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Biomedical subjects

S Fairchild

Publications and source records attributed to S Fairchild.

At least 19 recordsLinked to original sources
PubMed2005

Inflammatory arthritis and dermatitis in thymectomized, CD25+ cell-depleted adult mice.

OBJECTIVE: To investigate the effect of CD25+ or CTLA-4(+) cell depletion on the natural history of collagen-induced and spontaneous arthritis in male DBA1/J mice. METHODS: Male DBA/1J mice were treated with anti-CD25 depleting antibody (PC61) or isotype control (GL113), or with anti-CTLA-4 depleting antibody (4F10) at various time-points peri- and post-immunization with bovine collagen type II, emulsified in adjuvant. In order to develop a model system in which long-term depletion of CD25+ regulatory T cells can be achieved prior to immunization, adult male DBA/1J mice were thymectomized prior to administration of either PC61 or GL113. An ELISA demonstrated that PC61 and GL113 antibodies were undetectable by 21 days after administration and FACS analysis confirmed the long-term depletion of CD25+ cells in peripheral blood. RESULTS: In the thymectomized mice treated with PC61, the CD25+ population was depleted and a spontaneous arthritis developed (P = 0.03). In the non-thymectomized mice, administration of CTLA-4-depleting antibody prior to immunization exacerbated arthritis in mice immunized with bovine collagen type II emulsified in incomplete Freund's adjuvant (P < 0.01). However, no significant difference in the natural history of arthritis was evident in mice treated with CD25-depleting antibody (PC61) compared with control antibody (GL113). CONCLUSIONS: Two separate models implicate CD25+ CTLA-4(+) constitutive cells in suppression of arthritis in susceptible DBA/1 males: exacerbation of collagen-induced arthritis following CTLA-4 depletion at the start of induction and spontaneous arthritis in the thymectomy/CD25+ depletion model.

Animals↗
PubMed2004

The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis.

OBJECTIVES: In addition to its vasoactive effects, angiotensin II has proinflammatory properties. Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin II and could therefore act as anti-inflammatory agents. Here we investigated the capacity of the ACE inhibitor quinapril to modulate inflammatory arthritis. METHODS: We studied the effect of quinapril on disease activity in mice with collagen-induced arthritis (CIA). Mice received oral quinapril (10 mg/kg/day) at the time of arthritis induction (prophylaxis protocol) or at the onset of mild arthritis (therapy protocol). Concentrations of immunoglobulin G (IgG) subtypes specific for bovine Type II collagen and TNF-alpha were measured by enzyme-linked immunoassay. RESULTS: Quinapril significantly diminished the activity of CIA when given as prophylaxis or therapy (prophylaxis protocol, P<0.001; therapy protocol P=0.002). Antigen-specific IgG2a antibodies were reduced by 52% (P=0.02) in the quinapril prophylaxis protocol. Suppression of arthritis by quinapril was associated with reduced articular expression of TNF-alpha by 68% (P=0.01) in the prophylaxis protocol and 27% (P=0.06) in the therapy protocol. Quinapril therapy also inhibited expression of splenocyte TNF-alpha production following lipopolysaccharide (LPS) in vitro stimulation by 59% (P=0.02). In parallel human in vitro experiments, ACE inhibition suppressed LPS-stimulated production of TNF-alpha by monocytes. In order to confirm that the action of quinapril occurred predominantly through suppression of angiotensin II, parallel experiments with the angiotensin receptor antagonist candesartan cilexetil demonstrated that this agent also inhibited disease activity in CIA. CONCLUSIONS: These data suggest that angiotensin II is a mediator of chronic inflammation and that ACE inhibition may have therapeutic effects in human inflammatory arthritis.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2001

An immature rat lymphocyte marker CD157: striking differences in the expression between mice and rats.

We have established a novel monoclonal antibody that recognises mouse and rat CD157, and uncovered striking differences in both the level and stage of expression of this antigen in the primary lymphoid organs between these two species. Unlike mouse, the majority of rat thymocytes express CD 157. SHR and WKY rats were the exception, having unusually low levels (similar to those of the mouse) of these cells. However, in both species, a subset of CD3- CD4- CD8- thymocytes exhibited high levels of CD157. Surprisingly, these CD157high cells temporarily upregulated MHC class I molecules in both species. Furthermore, a third of CD157high rat thymocytes were CD45RC+, a marker found on immature thymocytes with regenerative capacity. Examination of the bone marrow lymphoid population shows that the expression of rat CD157 is largely observed at the CD45R+ IgM- pre-B-II cell stage, and unlike mouse, extension of expression into the IgM+ immature B cell stage was marginal. Similar to CD157high immature thymocytes, these immature B cells also expressed high levels of MHC class I. With the exception of the LEC, SHR and WKY rat strains, which have three- to four-fold less CD157+ bone marrow myeloid cells, percentages of these cells are similar between these two species. Thus, marked differences in the level and stage(s) of CD157 expression on lymphoid cells in mouse and rat indicate that CD157 may not, as previously thought, have a direct role in T or B cell differentiation.

ADP-ribosyl Cyclase↗
PubMed2000

Elder neglect assessment in the emergency department.

INTRODUCTION: Emergency departments are often the first point of contact for elder neglect victims. The purpose of this article is to describe a pilot study pertaining to the screening of patients and detection of elder neglect conducted in a large metropolitan medical center emergency department. The research question to be answered was, "Is it feasible for ED nurses to conduct accurate screening protocols for elder neglect in the context of their busy practice?" METHODS: During a 3-week period, 180 patients older than age 70 years (90% of all possible elderly patients during the screening hours) were screened to determine if they met the study criteria and could be enrolled into the protocol. RESULTS: Thirty-six patients met the eligibility criteria to enroll in the study, and 7 patients screened positive for neglect by a home caregiver. The nurses were able to screen and detect elder neglect with more than 70% accuracy, confirming the research question. The true-positive rate was 71%, and the false-positive rate was 7%. DISCUSSION: Elder neglect protocols are feasible in busy emergency departments, and neglect can be accurately detected in the emergency department when screening procedures are in place.

Aged↗
PubMed2000

Enhancing geriatric nursing scholarship: specialization versus generalization.

This article explores the relative merits of encouraging preparation of more nurses with specialization in geriatrics as compared to encouraging geriatric preparation among nurses whose major field of study is outside geriatrics. The article explores two approaches to examining capacity for geriatric nursing scholarship among nurse scholars not involved in geriatrics, and in schools of nursing with strength in research but with little geriatric research. The findings show an ongoing need to strengthen geriatric nursing as an area of specialization. Faculty prepared in geriatric nursing are underrepresented in schools of nursing, and only a small number of doctoral students specialize in geriatric nursing. Academic nursing programs with strength in geriatric nursing need ongoing support to maintain and expand current geriatric programs. Data support that encouraging individual non-geriatric nurse faculty and doctoral candidates to focus their work on areas of concern to geriatric nursing, and strengthening geriatrics in research-intensive schools of nursing that have not heavily invested in geriatric scholarship are viable options for strengthening academic geriatric nursing. Establishing mechanisms to attract nurse scholars working outside the scope of geriatric nursing to address clinical issues of concern to older adults offers promise in rapidly attracting new scholars to geriatric nursing.

Adult↗
PubMed1998

Prevalence estimates of cognitive impairment in medical model adult day health care programs.

Despite an increasing emphasis on adult day health care (ADHC) programs as alternatives to institutional care for persons with dementia, little research based on direct assessment of clients' cognitive status has been conducted in such settings. The goal of this analysis was to estimate the prevalence of cognitive impairment among ADHC clients using commonly used screening measures. Age-adjusted and non-age-adjusted prevalence estimates of cognitive impairment in New York State ADHC programs were developed using a probability sample of 336 clients. Estimates were made using traditional cutting scores on standard cognitive screening measures, such as the Mini-Mental State Examination (MMSE), as well as latent class analyses applied to the same item sets. Average prevalence estimates of cognitive impairment were 55% across age cohorts and 60% for persons aged 65 and over. The MMSE yielded a prevalence estimate of 58% across age cohorts and 63% for those aged 65 and over. Using a more conservative cut score, the estimate for the MMSE was 33%; latent class estimates of moderate to severe impairment indicate that approximately 30% of the ADHC clients had cognitive impairment suggestive of probable or definite dementia. Community alternatives to institutional care for the elderly are increasing in popularity. These findings suggest that 1. While institutions are serving the most severely cognitively impaired, age-adjusted prevalence ratios for the ADHC sample approach the bounds of the institutional estimates. 2. The institutional setting will continue to be an important mode of care for the more severely impaired individuals. 3. Daycare is serving a high proportion of the mildly and moderately cognitively impaired individuals. It follows, therefore, that such programs need to address the needs of these individuals by developing specialized care plans and tracks targeted for the cognitively impaired.

Adult↗
PubMed1997

Prevalence of behavior disorder and disturbance to family and staff in a sample of adult day health care clients.

Latent class-derived prevalence estimates of behavior disorder are provided for adult day health care (ADHC) clients; informal and formal caregivers reported 11% and 14%, respectively, of these clients as engaging in severe disturbed behavior (95% confidence intervals across sources are from 7% to 18%). The prevalences, estimated for informal and formal caregivers respectively, were 12% and 16% for affective disorder, 15% and 18% for cognitive disorders, 16% and 13% for verbal-vocal agitation, and 6% and 8% for socially inappropriate behavior. These rates can be contrasted with those of the institutional population which, while higher, overlap with the distribution of behavior disorder for ADHC community residents. The degree of reported disturbance to family and staff was similar across items.

Adult↗
PubMed1993

Influence of viral superantigens on V beta- and V alpha-specific positive and negative selection.

In mice, V beta-specific negative selection is mediated by a number of superantigens encoded by various mouse mammary tumor viruses. We have identified Mtv-3, Mtv-27, Mtv-44, Mtv-8, Mtv-9, Mtv-11, and MMTV(D2.GD), and have confirmed Mtv-1. Although specificities of superantigens correlate well with sequences of their carboxy terminal regions, Mtv-44 appears to be an exception: the product is specific for V beta 3, V beta 6, V beta 8.1, and V beta 9. It remains to be determined whether Mtv-44 produces one or two different superantigens to exhibit this specificity. V beta 5+ T-cell deletion is induced by two groups of superantigens: V beta 3-specific superantigens encoded by Mtv-1, Mtv-3, Mtv-6, Mtv-13, Mtv-27, and Mtv-44, and V beta 11-specific superantigens encoded by Mtv-8, Mtv-9, and Mtv-11. Furthermore, these V beta 3-specific superantigens are also specific for V beta 17a(cz). In contrast, V beta-specific positive selection and V alpha-specific positive and negative selection do not seem to involve non-H-2 (super)antigens, although their involvement can not be excluded. In the near future, superantigens, powerful modulators of T-cell functions, will be exploited for clinical applications.

Amino Acid Sequence↗
PubMed1993

Characterization of experimental allergic encephalomyelitis-susceptible, Biozzi AB/H (H-2dq1) mice which express H-2Anod: analysis of T-cell receptor expression and the detection of a deletion ligand encoded by Mtv-7.

Biozzi (H-2dq1) AB/H mice are marked not only by their high titre antibody responses following immunization with protein antigens but are also susceptible to experimental allergic encephalomyelitis (EAE) induction. The T-cell receptor (TcR) repertoire in this recently characterized strain was analysed. Biozzi AB/H mice were found to express the Thy-1a, Ly-1b, Ly-2b and Ly-5b alleles. Serological typing of the TcR-V beta + peripheral T cells suggested that the AB/H mice belong to the TcR-V beta b haplotype and express a deletion ligand for TcR-V beta 6+ and TcR-V beta 8.1+ T cells. This was confirmed by Southern blot analysis which revealed the presence of Mtv-17, Mtv-23, Mtv-31 (Y chromosome) and notably Mtv-7. Therefore the AB/H mice are Mls-1a. Despite the depletion/absence of the majority of TcR-V beta families in EAE-resistant (BALB/c) x EAE-susceptible (AB/H) F1 mice it was possible to induce EAE in these F1 animals. This suggests either that the deleted TcR-V beta-bearing T cells were not the principal encephalitogenic cells or that the TcR-V beta usage is sufficiently heterogeneous to accommodate such deletion events, in spinal cord-induced EAE.

Animals↗
PubMed1992

Positive and negative selection of Tcrb-V6+ T cells.

Tcrb-V6+ T cells are deleted by an endogenous superantigen probably encoded by a mouse mammary tumor provirus (Mtv), Mtv-7, in association with major histocompatibility complex (MHC) class II molecules. In contrast, Tcrb-V6+CD4+ T cells are positively selected by MHC class II E molecules in Mtv-7- mice. We have examined the levels of Tcrb-V6+CD4+ and Tcrb-V6+CD8+ T cells from six combinations of backcross mice. In this paper we show that: 1) Tcrb-V6+CD8+ T cells can be positively selected by MHC class I molecules; 2) MHC class II A molecules can also influence the levels of Tcrb-V6+CD4+ T cells; 3) Mtv-7- NZW mice have a new Mtv, Mtv-44, which cosegregates with a gene encoding the partial deletion ligand for Tcrb-V6+ T cells; 4) the remaining Tcrb-V6+ T cells from mice with partial deletion of these T cells appear not to be anergized in the periphery.

Animals↗
PubMed1992

Tcrb-V3+ T-cell deletion and a mouse mammary tumor provirus, Mtv-27.

Genes encoding superantigens which delete Tcrb-V3+ T cells co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-1, Mtv-3, Mtv-6, Mtv-13, and Mtv-44. We have examined percentages of Tcrb-V3+ T cells and Mtv integrations in [(B10 x NZB)F1 x B10.BR] mice, and show that Mtv-27 as well as Mtv-3 from NZB mice co-segregate with genes encoding deletion ligands for Tcrb-V3+ T cells without recombination.

Animals↗
PubMed1992

Tcrb-V3+ T-cell deletion and a new mouse mammary tumor provirus, Mtv-44.

Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13. In addition Mtv-1 has been implicated in deletion of these T cells. We have examined levels of Tcrb-V3+ T cells and Mtv integrations in the following offspring and their parental strains, [(CBA-T6 x NZW)F1 x CBA], [(CBA x C3H/He)F1 x CBA], and [(B10.S (9R) x NOD]F1 mice. We show that a new Mtv (Mtv-44) from NZW mice and Mtv-1 from C3H/He mice cosegregate with genes encoding ligands for partial deletion of Tcrb-V3+ T cells and that some NOD mice have an additional Mtv (Mtv-45) which is closely linked to Mtv-3.

Animals↗
PubMed1992

Endogenous ligands selecting T cells expressing particular V beta elements.

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular V beta segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple V beta 11 and V beta 3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the V beta 11/V beta 3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3' LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3' LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.

Animals↗
PubMed1991

Genes encoding ligands for deletion of V beta 11 T cells cosegregate with mammary tumour virus genomes.

The T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selection, others in negative selection. Negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive T cells. A group of self-ligands involved in clonal deletion was identified because they, like exogenous superantigens, were recognized by almost all T cells expressing particular TCR V beta genes. V beta 17a T cells are deleted by a tissue-specific ligand; V beta 6, V beta 7, V beta 8.1 and V beta 9 T cells are deleted by the minor lymphocyte-stimulating (Mls) determinant Mls-1a; V beta 3 T cells by Mls-2a and Mls-3a; V beta 11 T cells by ligands encoded by independently segregating genes; and V beta 5 T cells by ligands encoded by two genes. Chromosome mapping using recombinant inbred strains of mice and classic backcrosses show that Mls-1a in DBA/2 mice is encoded on chromosome 1, that one of the two ligand genes for deletion of V beta 5 T cells maps to chromosome 12 and that a ligand gene for V beta 11 deletion is linked to the CD8 locus on chromosome 6. Here we present evidence from three sets of backcross mice for concordance between V beta 11 deletion ligand genes on chromosomes 6, 12 and 14 and endogenous mouse mammary tumour virus integrant (Mtv) genomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Co-segregation of a gene encoding a deletion ligand for Tcrb-V3+ T cells with Mtv-3.

A gene encoding the endogenous superantigen Mlsc, which deletes Tcrb-V3+ T cells in the NOD inbred mouse strain, was found to co-segregate with Mtv-3 on chromosome 11. This identifies a fourth gene encoding a deletion ligand for Tcrb-V3+ T cells and extends recently published observations in support of the hypothesis that a number of endogenous superantigens are the products of Mtv proviruses.

Animals↗