Stochastic and deterministic radiation carcinogenesis.
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Bone Neoplasms↗
Biomedical subjects
W A Müller
Publications and source records attributed to W A Müller.
[Malignant melanoma in life insurance--thickness or anatomic layer?].
The incidence of malignant melanoma has tripled during the last 40 years and continues to increase. Among clinical criteria the single and most significant prognostic factor is the extent of tumor invasion expressed by thickness rather than anatomical structure. Patients with melanoma thinner than 0.76 mm have a five year survival of 96%. Thicker tumors bear a poor prognosis. Patients having survived 10 years have a life expectancy close to the normal population.
Cause of Death↗
Effect of smoking cessation on mortality of older men and women with coronary artery disease.
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Aged↗
Radiation-induced systemic and local bone tumors: two types of late effects with possible different origins?
Bone sarcomas may be induced throughout the skeleton (systemic) in mice by relatively low internal alpha-particle doses that are distributed over the whole skeleton. The induction of local (periosteal) bone sarcomas after paratibial deposition of insoluble radiocolloids required much higher doses, and in addition high energies of emitted particles. Paratibial deposition of alpha-particle-emitting radiocolloids of 227Th and 228Th resulted in formation of both local and systemic bone sarcomas. The latter were most probably induced by the released radium daughters of the thorium isotopes and were distributed about the skeleton. Paratibial injections with beta-particle emitters 144Ce+ 144Pr (29 kBq per mouse) showed an incidence of local bone sarcomas of more than 80%. An estimation of the local effective doses led to values of more than 1000 Gy for the beta-particle emitter 144Ce and around 150 Gy for the thorium isotopes. Thus induction of local bone sarcomas required doses considerably greater than those needed for systemic bone sarcomas. The local induction of bone sarcomas has been reported for high-energy beta particles using similar high doses of 144Ce+ 144Pr in rats and for external 90Sr+ 90Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different.
Animals↗
Ocular toxoplasmosis: the role of cellular immune defense in the development of recurrences. Results from animal experiments.
Five toxoplasmosis-free animals and ten animals that had been immunized intraocularly against toxoplasma organisms were used in a rabbit model of ocular toxoplasmosis. Five of the ten immune animals were immunosuppressed by cyclosporin A at a cellular level. Experimental toxoplasmic retinochoroiditis occurred in all animals, a process that in complete contradiction to experience reported previously. In the rabbit model, immunity after a past history of toxoplasma infection has thus far appeared to be a safe form of protection from experimental ocular toxoplasmosis. The concept of "immunological privilege of the eye" is discussed as the cause for the unexpected results.
Animals↗
An identical epitope in Pneumocystis carinii and Toxoplasma gondii causing serological cross reactions.
A monoclonal antibody raised against membrane proteins of Toxoplasma gondii with molecular weights of 35 and 21 kDa also reacts strongly and "specifically" with surface antigens of Pneumocystis carinii with molecular weights of 394.2 and 69 kDa when used in a direct immunofluorescence antibody test, on the one hand, and in a immunoblot after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), on the other. Whether or not this observation might have any phylogenetic relevance remains open.
Animals↗
Bone tumor induction after incorporation of short-lived radionuclides.
Temporally-limited internal irradiation after incorporation of short-lived bone-seeking radionuclides is a useful experimental tool for the investigation of extrinsic and intrinsic factors which modify the dose dependence of bone tumor risk. Here we describe some of the results obtained in experiments with female mice (mainly NMRI). The future aim of such experiments should be the prediction of risk of late effects using early molecular-biological changes. Molecular-biological descriptions in our model are at present very limited.
Animals↗
Stimulation of head-specific nerve cell formation in Hydra by pulses of diacylglycerol.
In Hydra magnipapillata, repeated pulses of diacylglycerol (DG) induce a lengthening of the body column and the formation of ectopic head structures (Müller, 1989). In the present study, seven pulses given on 7 successive days led, in the gastric region, to a 1.87-fold increase in the number of epithelial cells from 16,200 to 30,400; a 4.6-fold increase in the total number of nerve cells from 2900 to 13,400; and an 18-fold increase of RF-amide immunopositive nerve cells from 100 to 1800. This subset of neurons, which is normally distributed in the form of a density gradient having its high point around the mouth and ending below the tentacle whorl in the upper gastric column, displays an altered pattern in DG-treated animals. While the density peak in the original head persisted, a second peak developed in the lower gastric region at the site of imminent ectopic tentacle formation, reflecting the local increase in positional value. Thus, the temporal sequence in which DG-induced ectopic apical body structures arise is a function of the rise in positional value and reflects the normal spatial sequence of these structures along the body column: first RF-amide neurons appear, then tentacles, and finally hypostomes.
Animals↗
SIF, a novel morphogenetic inducer in hydrozoa.
By analogy to processes in angiogenesis (blood vessel formation), the development of the stolonal network in colonial hydrozoa involves stimulation of branching and mutual chemotropic attraction of the growing branches by means of soluble morphogenetic factors. We have identified a glycoconjugate of about 20 kDa, termed SIF (Stolon-Inducing Factor), which induces the formation of stolon branches when applied locally. Micropipettes ejecting SIF mimic the inducing action of stolon tips, the putative sources of SIF. When whole animals are exposed to SIF, stolons sprout not only from the base of the polyps but also from abnormal sites along the entire body, even from the head. In addition, the polyp (hydranth) secretes a chitinous periderm which, in the species under investigation, normally envelops stolons but not hydranths. At high SIF doses the whole hydranth is transformed into stolon tissue. The factor has been isolated from conditioned medium and from butanol extracts of Hydractinia echinata and Podocoryne carnea.
Animals↗
Identification of a virulence-associated antigen of Toxoplasma gondii by use of a mouse monoclonal antibody.
A monoclonal antibody generated against the mouse-lethal RH strain of Toxoplasma gondii was developed. Tachyzoites of virulent and avirulent T. gondii isolates grown in permanent macrophage cell cultures were examined for differences in reactivity with this antibody. Virulence of these Toxoplasma isolates was quantified by injecting different numbers of tachyzoites into NMRI mice and observing the animals for signs of infection or death. The monoclonal antibody identified a 23-kDa antigen expressed by the mouse-lethal strains BK and RH, whereas this antigen was not detected in low-mouse-virulent strains, which were all clinical isolates from Europe. Using Western blot (immunoblot), immunofluorescence, and immunoelectron microscopy, we localized the 23-kDa antigen to the membrane compartment. From these results, we suggest that this 23-kDa antigen is a marker of strain virulence upon which a virulence classification of T. gondii may be based.
Animals↗
[Experimental animal studies for the detection of circulating Toxoplasma antigens].
Rabbits and mice were infected by Toxoplasma gondii (RH and HanR) and Hammondia hammondi. An enzyme immunoassay with monoclonal antibodies was used to reveal circulating Toxoplasma antigens. They were found only in mice and rabbits that had been infected by the cyst-forming strain Toxoplasma HanR. In mice infected by Hammondia hammondi low antibodies titres were found that showed a cross-reaction with Toxoplasma. The enzyme immunoassay for evidence of Toxoplasma antigens demonstrated a negative reaction in these animals.
Animals↗
Induction of lymphoma and osteosarcoma in mice by single and protracted low alpha doses.
Internal doses from the short-lived alpha-emitter 22Ra were given to 4-wk-old female NMRI mice. One group of about 300 animals received a single injection of 18.5 kBq 22Ra kg-1 body weight, corresponding to a mean skeletal alpha dose of 0.15 Gy. A second group of about 300 animals received the same total amount of 224Ra in the form of 72 fractions of 257 Bq kg-1 each, applied twice weekly during 36 wk. The fractionated group received the same final mean total skeletal dose of 0.15 Gy as the single injected group, but with a mean skeletal dose rate of 1 mGy d-1. A rather high incidence, 13.5% (40/296), of early malignant lymphomas was observed in the fractionated group during and shortly after the injection period, followed by a 7% incidence (21/296) of osteosarcomas during the second half of the animals' lifetime. The group with a single injection did not develop early lymphomas but did develop osteosarcomas later with an incidence of 5.8% (17/295). The occurrence of osteosarcomas was similar up to day 800 in the two experimental groups. Surprisingly, however, after this period no additional case of osteosarcoma was observed in the single-injected group, whereas one-third of all osteosarcomas occurred after day 800 in the protracted group. The additional later occurrence of osteosarcomas occurred after indicates a longer lasting induction effect on osteosarcomas, or a promoting effect in older age, for this kind of treatment.
Alpha Particles↗
Ectopic head and foot formation in Hydra: diacylglycerol-induced increase in positional value and assistance of the head in foot formation.
In wild type Hydra magnipapillata, daily application of the protein kinase C activator diacylglycerol (DAG) evokes sprouting of periodically spaced ectopic heads along the body column and leads to loss of the ability to regenerate proximal structures including the foot. The present transplantation studies show that the appearance of ectopic heads is preceded by an early increase in the 'positional value' (P-value) or 'head activation potential' of the gastric column. Long before ectopic head structures emerge, pieces of DAG-treated tissue transplanted into the corresponding positional level of untreated hosts induce head formation instead of being integrated, whereas pieces implanted from untreated donors into DAG-treated hosts form feet. Foot formation implies a decrease in the P-value. This down-regulation is promoted through long-range assistance by the head. Thus, after termination of the DAG treatment ectopic feet are intercalated midway between the periodically spaced heads; moreover, untreated polyps onto which additional distal heads have been grafted regenerate feet faster than do one-headed polyps and may form supernumerary feet. Multiheaded animals can also be produced using two substances (K-252a and xanthate D609) that interfere with signal transduction, but the mode by which secondary heads arise is different from DAG-induced ectopic head formation. Presumably because the assistance by the parental head is impaired, buds fail to form a foot and detach and instead give rise to stable secondary body axes. It is assumed that the P-value along the body varies according to the number of cellular receptors for factors serving as intercellular signals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Detection of antibodies against Toxoplasma gondii in human sera in immunoblot procedures].
Proteins of Toxoplasma lysate were separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to a nitrocellulose sheet by electrophoretic blotting. Patient human sera reacted predominant with protein fractions of Toxoplasma antigen of 94 kD and 35 kD. Human sera were tested by Toxoplasma-IgG ELISA and Immunofluorescence assay (IgG-IFAT, IgM-IFAT).
Animals↗
Osteosarcoma risk after simultaneous incorporation of the long-lived radionuclide 227Ac and the short-lived radionuclide 227Th.
The effect of injection of 1.85 kBq/kg of the long-lived radionuclide 227Ac on the induction of osteosarcomas in female NMRI mice by different dose levels (18.5, 74, and 185 kBq/kg) of the short-lived radionuclide 227Th was investigated. The highest absolute osteosarcoma incidence was observed with the highest doses of 227Th. Addition of 227Ac resulted in an additional osteosarcoma incidence only at the lowest dose of 227Th and did not affect the osteosarcoma incidence resulting from higher doses of 227Th. The longest times to tumor appearance were observed with 227Ac alone. The latent period in two different age groups (4 weeks and 10-12 weeks) appeared to be similar following injection with combined doses of 227Th and 227Ac but different after injection of each radionuclide alone.
Actinium↗
[Hip joint endoprosthesis and metal sensitivity. Studies using the leukocyte migration test].
The Leukocyte-Migration-Test (LMT) is a sensitive method for the proof of metal sensitivity in organism. There were no difference in the sensitivity of chromium, cobalt and/or nickel in 42 patients suffering for coxarthrosis and 41 patients after total hip replacement. We found no connection between metal sensitivity and loosening of artificial hip joints in two groups of patients suffering as well from metal sensitivity as from loosening of the artificial hip joint.
Cell Migration Inhibition↗
[Characterization of monoclonal antibodies to Toxoplasma gondii].
Proteins of Toxoplasma lysate were separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to a nitrocellulose sheet by electrophoretic blotting. The range of protein bands was 6-100 kD. Monoclonal antibodies 1B2, 5B10, 4F6 reacted with antigens of 21 kD, 35 kD and 66 kD. Monoclonal antibodies reacted with major antigens of the RH-tachyzoiten surface and HanR-cysts.
Animals↗