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M Molls

Publications and source records attributed to M Molls.

124 records · Page 7Linked to original sources
PubMed1983

The effects of lead and X-rays, alone or in combination, on blastocyst formation and cell kinetics of preimplantation mouse embryos in vitro.

Two-cell embryos in late G2-phase (cytofluorometrically determined) at 32 hours post-conception were treated in vitro with PbC12 (0 . 1 or 1 . 0 micrograms per ml). An additional group was X-irradiated 1 hour later (0 . 94 Gy) with or without lead treatment. Lead alone impaired formation and hatching of blastocysts. The combined treatment increased this deleterious effect on preimplantation development but synergism was not observed. Cell proliferation was disturbed by lead alone but to a higher degree by lead plus X-rays. A pronounced reduction of cell number per embryo was found during the period after reaching the morula stage although the labelling index increased. Apparently cell death occurred. Unlabelled S-phase cell nuclei (comparison between autoradiographic results and cytofluorometric DNA-determinations on the same isolated cell nuclei) and cell nuclei with a hyperploid (0 . 1 microgram PbC12 + 0 . 94 Gy) or hypoploid (1 . 0 microgram PcC12 + 0 . 94 Gy) DNA-content may have contributed to this cell loss. Labelling of cell nuclei which according to their DNA-content were not in S-phase was only observed when 0 . 1 microgram PbC12 alone or in combination with X-rays was used. This effect may be due to unscheduled DNA-repair synthesis or to the induction of chromosome aberrations (acentric fragments or non-disjunction).

Animals↗
PubMed1983

Tritium distribution in newborn mice after providing mother mice with drinking water containing tritiated thymidine.

Throughout gestation pregnant mice received drinking water which contained [methyl-3H]thymidine (18.5 kBq/ml). The newborn mice were divided into two groups. One group was nursed by their own mothers, which were further supplied with tritiated thymidine until 4 weeks after delivery (Experiment I). The other group was nursed by "nonradioactive mothers" which were given no tritiated thymidine (Experiment II). Tritium incorporation into the small molecular components of the acid-soluble fraction, lipid, RNA, DNA, and protein was analyzed for the newborn mice at various ages. In Experiment II, total radioactivity per gram tissue decreased initially after birth with a half life of 2.5-2.9 days in spleen, liver, intestine, stomach, thymus, lung, kidney, heart, and brain. At about 2 weeks after birth, a slower component of tritium elimination due mainly to the DNA-bound tritium appeared. Specific activity of DNA at birth was organ specific, highest in heart and lowest in thymus. Cumulative absorbed dose in various organs was estimated for the first 4 weeks after birth based upon an assumption that total and DNA-bound tritium are uniformly distributed. The result showed that organ specificity of dose accumulation is obvious for DNA-bound tritium, highest in spleen (1.15 mGy) and lowest in brain (0.13 mGy). It was also shown that the tritium supply from mother's milk is of minor importance for dose accumulation of DNA-bound tritium in the cell nuclei of organs of suckling mice.

Animals↗
PubMed1983

A comparison of the cell kinetics of pre-implantation mouse embryos from two different mouse strains.

The progression of pre-implantation mouse embryos through the first, second and third embryonic cell cycle was investigated cytofluorometrically. In contrast to most of the previous studies, the ova were spontaneously ovulated and the mating period of the ova donors was short (06.00-09.00 hours). The embryonic cells proceeded through the first, second and third cell cycle as a cohort. Thus it was possible to estimate the duration of the cell cycle phases directly from the DNA histograms. The length of the cell cycle phases differed between the embryos of the two different mouse strains. The most pronounced differences were found for the G2 + M phases (first cell cycle: 8 hr for Strain I and 5 hr for Strain II; second cell cycle: 11.5 hr and 14 hr respectively). However, in accordance with previous investigations, common features of the early pre-implantation cell kinetics were also observed: increasing length of the S phases from the first to the second cell cycle and very short G1 phases in the second and third cell cycle. The cell proliferation of the embryos of both strains after the third cell cycle was characterized by exponential growth. The proliferation rate was higher in Strain I embryos than in Strain II embryos (steeper increase of the growth curve). At the end of the pre-implantation development (hatched blastocysts), the growth curves of both strains decreased. The differences concerning the durations of the cell cycle phases and the proliferation rates are considered to be strain specific. It is suggested that the differences in the pre-implantation cell kinetics which have been described generally reflect the strain specificities more than different investigational methods and/or different grades of synchrony of early pre-implantation embryos.

Animals↗
PubMed1982

[Irradiation of mouse embryos in pronucleus and 2-cell stages: dependence of micronucleus formation and cell proliferation upon DNA amount and cell cycle phase].

1-or 2-cell mouse embryos were X-irradiated with 1.88 Gy. At irradiation time both pronuclei of each 1-cell embryo (see introduction) had a haploid DNA-amount and were in G1-phase. In contrast the cell nuclei of the 2-cell embryos had a tetraploid DNA-amount and were in late G2. DNA-amount and the cell cycle phases respectively were determined cytofluorometrically. The blastocyst formation was more impaired after irradiation of 1-cell embryos (28%) than 2-cell embryos (73%; controls: 100%). Cell death, which was observed in the cell proliferation investigations, should be the most important reason for the impaired early embryonic development. The different extent of cell death can be explained with the different amount of micronucleus formation. This chromosomal damage, which leads to a hypoploid DNA-amount of the cell nuclei, was more bulky after irradiation of 1-cell embryos than 2-cell embryos. Mechanisms which could cause a higher micronucleus formation after irradiation of haploid cell nuclei (pronuclei) in G1-phase than after irradiation of tetraploid cell nuclei in G2-phase are discussed.

Animals↗
PubMed1981

Micronucleus formation in preimplanted mouse embryos cultured in vitro after irradiation with x-rays and neutrons.

Preimplanted mouse embryos cultured in vitro were irradiated with X-rays and neutrons in the late G2-phase of the 2-cell stage. Both radiation qualities induced micronuclei at very low doses. The kinetics of micronucleus formation during the first and second cell cycles after X-irradiation depended on the radiation dose and on the extent of the division delay. New micronuclei appeared to be formed even after the third and later post-irradiation mitoses. The shape of the various dose-effect curves and the mechanism of micronucleus formation by the two radiation qualities are discussed.

Animals↗
PubMed1980

Kinetics of cell proliferation in the pre-implanted mouse embryo in vivo and in vitro.

The cell proliferation of pre-implanted mouse embryos was investigated after development in vivo and in vitro. The studies were started at the pronuclear stage, 2 h post conception (p.c.) and continued until the hatching of blastocysts, 120-144 h p.c. The number of cell nuclei, the DNA content of each nucleus, the mitotic index and the labelling index were determined. From these data it was possible to calculate the length of the cell generation cycle and its various phases. With the exception of the first cell cycle the S-phase was constant. The G1- as well as the G2-phase varied in length during the different cell cycles. From 31-72 h p.c. the increase in cell number was exponential. After cultivation in vitro this increase was smaller than in vivo. At later periods the proliferation rate decreased with proceeding development. In late blastocysts most of the cells were in the G1-phase. The development of the embryos was somewhat faster in vivo than in vitro. But in principle conditions were comparable.

Animals↗
PubMed1976

Effect of catecholamines and sympatholytics on survival and circulatory parameters in protracted anaphylactic shock of guinea pigs.

Protracted anaphylactic shock of guinea pigs led to death in over 90% of the animals, and good protection was obtained with an infusion of adrenaline after dibenamine pretreatment. Adrenaline alone, in doses which prevented the anaphylactic fall of arterial blood pressure, had no beneficial effect. Practolol abolished the therapeutic action of the combination of dibenamine/adrenaline. Stimulation of beta-receptors by isoproterenol did not increase the survival rate. With dopamine, however, a significant prolongation of the survival times was obtained.

Anaphylaxis↗
PubMed1976

Influence of adrenaline, dibenamine and dopamine on acidosis, hemoconcentration and lethality in protracted anaphylactic shock of guinea-pigs.

Protracted anaphylactic shock of guinea-pigs was accompanied by a marked decrease in blood pH, and an increase in hematocrit. Death ensued in 58.3% of the animals within 3 hr of observation. Infusion of adrenaline (20 mug/kg/min), after eliciting anaphylaxis, intensified the acidosis, and increased the lethality to 100%. Pretreatment with dibenamine (5 mg/kg) reversed the effect of adrenaline. Dopamine, infused in amounts of 200 mug/kg/min, acted similarly to the combination dibenamine/adrenaline. Hemoconcentration was neither prevented nor intensified by adrenaline. Dopamine, however, reduced significantly the anaphylactic increase in hematocrit.

Acidosis↗
PubMedDate not supplied

Problems associated with CT-guided catheter insertions.

From October 1987 to August 1991 a total of 141 closed-tip catheters were inserted into deep-seated or half-deep-seated tumours in 95 treatment areas. Most of the catheters (n = 79) were implanted in the pelvic region. In 139 punctures no clinical evidence of bleeding was seen. A transient blood loss was evident in only two patients. In addition, no nerve injury was observed. The problems with 141 implanted catheters were evaluated. Nineteen catheters (13%) were lost during the treatment series. In five displacement of the catheters was verified by repeat CT scans during the whole treatment. Eight catheters had to be removed due to infection. In two patients with advanced disease who were receiving a combination of chemotherapy and hyperthermia a strong inflammatory response was evident. Another patient developed an acute pancreatitis after catheter insertion. No metastasis in the invasive tracks has been seen in the follow-up period. In conclusion the insertion of closed-tip catheters by CT guidance is a sure and well-tolerated method. There were a few problems only with the implanted catheters throughout the whole treatment series.

Catheters, Indwelling↗
PubMedDate not supplied

Clinical evidence for correlation of insufficient tissue oxygen supply (hypoxia) and tumor-associated proteolysis in squamous cell carcinoma of the head and neck.

Hypoxic tumors of patients with squamous cell carcinoma of the head and neck show a consistent trend towards poor treatment outcome. We now report that tumor hypoxia in these patients is correlated with elevated antigen content of the tumor-associated serine protease uPA (urokinase-type plasminogen activator), a marker of tumor cell invasion and metastasis.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Perspectives in the treatment of malignant gliomas in adults.

Over the last two decades, after establishing the role of postoperative radiotherapy for malignant gliomas, no definitive improvement in survival rate could be observed, despite advances in established treatment modalities such as radiotherapy and chemotherapy. Progress in exploration of the biology of these tumours allowed for translational research projects and the development of rational new approaches, such as gene therapy and immunotherapy, that could interfere with established treatment regimens or be used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called 'suicide genes'. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or 06-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro. This review discusses the available laboratory and clinical data as well as recent advances in our knowledge about prognostic and predictive factors and their implications for the design of future clinical trials.

Adult↗
PubMedDate not supplied

Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure.

BACKGROUND/AIMS: To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma. METHODOLOGY: Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission. RESULTS: Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients. CONCLUSIONS: The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.

Adenocarcinoma↗
PubMedDate not supplied

[Preoperative radio-chemotherapy and radical surgery for advanced carcinomas of the oral cavity. 4-year results of a prospective therapy study with DOSAK].

Based on the postoperative data evaluated in September 1989, the results of a regional prospective treatment study conducted by the DOSAK on preoperative radio-chemotherapy and radical surgery for carcinomas of the oral cavity and the oropharynx are presented. In the univariate analysis the histologic lymph node findings after pretreatment, the histologic grading, and the TPI correlated well with the survival rates. The multivariate analysis confirmed that the histologic demonstration of vital tumor cells in the neck lymph nodes after the end of pretreatment is of grat prognostic relevance. The histologic degree of differentiation, the demonstration of vital tumor cells in the primary tumor area after pretreatment and the length of time between radiotherapy and surgery were of secondary importance.

Adult↗
PubMedDate not supplied

[Preoperative irradiation, cisplatin sensitization and radical surgery of primarily operable carcinomas of the oral cavity. Results of a prospective DOSAK treatment study].

165 patients with carcinomas of the oral cavity or oropharynx, clinically appearing operable, were treated between 1985 and 1987 within the framework of a prospective multicenter study. The treatment concept consisted in preoperative irradiation with 32 Gy, cisplatin sensitization with 5 X 20 mg per m2 body surface area and subsequent radical removal of the primary tumor and the regional cervical lymph nodes. Regarding recurrence and survival rates the patient data were analyzed using one- and multi-dimensional statistical methods. The observed survival rates were compared with those assessed with the aid of the treatment-dependent prognosis index TPI (Platz et al. 1982). After 1 years the survival rates under the selected combination therapy were 12% and after 2 years 19% above the assessed survival rates under radical surgery alone.

Cisplatin↗