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Y C Smart

Publications and source records attributed to Y C Smart.

At least 37 records · Page 2Linked to original sources

Anaerobic exercise causes transient changes in leukocyte subsets and IL-2R expression.

There is evidence that the stress of intense athletic competition and training depresses cellular immunity and predisposes athletes to increased infection. This paper reports changes in circulating leukocyte subsets of trained (group I: VO2max = 67.2 +/- 5.4 ml.kg-1min-1; age = 22.0 +/- 6.2 yr) and untrained (group II: VO2max = 55.0 +/- 4.9 ml.kg-1min-1; age = 21.4 +/- 2.0 yr) males following 1 min of bicycle ergometry at maximum effort. Significant post-exercise increases in concentrations of total leukocytes, monocytes, lymphocytes, CD3+, CD4+, CD8+ lymphocytes were observed in both groups (all P < 0.01). The CD4/CD8 ratio decreased significantly (P < 0.01) but the granulocyte concentration was not altered (P > 0.05). Despite groups I and II not differing in either peak power or total work performed during the exercise test (P > 0.05), group II had a significantly greater concentration and percentage of CD8+ lymphocytes immediately after exercise (P < 0.01). All of the early changes were transient, with normalization occurring within 1 h. Only trained subjects showed a significant decrease in the percentage of CD25+ lymphocytes following PHA stimulation of whole blood obtained 6 h post-exercise. Alterations in leukocyte subpopulations found in response to predominantly anaerobic exercise appear to be associated with a significant, but possibly transient, alteration in the mitogenic responsiveness of lymphocytes that is restricted to aerobically trained subjects.

Adolescent↗

Studies on murine embryo-derived platelet-activating factor (EPAF).

Studies were carried out using the splenectomized mouse bioassay (SMB) to investigate the nature of embryo-derived platelet-activating factor (EPAF) and its relationship to synthetic platelet activating factor (PAF). While both C16-PAF and embryo conditioned media (ECM) induced a significant platelet decline in the SMB at 15 min postinjection, C18-PAF induced a similar effect at 30 min postinjection. The degree of EPAF activity in ECM was not altered with increasing embryo number from 2 to 40/ml of media. In contrast, PAF (C16/C18 mixture) induced a linear increase in activity with increasing concentration, leading to lethal effects at high concentrations. While EPAF activity was not significantly altered when ECM was diluted 1/1,000, PAF activity was abolished at 1/10 dilution. EPAF in ECM was not inactivated by mouse plasma; however, lipid extracted ECM, like PAF, underwent rapid inactivation in the presence of plasma. Aggregometer studies using horse platelets showed that ECM and lipid-extracted ECM were unable to induce platelet aggregation, while thin-layer chromatography (TLC) purified ECM (Rf 0.23) successfully aggregated horse platelets in vitro. Results suggested that EPAF and PAF are not homologous. EPAF might consist of PAF bound to a regulatory carrier molecule and appears to be associated with EPAF-inhibitor substance(s) in ECM.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

An evaluation of peripheral blood platelet enumeration as a monitor of fertilization and early pregnancy.

This paper reports our data that confirm the existence of early pregnancy-associated thrombocytopenia (EPAT) in the mouse and illustrate that the phenomenon is independent of age, parity, and strain differences. This paper also provides evidence that the EPAT phenomenon is induced by a soluble factor (EPAT-factor) released by the fertilized ovum. EPAT-factor was produced in vitro by mouse embryos from the 1-cell stage to the expanded blastocyst stage. The human study involved a "blind" analysis of serum samples, collected from in vitro fertilization-treated patients, for the presence of thrombocytopenic activity. Results suggest that measurement of this thrombocytopenic activity might be useful as an index of embryo viability and might be clinically applicable for the monitoring of implantation success in in vitro fertilization programs.

Animals↗

Mechanistic studies of early pregnancy associated thrombocytopenia (EPAT) in the mouse.

The preimplantation period of uterine pregnancy is associated with the transient (first 4 days of gestation) expression of a state of early pregnancy-associated thrombocytopenia (EPAT), a phenomenon shown to be mediated by the embryo-derived EPAT factor, which presumably causes platelet activation and subsequent removal. We previously investigated the time course of production of EPAT factor in mouse embryo culture medium and found a correlation between the production of this factor and the in vivo platelet alterations in pregnant mice. The present paper supports the postulation that the EPAT factor and PAF-acether (a phospholipid platelet-activating factor) are related by providing data showing that PAF-acether may be responsible for the thrombocytopenia. Finally, data are presented to suggest that platelet activation, though not affecting the rate of ovulation, is important for successful ongoing pregnancy. Results suggest that the EPAT factor, produced by the fertilized egg, might act to signal uterine decidualization and/or modulate maternal immunological rejection of the implanting conceptus.

Animals↗

Effects of captopril on circulating T lymphocyte subsets.

Six patients treated with captopril for severe essential hypertension were studied to determine whether the drug significantly altered circulating peripheral blood T (Thymus derived) lymphocytes and T lymphocyte subsets. OKT3+ (functionally mature T lymphocytes), OKT4+ (class II major histocompatibility complex [MHC] reactive T lymphocytes) and OKT8+ (class I MHC reactive T lymphocytes) T lymphocytes were monitored using monoclonal antibodies and flow cytometry before commencement of treatment and then at intervals during 14 months of captopril administration. Results showed a significant increase in the absolute numbers of OKT4+ cells at 2 h (p less than 0.05) and a decrease at 12 weeks (p less than 0.01) during captopril treatment. These findings indicate that captopril has an effect on cellular immunity in vivo.

Aged↗

Flow cytometric enumeration of absolute lymphocyte number in peripheral blood using two parameters of light scatter.

A method was developed to measure the absolute lymphocyte count (ALC) of whole blood using the Spectrum III automated flow cytometer. Ninety-nine samples of human peripheral blood were analysed on the Spectrum and the Coulter Counter S Plus II, to allow for comparison of the two machines. Regression analysis was used to test the extent of agreement between the sets of measurements on the two machines. The results demonstrated that the slope of the regression line was not significantly different from one, indicating a high level of correlation between Spectrum and Coulter ALC's. However, the mean difference between Coulter and Spectrum ALC's was not equal to zero, with the Spectrum giving counts approximately 10% lower than those of the Coulter machine. This is attributed to the different ways by which the two machines define a lymphocyte, the Spectrum III by two parameters of light scatter and the Coulter S Plus II by the single parameter of cell volume.

Flow Cytometry↗