Dennis Giuliani

Effect of mercuric chloride and methylmercury chloride exposure on tissue concentrations of six essential minerals

There are few data on the effects of mercury exposure on tissue concentrations of essential minerals. Male Sprague-Dawley rats were exposed to mercuric chloride and methylmercury chloride administered via the drinking water. Subsequently, the kidneys, spleen, liver, and brain were analyzed for mercury, calcium, copper, magnesium, manganese, iron, and zinc by atomic absorption spectrophotometry. Significant differences from controls were found for brain copper, kidney copper, and kidney zinc in the mercuric chloride-exposed animals; and for brain iron, kidney copper, kidney iron, kidney magnesium, spleen magnesium, and liver manganese in the methylmercury chloride-exposed rats. There was a fivefold higher mean kidney copper concentration in the mercuric chloride-exposed group; this may be related to the induction of renal metallothionein synthesis by mercury. Increased kidney copper may be a manifestation of heavy metal-induced renal toxicity. Both inorganic and methylmercury exposure produce significant changes in tissue concentrations of some essential minerals.

ADAPTATION OF HEMOPOIETIC TISSUE RESULTING FROM ESTRONE‐INDUCED OSTEOSCLEROSIS IN MICE

The redistribution of hemopoietic tissue resulting from estrone‐induced osteosclerosis in the mouse was studied. As the marrow was gradually replaced by bone, extramedullary hematopoiesis in the spleen increased at a rate sufficient to maintain hemopoietic homeostasis.

Erythropoiesis in pyridoxine deficient mice.

Summary Mice maintained on a pyridoxine deficient diet developed a progressive anemia characterized by hypochromia, microcytosis, reticulocytosis, and erythroid hyperplasia of the marrow and spleen. Circulating siderocytes were greatly increased. Hypertransfusion of these animals with red cells obtained from pyridoxine deficient donors resulted in erythroid aplasia. The response to exogenous erythropoietin was comparable to that observed in erythropoietin treated control hypertransfused mice. These data indicate normal erythroid differentiation and maturation in pyridoxine deficient mice. The authors thank Drs. H. Baker and O. Frank of the East Orange Veterans Administration Hospital, East Orange, New Jersey for the pyridoxine assays. The erythropoietin was collected and concentrated by the Department of Physiology, University of the Northeast, Corrientes, Argentina, further processed and assayed by the Hematology Research Laboratories, Childrens Hospital of Los Angeles, under Research Grant HE 10880 (National Heart and Lung Institute).

Potential effectiveness of stored cord blood (non-frozen) for emergency use

Bone marrow has been used for a number of years to assist patients who have accidentally received potentially lethal levels of irradiation. The intent of the transplant is to replace the victims own bone marrow that has been injured from the irradiation or to act as temporary support to allow the patients own marrow to recover. Following the Chernobyl disaster, some victims received bone marrow that was HLA matched or partially matched. However, donor marrows were difficult to obtain in adequate numbers; as a substitute for bone marrow, frozen fetal liver cells were used as a source of hematopoietic stem cells. The use of fetal livers, however, was unsuccessful. Human umbilical cord blood, currently considered an excellent source of hematopoietic stem cells, was not used at Chernobyl. For several years, we have been able experimentally to keep SJL/J mice alive with the use of human umbilical cord blood after the animals received lethal levels of irradiation. This finding suggests that under certain conditions human cord blood does not have to be HLA matched to facilitate rescue from irradiation. In addition, there are reports of unmatched HLA cord blood being used successfully for marrow transplantation. If human cord blood does not have to be matched for HLA, there may be emergency cataclysmic circumstances where the availability of umbilical cord blood may be of considerable value. To simulate a clinical situation such as a nuclear accident, in which human cord blood might serve as a source of stem cells for marrow transplantation, we attempted to rescue immunocompetent mice after 900 cGY of irradiation with the use of (nonfrozen) human cord blood stored in a blood bank. The blood was stored under routine conditions (3-6 degrees C) for 5 and 7 days in special bags that allow transmission of oxygen. Following lethal levels of irradiation, the cord blood was administered to the animals and a significant survival rate was obtained.

Murine survival of lethal irradiation with the use of human umbilical cord blood

We have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over seventy percent (70%) of mice injected with HUCB survived 900 cGy or irradiation, which produced 100% deaths in the uninjected control animals. Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti-Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation.

Effects of Radiation on Bone Formation: A Functional Assessment

MORSE, B. S., GIULIANI, D., AND GIULIANI, E. R. Effects of Radiation on Bone Formation: A Functional Assessment. Radiat. Res. 60, 307-313 (1974). A reduction of estrone-induced endosteal bone formation was noted in the tibia of mice locally X-irradiated with doses in excess of 900 R. When estrone injections were started 4 days postirradiation, increased bone formation was noted between 300 and 900 R. As the dose of radiation was increased above 900 R, there was a progressive impairment of the response to estrone injections. Bone formation, though substantially reduced, was still demonstrable after 2220 R. Little recovery was noted over a 7-mo period following this dose. A functional separation of hemopoietic and osteogenic precursor cells was achieved; the former displayed greater radiosensitivity than the latter.

Chromium-51 dosimetry of lymphocytes labeled incidentally during nuclear medicine procedures☆

Conventional dosimetry based on MIRD procedure fails to consider the localized energy deposition from the radionuclides decaying by the emission of Auger electrons. The cellular dosimetry of human peripheral blood lymphocytes labeled with 51 Cr, an Auger electron emitter, was calculated. Conventional dosimetric calculations reveal a dose of 0.024-0.17 rad/h/tube. In contrast the lymphocyte dose ranged from 0.053-0.339 rad/h with projected cumulative values of 51-324 rad for surviving lymphocytes.