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Biomedical subjects

A H McDonald

Publications and source records attributed to A H McDonald.

11 recordsLinked to original sources
PubMed1998

Silicone gel enhances the development of autoimmune disease in New Zealand black mice but fails to induce it in BALB/cAnPt mice.

Anecdotal evidence links silicone gel breast implants with the development of autoimmune connective tissue disease in women. To investigate whether silicone gel is capable of directly inducing and/or enhancing the development of autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice were injected subcutaneously with silicone gel, pristane, a nonmetabolizable substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and monitored for the development of glomerulonephritis and autoantibody production. NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly screening for proteinuria revealed increases in urinary protein in NZB mice that received multiple injections of either silicone gel or pristane. In contrast, urinary protein was unaffected in identically treated BALB/c mice. Although, silicone gel had no effect on serum titers of antierythrocyte antibodies in NZB mice, the hematocrits were significantly decreased. Moreover, silicone gel both increased the concentration of IgM anti-type I collagen antibodies and skewed the immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In contrast, silicone gel failed to induce the production of anti-erythrocyte or antinuclear antibodies in BALB/c mice and induced only slight increases in IgG anti-type I collagen antibodies. These results suggest that silicone gel can exacerbate the development of autoimmune disease in autoimmune NZB mice, but fails to induce disease in normal BALB/c mice. This is consistent with several epidemiological studies failing to demonstrate an increase in the incidence of autoimmune disease in women with breast implants. However, because silicone gel was able to exacerbate autoimmune disease in NZB mice, it may play a similar role in the development of autoimmune disease in a small percentage of women who are genetically susceptible to such diseases.

Animals↗
PubMed1996

Plasmacytoma-refractory BALB/cAnPt mice have naive T cell and highly specific B cell responses to antigen.

Recently, a reduction in the incidence of pristane-induced plasmacytomas in BALB/cAnPt (BALB/c) mice that were kept in viral specific pathogen-free (SPF) conditions has been reported. Environmentally, these SPF-BALB/c mice differed from conventionally-housed (CON) mice only in viral exposure and diet (i.e. sterilization of mouse chow), since microbial colonization of the intestinal tract was seen to be equivalent. This report assessed the ability of SPF- and CON-BALB/c mice to respond to immunologic challenge with soluble antigen, i.e. hen egg white lyzosyme (HEL), as a means of evaluating differences in T and B cell function and, indirectly, evaluating the possible effects these differences might have on plasmacytoma development. When cultured in vitro for 5 days with HEL, HEL-primed lymph node cells (LNC) from SPF-BALB/c mice proliferated to a significantly lesser extent than HEL-primed CON-BALB/c LNC. Moreover, HEL-induced production of IFN-gamma and IL-5 was significantly lower in SPF LNC. Serum IgG1 levels were 10-fold lower in SPF-BALB/c mice with, or without prior immunization with HEL and were not reconstituted by repeated injections of HEL in adjuvant. Serum IgM levels of SPF- and CON-BALB/c mice were equivalent. This reduction in immune responses could not be attributed to a lack of colonization of secondary lymphoid organs, since flow cytometric analysis of LNC revealed no difference in the number of recoverable cells and the proportion of lymphocyte subsets (CD4+, CD8+ and CD45+ cells) obtained from SPF- and CON-BALB/c mice. However, only CON LNC were induced to increase surface expression of CD44 after antigenic or mitogenic stimulation in vitro. Antibody responsiveness to HEL, as evidenced by serum anti-HEL binding or splenic hybridoma studies, demonstrated higher levels of IgG1 antibodies in CON BALB/c mice than in SPF mice. However, a greater proportion of the SPF IgG1 antibodies present were specifically directed against HEL, so that specific activity was greater in SPF-BALB/c mice. Therefore, while SPF BALB/c mice have a more restricted response to HEL than CON-BALB/c mice, those antibodies that are produced are more specifically directed against HEL with very little apparent bystander/polyclonal activation of multireactive cells. Resistance to plasmacytomas in SPF-BALB/c mice, therefore, may stem from a reduced number of circulating memory T and B cells, which are capable of reacting and/or crossreacting with a chronic inflammatory stimulus.

Animals↗
PubMed1993

Pristane induces an indomethacin inhibitable inflammatory influx of CD4+ T cells and IFN-gamma production in plasmacytoma-susceptible BALB/cAnPt mice.

In BALB/cAnPt (BALB/c) mice, the intraperitoneal injection of pristane induces the formation of chronic oil granulomatous tissue and a high incidence of plasmacytomas (PCT). DBA/2N (DBA) and (BALB/c x DBA)F1 hybrid (CDF1) mice develop oil granulomas but no PCT. Recent studies comparing pristane-injected conventionally housed BALB/c mice with specific pathogen-free BALB/c mice (SPF) demonstrated a significant reduction in both the incidence of PCT and the T cell infiltration of oil granulomatous tissue in SPF mice. In this study, FACS analysis was performed to determine the proportion of myeloid, T. and B cells present in pristane-induced peritoneal exudate (PE), and oil granulomas (OG) of BALB/c, DBA, and CDF1 mice. At all time points studied, the majority of cells recovered from the PE and OG of all three strains of mice were Mac-1+, presumably macrophages and neutrophils. Neither Ly-5(B220)+ B cells nor CD8+ T cells were significantly altered by pristane injection. BALB/c mice had a dramatic influx of CD4+ T lymphocytes (three- to fivefold) more than 50 days after the initial injection of pristane. The PCT-resistant DBA and CDF1 mice did not. This increase in CD4+ cells in BALB/c mice was not significantly affected by a second injection of pristane nor was it induced by a second injection in DBA mice. Indomethacin, which has been shown to prevent the development of PCT in BALB/c mice, prevented the infiltration of CD4+ T cells. In addition, pristane-induced levels of interferon-gamma greater than controls were found in the peritoneal lavages of BALB/c mice at all time points tested but not in DBA or indomethacin-treated BALB/c mice. In contrast, pristane injection increased levels of interleukin-5 in DBA but not BALB/c mice.

Animals↗
PubMed1991

Specific pathogen-free BALB/cAn mice are refractory to plasmacytoma induction by pristane.

Forty to sixty percent of conventionally (CON) raised BALB/cAnPt (BALB/c) mice develop plasmacytomas (PCT) when injected with three 0.5 ml i.p. injections of pristane. When CON-BALB/c mice were converted to specific pathogen free (SPF) status by foster nursing caesarean delivered term mice on C3H/HeN SPF mothers and maintained under strict SPF conditions, less than 5% of the mice developed pristane-induced PCT. FACS analysis of the cellular composition of oil granulomatous tissue revealed a dramatic influx of CD4+ cells in CON mice that was significantly reduced in SPF mice. Moreover, while both CON and SPF mice had similar patterns of gut flora colonization, only CON-BALB/c mice had occasional circulating antibodies to mouse hepatitis virus and Sendai viruses. Maintenance in strict SPF conditions, therefore, results in a prolonged state of relative Ag deprivation and a failure to continuously activate new T and B cell populations. The results suggest that PCT formation depends on exogenous antigenic stimulation and that the presence of minimal gut flora is insufficient to render these mice susceptible to PCT induction.

Animals↗
PubMed1990

Fine needle aspiration biopsy in the diagnosis of breast cancer.

A prospective study of 176 Fine Needle Aspiration Biopsies (FNAB) in 172 patients was carried out to assess the accuracy of FNAB in diagnosing breast cancer at the University Hospital of the West Indies. The results showed 99 per cent and 97 per cent accuracy and sensitivity rates, respectively. There were no false positives and a one per cent false negative rate. FNAB provides a rapid, safe and cheap method of accurately diagnosing breast cancer.

Biopsy, Needle↗
PubMed1990

Ruptured rectal prolapse.

Rectal prolapse is not a common surgical disorder. The complication reported here, of evisceration of small bowel through a prolapsed rectum, is extremely rare and is the first case reported in the West Indies. Some of the features of rectal prolapse are described, and the surgical management of this particular complication is discussed.

Aged↗
PubMed1988

Antigen-specific inhibition of immune interferon production by suppressor cells of autoimmune encephalomyelitis.

Previous work from this laboratory has revealed that spleen and/or lymph node cells from Lewis rats, that have recovered from an acute episode of experimental autoimmune encephalomyelitis (EAE), suppress the development of EAE when injected into syngeneic recipients subsequently challenged with myelin basic protein (MBP) in CFA. In an effort to understand the mechanism of this suppression, we measured the production of immune IFN-gamma, which may be required for the induction of an immune response, by EAE effector T cells (which transfer disease) and EAE suppressor cells when cultured in vitro with MBP. We now report that EAE effector T cells produce IFN-gamma when cultured in vitro with MBP. In contrast, spleen cells from recovered rats (which manifest suppressor activity in vivo) do not produce IFN-gamma. Moreover, in cell mixing experiments, these suppressor spleen cells inhibited the production of IFN-gamma by EAE effector cells. This inhibition was not eliminated by the removal of macrophages nor by the inhibition of PG synthesis by indomethacin. Furthermore, the inhibition was shown to be Ag-specific and mediated by nylon-adherent, radiation-sensitive splenic T cells. The findings suggest that suppressor cells regulate EAE by inhibiting IFN-gamma production by effector cells. This inhibition may result in the down-regulation of IFN-gamma-induced expression of class II major histocompatibility Ag on cells of the central nervous system, thus reducing the presentation of tissue-specific Ag (i.e., MBP) to autoreactive lymphocytes.

Acute Disease↗
PubMed1985

Transient interactions between blood pressure, respiration and heart rate in man.

Auto regressive spectral estimation techniques have been used to follow transient interactions between mean blood pressure, respiration and heart rate. This demonstrates that these inter-relationships are variable. It is concluded that while central modulation of heart rate is the major factor in the interactions, when the heart rate is fixed, peripheral modulation of the blood pressure by respiration is clearly demonstrated.

Adult↗