonabsorbable single knot sutures not removed before 1 year after surgery, and no local or systemic use of cortisone.

Adult↗
PubMed1986

Microcell-mediated chromosome transfer from human tumor cells to human recipient cells evidenced by premature condensation of the transferred chromosomes.

Micronucleation was induced by vincristine, colcemid, and colcemid in combination with cytochalasin B in cells of a human metastatic breast carcinoma cell line (MDA MB 231). Cells treated with the latter combination were enucleated subsequently by centrifugation in the presence of cytochalasin B. The resulting "microcell" fraction was fused with mitotic human primary fibroblasts or mitotic HeLa cells using polyethyleneglycol (PEG). The success of the microcell-mediated chromosome transfer thus could be demonstrated as premature condensation in the mitotic recipient of the transferred micronuclei. This technique of cytogenetic analysis allowed a fast and simple control of the influence of different conditions on micronucleation and fusion of micronuclei with recipient cells. It could be shown that microcell-mediated chromosome transfer from human tumor cells into human normal, as well as human tumor, recipient cells is practicable if the techniques figured out by the present study are employed.

Breast Neoplasms↗
PubMed1986

Premature chromosome condensation--studies on human metastatic carcinoma cells.

Utilizing the phenomenon of premature chromosome condensation (PCC) studies were carried out on interphase chromatin of metastatic cells from 52 cancerous effusions obtained from 45 patients presenting with various solid carcinomas. A highly individual pattern of distribution of the various interphase stages was detected, reflecting the heterogeneity of human solid tumors in an advanced stage. Nevertheless a variety of clinical, biologic, and technical factors were examined for their possible influence on these PCC patterns. The duration in culture was one of the influencing factors, as were the time lapse between the first diagnosis and the sampling of the respective effusion, or the nature of cytostatic therapy. Cytogenetic equivalents of gene amplification, as represented by "double minutes", could be found in the prematurely interphase chromatin of 35 of the 52 effusions. G1-PCC proved to be most reliable with regard to screening of double minutes. In addition, an adequate quality of Giemsa banding was achieved in PCC of 21 out of 24 effusions yielding a sufficient number of well-spread PCC. In six of these 21 cases PCC was superior to metaphase analysis in obtaining karyotypes, while the same was true for 14 of the 52 effusions screened for double minutes. Thus the PCC technique was shown to be an indispensable additional source of cytogenetic information in cells of human solid tumors.

Adult↗
PubMed1986

Cytogenetic studies on human breast carcinomas.

Cytogenetic studies were performed on cell material obtained from surgical specimens of 50 human breast carcinomas and from 61 cancerous effusions of 46 patients. Classical cytogenetic analyses of numerical chromosome changes and marker chromosomes revealed the non-random involvement of chromosomes #X and #22 as monosomics, of chromosomes #3, #7, and #19 as trisomics, and chromosome #1 (particularly p 13 to q 12) in marker formation. Karyotypic evolution was followed in vitro and in vivo and showed a highly individualistic pattern of stability and variability. In addition, a systematic screening for the presence of cytogenetic equivalents of gene amplification (double minutes 'DM', homogeneously staining regions 'HSR') was carried out. A high incidence of DM-positive cases was detected in primary tumors (48%) as well as in metastatic cells from effusions (40%), with the frequency of DM-containing metaphases ranging from 1 to 100% in the positive cases. This finding supports the assumption of the fundamental biological importance of gene amplification in human solid tumors. Furthermore, chromosome breakage and micronuclei were observed in breast carcinoma cells as an apparent consequence of therapy-independent mutability.

Breast Neoplasms↗
PubMed1985

Double minutes in prematurely condensed chromatin of human tumor cells.

Comparative studies on the occurrence of double minutes (DMs) were performed on metaphases and prematurely condensed interphases (G1, G2) of cells from 28 cancerous effusions of 24 carcinoma patients. In 21 of these effusions, agreement between metaphase and prematurely condensed chromatin (PCC) data was obtained concerning occurrence or nonoccurrence of DMs (10 DM positive, 11 DM negative). In two cases, DMs were observed in metaphases only, whereas in five cases, they were found in interphases only. In normal cells, no DMs could be found, neither in metaphase nor in PCC. No causal correlation of the occurrence of DMs and cytostatic therapy was found. The data suggest that cytogenetic screening of prematurely condensed interphase cells from human tumors or cancerous effusions provides a valuable method for estimating the incidence of gene amplification in malignant cells, particularly in those with poor mitotic yield.

Adult↗
PubMed1985

Cytogenetic analyses utilizing various clastogens in two sibs with Fanconi anemia, their relatives, and control individuals.

Structural chromosome damage, sister chromatid exchange (SCE), and proliferation kinetics were studied on lymphocyte cultures from the peripheral blood of two sibs exhibiting signs of Fanconi anemia, their relatives, and control individuals. While the rate of spontaneous chromosome breakage was at the lower limit of that known for Fanconi anemia in our patients, a distinctly greater increase than in controls of breakage frequency could be induced by isoniazid (INH), 4-nitroquinoline-1-oxide (NQO), and diepoxybutane (DEB) in their lymphocytes. Increased aberration frequencies as compared with controls were also observed in the clastogen-exposed lymphocyte cultures of the parents of both sibs, but in some experiments (NQO, DEB 24 h) only in the cells of the healthy brother. There was an increase in the breakage rate of bromodeoxyuridine (BrdU)-labeled consecutive mitoses under the action of NQO, but a decrease with INH as the test clastogen. No significantly higher SCE frequency was found throughout the study in untreated and clastogen-exposed FA lymphocytes as compared with the respective controls. Proliferation was clearly inhibited by INH and NQO as indicated by a distinct increase of the percentage of BrdU-labeled first and a drastic decrease of third metaphases. The present test clastogens were shown not only to be suitable for ensuring the diagnosis of FA in patients with a low incidence of spontaneous breakage but also for determining clastogen-sensitive heterozygotes. According to these results cross-link repair cannot be the only mechanism affected by the basic defect of Fanconi anemia.

4-Nitroquinoline-1-oxide↗
PubMed1985

Cytogenetic studies using various clastogens in two patients with Werner syndrome and control individuals.

Chromosome studies were performed on peripheral lymphocytes from two patients with Werner syndrome and two healthy control individuals to detect spontaneous and/or mutagen-induced chromosomal instability of this disease. Diepoxybutane, isonicotinic acid hydrazide, 4-nitroquinoline-1-oxide, and bleomycin were used as standard clastogens. While the spontaneous frequency of chromosomal breakage was much higher in lymphocytes from both patients than in the control cells, the basic rate of sister chromatid exchange (SCE) was found to be in the control range. The sensitivity to clastogens of the patients' cells, however, was not substantially increased as compared with the controls if the degree of multiplication of the spontaneous breakage rate or SCE frequency was taken as the basis for comparison. No indication of a greater inhibition of proliferation by the clastogens in the patients' cells than in normal cells was observed using BrdU-labelled lymphocytes. Thus, the lymphocytes from both patients of the present study lacked essential features of the classical chromosome instability syndromes.

Cell Division↗
PubMed1985

The action of anticlastogens in human lymphocyte cultures and their modification by rat-liver S9 mix. II. Studies with vitamins C and E.

The action of vitamins C (VC) and E (VE) on the clastogenic activity of trenimon (TR), cyclophosphamide (CP) and bleomycin (BM) was tested on cultures of human peripheral blood lymphocytes with and without addition of rat-liver S9 mix. In addition, the influence of both anticlastogens on the SCE-inducing activity of TR and CP was examined under the same conditions. A distinct dose-dependent anticlastogenic effect of VC was detected in the action of long-term treatment (24 h) with TR, if the vitamin was added to the cultures simultaneously with or before the clastogen. In the short-term tests (2 or 3 h clastogen treatment ending 23 h or 21 h before harvesting) simultaneous addition of both vitamins did reduce the chromosome-damaging action of TR whether S9 mix was present or absent. While VC also decreased the frequency of chromosome damage induced by S9-mix-activated CP, VE was inactive under the same conditions. Neither vitamin significantly affected the chromosome-breaking activity of BM if S9 mix was absent, but they increased the clastogenicity of BM metabolized by S9 mix. In contrast to their anticlastogenic efficacy neither of the vitamins displayed any significant anti-SCE effect, nor were they active in affecting the inhibition of cell proliferation caused by TR or CP.

Animals↗
PubMed1984

Incidence of double minutes, cytogenetic equivalents of gene amplification, in human carcinoma cells.

Screening of the occurrence of double minutes (DM) was performed in more than 1,000 metaphases obtained from a total of 22 solid human breast tumours and more than 3,600 metaphases from a total of 55 malignant effusions (45 patients with different types of carcinomas). DM were observed in 15 of these breast tumor cases and in 34 of the effusions (obtained from 29 cancer patients). The percentage of cells exhibiting DM as well as the number of DM per respective cell varied widely. It could be seen that metastatic cells from malignant effusions exhibited on the average more DM per cell than did cells of primary breast carcinomas. Differences in the incidence of DM could be observed between different carcinomas as well as between different age groups. In addition, it did not appear that DM could be induced by mutagenic tumor therapy. DM are thus not a rare finding in human solid tumors but, as cytogenetic equivalents of gene amplification, they rather represent a fundamental biological characteristic of tumor development.

Breast Neoplasms↗
PubMed1984

The action of anticlastogens in human lymphocyte cultures and its modification by rat liver S9 mix. I. Studies with AET and sodium fluoride.

The action of beta-aminoethylisothiouronium bromide hydrobromide (AET) and sodium fluoride (NaF) on the clastogenic activity of Trenimon, cyclophosphamide, and bleomycin was tested on cultures of human peripheral lymphocytes with and without the addition of rat liver S9 mix. In addition, the influence of both anticlastogens on the SCE-inducing activity of Trenimon and cyclophosphamide was examined under the same conditions. In the absence of S9 mix both substances displayed the known anticlastogenic action when TR was the standard clastogen but acted coclastogenically in the experiments with BM. Under the influence of rat-liver S9 mix this action on TR-induced chromosome damage was decreased and only a slight anticlastogenic effect was observed in the experiments with activated cyclophosphamide. S9-activated BM lost some of its strong chromosome-damaging effect and AET proved clearly anticlastogenic under these test conditions. AET displayed a slight decreasing effect on SCE induced by TR, but had no effect on CP-induced SCE. No anti-SCE effect at all was found in the experiments with NaF. Detailed analyses revealed different actions of both anticlastogens on the different types of structural chromosome damage.

Animals↗
PubMed1981

Sister chromatid exchange (SCE) and structural chromosome aberration in mutagenicity testing.

Data from previous studies published on the induction by mutagens of sister chromatid exchanges (SCEs) and structural chromosome damage were compared qualitatively and quantitatively. Although a good correlation between the incidence of both cytogenetic phenomena has been pointed out in many previous publications, about 30% of the agents for which comparable data were available yielded non-corresponding qualitative results concerning both indicator effects. However, even in groups with good qualitative agreement distinct quantitative differences indicated different molecular mechanisms of the formation of SCEs and breaks. Additional information supporting the importance of these differences for the validity of both indicator systems has been derived from the results obtained using strong clastogens exhibiting a low or no SCE-inducing activity and vice versa, from special observations on chromosomal breakage syndromes, and from studies on the action of known co- and anti-clastogens on SCE-induction by chemical mutagens. As a result, it has been suggested that the SCE-technique should be considered as a valuable additional method for cytogenetic mutagenicity testing, which, however, is not adequate to replace the classical methods of analysis of structural chromosome damage.

Animals↗
PubMed1980

The action of three anticlastogens on the induction of sister chromatid exchange by trenimon and 8-hydroxyquinoline sulfate in human lymphocyte cultures.

The influence of the anticlastogens beta-aminoethylisothiouronium (AET), d,l-homocysteinethiolactone (HCT), and 1-cysteine (CYS) on the frequency of sister chromatid exchanges (SCEs) induced by the chromosome damaging chemicals Trenimon and 8-hydroxyquinoline sulfate (8-HQS), was investigated in human lymphocyte cultures. None of the anticlastogens significantly influenced the SCE rate, whereas in the same or previous experiments the chromosome-breaking effect of these clastogens was distinctly reduced by the anticlastogens. These results suggest that the sites of anticlastogenic activity do not coincide with the sites of SCE formation. SCE analysis, although it yields interesting and important information about the action of chemicals on genetic material, cannot replace classical aberration analysis, because the two parameters apparently reflect different patterns of molecular and cytogenetic activity of mutagens.

Alkylating Agents↗
PubMed1980

Chromosome studies on lymphocytes of patients under cytostatic therapy. II. Studies Using the BUDR-labelling technique in cytostatic interval therapy.

Lymphocyte cultures from the peripheral blood of 38 patients undergoing a cytostatic interval therapy with a regimen of methyl-CCNU (1-[2-chloroethyl-3-(4-methyl-cyclohexyl)]-1-nitrosourea), 5-fluorouracil, and vincristine (each 5-day course of therapy was followed by a therapy interval of 4 weeks) were supplied with 5-bromodeoxyuridine (BUDR) for the whole culture time to determine the sister chromatid labelling pattern. From a total of 92 individual blood samples sister chromatid exchange (SCE) studies were performed including analyses before the start of the therapy, and immediately and 4 weeks after each course of therapy. In addition, the frequency of first, second, and third metaphases in the 72-h cultures was estimated using the characteristic labelling patterns. A distinct increase of SCE frequency over the control level (i.e., lymphocyte cultures of patients before the start of therapy) was observed at all phases of therapy. It was clearly correlated with the number of courses of therapy up to course 7, later on the SCE rate remained more or less at the level reached. The influence of the composition of each drug regimen on the SCE rate was less pronounced than it was on the breakage rate. Moreover, although a clear correlation existed between the individual rates of breakage and SCE, the formation of the latter appeared to reflect a long-term effect of the therapy rather than did the formation of break aberrations. In addition, as the intercellular variability of the number of SCEs per cell was much higher than that of breaks, the interindividual variability (variation of the mean values for each patient) was small compared to the respective variability of breakage rates. The proportion of first, second, and third metaphases present in 72-h cultures evidently was influenced by single courses of therapy. The observed delay of proliferation was also reflected in different amounts of chromosome damage. Although the BUDR treatment enhanced the cytostatic effect of the therapy on the lymphocytes in culture rendering SCE analysis rather difficult in several cases, the other data of this study and in particular the experiences with the "long-term effect" make it imperative to include BUDR-labelling in further cytogenetic studies in subjects with exceptional exposure to chemicals. However, the SCE method can by no means, replace the classic cytogenetic analysis.

Adult↗