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Biomedical subjects

D M Hoover

Publications and source records attributed to D M Hoover.

At least 55 records · Page 3Linked to original sources

Effects of cefamandole on spermatogenic development of young CD rats.

The testicular toxicity of cefamandole, a beta-lactam antibiotic with an N-methylthiotetrazole side chain, was evaluated in neonatal rats. Cefamandole caused delayed maturity of the germinal epithelium of neonatal rats when given on Postpartum Days 6 through 36. In rats given daily subcutaneous injections of 1000 mg/kg during this period, the most mature germinal cells were acrosome phase spermatids, whereas control rats had spermatids in the maturation phase. In studies of specific developmental phases, the effect of 1000 mg/kg daily cefamandole was primarily on the initial waves of spermatogonia during the period of rapid development (Postpartum Days 4 through 13). In animals treated from birth to Postpartum Day 8 and evaluated sequentially on Postpartum Days 5 through 9, there were no morphologically discernible effects on the transformation of gonocytes to immature spermatogonia, but there were slight degenerative changes in the first waves of developing spermatogonia. Cefamandole, 1000 mg/kg daily, given Postpartum Days 14 through 18 during the initial phase of spermatocyte development, also caused a slight degenerative change of the initial waves of pachytene spermatocytes. The significance of the findings in neonatal rats is unknown because differences in spermatogenic development between rat and human preclude direct extrapolation of the effects of cefamandole in neonatal rats to effects in humans.

Aging↗

Teratology studies of compound LY171883 administered orally to rats and rabbits.

The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.

Acetophenones↗

A light and electron microscopical study of intranuclear cytoplasmic invaginations in interstitial cell tumours of dogs.

Intranuclear cytoplasmic invaginations, so-called "pseudoinclusions", were seen in all 7 interstitial cell tumours identified among 32 consecutive canine testicular tumours examined. The proportion of cells with intranuclear cytoplasmic invaginations varied from less than 1 per cent to 15 per cent. Similar "pseudoinclusions" were not seen in any other canine testicular tumours examined; this finding might be helpful in differential diagnosis, especially in less differentiated tumours. Histologically, the cytoplasmic invaginations appeared as round, eosinophilic, clearly demarcated intranuclear inclusions and stained with periodic acid-Schiff. Affected nuclei were enlarged. The process of progressive cytoplasmic invaginations into the nucleus and replacement of most of the nuclear volume of the neoplastic interstitial cells with cytoplasmic material was examined by transmission electron microscopy. Two or more cytoplasmic invaginations were sometimes present within a single nucleus. The nuclear membrane could be followed continuously around the cytoplasmic invaginations and nuclear pores were present in the membrane covering invaginations. The invaginations contained smooth and rough endoplasmic reticulum, vesicles, lipid vacuoles, myelin figures and disrupted membranous profiles. Bundles of interwoven cytoplasmic filaments were among the organelles seen in the invaginations in one tumour. Possible reasons for the formation of intranuclear cytoplasmic inclusions are discussed and maintenance of the normal ratio of nuclear surface to nuclear volume is suggested as the mechanism promoting formation of inclusions in interstitial cell tumours.

Animals↗

Metastatic spread of the PAIII prostatic adenocarcinoma after implantation in the tail of the rat.

The spontaneous metastatic spread of a suspension of PAIII prostatic adenocarcinoma cells from the tail site of implantation was analyzed over a period of 5 weeks in male Lobund-Wistar (LW) rats. Following subcutaneous injection of the PAIII cells, the tumor metastasized through the primary lymphatic drainage. PAIII microfoci were evident in the gluteal and iliac lymph nodes prior to colonization of the lungs. Growth of the primary tumor was evidenced by significant weight differences of the tails of PAIII-bearing and control rats 1 week after tumor implantation. Time-dependent sequential spread of the adenocarcinoma was quantitated. Significant differences were noted between PAIII-bearing and control animals with respect to the gluteal lymph node weights (+2 weeks), iliac lymph node weights (+3 weeks), dry lung weights, and lung colony numbers (+4 weeks) after tumor implantation. During the course of these studies, the whole blood prothrombin, activated partial thromboplastin, and recalcification times for the PAIII-bearing animals were similar to those of the control group. These findings indicate that there were no gross changes in systemic blood coagulation accompanying the metastasis of PAIII cells from the primary tumor. The tumor in LW rats produced a consistent pattern of growth and metastasis that is suitable for quantitation. The PAIII prostatic adenocarcinoma is a sensitive and reproducible system that may be useful to evaluate potential antimetastatic and cytotoxic agents for the treatment of hormone-insensitive prostatic cancer.

Adenocarcinoma↗

Hepatic peroxisomal changes induced by a tetrazole-substituted alkoxyacetophenone in rats and comparison with other species.

Previous work in this laboratory indicated that compound LY171883, a tetrazole-substituted alkoxyacetophenone with leukotriene D4 antagonist activity, caused dose-related hepatomegaly in rodents without other histological evidence of liver toxicity. In the present studies, administration of LY171883 at dietary concentrations of 0.25 or 0.50% to rats for 2 weeks increased peroxisomal beta-oxidation, catalase activity, and peroxisome volume fraction in the liver. The effects were dose-related and corresponded with increases in liver weight. Dietary concentrations of 0.05 and 0.1% LY171883 did not significantly alter peroxisome morphology, enzyme activity, or liver weight. Serum triglycerides were lowered equivalently by all four dietary concentrations of LY171883, indicating that the hypotriglyceridemia was dissociated from induction of peroxisomal beta-oxidation. The hepatic effects in rats reversed within 16 days after discontinuing treatment with LY171883. Liver weight and peroxisomal enzyme activities were increased in mice by LY171883 in a manner comparable to that observed in rats, whereas hamsters were less responsive. In guinea pigs there was a minor increase in beta-oxidation at a toxic dose of LY171883, but no change in catalase or liver weight. Neither hepatomegaly nor induction of peroxisomal enzymes occurred in beagle dogs or rhesus monkeys given LY171883. Since the hepatic effects of LY171883 in rats are not observed in higher species at a significant multiple of the anticipated clinical dose, it is unlikely that such effects will occur in humans.

Acetophenones↗

Inhibitory effect of warfarin on the metastasis of the PAIII prostatic adenocarcinoma in the rat.

The PAIII rodent metastatic prostatic adenocarcinoma model was employed to evaluate the effects of dietary warfarin, a prototypic antagonist of thrombin generation on the lymphatic and pulmonary metastases of the tumor from the tail site of subcutaneous transplantation in male Lobund Wistar (LW) rats. In addition, the anticoagulant effects of warfarin were determined in the same animals. Warfarin, administered in the diet at concentrations equivalent to 0.063, 0.125 or 0.250 mg./kg. b.w. for 30 days had no effect on final body weight, gluteal or iliac lymph node weights. Significant (p less than 0.05) dose-dependent extensions of whole blood prothrombin (WBPT), activated partial thromboplastin (WBAPTT) and clotting times (WBCT) over control values were observed with warfarin treatment. Preliminary studies demonstrated that the 0.500 mg./kg. dose produced 50 per cent mortality at +14 days. Warfarin produced significant (p less than 0.05) dose-dependent decreases in the number of PAIII pulmonary metastases as indicated by reductions in dry lung weights and lung colony numbers when compared to untreated tumor-bearing controls. While the therapeutic index of warfarin is a limiting factor in clinical use as an antimetastatic agent, these results suggest that compounds capable of altering hemostatic mechanisms may be potential inhibitors of tumor metastasis. The PAIII prostatic adenocarcinoma model may be a useful system to quantitatively evaluate potential antimetastatic and cytotoxic agents.

Adenocarcinoma↗

Campylobacter colitis in ranch mink in Ontario.

Outbreaks of colitis, where Campylobacter jejuni and Campylobacter coli were the only pathogens isolated occurred in weanling mink (Mustella vision) on two commercial mink ranches in Ontario. Lesions were restricted to the proximal colon and were characterized by multiple 1 mm focal or 1 mm linear erosions/ulcers in the region 2 cm distal to the ileal-colonic junction. Histological changes included thickening of the colonic mucosa, inflammatory cell infiltrate in the lamina propria and submucosa, cellular debris and inflammatory exudate within cryptal lumens and multiple areas of mucosal erosion/ulceration. Four C. jejuni negative mink were challenged with 5.1 X 10(9) colony forming units of C. jejuni by oral inoculation. Three of four experimentally infected mink developed diarrhea by day 4 postinfection with lesions grossly and microscopically similar to mink in the naturally occurring outbreak. Examination of lesions by transmission electron microscope failed to show evidence of C. jejuni invasion of intestinal epithelium. Feeding uncooked slaughterhouse chicken offal was the likely source of C. jejuni in the naturally occurring outbreaks.

Animals↗

Mesenchymal-epithelial interactions as factors influencing male accessory sex organ growth in the rat.

Mesenchyme (UGM) and epithelium (UGE) isolated from the urogenital sinuses (UGS) of 17-day male and female rat embryos were separated by using a trypsinization procedure, grown on soft agar, transplanted into syngeneic pubertal male hosts as subcapsular renal grafts, and then collected after 29-30 days. Neither UGM nor UGE underwent prostatic morphogenesis when grown under these conditions. However, tissue recombinants composed of UGM + UGE grew and produced prostatic glands with acinar secretory material. Further, UGM + UGE recombinants were made by varying the proportions of mesenchymal and epithelial tissues. The size of the implants was a function of the absolute amount of mesenchyme; increasing the absolute amount of UGM produced larger specimens whereas varying the UGE had no effect. The UGM was also found to be essential for supporting the growth of small glandular elements derived from the ventral prostate of pubescent rats. Segments isolated from the terminal vesicles (TIPs) and from prostatic tissue adjacent to the urethra (PDCT) regressed when implanted alone under the kidney capsule. However, combination of the prostatic segments with UGM produced prostatic glands with relative wet weight and DNA content responses of the following order: UGM + TIP greater than UGM + PDCT = UGM + UGE. Two-dimensional gel electrophoretic protein patterns from UGM + PDCT and UGM + TIP specimens had differential expression of three protein regions unique to the ventral prostate Quantitative and qualitative responses of the TIP and PDCT segments to UGM inductive influences indicate that differences exist between the epithelia of the TIP and PDCT regions of the ventral lobes of the rat prostate.

Animals↗

Primary cardiac granular cell tumor in a dog.

The histological, histochemical, and ultrastructural features of a granular cell tumor in the wall of the right atrium of the heart in a nine-year-old dog are described. The histologic appearance of the mass varied from areas of spindle-shaped cells to sheets of globoid cells with foamy granular cytoplasm. The globoid neoplastic cells contained numerous cytoplasmic granules which were variably positive to periodic acid-Schiff staining, with and without disastase digestion. Ultrastructurally, the globoid cells had numerous various-sized, heterogeneous lysosomes with pleomorphic content. A granular cell tumor originating in the heart has not been reported previously in animals. The support for a neural origin of these tumors by the recent identification of several nervous tissue specific proteins in their granular cells is discussed.

Animals↗

Virus isolation studies in an outbreak of porcine encephalomyelitis.

An outbreak of central nervous system disease affecting young pigs occurred in the fall of 1981 in eastern Ontario. A diagnosis of viral encephalomyelitis was made on pathological grounds and virus isolation studies were subsequently initiated to determine the causative agent. Cultural isolation procedures using several biological systems failed to detect virus in nervous tissues from affected animals. Direct extraction of similar tissues by combined biochemical and biophysical procedures yielded nonenveloped , spherical particles with a diameter of 30 nm and a buoyant density of 1.34 g/mL in CsCl. A tentative diagnosis of enterovirus infection was made on this basis.

Animals↗

Enteric adenovirus infection in pigs.

Intranuclear adenovirus inclusion bodies were identified in intestinal epithelium by histological, electron microscopical or cytological examination of 43 conventionally raised pigs submitted for diagnostic evaluation from 38 farms between August 1981 and January 1983. The affected pigs were usually less than three weeks old, but ranged from five days to 24 weeks of age. The inclusion bodies occurred in the epithelium of ordinary intestinal villi, or more commonly, in the epithelium covering the blunt villi located over Peyer's patches in the ileum. Fifty-three percent of these adenovirus infected pigs had diarrhea. In most of these pigs with diarrhea (19 of 23) however, agents previously established as causes of porcine enteric disease were also identified. Of the pigs with enterocyte inclusion bodies but without diarrhea, the adenovirus infection appeared incidental to the major disease processes in the pigs. These findings suggest that this adenovirus is an asymptomatic and probably incidental infection in conventional farm-raised pigs.

Adenoviridae Infections↗

The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs. I. Clinical disease.

The clinical and clinicopathologic effects of excess oral pyridoxine hydrochloride (150 mg/kg body weight/day) and clioquinol (200 mg/kg body weight/day) alone and in combination were evaluated in adult Beagle dogs over an experimental period of approximately 100 days. Anorexia and loss of body weight occurred in the first weeks of the trial period in each treatment group, but was most severe in dogs given both compounds. Dogs in each treatment group (10 of 10 pyridoxine-treated dogs, 6 of 13 clioquinol-treated dogs and 12 of 13 pyridoxine plus clioquinol-treated dogs) developed neurologic disease, manifested principally by ataxia. Pyridoxine-treated dogs had proprioceptive loss involving both fore- and hindquarters, characterized by stiff, spastic, dysmetric leg movements. In clioquinol-treated dogs, dysmetric leg movements were accompanied by failure to support body weight in the hindquarters, but similar forelimb involvement occurred in severely affected dogs. The neurologic disease in dogs given both compounds varied; signs in some dogs resembled those of affected dogs of the pyridoxine-treated group, and in others, those in clioquinol-treated group. Erythrocyte counts, hemoglobin concentrations and packed cell volumes were reduced in dogs in each treatment group and were lowest in dogs given both compounds. Plasma protein was mildly reduced in dogs given pyridoxine or pyridoxine plus clioquinol. Few or no differences were present in the leukocyte counts, blood urea nitrogen concentrations, in activities of serum alanine aminotransferase and aspartate aminotransferase, and in concentrations of sodium, chloride or potassium in treated dogs as compared to control dogs.

Animals↗

The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs. II. Pathology.

The lesions caused by excess oral pyridoxine hydrochloride (150 mg/kg body weight/day) and clioquinol (200 mg/kg body weight/day), given individually and in combination to adult Beagle dogs, were evaluated. The experimental period was 100 to 112 days, except that four dogs in each of the clioquinol and combined-treatment groups were killed early because of severe debilitation or neurologic disease, and one dog given both compounds died on the third day of compound administration. Degenerative neurologic lesions had distribution specific for the compound given. Pyridoxine-treated dogs had lesions limited to tracts and nerves with neuronal bodies of their nerve fibers in the spinal and trigeminal ganglia. Clioquinol-treated dogs had neurologic lesions limited to the central nervous system. The most lesions were in the rostral dorsal funiculus and distal aspects of the optic nerve fibers, but minimal to mild degenerative changes also occurred in distal aspects of the corticospinal and spinocerebellar tracts. Dogs given both pyridoxine hydrochloride and clioquinol had a combination of the lesions in dogs given pyridoxine or clioquinol individually. Several dogs given clioquinol or pyridoxine plus clioquinol had extraneural lesions, including myocardial degeneration and thyroidal alterations.

Animals↗

Ultrastructural lesions of pyridoxine toxicity in beagle dogs.

Three adult Beagle dogs given pyridoxine hydrochloride orally at a dose of 150 mg/kg body weight/day for about 100 days developed ataxia and had spastic, dysmetric leg movements. Ultrastructural alterations in the dorsal funiculus of the spinal cord were degeneration and loss of axons and myelin, and secondary changes of the myelin sheaths. Possible pathogenic mechanisms of pyridoxine neurotoxicity are discussed.

Animals↗

Ovine pulmonary cytomegalovirus.

Cytomegalic cells with intranuclear inclusions were identified in lung tissue from one of two weanling Western lambs with pneumonia and Mycoplasma ovipneumoniae infection. On the basis of light and electron microscopy, cytomegalovirus infection was diagnosed. Arrays of viral particles whose morphology was consistent with that of viruses of the herpes group were in the intranuclear inclusions of cytomegalic cells.

Animals↗