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M G Baines

Publications and source records attributed to M G Baines.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of sensory stimuli on the incidence of fetal resorption in a murine model of spontaneous abortion: the presence of an alien male and postimplantation embryo survival.

Pregnancy outcome may be altered by both genetic and environmental factors. The mating of CBA/J female mice with DBA/2 males normally results in pregnancies characterized by a relatively high incidence of early embryo compared with most other syngeneic or allogeneic matings. This study addressed the role of normal laboratory stress in the induction of early embryo loss. The previously studied 'Bruce effect' describes the total loss of preimplantation embryos (pregnancy block) that is apparently caused by the stress induced by the presence of an alien male and mediated by neuroimmunological effects on prolactin activity. To determine whether this effect could be responsible for the high incidence of postimplantation embryo losses in the CBA/J x DBA/2 model, the original DBA/2 male was replaced on day 6 of gestation by another DBA/2 male, a CBA/J, a C57Bl/6 or a BALB/c male. The relatively high incidence of embryo loss was not affected by removing the original DBA/2 male or introducing another DBA/2 or a CBA/J male, indicating that stress induced by an alien male did not increase the postimplantation losses in this model. Furthermore, the introduction of a DBA/2 male to a CBA/J female that had been mated with a BALB/c male did not elicit early embryo loss. However, the replacement of the original DBA/2 male by a BALB/c male dramatically reduced the incidence of early embryo loss in pregnant CBA/J female mice. The introduction of a C57Bl/6 male also reduced embryo loss but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1993

Effects of lovastatin on natural killer cell function and other immunological parameters in man.

Suppression of cholesterol synthesis by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, has been shown to inhibit mitogen stimulated proliferation of natural killer (NK) cells and other lymphocytes in vitro. This effect is only partially overcome by provision of exogenous free or lipoprotein cholesterol but is reversed by mevalonate, suggesting that proliferating lymphocytes have a specific requirement for a nonsterol isoprenoid product of mevalonate. The effect of lovastatin (20 mg bid) on a range of immune function parameters was determined in a randomized, placebo-controlled, double-blind ex vivo study in 52 patients with primary hypercholesterolemia. No significant differences (P < 0.05) were found between lovastatin and placebo groups for basal NK or interleukin-2 (IL-2)-induced cell-mediated cytotoxicity, PHA-stimulated lymphocyte proliferation, or relative numbers of T lymphocytes (CD3+), B lymphocytes (CD19+), total NK cells (CD3-, CD16+, CD56+) and CD57+ NK cells or in immunoglobulin levels after 4 or 8 weeks of treatment. In contrast to previous in vitro data, no statistically or clinically significant changes were observed in any parameter of lymphocyte function in patients treated with lovastatin.

Adult↗
PubMed1992

Murine pregnancies predisposed to spontaneous resorption show alterations in the concentrations of leukotriene B4 and prostaglandin E2.

Female CBA/J mice mated with DBA/2 males exhibit an increased spontaneous resorption rate (30-35%) in their first pregnancy. Second pregnancies show a decreased resorption rate (15-20%). In contrast, resorption in CBA/J females mated with BALB/c males (identical to DBA/2 at the H-2 major histocompatibility locus) occurs with a frequency of 5-10%. Resorption is preceded by fetoplacental infiltration of natural killer (NK)-like cells and a deficiency in a lipophilic NK-suppressive activity. The eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are known to modulate NK activity in vitro. We measured the concentrations of LTB4 and PGE2 in extracts of individual fetoplacental units at Day 8 of gestation from (1) primigravid CBA/J x DBA/2 resorption-prone matings (RES); (2) second CBA/J x DBA/2 matings (SEC); and (3) primigravid CBA/J x BALB/c control matings (CON). We detected a significant decrease in the mean concentration of LTB4 in RES fetoplacental units (176.4 +/- 11.8 pg/ml; n = 42) compared with CON and SEC fetoplacental units (570.2 +/- 45.5 pg/ml; n = 21 and 420.2 +/- 59.5 pg/ml; n = 39, respectively). To confirm that the LTB4 deficiency is associated with decreased NK suppression in RES matings, we supplemented RES extracts, in vitro, with exogenous LTB4 (0-500 pg/ml). The effect of the addition of LTB4 to RES extracts was biphasic. Addition of LTB4 in the range of 30-125 pg/ml increased the extract's NK suppressive capacity, whereas LTB4 alone either stimulated NK activity or was without effect. These results suggest a critical role for LTB4 in averting NK-mediated early spontaneous fetal resorption.

Animals↗
PubMed1992

The immunology of the eye and its systemic interactions.

Advances in immunology have provided us with new insights about the ocular inflammatory response. Still, the etiology and pathophysiology of many uveitides remain unclear. Factors such as the blood-ocular barrier, sequestration of retinal antigens, local immunomodulators in the aqueous humor, and anterior chamber-associated immune deviation (ACAID) interact and render the eye an immunologically "privileged" site. On the other hand, human leukocyte antigen complex (HLA) interactions, the immunopathology of hypersensitivity reactions, T-cell mediated disease, and autoimmunity are associated pathogenic mechanisms of immune-related ocular disease. In this paper, we review some of the immunologic characteristics of the eye and their relationship to intraocular inflammation. Clinocopathologic correlations are presented. Also, perspectives of current and future research, as well as diagnostic and treatment strategies, are discussed.

Animals↗
PubMed1992

Acquired ocular syphilis: diagnosis and treatment.

We present our findings in 14 patients with a serologically verified diagnosis of ocular syphilis. Although most patients had iridocyclitis, other ocular findings included episcleritis, scleritis, vitritis, retinitis, papillitis, panuveitis, cystoid macular edema, and retinal detachment. Most patients had only ocular manifestations of syphilis with no other definitive symptoms. Without the use of specific treponemal serologic tests, the diagnosis of ocular syphilis would have been missed in at least 20% of patients. Furthermore, 80% of patients were negative for antibody to syphilis in the cerebrospinal fluid, and therefore, this test should not be used to determine treatment for ocular syphilis. Currently, the most effective therapy for ocular syphilis is the same as that for neurosyphilis (i.e., high-dose intravenous penicillin G 12 to 24 million units/day for ten to 14 days). Human immunodeficiency virus-positive patients should receive a full 14 days of high-dose intravenous penicillin G plus intramuscular benzathine penicillin 2.4 million units weekly for three weeks because their immune defenses are likely to be impaired.

Adult↗
PubMed1991

Expression of tumor necrosis factor alpha in the developing nervous system.

We present evidence that tumor necrosis factor alpha (TNF-alpha) is transiently expressed at specific times during embryogenesis in precisely defined areas of the nervous system in two different classes of vertebrates. In murine embryos, TNF-alpha was detected in the brain, neural tube and peripheral mixed spinal nerves. In the chick embryo, TNF-alpha was observed in the brain neuroepithelium and in the developing Purkinje neurons of the cerebellum. Western immunoblot analysis revealed that brain tissue from both mouse and chick embryos contained a 50 kDa protein showing immunoreactivity with anti-TNF-alpha antibody. These results suggest that TNF-alpha participates in the normal development of the vertebrate brain and spinal cord.

Animals↗
PubMed1991

Ocular hypersensitivity to thimerosal in rabbits.

Rabbits were immunized to thimerosal conjugates and challenged with specific antigen-sensitized contact lenses. The symptoms of acute ocular hypersensitivity observed included corneal edema, corneal infiltration and erosion, infiltration of the anterior chamber, iritis, conjunctival edema and hyperemia, and a significant increase in mucous production. Occasional evidence of corneal neovascularization and giant conjunctival papillae were seen. All these parameters were assessed on a five-point scale (0 to +4) and tabulated as an ocular index. The index of ocular hypersensitivity correlated with the titers of the serum antibodies to thimerosal. The major class of serum antibodies consisted of immunoglobulin (Ig) G, with IgA compromising approximately 5% of serum antibodies. During the ocular challenge, the total and IgG tear antibody titers increased as a result of increased vascular permeability. The tear IgA titers increased to a lesser extent than IgG. The influx of serum proteins directly into the tear film was confirmed by a protein-dye tracer technique. Histologic analysis showed that the ocular inflammatory response was accompanied by both polymorphonuclear and mononuclear cell infiltrates into the cornea and conjunctiva. In conclusion, thimerosal-immunized rabbits show an exquisite sensitivity to the minute quantities of thimerosal conjugates adsorbed to contact lenses. Both serum and tear antibodies correlate with the severity of the ocular inflammatory response. This model would appear to simulate an antibody-mediated immune complex or Arthus type of ocular hypersensitivity commonly seen to foreign antigens including preservatives.

Animals↗
PubMed1990

Adsorption and removal of protein bound to hydrogel contact lenses.

Tear film proteins are known to adsorb to new hydrogel contact lenses. Using a radioiodine tracing technique, proteins were shown to adsorb to contact lens surfaces. The quantity of protein adsorbed to the contact lenses within 2 to 4 h was 1 to 3 micrograms/lens. The degree of protein adsorption varied from lens-to-lens depending in part on the water content of the lens. High water content ionic lenses bound the most protein, whereas lower water content and nonionic lenses bound less protein. Enzyme cleaning of the protein-coated contact lenses removed about 75% of the adsorbed protein. When the enzyme-cleaned lenses were reincubated with protein, similar quantities were quickly readsorbed within a similar period of time. The rate of readsorption appeared to vary with the type of enzyme used to clean the lenses. Hydrogel lenses adsorb protein from the tear film rapidly and irreversibly. Cleaning the lenses has only a partial and temporary effect on the bound protein. The lens-bound proteins could become partly denatured during their binding to the lenses. These observations suggest a possible role for such proteins in ocular sensitivity to contact lenses.

Adsorption↗
PubMed1990

Resorption of CBA/J x DBA/2 mouse conceptuses in CBA/J uteri correlates with failure of the feto-placental unit to suppress natural killer cell activity.

Lipid extraction was used to study the natural killer (NK) suppressive activity of individual feto-placental units. Normal pregnancies showed a lipophilic NK cell suppressive factor that was gestational day specific. Feto-placental units from CBA/J x DBA/2 pregnancies were deficient in the NK cell suppressive factor when compared to normal CBA/J x BALB/c pregnancies. The frequency of non-suppressive feto-placental units from CBA/J x DBA/2 pregnancies correlated with the frequency of feto-placental units infiltrated with NK cells and the frequency of spontaneous resorption. Our results implicate a deficiency of NK suppressive activity in the feto-placental unit as a contributing factor in spontaneous fetal resorption.

Animals↗
PubMed1990

Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha.

Certain strains of mice display an increased frequency of fetal resorption, but little is known about the effector mechanisms involved. We have examined the events associated with lipopolysaccharide (LPS)-induced fetal resorption in mice. Administration of 25 micrograms LPS on Day 12 of gestation resulted in the appearance of tumour necrosis factor-alpha (TNF-alpha) in the amniotic fluid and fetal resorption. Levels of LPS-induced TNF-alpha were reduced by 90% after pretreatment with the TNF-alpha-suppressing drug pentoxifylline (PXF). Treatment of pregnant mice during early gestation with 0.1 micrograms LPS resulted in fetoplacental resorption which was maximal when the LPS was given on Day 8. Resorption induced by 0.1 micrograms LPS on Day 8 of gestation was significantly reduced by pretreatment with PXF. Infiltration of asialo-GM1-positive cells was observed in the decidual-ectoplacental cone area of embryonic units from LPS-treated mice. In addition, treatment with anti-AGM1 antiserum prevented the LPS-induced resorption. Our results suggest that TNF-alpha and asialo-GM1-positive cells are involved in LPS-induced fetal resorption.

Amniotic Fluid↗
PubMed1990

Clinical evaluation of liposomal tumor antigen vaccines in patients with stage-III melanoma.

In this study, we report the results of an active-specific immunotherapy phase I study using autologous tumor-associated antigens (TAA) incorporated within liposomal carriers in patients with metastatic malignant melanoma. A group of 13 patients were entered into the study and given subcutaneous (s.c.) injections of liposome-TAA preparations at 2- to 4-week intervals. Clinical and laboratory monitoring did not reveal any short- or long-term systemic or local toxicity. Three patients had a complete response, and two patients had a partial response (50% or greater size reduction in one or more tumor sites). The remaining eight patients showed no response with disease progression. Two of these eight patients are still undergoing treatment. The TAA preparations stimulated peripheral blood lymphocyte proliferation (PBL) in vitro in those patients exhibiting a clinical response: no such responses were observed in the nonresponder patients. NK cell activity did not correlate with PBL proliferation or clinical response status, whereas PBL cytostatic activity against heterologous melanoma tumor cells correlated with clinical responsiveness. This form of immunotherapy appears to be a safe and feasible candidate for a much larger phase I/II study.

Adult↗
PubMed1989

Augmented natural killer cell activity during neonatal graft-versus-host disease is of predominantly donor origin.

Natural killer cells have been postulated to play a role in the immunopathogenesis of graft-versus-host disease (GVHD). This is based on reports of augmented natural killer (NK) activity, both in animal models and in humans. It has not been elucitated from previous reports, however, whether the cells mediating this activity are of donor or recipient origin. We have investigated the origin of the effector cells using highly specific antisera. Our results indicate that the augmented lytic activity seen during the course of GVHD is mediated primarily by donor lymphocytes. Depletion with anti-Class I antisera followed by immuno-staining with anti-asialo GM-1 indicate that the effector cells are also asialo GM-1 positive. We report here that the augmented non-specific lytic activity seen during GVHD is mediated by asialo GM-1 positive lymphocytes predominantly of donor origin.

Animals↗
PubMed1989

The production and characterisation of monoclonal antibodies against human prolactin and the development of a two-site immunoradiometric assay.

Monoclonal antibodies against human prolactin (PRL) have been produced and characterised and used to develop a sensitive two-site immunoradiometric assay (IRMA). Nine anti-PRL monoclonal antibodies were assessed for reactivity in immunoblotting experiments with PRL, hPL, hGH and pituitary gland extract. There was no detectable crossreactivity with hPL or hGH. In liquid phase radioimmunoassay (RIA) studies using three of the antibodies there was no detectable crossreaction from hPL or hGH. Five antibodies were positive in immunocytochemical studies using sections of human pituitary gland. Using FPLC purified monoclonal antibodies, a two-site IRMA was developed that could assay PRL over the range 17.5-3500 mIU per litre and was readily adapted to assaying serum samples from patients. The two-site IRMA could be performed within one day without loss of sensitivity and has potential as a rapid and simple method for screening clinical samples.

Antibodies, Monoclonal↗
PubMed1988

Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice.

Immunohistochemistry was used to study a murine model which spontaneously aborts at a frequency of 25 to 30%. Our results show that natural killer (NK) cells are not only the predominant infiltrating cells in aborting feto-placental units, but that they also appear in a similar proportion of feto-placental units before abortion is detectable. The frequency of feto-placental units with significantly elevated NK infiltrates corresponds to the subsequent abortion frequency, indicating a causal relationship. Immunization of the mother with BALB/C splenocytes prevents these NK infiltrates and decreases the abortion frequency to normal levels. These results suggest for the first time that maternal NK cells may have an instrumental role in the etiology of spontaneous abortion.

Animals↗
PubMed1988

Thimerosal: an ophthalmic preservative which acts as a hapten to elicit specific antibodies and cell mediated immunity.

A rabbit model for the study of hypersensitivity to thimerosal was established in order to develop better techniques for screening patient sera and tears for specific antibodies to lens care re-agents. Thimerosal (sodium ethylmercury thiosalicylatelate) was successfully coupled to several protein carriers using a water soluble carbodiimide which linked the carboxyl group of thimerosal to free amino groups of the carrier proteins. Thimerosal was also shown to spontaneously react with proteins as detected by the irreversible binding of mercury to the protein carrier. Immunization of rabbits with the chemically coupled thimerosal resulted in the production of antibodies which specifically reacted with thimerosal. The rabbits also manifested delayed and immediate forms of hypersensitivity to the thimerosal conjugates. The ELISA assay for specific serum antibodies was found to be a sensitive, reliable and specific screening tool However, there was no immunological cross reactivity between the chemically coupled thimerosal and the spontaneously coupled thimerosal. Therefore, the epitopes produced by these two reaction mechanisms were probably immunochemically different even though both contained detectable thimerosal derived mercury.

Animals↗
PubMed1987

Modulation of the natural killer cell activity in pregnant mice alters the spontaneous abortion rate.

Effector cells associated with an aborting fetus appear to be both thymus derived (T) and natural killer (NK) cells. In order to test the hypothesis that NK cells are a major effector mediating early spontaneous abortion (less than day 8-10), CBA female mice mated by DBA/2 males were treated with either polyinosinic/cytidylic acid (poly I:C) to boost NK activity, or rabbit anti-asialo GM1 (RaASGM1) to decrease NK activity. The results of the NK assays of the spleens of treated mice confirmed that the reagents had the expected effect on NK activity and an inspection of the uteri indicated a significant increase in aborted embryos after poly I:C and a marked decrease in spontaneous abortions after RaASGM1 treatment. Therefore, spontaneous abortions may be mediated in part by the cytotoxic activity of unregulated NK cells.

Abortion, Spontaneous↗