Thomas E. Fritz

Pathology and familial incidence of orchitis and its relation to thyroiditis in a closed beagle colony

Abstract Lymphocytic orchitis occurs spontaneously in a closed colony of beagle dogs with an incidence of 32% among 69 untreated males over 1 year of age. This disease is genetically influenced as determined by an analysis of the ancestral composition of each animal. Orchitis is related in its occurrence to lymphocytic thyroiditis which has been previously described in this colony. The incidence of both diseases increases with increasing degrees of relatedness to three sibling progenitors of a partially inbred line which comprises a significant portion of the colony. Among the dogs that derived all of their genes from the three progenitors, 85% had lymphocytic thyroiditis and 65% had lymphocytic orchitis. The pathologic changes in the testes result in a significant reduction in testis size and weight as well as sterility or reduced fertility.

RESPONSE OF THE BEAGLE DOG TO

The

sup 60

{\rm LD}_{50(30)}

Co GAMMA RADIATION: DETERMINATION OF THE LD/sub 50(30)/ AND DESCRIPTION OF ASSOCIATED CHANGES.

of

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

{}^{60}{\rm Co}\ \gamma \text{-radiation}

Circulating Micromegakaryocytes Preceding Leukemia in Three Dogs Exposed to 2.5 R/day Gamma Radiation

, given as a single, bilateral exposure at a rate of approximately 15 R/min to the whole body of 13-month-old, purebred beagle dogs, was determined to be 258 rads, expressed as the average absorbed dose. The method for computing radiation dose allows compensation for the individual variations in size of dogs. This has a significant effect on the overall result. Detailed examination of the dogs-by clinical methods, hematology, blood biochemistry, and gross and microscopic inspection of tissues-led to the conclusion that acute bacteremia, secondary to bone marrow damage was the primary cause of death. There were no sex-related differences. Bacteremia intervenes in the progression of the radiation syndrome as the granulocyte count approaches the critical level of about

Continuous Irradiation of Beagles with Gamma Rays

1000\ \text{cells}/{\rm mm}^{3}

Acute Monocytic Leukemia in an Irradiated Beagle

of blood. Thus the complete expression of biologic response versus radiation dose is masked by the invasion of bacteria. The effect of such...

Biological effects of 137CsCl injected in beagle dogs of different ages

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Responses of the Beagle to Protracted Irradiation' I. Effect of Total Dose and Dose Rate

The presence of micromegakaryocytes in the blood and bone marrow of humans during the preleukemic phase of acute and chronic myelogenous leukemia and myelomonocytic leukemia is well documented [I, 4, 5, 7, 8, 10, 15), and it has been suggested that it is the single most typical abnormality suggesting a subsequent course towards overt leukemia (6). Three adult purebred beagles that died with myelogenous leukemia during continuous whole-body exposure to 2.5 roentgens/22-hour day of 6OCO gamma irradiation had micromegakaryocytes and megakaryoblasts in the peripheral blood three to ten weeks before leukemic myeloblasts were observed in buffy coat preparations. The cells of interest were 6 to 30 JLm in diameter, mono-, or binucleated, with round or oval nuclei, indistinct nucleoli, and they had a high nuclear/cytoplasmic ratio (fig. I). Many cells had cytoplasmic blebs (fig. 2). Cytochemical characterization revealed strong positive staining for both acetylcholinesterase, and a-naphthyl acetate esterase, as well as abundant glycogen with the periodic acid-Schiff stain. The cells were negative with Sudan black, and no detectable myeloperoxidase or naphthol AS-D chloroacetate esterase activity was seen. Other hematologic abnormalities observed during this preleukemic period included progressive refractory anemia, occasional nucleated red blood cells, anisopoikilocytosis, monocytosis, giant platelets, and a left shift to metamyelocytes. Over the same period, bone marrow preparations from iliac crest aspirates and rib biopsies revealed granulocytic hyperplasia with a moderate left shift but without an excess of myeloblasts. There was also erythroid depletion, and increased numbers of mono-, bi-, and multinucleated megakaryocytes (fig. 3). Ultrastructural characterization clearly indicated the cells to be micromegakaryocytes and megakaryoblasts. Even in the most immature cells, the cytoplasm contained both dense serotonin granules and the characteristic a (bulls-eye) granules, indicating their megakaryocytic lineage (fig. 4). Although the majority of micromegakaryocytes showed dysgenesis of the demarcation membrane system, the cytoplasm did contain smooth, membranous vesicular sacs of a rudimentary demarcation membrane system (fig. 4) and in a few cells there were flattened, laminar cisternae of the demarcation membrane system with peripheral formation of dystrophic (i.e., agranular, giant) platelets. Terminally, the dogs were severely anemic (0.94, 1.10, and 1.70 X 10 red blood cells/ul), and thrombocytopenic (5.0, 7.5, and 90.0 X 10 Total leukocyte counts were 11.5, 14.8, and 57.1 X 10/ JLI, respectively. The terminal peripheral blood differential leukocyte count showed a marked left shift (17%myeloblasts) in only one dog. However, bone marrow imprints obtained at necropsy from sternum, rib, and femur showed, in all dogs, a granulocytic hyperplasia with maturation defects and myeloblast counts of 21.0, 11.0, and 35.5% of the total granulocytic series. In all dogs there was a paucity of erythroid elements and in only one dog were there a few remaining megakaryocytes.