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Peter Kerr

Publications and source records attributed to Peter Kerr.

14 recordsLinked to original sources
PubMed2006

p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene.

DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild-type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild-type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild-type p53, favoured by DNA damage. Moreover, wild-type p53 inhibits Rad51 foci formation in response to double-strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.

Blotting, Western↗
PubMed2006

Comparison of biochemical, haematological and volume parameters in two treatment schedules of nocturnal home haemodialysis.

BACKGROUND: The biochemical, haemodynamic, clinical and nutritional benefits of nocturnal home haemodialysis (NHHD) compared with 4 h, three times per week conventional haemodialysis are well known and accrue by increasing dialysis time and frequency either for 8 h alternate night per week (NHHD3.5) or for 8 h six nights per week (NHHD6). However, there are little data comparing NHHD3.5 with NHHD6. METHOD AND RESULTS: Thirteen patients on NHHD6 were compared with 21 patients on NHHD3.5, all with similar demographic profiles. Pre- and post-dialysis phosphate (PO4) control was ideal between the groups. However, all NHHD6 needed PO4 supplementation compared with 4/21 (19%) NHHD3.5. In the present study, 8/21 (38%) NHHD3.5 needed PO4 binders whereas none was required with NHHD6. The pre-haemoglobin (Hb) 122.8 g/L (NHHD6) versus 124.9 g/L (NHHD3.5) and the pre-albumin 38.31 g/L (NHHD6) versus 37.71 g/L (NHHD3.5) were not significantly different. NHHD6 had significantly lower pre-blood urea and creatinine (10.16 vs 19.54 mmol/L and 437.0 vs 812.3 micromol/L, respectively). Less interdialytic urea and creatinine fluctuation were also noted in NHHD6. Of major significance was the significantly lower ultra filtration rate and intradialytic weight gains (mean +/- SEM) of NHHD6 (249 +/- 76 mL/h and 2.0 +/- 0.65 kg) versus NHHD3.5 (425 +/- 168 mL/h and 2.9 +/- 1.2 kg). CONCLUSION: The authors conclude that NHHD6 offers the optimum biochemical, volume and clinical outcome, but NHHD3.5 has additional appeal to providers seeking home-based therapy cost advantages and consumable expenditure control. A flexible dialysis programme should offer all the time and frequency options of NHHD but in particular, should support NHHD at a frequency sympathetic to the clinical rehabilitation and lifestyle aspirations of individual patients.

Adult↗
PubMed2005

Lymphocytes and MHC class II positive cells in the female rabbit reproductive tract before and after ovulation.

In this study, we identified lymphocytes and MHC class II positive (MHC-II+) cells in the reproductive tract of female rabbits both before and after ovulation. CD43+ T cells were frequently present in the mucosa of the oviduct, cervix, and vagina, but far fewer positive cells were seen in the endometrium. The induction of ovulation did not change the cell density in these regions. KEN-5+ T cells and MHC-II+ cells were also frequently seen in the mucosa of the oviduct, cervix, and vagina both before and after ovulation. However, in the uterus, there were very few positive cells before ovulation, but the number increased dramatically after ovulation. Associated with the increase of KEN-5+ T cells, IL-2 mRNA expression in the uterus also increased after ovulation, suggesting that the uterus experienced an increase of T-cell activation. IgM- and IgA-positive B cells were not commonly seen in the reproductive tract and the induction of ovulation did not alter this. Our results suggest that the reproductive tract of female rabbits has the capacity to mount an immune response and that the immune cell distribution of the rabbit reproductive tract has some distinctive features compared with that found in other species.

Animals↗
PubMed2004

Immune response in rabbit ovaries following infection of a recombinant myxoma virus expressing rabbit zona pellucida protein B.

In this study, we investigated the autoimmune response in rabbit ovaries following infection with a recombinant myxoma virus expressing rabbit zona pellucida protein B (MV-ZPB). A specific IgG antibody response to ZPB was elicited in the serum of infected rabbits and the antibody strongly bound to the zona pellucida of oocytes in secondary and tertiary follicles. T cell infiltration in the ovary was detected in a small proportion of the infected rabbits. In spite of this, the mean number of preovulatory and tertiary follicles in the ovary was significantly reduced at 30 days postinfection compared with that of the infected and uninfected controls. Histological analysis revealed that the cortex and medulla of these ovaries had accumulated a large number of probably luteinized cells and there were no follicles in these areas, indicating the ovaries were in a severe pathological condition. The data suggest that the delivery of ZP antigens using a recombinant myxoma virus is a prospective way to develop immunocontraceptive vaccines for rabbit population control, but that more understanding of the kinetics of the autoimmune response induced by viral delivery is needed.

Animals↗
PubMed2004

Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial.

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.

Anemia↗
PubMed2003

Antibody response in the female rabbit reproductive tract to influenza haemagglutinin encoded by a recombinant myxoma virus.

The antibody response in serum and the reproductive tract of female rabbits to a model antigen, influenza virus haemagglutinin (HA), encoded by a recombinant myxoma virus was investigated. Strong and lasting IgG antibody responses to HA were induced in serum following intradermal, intranasal, and intravaginal immunisations. HA IgG was also detected in reproductive tract fluids but was only about 1% the titer of that in serum. HA IgA was not detected in serum of any infected groups and was occasionally detected in reproductive tract fluids at a low titer only after infections through mucosal sites. HA IgM was also detected only in some of the reproductive tract fluids at very low levels. Induction of ovulation did not change these patterns and B cell homing to the reproductive tract was not profound. In contrast, HA IgG and IgM titers in ovarian follicular fluids were comparable to that in serum. These data suggest that if this virus is used to deliver an immunocontraceptive vaccine that requires a high-level antibody response, the target antigen needs to be accessible to serum antibody or in the ovary.

Animals↗
PubMed2003

Cell cycle and genetic background dependence of the effect of loss of BRCA2 on ionizing radiation sensitivity.

Carriers of mutations in the BRCA2 gene are at a highly elevated risk of breast and other cancers. The BRCA2 gene encodes a very large protein thought to play a role in DNA repair. To examine the effect of mutation of BRCA2 on sensitivity to ionizing radiation, we used a previously described mouse model system (Brca2(Tr)) in which the Brca2 open reading frame is truncated. Mouse embryo fibroblasts carrying this mutation have a proliferative defect, which we show here can be substantially rescued by genetic ablation of p53. Proliferating Brca2(Tr/Tr)/p53(-/-) cells, like Brca2(Tr/Tr) cells, show genomic instability. We used the clonogenic survival assay, which depends on the ability of cells to proliferate, to examine the cell cycle dependence of radiation sensitivity of Brca2(Tr/Tr)/p53(-/-) compared to p53(-/-) and wild-type cells. This showed that the Brca2 mutation had little effect on cells irradiated in quiescence but sensitized proliferating cells to ionizing radiation on a p53(-/-) background. These results suggest that the major role of Brca2 in mediating cell survival after irradiation is in the S and G(2) phases of the cell cycle.

Animals↗
PubMed2002

Immune responses to myxoma virus.

Myxoma virus causes the systemic disease myxomatosis in the European rabbit (Oryctolagus cuniculus). Originating in the South American rabbit Sylvilagus brasiliensis, where it causes a relatively localized fibroma, myxoma virus is a classic example of a virus that has jumped species to produce an exotic disease and then coevolved with its new host. Like other poxviruses, myxoma virus encodes multiple proteins capable of downregulating the host innate and acquired immune responses. Other virus-encoded proteins enable replication in host lymphocytes and monocytes, for example, by inhibiting apoptosis. Detailed studies on these proteins have demonstrated novel methods of interactions with the host immune system and added substantially to the understanding of the interaction of large DNA viruses with their hosts. Despite the increasingly detailed molecular knowledge of myxoma virus, relatively little is known about the dynamics of the interaction of the virus with the integrated host-immune system during infection and, in particular, about the evolution of resistance to the virus in wild rabbits or the species barrier. This review will focus on the detailed molecular studies that have been done with myxoma virus and discuss the more limited knowledge of the pathogenesis of myxoma virus in rabbits and the ways that the consolidated immune responses may determine genetic resistance to myxomatosis.

Animals↗
PubMed2002

Karyomegalic nephropathy: an uncommon cause of progressive renal failure.

BACKGROUND: Karyomegalic nephropathy, first identified in 1974, represents an increasingly recognized, but perhaps underdiagnosed condition associated with interstitial nephritis. It undoubtedly leads to end-stage renal disease requiring renal support. METHODS AND RESULTS: We present a series of six cases of karyomegalic nephropathy. The age at diagnosis was 9-51 years, median 33 years. Impaired renal function, proteinuria, and haematuria were present in the majority of cases. Non-specific elevated liver enzymes were present in three cases. Two patients died soon after transplantation from overwhelming respiratory sepsis. The classical histological features of large, abnormal hyperchromatic nuclei with irregular outlines within epithelial cells were present in renal epithelial cells. Abnormality of DNA ploidy distributions compared with age- and sex-matched controls, and characterized by the presence of significant numbers of cells with high ploidy values was present in cases but not in controls. Mitotic figures were absent. Proliferation markers, Ki-67 and proliferating cell nuclear antigen/cyclin were not significantly elevated in those cases examined. Human leukocyte antigen analysis did not support the clustering of A9 or B35, in the cases or their families. CONCLUSIONS: The presence of significant renal impairment, positive urine sediment, abnormal liver enzymes, and early age of onset should alert one to the presence of karyomegalic nephropathy. It represents an underdiagnosed disorder with a high degree of ploidy indicative of karyotypic abnormality.

Adult↗