Bovine protoporphyria: the first nonhuman model of this hereditary photosensitizing disease.

Protoporphyria, a photosensitizing disease documented only in humans, was transmitted as a recessive trait to seven female calves. Cutaneous lesions were extensive, and erythrocyte and fecal protoporphyrin concentrations exceeded by far those of human protoporphyria. Average ferrochelatase activity was decreased to one-half of normal in the liver of carriers, and to about one-tenth of normal in liver, kidney, heart, spleen, lung, and marrow of protoporphyrics.

A novel stop codon mutation (X417L) of the ferrochelatase gene in bovine protoporphyria, a natural animal model of the human disease.

Protoporphyria (PP) is caused by a deficiency of ferrochelatase (FC) activity, which catalyzes the final step in the heme biosynthesis pathway. Bovine are the only species other than man with naturally occurring PP. For expression of the PP phenotype, two copies of the mutated gene are necessary in bovine, whereas one copy is sufficient in humans. We report the first potential disease-causing mutation in the bovine FC gene. The coding region of FC was sequenced from the liver tissue of protoporphyric and normal bovine. A transversion was identified at nucleotide position 1250 which changed the stop codon to leucine (TGA-->TTA) in the protoporphyric FC sequence. As a consequence, the mutant protein is predicted to have an additional 27 amino acids. To screen other bovine for the G-->T transversion, cDNAs from liver tissue of clinically and biochemically normal, and from heterozygous and homozygous affected animals were used for allele-specific polymerase chain reaction. Three normal animals had only the G allele, five affected animals had only the T allele, and three heterozygous animals had both the G and T alleles. These results support our hypothesis that this mutation causes PP in bovine.

Lesions of perirenal hemorrhage syndrome in growing turkeys.

Turkeys from six market flocks were examined at 8 to 19 weeks of age to assess morphologic lesions of perirenal hemorrhage syndrome (PHS). PHS was diagnosed in 165 of 715 turkeys necropsied, and 82 turkeys served as age- and weight-matched controls. The most consistent gross findings were rounded pectoral muscles of normal color, ingesta-filled crops and gizzards, variable retroperitoneal perirenal hemorrhage, a swollen dark red and light purple spleen, congested intestinal blood vessels, and pulmonary edema and/or hemorrhage. The main histologic lesions of PHS were perivascular edema in lungs and kidneys, vascular congestion of various organs, renal perivenous hemorrhage, and proliferative arterial and arteriolar lesions in the spleen and kidneys that were more severe than those in controls. Heart weights, including mean relative weights of the right and combined left ventricles and interventricular septa, were significantly greater in turkeys that died with PHS than in controls. Scores for tibial dyschondroplasia and "breast blisters" were more severe in turkeys that died with PHS than in controls. The cardiovascular system appeared to be the PHS target system.

The incidence of perirenal hemorrhage syndrome in six flocks of market turkey toms.

Four flocks of the Nicholas strain and two of the British United turkey (BUT) strain of large white market turkey toms were monitored from 8 to 19 weeks of age to identify the presence, incidence, age distribution, and possible cause(s) of perirenal hemorrhage syndrome (PHS), or acute hypertensive angiopathy. Mortality rates varied among the flocks from 0.81% to 1.78% of total poults started. Nicholas flocks has a distinct peak in mortality between 9 and 14 weeks of age. PHS was the main cause of mortality from 8 to 14 weeks of age in all flocks except one, and the incidence diminished after 15 weeks of age. No significant bacterial pathogens were detected in any of the PHS cases. Distinct peaks in overall weekly mortality between 10 and 13 weeks of age similar to those in the four Nicholas flocks were also observed in six of 10 Minnesota flocks surveyed separately.

Perirenal hemorrhage syndrome in market turkey toms: effect of management factors.

Differences in the overall mortality rates and mortality due to perirenal hemorrhage syndrome (PHS) were compared in large white Nicholas tom turkeys. The study evaluated the effects of 1) four different light and temperature treatments; 2) three feed additives proposed to have anti-stress effects (reserpine, acetylsalicylic acid, and increased calcium); 3) toe-clipping on mortality, various disease conditions, and production parameters. Mortality varied from 0.60% to 3.57% among groups. Increased room temperature (21 C), toe-clipping, step-up/step-down lighting, and dietary reserpine reduced the incidence of PHS as compared with lower room temperature (13 C), no toe-clipping, intermittent lighting (2 hours light, 4 hours dark), and no dietary reserpine. Dietary aspirin or elevated calcium levels had no effect on PHS incidence. Overall mortality was greatest in the warmer rooms.

A chromosomal reciprocal translocation (1q+; 14q-) in a boar siring reduced litter sizes.

In our initial cytogenetic surveillance of boars one of 15 was found to be hypoprolific. It averaged 7.1 piglets per litter in over 51 monospermic matings with sows which, with other boars averaged 10.8 piglets per litter. Cytogenetic evaluations revealed only the hypoprolific boar to have an abnormal karyotype, namely {38XY, t(1;14) (q2.12, q2.2)}. This represents a new type of 1;14 reciprocal translocation, and also the first report of a reciprocal translocation for swine in the United States.

Angiomicrographic investigation of the vessels associated with physes in young pigs.

There is little information available relating to the vasculature of physes of pigs, hence the object of the present study was to establish the distribution of blood vessels in normal physes of pigs at one and 15 days old. By the use of an angiomicrographic technique it was possible to demonstrate that vessels were in two main categories; first, those which entered the physis from the epiphysis and terminated, or branched and then terminated half to two thirds of the distance into the depth of the physis; second, vessels which crossed the full depth of the physis. Since vessels that cross the physis from epiphysis to metaphysis were a frequent feature of normal physes they do not seem to be a congenital defect which predisposes to the development of dyschondroplasias in young pigs.

Health and metabolic responses of young calves housed at -30 degrees C to -8 degrees C.

Newborn, male, Holstein calves, were continuously housed for three weeks in calf hutches at 17 degrees C or in a thermal environment which varied rhythmically on a daily basis either between -20 degrees C and -8 degrees C (experiment A) or between -30 degrees C and -18 degrees C (experiment B). Compared to warm-housed calves, cold-housed calves in experiment A had metabolic rates which were significantly higher (p less than 0.001) in a standing position but which were not significantly different (p less than 0.05) in a recumbent position. Recumbent and standing cold-housed calves in experiment B had an increased (p less than 0.05) metabolic rate compared to warm-housed controls. Heat loss was less (p less than 0.05) for recumbent cold-housed calves in experiment B than for standing calves in a thermoneutral environment. Localized subcutaneous hemorrhages of hindlimbs were a consistent necropsy finding among all cold-housed calves. Average daily gains of cold-housed calves were not significantly different from warm-housed controls. Clinical, physiological and pathological findings indicated that cold treatments used in the present study did not cause serious harm to calves. It was concluded that calves housed in properly managed hutches are remarkably cold tolerant.

Thermal insulation of young calves exposed to cold.

Tissue, external and whole animal insulation values were determined for 12 newborn male Holstein calves continuously housed for two weeks in hutches within environmental chambers in which temperature was maintained at a constant 17 degrees C (three calves) or cycled on a daily basis either between -20 degrees and -8 degrees C (three calves) or between -30 degrees and -18 degrees C (six calves). Three of the six calves at the coldest temperature were outfitted with an insulated coat. The insulated coat provided calves a 52% increase in total insulation. Tissue insulation of cold-housed calves increased 37.2% over the first two weeks of life. It was concluded that the capacity for vasoconstriction improved with age. External insulation did not change significantly except during the first week in cold-housed calves without insulated coats. External insulation values were five to eight times those of tissue insulation values for all treatment groups. This indicated that insulation of structures external to the skin (hair, bedding, ground, etc.) provided most of the insulation for calves.

Ferula communis variety brevifolia intoxication of sheep.

Sheep given powdered Ferula communis variety brevifolia at dosage of 2.5 g/kg of body weight/d for 15 days developed classical clinical signs of intoxication: anorexia, somnolence, apparent weakness, and hemorrhage. Marked reduction of vitamin K-dependent coagulation factors and prolongation of prothrombin time and activated partial thromboplastin time were consistent with presence of ferulenol, a toxic coumarinic factor in the plant. Changes induced in the coagulation system developed by the second day of plant administration and were normal within 4 days after dosing was stopped. There was no evidence of primary liver damage or platelet malfunction. Of 6 intoxicated sheep, 2 died with only minimal evidence of hemorrhage.

Plasma ferulenol concentration and activity of clotting factors in sheep with Ferula communis variety brevifolia intoxication.

Dynamics of plasma ferulenol concentration and its effect on the vitamin K-dependent coagulation factors, prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined in 4 sheep intoxicated individually with 600 g of powdered Ferula communis variety brevifolia (FCb) given in 8 doses at intervals of 6 hours. Ferulenol was detected in the plasma of all sheep at initial blood sample collection, 6 hours after the first dose of approximately 75 g of FCb was placed in the rumen. The last observed peak of approximately 20 micrograms/ml was detected at about 12 hours after the last of 8 doses, and the mean concentration then decreased to < 1 microgram/ml during the next 70 hours. Maximal concentration of ferulenol and time for plasma clearance varied with individual sheep. The PT increased steadily to a maximum of 6 times normal about 70 hours after the last peak plasma ferulenol concentration and about 80 hours after FCb administration was stopped. The PT then returned to almost normal (ratio of 1.12) from the maximum (ratio of 6.12) within approximately 5 days. The APTT results generally paralleled the PT results, but the change was not as marked. Maximal PT and APTT ratios were animal-dependent and not always related to plasma ferulenol concentration. The activity of all the vitamin K-dependent coagulation factors was depressed, but the variations were unique to each factor. Factor V, a vitamin K-independent coagulation factor actually had a brief period of increased plasma activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyschondroplasias, including osteochondrosis, in boars between 25 and 169 days of age: histologic changes.

Microscopic sections of physeal and articular-epiphyseal (A-E) cartilages from major limb bones of 60 boars between 25 and 169 days of age were examined. The objectives in this study were to determine the age of onset and pathogenesis of osteochondrosis, a defect of endochondral ossification. Lesions regarded as typical of osteochondrosis were associated with physes of pigs from 25 days of age, indicating an earlier age of onset than has generally been documented. Two morphologically distinct lesions were observed, but both had areas with increased depth of the zone of hypertrophying chondrocytes. Some lesions were repairing. With increasing age of the pigs, the number of involved physes increased in each of 6 different age groups up to 169 days. Lesions associated with physes were observed in boars younger than those with lesions associated with A-E complexes. A few pigs at, or older than, 53 days of age, had osteochondrosis-like lesions involving epiphyseal growth cartilages. However, a dyschondroplasia different from osteochondrosis and typified by chondrolysis was more frequently associated with A-E complexes of pigs at or greater than 79 days of age. The number of affected cartilages and sites with this type of lesion also increased with age. Although osteoarthrosis had not developed in any of the pigs, it is probable that chondrolytic areas were precursors of degenerative joint disease. To date, osteochondrosis has been used to encompass lesions involving physes and A-E complexes. However, in view of the findings in the present study, dyschondroplasia is the preferred term to be used generically and then qualified by morphologic description, since causations may be different.

Dyschondroplasias, including osteochondrosis, in boars between 25 and 169 days of age: radiologic changes.

Boars in 6 different groups (between 25 and 169 days of age) were examined radiographically to determine the age of onset of lesions associated with the sites of endochondral ossification in limb bones. Although lesions were in histopathologic sections of physes from all groups of pigs, they were not found frequently in radiographs of live animals until boars were more than 100 days old. Microscopic lesions were infrequent in articular-epiphyseal (A-E) complexes of pigs less than 80 days old, and radiographic examination of live animals had limited value until animals were greater than 100 days old. Radiographs of slabs of bone were useful in the detection of physes with lesions in all age groups and A-E complexes with lesions in boars 100 days of age or older. So that the accuracy of radiographic examination of live animals for the diagnosis of dyschondroplasias could be evaluated, a comparison was made between the numbers of growth cartilages with lesions as determined by radiologic examination of live animals, radiographic examination of slabs of bone, and light microscopy (examination of tissue sections). Only 21% of the lesions associated with physes and 22% of the lesions associated with A-E complexes were detected in radiographs of bones of live pigs. The authors concluded that the latter method was inaccurate for the identification of dyschondroplastic foci. Identification of lesions by examination of radiographs of slabs of bone was only slightly more accurate, since 33% of physes and 23% of A-E complexes which had lesions were found. Potential errors in evaluation of radiographs were discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of bile porphyrin concentrations in cattle and human beings with protoporphyria.

Blood and bile porphyrin concentrations were measured in cattle with protoporphyria and compared with those in human beings with the disease. Whereas the mean RBC porphyrin concentration in cattle was 18-fold greater than in human beings, the mean bile porphyrin concentration was only 78% greater. Sequential measurements over a 30-hour period in 1 animal with a bile fistula indicated that the ratio of total porphyrin to total bile acid in bile varied minimally. When the animal was given an IV infusion of taurocholate, the biliary excretion rate of porphyrin increased in parallel with that of bile acid, because of enhancement of bile flow. Thus, in cattle with protophorphyria, the concentration of porphyrin in bile is low compared with that of porphyrin in RBC, in contrast with findings in human beings, and adequate amounts of bile acids are secreted to maintain efficient protoporphyrin excretion. This explains, in part, why hepatobiliary disease has not been observed in cattle with protoporphyria, but has been seen in human beings with the disease.

Efficacy and safety of selenium-vitamin E injections in newborn pigs to prevent subclinical deficiency in growing swine.

Seventy-eight newborn pigs were allotted to 4 treatment groups: 22 pigs in group A were given no selenium-vitamin E (Se-E), 22 pigs in group B were given small doses of Se-E, 22 pigs in group C were given medium doses of Se-E, and 12 pigs in group D were given large doses of Se-E. Pigs were intramuscularly injected before 7 days of age and at weaning (40 days of age), respectively, as follows: group A--1 ml of physiologic saline solution/pig each time, group B--0.25 mg of Se/pig and later 0.06 mg of Se/kg of body weight, group C--1.0 mg of Se/pig and later 0.24 mg of Se/kg, and group D--1.5 mg of Se/pig and later 0.72 mg of Se/kg. Selenium was supplied as sodium selenite in commercially available Se-E injectable compounds. From 2 weeks of age to weaning, the pigs were fed a corn-torula yeast creep feed containing Se at the concentration of 0.03 ppm, and from weaning to slaughter, a corn-soybean meal ration was fed containing Se at the concentration of 0.07 ppm and alpha-tocopherol at the concentration of 15.7 mg/kg. Subclinical Se-E deficiency developed in control pigs of group A and was characterized by subtle muscular stiffness, significant increases in plasma activities of glutamic oxalacetic transaminase (GOT) and creatine phosphokinase (CPK), and typical residual lesions in heart and skeletal muscle, but not in liver, at slaughter at 165 days of age. Pigs injected with Se-E did not develop these evidences of subclinical deficiency. Pigs in group D were stunted for several weeks after the 2nd Se-E injection, and plasma GOT and CPK activities were significantly increased at 3 weeks after injection. Growth rates were otherwise similar between groups. Significant difference in Se content of liver, muscle, serum, and hair was not seen between pigs in the 4 groups at 120 and 165 days of age. A test period of physical exertion and heat stress resulted in significant increase of plasma GOT and CPK activities in 4 of 8 pigs at 110 days of age.

Histochemical morphologic features of growth cartilages in long bones of pigs of various ages.

Growth cartilages were obtained from humeri, femora, and ulnae of 31 pigs between 1 and 169 days old. On the basis of stain uptake and distribution, distinct layers were identified in articular-epiphyseal cartilage complexes and growth plates. The laminated appearance was dependent on stain uptake by territorial and interterritorial matrices and was more distinct in pigs greater than 15 days old. There was morphologic heterogeneity, which probably represented a functional heterogeneity, among chondrocytes in all layers and zones of both types of growth cartilage. The laminar appearance of growth cartilages and the distribution of different types of cells were similar for all pigs in each age category and for all sites.

Blastomycosis in wild wolves.

Blastomycosis was fatal to a wild wolf in Minnesota, and serologic evidence of blastomycosis was found in a Wisconsin wolf. No unusual movements were detected in the Minnesota animal from October 1983 through October 1985. However, by early December 1985, this wolf was weak and debilitated, and it perished on 14 December after approaching a human residence.

Trichophyton mentagrophytes dermatophytosis in wild fox.

Dermatophytosis caused by a zoophilic varient of Trichophyton mentagrophytes was diagnosed in a litter of eight captured wild red fox (Vulpes fulva). The animals had widespread partial alopecia and scattered crusty foci 2 to 3 cm in diameter on the skin. Treatment with 7 mg/kg/body weight/day of griseofulvin in the feed effectively controlled the infection.

XX/XY chimerism and freemartinism in a female llama co-twin to a male.

A 20-month-old female llama was examined because at the time of mating, the male llama was apparently unable to achieve intromission. The female llama had been born co-twin to a male. On physical examination, the vaginal vestibule appeared to end in a blind pouch, and the uterus, cervix, and ovaries could not be identified during transrectal palpation or ultrasonography. Karyotyping was done, and 43% of blood lymphocytes had 2 X chromosomes, and 57% had 1 X and 1 Y chromosome. All skin fibroblasts had 2 X chromosomes. A diagnosis of freemartinism and XX/XY chimerism was made. Because conception of twins may be more common in llamas than birth of twins, it is possible that freemartinism could develop in singleton females, if, for instance, a male twin was conceived and died after the placentas had anastomosed. More widespread use of karyotyping in llamas with congenital defects of the reproductive tract will help to define the incidence of freemartinism.

Prevalence of the 14/20 centric fusion chromosomal aberration in US Simmental cattle.

Cytogenetic evaluation was made on 353 Simmental cattle (166 male, 187 female) from 113 herds in 26 states. One hundred thirty-eight (39%) were found to be heterozygous-positive for the 14/20 centric fusion chromosomal translocation, including 41 (25%) males and 97 (52%) females. One submitted heparinized blood sample from a Simbrah bull was found to be positive for 14/20 and 1/29 centric fusions. Sampling, which was based on requests, was highly selective. Thus, the 39% prevalence found was not representative of 14/20 centric fusion in the national Simmental breed. On the basis of our findings, cytogenetic evaluation of breeding stock was consistent with modern management practice.