Organ distribution studies of lutetium-177 in mouse.
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Biomedical subjects
Publications and source records attributed to W A Müller.
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224Ra is used within the therapy of rheumatoid arthritis. The distribution of this radionuclide in the organism was investigated up to 7 days after incorporation in order to estimate a possible risk of late effects. In the autoradiographs we found strong blackenings at those bonesurfaces which faced the injected knee-joint hole. In addition the radionuclide was deposited in skeletal growth-zones similarly as after i.v. and i.p. injections. The dosimetric data (particularly of knee-joint and skeleton) were calculated and compared with those which occur after the therapy of ankylosing spondylitis using i.v. 224Ra injections.
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The release of glucagon induced in isolated rat islets by arginine or by calcium deprivation has been subjected to combined functional and morphological quantifications. Arginine-stimulated glucagon release was associated with a significant increase of morphological events linked to exocytosis. By contrast, the paradoxical events linked to exocytosis. By contrast, the paradoxical release of glucagon provoked by calcium deprivation, although accompanied by a significant loss of granule stores, was not associated with an increase of morphologically detectable exocytosis.
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Single and repeated applications of 224Ra and single applications of 227Th to more than 600 female NMRI mice 3 - 4 weeks old, and to male NMRI mice have led to a high rate of osteosarcomas. Tumor incidence is dose-related. 227Th is more carcinogenic than 224Ra which induced the highest tumor incidence of 60% after a single injection of 5 muCi per Kg body weight or more. Repeated injections of 224Ra to female mice yielded a tumor incidence of up to 92%. Most of these osteosarcomas consist of well-differentiated bone-forming osteoplastic tissue. Half of the tumors occurred in the spine, particularly in the lumbar region. In protraction experiments, multifocal osteosarcomas have been observed. Less than 10% of the mice with osteosarcoma had developed metastases in lung, spleen, liver, and kidney. The possible mechanisms of the protraction effect are discussed.
The importance of glucagon in the regulation of carbohydrate metabolism is clearly established. However, the role played by this hormone in the regulation of the overall fuel economy is less certain, particularly with respect to such nonglucose fuels as free fatty acids, glycerol, and ketoacids. In order to elucidate glucagon's role with respect to the latter substrates, dogs were infused with solutions of these three fuels, and their A-cell responses to concomitant insulin-induced hypoglycemia were studied. In addition, epinephrine levels were also monitored. It was found that while these infusions failed to suppress glucagon release, the ketoacid infusion did significantly reduce epinephrine secretion during the insulin-induced hypoglycemic period. It was therefore concluded that glucagon secretion under these experimental conditions is not responsive to prevailing non-glucose fuel levels. Indeed, these data suggest that the sympathetic nervous system may play an important role in the regulation of the over-all fuel economy.
To characterize further the role of blood cells in amino acid transport, four normal volunteers were asked to ingest 200 g of broiled ground sirloin within a 10-min period. Blood samples from a radial artery, a deep vein draining forearm muscle bed, and a tributary of the hepatic vein were obtained prior to and for 4 hr after the meal and analyzed for various hormones and substrates. At rest, analysis of arterio-deep venous differences across the forearm revealed the blood cell and plasma amino acid compartmentmental contents to be relatively constant except for alanine and glutamine. Whole blood arterio-hepatic venous (A-HV) amino acid differences were not significantly different from zero; however, blood cell A-HV difference analysis revealed a significant release of threonine from the splanchnic bed while plasma A-HV difference analysis revealed modest but significant releases of glutamate and ornithine and uptakes of phenylalanine and histidine. After the ingestion of the meat meal, plasma and blood cell levels of almost all of the measured amino acids increased significantly. Notable exceptions included glycine and alanine, levels of which did not change significantly and glutamine. The arterial blood cell content of the latter amino acid paradoxically decreased while arterial plasma levels increased significantly. Most importantly, large quantities of branched chain amino acids were released from the splanchnic bed and removed by forearm muscle. These data suggest that the blood cells of normal man do actively participate in amino acid transport, and that the magnitude and direction of change induced by the ingestion of a proteins meal varies with the individual amino acid.
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It is reported on the affection with intestinal parasites in 438 persons who returned from the tropics. In these test persons were also established only those species of parasites which were proved in the Dresden inhabitants. However, there were remarkable quantitative differences between the affection of the persons returning from the tropics and the Dresden inhabitants. Thus by laboratory examinations in Dresden in the persons returning from the tropics were established infections with Entamoeba histolytica (7.0%), with Dientamoeba fragilis (17.9%), with Lamblia intestinalis (9.0%) as well as with Trichuris trichiura (3.4%), where as the extensity of affection with the corresponding parasites is for the Dresden inhabitants 1.9%, 4.7%, 5.0%, and 1.6%. It is referred to the fact that all persons who returned from the tropics should parasitologically be examined for an infection with Entamoeba histolytica.
It is reported on the data of helminthological investigations performed on 1323 Dresden inhabitants at the age of 14 to 70 years. Furthermore the notifications of the affections with tapeworm which had come into the district hygiene inspection of Dresden were evaluated. An affection with Ascaris lumbricoides of 1.2%, with Trichuris trichiura of 1.6%, with Enterobius vermicularis of 14.5% and with Taeniarhynchus saginatus of about 1% were proved. In the case of Enterobius vermicularis the for the most part affected age groups were the 14- to 20-year-old test persons and concerning Taeniarhynchus saginatus the 21- to 70-year-old test persons. Accumulations of the extensity of the affection with helminths bound to a species of hosts were not detected. Concerning the taeniarhynchosis since 1966 a permanent increase of the extensity of affection is to be registered. The duty of notification concerning taeniarhynchosis is often neglected. Only about 1/6 of the affection with tapeworm is notified in the district hygiene inspection.
After a description of modern knowledge of the biology and epidemiology of toxoplasma gondii the author enters into the affection in Dresden inhabitants. Males as well as females at the age of 16 to 60 years are infected on the average at 74%. The most frequently affected age groups are the 41-year-old to 50-year-old persons. IFAR-titres to 80 are very frequently to be found in clinically healthy probands and, as a rule, plead for the existence of a latent toxoplasma affection. Titre values of more than 80 should always give rise to repeated examinations.
227Th (alpha-emitter, half-life 18.7 days) was inhaled by rats from solution in nitrate form. Organ doses were calculated after whole body measurements and measuring of activity concentrations in the organs over a longer incorporation period. An initial deposition of 100 nCi 227Th in the lung resulted in mean total doses of 150 rad in lung and 36 rad in bone. The data for kidney and liver were 2 rad and 0.1 rad, respectively. For long-term experiments two dosages were applied to two groups of animals with mean values of 900 rad and 300 rad in the lung. The consequences for lung and bone tumor induction are discussed.
The protein-sparing capability of glucose was investigated in overweight subjects prior to and during the performance of prolonged therapeutic fasts. Blood (for hormones and substrates) and urine (for nitrogen and ketoacids) specimens were collected prior to, during, and subsequent to the performance of the following studies. Three subjects ingested, as their only source of calories, 37.5 g of glucose every 6 hours for 7 days (glucose I). The same group of subjects was then fasted for 3 weeks following which the above glucose protocol was repeated (glucose II). In both groups, glucose administration diminished nitrogen excretion, urea being decreased in the first group and ammonia in the second.
Changes in blood levels of glucagon, insulin and glucose in response to infusions of alanine and glycine have been studied in postabsorptive and fasting obese human subjects. Four-to-five-fold elevations of baseline plasma alanine levels stimulated glucagon secretion significantly. Supraphysiological plasma levels of glycine had a small but insignificant stimulatory effect on glucagon secretion. The glucose increase (6 to 10 mg per 100 ml) observed within 30 min of a supraphysiologic alanine infusion in subjects fasted for 2 or more weeks may be secondary to glucagonmediated glycogen breakdown. However, despite equivalent glucagon rises in the other two study periods, no significant rise in blood sugar was noted during the period of infusion.
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