Biomedical subjects

G M Galbraith

Publications and source records attributed to G M Galbraith.

At least 19 recordsLinked to original sources

PubMed1999

Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis.

The distributions of the bi-allelic interleukin-1beta+3953 and tumor necrosis factor-alpha-308 genotypes were determined in 20 patients with advanced adult periodontitis, 20 patients with plaque associated gingivitis, and 45 referent population subjects. A significant increase in IL-1beta+3953 allele 2 frequency was found in patients with advanced periodontitis compared to referent subjects (the Fisher exact test; p=0.013). Furthermore, the frequency of TNF-alpha-308 allele 1 was significantly greater in patients with advanced disease compared to those with plaque associated gingivitis (the Fisher exact test; p=0.014). No significant correlation was observed between genotype and cytokine production in these patient populations.

Adult↗

PubMed1999

Contribution of interleukin 1beta and KM loci to alopecia areata.

Alopecia areata is a common skin disease in which proinflammatory cytokines such as IL-1beta may play a pathogenic role. In this study, we examined the distribution of genotypes of an IL-1beta single base change polymorphism at position +3953 in patients with alopecia areata. The distribution of immunoglobulin kappa light chain (KM) genotypes was similarly examined. The data obtained showed that the IL-1beta and KM loci act cooperatively to significantly increase susceptibility to alopecia areata.

Adolescent↗

PubMed1998

Interleukin-1beta+3953 allele 2: association with disease status in adult periodontitis.

Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. The pro-inflammatory and bone resorptive properties of interleukin-1 beta (IL-1beta) strongly suggest a role for this cytokine in the pathogenesis of periodontal disease. In the study reported here, the frequency of IL-1beta genotypes including allele 2 of the IL-1beta+3953 restriction fragment length bi-allelic polymorphism was significantly increased in patients with advanced adult periodontitis compared to those with early and moderate disease. Furthermore, allele 2 was associated with increased production of IL-1beta by activated peripheral blood polymorphonuclear cells of patients with advanced disease, although this increase failed to reach statistical significance. Finally, the data obtained revealed significant linkage disequilibrium between allele 2 of the IL-1beta+3953 polymorphism and allele 2 of the bi-allelic IL-1alpha-889 polymorphism in both patients and orally healthy controls. These findings provide new insight into the possible role of IL-1alpha and beta gene polymorphisms in the susceptibility to adult periodontitis.

Adult↗

PubMed1998

Tumor necrosis factor alpha production by oral leukocytes: influence of tumor necrosis factor genotype.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that is thought to play a role in the pathogenesis of periodontal disease. TNF-alpha production is regulated by many factors, including certain alleles of TNF gene polymorphisms. In the present study, TNF genotypes of 3 bi-allelic polymorphisms were determined in 32 Caucasian patients with adult periodontitis and 32 orally-healthy matched controls, and correlated with TNF-alpha production by oral polymorphonuclear leukocytes (PMN). No differences in distribution of TNF alleles of the -238, -308, or +252 gene polymorphisms were observed between patients and controls or between patients with different disease severity. However, the level of TNF-alpha production by oral PMN correlated with the TNF-alpha 308 genotype in patients with adult periodontitis, with increased production found in patients with the T1,2 genotype (t-test; P=0.037). When cytokine production was examined in patients according to disease severity, an association between the T1,2 genotype and increased production was observed only in patients with advanced disease (t-test; P=0.05). These findings suggest that further studies are warranted to determine if the TNF genotype is a risk factor for severity of disease in adult periodontitis.

Adult↗

PubMed1997

Cytokine production by oral and peripheral blood neutrophils in adult periodontitis.

Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.

Adult↗

PubMed1995

Activation of human monocyte-derived macrophages by immune complexes containing low-density lipoprotein.

Human monocyte-derived macrophages are transformed into foam cells upon incubation with immune complexes containing low-density lipoprotein (LDL-IC), which are internalized predominantly through Fc gamma receptor-mediated phagocytosis. We investigated whether the FcR gamma-mediated ingestion of LDL-IC is associated with functional and metabolic activation of the ingesting cells. As end points we used the assay of released interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and the reduction of nitroblue tetrazolium, which measures the respiratory burst. LDL-IC, added to the macrophages in concentrations known to induce intracellular accumulation of cholesterol esters and foam cell transformation, stimulated both the cytokine release and the respiratory burst more efficiently than control immune complexes. Time course studies of cytokine release and mRNA expression suggest that the synthesis and release of these two cytokines is under independent control. TNF alpha was released almost immediately after addition of LDL-IC to the macrophages, coinciding with increased early expression of TNF alpha mRNA, detectable 30 min after stimulation. In contrast, IL-1 beta was only increased in stimulated cell supernatants after 8 hr, and the onset of expression of IL-1 beta mRNA was also delayed in comparison to that of TNF alpha mRNA. We noted wide variations in the amounts of TNF alpha released by monocyte-derived macrophages from different donors. We also found that those macrophages which released higher levels of TNF alpha also took up higher amounts of 125I-labeled LDL, suggesting that the expression of LDL receptors by LDL-IC-stimulated macrophages is somehow linked to the degree of activation of these cells. Experiments using the measurement of the oxidative burst as end point corroborated that LDL-IC cause a general activation of macrophage functions. In conclusion, human macrophages are efficiently activated by LDL-IC, as reflected by the release of IL-1 beta and TNF alpha and by the release of oxygen active radicals. Thus, the presentation of LDL-IC to human macrophages induces a variety of metabolic and functional changes which are likely to contribute, directly or indirectly, to endothelial damage and progression of the atheromatous lesion.

Antigen-Antibody Complex↗

PubMed1995

Tumor necrosis factor alpha (TNF-alpha) gene polymorphism in alopecia areata.

Tumor necrosis factor alpha (TNF-alpha) phenotypes of two polymorphic systems were determined in 50 patients with alopecia areata, a common inflammatory disease of the skin. The distribution of TNF-alpha T1, T2 phenotypes differed between patients with the patchy form of disease and patients with totalis/universalis disease. There was no significant difference in the distribution of TNF-alpha G,A phenotypes between patient groups. The results of this study provide evidence of genetic heterogeneity between the two forms of alopecia areata, and suggest that the TNF-alpha gene or a closely linked locus within the major histocompatibility complex may play a role in the pathogenesis of the patchy form of disease.

Adolescent↗

PubMed1995

Interleukin-1 beta gene expression in human oral polymorphonuclear leukocytes.

Oral polymorphonuclear leukocytes (PMN) were obtained from 10 adult donors in good oral health using a method employing repeated mouth rinse collection. Interleukin-1 beta (IL-1 beta) mRNA was detected in freshly obtained cells by blot hybridization of total cellular RNA with a biotin labeled cDNA probe. Supernates from oral PMN placed in culture for 3 hours contained substantial amounts of IL-1 beta measured by ELISA. Significantly greater numbers of PMN and amounts of PMN-derived IL-1 beta were obtained from the same donors 2 hours subsequent to an oral sucrose challenge (3.23 x 10(6) vs. 1.57 x 10(6) mean PMN number, P = 0.004; 59.80 vs. 20.05 mean pg/ml IL-1 beta, P = 0.036, respectively). However, the elevated levels of IL-1 beta were due to the higher cell number rather than to increased production by individual cells. Stimulation of oral PMN with recombinant granulocyte-macrophage colony stimulating factor did not enhance their cytokine production. In most instances. IL-1 beta production by oral PMN was dramatically greater than that of their blood counterparts. These findings suggest that oral PMN are an important source of IL-1 beta, which plays a central role in oral immunity and inflammatory disease states.

Adult↗

PubMed1989

Elastic characteristics of the airway wall.

To examine the elastic behavior of the upper airway, we obtained pressure-area plots from data gathered from acoustic images of the airway and measurements of mouth pressure during tidal breathing in 10 adult human volunteers (dA/dP). These plots revealed both tidal hysteresis and a change in slope as a function of distance along the airway. The slope of the regression line of the dA/dP plots decreased from the pharyngeal region to the trachea and became 0 at the thoracic inlet, the location of which was independently assessed. In most subjects the slope became negative distal to the thoracic inlet. Correlation coefficients between pressure and area approached 1 in the pharyngeal region and 0 at the thoracic inlet. When subjects breathed against a small resistive load (10 cmH2O.1(-1).s) pharyngeal, extrathoracic, and intrathoracic pressure-area plots were exaggerated but the slope at the thoracic inlet was unchanged. We conclude that this pressure-area characteristic defines regional differences in upper airway elasticity and delineates the transition point between the intra- and extrathoracic airways.

Acoustics↗

PubMed1989

Km1 allotype association with one subgroup of alopecia areata.

The distribution of the immunoglobulin kappa light-chain determinant, Km1, was examined in 52 patients with alopecia areata, 22 of whom possessed serum antibodies to thyroid antigens. The allotype frequency was significantly higher than that found in a referent population of 105 healthy subjects. Furthermore, it was determined that within the patient population, the Km1 allotype was associated with the absence of detectable serum autoantibodies. In such patients, this association may be due to linkage disequilibrium between the chromosome 2 gene coding for Km1 and a chromosome 2 gene coding for susceptibility to alopecia areata.

Alopecia Areata↗

PubMed1988

Western blot analysis of serum antibody reactivity with human melanoma cell antigens in alopecia areata and vitiligo.

Antibody reactivity to melanocyte-derived cells was investigated in patients with alopecia areata or totalis by use of Western blot analysis of detergent-solubilized membrane antigens of a human melanoma cell line, M14. Reactivity was detected in the sera of 9 of 27 alopecia areata or totalis patients, 8 of 13 vitiligo patients, and 6 of 24 normal control subjects. Significant differences between patient and control sera were found in the number and distribution of antibody specificities detected. In vitiligo sera, there was an increased prevalence of reactivity to a melanoma antigen of 52,000 mol wt. In contrast, the predominant specificities in alopecia areata sera were for antigens of 74,500 and 70,800 mol wt, and the majority of positive sera were from patients with total hair loss. These findings suggest that autoreactivity to pigmented cells occurs in certain patients with alopecia areata or totalis.

Alopecia↗

PubMed1988

Therapeutic immunomodulation.

Several of the cytokines that regulate the immune system have been tested for efficacy in the clinical setting. Of these, interleukin-2 shows particular potential for antitumor therapy when used in combination with autologous lymphokine-activated killer cells; the interferons have proved effective in the treatment of certain viral diseases and malignancies, particularly those of hematologic origin; and the colony-stimulating factors show great promise for treatment of diseases associated with bone marrow dysfunction. Heterologous monoclonal antibodies have proved effective in control of acute allograft rejection and prevention of graft versus host disease by selective elimination of cell types. Anti-idiotype antibodies are being investigated for their potential as vaccines. Many synthetic compounds possess immunomodulatory properties; one of these, inosiplex, may prove effective in enhancing immune function in patients with immune deficiencies such as AIDS.

Antibodies, Monoclonal↗

PubMed1988

Chemotactic peptide-induced arachidonic acid mobilization in human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes prelabeled with tritiated arachidonic acid liberated radiolabeled products when exposed to the chemotactic peptide fMet-Leu-Phe. The effect was enhanced in the presence of phorbol-12-myristate 13-acetate or 1-oleoyl-2-acetyl glycerol; these agents activate phospholipid- and Ca2+-dependent protein kinase C. In contrast, arachidonic acid mobilization was suppressed by two compounds known to inhibit protein kinase C activity: polymyxin B and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. These results suggest that protein kinase C was involved in arachidonic acid mobilization in leukocytes stimulated with chemotactic peptide.

Arachidonic Acid↗

PubMed1987

A randomized double-blind study of inosiplex (isoprinosine) therapy in patients with alopecia totalis.

Twenty-five of 34 patients with alopecia totalis of at least 1 year's duration and associated defects in cell-mediated immunity completed a randomized, double-blind, placebo-controlled crossover trial of the therapeutic effect of inosiplex, a synthetic immunomodulator. Each patient received 20 weeks of treatment with inosiplex and 20 weeks with placebo in randomized order. Eleven patients were identified clinically as responders to inosiplex in terms of hair regrowth. Scalp biopsy results correlated well with drug therapy. Enhanced immune function was found in the majority of responding patients; however, statistical analysis of the results of the entire patient population revealed limited significant differences. No patient experienced adverse side effects attributable to therapy. These results show that inosiplex is a safe and effective therapy for certain patients with alopecia totalis.

Adult↗

PubMed1986

Inhibition of interleukin-2-induced T-cell proliferation by sera from patients with the acquired immune deficiency syndrome.

Sera from 22 patients with either lymphadenopathy syndrome (LAS), acquired immune deficiency syndrome (AIDS)-related complex (ARC), or acquired immune deficiency syndrome were examined for their effect on the interleukin-2 (IL-2)-induced proliferative response of an IL-2-dependent cytotoxic T-cell line, CTL-20. All of the patient sera included in this study were positive for the presence of antibodies against human T-cell lymphotropic virus type III (HTLV-III) as determined by an HTLV-III-specific enzyme-linked immunosorbent assay (ELISA). Eighteen of the 22 patient sera examined (81.8%) exhibited at least a modest suppressive effect on the proliferative response of CTL-20 cells. The inhibitory effect was dose-dependent and varied in intensity for each individual serum. In many cases, the magnitude of suppression was absolute in that it totally abrogated IL-2-induced DNA synthesis. Normal human serum (NHS) exerted no suppressive influence on the IL-2-induced proliferative response of identical control cultures. This same panel of 22 patient sera exhibited no significant inhibitory effects on the levels of protein synthesis in cultures of a non-IL-2-dependent human T-cell line, CCRF-HSB-2, indicating that the suppressive effect was not mediated by nonspecific serum cytotoxicity. The inhibitory effect of patient sera in the IL-2-dependent target cell assay correlated with the ability of these same sera to suppress the mitogen-induced proliferative response of normal human peripheral blood lymphocytes (PBL). These observations are particularly striking in view of the recognized defects of IL-2-dependent effector T-cell functions in AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Isoprinosine effects on interleukin-1 production in acquired immune deficiency syndrome (AIDS).

The in vitro effects of isoprinosine (ISO) on the production of IL-1 in AIDS patients and normal controls were investigated in this study. IL-1 production from adherent cells was measured by an indirect method using EL-4 cells. Five of eleven AIDS patients had depressed IL-1 production. Various concentrations of ISO were used to treat the adherent cells in vitro and the optimal concentration for stimulating IL-1 production was determined to be 100 micrograms/ml/10(6) cells. IL-1 production was augmented to normal or to near normal levels in four of five AIDS patients. Our results indicate that depressed immunity seen in some AIDS patients may be partly due to the depressed in IL-1 production and also that ISO can act as an immune potentiation in enhancing the production of this lymphokine in vitro.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Refractory esophageal candidiasis associated with a low molecular weight plasma inhibitor of T-lymphocyte function.

In a patient with chronic esophageal candidiasis due to C. tropicalis that was refractory to mycostatin and ketoconazole, a generalized cell-mediated immunodeficiency state was detected. Samples of plasma from this patient inhibited T-lymphocyte function, suppressing both rosette formation and mitogen responsiveness of T-cells derived from the patient and from normal individuals. Following plasma exchange, the patient's immune defect resolved and her candida infection disappeared. On further analysis, the plasma inhibitory factor was found to be of low molecular weight (less than 10,000) and heat labile. Preliminary studies suggested that this inhibitor was candida-derived, since it was removed from plasma by anti-candida antibodies in solid phase. Immunodeficiency in chronic candidiasis may be improved by removal of circulating inhibitory factors through plasma exchange.

Adult↗

PubMed1986

Antibodies to neurofilament protein in retinitis pigmentosa.

Antibodies reactive with heterologous neural tissue were detected by indirect immunofluorescence microscopy in the sera of 17 of 34 patients with retinitis pigmentosa, one of 30 normal control sera, and a variable percentage of sera derived from subjects with diverse ocular and neurological diseases. These antibodies were also found both in disease-free first degree relatives and in spouses of patients with retinitis pigmentosa. Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human spinal cord components followed by immunoblots with sera under study revealed that the serum antibody was specific for the high molecular weight protein subunit of neurofilaments. No correlation was found between the presence of these antibodies and other immunological and clinical parameters in retinitis pigmentosa. These findings suggest that release of piled-up neurofilaments from damaged neurones in retinitis pigmentosa triggers B lymphocytes autoreactive to neurofilament antigens.

Adult↗