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R C Burton

Publications and source records attributed to R C Burton.

At least 19 recordsLinked to original sources
PubMed1995

Analysis of public education and the implications with regard to nonprogressive thin melanomas.

Public education campaigns to encourage early diagnosis of melanoma have been conducted in a number of countries with predominantly white populations for more than a decade. During the mid to late 1980s the incidence of melanoma has increased sharply above long-term trends in some of these populations. There is evidence that these campaigns can lead to earlier diagnosis of the disease, and thus advancement of the time of diagnosis certainly accounts for some of the recent incidence increases. However, it is possible that earlier diagnosis has also uncovered a preexisting nonfatal (nonmetastasizing) form of melanoma, and that this accounts for a substantial proportion of increases in incidence. Although this should not alter public education for early diagnosis of melanoma, it should give caution to current enthusiasm for population screening for the disease.

Australia↗
PubMed1994

Monoclonal antibody 2B6-F2 identifies a subset of murine natural killer cells with receptors for YAC-1 and WEHI-164 targets.

This study reports the generation of rat MoAb 2B6-F2 (IgG2a) that identifies a subpopulation of murine NK cells in the spleen, bone marrow, peripheral blood, lung, and peritoneal leukocytes. By flow cytometry, 2B6-F2 reacted with 10% of naive CBA (immunizing strain) spleen leukocytes of which 3% exhibited small lymphocyte morphology while 7% were large granular leukocytes. This pattern of binding was similarly obtained for BALB/c, C57BL/6, CE, and DBA/2 mice. 2B6-F2 and complement reduced splenic NK activity 40-57% in CBA, C57BL/6, BALB/c, CE, and DBA/2 strains. In CBA, C57BL/6, and CE mice < or = 15% reduction in splenic NC activity was observed while DBA/2 and BALB/c mice displayed 55-73% reduction. Cellular competitive inhibition studies showed that 2B6-F2+ NK cells in BALB/c and DBA/2 mice bind and kill YAC-1 and WEHI-164 target cells via a receptor that recognizes a shared determinant on these targets. Western blot and radioimmunoprecipitation studies indicated that 2B6-F2 identifies a 14-kDa monomeric cell surface molecule.

Animals↗
PubMed1994

Phenotype and morphology of murine NC-1.1+ natural cytotoxic cells.

The morphology and phenotype of cells identified by the anti-NC-1.1 mAb, 1C4, were studied in CBA and (CBA x C57BL/6) F1 mice. This mAb blocked splenic natural cytotoxic (NC) cell activity in vitro and in vivo. Single colour flow cytometric analysis showed that 6 +/- 1% of all CBA splenocytes were NC-1.1+, and that granular cells of varying sizes, as defined by their forward and side light scatter, contained the highest proportion of NC-1.1+ cells (29 +/- 7%). When analysed by two colour flow cytometry, the large and the granular NC-1.1+ spleen cells in CBA mice were shown to co-express Thy-1.2 and L3T4 (< or = 33%), Mac-1 (< or = 26%), IgM (< or = 60%) and FcR gamma II and J11d (< or = 100%). In contrast, T cell markers were not co-expressed on the small agranular NC-1.1+ spleen cells. This pattern of marker expression was evident in CBA spleens from 2 days of age. When (CBA x C57BL/6) F1 spleen cells were similarly analysed, 82% of granular NC-1.1+ cells also co-expressed NK-1.1. Single colour analysis of CBA bone marrow, thymus, lymph node and peripheral blood leucocytes revealed that < or = 10% of all cells examined were NC-1.1+ while the most granular cells in these organs were 16-43% NC-1.1+. These results support the 'horizontal lineage' theory that NC cells are cells of different lymphohaemopoietic cell lineages at particular stages of differentiation.

Aging↗
PubMed1994

Recent incidence trends imply a nonmetastasizing form of invasive melanoma.

In the mid- to late-1980s white populations in Australia, New Zealand and Scotland showed a sharp increase in melanoma incidence above preceding long-term trends, in some cases as much as doubling in as little as 2 years. Most of this increase was in thin melanomas, (< 1.50 mm thick), and males were more affected than females. Thicker melanomas also generally increased in incidence, particularly in males aged 65 years or older. Examination of Australian Medicare and pathology laboratory data indicated that excision of skin lesions and laboratory diagnosis of pigmented lesions also rose sharply in this period, suggesting that advancement of the time of diagnosis was a likely factor in the increase in melanoma incidence. However the maintenance of new higher incidence levels and the increase in incidence of thicker lesions suggests that advancement of diagnosis cannot explain all of the increase. A real increase in incidence and increasing diagnosis of a preexisting, non-metastasizing form of thin melanoma may also have contributed.

Adolescent↗
PubMed1993

Allogeneic blood transfusion reduces murine pulmonary natural killer (NK) activity and enhances lung metastasis of a syngeneic tumour.

A model was established whereby C57BL/6 (B6) blood injected i.v. into C3H mice 7 days prior to i.v. injection of syngeneic UV-2237 tumour cells significantly increased the number of pulmonary metastases counted 21 days later as compared with levels observed in mice treated with saline, C3H or NZW blood or SRBC. This regimen of B6 allogeneic blood transfusion of C3H mice also significantly depressed splenic and pulmonary NK activity as assayed by lysis of 51Cr YAC-I in vitro and by clearance of 111In YAC-I in vivo respectively. Anti-asialo GMI treatment, which depletes NK activity in vivo, and Poly I:C treatment, which enhances NK activity in vivo, were associated with significantly increased and decreased pulmonary metastasis of UV-2237, respectively, in C3H mice. Depletion of CD4+ and CD8+ T cells had no effect. Cyclophosphamide pretreatment which, among other effects, depletes NK cells, significantly increased pulmonary metastasis of UV-2237 in C3H mice. This was corrected by adoptive transfer of normal C3H spleen cells but not spleen cells from anti-asialo GMI-treated C3H mice or B6-blood-transfused C3H mice. Furthermore, a 1:1 mixture of normal C3H spleen cells with spleen cells from B6-blood-transfused C3H mice also failed to reconstitute the cyclophosphamide-pre-treated C3H mice. We conclude that allogeneic blood transfusion augments pulmonary metastasis of the UV-2237 sarcoma in C3H mice and that the mechanism involves suppression of NK activity.

Animals↗
PubMed1993

An analysis of a melanoma epidemic.

Between 1986 and 1988 the annual incidence of invasive melanoma in the Hunter area of New South Wales, Australia, almost doubled to 52.5 per 100,000 in men and 42.9 per 100,000 in women. These rates have been maintained and are similar to those reported for 1987 in Queensland, Australia, which are the highest in the world. Most of the increase in incidence was in melanomas less than 1.50 mm in thickness, and adults of both sexes and all ages were affected. Thicker melanomas also increased in incidence but only in adults 45 years and older, and mainly in men. An analysis of health insurance data on treatment of skin lesions and data from a histopathology laboratory suggested that diagnosis and treatment of skin lesions generally in the Hunter area had increased almost 2-fold over this period. Advancement of the time of diagnosis and a real increase in incidence were likely explanations for some of the observed trends. Increasing diagnosis of a non-metastasising form of thin melanoma, consequent upon increasing removal of pigmented skin lesions by medical practitioners, may also explain some of the observed increase in the incidence of the disease. This possibility has important implications for proposed population screening programs, and methods are needed to distinguish such lesions, if they exist, from potentially fatal melanoma.

Adult↗
PubMed1992

The effect of the Cmv-1 resistance gene, which is linked to the natural killer cell gene complex, is mediated by natural killer cells.

The resistance of mice to lethal infection by murine CMV (MCMV) is under complex host genetic control with contributions from both H-2 and non-H-2 genes. We have previously shown that an autosomal, non-MHC encoded gene, Cmv-1, controls MCMV replication in the spleen. We have investigated the mechanism by which the Cmv-1 resistance gene confers protection against MCMV infection. Using H-2 compatible irradiation bone marrow chimeras, the enhanced resistance to MCMV infection that is associated with the Cmv-1l allele in the C57BL background was shown to be mediated by an irradiation-sensitive bone marrow-derived cell population, or a factor produced by these cells. The lack of correlation between serum IFN titers and the strain distribution pattern of Cmv-1 in CXB recombinant inbred mouse strains suggests that IFN does not mediate resistance conferred by this gene. Similarly, the lack of effect of in vivo depletion of mature CD4+ and CD8+ T cells on virus replication in C57BL/6J mice indicates that T cells are unlikely to be involved. In contrast, in vivo depletion of NK cells by injection of the anti-NK1.1 mAb PK136 abrogated restricted splenic virus replication in C57BL/6J----BALB.B chimeric mice and in the Cmv-1l CXB strains. These data indicate that the effect of the Cmv-1 gene is mediated by NK cells. The significant augmentation in NK cell activity after MCMV infection of the susceptible Cmv-1h strains (BALB/cBy), CXBG/By, CXBH/By, CXBI/By, and CXBK/By) indicates the existence in these mice of NK cells that are functionally and phenotypically distinct from those in Cmv-1l strains. NK cells present in the Cmv-1h strains are unable to restrict efficiently splenic MCMV replication in vivo, possibly due to a lack of specificity for virus-infected target cells. Finally, flow cytometric analysis of NK1-1 expression in CXB and BXD RI mice together with MCMV replication studies in the BXD RI strains indicate that Cmv-1 is closely linked to NK1.1 and other loci that reside on a distal segment of murine chromosome 6 in a region that has recently been defined as the natural killer complex.

Animals↗
PubMed1992

Correlation of growth of tumours in NC-cell-depleted mice with NC- and NK-cell-mediated lysis in vitro.

The anti-tumour surveillance activity of natural cytotoxic (NC) cells was studied in vivo using the transplantable tumours WEHI-164 fibrosarcoma, MPC-II plasmacytoma, WEHI-7 T-lymphoma, B16 melanoma and EL-4 thymoma in syngeneic and semi-allogeneic mice. Experimentally, mice were treated with the anti-NC-I.I monoclonal antibody (MAb) IC4 to abrogate splenic NC activity. This was followed by s.c. inoculation of MTD100 doses of the tumours. Comparison of the diameters of the tumours in the anti-NC-I.I-treated mice with control mice using non-parametric statistics showed significantly faster growth of WEHI-164 (p less than 0.01), MPC-II (p less than 0.05) and WEHI-7 (p less than 0.05) when the mean tumour diameters were less than 15 mm in the anti-NC-I.I-treated mice. Significantly faster growth was also observed in anti-NC-I.I-treated mice with the B16 tumour (p less than 0.05), but at a later stage of growth, when the tumour diameter was greater than 15 mm. In vitro, WEHI-164, MPC-II and WEHI-7 were shown to be predominantly sensitive to lysis by mouse splenic NC cells, while B16 was predominantly lysed by splenic natural-killer (NK) cells. Anti-NC-I.I treatment of mice did not affect the growth of EL-4 in vivo and in vitro experiments with anti-NK-I.I and anti-NC-I.I MAb indicated that this tumour was lysed by sub-sets of NK and NC cells distinct from those which lysed the other tumours. We conclude that, in mice at least, NC cells have an in vivo role in controlling the growth of some transplantable tumours, and this correlates with the in vitro NC cell lysis of these same tumours.

Animals↗
PubMed1991

Factors related to the presentation of patients with thick primary melanomas.

OBJECTIVE: To identify any characteristics of patients that are associated with presentation with thick primary melanoma. DESIGN: This was a retrospective survey of the clinical records of 1300 patients attending the Newcastle Melanoma Unit. Characteristics of 131 patients with thick melanomas (defined as 3 mm or greater in thickness) were compared with those of 543 patients with thin melanomas (defined as 0.75 mm or less in thickness). Comparisons were made using contingency table analysis, Wilcoxon rank sum tests, log rank analysis and logistic regression. SETTING: The Newcastle Melanoma Unit is a tertiary referral centre for the treatment of primary melanoma. PATIENTS: We surveyed all 1300 patients attending the Newcastle Melanoma Unit over the years 1981-1990. They represented approximately 90% of the patients in the Hunter region of New South Wales who developed melanoma during this period. Excluded from analysis were 39 patients with occult primary melanomas, 79 with multiple primary melanomas, 51 with primary melanomas of unknown thickness and seven with incomplete records, leaving 1124 patients in the study. MAIN OUTCOME MEASURES: These were selected before the results were known. The hypothesis was generated following analysis of the data. RESULTS: Patients with thick primary melanoma were more likely to be men (68% men and 32% women in the thick melanoma group, compared with 45% and 55% respectively in the thin melanoma group, P less than 0.005) over 60 (75% were over 50 years of age in the thick group versus 33% in the thin melanoma group, P less than 0.001) with nodular melanoma (62%, versus 2% in the thin melanoma group, P less than 0.001) and with melanoma on the head and neck (27%, versus 12% in patients with thin melanoma, P less than 0.005). The time from detection of a change in skin to diagnosis was not longer for those with thick compared to those with thin melanomas. CONCLUSION: The greatest problem of those with thin melanomas. CONCLUSION: The greatest problem of detecting melanoma at an early (surgically curable) stage appears to be in patients over the age of 50 who have nodular melanoma, particularly in the head and neck.

Adolescent↗
PubMed1991

Studies on murine natural killer (NK) cells. V. Genetic analysis of NK cell markers.

This paper attempts to clarify the number and nomenclature of murine natural killer (NK) cell specific alloantigens by defining the genetic relationships between them, that is, are they coded by loci which are independent, allelic, or linked. Strain typing and F2 analyses using five alloantisera (C3H X BALB/c)F1 anti-CE, CE anti-CBA, NZB anti-BALB/c, C3H anti-ST, and BALB/c anti-DBA/2 revealed that (a) the alloantigens NK-1.1 and NK-3.1 are determined by distinct loci which are linked on the same chromosomes, (b) the alloantigen NK-2.1 is determined by an independently segregating locus to those coding for NK-1.1 and NK-3.1, (c) the alloantisera, CE anti-CBA and NZB anti-BALB/c, which have been designated anti-NK-2.1 alloantisera recognize different alloantigens coded by independent genetic loci. Thus, these five alloantisera detect four NK cell specific alloantigens which, based on the chronology of their discovery, have been designated NK-1.1-(C3H X BALB/c)F1 anti-CE, NK-2.1-CE anti-CBA, NK-3.1-C3H anti-ST, and BALB/c anti-DBA/2 and NK-4.1-NZB anti-BALB/c.

Animals↗
PubMed1990

Mammary serum antigen (MSA) in advanced breast cancer.

An Enzyme Linked Immunosorbent Assay (ELISA) based on a monoclonal antibody, 3E1.2, was used to measure circulating Mammary Serum Antigen (MSA) in a study of 123 advanced breast cancer patients. Fifty two patients were monitored serially to investigate whether measurements of circulating MSA levels were of value in the management of advanced breast cancer patients on palliative therapy. Analysis of variance showed that circulating MSA levels at first presentation correlated with disease status both at initial presentation (p = 0.01) and also 4 months later (p = 0.003). At first presentation, the circulating MSA level also significantly correlated with the number of metastatic sites (p = 0.04), but this did not hold at 4 months. The circulating MSA levels did not at any time correlate with the type of treatment given nor age of the patient. We conclude that MSA might ultimately be useful in the management of advanced breast cancer patients as a prognostic marker for the course of the disease and for monitoring patient response to palliative hormonal therapy and chemotherapy.

Adult↗
PubMed1990

Production of a monoclonal allo-antibody to murine natural cytotoxic cells.

A mouse IgG1 monoclonal antibody (1C4), which recognizes a cell surface molecule on murine natural cytotoxic (NC) cells was produced. By flow cytometry, 1C4 preferentially reacted with less than 5% of fresh CBA spleen cells and 20-50% of CBA-interleukin-3 (IL-3) cells, an in vitro derived NC-like cell line. In vitro treatment of spleen cells from a number of inbred mouse strains either with 1C4 alone or 1C4 coupled to dynabeads markedly decreased or abolished NC activity of the cells against 51Cr-labelled WEH1-164 targets. Splenic NC activity of these same mouse strains was also reduced or abolished by in vivo administration of 1C4. The effect was evident within 2 h of treatment and persisted for at least 1 week. In contrast 1C4 had little or no effect on splenic NK activity against 51Cr-labelled YAC-1 targets over the same range of experiments in vitro and in vivo. Results of strain surveys for both in vitro and in vivo reduction of splenic NC activity by 1C4 treatment showed that CBA, C57BL/6, BALB/c and NZB mice were positive and CE and DBA/2 mice were negative, indicating that 1C4 recognizes an allo-antigen on mouse NC cells. This allo-antibody has been designated NC-1.1, and thus 1C4 is an anti-NC-1.1 monoclonal antibody.

Animals↗
PubMed1989

Expression of natural killer (NK) cell-specific alloantigens on a mouse NK-like cell line.

As part of the strategy for screening for natural killer (NK) cell-specific monoclonal antibodies (MoAb) we have raised a number of murine NK-like cell lines in media containing interleukin-2 (IL-2). The detection of specific NK cell alloantigens on a C57BL/6 cell line in long-term culture in IL-2 is the subject of this paper. The C57BL/6 cell line has the morphology of large granular lymphocytes (LGL) and exhibits strong cytolytic activity against the archetype NK cell target, YAC-1. Absorption of three anti-NK antiserum, NZB anti-BALB/c (anti-NK-2.1), BALB/c anti-DBA/2 (anti-NK-3.1) and CE anti-CBA (anti-NK-4.1), with the C57BL/6 cell line removed the anti-NK activity from these antisera. Flow cytometric studies of the C57BL/6 cell line demonstrated significant binding of the anti-NK-1.1 MoAb produced by hybridoma PK136. Our results suggest that the C57BL/6 NK-like cell line exhibits some of the properties of naive NK cells and expresses all the known NK cell-specific alloantigens, NK-1.1, NK-2.1, NK-3.1 and NK-4.1 and therefore is potentially useful in selecting NK specific hybridomas and in studying the biology of NK cells.

Animals↗
PubMed1989

Studies on natural killer (NK) cells IV NK-3.1: a new NK cell specific alloantigen.

A new murine natural killer (NK) cell alloantigen, NK-3.1, has been identified by analysis of the complement dependent anti-NK cell activity of C3H anti-ST and BALB/c anti-DBA/2 alloantisera. Flow cytometric studies with a specific antiserum made in backcross mice indicate that this alloantigen is expressed by 2-3% of the spleen cells of NZB and C57BL/6 mice, positive strains, but is undetectable on the spleen cells of C3H mice, a negative strain. Since NK-1.1 and NK-2.1 are also expressed on 2-3% of spleen cells of positive strains we suggest that all three alloantigens identify the NK cells in normal mouse spleen which lyse the lymphoma target cell line YAC.

Absorption↗
PubMed1989

Factors affecting MSA levels in normal women and women with breast cancer.

Blood from 1497 women who were either non-pregnant, pregnant at all stages of gestation, lactating after parturition, postmenopausal, or who had benign breast lumps, primary breast cancer or advanced breast cancer were tested for their peripheral blood mammary serum antigen (MSA), using the 3E1.2 monoclonal antibody (MoAb) in an inhibition enzyme linked immunosorbent assay test system. The study aimed to establish normal ranges for comparison with MSA levels in breast cancer and benign breast disease. Compared with normal premenopausal women, which included women measured 8-10 times throughout their menstrual cycle, circulating MSA levels were significantly elevated throughout pregnancy (P less than 0.0001), in postmenopausal women (P less than 0.05), in women with primary breast cancer (P less than 0.05) and women with advanced (metastatic) breast cancer (P less than 0.0001). As a group, the 30 women with benign breast disease did not demonstrate significantly different MSA level from normal. However, 3% of the group did have levels above the 'cut off' for normal (400 IU/mL). Analysis of the normal premenopausal women according to age, parity and stage of the menstrual cycle and during lactation showed that these parameters did not affect MSA levels. It is concluded that the test is potentially valuable in the detection of metastatic but not primary breast cancer, and the effects of pregnancy and postmenopausal status on the circulating MSA levels need to be considered in the interpretation of MSA measurements.

Antibodies, Monoclonal↗