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Biomedical subjects

W U Müller

Publications and source records attributed to W U Müller.

At least 55 records · Page 3Linked to original sources
PubMed1991

Cell proliferation and vascularization in human breast carcinomas.

Cell proliferation and vascularization were studied in 10 human breast carcinomas by an immunoenzyme technique. The monoclonal antibody (MAb) Ki-67 was used as a marker for proliferating cells and a polyclonal antibody directed against human von-Willebrand factor to identify blood vessels. The proportion of Ki-67-labelled cells varied from 1% to 20%, the number of small blood vessels from 4.4/mm2 to 57.6/mm2. Within single histological sections of individual tumours the percentage of proliferating cells was not related to the number of small blood vessels. However, after evaluation of 5 sections of each tumour, the average values showed that tumours with a high grade of vascularization had a higher percentage of Ki-67-positive cells than poorly vascularized samples. The influence of vascular density on cell proliferation was investigated in a selected area of one of the tumours (in 2-dimensions) and with regard to the over- and underlying sections (in 3-dimensions). After 2-dimensional evaluation, distances from proliferating cells to the closest blood vessel between 10 and 390 microns were observed, and after 3-dimensional evaluation none of the proliferating cells measured was located more than 130 microns away from the closest vessel.

Antibodies↗
PubMed1991

Direct evidence that radiation induced micronuclei of early embryos require a mitosis for expression.

The naturally synchronous development of early mouse embryos was exploited to address the question, whether micronuclei require a mitosis for expression or whether they can be expressed in the same cell cycle, in which exposure to X-rays or caffeine took place. Experiments with 2-cell and with 4-cell embryos showed that micronuclei are expressed only if a mitosis is completed. There was no indication, even after doses up to 20 Gy, that micronuclei can be expressed before the mitosis was reached, which followed exposure. Furthermore, no nuclear fragmentation pointing to apoptosis could be detected in the cycle, in which cells were exposed. The same results were obtained when caffeine (5 mM) was used as micronucleus inducing agent.

Animals↗
PubMed1991

Biological indicators for radiation damage.

Methods for estimating radiation dose using biological indicators have made rapid progress during recent years. Chromosome analysis in lymphocytes still plays a central role, but it is no longer the only quantitative system in biological dosimetry. The best approach seems to be to combine several of the assays exploiting their specific advantages: the high sensitivity in the case of dicentrics in lymphocytes (starting at about 0.05 Gy low-LET radiation), the broad dose range covered by the electron spin resonance technique (0.5-100 Gy), the possibility of identifying the localization of partial-body exposure when determining hair diameter, and the individual prognostic information obtained from changes in the frequency of blood cells after exposures exceeding about 1 Gy. In specific situations other methods may replace or supplement these indicators for radiation damage.

Biomarkers↗
PubMed1991

Micronuclei in human lymphocytes irradiated in vitro or in vivo.

Venous blood from healthy donors or from patients with various lympho- and myeloproliferative diseases was incubated in vitro in the presence of cytochalasin B for the induction of binucleated lymphocytes. The time at which cytochalasin B was added depended on the proliferation rate of the lymphocytes. Proliferation was monitored using a semiautomatic microscope photometer/computer system. The background level of micronuclei in binucleated lymphocytes of the patients before radiotherapy was statistically indistinguishable from that of healthy persons. Blood from both groups was irradiated in vitro for the study of the dose-response relationship. The dose-response curves were very similar up to 3.75 Gy, and a somewhat lower micronucleus frequency was found in lymphocytes of patients after a 5-Gy exposure. These in vitro results were compared with in vivo exposure after total-body irradiation of leukemic patients. Due to heavy medication that accompanied radiation therapy, only two doses (1.25 and 2.5 Gy) could be checked after in vivo exposure. There was no statistically significant difference between in vitro and in vivo results after 1.25 Gy, but a slightly lower number of micronuclei was observed after in vivo exposure to 2.5 Gy.

Adult↗
PubMed1990

Lethal and teratogenic effects after exposure to X-rays at various times of early murine gestation.

Various well-defined stages during completion of the second meiotic division and early organogenesis of mouse embryos were X-irradiated with doses of 1-4 Gy (100-400 rad). The major risk was prenatal mortality with radiation sensitivity changing markedly with dependence on the developmental stage irradiated; in the case of day 1 even within hours. The surviving fetuses did show a significantly enhanced frequency of malformations on day 19 of gestation (mostly gastroschisis and some exencephalies). This was true for all stages between days 1 and 8; only sensitivity again changed considerably. The radiation doses used in this study are markedly higher than doses that can be expected from radiation diagnostics, but exposure is in a range comparable to doses that can occur in radiation therapy (e.g., Morbus Hodgkin).

Abnormalities, Radiation-Induced↗
PubMed1990

Temperature dependence of combined exposure of preimplantation mouse embryos to X-rays and mercury.

Usually preimplantation mouse embryos are cultured in vitro at 37 degrees C. In this study, mouse embryos (starting with the 2-cell stage) were incubated in vitro throughout the preimplantation period at 34 degrees, 35 degrees, 36 degrees, 37 degrees, 38 degrees or 39 degrees C. Embryonic development, in particular hatching of blastocysts (144 h after conception), and cell numbers (at the same time) were analysed. Embryos were exposed to X-rays (1 Gy) or to mercuric chloride (3 microM, 10 microM) or to a combination of the two agents. Control embryos developed rather well in a temperature range of 35 degrees to 38 degrees C. A combined risk greater than expected from the sum of the individual effects was observed only at the optimum temperature (for a combination of 1 Gy + 3 microM) or in the range of the optimum temperature, that is between 36 degrees to 38 degrees C (for a combination of 1 Gy + 10 microM).

Animals↗
PubMed1989

Micronucleus formation in 2-cell embryos after in vitro X-irradiation of mouse spermatozoa.

Mouse spermatozoa were exposed in vitro to various X-ray doses and added to a medium containing superovulated oocytes. The percentage of fertilized oocytes was determined 24 h after sperm addition and 2-cell embryos were investigated for micronucleus formation. The fertilization rate was drastically decreased after exposure to 470 cGy whereas smaller doses had no effect. The dose-response relationship for micronucleus formation per embryo was linear-quadratic and the number of embryos with micronuclei increased linearly with dose. The distribution of micronuclei among 2-cell embryos showed a significant overdispersion relative to the Poisson distribution after sperm irradiation for doses above 188 cGy.

Animals↗
PubMed1989

Toxicity of various combinations of X-rays, caffeine, and mercury in mouse embryos.

Preimplantation mouse embryos in vitro were exposed to various doses of X-rays (0.25-2 Gy) and to different concentrations of two chemicals: caffeine (0.5-2 mM) and mercury (0.5-5 microM). X-irradiation was given first, followed immediately by exposure to the chemicals. The effects of the agents, applied either singly or in combination of two or of three, were studied using morphological, proliferative and cytogenetic endpoints (formation of blastocysts, hatching, trophoblast outgrowth, formation of inner cell mass, cell numbers, micro-nucleus frequency). The term 'enhancement in risk' was used whenever the effects observed after combined exposure (two or three agents) significantly exceeded the sum of the effects due to the component individual agents. The enhancement in risk observed after exposure to the three agents could be explained by the interactions already detected at the level of a combined exposure to only two agents. There was no increase in risk specific for the presence of all three agents.

Animals↗
PubMed1988

Time factors in combined exposures of mouse embryos to radiation and mercury.

There are situations in which the exposure to more than one agent results in an enhanced risk for the exposed organism, that is in which the observed effect exceeds the effect expected from the addition of the individual effects. Our knowledge of such hazards is rather limited, in particular for those agents that occur in the environment of man. When early mouse embryos in vitro were exposed to ionizing radiation and mercuric chloride, the observed risk was higher than expected from the individual effects. This increase in risk was due to an interaction between mechanisms induced by ionizing radiation and mercury. To gain some more insight into the mode of interaction, the time requirements of mercury exposure were studied. The amount of interaction did not depend on mercury exposure before or during irradiation. However, to achieve an enhanced risk, exposure had to start as soon as possible after irradiation and had to last as long as possible. This time dependence suggests that if inhibition of DNA-repair is involved in the mechanism of interaction at all, then there must be an additional late process that is also impaired by mercury.

Animals↗
PubMed1987

Dose-effect relationships and general mechanisms of combined exposures.

Organisms are exposed to a multitude of physical, chemical and biological agents. Many data are available on the risks associated with these agents when applied individually. However, an assessment of the overall risk has to take into consideration the possibility of unexpected risks after combined exposures. There is no way of testing all conceivable combinations of agents. Thus, we have to look for general mechanisms that permit extrapolations to situations not yet tested. The study of mechanisms requires the knowledge of the shape of the dose-response relations for all agents participating in the combined exposure. Possibilities for the analysis of effects after combined exposures are described. It emerges that very specific processes in the chain of events must be affected in order to influence radiation risk by another agent. Two such specific processes of importance are recovery phenomena and cell proliferation.

Cell Survival↗
PubMed1987

Risk to preimplantation mouse embryos of combinations of heavy metals and radiation.

The influence of arsenic, cadmium, lead or mercury on radiation risk to preimplantation mouse embryos in vitro was studied under various conditions. Morphological development, cell proliferation, and formation of micronuclei were used for assessment of risk after combined exposure to these metals and X-rays. No conditions were found under which arsenic altered radiation risk; the effects were merely additive. Cadmium acted similarly, though a few results indicated that morphological development might be impaired more strongly after combined exposure than expected from the addition of the single effects. Lead enhanced radiation risk with regard to micronucleus formation, but had an additive effect only in the case of morphological development and cell proliferation. Of all four metals, mercury had the greatest potential for enhancement of radiation risk, when morphological development and cell proliferation were studied. The observed combination effects exceeded even those effects which were calculated by taking into account the shape of the dose-effect curves (isobologram analysis, envelope of additivity). Mercury neither induced micronuclei nor enhanced their formation in combination experiments.

Animals↗
PubMed1987

Does tributyl phosphate influence the radiation risk of a highly proliferating system--the early mouse embryo in vitro?

Two-cell mouse embryos were exposed in vitro to tributyl phosphate, x rays, or a combination of both. In-vitro development of the embryos was followed microscopically (cleavage to four- and eight-cell embryos, formation of morulae and blastocysts, and hatching of blastocysts). Effects on proliferation were estimated by counting the number of cells per embryo early (48 h p.c. = 48 hours post conceptionem) and late (144 h p.c.) in the preimplantation period. Cytogenetic damage was studied using micronucleus formation as the end point. Tributyl phosphate did not reveal toxic effects up to a concentration of about 5 microM after an exposure time of 18 h. At a concentration of about 15 microM, 50% of late preimplantation embryos showed effects on morphological development and on cell proliferation, and at about 40 microM, 90% of the embryos were affected. Tributyl phosphate did not induce micronuclei. Small effects by x irradiation were observed between 0.25 Gy and 0.5 Gy, depending on the end point measured in the late preimplantation stage. Fifty percent of the embryos were affected by a dose slightly higher than 1 Gy, and 90% after about 4 Gy. No enhancement in risk was found after combined treatment of the embryos with tributyl phosphate and x rays.

Animals↗
PubMed1987

Radiotoxicities of [3H]thymidine and of [3H]arginine compared in mouse embryos in vitro.

Tritium that is bound to organic molecules is of special risk for living systems, in particular when such molecules are components of the cell nucleus. Therefore, [3H]thymidine and [3H]arginine were studied for radiotoxicity in early mammalian embryo development. Starting with the two-cell stage, mouse embryos were incubated in vitro with [3H]thymidine or [3H]arginine at either 370 Bq/ml (10 nCi/ml) or 925 Bq/ml (25 nCi/ml). Development in vitro was followed up to the formation of the inner cell mass at 192 h postconception (p.c.). There was no difference in radiotoxicity of the two substances with respect to cell proliferation; however, formation of blastocysts, hatching of blastocysts, trophoblast outgrowth, and formation of inner cell mass were impaired more strongly by [3H]arginine than by [3H]thymidine when the external exposure concentrations were the same. Similarly, micronuclei were seen in blastocysts at 96 h p.c. at higher frequency after incubation with [3H]arginine. However, uptake of [3H]arginine by the embryos was considerably faster than that of [3H]thymidine, and this most probably accounts for the apparent difference in radiotoxicity.

Animals↗
PubMed1986

Induction of sister chromatid exchange in preimplantation mouse embryos in vitro by 3H-thymidine or ultraviolet light in combination with caffeine.

Preimplantation mouse embryos were exposed in vitro to 3H-thymidine (25, 100, or 250 Bq/ml) or ultraviolet (UV) light (1.35 or 4.05 J/m2), either alone or in combination with caffeine (1 mM with 3H-thymidine and 0.5 mM with UV light). Exposure to 3H-thymidine lasted for 2 days, from the two-cell stage to the late morula/early blastocyst stage, and UV radiation was applied acutely at the late morula/early blastocyst stage. The effects were quantified by the sister chromatid exchange (SCE) assay. All three agents induced SCEs when used singly. 3H-thymidine was effective in inducing SCEs only at 250 Bq/ml, whereas UV light was effective at both fluences. Although caffeine did not induce SCEs when it was added before exposure to bromodeoxyuridine (BrdUrd), which is used to visualize SCEs, it did induce SCEs when present during the entire culture period (3H-thymidine experiments) or during incubation in BrdUrd (UV experiments). Caffeine markedly enhanced the SCE-inducing effect of UV light but did not influence the effect of 3H-thymidine.

Animals↗
PubMed1986

Toxicity of sodium arsenite in mouse embryos in vitro and its influence on radiation risk.

Mouse embryos at the preimplantation stage were used in vitro for assessing the risk exerted by arsenic on early stages of embryonal development. We studied the effects of sodium arsenite on morphological development, proliferation, and micronucleus formation. A concentration of 100 microM sodium arsenite immediately killed the embryos, and 1 microM almost completely inhibited formation of blastocysts. Micronuclei were induced starting from 0.7 microM arsenite. Concentrations below 0.1 microM (0.1 microM corresponds to 7.5 ppm arsenic) did not show significant effects with respect to any of the end-points examined. Arsenic did not influence radiation risk under various experimental conditions; all the effects after combining moderately toxic doses of sodium arsenite and X-rays corresponded to the effect obtained by the addition of the single effects.

Animals↗
PubMed1986

Enhancement of radiation effects by mercury in early postimplantation mouse embryos in vitro.

Two-cell mouse embryos were X-irradiated (1 Gy) and immediately thereafter exposed to mercuric chloride (3 microM) up to the blastocyst stage. When combined treatment started shortly (about 1 to 2 h) before mitosis to the four-cell stage, blastocyst formation, hatching of blastocysts, trophoblast outgrowth and ICM formation were impaired stronger than expected from the addition of the single effects. The enhancement of risk was maximal for hatching of blastocysts and no further increase was observed for trophoblast outgrowth and ICM formation. When exposure of embryos to X-rays and mercury began about 5 to 6 h before mitosis to the four-cell stage, only additive effects were obtained for the endpoints mentioned above.

Animals↗