Diagnostic exercise: cutaneous lesions in frogs.
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Animals↗
Biomedical subjects
L C Stephens
Publications and source records attributed to L C Stephens.
Epidermal capillariasis in South African clawed frogs (Xenopus laevis).
Significant morbidity and mortality of South African clawed frogs, Xenopus laevis, can be caused by parasitism of the epidermis by a capillarid nematode. These worms produce an erosive dermatitis that is complicated by infection with gram-negative microorganisms. The nematode apparently has a direct life cycle that can be completed within the epidermis of the frog. These characteristics are suggested by the lack of an intermediate host and failure to detect visceral migration. Another unique feature of the parasite was the presence of larvated eggs, in utero. Some have named the parasite Capillaria xenopodis, whereas others called it Pseudocapillaroides xenopi to distinguish it form the typical members of the genus Capillaria.
Animals↗
Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.
The dose effects of continuous alpha-difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene-induced sarcoma received intravenously either 0.45% NaCl or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose-related inhibition of tumor growth was noted after the 12-day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet suppression was associated with the 1,000- and 2,000-mg doses with the 12-day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000-mg dose, but none of the animals developed diarrhea. The 500-mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500-mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose-limiting side-effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.
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Survival in radiation myelopathy.
Survival in radiation myelopathy has been the subject of analysis. Factors affecting survival are the level of the lesion, the age of the patient, and the latent period of the injury. The influence of age and level of the lesion is compared with the effects of these same parameters in traumatic myelopathy. Patients with cervical cord lesions have more rapid morbidity in both radiation and traumatic myelopathy. For thoracic but not cervical lesions, younger patients have a greater survival expectation than older patients. Patients with shorter latent periods have a more rapid mortality in cervical radiation myelopathy, but no demonstrable effect is seen in thoracic radiation myelopathy.
Adult↗
Target cell and mode of radiation injury in rhesus salivary glands.
Morphological alterations of parotid and submandibular salivary glands of rhesus monkeys were studied 1-72 h and 16-40 weeks postirradiation (PI) with single photon doses of 2.5-15.0 Gy, or 10.2 Gy given in 6 fractions. Acute degeneration and necrosis of serous cells in both parotid and submandibular glands were clearly expressed by 24 h PI and occurred in a dose-related fashion. In submandibular glands, doses of 12.5 or 15.0 Gy damaged mucous cells, but to a considerably lesser extent than the serous cells in the same glands. No significant sparing was evident with dose fractionation. These observations demonstrate the unique sensitivity of serous cells which appear to undergo interphase cell death after irradiation. The results also show that late atrophy was the direct result of acute loss of serous acini and reflects a lack of regeneration of acinar cells receiving acute injury.
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Mechanisms of synergism between arteriolar embolization and hyperthermia in a rabbit V-2 model of solitary hepatic metastasis.
In a V-2 model of solitary hepatic metastasis, residual tumor was histologically identified in the treatment field in only three of 14 (21%) animals subjected to microsphere embolization of tumor arterioles plus focal (43 degrees C, 40 min) hyperthermia compared with seven of ten (70%) subjected to focal (43 degrees C, 40 min) hyperthermia alone (P less than or equal to 0.05), five of seven (71%) (P less than or equal to 0.05) treated by occlusion plus sham heating, and five of five (100%) (P less than or equal to 0.01) sham-treated controls. Prior occlusion tended to reduce the radiofrequency power required for heat up and steady-state temperature maintenance of tumors (P less than or equal to 0.09 and P less than or equal to 0.06, respectively) and reduced the cooling rate after heating compared to unoccluded tumors (P less than or equal to 0.02) but did not affect mean time to temperature, maximum and minimum temperature measured at the tumor-normal tissue interface, and animal core temperature compared with that of the hyperthermia alone treatment group. In ten other animals with hepatic V-2 tumors of comparable size subjected to focal hyperthermia plus or minus arteriolar embolization, temperatures were continuously monitored at four additional intratumor sites in a fixed geometric orientation around the heating probe. No significant differences were noted in maximum and minimum temperatures in comparably oriented probes over a 40-min heating period between the hyperthermia and the occlusion-hyperthermia treatment groups. In five other animals with solitary V-2 hepatic implants, comparable microembolization plus or minus focal tumor heating to 43 degrees C, 40 min, did not significantly reduce tumor interstitial pH compared with pretreatment values. This study reproduces previously observed synergism between arteriolar embolization and hyperthermia but suggests the mechanism may be unrelated to observable differences in intratumor pH and thermal profile and may result from other mechanisms, perhaps by mimicking the angioocclusive effects of hyperthermia itself.
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Acute and late radiation injury in rhesus monkey parotid glands. Evidence of interphase cell death.
Acute and chronic salivary gland dysfunction are common sequelae of radiotherapy for head and neck cancer; but the associated morphologic changes, especially of the acute damage, have received relatively little study. For investigation of the morphologic characteristics of acute radiation injury to parotid glands, rhesus monkeys were studied 1-72 hours after parotid irradiation with single doses of 2.5-15.0 Gy. The acute damage from all doses was clearly expressed by 24 hours. Histologically, parotid glands irradiated with 2.5 or 5.0 Gy had random degeneration and necrosis of the serous acinar cells. Doses of 7.5-15.0 Gy produced widespread degeneration along with necrosis of whole acini. Serous cell damage was accompanied by neutrophilic inflammation that subsided after 24 hours to become replaced by plasma cell and lymphocytic infiltrates. Parotid glands receiving 7.5-15.0 Gy were atrophic at 16-22 weeks after irradiation and showed no recovery by 40 weeks. Although parotid acinar cells are well-differentiated nondividing cells, these observations show that they express lethal radiation injury in interphase within hours of receiving a radiation dose as low as 2.5 Gy. This is unlike most mammalian cells that express radiation injury during mitosis. Chronic atrophy is a consequence of this direct, irreversible, and early injury, rather than the result of radiation-induced changes in the vasculature.
Acute Disease↗
Unique radiosensitivity of serous cells in rhesus monkey submandibular glands.
The saliva of patients undergoing radiation therapy for head and neck cancer contains increased acidic mucosubstances associated with a reduced serous component. To assess the morphologic features of the acute radiation damage in serous versus mucous acinar cells, the mixed serous/mucous submandibular glands of 18 rhesus monkeys were studied 1-72 hours after irradiation with single doses of 2.5-15.0 Gy. Selective degeneration and necrosis of serous cells was observed with doses of 2.5-7.5 Gy. Doses of 10.0-15.0 Gy caused widespread destruction of whole serous acini, but only isolated mucous cells were affected. The lesions were clearly expressed by 24 hours. Transient exudation of neutrophils was replaced by plasma cells and lymphocytes. Examination at 16, 22 and at 40 weeks revealed that late atrophy was caused solely by loss of serous acini in glands treated with 7.5 and 10.0 Gy. Although both serous and mucous acini were reduced in glands treated with 12.5 and 15.0 Gy, the atrophy was mainly due to loss of serous acini. The finding that serous cells are more vulnerable to radiation injury than mucous cells provides a morphologic explanation for early and late changes in saliva composition after salivary gland irradiation.
Animals↗
Surgical and microscopic anatomy of parotid and submandibular salivary glands of rhesus monkeys (Macaca mulatta).
Wedge biopsy of the caudal borders of the parotid or submandibular salivary glands of rhesus monkeys avoids major nerves, ducts, and blood vessels. This is a minor surgical procedure that provides adequate material for in vitro studies and causes no significant postoperative complications. Gross and light microscopic anatomy of the rhesus and human salivary glands are similar. We have concluded that rhesus monkeys are good models for human salivary diseases, including radiation sialoadenitis.
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Antitumor effects of gossypol on murine tumors.
Since the male antifertility drug, gossypol, was shown to be a specific inhibitor of DNA synthesis at moderately low doses in cultured cells, its antitumor potential has been evaluated in three murine tumor models. The effects of gossypol on tumor growth and the survival of 10- to 12-week-old BDF1 mice bearing mouse mammary adenocarcinoma 755 (Ca 755) or P388 or L1210 leukemias, all injected IP, were measured. At an optimum dose of 0.5 mg/mouse given as a single injection at 2 days (48 h) after the inoculation of 10(5) Ca 755 tumor cells, gossypol rendered 66% of the mice free of tumor cells, whereas the remaining 34% died of drug toxicity. The survival rate decreased sharply at doses on either side of the optimum. At suboptimal doses a major proportion of the tumor-bearing mice died of tumor, whereas at higher doses all the animals died of drug toxicity. In other words, the effective dose range of gossypol was rather narrow. The rapidly proliferating mouse leukemias, P388 and L1210, failed to respond to gossypol. Histopathological studies of various organs in the gossypol-treated mice revealed no consistent lesions that could give an indication of organ-specific toxicity of gossypol. The reduction in the myeloid series in the bone marrow of gossypol-treated mice may have been due to depletion rather than direct toxic effect. Further studies are essential to evaluate this compound with regard to its antitumor activity in other murine models.
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Selective occlusion and focal hyperthermia therapy of V-2 tumors in the rabbit hindlimb.
Utilizing technology recently developed in our laboratory, hypervascular, heat-resistant V-2 tumors growing in the rabbit hindlimb were variously subjected to selective vascular occlusion by embolization with Dextran M microspheres and focal hyperthermia to minimum intratumor temperatures of 43 degrees C X 40 minutes (OH), focal 43 degrees C X 40 minutes hyperthermia alone (H), selective occlusion plus sham hyperthermia (O), and sham treatment. Regional toxicity observed consisted of skin burns and muscle fibrosis in the H and OH groups and peripheral embolization in the O alone group. Tumors subjected to a single OH treatment had significantly reduced growth rate over a 28-day period of observation compared with all other treatment groups and sham-treated controls (P less than or equal to .05). Our findings suggest that the combination of selective vascular embolization and focused hyperthermia may be useful in therapy of hypervascular, heat-resistant human tumors in anatomic locations where selective occlusion and relatively intense focal heating can be performed. The regional toxicity encountered in this model reemphasizes the need for extensive thermal mapping over the heated region.
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Treatment of the rabbit V-2 carcinoma with intralesional cisplatin.
New Zealand white rabbits were used in the evaluation of intralesional injections of cisplatin for the management of experimentally induced V-2 carcinomas. The tumors were implanted into the right hip by intramuscular injections of an inoculum containing freshly harvested V-2 fragments which gave rise to a single, spherical mass (2-3 cm) 2 weeks after inoculation. All rabbits received two courses of either intralesional cisplatin or saline beginning 2 weeks after inoculation. Cisplatin injections significantly slowed the growth and spread of the primary tumor in all treated rabbits. In addition, intralesional chemotherapy prevented the development of lung metastases in 71% of the animals and produced approximately a threefold increase in survival time. Results indicate that not only is cisplatin active against experimentally induced V-2 carcinomas in rabbits, but direct intralesional injection is also an easy and effective means of administering chemotherapy.
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Insular amyloidosis and diabetes mellitus in a crab-eating macaque (Macaca fascicularis).
Clinicopathologic examination of a crab-eating macaque (Macaca fascicularis) with chronic weight loss and bilateral cataracts revealed high fasting serum glucose, glucosuria and hypercholesterolemia. Clinical signs were eliminated by treatment once a day with isophane insulin suspension. Extensive insular amyloidosis was found microscopically sixty days later.
Amyloidosis↗
Effects of calcium supplementation and sunlight exposure on growing beagle dogs.
Nine 7-week-old Beagle dogs were given 2.3 g of dietary calcium supplementation once a day and were exposed to sunlight to permit endogenous vitamin D formation. After 70 days, the serum calcium and phosphorus concentrations, thyroid morphometry, and bone density and composition were compared with those values in a similar group of 10 dogs not given calcium supplementation and maintained in restricted, artificial light. Lower serum calcium and phosphorus concentrations in the supplement-fed dogs may be attributed to hypercalcitonism, which was assumed to be present because of increased proportions of C cells and decreased proportions of thyroid follicles. They also had significantly more trabecular bone of a lower specific gravity containing more water and less combustible matter. The findings indicate that the high dietary calcium intake and sunlight exposure induced C-cell hyperplasia during a relatively short period of 70 days. It is possible that Beagles maintained through maturity on a diet high in calcium concentration and in outdoor runs may develop chronic C-cell hyperplasia. The possible contribution of high calcium intake and chronic C-cell hyperplasia to reduced thyroid function and skeletal changes is not yet clear.
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Transplantation of normal and ectopic human endometrial tissue into athymic nude mice.
Implants or tiny circumscribed nodules of endometrial tissue were found in all female mice given intraperitoneal injections of fragments of human normal (proliferative and secretory) or ectopic (endometrioma) endometrium. Half of these animals received estrogen supplementation and the other half received none. The endometriosis tissue present in these animals at 28 or 56 days after inoculation consisted of glands and stroma with an infiltration of hemosiderin-laden macrophages. Glands in tissue transplants of animals given supplemental estrogen tended to be larger, and the secretory endometrium tended to revert to a proliferative pattern. Palpable nodules at the site of subcutaneous inoculations of proliferative endometrium became undetectable grossly and microscopically within 24 to 32 days, whereas endometrioma tissue remained detectable for up to 70 days and resembled the intraperitoneal tissue microscopically. This study demonstrates that human endometrial tissue can be successfully transplanted into the nude mouse and will retain its basic morphology.
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Attempted transmission of a feline virus-associated liposarcoma to newborn kittens.
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Animals↗
Inhibition of radiation carcinogenesis in mice by S-2-(3-aminopropylamino)-ethylphosphorothioic acid.
We have demonstrated that S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) given to mice prior to ionizing radiation inhibits development of radiation-induced sarcomas. The right hind legs of C3Hf/Kam mice were exposed to single doses of gamma-rays ranging from 3400 to 5700 rads. Thirty min before irradiation, approximately one-half of the mice were given i.p. injections of WR-2721 (400 mg/kg). Mice were checked for development of radiation-induced tumors within the irradiated tissue of legs from 250 up to 786 days after irradiation. Tumors first appeared in both groups of mice at approximately 300 days after irradiation. Thereafter, the rate of tumor development was slower in mice that received both WR-2721 and leg irradiation. At the end of the observation period, the overall actuarial tumor incidence in these mice was 26%, compared to 87% in mice exposed to radiation only. Since WR-2721 has the ability to protect against radiation carcinogenesis, it may also afford protection against the carcinogenic effect of alkylating agents.
Amifostine↗
Virus-associated liposarcoma and malignant lymphoma in a kitten.
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Animals↗