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Biomedical subjects

J H Cox

Publications and source records attributed to J H Cox.

At least 55 records · Page 3Linked to original sources
PubMed1991

An L (polymerase)-deficient rabies virus defective interfering particle RNA is replicated and transcribed by heterologous helper virus L proteins.

A rabies virus-derived defective interfering particle (DI) was isolated and characterized. The DI genome contained an internal deletion of 6.4 kb spanning the 3' moiety of the pseudogene region (psi) and most of the L gene. DI-specific monocistronic N, NS, and M mRNAs as well as a G/L fusion mRNA were transcribed in cells coinfected with DI and helper virus. In addition, polycistronic DI RNAs and standard virus RNAs with internal A stretches and intergenic regions were found. Superinfection experiments showed that heterologous rabies-related viruses (Lyssavirus serotypes 2, 3, and 4) can complement the L deficiency of the DI genome. The heterologous polymerase proteins recognize correctly the replicational and transcriptional signal sequences of the Lyssavirus serotype 1-derived DI.

Base Sequence↗
PubMed1990

Intra-abdominal hemorrhage associated with a granulosa-thecal cell neoplasm in a mare.

A 9-year-old American Saddlebred mare was referred because of abdominal distention and signs of abdominal pain. Copious peritoneal fluid obtained by abdominocentesis appeared to be frank blood. Rectal and ultrasonographic evaluation of the abdomen revealed a large mass at the distal tip of the right uterine horn. The mare was euthanatized and necropsied and the mass was determined to be a granulosa-thecal cell neoplasm. The most common clinical sign of granulosa-thecal cell neoplasm is infertility or abnormal sexual behavior. Hemoperitoneum is infrequently associated with neoplasms in horses.

Acute Disease↗
PubMed1990

Antigen presentation requires transport of MHC class I molecules from the endoplasmic reticulum.

The role of exocytosis of major histocompatibility complex (MHC) class I molecules in the presentation of antigens to mouse cytotoxic T lymphocytes (CTLs) was examined by use of a recombinant vaccinia virus that expresses the E19 glycoprotein from adenovirus. E19 blocked the presentation of vaccinia and influenza virus proteins to CTLs in a MHC class I allele-specific manner identical to its inhibition of MHC class I transport from the endoplasmic reticulum. This finding indicates that (i) the relevant parameter for antigen presentation is the rate of MHC class I molecule exocytosis, not the level of class I cell surface expression, and (ii) association of class I molecules with antigen is likely to occur within the endoplasmic reticulum.

Adenovirus Early Proteins↗
PubMed1990

Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19.

Complementary DNA spanning the entire genome of the attenuated rabies virus strain SAD B19 which is used for oral immunization of foxes in Europe was cloned and sequenced. The viral genome comprises 11,928 nucleotides and encodes the five viral proteins N, NS, M, G, and L. Deduced protein sequences are highly similar to those of the pathogenic PV strain, homologies ranging from 90.6% for the M to 98.6% for the L protein. The five cistrons are separated by intergenic regions of 2, 5, 5, and 24 nucleotides, respectively. The G transcription stop/polyadenylation consensus signal in SAD B19 is destroyed by a deletion of three A residues. The strong conservation of both noncoding and coding nucleotide sequences indicates a high selective pressure on the primary structure of rabies virus genomic RNA.

Amino Acid Sequence↗
PubMed1990

Identification of fox rabies by a monoclonal antibody directed against nucleocapsid of a street rabies virus.

Hybridomas were prepared by fusion of spleen cells from BALB/c mice immunized with dog rabies isolates from Nigeria with P3x63Ag8 myeloma cells. More than 69 hybridomas secreted antinucleocapsid (antiNC) antibodies when tested with homologous viruses by indirect immunofluorescence. One hybridoma (Z144-88) was found which secreted antiNC antibody that reacted negatively with fox rabies isolates from the Federal Republic of Germany, Switzerland and France and with rabies-related viruses and European bat isolates. It reacted positively with other strains/isolates of rabies virus. It is possible to use this antiNC monoclonal antibody (mab) for the investigation of fox rabies outbreaks in Europe.

Animals↗
PubMed1990

Antigenic characterization of street rabies virus isolates from Nigeria using monoclonal antibodies.

Twenty isolates of street rabies virus were recovered in mouse neutroblastoma cells from 84 rabies suspect brain specimens from Nigeria dogs and a cat. They were characterized with the Tübingen monoclonal antibody panels directed against nucleocapsid and glycoprotein antigens. Antigenic variations were detected both with antinucleocapsid (anti-NC) and antiglycoprotein (anti-GP) monoclonal antibodies (mabs). One isolate reacted positively with anti-NC mab P41 which hitherto has been known to react positively with polar rabies. Another isolate did not react with anti-NC mab 187.5; a reaction normally seen with ERA/SAD strains of rabies virus. With anti-GP mabs it was possible to group the isolates by their area of origin. Isolates from Plateau State were not neutralized by anti-GP mabs ERA 543 and P44.7.2. The isolates studied had glycoprotein antigenic patterns different from the pattern for low egg passage (LEP) Flury strain vaccine virus used in Nigeria for immunization of dogs.

Animals↗
PubMed1989

Congenital malignant melanoma in two foals.

Two cases of congenital malignant melanomas in horses are described in this report. In each case, wide surgical excision of the mass was performed; no recurrence or metastasis was detected after a minimum of 15 months' follow-up. Melanomas are among the most common neoplasms of horses, but they typically develop in gray horses greater than 6 years old.

Animals↗
PubMed1989

Differential pattern of T cell recognition of the 65-kDa mycobacterial antigen following immunization with the whole protein or peptides.

The 65-kDa stress protein from Mycobacterium bovis (Bacillus Calmette Guérin) elicited T cell proliferation and antibody responses in seven B10 congenic mouse strains with different H-2 haplotypes. To analyze T cell determinants on this antigen, seven peptides corresponding to six predicted T cell epitopes, and one defined B cell epitope were synthesized. Mice were either immunized with the whole antigen and the specificity of the response was ascertained in respect of the six peptides, or mice were immunized with seven of the peptides and tested for proliferative responses to the whole molecule. The results showed that three peptides carried epitopes to which mice responded following injection of the whole molecule and that immunization with two additional peptides could prime for in vitro stimulation with the native antigen. The latter result indicates the feasibility of generating T cell responses to "cryptic" epitopes on proteins by immunizing with peptides. The peptide-specific T cell responses were distinctly influenced by the H-2 haplotype of mouse strains. However, two peptides were recognized by several H-2-disparate mouse strains, and one peptide could be presented by both I-A and I-E molecules. Immunization with several peptides induced a cross-reactive T cell proliferative response to the homologous GroEL protein isolated from E. coli. The amount of cross-reactivity was influenced by the extent of sequence homology between mycobacterial and E. coli proteins and the major histocompatibility complex class II molecule used to present the peptide.

Amino Acid Sequence↗
PubMed1989

Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4 to 6 months after infection. The magnitude of reactivation was more pronounced in innately resistant CBA/Ca mice than in the susceptible C57BL/6 strain of mice. Splenic bacterial counts were also amplified by anti-L3T4 antibody when the antibody was injected at the chronic phase, whereas cyclosporin A had an effect only during the initial 6 weeks after BCG infection. Cultures of spleen cells from chronically infected mice showed a significant increase in the numbers of viable BCG recovered after 7 days of incubation in the presence of dexamethasone but not with cyclosporin A. The observed differences between the tested immunosuppressive agents indicate that the stationary bacterial counts during chronic BCG infection are maintained by discrete T-cell actions on the infected macrophages.

Animals↗
PubMed1989

Oral vaccination of raccoons (Procyon lotor) with an attenuated (SAD-B19) rabies virus vaccine.

Unlike previous reports to the contrary, raccoons (Procyon lotor) were successfully vaccinated against rabies with a liquid SAD-B19 attenuated virus vaccine administered per os and given in vaccine-laden baits. There was neither evidence of vaccine-induced rabies in raccoons nor in a limited safety trial with opossums (Didelphis virginiana) given SAD-B19. Protection from lethal street rabies virus infection was not absolute: only three of nine raccoons given 1 x 10(6.0) TCID/ml were protected versus five of 10 raccoons given 1 x 10(7.0) TCID/ml of SAD-B19 and challenged 4 mo after consumption of vaccine-laden baits. Six of eight raccoons consuming 1 x 10(8.8) TCID/ml of SAD-B19 vaccine in baits survived street rabies virus challenge 2 mo postvaccination. Raccoon survivorship was not wholly dependent upon rabies virus-neutralizing antibody titer on the day of challenge. Vaccinated raccoons demonstrated a prominent anamnestic response within 1 wk following challenge. Surviving raccoons were observed for a minimum of 3 mo following street rabies virus challenge with neither clinical nor pathologic evidence of rabies. The SAD-B19 rabies vaccine administered within baits in captivity appears less effective for raccoons than for its demonstrated efficacy in the immunization of free-ranging foxes (Vulpes vulpes) in Europe.

Administration, Oral↗
PubMed1989

The phenotypic and molecular characterization of Nb2 lymphoma cells activated with IL-2 and human growth hormone.

The Nb2 rat lymphoma cell line has the unique property that its growth is dependent on lactogenic pituitary hormones. Cell surface staining with monoclonal antibodies showed expression of class I MHC alloantigens of the RT1u haplotype, but no expression of class II MHC antigens. Staining for differentiation markers was strongly positive with antibodies OX52, W3/13 and OX44. Partial and weaker staining was obtained with CD2, P4/16 and the transferrin receptor. Nb2 cells were negative with CD5, OX40 and CD4, whilst CD8 stained only a minor fraction (1%) and certain variant clones of the cell line. This general pattern of staining is consistent with the phenotype of a small subpopulation of immature T cells. Nb2 cells proliferated in response to recombinant human IL-2, although they did not stain with antibodies against the IL-2 receptor. Enhancement of the stimulation by IL-2 in the presence of a submitogenic concentration of hGH indicated a synergism between these two hormones, and responses were suppressed by a similar dose of cyclosporin A (ID50=2 microg/ml). Although IL-2 could not be identified in culture supernatants, the presence of mRNA for IL-2, IL-2R and IL-4 was demonstrated by dot blot analysis. Finally, evidence that the Nb2 lymphoma is of T-cell lineage was given by Northern blot detection of mRNA for the alpha and beta chains of the T-cell receptor.

Animals↗
PubMed1988

Orientation of epitopes influences the immunogenicity of synthetic peptide dimers.

The immunogenicity of synthetic peptide dimers based on epitope sequences derived from the mycobacterial 65-kDa antigen and the foot and mouth disease virus (FMDV) VP1 protein was examined in inbred mice. The analysis was directed towards the potential helper role of a T cell stimulatory mycobacterial epitope (65-85) with respect to poorly immunogenic sites either from the same molecule (422-436) or from VP1 (141-160). The 65-85 repeat homodimer induced an antibody response in CBA/ca but not in C57BL/6 mice, both nonresponders to the 65-85 monomer, and amplified the antibody response in BALB/c, monomer-responder mice. Analysis of the immunogenicity of hybrid dimers in BALB/c mice showed that the orientation of peptides within the dimer is critical for the extent of the produced antibody response. Only the 422-436/65-85 but not the 65-85/422-436 induced antibodies binding to the 422-436 sequence which was nonimmunogenic when injected either as a monomer or dimer. Despite the striking difference in immunogenicity, both tested hybrid dimers reacted equally in the solid-phase immunoassay with antisera raised to 65-85-dimer or 422-436/65-85 peptides or with a monoclonal antibody to the 422-436 epitope. The described differences in antibody responsiveness also cannot be attributed merely to the extent of T cell stimulation since the proliferative responses were uniformly expressed for all relevant combinations of peptides. Antisera to 65-85 dimer and 422-436/65-85 hybrid also reacted with the native 65-kDa protein. Furthermore, the production of FMDV-neutralizing antibodies in response to the 141-160 (VP1-derived)/65-85 hybrid peptide in 141-160 nonresponder B10.D2 mice also confirmed the helper activity of the 65-85 epitope. Thus, combining heterologous peptides with the N-terminal of the mycobacterial 65-85 sequence may be generally applicable for the potentiation of peptide vaccines.

Animals↗
PubMed1988

The role of host factors for the chemotherapy of BCG infection in inbred strains of mice.

Host factors have previously been considered to play a role in the efficacy of "incomplete" antituberculous chemotherapy. We investigated this aspect using a model of intravenous infection with M. bovis-BCG in three inbred strains of mice. Viable splenic counts of bacilli (CFU) were monitored following a three week regimen of rifampicin (R) and isoniazid (H) given either immediately or from three weeks after infection. At the end of the immediate (0-3 weeks) therapy the spleens of all mice were sterile and only a minority of animals had demonstrable CFU's at 23 weeks after infection. However, following the delayed-onset (3-6 weeks) therapy we found a pronounced relapse of BCG growth which was about 10 times higher in CBA/Ca and BALB/C than in C57B1/6 mice. These results indicated that host immunity which developed during the first three weeks after infection may have aggravated the relapse of bacterial growth following chemotherapy. This interpretation was corroborated by the finding that the immunosuppressive drug cyclosporin given concurrently with R/H reduced the splenic viable counts of BCG.

Animals↗
PubMed1987

Colic-like discomfort associated with ovulation in two mares.

Discomfort manifested by colic-like clinical signs in 2 young mares was presumed to be attributable to ovarian pain associated with follicular enlargement and ovulation. Diagnosis was based on the lack of detectable evidence of gastrointestinal disease, the finding of a large ovarian follicle or recent ovulation, the repetition of signs during several subsequent estrual periods, and the clinical response to pharmacologic suppression of estrus and ovulation. The similarity of the clinical signs in these 2 mares to cyclic intermenstrual pain in women was considered.

Animals↗
PubMed1987

Mechanism of action of cyclosporine in preventing cardiac allograft rejection. II. Graft tissue levels of prostacyclin and thromboxane.

Four cyclo-oxygenase products (COP) of arachidonate were measured in tissue homogenates of rat cardiac allografts at intervals after transplantation. In rejecting graft tissue, there was a progressive decrease in the levels of prostaglandin E2 (PGE2) and PGF2 alpha from the time of grafting, which was accompanied by a rise in the levels of prostacyclin (PGI2, measured as its stable hydrolysis product 6-oxo-PGF1 alpha) and thromboxane A2 (TxA2, measured as its stable hydrolysis product TxB2). When the level of each individual COP in rejecting graft tissue was expressed as a percentage of the total COP measured, PGI2 and TxA2 increased from 9% to 36% and from 7% to 25%, respectively, from day three after grafting until the time of graft rejection. In contrast to these changes in COP levels in rejecting grafts, the levels of all four COP in nonrejecting allografts maintained by treatment of the graft recipients with cyclosporine remained normal--i.e., comparable to the levels in the recipients' own hearts.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Mechanism of action of cyclosporine in preventing cardiac allograft rejection. I. Rate of entry of lymphocytes from the blood, fibrin deposition, and expression of Ia antigens on infiltrating cells.

The rate of entry of 3H-leucine-labeled lymphocytes was monitored in cyclosporine (CsA) treated or untreated rats that had received a cardiac allograft 5 days previously. In the untreated recipients there was a preferential localization of labeled cells in the graft heart compared with the native heart, which was evident within the first hour as well as at 3 and 24 hr after injection. In CsA-treated recipients, the rate and extent of entry of lymphocytes in the graft heart was not substantially different from the native heart. Fibrin deposition within allografts, thought to be a consequence of T cell activation, was substantially reduced by CsA treatment of the recipients. A double immunoenzyme staining technique was used to identify Ia-positive macrophages and Ia-positive T cells in cryostat sections of grafts: although the number of macrophages and T cells was reduced in CsA treated recipients, there was no difference in the extent to which these cells were Ia-positive.

Animals↗
PubMed1985

The effects of cyclosporin on lymphocyte activation in a systemic graft-vs.-host reaction.

We have investigated the effects of cyclosporin (CsA) on each of three stages of lymphocyte activation in vivo viz. sequestration of alloantigen-reactive lymphocytes from the circulation into the spleen and lymph nodes, blast transformation and induction of DNA synthesis in the activated cells and release of these cells and their progeny into the circulation. Parental strain lymphocytes injected i.v. into semi-allogeneic rats and recovered from the thoracic duct within 36 h are profoundly unresponsive in a local graft-vs.-host assay to the alloantigens of the F1 hybrid but have normal activity against unrelated alloantigens (negative selection). CsA treatment of the F1 hybrid recipients did not prevent this selective sequestration of antigen-reactive cells. In the untreated F1 hybrid, from 36 h after injection, large numbers of dividing blast cells were released into the lymph. These cells did not appear in the lymph of recipients treated with CsA. However, CsA did not prevent the activation of cells sequestered in the spleen or lymph nodes as assessed by [3H] thymidine incorporation and autoradiography. This unexpected finding suggests that CsA inhibits lymphocyte responses to alloantigens in vivo after DNA synthesis which is a later stage than the in vitro studies have shown.

Animals↗