Endogenous retroviral gene elements (syncytin-Rum1 and BERV-K1), interferon-τ, and pregnancy associated glycoprotein-1 are differentially expressed in maternal and fetal tissues during the first 50 days of gestation in beef heifers.

We hypothesized that the endogenous retroviruses [ERV: syncytin-Rum1 and (BERV-K1)], and pregnancy hormones [interferon-τ (IFN-τ), and pregnancy associated glycoprotein-1 (PAG-1)] would be differentially expressed whereas progesterone and insulin concentrations in maternal blood would remain steady during early gestation. To test this hypothesis Angus crossbred heifers (n = 46; ∼15 mo of age; BW = 363 ± 35 kg) were fed native grass hay, supplemented with cracked corn to gain 0.3 kg/d, and given ad libitum access to water. All heifers were subjected to a 5-d CO-Synch + CIDR estrous synchronization protocol and AI (breeding = d 0). Ovariohysterectomies were performed on d 16, 22, 28, 34, 40, and 50 of gestation and at d 16 of the estrous cycle for non-pregnant (NP) controls. Utero-placental tissues [maternal caruncle (CAR); maternal intercaruncular endometrium (ICAR); and fetal membranes, (FM, chorion on d 16, chorioallantois on d 22 to 50)] were collected from the uterine horn ipsilateral to the corpus luteum (CL). Tissues were flash frozen and stored at -80°C. Expression of mRNA was evaluated using qPCR. In CAR, syncytin-Rum1 expression was greater (P < 0.01) on d 50 (81.5-fold) compared with NP controls or any other day of early pregnancy. In contrast, syncytin-Rum1 expression in I-CAR only tended (P = 0.09) to change across days of early pregnancy and did not differ (P = 0.27) in FM tissues. In CAR, the expression of BERV-K1 was not different (P > 0.79) at d 16 and 22, was intermediate at d 28, 34, and 40, and was greatest on d 50 (108-fold increase compared with NP). Expression of BERV-K1 in FM was increased (P < 0.01) on d 28, 34, and 50 compared with NP controls, but at d 40 did not differ from NP controls. The mRNA expression of IFN-τ in FM at d 22 was greater (P < 0.01) than all other days of gestation. In CAR, expression of PAG-1 increased (P < 0.001) dramatically on d 40 (20,000-fold) and d 50 (86,000-fold) compared with NP heifers (P < 0.01). In ICAR, expression of PAG-1 was greater (P < 0.05) on d 28 and 40 (fold increases of 113 and 102, respectively, compared with NP). Insulin concentrations were not different (P = 0.53) but progesterone was greater (P < 0.01) on d 16, 22, 28, 34, and 40 compared with d 50 of gestation. These data confirm differential ERV, IFN-τ, and PAG-1 gene expression during critical time points of early gestation in utero-placental tissues.

RAPID COMMUNICATION: Expression of an endogenous retroviral element, during early gestation in beef heifers.

Endogenous retroviral gene elements have been implicated in development and formation of the feto-maternal interface. A variant of the syncytin endogenous retroviral envelope gene family, , was recently found in ruminants. We hypothesized that mRNA would be differentially expressed in utero-placental tissues and would fluctuate during key time points of early gestation in beef heifers. Commercial Angus crossbred heifers ( = 46; ∼15 mo of age; BW = 362.3 ± 34.7kg) housed in 6-animal pens were fed daily with native grass hay and supplemented with cracked corn to gain 0.3 kg/d. The heifers were estrus synchronized, artificially inseminated, (d of breeding= d 0) and ovariohysterectomized on d 16, 22, 28, 34, 40, and 50 ( = 9, 6, 6, 7, 6, and 5, respectively) of gestation and at d 16 of the estrous cycle for non-bred, non-pregnant controls (NP; = 7). Harvested tissues were separated into maternal caruncle (CAR), intercarunclar endometrium (ICAR), and fetal membranes, (FM; chorioallantois, d 22 and later). All tissues were obtained from the ipsilateral uterine horn to the CL. Statistical analyses were conducted via the GLM procedure of SAS. Maternal CAR expression of was greater ( = 0.003) on d 50 by 81.5-fold compared to NP controls. At d 50 expression of in CAR was 190.3-fold greater than ( < 0.0001) ICAR. Fetal membranes had greater ( < 0.002) expression of from d 22 until d 50 of gestation compared to maternal ICAR (d 16 not analyzed). Expression of in FM was greater ( < 0.004) than in CAR until d 40 of gestation. Therefore, we conclude that is differentially expressed in utero-placental tissues and may be involved in the establishment of pregnancy. The expression of in maternal tissues is completely novel and indicates unique functions of syncytin in ruminant pregnancy.

Evaluation of implant strategies in Angus-sired steers with high or low genetic potential for marbling and gain.

Sixty-nine Angus-sired steer calves (332.3 kg initial BW) were used to determine the effects of single or double implant strategies on steers of high or low genetic potential (GP) determined by the GeneMax (Zoetis, Florham Park, NJ) genetic profiling test. Steers were assigned to treatments in a 2 × 2 factorial design with factors of 1) composite GP score (high, mean GP score of 86.5 [HI]; low, mean GP score of 25.3[LO]) and 2) implant strategy (single, steers implanted on d 70 [1X], or double, steers implanted d 0 and 70 [2X]). All steers were given the same implant (Revalor-S; Merck Animal Health, Summit, NJ), with the 2X group implanted on d 0 and 70 and the 1X group implanted only on d 70. A diet containing 1.38 Mcal NEg/kg DM was fed ad libitum, once daily. Ultrasound was used to measure body composition characteristics on d 0 and 70. Steers were harvested after 140 d on feed. At both the d-0 and d-70 ultrasound, HI steers had greater ( < 0.001) percent intramuscular fat (IMF) than LO steers, but no differences ( ≥ 0.24) were observed in LM area (LMA), rib fat thickness (RF), or rump fat thickness (RMFT). Steers in the 2X group had larger ( = 0.02) LMA and less ( = 0.03) IMF on d 70 than 1X steers and no differences ( ≥ 0.50) in RF or RMFT were observed. From d 0 to 70, HI steers had ADG, DMI, and G:F ( ≥ 0.60) similar to LO steers; however, 2X steers had greater ( < 0.001) ADG and were more ( < 0.001) feed efficient compared with 1X steers during the same interval. Over the entire 140-d feeding period, there were no differences ( ≥ 0.6) in BW, ADG, DMI, or G:F between GP groups; however, 2X steers had greater ( = 0.03) ADG compared with 1X steers and still had similar ( ≥ 0.12) DMI and G:F. Upon slaughter, marbling score tended to be impacted by a GP × implant interaction (499.9 ± 18.5, 545.6 ± 18.5, 487.1 ± 18.5, and 469.8 ± 18.5 for HI and 2X, HI and 1X, LO and 2X, and LO and 1X, respectively; = 0.06). No differences ( ≥ 0.7) were observed between GP groups for HCW, LMA, RF, KPH, or yield grade (YG). Steers in the 1X group had less ( = 0.003) RF than 2X steers but similar ( ≥ 0.14) HCW, marbling, LMA, KPH, and YG. A greater proportion ( = 0.03) of HI steers had choice carcasses (100 ± 0.0%) compared with LO steers (87.8 ± 3.9%). Results of this study indicate that the GP test used in the current study predicted differences in IMF, carcass marbling, and percent carcasses graded as choice.

Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism.

Aicardi-Goutiéres syndrome (AGS) is an early onset, progressive encephalopathy characterised by calcification of the basal ganglia, white matter abnormalities, and a chronic cerebrospinal fluid (CSF) lymphocytosis. Cree encephalitis shows phenotypic overlap with AGS although the conditions have been considered distinct because of immunological abnormalities observed in Cree encephalitis. We report that levels of interferon alpha (IFN-alpha), a marker of AGS, are raised in Cree encephalitis. Moreover, linkage analysis indicates that the disorders are allelic and refines the AGS1 locus to a 3.47 cM critical interval. Our data show that a CSF lymphocytosis is not necessary for the diagnosis of AGS and strongly suggest that AGS and pseudo-TORCH syndrome are the same disorder. Recognition of immunological dysfunction as part of the AGS phenotype provides further evidence of a primary pathogenic role for abnormal IFN-alpha production in AGS.

Development of a dual recombinant vaccine to protect small ruminants against peste-des-petits-ruminants virus and capripoxvirus infections.

A recombinant capripoxvirus vaccine containing a cDNA of the peste-des-petits-ruminants virus (PPRV) fusion protein gene was constructed. A quick and efficient method was used to select a highly purified recombinant virus clone. A trial showed that a dose of this recombinant as low as 0.1 PFU protected goats against challenge with a virulent PPRV strain.

Goat immune response to capripox vaccine expressing the hemagglutinin protein of peste des petits ruminants.

Sheep-pox and capripox are contagious diseases of domestic small ruminants for which the causal agent is a poxvirus classified into the Capripoxvirus genus. Viruses of this group have a host range specific to sheep, goats, cattle, and possibly buffalo. Thus, they are clearly indicated as vectors for the development of recombinant vaccines for peste des petits ruminants (PPR). Here we report the immune response of goats inoculated with a recombinant capripox-PPR hemagglutinin.

Long term immunity in African cattle vaccinated with a recombinant capripox-rinderpest virus vaccine.

Cattle were vaccinated with a recombinant capripox-rinderpest vaccine designed to protect cattle from infection with either rinderpest virus (RPV) or lumpy skin disease virus (LSDV). Vaccination did not induce any adverse clinical responses or show evidence of transmission of the vaccine virus to in-contact control animals. Approximately 50% of the cattle were solidly protected from challenge with a lethal dose of virulent RPV 2 years after vaccination while at 3 years approx. 30% were fully protected. In the case of LSDV, all of 4 vaccinated cattle challenged with virulent LSDV at 2 years were completely protected from clinical disease while 2 of 5 vaccinated cattle were completely protected at 3 years. The recombinant vaccine showed no loss of potency when stored lyophylized at 4 degrees C for up to 1 year. These results indicate that capripoxvirus is a suitable vector for the development of safe, effective and stable recombinant vaccines for cattle.

Leukotomy revisited: late cognitive and behavioral effects in chronic institutionalized schizophrenics.

BACKGROUND: In the 1940s and 1950s, prefrontal lobotomy was widely used to treat aggressive, disruptive and psychotic behavior in schizophrenics. Subsequent observations have confirmed its ineffectiveness in schizophrenia. Few studies have addressed its long-term consequences. METHODS: We conducted tests of frontal function, behavior (Frontal Behavioral Inventory), psychopathology (PANSS), neurological examinations and CT scans in 19 chronically institutionalized schizophrenic patients (mean age 74) who had undergone orbitofrontal leukotomy between 1948 and 1972 and 11 controls (mean age 74) matched for age, length of hospitalization, education, and diagnosis. RESULTS: There were no significant differences between leukotomized patients and controls on: Folstein Mini-Mental score (leuko 22.13+/-5.66; controls 23.55+/-5.93), utilization behavior, Luria alternating written and motor sequences, verbal fluency, imitation behavior, motor impersistence, primitive reflexes, or psychopathology. Significant differences were found on clock drawing and on the go/no-go test, which may reflect the presence of an orbitofrontal lesion in the leukotomized group. There was a tendency for the leukotomized group to have fewer indices of frontal behavioral dysfunction. Both groups showed comparable impairment on the Stroop test and cognitive rigidity on the Odd Man Out test of category shifting. CONCLUSIONS: With few exceptions, elderly leukotomized and nonleukotomized schizophrenic patients show varying degrees of distractibility, difficulty in set shifting, poor planning and organization, susceptibility to interference, primitive reflexes and signs of global cognitive impairment. Allowing for the small sample size, variability in the surgical frontal lesion, and the long interval from surgery to testing, these observations likely reflect the long-term consequences of severe schizophrenia in both groups.

Cree leukoencephalopathy: neuroimaging findings.

PURPOSE: To describe the computed tomographic (CT) and magnetic resonance (MR) imaging findings in Cree leukoencephalopathy. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records and neuroimaging studies in 12 infants with Cree leukoencephalopathy (CT in 12 infants, MR in six). The diagnosis was established clinically in six patients and at autopsy in the other six. RESULTS: At CT, extensive, diffuse, and symmetric hypoattenuation was seen in the cerebral and cerebellar white matter in all 12 patients. Hypoattenuation was also seen in the corpus callosum in 11 (92%), internal capsule in 10 (83%), globus pallidus in nine (75%), brainstem in nine (75%), and thalamus in four (33%). The caudate nucleus and putamen were spared. On T2-weighted MR images in six patients, the cerebral and cerebellar white matter, including the subcortical arcuate fibers, was hyperintense as were the internal capsule, corpus callosum, corticospinal tracts, and globus pallidus. The thalamus was affected in four (67%) patients, pons in five (83%), and medulla in four (33%). The caudate nucleus and putamen were not affected. CONCLUSION: Cree leukoencephalopathy causes striking symmetric and diffuse involvement of the cerebral and cerebellar white matter and brainstem with sparing of the caudate nucleus and putamen.

[Neurologic sequelae secondary to acute lithium poisoning]. / Séquelles neurologiques secondaires à une intoxication aiguë au lithium.

OBJECTIVE: To review the literature on the permanent neurological sequelae resulting from acute lithium poisoning. METHOD: Sixty-six articles were reviewed in English and in French. They were accessed through Medline and cover the period from 1968 to 1997. RESULTS: Fifty-nine case studies were broken down into 3 groups: lithium intoxications without a neuroleptic that has provoked a cerebellar syndrome; those in which there was a neuroleptic; and those with diverse neurological consequences, with or without a neuroleptic. CONCLUSIONS: Lithium has an intrinsic toxicity for the central nervous system and provokes a tropism specific to the cerebellum. The association with neuroleptics appears to increase toxicity as well as some associated factors, including infections and the rapid correction of the lithium level in the blood. We discuss the psychopathological mechanisms invoked to explain lithium's neurotoxicity.

Trial of a capripoxvirus-rinderpest recombinant vaccine in African cattle.

Cattle were vaccinated with differing doses of an equal mixture of capripox-rinderpest recombinant viruses expressing either the fusion protein (F) or the haemagglutinin protein (H) of rinderpest virus. Animals vaccinated with 2 x 10(4) p.f.u. or greater of the combined viruses were completely protected against challenge, 1 month later, with both virulent rinderpest and lumpy skin disease viruses. Vaccination with any of the doses did not induce any adverse clinical response in the animals or transmission of the vaccine virus between animals. All cattle challenged 6 or 12 months after vaccination with 2 x 10(5) p.f.u. of the mixture of recombinant viruses were protected from severe rinderpest disease. Ten out of 18 were completely protected while the remaining 8 developed mild clinical signs of rinderpest. Cattle vaccinated with the recombinant vaccines after prior infection with the parental capripox virus showed more marked clinical signs of rinderpest after challenge with virulent rinderpest, but 9 out of 10 recovered, compared with 80% mortality in the unvaccinated controls.

Expression of the major core structural protein (VP7) of bluetongue virus, by a recombinant capripox virus, provides partial protection of sheep against a virulent heterotypic bluetongue virus challenge.

A recombinant capripox virus was constructed containing a cDNA copy of genome segment 7 of bluetongue virus (BTV) serotype 1 from South Africa (BTV 1SA), which expressed high levels of the major BTV core protein VP7 in infected lamb testis (LT) cells. Sheep vaccinated with this recombinant virus developed antibodies to VP7 (detected by ELISA) but no neutralizing antibodies to either the homologous or heterologous BTV serotype, prior to challenge (BTV 1 or BTV 3, respectively). Following challenge with a virulent heterotypic strain of BTV (BTV3 SA), all of the animals developed clinical signs of disease, indicating that they were infected and that the challenge virus did replicate. While all of the control animals died, six of the eight animals that were vaccinated with the recombinant capripox virus expressing VP7 recovered fully. This is the first report of a significant level of cross serotype protection against the lethal effects of a challenge with virulent BTV, produced by vaccination with a single BTV core protein, which did not generate a neutralizing antibody response.

Sequence analysis of HindIII Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue.

The DNA sequence of the HindIII Q2 fragment near the left terminus of the capripoxvirus (KS-1 strain) genome was determined. The sequence contains two complete open reading frames (ORFs) and a part of a third. Analysis of the deduced amino acid sequence of one of these ORFs, Q2/3L, revealed that this gene has the capacity to encode a protein which is related to members of the G-protein coupled chemokine receptor subfamily, the swinepoxvirus K2R and the human cytomegalovirus US28 ORFs. It has the key structural characteristics of the G-protein-coupled receptor superfamily, e.g., seven hydrophobic regions, predicted to span the cell membrane, and the cysteine residues in the first and second extracellular loops that are implicated in formation of a disulfide bond. Southern blot analysis showed that all three species of the Capripoxvirus genus, i.e., sheep pox, goat pox, and lumpy skin disease of cattle, contain copies of this putative G-protein-coupled chemokine receptor homologue.

Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus.

Goats were protected against a lethal challenge of peste des petits ruminants (PPR) virus following vaccination with a recombinant capripoxvirus containing either the fusion (F) gene of rinderpest virus or the haemagglutinin (H) gene of rinderpest virus. The H gene recombinant produced high titres of neutralizing antibody to rinderpest virus in the vaccinated goats, whereas the F gene recombinant failed to stimulate detectable levels of neutralizing antibody. A similar response to the two recombinant vaccines has previously been reported for cattle. Neither recombinant produced detectable levels of specific antibodies to PPR virus.

Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Western blot analysis of virus-specific antibody responses for capripox and contagious pustular dermatitis viral infections in sheep.

This paper reports the development and evaluation of serological tests for the differentiation of antibodies in animals infected with capripox and parapox viruses. Agar-gel immunodiffusion tests using sera from sheep with naturally-acquired infections and from sheep experimentally inoculated with orf or capripox viruses showed cross reactions. Virus-specific antibody responses to structural proteins of the viruses were analysed by Western-blot analysis. This analysis readily differentiated the infections as either capripox or contagious pustular dermatitis. The antibody responses to the 32 kDa and 26 kDa proteins of capripoxvirus provided a firm basis for differentiation.

Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus.

Cattle were protected against challenge with rinderpest and lumpy skin disease viruses by vaccination with a recombinant capripoxvirus containing the fusion protein (F) gene of rinderpest virus. The minimum protective immunising doses for rinderpest and lumpy skin disease were 5.5 x 10(4) plaque forming units (pfu) and 1.5 x 10(3) pfu, respectively.