Gene/Protein Disease Symptom Drug Enzyme Compound
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An intensive vaccination programme with the glycoprotein I (gI) and thymidine kinase-deleted vaccine strain 783 was applied on all the pig farms in a region with a high pig density. To monitor the spread of Aujeszky's disease virus within breeding herds in that region, all the breeding stock in nine herds were examined for antibodies to gI six times at intervals of four months. The prevalence of gI-seropositive sows decreased greatly in all nine herds. The mean percentage of gI-seropositive sows decreased from 56.4 per cent (range 80.0 to 13.6 per cent) at the start, to 20.3 per cent (range 29.1 to 1.6 per cent) after two years. Nevertheless, seroconversions to gI were detected in all the herds, and in six out of the nine breeding herds even during the second year of the study. The intensive regional vaccination apparently did not completely prevent Aujeszky's disease virus infections within these herds. The source of the virus responsible for these infections was not identified. However, because in most herds only a few sows seroconverted, the virus either circulated at a low level within the herds, or its introduction or reactivation did not lead to an extensive spread of the virus.
Vet Rec 1994 Mar 26
PMID:Spread of Aujeszky's disease virus within pig herds in an intensively vaccinated region. 820 8

Sertoli cell sulfated glycoprotein-1 (SGP-1) is a heavily glycosylated and sulfated 70 kDa protein that is secreted into the lumen of the seminiferous tubule where it binds to spermatozoa. Recent light and electron microscope immunocytochemistry has suggested that the testicular SGP-1 detaches from the surface of spermatozoa in the lumen of the efferent ducts to be endocytosed within the endocytic apparatus of the epithelial nonciliated cells. The finding of SGP-1 mRNA together with anti-SGP-1 immunogold labeling of the lysosomal compartment suggest that these cells synthesize an efferent duct form of SGP-1. In the present study, a number of different experimental approaches (ligation, tunicamycin treatment and a combination of both) in combination with quantitative electron microscope immunogold labeling and Western blot analysis were performed in order to test this hypothesis. The number of gold particles and the profile area of the early (endosomes, pale multivesicular bodies) and late (dense multivesicular bodies, secondary lysosomes) endocytic apparatus were estimated in each of the experimental groups and expressed as the number of gold particles per micron 2 (labeling densities). The data revealed that ligation produced a significant reduction of anti-SGP-1 immunogold labeling of the early endocytic apparatus but not of the late endocytic apparatus. Tunicamycin treatment on the other hand produced a significant reduction of immunogold labeling of both the early and late endocytic apparatus. The combination of both treatments resulted in a more effective reduction of the labeling densities of these two endocytic compartments. These results thus indicate that the nonciliated cells of the efferent ducts are involved both in the endocytosis of the Sertoli-derived SGP-1 and in the synthesis of an efferent duct form of SGP-1 that is targeted from the Golgi apparatus to secondary lysosomes after its glycosylation. In order to determine the biosynthetic pathway of SGP-1 within the efferent ducts, an I.V. injection of 35S-cysteine followed by immunoprecipitation and SDS-PAGE revealed that SGP-1 was initially biosynthesized as a 55 kDa protein. This protein appears to be post-translationally modified to a 65 kDa form after 1 hour, which preceded the appearance of the 70 kDa form, and smaller peptides of about 15 kDa characteristic of saposins after 3-4 hours. Western blot analysis of ligated efferent ducts showed an increase in the biosynthesis of the 70 kDa form of SGP-1 when compared to untreated controls, however, it has yet to be established if this protein is secreted or retained in an intracellular compartment.(ABSTRACT TRUNCATED AT 400 WORDS)
Anat Rec 1993 Mar
PMID:Nonciliated cells of the rat efferent ducts endocytose testicular sulfated glycoprotein-1 (SGP-1) and synthesize SGP-1 derived saposins. 843 Sep 11

Coagulation factor XI is a glycoprotein of the contact factor system. Its deficiency is associated with a highly variable bleeding tendency, thus a role in relation to hemostasis appears to exist. However, the importance of factor XI for stimulating intrinsic coagulation in vivo has not yet been determined. To study the procoagulant effects of human factor XIa in vivo, we infused the purified enzyme into normal chimpanzees (100 micrograms) in the absence or presence of the thrombin inhibitor rec-hirudin (1.0 mg/kg loading dose plus 0.3 mg/kg body wt continuous infusion). Factor XIa elicited an immediate activation of factors IX, X, and prothrombin, as measured by their respective activation fragments. However, whereas the activation of factors IX and X was immediate and shortlasting, (peak increments of 6- and 1.4-fold of baseline at 5 minutes after injection), the conversion of prothrombin gradually increased, reaching a summit of 6-fold baseline values after 60 min, and remaining elevated during the course of the experiments. Thrombin-antithrombin complexes also remained elevated during the study period. In the presence of hirudin, the initial activation of factors IX, X, and prothrombin was unchanged, however the further increment in prothrombin fragment F1 + 2 was markedly inhibited. These results demonstrate that factor XIa is a potential agonist of the intrinsic cascade in vivo, which activity is enhanced in the presence of thrombin.
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PMID:Factor XIa induced activation of the intrinsic cascade in vivo. 870 5

The virus epizootic which resulted in significant mortality in Siberian seals (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper virus. Sequence analysis of the virus glycoprotein genes revealed that it was most closely related to recent European field isolates of canine distemper virus. This paper presents evidence that the same virus continued to circulate in seals in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples collected from seals culled in the spring of 1992 were positive for canine distemper virus-specific nucleic acid by the reverse transcription/polymerase chain reaction and the sequences were closely related to that of the original virus isolated in 1988.
Vet Rec 1996 May 04
PMID:Canine distemper virus in Lake Baikal seals (Phoca sibirica). 873 61

Osteopontin (OPN), a noncollagenous, extracellular matrix sialoprotein found at relatively high levels in both normal and pathological mineralized tissues, is expressed by tissue-specific cells in bone, calcified cartilage, and teeth. On the other hand, a hallmark of OPN expression in pathologically mineralizing tissue, and in other soft tissues experiencing a more generalized type of necrotic injury, is the production of OPN by macrophages at the lesion site. In the present study, we have localized OPN and other noncollagenous proteins by ultrastructural colloidal-gold immunocytochemistry using a rat model in which mineralized tissue defects are surgically created in mandibular bone and teeth. The healing response was examined by immunocytochemistry and transmission electron microscopy at 10 min, 3 days and 7 days post-surgery using antibodies against OPN, bone sialoprotein, osteocalcin, bone acidic glycoprotein-75, fibronectin, and amelogenin. Whereas most of these proteins were characteristically distributed within their respective extracellular matrices as described previously, OPN was additionally observed to accumulate as a lamina limitans at surgically exposed bone and tooth surfaces, as well as at the surface of particulate, mineralized tissue debris. Intracellular labeling of the Golgi apparatus and secretory granules of macrophages at the lesion site demonstrated that OPN production by macrophages was a prominent secretory event of the inflammatory response during wound healing in mineralized tissues. Pseudopodal and lamellipodal cytoplasmic extensions of macrophages were observed in direct contact with the OPN-containing lamina limitans at these surfaces. Particulate, calcified debris internalized by macrophages also displayed a prominent surface "coating" of OPN. In conclusion, our interpretation of the present data is that OPN secreted by macrophages may serve as a macrophage adhesion protein, and where concentrated at the surface of small particulate, mineralized tissue debris, may act as an opsonin, thereby facilitating cell adhesion and phagocytosis by macrophages, a process likely mediated by integrin-binding, signal transduction, and cytoskeletal restructuring.
Anat Rec 1996 Jun
PMID:Secretion of Osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: a potential requirement for macrophage adhesion and phagocytosis. 876 75

The efficacy of three feline leukaemia virus (FeLV) vaccines was compared. Kittens were immunised with either a recombinant subunit vaccine, Leucogen, or one of two inactivated virus vaccines, Leukocell 2 or Leucat. On subsequent challenge by intraperitoneal inoculation of FeLV of subgroup A (FeLV-A), only Leucogen gave significant protection. In a second experiment, kittens vaccinated with Leucogen were protected against oronasal challenge with a phenotypic mixture of FeLV of subgroups A, B and C. These results indicate that a recombinant vaccine, containing only the protein moiety of the surface glycoprotein of FeLV-A, can provide better protection than the inactivated virus vaccines tested against challenge with virus of the same subgroup, and can also protect against challenge by all three subgroups of FeLV.
Vet Rec 1996 Jan 06
PMID:Comparative studies of the efficacy of a recombinant feline leukaemia virus vaccine. 882 25

An attenuated glycoprotein I-negative (gI-)/thymidine kinase-negative (TK-) constructed vaccine was used to eradicate Aujeszky's disease virus from a large farrow-to-finish herd in Sweden. The herd had had problems every year for seven years and two attempts to eradicate the virus without vaccination had failed. At the start of the vaccination programme 86 per cent of the 396 breeding animals were seropositive to the virus. In spite of evidence of virus circulation in the fattening units, no fatteners were vaccinated. The breeding stock was vaccinated every four months and monitored serologically. Seropositive sows and boars were culled at an economic rate. During the programme, four breeding animals seroconverted to gI. Another seven animals which seroconverted to gI were suspected to have been infected shortly before the first test and vaccination. When all the seropositive breeding animals had been culled, the fattening units were sampled and no seropositive animals were found. The herd was declared gI-negative 39 months after the start of the programme. Monitoring of the herd for another four years, until all the vaccinated animals had been culled, showed that the herd remained free from Aujeszky's disease virus.
Vet Rec 1997 May 10
PMID:Eradication of Aujeszky's disease virus from a Swedish pig herd using gI-/TK-vaccine. 917 94

We have constructed chimeric retroviral envelopes displaying N-terminal polypeptides that are known to form homotrimeric associations. The amphotropic receptor (RAM-1) binding domain from the trimeric surface (SU) glycoprotein of 4070A murine leukemia virus (MLV)-inhibited ecotropic receptor (Rec-1) mediated infection by the SU glycoprotein of Moloney MLV when grafted to its N-terminus. The block to Rec-1-mediated infection was reversed when the RAM-1 binding domain was cleaved from the vector particles using an engineered factor Xa protease-sensitive cleavage signal between the envelope glycoprotein and its N-terminal extension. Trimeric leucine zipper peptides and the trimeric C-terminal domain of CD40 ligand were shown to inhibit RAM-1-mediated infection of NIH3T3 cells by the 4070A envelope when fused to its N-terminus, whereas monomeric helical peptides and the monomeric epidermal growth factor domain did not. The block to RAM-1-mediated infection was reversed when the trimeric polypeptides were cleaved from the vector particles by addition of factor Xa protease. Envelope binding assays using cleaved and uncleaved chimeric 4070A envelopes revealed that binding to RAM-1 receptors on mammalian cells was hindered by trimeric, but not by monomeric, N-terminal polypeptides. These results have important implications for the design of protease-activatable vectors for targeted gene delivery.
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PMID:Masking of retroviral envelope functions by oligomerizing polypeptide adaptors. 923 46

Feline infectious peritonitis (FIP) is notoriously difficult to differentiate from the many other diseases with similar clinical signs and at present the only conclusive diagnostic test is the histopathological examination of a biopsy. The potential value of raised levels of the acute phase reactants, alpha 1-acid glycoprotein (AGP) and haptoglobin in the diagnosis of the disease was investigated. The concentrations of the two proteins were determined in serum samples from healthy cats and gave reference ranges of 0.1 to 0.48 g/litre and 0.04 to 3.84 g/litre, respectively. Levels of AGP greater than 1.5 g/litre in serum, plasma or effusion samples were found to be of value in distinguishing field cases of FIP from cats with similar clinical signs and differentiated these two groups of cats more effectively than the albumin:globulin ratio. The concentration of haptoglobin was higher in cats with FIP than in the group of healthy cats, but this protein was not of value in the diagnosis of FIP. Serum samples from feline immunodeficiency virus-infected cats were also analysed for these proteins and their concentrations were significantly elevated, illustrating that raised levels of AGP and haptoglobin are not pathognomonic for FIP.
Vet Rec 1997 Sep 20
PMID:Value of alpha 1-acid glycoprotein in the diagnosis of feline infectious peritonitis. 933 Apr 74

Biologically active recombinant porcine FSH (rec-pFSH) free from the cognate pituitary glycoprotein hormone LH was produced. It was synthesized by a baculovirus vector-insect cell system using two cDNAs encoding the glycoprotein alpha and FSH beta subunits. Its antigenicity was the same as that of pFSH prepared from the pituitary. Glycosylation of rec-pFSH was shown by tunicamycin treatment but the molecular mass of each subunit was lower than that of pituitary-derived FSH, because of the absence of trimming of terminal sugars in insect cells. Rec-pFSH was secreted into the culture medium at about 1 mg/l and purified in six fractions, because of the heterogeneity of the sugar group, by S-Sepharose and concanavalin A-Sepharose column chromatography. The biological activity of rec-pFSH was examined by measuring its effect on progesterone secretion from porcine granulosa cells and germinal vesicle breakdown (GVBD) of porcine oocytes. It showed adequate activity with respect to progesterone secretion, although some fractions rich in the sugar group showed lower activity than that of pituitary-derived FSH. It exhibited higher GVBD activity than that of pituitary-derived FSH at concentrations as low as 1 ng/ml. These results demonstrate that the baculovirus vector-insect cell system can provide biologically active rec-pFSH.
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PMID:Expression and purification of biologically active porcine follicle-stimulating hormone in insect cells bearing a baculovirus vector. 951 82


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