Successful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow.
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Animals↗
Biomedical subjects
R F Meredith
Publications and source records attributed to R F Meredith.
Genetic influence in murine viral leukemogenesis.
Studies carried out over the past four decades on factors controlling the susceptibility to viral leukemias in mice have shown the existence of specific controlling gene loci. Evidence from a number of studies using various mouse strains and different leukemia viruses has shown that the controlling genes may act either directly or indirectly. "In vitro" experiments have shown controlling effects directed by the prospective target cells themselves in which effective virus infection and/or and/or replication is inhibitied. From "in vivo" experiments it is also evident that susceptibility may be controlled through indirect means mediated by immune relationships and other factors involved in the basic regulations of hematopoiesis. The present paper presents a brief review of the various genes known to control susceptibility and resistance to murine leukemia viruses. Certain conflicts in the literature relating to the naming of particular specific genes by different laboratories is also discussed, and some minor revisions in nomenclature designed to resolve some of the existing confusion are proposed.
Animals↗
Dosimetry of solid tumors.
Dosimetry data arising from a decade of radioimmunotherapy are summarized along with techniques utilized to arrive at the reported dose estimates. Generality of the MIRD methodology allows it to serve as a vehicle for the calculation of solid tumor dosimetry although several limitations exist. Nonstandard geometries of solid tumors will ultimately necessitate determination of absorbed fractions for the individual tumors. Several approaches currently under investigation are described. For reasons of practicality, solid tumor dosimetry estimates continue to use the assumption of homogeneous activity distribution in a source organ, accounting for either all radiation or only nonpenetrating radiation. As computation tools become available for incorporating inhomogeneous cellular level data, the currently used "average dose" as an index of tumor sterilization will likely be replaced with a statistical distribution based on the number of viable cells in the tumor volume. Estimates of a tumor control dose would be based upon a linear extension of dose coupled with a threshold dose for cell sterilization.
Humans↗
Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds.
Investigations with thermally self-regulating ferromagnetic implants (thermoseeds) were done on healthy rats and pet animals with spontaneous and transmissible venereal tumours (TVT). The thermoseeds were produced from a nickel-copper alloy and electroplated with a gold-silver layer. Manufacturing conditions were varied to produce thermoseeds with various operating temperatures, the critical temperature above which heating power production sharply declines. To test for toxicity, thermoseeds were implanted into the liver of rats and left in place for up to 14 months. While atomic absorption spectroscopy showed increased nickel and copper levels in tissues near the implants, no clinical evidence of ill-effects was noted. For hyperthermia treatment, thermoseeds were implanted into tumours of pet animals, and these were placed into an induction coil which produced an 89 kHz frequency, 4000 A/m amplitude field. The highest recorded tumour temperature correlated with the nominal operating point of the thermoseeds, demonstrating their ability to regulate the temperature. Of the 15 evaluable animals with spontaneous tumours treated, 12 received concomitant 60Co radiation (two of them only after tumour recurrence following an initial treatment course of hyperthermia alone). Five of those treated with both modalities experienced complete response, five responded partially and two had no change. The treatment course of hyperthermia alone resulted in one animal achieving a complete response, and in three partial responders. Animals bearing TVT had a complete local response with hyperthermia alone. Massive tissue necrosis and seed migration caused the major treatment-related toxicity. Our findings suggest that self-regulating thermoseeds offer the possibility of predictable heat delivery to defined tissue volumes, and may be useful in the treatment of human tumours which are amenable to implantation. Until migration can be controlled, clinical trials should be limited to removable implants.
Animals↗