Feline oral neoplasia: a ten-year survey.

A retrospective histological study was conducted on 371 neoplasms of the oral cavity in cats. Oral neoplasia accounted for 10% of feline neoplasms identified during the survey period. Eighty-nine percent of the oral neoplasms were malignant. Twenty different oral neoplasms were found. The most common were squamous cell carcinoma (61.2%), fibrosarcoma (12.9%), and fibromatous epulis of periodontal ligament origin (7.8%).

Equine juvenile mandibular ossifying fibroma.

Benign proliferative fibro-osseous lesions of the rostral mandible in six young horses are classified as equine juvenile mandibular ossifying fibroma. Histologically there is a characteristic abrupt transition from subgingival fibroblastic stroma to a zone of proliferating osteoblasts that form irregular spicules of osteoid. The layer of proliferating osteoblasts blends with a deeper zone of bony trabeculae rimmed by osteoblasts and separated by intertrabecular spaces of moderate cellular density. Incomplete surgical excision resulted in local recurrence, while rostral mandibulectomies resulted in no recurrence. The predilection for the rostral mandible of young horses coupled with the similar clinical, radiographic, and histological characteristics supports the classification of this lesion as a distinct entity.

Gastric hyperplastic polyp in a horse.

An unusually large, pedunculated (20 cm long) mass arising the gastric pylorus which produced complete obstruction of the proximal duodenum and severe gastric distension was found in a 13-year old castrated male Arabian horse. The histological diagnosis was gastric hyperplastic polyp, which has not been reported previously in the horse. The clinico-pathological findings in this horse are compared with hyperplastic (inflammatory) gastric polyps of man.

Esophageal phytobezoar in a horse.

A 23-year-old Thoroughbred stallion was admitted to the hospital for treatment of acute esophageal obstruction. Clinical examination and contrast radiography confirmed the presence of an esophageal obstruction. The horse was euthanatized, and examination revealed a bolus of feed material occluding the esophageal lumen 6 cm caudal to the thoracic inlet, with underlying necrosis of the esophageal mucosa. A large pulsion diverticulum was identified in the caudocervical portion of the esophagus. Apparently, the phytobezoar was formed within the esophageal diverticulum and subsequently became dislodged, occluding the esophagus.

Skeletal muscle ventricles in circulation. One to eleven weeks' experience.

Skeletal muscle ventricles were constructed from canine latissimus dorsi and connected to the thoracic aorta in six dogs. These ventricles were stimulated to contract synchronously during diastole. The skeletal muscle ventricles were capable of continuous stroke work when placed within the arterial circulation for several weeks. Effective synchronous diastolic counterpulsation was produced. These results demonstrate that diastolic counterpulsators can be constructed from skeletal muscle and in the future may provide a feasible therapeutic alternative for the treatment of end-stage cardiac failure.

Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene.

The structure and expression of the c-myc oncogene were examined in 29 primary human colon adenocarcinomas. Dot blot hybridization of total RNA showed that 21 tumors (72%) had considerably elevated expression of c-myc (5- to 40-fold) relative to normal colonic mucosa. These data were corroborated by Northern blots of polyadenylated RNA, which showed a 2.3-kilobase transcript. Southern analysis of the c-myc locus in these tumors indicated the absence of amplification or DNA rearrangement in a 35-kilobase region encompassing the gene. In a parallel study, elevated expression of c-myc without amplification or DNA rearrangement was also observed in three of six colon carcinoma cell lines examined; in addition, unlike a normal colon cell line control, these three cell lines exhibited constitutive, high-level expression of the gene during their growth in cultures. These results indicate that elevated expression of the c-myc oncogene occurs frequently in primary human colon carcinomas and that the mechanism involved in the regulation of c-myc expression is altered in tumor-derived cell lines.

Cell kinetics in mouse lung following administration of carcinogens and butylated hydroxytoluene.

A series of experiments is described which was designed to test the hypothesis that, in mouse lung, enhancement of tumor development could occur independently of overall alveolar cell hyperplasia. Male A/J mice were given 1000 mg/kg of urethan or 10 mg/kg of 3-methylcholanthrene (MCA). Alveolar cells were labeled through continuous infusion of [3H]thymidine for 6 weeks after administration of the carcinogen. Urethan produced a significant hyperplasia of the type II alveolar cell population, whereas MCA had no such effect. Five repeated injections of 300 mg/kg of butylated hydroxytoluene (BHT), a procedure known to enhance lung tumor development, produced cell hyperplasia only during the first 2 weeks; later the mice became resistant to the action of BHT. In animals treated with piperonyl butoxide prior to BHT, cell proliferation was abolished. BHT still had a small but significant enhancing effect on tumor development. However, this effect was dwarfed by the observation that piperonyl butoxide alone greatly inhibited tumor development. The data do not allow exclusion of alveolar cell hyperplasia as a mechanism in BHT-mediated enhancement of mouse lung tumor development.

Pulmonary toxicity of cyclophosphamide: a 1-year study.

The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure-volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion.

The effect of 3-methylfuran inhalation exposure on the rat nasal cavity.

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in female CD/CR rats. Animals were killed 1, 3, 6, 9, 12, 15 and 30 days following a 1-h exposure to 148 mumol 3MF/1. Relatively selective 3MF-induced necrosis of the olfactory epithelium was seen at day 1 post exposure. Subsequent resolution of the acute olfactory necrosis was not complete and resulted in partial occlusive fibrosis of the nasal cavity as seen at 30 days. Pretreatment of the animals with piperonyl butoxide (PB) did not block 3MF-induced olfactory epithelial necrosis although it prevented Clara cell necrosis when given at a dose of 800 mg/kg intraperitoneally 1 h before exposure to 3MF.

Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster.

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC50, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 mumole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC50 in the male rat of 81 mumole/liter-1 hr as compared to 222 mumole/liter-1 hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 mumole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of "small airway disease" of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

Enhancement of lung tumor formation in mice by dietary butylated hydroxytoluene: dose-time relationships and cell kinetics.

Strain A/J mice given injections of 1,000 mg urethan/kg and fed for 12 weeks a diet containing 0.75% of butylated hydroxytoluene (BHT) had significantly more tumors per lung 4 or 9 months later than animals given urethan and fed a control diet. A 2-week exposure to dietary BHT (0.75%) was sufficient to significantly enhance tumor development, and the lowest effective BHT concentration was 0.1%, fed for 8 weeks. Tumor development was also enhanced in animals treated once with 3-methylcholanthrene, benzo[a]pyrene, or N-nitrosodimethylamine and, beginning 24 hours later, fed BHT for 8 weeks. Cell kinetic studies showed that BHT given in the diet produced increased proliferation of type II alveolar cells during the first 2 weeks and that initial cell proliferation was delayed in urethan-treated animals.

Isolation of the ARO1 cluster gene of Saccharomyces cerevisiae.

The AROl cluster gene was isolated by complementation in Saccharomyces cerevisiae after transformation with a comprehensive yeast DNA library of BamHI restriction fragments inserted into the shuttle vector YEp13. Most of the transformants exhibited the expected episomal inheritance of the ARO+ phenotype; however, one stable transformant has been shown to be an integration of the AROl fragment and the vector YEp13 at the arol locus. The insert containing AROl is a 17.2-kilobase pair (kbp) BamHI fragment which complements both nonsense and missense alleles of arol. Subcloning by Sau3AI partial digestion further locates the AROl segment to a 6.2-kbp region. An autonomously replicating sequence (ars) was found on the 17.2-kbp fragment. Yeast arol mutants transformed with the AROl episome express 5 to 12 times the normal level of the five AROl enzyme activities and possess elevated amounts of the AROl protein. The yeast AROl fragment also complemented aroA, aroB, aroD, and aroE mutants of Escherichia coli. The expression of AROl in both S. cerevisiae and E. coli was independent of the orientation of the fragment with respect to the vector.

Effect of lung, liver, and kidney toxicants on respiratory rate in the mouse.

The intraperitoneal administration of either butylated hydroxytoluene (BHT) +/- thoracic X-irradiation, or cyclophosphamide, and intravenous injection of oleic acid, resulted in lung injury and repair in BALB/c mice which could be assessed in unanesthetized animals by changes in respiratory rate (RR) using a total body plethysmograph. Studies with BHT +/- X-rays, and cyclophosphamide found that the RR right before sacrifice (2 weeks after BHT and 3 weeks after cyclophosphamide) correlated well (r = 0.19) with the degree of pulmonary fibrosis as measured by changes in hydroxyproline content. However, prior to this timepoint, there was a peak and trough in respiratory rate response that could not be correlated with the time course of fibrosis development in the BHT-X-ray model. In an effort to determine the influence of pulmonary edema and lung cell proliferation on respiratory rate changes, an agent (oleic acid) capable of producing lung injury followed by a high level of cellular proliferation with only minimal development of fibrosis was studied. These studies showed that good correlations were found on day 3 following injection (day of peak increase in respiratory rate) between respiratory rate and either lung wet weight (r = 0.81) or the degree of cellular proliferation as measured by the incorporation of thymidine into pulmonary DNA (r = 0.80). Liver (carbon tetrachloride) and kidney (mercuric chloride) toxicants, and starvation produced decreases or no change in RR.

Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs.

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.