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D Grennan

Publications and source records attributed to D Grennan.

At least 19 recordsLinked to original sources
PubMed2006

Disease and psychological status in ankylosing spondylitis.

OBJECTIVES: Psychological factors may be important in the assessment and management of ankylosing spondylitis (AS). Our primary objective was to describe associations between disease and psychological status in AS, using AS-specific assessment tools and questionnaires. Our secondary objectives were to identify patient subgroups based on such associations and to determine the stability of the measures over time. METHODS: A total of 110 patients were assessed at 6-monthly intervals up to four times using tools to measure disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI)], psychological [Hospital Anxiety and Depression Questionnaire (HADS), Health Locus of Control-Form C Questionnaire (HLC-C)] and generic health [Short form (SF)-36] status. RESULTS: Eighty-nine participants completed all four assessments. Throughout the study, BASDAI, BASFI and BASMI scores correlated significantly with anxiety, depression, internality and health status, but not with levels of belief in chance or powerful others. Clinically anxious or depressed subgroups had significantly worse BASDAI and BASFI, but not BASMI, scores. BASMI scores were the least closely linked to psychological status. Mean scores for disease, psychological and health status were clinically stable over the 18 months period. CONCLUSIONS: Disease status scores in AS correlated significantly with anxiety, depression, internality and health status. Interpretation of AS disease scores should take an account of psychological status and the choice of measures used. These findings have important potential applications in AS management and monitoring, including the identification of patients for biological therapies.

Adolescent↗
PubMed1997

Lack of linkage between anti-nuclear antibody or clinical features of systemic lupus erythematosus (SLE) and TCR-A/Vbeta loci in families of subjects with SLE.

The role of the TCR-A and TCR-Vbeta genes in the genetic predisposition to SLE expression and anti-nuclear antibody (ANA) production were examined by linkage analysis in eighteen multiplex and forty-three simplex SLE families. All subjects were Caucasian. A significantly increased prevalence of positive ANAs in first-degree relatives of SLE patients from multiplex families was noticed compared to that of simplex families. Linkage between TCR-A/Vbeta genes and SLE expression and ANA production were analysed by affected sib-pair method. Results showed that the haplotypes identical by descent sharing TCR-A and TCR-Vbeta genes in the affected sib-pairs was not different from that expected (P = 0.93 and P = 0.74, respectively). There was no linkage between ANA positivity and TCR-A and TCR-Vbeta genes in ANA positive sib-pairs from both multiplex and simplex families. This study suggests that germline TCR-A and TCR-Vbeta gene loci confer no susceptibility to ANA and SLE expression.

Adult↗
PubMed1995

Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism.

Monocytes from different individuals show variable cytokine production in response to a variety of stimuli. We wished to determine the sets of conditions (cytokine combinations) that would enable us to demonstrate stable inter-individual differences in the production of IL-1 alpha, IL-1 beta, IL-1Ra, on-6 and tumour necrosis factor-alpha (TNF-alpha) by monocytes. We assessed the ability of a number of recombinant human cytokines (granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), TNF-alpha, IL-4, IL-6, transforming growth factor-beta (TGF-beta), IL-10 and IL-1Ra)) to stimulate or inhibit the production of one or more of these monocyte products. GM-CSF was found to stimulate the production of all five of these cytokines in a highly reproducible manner. TNF-alpha also up-regulated production of IL-1 alpha, IL-1 beta, IL-1Ra and IL-6 by monocytes, but the variability in the results of cells cultured from the same individuals on different occasions was greater. Other cytokines either stimulated production of only some of the five cytokine products tested, or stimulated the production of some cytokine products while inhibiting production of others. This was especially evident when cytokines were used in combination with GM-CSF: IFN-gamma down-regulated production of IL-1Ra while up-regulating the production of IL-1 alpha/beta, IL-6 and TNF-alpha, while IL-4 had the exact opposite effect. Polymorphisms in regions of cytokine genes that affect transcription may account for some of the interindividual variation in cytokine production. We have shown that a stable estimate of cytokine production phenotype can be obtained when monocytes collected on at least two separate occasions are stimulated by GM-CSF in vitro. We have looked for a relationship between IL-1 production and an 86-bp variable repeat polymorphism in intron 2 of the IL-1Ra gene. A less common allele of this polymorphism (allele 2) was associated with increased production of IL-1Ra protein, and also reduced production of IL-1 alpha protein by monocytes.

Cells, Cultured↗
PubMed1995

Lack of association between an interleukin-1 receptor antagonist gene polymorphism and systemic lupus erythematosus.

Non-MHC linked genes may contribute to genetic predisposition to the development of systemic lupus erythematosus. The possibility that cytokine genes may be involved was raised by the observation of increased frequency in expression of an uncommon allele of an interleukin-1 receptor antagonist gene polymorphism and SLE in a recent U.K. study. We have not been able to show any significant differences in expression of this allele in SLE patients as a whole or in any patient subgroups. Our results actually show a slight decrease in the expression of this allele in SLE patients compared with healthy controls and in SLE patients with malar rash compared with SLE patients without malar rash.

Alleles↗
PubMed1995

Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorphism in rheumatoid arthritis and systemic lupus erythematosus.

The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TNF alpha) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1 alpha protein production but there were no differences in the production of TNF alpha protein.

Alleles↗
PubMed1987

Monoclonal antibodies to restricted and cross-reactive idiotopes on monoclonal rheumatoid factors and their recognition of idiotope-positive cells.

Four human monoclonal rheumatoid factors (MRF) were used to raise a panel of mouse monoclonal antibodies (mAb) which were selected in a solid-phase radioimmunoassay for binding to MRF but not normal IgM. Three mAb, each raised against a different MRF, bound to the majority of MRF and also to most polyclonal RF. Four other mAb bound selectively to the MRF against which they were raised and to no other MRF, and rarely to any polyclonal RF. Competition studies using cold and radiolabeled mAb further indicated that these mAb recognize distinct and different epitopes on MRF. RF activity of MRF was inhibited by 3 of the 4 mAb binding to a single MRF and 2 of the 3 mAb binding to multiple RF. It was thus concluded that of this panel of mAb 3 recognized cross-reactive idiotopes and the remainder demonstrated highly restricted idiotopes on MRF. These mAb identified MRF idiotope-bearing cells in the peripheral blood of 3 of the MRF donors (and a further subject with type II essential cryoglobulinemia), with a frequency ranging from 0.3-10% of all mononuclear cells with the mAb to restricted idiotopes or 1.5-17% with mAb to cross-reactive idiotopes. These anti-idiotopic mAb should thus provide a highly specific means of identifying and monitoring MRF-producing cells in vivo.

Antibodies, Monoclonal↗
PubMed1985

Splenic dependence of the antibody response to thymus-independent (TI-2) antigens.

The murine antibody response to T-independent (TI)-2 antigens [2,4-dinitrophenyl-Lys-Ficoll (DNP-FIC) and DNP-hydroxyethyl starch (HES)] was impaired long after splenectomy, while responses to TI-1 [trinitrophenylated lipopolysaccharide (TNP-LPS)] and thymus-dependent [TNP-keyhole limpet hemocyanin (KLH)] antigens were largely unaffected. The antibody response to these TI-2 antigens was exclusively against the conjugated epitopes [DNP-, fluorescein isothiocyanate (FITC)- or tetramethylrhodamine isothiocyanate (TRITC)-Ficoll or -HES]. Fluorescent conjugates of Ficoll and HES localize selectively to the splenic marginal zone macrophages. This localization was not affected by 750 cGy of X-irradiation, but the antibody response to the TI-2 antigens was abrogated for 14 days. Administration of spleen cells restored the antibody response to these TI-2 antigens in otherwise intact irradiated mice but not if they had been splenectomized. Our findings indicate that the antibody response to TI-2 antigens depends upon stimulation of B cells in a splenic environment. This probably involves antigen presentation by marginal zone macrophages.

Animals↗
PubMed1985

Mononuclear and multinuclear macrophages in filarial infections.

Filarial infections commonly involve chronic tissue responses to these complex and resiliant organisms. These responses, which occur with a number of the parasitic stages of filariae, involve macrophages, and these cells appear to be important in immunologically induced destruction and removal of these important parasites of man and animals. Details of their presence and experimental induction as well as their distinction into a number of morphological types, including multinuclear (giant cell) forms, is described in this communication. The ability of these various forms to function in phagocytic and immunologically mediated adherence assays is also described.

Animals↗
PubMed1985

The induction of functional mononuclear and multinuclear macrophages in murine brugian filariasis: morphological and immunological properties.

This present study describes the ontogeny and morphology of mononuclear and multinuclear macrophages in murine Brugia pahangi infections. Intraperitoneal infection with L 3 resulted in the development of adult worms and the production of microfilariae in many mice; however, all worms were usually removed by 100 days post infection (p.i.). The infection induced predominantly mononuclear and multinuclear macrophage responses in the peritoneal cavity, with maximum numbers of peritoneal cells being achieved by 8-12 weeks p.i. and at this time some 20% of the macrophages were multinucleated. Lymphocyte numbers were also increased during infection. The reactions around the filariae involved macrophages (both single and multinucleated), eosinophils, fibroblasts and the laying down of collagen. Most worms were involved in these cellular reactions by 5-6 weeks p.i., with the multinuclear macrophages generally seen lying close to the parasites. All stages of parasites developed vacuolar internal changes early in their degeneration with calcification being a later change. The destruction and removal of the sheath was not apparently a prerequisite for degeneration of the body of microfilariae. Rosetting techniques showed that 75% of peritoneal cells (macrophages) in infected animals possessed Fc receptors compared with 32% of those in uninfected mice, and for C3 receptors the respective results were 35% and 5%. The multinuclear cells possessed both types of receptors at levels similar to those of mononuclear macrophages. Likewise both cell types were found to readily phagocytose yeast and latex particles, as well as staining positively for non-specific esterases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them.

F1----parental bone marrow chimeras between CBA and B10 mice were used to show that even after 1 year follicular dendritic cells (FDC), also termed dendritic reticular cells, are not derived from bone marrow stem cells. However clusters of cells wrapped in the dendritic processes of FDC, isolated by enzyme digestion of the spleen contain B cells originating from donor marrow. This implies that evidence for the presence of antigens such as Ia-like detected by others (Gerdes, J. and Stein, H., Clin. Exp. Immunol. 1982. 48: 348) by immunohistology in or on FDC clusters should be interpreted with caution. Deposition of immune complexes on mouse spleen FDC depends upon the presence of a radio- and cyclophosphamide-sensitive population of cells, although FDC themselves are resistant to such treatments. After whole body irradiation the capacity to localize fluorescein isothiocyanate-labeled aggregated human gamma globulin can be restored by normal or T-deprived spleen cells, but restoration requires an interval of more than 1 though less than 5 days. These findings are compatible with the evidence of Gray et al., Eur. J. Immunol. 1984. 14: 47, that in the rat immune complexes are transported to FDC by a sessile population of marginal zone lymphocytes, as first suggested by Brown et al., Immunology 1973. 24: 955.

Animals↗
PubMed1984

Suppressor cells and their role in the survival of immunologically enhanced rat kidney allografts.

A search has been made for suppressor cells in the spleens of AS rats bearing long-surviving, enhanced AUG strain kidney allografts. The assay consisted of an adoptive transfer of splenocytes from AS rats with enhanced AUG kidneys to normal AS rats that also received test grafts of AUG kidneys. The critical feature of the AUG kidney test grafts was that the native population of passenger cells had been replaced by AS passenger cells--thus reducing, but not eliminating, immunogenicity of the graft. With this assay, it was shown that 2.7-3.5 X 10(8) spleen cells transferred substantial and statistically significant suppression of graft rejection. Suppression was also transferred by spleen cells that did not adhere to nylon wool. It is concluded that suppressor cells are one of the mechanisms ensuring continued survival of enhanced kidney allografts.

Animals↗
PubMed1982

Human marrow stromal cells in culture: changes induced by T-lymphocytes.

Suspension cultures of human bone marrow mononuclear cells form colonies of fibroblastoid cells which expand to form confluent monolayers. These fibroblastoid cells are thought to represent elements of the bone marrow stroma. Fibroblastoid cells failed to proliferate when the cultures were initiated and maintained in the presence of 50% (v/v) of medium conditioned by phytohaemagglutinin (PHA)-stimulated blood mononuclear cells or supernatant media from one-way mixed lymphocyte reactions (MLR). Under these conditions, the cultures contained a pleomorphic population of macrophage-like cells. Some of the characteristics of the fibroblastoid and macrophage-like cells have been compared and a separate origin of the two cell types has been demonstrated. Further experiments indicated that T lymphocytes were the source of the factor(s) in the conditioned media which was responsible for the growth of the macrophage-like cells at the expense of the fibroblastoid cells and suggested that activation of the T cells was necessary for them to exert their effect. The results support the idea that T lymphocytes can influence the haemopoietic microenvironment of the bone marrow.

Bone Marrow Cells↗
PubMed1981

Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal-zone macrophages.

Fluorescent conjugates of hydroxyethyl (OEt) starch of Ficoll are selectively ingested and retained in vivo by spleen marginal-zone (MZ) and lymph node marginal-sinus macrophages of mice, whereas similar conjugates of type 3 pneumococcal capsular polysaccharide (SIII) are generally retained by macrophages (Kupffer cells, histiocytes, macrophages of spleen, lymph nodes, bone marrow and peritoneal cavity). MZ and other macrophages are readily identifiable by fluorescence after injection in vivo of OEt starch and SIII labeled with tetraethylrhodamine isothiocyanate and fluorescein isothiocyanate. Collagenase digestion was required for recovery of intact MZ macrophages from spleen in single cell suspensions and for maximum yields of other macrophages. MZ macrophages are larger and morphologically distinct from other macrophages, but resemble them in respect of EA, EAC receptors and acid phosphates and nonspecific esterase content and are equally radio-resistant. The appear normal in CBA/N nude and in beige mice. Freshly isolated MZ macrophages in suspension have adherent lymphocytes, dispersible by EDTA treatment, with B but not T cell markers. It is suggested that selective adherence to MZ macrophages is a factor in determining B cell traffic. MZ macrophages did not have demonstrable surface I-A or I-EC antigens. Only 4--8% of other spleen macrophages freshly isolated by collagenase treatment expressed I-A in the same preparation, whereas 35% of other cells (lymphocytes and blasts) reacted with monoclonal anti-I-A and anti-I-EC. After adherence to glass or plastic, 40% or more red-pulp, but not MZ macrophages, became I-A-positive. When taken from mice recently restimulated with sheep erythrocytes, half the red-pulp macrophages expressed I-A even before adherence. The relation of MZ to other macrophages is not known. However, their properties are consistent with the demonstrated ability of thymus-independent antigens selectively taken up by these cells to elicit long-lasting IgM antibody responses by direct interaction with B cells. The unexpected observation that only a small proportion of spleen macrophages freshly isolated from unstimulated mice had detectable surface I-A, but that this proportion was much increased after attachment to plastic, is discussed in relation to the possibility that macrophages do not express surface Ia antigens unless they have been stimulated.

Animals↗
PubMed1980

Immunosuppression in BALB/c mice bearing the plasmacytoma TEPC-183: massive increase in red pulp macrophages induced by the tumour.

An increase was found in total macrophage numbers in the spleens of BALB/c mice bearing the plasmacytoma TEPC-183 compared with controls. The increase was shown to be confined to red pulp macrophage; white pulp macrophage numbers were normal as were the number of macrophages which took up hydroxyethyl starch. It is suggested that this increase in red pulp macrophages may account for the suppression of primary immune responses caused by spleen cells from TEPC-183 bearing mice. This effect may be due to increased numbers of normal macrophages rather than the generation of distinctive suppressor macrophages as suggested previously.

Animals↗