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Biomedical subjects

P D Moorhead

Publications and source records attributed to P D Moorhead.

At least 19 recordsLinked to original sources

Influence of selection for increased body weight on the incidence of leiomyomas and leiomyosarcomas in Japanese quail.

Leiomyomas and leiomyosarcomas were observed in adult laying hens from lines of Japanese quail selected solely (HW) or partly (HW-HP; HW-LP) for increased 4-wk BW and the corresponding randombred control (R1). No neoplasms were observed in a line (LW) selected for decreased 4-wk BW based on observations in one generation. Line R1 served as the base population for Lines HW and LW and was maintained without conscious selection for any trait, Lines HW-HP and HW-LP were sublines of Line HW in which the males were selected for increased 4-wk BW and the females were selected for high or low levels of plasma total phosphorus, respectively. Hens of all lines were necropsied after completing a 120-day production period. A high incidence of neoplasms were found in the dorsal and ventral ligaments of the oviduct in the immediate vicinity of the magnum, and the incidence was much greater in the lines selected for increased growth than in Line R1. These results suggest that selection for increased BW in Lines HW, HW-HP, and HW-LP has resulted in genetic changes that are conducive to neoplastic growth. Based on the results of one generation, it appears that selection for decreased 4-wk BW reduced incidence of neoplasms.

Animals↗

Pathogenesis of porcine enteric calicivirus-like virus in four-day-old gnotobiotic pigs.

Eighteen 4-day-old gnotobiotic pigs were orally inoculated with porcine enteric calicivirus-like virus (C strain). Seven additional gnotobiotic pigs served as noninoculated controls. Mild diarrhea developed in all inoculated pigs by postinoculation day (PID) 3 and persisted for 3 to 7 days. Severe diarrhea developed in 2 inoculated pigs between PID 4 and 5. Twelve inoculated and 7 control pigs were euthanatized over a 7-day period. Small intestinal mucosal smears were stained with a fluorescein-conjugated anti-porcine enteric calicivirus-like virus serum. Immunofluorescence was observed in villous epithelial cells (primarily in the duodenum or jejunum) of all inoculated pigs, except for 1 pig euthanatized at PID 7. Villus length was determined in histologic sections of the small intestinal specimens from control and inoculated pigs. Statistically significant (P less than 0.01) villus atrophy was found in the duodenum and/or jejunum of inoculated pigs at PID 3 to 7. These observations were confirmed by scanning electron microscopy, which revealed shortening, blunting, fusion, or absence of villi in the duodenum and jejunum of inoculated pigs at PID 3 to 7. Lesions were not seen in control pigs. Calicivirus-like particles were detected by immune electron microscopy in the large intestinal contents and feces of inoculated pigs from PID 1 to 7.

Animals↗

Changes in hepatic function tests to induced toxicity in the bovine liver.

Graded hepatic damage was induced in mature lactating dairy cows to measure the sensitivity of several hepatic diagnostic tests. In a preliminary study, cows were dosed with .05, .10 and .20 ml/kg body weight of carbon tetrachloride. Extreme changes occurred in hepatic tests by 24 h post-dosing, and all died by 35 h with massive diffuse centrilobular necrosis of hepatic cord cells. Dosing was decreased to induce non-fatal hepatic changes. Cows in Groups 1, 2, 3 and 4 were orally dosed with .002, .004, .006 or .01 ml/kg body weight of carbon tetrachloride, respectively. Serum enzymes of hepatic origin, bilirubin, plus bromosulfophthalein dye clearance were assayed before dosing and up to d 14 post-dosing. Liver biopsies were performed 24 h post-dosing for histological evaluation and cytochrome P-450 content. Hepatic concentrations of cytochrome P-450 were decreased in all the dosed cows. Serum activities of sorbitol dehydrogenase and gamma-glutamyl transferase were elevated in cows of Groups 3 and 4 and glutamic-oxaloacetic transaminase in cows of Group 4 by 24 h. Serum alkaline phosphatase, glutamic-pyruvate transaminase, lactate dehydrogenase, bilirubin, urobilinogen and bromosulfophthalein dye clearance were not significantly different. Mild to moderate diffuse centrolobular necrosis was observed in livers of cow of Groups 3 and 4, but no pathological changes were seen in Groups 1 and 2.

Animals↗

Serum isocitrate dehydrogenase during polybrominated biphenyl toxicosis in dairy cattle.

Bovine serum isocitrate dehydrogenase (sICDH) was investigated in dairy cattle as a clinical measurement indicative of hepatic injury. Conditions for optimization of isocitrate dehydrogenase assays for bovine serum are described. Assays of sICDH in normal cattle show average activities of .814 (SD = .202) units/ml serum with a range of .316 to 1.268 for 83 samples taken from 32 animals. Investigation of sICDH in pregnant dairy cattle experimentally dosed with polybrominated biphenyl (PBB) showed no discernible elevations until doses were sufficient to cause toxicosis (25,000 mg PBB/d). Cows lethally dosed with 25,000 mg PBB/d had moderate elevations of sICDH (approximately a twofold increase) concomitant with severe toxicosis in some but not all animals. This PBB dose also caused abortion or fetal death in pregnant animals; elevation of sICDH in these animals was coincident with fetal trauma. This suggests that sICDH may be influenced by fetoplacental contributions in pregnant animals. Non-pregnant cows, intoxicated with PBB, had minimal sICDH elevation as compared with 10-fold in a calf with experimentally induced hepatotoxicity (thioacetamide). This observation was consistent with histopathological findings of minimal, if any, hepatic involvement in dairy cattle lethally intoxicated with PBB. Serum isocitrate dehydrogenase appears to be a useful adjunct to the ordinary complement of serum chemistries used for clinical diagnosis; however, it does not appear to reflect exclusively hepatic injury.

Animals↗

Comparison of bone and muscle growth in turkey lines selected for increased body weight and increased shank width.

A subline (FL) of a long-term growth-selected line (F) of turkeys was established by mass selecting solely for increased shank width at the narrowest point (dew claw). A comparison was made of bone and muscle growth in Line FL (fourth generation of selection), Line F (17th generation of selection), and a randombred control (RBC2, the base population of F) at 8, 16, and 20 wk of age. Also, a sample of the tibiotarsal and femur bones was studied histologically for evidence of pathological conditions. No significant pathological changes were observed in bones from turkeys of the different lines at the ages examined. Samples for histological study were taken at Day 1, 27, 56, 84, 112, and 140 posthatching. Genetic increases in body weight (F and FL lines) resulted in a significant decline in the relative amount of leg muscles from 16 to 20 wk of age while in Line RBC2 the relative amount of leg muscles increased slightly from 16 to 20 wk of age. This resulted in a significant line x age interaction. No significant differences in the amount of leg muscles were detected between turkeys of Lines F and FL. Amount of breast muscles increased consistently with age in all lines. Amount of breast muscles (absolute and as a percentage of body weight) was larger in Line F than in the FL and RBC2 lines. The actual weight of the breast muscles was larger in Line FL than in the RBC2 line but as a percentage of body weight there was no significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)

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Experimentally induced coronavirus infections in calves: viral replication in the respiratory and intestinal tracts.

Eleven 3- to 50-day-old colostrum-deprived gnotobiotic calves and seven 25- to 63-day-old colostrum-deprived conventional calves were allotted into 3 groups. Each group was inoculated with a fecal isolate of bovine coronavirus via different routes: orally/intranasally OR/IN, No. 1 through 8, group 1 calves; OR, No. 9 through 13, group 2 calves; IN, No. 14 through 18, group 3 calves. Nasal swab specimens and fecal specimens were collected daily and were examined for coronavirus antigen by use of direct immunofluorescent staining (nasal epithelial cells) or by use of immune electron microscopy (fecal specimens). All but 4 calves (No. 11, 13, 17, and 18) were euthanatized on postinoculation days (PID) 3 to 7. Calves 11 and 17 became severely dehydrated and died at PID 5. Calves 13 and 18 were evaluated for nasal and fecal shedding of coronavirus through PID 14. Distribution of coronavirus antigen in the respiratory and intestinal tracts of the 14 euthanatized calves was evaluated by use of direct immunofluorescent staining. All calves developed profuse diarrhea by PID 2 to 4; however, calves did not develop clinical signs of respiratory tract disease before euthanasia or death. Inoculated calves shed coronavirus in their feces as detected by use of immune electron microscopy. Infected nasal epithelial cells were detected in all but 2 orally inoculated calves (No. 9 and 10). Route of inoculation influenced the sequence of initial detection of coronavirus antigen from fecal specimens or nasal swab specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

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Porcine rotavirus-like virus (group B rotavirus): characterization and pathogenicity for gnotobiotic pigs.

A rotavirus-like virus (RVLV) was isolated from a diarrheic pig from an Ohio swine herd. This virus infected villous enterocytes throughout the small intestine of gnotobiotic pigs and induced an acute, transitory diarrhea. Complete virions were rarely observed in the intestinal contents of infected animals; the predominant particle detected by immune electron microscopy was a corelike particle 52 nm in diameter. The genome of the porcine RVLV was composed of 11 discrete segments of double-stranded RNA that produced an electropherotype distinct from the genome electropherotypes of reovirus, rotavirus, and porcine pararotavirus. Porcine RVLV was antigenically unrelated to rotavirus, porcine pararotavirus, or reovirus but was antigenically related to a bovine RVLV.

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Effects of polybrominated biphenyls on the excretion of steroids.

When polybrominated biphenyls (fireMaster BP-6, PBB) are ingested by cattle, they have been shown to alter hepatic enzyme systems, and produce renal lesions with chronic high exposure. These changes provide mechanisms for alteration of the metabolism and clearance of steroid hormones that might then affect reproductive function. This study was conducted to examine the effects of PBB on the excretion of radiolabel from injected estradiol-17 beta and progesterone. Toxicity was induced by dosing two Holstein cows with 25 g of fireMaster BP-6/d for 39 or 50 d. Single iv injections of 35 microCi [4-14C] progesterone and 400 microCi [2,4,6,7-3H] estradiol-17 beta were given on d -5, 10, 30 and 38 or 48 relative to dosing. Last injections were given when animals were terminally toxic. Clinical signs and necropsy findings confirmed the typical toxic syndrome and renal lesions. Excretion of 14C was primarily in feces, while 3H appeared in both urine and feces. As toxicosis developed, the excretion of steroids in feces was delayed as anorexia reduced mass and rate of passage of feces. This had little effect on the amount of steroid excreted and the rate of urinary excretion was affected only minimally. Recovery of both radiolabels declined 10 to 20% by d 30 of dosing as excretion rate was reduced from pre-PBB dosing. Excretion declined sharply when animals were moribund. Despite developing toxicosis, both animals continued to have estrous cycles with normal periodicity.

Animals↗

Performance and health of offspring of cows experimentally exposed to polybrominated biphenyls.

Offspring of cows experimentally given polybrominated biphenyls(fire-Master BP-6) were studied from May 1976 through January 1981. Daily doses were 0,.25, and 250 mg for 60 days for Groups I, II, and III, and 250 mg for 180 or 202 days for Group V. Concentrations of polybrominated biphenyls in fat of dosed animals in Groups I, II, and III, and V were .05, .20, 25, and 30 micrograms/g at the end of dosing. Residue concentrations in body fat declined with a half life of about 1 yr. Seventy-five calves were born to these cows and their offspring, representing first through fifth parturition. Fifteen calves died, 10 of which were in Groups III and V. All deaths in Groups III and V were attributable to dystocia. Incidence od dystocia and calf mortality were related to birth weight of the calf which in turn was correlated with concentrations of polybrominated biphenyls in blood and tissues of the dam. Other variables that influenced birth weight were sex of calf, length of gestation, and parturition number of dam. There were no significant differences in growth and performance of calves from the four dosed groups. Clinical signs of polybrominated biphenyl toxicosis were not evident, and general health of offspring was not influenced. Number of inseminations for conception was greater among offspring from Groups III and V. Mechanisms for this dysfunction have not been determined.

Animals↗

Comparative effects of sodium selenite and selenomethionine upon nutritional muscular dystrophy, selenium-dependent glutathione peroxidase, and tissue selenium concentrations of turkey poults.

Day-old poults from hens depleted of Se were fed low-Se basal diets (containing corn, soybean meal, and torula yeast but no added vitamin E) with graded levels of Se supplied by Na2SeO3 or seleno-DL-methionine for 28 and 35 days in Experiments 1 and 2, respectively. Adding .04 ppm Se to the basal diet significantly increased body weight and reduced both the incidence of gizzard myopathy and plasma glutamic-oxaloacetic transaminase (PGOT) activity. Further plasma Se and Se-dependent glutathione peroxidase (SeGSHpx) were elevated by increasing levels of dietary Se. There were no differences in these parameters due to the Se compound fed. Plasma SeGSHpx was significantly correlated with both dietary and plasma Se levels. Poults fed selenomethionine had significantly higher concentrations of Se in the gizzard, breast muscle, and pancreas, but not in the liver and heart, compared to poults fed Na2SeO3. These studies indicate that the utilization of Se in both Na2SeO3 and selenomethionine is approximately equal in young turkey poults.

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Rapid, simple method of preparing rotaviral double-stranded ribonucleic acid for analysis by polyacrylamide gel electrophoresis.

A procedure for extracting rotaviral double-stranded ribonucleic acid (RNA) directly from fecal and intestinal specimens collected from calves and pigs is described. This procedure provides a rapid, simple, reproducible method of obtaining rotaviral double-stranded RNA preparations suitable for electrophoretic analysis in polyacrylamide-agarose composite gels. The rotaviral genome electrophoretic migration pattern produced by double-stranded RNA extracted directly from a specimen by this procedure was qualitatively identical to the electrophoretic migration pattern obtained with double-stranded RNA extracted from purified rotavirus derived from the same specimen. Direct extraction of specimens containing porcine rotavirus-like virus by this procedure gave preparations that had electrophoretic migration patterns similar, but not identical, to the characteristic electrophoretic migration pattern of the rotaviral genome. Sufficient rotaviral double-stranded RNA could be extracted from 6 ml of fecal or intestinal specimen by this procedure to permit 15 or more electrophoretic assays.

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Ornithine decarboxylase, serum isocitrate dehydrogenase and clinical chemistry changes during thioacetamide-induced hepatotoxicity in a calf.

Our previous studies showed that polybrominated biphenyl (PBB) induced hepatic microsomal cytochrome P-450 in dairy cattle but did not elevate hepatic cytosolic ornithine decarboxylase or serum isocitrate dehydrogenase. These enzymes would be expected to increase during hepatotoxic injury and regeneration. Thus, PBB appeared to be a hepatotoxin in rats but not in cattle. In order to identify and confirm the response capability of bovine liver to hepatotoxins, we administered thioacetamide, a hepatotoxin known to induce hepatonecrosis, to a dairy calf. A progression of clinical signs of toxicosis was evident until the animal was moribund by 23 hr postdosing. Histolopathologic alterations in the liver included centrilobular necrosis with congestion and subcapsular microhemmorrhage. Marked changes in serum protein profiles were not noted. However, distinct increases in serum Fe and bilirubin occurred with progressing toxicosis, as did sharp declines in glucose and triglycerides. Serum lactic dehydrogenase, alkaline phosphatase, glutamic-oxaloacetic transaminase, isocitrate dehydrogenase and glutamic-pyruvate transaminase were elevated. Elevation of ornithine decarboxylase was dramatic when compared to the level in normal fetal bovine liver. From studies of its kinetic properties, bovine liver ornithine decarboxylase appears to have an apparent Km for ornithine decarboxylase of .45 mM. Liver homogenates from PBB-treated animals did not form inhibitors to ornithine decarboxylase. Compared with the thioacetamide-treated calf, the normal adult bovine, pregnant adult and 6-month fetus had relative activities of .2 .4 and 5.8%, respectively. These studies show that ornithine decarboxylase is low in liver of normal cattle, but is elevated markedly by agents that cause hepatonecrosis.

Acetamides↗

Long-term performance and health cows experimentally exposed to polybrominated biphenyls.

Fifteen Holstein cows were studied for up to 15 00 days to determine whether exposure to polybrominated biphenyls produced latent or subtle toxicosis not evident in previous acute or short studies. Animals for these long studies came from three groups given 0, .25, or 250 mg of fireMaster BP-6 per day for 60 days in 1975. Another group that received 250 mg of BP-6 for 180 or 202 days in 1976 also was studied. Individual animals were in their second, third, or fourth lactations. Milk production was not different among experimental groups, and mature body weights were similar. Increases in the amount or duration of exposure did not increase number of infections, dysfunctions, or general injuries. Exposure to 250 mg/day for 60, 180, or 202 days increased frequencies of reproductive disorders at parturition, particularly related to and following a high incidence of dystocia. A contributing factor to dystocia was larger birth weights of calves from cows exposed to 250 mg daily as compared to calves from cows exposed to 0 or .25 mg polybrominated biphenyls. Although reproductive dysfunctions required more veterinary care, numbers of services per conception were not different among groups.

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Effects of PBB on cattle. II. Gross pathology and histopathology.

Toxicosis was induced in pregnant Holstein heifers by feeding FireMaster BP-6 (polybrominated biphenyls) in daily oral doses of 25 g/head/day for 33--60 days. The individual heifers were dosed until each became moribund (days 33, 36, 39, 40, 41, or 66), at which time they were necropsied. Gross findings included dehydration, subcutaneous emphysema and hemorrhage, atrophy of the thymus, fetal death with concomitant necrosis of cotyledons, thickened wall of the gallbladder, inspissated bile, edema of abomasal folds, mucoid enteritis, linear hemorrhage and edema of the rectal mucosa, and secondary pneumonia. The livers were enlarged approximately 40%. Kidneys were approximately double the normal size and were pale tan to grey in color. The perirenal lymph nodes were enlarged and edematous. Microscopic changes were the most marked in the kidneys, gallbladder and eyelid. Extreme dilatation of collecting ducts and convoluted tubules with epithelial degenerative changes of cloudy swelling, hydropic degeneration and separation from the basement membrane were principal changes in the kidney. Hyperkeratosis with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands were characteristic findings in sections of eyelids. Moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria were common changes in the gallbladder. Foci of fatty degeneration and glycogen depletion were observed in liver sections. Necropsy of heifers immediately after 60 days exposure to 0.25 and 250 mg/head/day of PBB showed no gross or histopathological signs indicating toxicosis. Following parturition, at approximately 220 days after the PBB doses, heifers from the 0.25 and 250 mg/head/day groups and their calves were necropsied and displayed no signs of toxicosis.

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Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry.

Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5-1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with (131)I-sodium-iodohippurate and (125)I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained.

Animals↗

Effects of PBBs on cattle. I. Clinical evaluations and clinical chemistry.

Toxicosis was induced in pregnant heifers by feeding 25,000 mg/head/day of FireMaster BP-6, a commercial blend of polybrominated biphenyls (PBB). The PBB feeding decreased dry matter intake approximately 50% by 4 days exposure. Emaciated animals became anorexic a few days prior to death at 33 to 66 days. Weight losses of heifers average 80 kg. Other clinical signs observed were dehydration, diarrhea, excessive salivation and lacrimation, fetal death, abortion, and general depression as evidenced by depressed heart and respiratory rates. Clinical signs were apparent after 10 days exposure and progressively intensified along with loss of condition until death. Clinicopathologic changes included significantly increased serum glutamic-oxaloacetic transaminase and decreased serum calcium by 30 days exposure. Lactate dehydrogenase, urea nitrogen, and bilirubin were elevated, and serum albumin decreased by 36 to 40 days. Principal urine changes were decreased specific gravity and moderate proteinuria. Pregnant heifers fed 0.25 or 250 mg/head/day for 60 days and nonpregnant heifers fed 250 mg/head/day for 180 days displayed neither clinical signs nor clinicopathologic changes indicating adverse effects from PBB exposure. Post-exposure, all heifers exposed to PBB for 60 days calved normally with zero calf mortality and were successfully rebred. Milk production was not different from control animals. Birth weights of calves from dams exposed to 250 mg PBB/head/day were significantly greater than calves of dams exposed to 0 mg or 0.25 mg/head/day. PBB exposure of dams produced no detrimental effects on calves as indicated by clinical signs, clinicopathologic changes, or performance.

Animal Diseases↗

Use of the double-isotope, single-injection method for estimating renal function in normal and polybrominated biphenyl-exposed dairy cows.

A method is described for conducting a rapid and efficient renal function test in dairy cattle. The method, adapted from methods used for man and dogs, utilizes radiolabeled 131I-sodium iodohippurate to determine effective renal plasma flow (ERPF) and 125I-sodium iothalamate to determine glomerular filtration rate (GFR). The mean GFR for adult cattle was determined to be 2.8 +/- 0.4 ml/kg/minute with a biological half-life of 35.5 +/- 1.4 minutes. The mean ERPF was found to be 10.5 +/- 1.9 ml/kg/minute with a half-life of 17.9 +/- 0.6 minutes. These values are comparable with those in man, but are lower than values in dogs. A toxcity study was done with dairy cattle exposed to polybrominated biphenyls (PBB). Efforts were made to determine the amount of time required for kidney lesions to develop and, if possible, to delineate the potential site of action of PBB. Apparently PBB do not affect GFR or ERPF, even though they produce nephrotoxic effects. Potential mechanisms to explain these results are described.

Animals↗