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PubMed2001

Biomechanical and morphologic evaluation of a three-dimensional fabric sheep artificial intervertebral disc: in vitro and in vivo analysis.

STUDY DESIGN: We have developed a new artificial intervertebral disc consisting of triaxial three-dimensional fabric for the sheep lumbar spine. To clarify the characteristics of the new implant, a series of biomechanical tests and morphologic evaluations were conducted. OBJECTIVES: To investigate the static, viscoelastic, and fatigue properties of the three-dimensional fabric disc in comparison with natural sheep disc and to evaluate their biomechanical and morphologic alteration in vivo. SUMMARY OF BACKGROUND DATA: In its human dimensions the three-dimensional fabric disc revealed mechanical properties similar to a natural human disc. METHODS: The disc-body units from sheep spine and the sheep three-dimensional fabric discs underwent tensile-compressive (200 N), torsional (5 Nm), and creep-recovery tests (30 minutes-30 minutes, 200 N). After fatigue loading (2 million, compressive 200 N) the biomechanical changes and the debris were investigated. For in vivo evaluation after placing in the sheep psoas muscles for 6 months, the surface of the three-dimensional fabric disc was evaluated using macroscopy and scanning electron microscopy, followed by previous biomechanical tests. RESULTS: The behavior of the sheep three-dimensional fabric disc was similar to that of natural sheep disc in tensile-compressive and creep-recovery tests. In torsional testing the behavior of natural sheep disc was more rigid than that of the sheep three-dimensional fabric disc. After fatigue loading there was no biomechanical change and no debris detected. Six months after surgery no morphologic deterioration was observed nor were there changes in biomechanical parameters. CONCLUSIONS: The sheep three-dimensional fabric disc exhibited biomechanical and morphologic biostability, appropriate viscoelasticity, and excellent fatigue properties. The three-dimensional fabric disc has a potential for clinical application of human intervertebral disc replacement.

Animals↗
PubMed1992

Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration.

Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one-compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats.

Administration, Oral↗
PubMed1995

Comparative pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous administration to sheep and goats.

The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination was studied after intravenous administration of single doses (20 mg/kg per kg body weight) to five sheep and six goats. The objective was to determine whether there are differences between sheep and goats in the disposition of amoxicillin and clavulanic acid. The plasma concentration-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in sheep and goats. The elimination half-lives of amoxicillin were 1.43 +/- 0.16 h in sheep and 1.13 +/- 0.19 h in goats, and of clavulanic acid were 1.16 +/- 0.01 h and 0.85 +/- 0.09 h in sheep and goats respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. Body clearances of amoxicillin were 0.09 +/- 0.01 L/h kg in sheep and 0.11 +/- 0.01 L/h kg in goats, and of clavulanic acid were 0.07 +/- 0.01 L/h kg and 0.12 +/- 0.01 L/h kg in sheep and goats respectively. The half-lives and body clearances of amoxicillin and clavulanic acid differed significantly between sheep and goats. It was concluded that the disposition of amoxicillin and clavulanic acid administered intravenously as an amoxicillin/clavulanic acid combination to sheep and goats differed between the two ruminant species. Even though the differences in disposition kinetics of both drugs were statistically significant, the same intravenous dosing rate of this antimicrobial combination can generally be used in sheep and goats.

Amoxicillin↗
PubMed1992

Cell-surface regulation of the human alternative pathway of complement. Sheep but not rabbit erythrocytes express factor I-dependent cofactor activity.

When incubated in normal human serum, rabbit erythrocytes are haemolysed as a result of activation of the alternative pathway of complement (APC), but sheep erythrocytes do not spontaneously activate the human APC under physiological conditions. The mechanism for this difference has been attributed to differences in the relative affinity of membrane-bound C3b for its natural ligands, factor B and factor H, that favour the formation and stability of the APC C3 convertase on rabbit erythrocytes and inhibit convertase activity on sheep erythrocytes. Previous studies have also suggested that factor I inactivated C3b on sheep erythrocytes more effectively than on rabbit erythrocytes. Further, sheep erythrocytes have recently been shown to have a membrane protein that associates non-covalently with cell-bound C3b, but rabbit erythrocytes lack a predominant C3b binding protein. Together, these results suggested the possibility that sheep but not rabbit erythrocytes have a membrane constituent with factor I cofactor activity. To investigate this hypothesis, rabbit and sheep erythrocytes bearing radiolabelled C3b were treated either with factor I or with factor I and factor H, and conversion to iC3b was assessed by autoradiography. Factor I caused a concentration-dependent conversion of C3b to iC3b on sheep erythrocytes; however, only trace amounts of C3b on rabbit erythrocytes were degraded even when high concentrations of factor I (83 micrograms/ml) were used. While C3b on rabbit erythrocytes was converted to iC3b by the combination of factor H and factor I, much less factor H was required for the same degree of conversion of C3b on sheep erythrocytes. Treatment of sheep erythrocytes with neuraminidase had no effect on either factor I-dependent cofactor activity or the capacity of factor H to serve as a factor I cofactor. Sheep erythrocytes did not manifest decay accelerating activity, however, suggesting that the factor I cofactor constituent is a functional analogue of the human membrane cofactor protein.

Animals↗
PubMed1998

Characterisation of human natural anti-sheep xenoantibodies.

Currently, the pig species is regarded as the most likely organ donor for human xenotransplantation in the future. However, it cannot be granted that the pig will be the optimal species of choice. We have studied human anti-sheep antibodies in comparison with anti-pig antibodies. The anti-sheep lymphocytotoxic and hemagglutination titers were in the range 8 to 128 and 2 to 32, respectively, in single individuals, which were considerably lower than the anti-pig titers of these individuals. Perfusion of sheep kidneys with human blood reduced the anti-sheep xenoantibody titers to zero as measured by lymphocytotoxic, hemagglutination, and sheep aortic endothelial cell antibody binding assays. The perfused kidneys showed generalised depositions of human IgM and C3c in the vascular tree and focal depositions of C1q and fibrin. Obliteration of capillaries by human platelets and polymorphonuclear cells were observed. Total neutral glycolipid fractions were isolated from sheep intestinal, pancreatic, and kidney tissues. By using a chromatogram binding assay, a monoclonal anti-Forssman antibody identified a single compound with five sugar residues in all organs. Several glycolipid bands were stained in all organs by the Gal(alpha)1-specific lectin I-B4 from Griffonia (Bandeiraea) Simplicifolia. A human AB serum pool showed staining by both IgG and IgM antibodies of the Forssman and Gal(alpha)1-terminating components as well as some other, not structurally identified, components. The Forssman and Gal(alpha)1-reactivity in human sera could be eliminated by immunoadsorption using Forssman and Gal(alpha)1-3Gal-immunoadsorbent columns, respectively. Immunostaining of sheep kidney tissue sections showed the presence of Gal(alpha)1-terminating epitopes by immunoperoxidase and immunogold silver staining techniques. Proximal convoluted tubules showed a strong staining, while thin loops of Henle, collecting ducts, urothelium, and vessels showed a weaker staining. Distal convoluted tubules and thick loops of Henle were completely negative. In summary, human serum contains anti-sheep xenoantibodies reacting mainly with the Forssman and Gal(alpha)1-determinants in sheep tissues and the anti-sheep antibody titers are lower than the corresponding anti-pig titers.

Animals↗
PubMed1999

[Basic study of Beutin's washed sheep blood agar plate used for selective screening of verocytotoxin-producing/enterohemorrhagic Escherichia coli (VTEC/EHEC)].

Enterohemolysin production of Beutin's washed sheep blood agar plate has been used as an epidemiological marker for selective screening of Verocytotoxin-producing/Enterohemorrhagic Escherichia coli (VTEC/EHEC). In this study, we examined about the component of Beutin's washed sheep blood agar for further improvement of hemolysin production media. The following items were studied: the numbers of washings of sheep blood with phosphate buffered saline (PBS) (pH 7.2), concentration of sheep blood, kind and concentration of divalent metal ion (Ca2+, Mg2+) and basal medium. Twenty-seven strains of VT-producing E. coli of 7 different O-serotypes, 74 strains of VT-nonproducing E. coli of 24 different O-serotypes and one strain of O157 coded Escherichia hermanii were used for this basic study. In comparison of washing times of sheep blood with PBS, 5 times washing was better than 3 times, the original. In sheep blood concentration, supplement with 4% sheep blood was best for hemolysis observation. In experiment of addition of 2 divalent metal ions, Ca2+ and Mg2+, supplement with Ca2+ was more suitable than Mg2+ for hemolysis, and the supplement with 10 mM CaCl2, the original, was the best concentration. On the basal medium used in Beutin's sheep washed blood agar, 4 kinds of media were compared. In addition to Soybean-Casein Digest (SCD) agar, the original, Nutrient agar, Heart Infusion (HI) agar and Brain Heart Infusion (BHI) agar were examined, HI agar was the best blood agar base in the four media. As the above experimental results, the composition of the better Beutin's washed sheep blood agar may be summarize as follows: Heart Infusion agar 'Eiken' used for blood agar base, supplemented with 10 mM CaCl2 and 4% defibrinated sheep blood (Japan biosupp. Center) washed five times in phosphate-buffered saline, pH 7.2.

Animals↗
PubMed2004

Molecular diversity of rumen methanogens from sheep in Western Australia.

The molecular diversity of rumen methanogens in sheep in Australia was investigated by using individual 16S rRNA gene libraries prepared from the rumen contents obtained from six merino sheep grazing pasture (326 clones), six sheep fed an oaten hay-based diet (275 clones), and five sheep fed a lucerne hay-based diet (132 clones). A total of 733 clones were examined, and the analysis revealed 65 phylotypes whose sequences (1,260 bp) were similar to those of cultivated methanogens belonging to the order Methanobrevibacter: Pasture-grazed sheep had more methanogen diversity than sheep fed either the oaten hay or lucerne hay diet. Methanobrevibacter strains SM9, M6, and NT7 accounted for over 90% of the total number of clones identified. M6 was more prevalent in grazing sheep, and SM9, despite being found in 16 of the 17 sheep, was more prevalent in sheep fed the lucerne-based diet. Five new species were identified. Two of these species exhibited very little sequence similarity to any cultivated methanogens and were found eight times in two of the six sheep that were grazing pasture. These unique sequences appear to represent a novel group of rumen archaea that are atypical for the rumen environment.

Animals↗
PubMed2002

Lotus corniculatus condensed tannins decrease in vivo populations of proteolytic bacteria and affect nitrogen metabolism in the rumen of sheep.

Condensed tannins in forage legumes improve the nutrition of sheep by reducing ruminal degradation of plant protein and increasing crude protein flow to the intestine. However, the effects of condensed tannins in forage legumes on rumen bacterial populations in vivo are poorly understood. The aim of this study was to investigate the specific effects of condensed tannins from Lotus corniculatus on four proteolytic rumen bacteria in sheep during and after transition from a ryegrass (Lolium perenne)-white clover (Trifolium repens) diet (i.e., low condensed tannins) to a Lotus corniculatus diet (i.e., higher condensed tannins). The bacterial populations were quantified using a competitive polymerase chain reaction. Lotus corniculatus was fed with or without ruminal infusions of polyethylene glycol (PEG), which binds to and inactivates condensed tannins, enabling the effect of condensed tannins on bacterial populations to be examined. When sheep fed on ryegrass-white clover, populations of Clostridium proteoclasticum B316T, Butyrivibrio fibrisolvens C211a, Eubacterium sp. C12b, and Streptococcus bovis B315 were 1.5 x 10(8), 1.1 x 10(6), 4.6 x 10(8), and 7.1 x 10(6) mL(-1), respectively. When the diet was changed to Lotus corniculatus, the average populations (after 8-120 h) of C. proteoclasticum, B. fibrisolvens, Eubacterium sp., and S. bovis decreased (P < 0.001) to 2.4 x 10(7), 1.1 x 10(5), 1.1 x 10(8), and 2.5 x 10(5) mL(-1), respectively. When PEG was infused into the rumen of sheep fed Lotus corniculatus, the populations of C. proteoclasticum, B. fibrisolvens, Eubacterium sp., and S. bovis were higher (P < 0.01-0.001) than in sheep fed Lotus corniculatus without the PEG infusion, with average populations (after 8-120 h) of 4.9 x 10(7), 3.8 x 10(5), 1.9 x 10(8), and 1.0 x 10(6), respectively. Sheep fed the Lotus corniculatus diet had lower rumen proteinase activity, ammonia, and soluble nitrogen (P < 0.05-0.001) than sheep that were fed Lotus corniculatus plus PEG. The Lotus corniculatus diet reduced rumen nitrogen digestibility (P < 0.05) and ammonia pool size and increased the flow of undegraded feed nitrogen to the abomasum. The nitrogen intake, rumen non-ammonia nitrogen pool size, rumen microbial non-ammonia nitrogen pool size, and abomasal microbial non-ammonia nitrogen fluxes were similar both in sheep fed only Lotus corniculatus and in sheep fed Lotus corniculatus plus PEG, but nonmicrobial non-ammonia nitrogen flux to the abomasum was higher (P < 0.01) for the sheep fed only Lotus corniculatus. Although condensed tannins in Lotus corniculatus reduced the populations of some proteolytic bacteria, total ruminal microbial protein and microbial protein outflow to the abomasum were unchanged, suggesting a species-specific effect of condensed tannins on bacteria in the rumen.

Animals↗
PubMed1986

Effects of methylprednisolone on lung oxygen toxicity in awake sheep.

The purpose of this study was to measure the effects of high doses of corticosteroids on the response to breathing 100% O2 in sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies were made for accurate delivery of gas mixtures. Eight sheep received methylprednisolone 30 mg/kg body wt every 6 h for eight doses, four for the first 48 h, and four for the final 24-48 h of 100% O2 breathing. Eight control sheep breathed 100% O2 without methylprednisolone, four sheep breathed compressed air without methylprednisolone, and two breathed compressed air and received methylprednisolone. Sheep had daily measurements of hypoxic vasoconstriction (fractional concentration of O2 in inspired gas = 0.12), gas exchange, lymph flow, and lymph and plasma protein concentration. Polymorphonuclear leukocyte (granulocyte) function in experimental and control sheep was assessed ex vivo by tests of chemotaxis, aggregation, and superoxide production. The number of granulocytes in peripheral lung was measured in biopsy tissue taken at the time of original surgery and postmortem. Methylprednisolone did not affect the time course nor magnitude of gas exchange abnormality, lymph flow and composition, loss of hypoxic vasoconstriction, lung granulocyte accumulation, nor postmortem lung water caused by 100% O2 breathing. Sheep receiving methylprednisolone had a shorter survival by several h, independent of the timing of the drug. Granulocytes from methylprednisolone-treated sheep showed normal function ex vivo by all three assays. We conclude that high doses of methylprednisolone unfavorably affect the rate and progression of lung injury in sheep breathing 100% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages.

The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1-20 micrograms) in young sheep produced dose-dependent vasodilation (6.1-15.5% fall in perfusion pressure) and smooth muscle contraction (0.06-0.28 mm reduction in tracheal diam). In old sheep, antigen (1-20 micrograms) produced vasoconstriction (4.1-16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep.

Age Factors↗
PubMed2001

The calpain system in three muscles of normal and callipyge sheep.

Activities of mu- and m-calpain and of calpastatin were measured at four different times during postmortem storage (0, 1, 3, and 10 d) in three muscles from either callipyge or noncallipyge (normal) sheep. The weights of two muscles, the biceps femoris and the longissimus, are greater in the callipyge phenotype, whereas the weight of the infraspinatus is not affected. The activity of m-calpain was greater (P < 0.05) in the biceps femoris and longissimus from callipyge than in those from normal sheep, but it was the same in the infraspinatus in the two phenotypes. The extractable activity of m-calpain did not change (biceps femoris and infraspinatus) or decreased slightly (longissimus) during postmortem storage. Extractable activity of mu-calpain decreased to zero or nearly zero after 10 d postmortem in all muscles from both groups of sheep. The rate of decrease in mu-calpain activity was the same in muscles from the callipyge and normal sheep. At all time points during postmortem storage, calpastatin activity was greater (P < 0.05) in the biceps femoris and longissimus from the callipyge than from the normal sheep, but it was the same in the infraspinatus from callipyge and normal sheep. Calpastatin activity decreased (P < 0.05) in all three muscles from both phenotypes during postmortem storage; the rate of this decrease in the callipyge biceps femoris and longissimus and in the infraspinatus from both the callipyge and normal sheep was slow, especially after the first 24 h postmortem, whereas calpastatin activity in the biceps femoris and longissimus from the normal sheep decreased rapidly. During postmortem storage, the 125-kDa calpastatin polypeptide was degraded, but the 80-kDa subunit of mu-calpain was cleaved only to 76- and 78-kDa polypeptides even though extractable mu-calpain activity declined nearly to zero. Approximately 50 to 60% of total mu-calpain became associated with the nonextractable pellet after 1 d postmortem. The myofibril fragmentation index for the biceps femoris and longissimus from normal sheep increased significantly during postmortem storage. The fragmentation index for the infraspinatus from the callipyge and normal sheep increased to an intermediate extent, whereas the index for the biceps femoris and longissimus from the callipyge did not change during 10-d postmortem storage. The results suggest that postmortem tenderization is related to the rate of calpastatin degradation in postmortem muscle and that calpastatin inhibition of the calpains in postmortem muscle is modulated in some as yet unknown manner.

Animals↗
PubMed1992

Renin-angiotensin and autonomic mechanisms in cardiovascular homeostasis during haemorrhage in fetal and neonatal sheep.

The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed2003

[Study on the level of specific IgG, IgG1 and IgE during anaphylactic shock in sheep induced by Echinococcus granulosus].

OBJECTIVE: To investigate the change of specific antibodies IgG, IgG1 subclass and IgE in sheep infected with Echinococcus granulosus (E. g) during anaphylactic shock, and to observe antigen B reactivity against IgG antibody in E. g-infected sheep. METHODS: Antigen B and crude antigen were prepared with E. g cyst fluid (EgCF) from infected sheep. The enzyme-linked immunosorbent assay(ELISA) was used for detecting the level of specific IgG, IgG1 and IgE during anaphylactic shock in sheep induced by E. g. RESULTS: The level of specific IgG, IgG1 and IgE was significantly higher in the infected sheep after 6 months than that of the uninfected control group (P < 0.01). The IgE level decreased rapidly after anaphylactic shock induced, especially when the sheep was dying. Following an antigen challenge the sheep showed a general decrease in total IgG and IgG1 subclass. The total IgG showed a slight change at the beginning, followed by a decrease 1 h after challenge. The decrease of IgG1 subclass was more significant than the total IgG in 40 min after challenge injection. The positive rate was 91% for antigen B and 32% for crude antigen of EgCF against IgG antibody in E. g-infected sheep. CONCLUSION: The specific IgE plays a major role in the anaphylactic shock, while IgG and IgG1 antibodies are also important. Antigen B derived from sheep E. g cyst fluid appears to be useful in serodiagnosis of and monitoring on the infection status in sheep.

Anaphylaxis↗
PubMed1987

N-terminal amino acid sequence analyses of the alpha and beta polypeptides from four distinct subsets of sheep major histocompatibility complex class II molecules.

Four monoclonal antibodies, SBU.II 28-1, 37-68, 38-27, and 42-20, each recognizing a distinct, non-overlapping subset of sheep class II molecules, were used to purify class II molecules from a single sheep. Four class II alpha subunits designated 28-1 alpha, 37-68 alpha, 42-20 alpha, and 38-27 alpha and five class II beta subunits designated 28-1 beta, 37-68 beta 1, 37-68 beta 2, 42-20 beta, and 38-27 beta were compared by N-terminal sequence analyses. Two distinct alpha subunits were identified; the 28-1 alpha, 37-68 alpha, and 42-20 alpha subunits all had identical N-terminal amino acids sequences, which exhibited about 75% homology with HLA-DR alpha and mouse E alpha polypeptides. In contrast, the 38-27 alpha sequence exhibited about 80% sequence homology with HLA-DQ alpha and mouse A alpha polypeptides. In general, sheep beta subunits displayed insufficient sequence homology to enable correlation with human beta-chain sequences; however, the 38-27 beta-chain sequence showed homology with the HLA-DQ beta sequence. The conserved sequence surrounding the site for N-linked glycosylation within human/mouse beta polypeptides (residues 19 to 21) was not present in sheep beta sequences and in contrast with the beta-chains of mouse and man, sheep beta polypeptides contained between 1 and 3 positionally variable cysteine residues (residues 13 to 15 inclusive). Individual sheep beta subunits exhibited extensive sequence heterogeneity and each consisted of a unique population of beta polypeptide species. At least 16 different beta polypeptide sequences were identified from a single sheep and the existence of no fewer than nine non-allelic beta genes was inferred from the sequence data. We have previously provided evidence suggesting that the sheep has multiple major histocompatibility complex class II alpha and beta genes related to those of all three HLA-D subregions. The present results suggest that a number of these genes encode HLA-DQ-like heterodimers and that a sheep DR-like alpha gene product is shared with the products of a large and heterogeneous sheep beta gene family.

Amino Acid Sequence↗
PubMed1986

Nephritogenic potential of sheep antibodies against glomerular basement membrane laminin in the rat.

Antilaminin antibodies have been shown to bind to laminin within the glomerular basement membrane (GBM) and mesangium of experimental animals but have induced little or no glomerular injury. We used a sheep antiserum to murine Englebreth-Holm-Swarm sarcoma laminin (sheep antilaminin) to further study the potential of antilaminin antibodies to cause glomerular injury. Intravenous injections of sheep antilaminin into rats produced intense linear GBM deposits of sheep IgG but consistently failed to induce heterologous phase proteinuria as previously shown. In addition, no autologous phase injury appeared even after preimmunization with sheep IgG (N = 4) or passive administration of rat anti-sheep IgG (N = 3) (mean urine protein less than 4 mg/24 hours up to 16 days). GBM deposits of rat C3 in vivo were absent despite the ability of both sheep antilaminin and rat anti-sheep IgG to fix human and rat C3 in vitro as determined by an indirect immunofluorescent assay. In contrast, when kidneys containing sheep antilaminin were transplanted into naive recipients that were passively immunized with rat anti-sheep IgG, severe proteinuria occurred (range 7 to 109 mg/24 hours on day 2; 49 to 350 mg/24 hours on day 5 posttransplantation) in association with glomerular deposition of C3. Histological evaluation at day 5 showed a severe proliferative glomerulonephritis with infiltrating polymorphonuclear and mononuclear leukocytes. Electron microscopy showed endothelial and epithelial cell detachment from the GBM and inflammatory cell adherence to denuded GBM. Epithelial foot process effacement and cytoplasmic absorption droplets were also noted. Identical kidneys transplanted into nonimmunized recipients or immunized recipients depleted of complement had significantly less (p less than 0.05) proteinuria (nonimmunized: 5 to 18 mg/24 hours on day 2, 4 to 9 mg/24 hours on day 5; complement-depleted: 6 to 13 mg/24 hours on day 2, 4 to 27 mg/24 hours on day 5) and no glomerular complement fixation was seen in these animals. Thus, severe glomerular injury can be induced by a focused, amplified, complement-dependent immune attack on glomerular laminin. In contrast, the widespread distribution of laminin and antilaminin probably dilutes the total glomerular immune reaction and precludes effective complement fixation and glomerular injury during the autologous phase in nontransplanted kidneys. A similar explanation might account for the lack of glomerular injury in previous studies that utilized antisera to known GBM constituents.

Animals↗
PubMed1987

Pharmacokinetics of selenium administered parenterally at toxic doses in sheep.

Pharmacokinetics of Se were evaluated in 24 female crossbred sheep, 8 to 14 months of age, after toxic doses of Se were administered. Five groups of 4 sheep each were given 0.4, 0.6, 0.7, 0.8, or 1 mg of Se/kg of body weight, IM. Nine of these sheep died within 36 hours after Se administration. Blood Se disappearance curves were triphasic for the 11 sheep that lived for at least 36 hours after Se administration and were biphasic for the 9 sheep that died within 36 hours. The lambda 2 rate constants of Se disposition after IM administration indicated a dose dependency. Sheep given 0.4, 0.6, 0.7, or 0.8 mg of Se/kg had lambda 2 rate constants of 0.110, 0.079, 0.046, and 0.034 hour-1, respectively (r2 = 0.97). The respective half-lives of the 2nd distributive phase after IM administration were 6.3, 8.8, 15.1, and 20.4 hours. In the 11 sheep that had triphasic pharmacokinetics, the mean lambda 3 elimination rate was 0.0011 hour-1. Four additional sheep were given 0.7 mg of Se/kg, IV. These sheep survived and had blood Se disappearance curves that were triphasic. In the 4 sheep given Se IV, the mean lambda 3 elimination rate was 0.0020 hour-1, which represented a biological half-life of 354 hours or 14.7 days.

Animals↗
PubMed1983

Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared by fetal or adult sheep and human GBM, by lung basement membranes, and by certain nonvascular basement membranes. Sheep given homologous GBM had two populations of autoantibodies: one was neither species- nor organ-specific; the other was sheep-specific. No sheep given autologous GBM had any evidence of anti-GBM autoantibodies or nephritis. Their kidneys were indistinguishable by histologic, immunohistologic, and functional studies from CFA-treated controls. Thus, sheep seem very tolerant to autologous GBM. These findings suggest that human anti-GBM nephritis may occur if the GBM is altered so that it becomes cross-reacting and induces autoantibodies, as does homologous GBM.

Animals↗
PubMed2000

Strategies for the avoidance of faeces by grazing sheep.

Experiments were conducted to investigate which environmental cues were used by sheep when discriminating against patches of pasture contaminated with faeces. The influence of the spatial distribution of contaminated patches and the parasite infection status of sheep on avoidance of contaminated patches and ingestion of parasite larvae was also investigated. In experiment 1, sheep infected with the parasite Ostertagia circumcincta were given the opportunity to graze in uncontaminated or aggregated contaminated patches. Patch contamination comprised of either faeces from sheep infected with O. circumcincta larvae, faeces from uninfected sheep, or O. circumcincta larvae only. Infected sheep discriminated against faeces from parasite-infected animals and faeces from uninfected animals equally. Sheep did not discriminate against patches contaminated with parasite larvae only. In experiment 2, sheep infected with O. circumcincta and uninfected sheep grazed experimental plots with differing spatial patterns of faecal-contaminated patches, allowing animals the opportunity to forage in contaminated or uncontaminated patches of herbage. Plots were also grazed by infected and uninfected animals that were fistulated at the oesophagus to enable the collection of ingested herbage. Sheep spent a greater proportion of their time foraging in uncontaminated patches than in contaminated patches. Where patches were highly aggregated, infected animals spent a greater proportion of total grazing time in uncontaminated patches than did uninfected animals, and grazed uncontaminated patches for longer on each sampling occasion. On grazing plots where all patches were contaminated, the difference between the numbers of larvae isolated from pasture herbage and ingested herbage was greatest for infected animals. In this situation, infected animals avoided parasites most. On grazing plots consisting of both contaminated and uncontaminated patches, the difference between the numbers of larvae isolated from pasture herbage and ingested herbage was greatest for uninfected animals. In this situation, uninfected animals were most effective at parasite avoidance as they consumed fewer parasite larvae relative to what was available on pasture.

Journal Article↗