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P Millar

Publications and source records attributed to P Millar.

16 recordsLinked to original sources
PubMed1996

A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats.

The carcinogenic potential of the nonsteroidal triphenylethylene antiestrogen toremifene (Fareston) was evaluated in a standard 104-week rat dietary carcinogenicity study. The doses were 0, 0.12, 1.2, 5.0 and 12 mg/kg/day and the number of animals 50/sex/dose group. The body weight gain and food consumption were monitored once weekly (study weeks 1-16) or once every four weeks thereafter (study weeks 17-104). Blood samples were taken at weeks 34, 52 and 104 and the plasma concentrations of toremifene, as well as the two main metabolites (deaminohydroxy)toremifene and N-demethyltoremifene, were measured. All doses of toremifene reduced food intake and body weight gain. Toremifene caused a significant reduction in mortality, which was mainly due to reduced incidences of pituitary tumors. This was evident in all dose groups. Drug-related decrease of mammary tumors in females (at all doses) and testicular tumors in male rats (doses > or = 1.2 mg/kg/day) were also evident. The incidence of the preneoplastic foci of basophilic hepatocytes were significantly decreased in treated female groups. Toremifene induced no preneoplastic or neoplastic lesions. Based on histopathology, no obvious toxicity could be observed. Drug-related changes were observed in the genital organs, thyroid, spleen, mammary gland, adrenal, kidney, stomach and lung. These changes were due to hormonal disturbances or as a result of reduced food consumption or reduced incidences of pituitary, mammary or testicular tumors. This study indicates that toremifene is an efficient antiestrogen in long-term treatment, is well tolerated and has no tumorigenic potential in rats.

Aging↗
PubMed1995

Bovine T cells preferentially recognize non-viral spacer epitopes in a putative FMDV vaccinal peptide.

In a group of immunized cattle with a variety of MHC class II types, T-cell responses were detected to a synthetic peptide (FMDV15) proposed as a basis for a vaccine against foot-and-mouth disease. This peptide combines the loop region of VP1 with the C-terminal sequence connected by a spacer (PPS). Two major immunodominant regions of FMDV15 for bovine T cells were detected, one within the loop region and the other around the spacer. A substantial proportion of the T-cell response to FMDV15 was directed to the spacer region in 5/12 animals, and in vitro generation of FMDV15-specific T cells preferentially selected for spacer-specific T cells. This pattern of response was associated with a particular MHC class II type which is very common in cattle. Focusing of the T-cell response to non-native virus epitopes may explain why FMDV15 is inefficient at inducing protection.

Amino Acid Sequence↗
PubMed1994

Induction of effective cross-reactive immunity by FMDV peptides is critically dependent upon specific MHC-peptide-T cell interactions.

BoCD4+ T-cell clones specific for a peptide derived from foot-and-mouth disease virus envelope protein, VP1 (FMDV15) were generated from two responder cattle. One animal was a high and the other was an intermediate responder in terms of both T-cell and antibody responses. However both animals had identical major histocompatibility complex (MHC) class II DR-like types (DRBF3,6) according to a one-dimensional isoelectric focusing method which distinguishes DR-like alleles. In contrast, mixed lymphocyte reaction (MLR) responses indicated that they shared only one haplotype (DRBF3) and anti-DRBF6 alloclones also differentiated between the animals. This suggested that the animals differed at a non-DR-like locus. Restriction patterns of FMDV-specific clones derived from these animals indicated that FMDV15 was presented by the non-DR-like class II molecules associated with DRBF6. Only one clone, derived from the high responder animal, was restricted to DRBF3. Thus products from the non-DR-like locus (probably DQ-like) are functionally important for presentation of FMDV peptides. Furthermore the allelic differences detected by the alloclones are also critical for peptide binding. The majority of clones from the high responder animal recognized an immunodominant region containing a Rothbard epitope whereas none of the clones from the intermediate responder did so. This suggests that the region recognized by T cells, which is dependent upon MHC type, influences the B-cell response and thus the degree of protection obtained. This has major implications for rational vaccine design involving T- and B-cell epitopes.

Animals↗
PubMed1992

Alloreactive T-cell recognition of bovine major histocompatibility complex class II products defined by one-dimensional isoelectric focusing.

T-cell recognition of bovine MHC (BoLA) class II antigens was investigated in relation to BoLA class II polymorphisms defined by one-dimensional isoelectric focusing (1D-IEF). One-way mixed lymphocyte reactions (MLRs), and allospecific cell lines and clones were used. In general, T-cell responses correlated with the 1D-IEF defined haplotypes (EDF types). However, with MLRs some responses appeared to be associated with BoLA class I differences. All combinations of responder-stimulator pairs produced alloreactive T-cell responses both in MLR and in generation of allolines/clones. Thus allospecific lines and clones were generated to all EDF types tested. Splits in the IEF typing were observed with EDF6 and EDF3, indicating that distinct BoLA class II haplotypes are not necessarily distinguished by 1D-IEF alone. Furthermore, the patterns of reactivity with EDF3 expressing cells were complex with the T-cell specificities splitting EDF3 into several distinct types. Also, in some cases it was clear that more than one T-cell specificity per EDF type was detectable. Thus, allospecific lines and clones provide complementary and additional information to the 1D-IEF typing for polymorphism of the BoLA class II complex. This extra information is particularly important in terms of the functional significance of the BoLA complex for antigen presentation and immune response gene effects.

Animals↗
PubMed1989

The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneic Theileria annulata-infected lymphoblastoid cell lines.

Two groups of animals were immunized with either 10(6) autologous or 10(6) allogeneic Theileria annulata-infected lymphoblastoid cells cultured in vitro. The development and specificity of cytotoxic cells generated in vivo were measured throughout immunization and challenge using a panel of target cells that were either Theileria-infected or uninfected blast cells of known bovine lymphocyte antigen (BoLA) specificities. After inoculation of the cell lines the two groups showed distinct differences in both their clinical responses and the target specificity of the cytotoxic cells detected. The allogeneic T. annulata cell line recipients showed a very mild clinical response, and on day 9 after inoculation a strong cytotoxic response was detected. The response appeared to be directed against the allogeneic major histocompatibility complex (MHC) antigens of the inoculated cell line in some form of graft rejection response. By day 23 the predominant cytotoxic response was directed against the recipient animals' own cells infected with the parasite. In contrast, the autologous T. annulata cell line recipients showed very severe clinical reactions, and low levels of cytotoxicity were detected. The cytotoxicity was directed against parasite-infected targets but did not appear to be MHC restricted until day 20. Both groups were immune to a heterologous sporozoite challenge that proved lethal to two susceptible control animals, and on day 10 after challenge a peak of cytotoxicity was detected which was directed against the autologous infected target cell. This would suggest that this cytotoxic response was MHC restricted and was also cross-reactive between the heterologous parasite stocks used.

Animals↗
PubMed1989

In vitro infection of bovine alloreactive cytotoxic T cell lines with sporozoites of Theileria annulata and T parva.

Bovine alloreactive cytotoxic lymphocyte (CTL) lines of known target specificity were infected in vitro with sporozoites of Theileria annulata and T parva and cultured in limiting dilution. The phenotypes of the CTL lines both pre- and post infection were assessed using a panel of monoclonal antibodies specific for defined bovine lymphocyte subpopulations. The effector function of the resultant infected cell lines was determined using a Cr51 release assay and compared to the uninfected control CTL line. The results indicated that T parva sporozoites consistently infected and transformed the CTL lines very efficiently even at the lowest cell doses. In contrast the T annulata sporozoites were largely unable to infect and transform the alloreactive CTL except at the very highest cell and sporozoite doses. A factor which appeared to influence susceptibility to T annulata infection was an increased level of class II expression on the CTL line. None of the cell lines showed cytotoxic effector function after infection with either T annulata or T parva sporozoites.

Animals↗
PubMed1988

Bovine mononuclear cell lines transformed by Theileria parva or Theileria annulata express different subpopulation markers.

Bovine mononuclear cell lines infected with the protozoan parasites Theileria annulata and T. parva have been studied with a panel of monoclonal antibodies reacting with bovine lymphocyte subpopulation markers. All infected lines are MHC class II positive, though the amount of class II antigen expressed varied between lines, and within individual lines there was variation in the proportion of positive cells from 100% with many, to less than 10%. All lines were negative for a macrophage/monocyte marker and for surface IgM. The T. parva lines tested were all positive for BoT4 or BoT8 or both, whereas T. annulata lines were uniformly negative for both of these markers. These results suggest that the two parasites preferentially infect different lymphocyte subpopulations.

Animals↗
PubMed1987

Bovine alloreactive cytotoxic cells generated in vitro detect BoLA w6 subgroups.

Alloreactive cytotoxic T cells (CTL) were generated in mixed lymphocyte culture against cells bearing subgroups of BoLA w6, as well as in BoLA w4, w10 and w16. Primary cultures were restimulated at weekly intervals with irradiated stimulator cells and tested in a 51Cr-release assay with target cells derived from Theileria annulata-infected cell lines. Generation of CTL was accelerated in animals that had been previously primed in vivo by skin grafting. CTL were generated that were specific for BoLA w6 subgroups and not w6. With w6.1 the specific killing was significant at the 5% level, and with w6.2, 6.3 and 6.4 it was significant at the 0.1% level. Where CTL were potentially generated against two BoLA-A locus allele products at the same time (i.e. with heterozygous stimulator cells), one of which was a w6 subgroup, there was similar CTL activity against both products when w6.4 and w16 or w6.1 and w4 were the combinations involved. In two generations against w10 and either w6.1 or w6.2 there was significantly more killing of w10-bearing targets than those with the w6 subgroup.

Animals↗
PubMed1981

A genetic study of bovine lymphocyte antigens (BoLA) and their frequency in several breeds.

Using sera which defined the BoLA specificities at the two International BoLA workshops (Edinburgh, 1978 and Wageningen, 1980) and the European Regional workshop (Paris, 1979), 142 informative matings from 15 bulls have been studied. On the basis of this data, 11 of the 15 internationally agreed specificities and one of the regionally defined specificities behave as if controlled by alleles at a single autosomal locus. Data has not as yet been obtained for the other four internationally agreed specificities which are also believed to be at this locus. - The frequencies of 13 of the internationally agreed specificities and one of the regionally defined specificities have been studied for both sexes in one breed and for a single sex in another five breeds. The other two internationally agreed specificities are very recent and the populations have not been tested for them. The frequencies between sexes within a breed and within sexes between breeds differ significantly.

Alleles↗
PubMed1979

Analysis of alloantisera against bovine lymphocytes. Joint report of the 1st International Bovine Lymphocyte Antigen (BoLA) workshop.

The results and agreements of the 1 international BoLA workshop, held in Edinburgh, Scotland in August 1978, are reported. Most of these concern the results from a comparison test of 249 alloantisera to bovine lymphocytes, the antisera being contributed by 9 laboratories. These sera were compared directly in Edinburgh on a panel of lymphocytes from 130 cattle of 21 breeds. In the microlymphocytotoxicity test used 75% of the sera reacted. Sixty eight of these sera were grouped into clusters according to their reaction patterns against the lymphocyte panel. Eleven of these clusters were clearly defined and were given workshop BoLA designations. In addition 22 sera were assigned to subgroups of the agreed clusters. There was no evidence that the method of production of the sera had any effect on their specificity. Although genetic data was not available, the phenotypes of the test panel of lymphocytes are consistent with the clusters detecting antigens controlled by multiple alleles at a single autosomal locus. It was agreed to name the genetic region where this putative locus is located BoLA (bovine lymphocyte antigen).

Animals↗
PubMed1979

The production and analysis of antilymphocyte sera following pregnancy and skin grafting of cattle.

This paper presents evidence to show that high titre antilymphocyte sera can be prepared more easily by skin grafting than from parous sera. It also shows that it is possible to analyse complex antilymphocyte sera by absorption with lymphocytes to produce working reagents. Following the 1 International BoLA Workshop the genotype of some of the animals used for skin grafting was ascertained and it was found that in each case where the resulting serum had been studied the main antiserum specificity that had been produced reacted with one of the BoLA specificities present in the skin donor.

Animals↗
PubMed1979

Changes in serum immunoglobulin levels in Jerseys and Friesians near calving.

IgG1 and IgM levels were significantly lower in bovine serum from four weeks before, until at least two months after calving, whereas IgG2 levels were elevated at this time. The shapes of the changes in Ig levels were different for first and second calving and it appeared that IgG1 levels were secreted earlier, from serum to colostrum, in heifers. Changes in management caused marked changes in Ig levels particularly after third calving when the cows were transferred from a balanced complete diet to grass or hay. IgG1 levels increased by 130 per cent and stayed high whereas the increase in IgM was transitory, and IgG2 levels largely unaffected. In Friesians the IgG2 levels increased with age as anticipated from previous studies but in Jerseys the levels appeared to decline with age. Mean IgG2 levels in Jerseys were also significantly lower than in Friesians.

Animal Feed↗
PubMed1978

Changes in IgG2 levels with age in British cattle.

IgG1, IgG2 and IgM levels were measured in serum samples from 282 cattle of various ages and the results analysed by least squares. There were marked increases with age in IgG2 levels in bulls, and in dairy cattle in the absence of culling for disease or low production traits. There was about a 300% increase between one year and eight years of age for IgG2 compared with the small increase of about 20% for IgG1 but there was no apparent effect of age on IgM levels. There were no differences between Hereford and Friesian bulls for any of the immunoglobulins but there were environmental differences, between AI centres, for IgG1 and IgM. No animals were found to be immunodeficient but IgG2 levels ranged widely from 1 mg/ml to 35 mg/ml in different bulls.

Aging↗
PubMed1976

An IGG1 allotype in cattle.

This paper presents evidence for an IgG1 allotype detected by a sheep antibovine serum. The character which appears to be inherited in a simple Mendelian way has been named G1a1.

Animals↗