Prevalence and risk factors of suicide and suicidal ideation in veterans who served in the British Armed Forces: a systematic review.

INTRODUCTION: Research into the factors resulting in suicide in the military veteran population has yet to reach a consensus. Available research is concentrated on a small number of countries, and there is a lack of consistency with contradictory conclusions. The USA has produced a significant amount of research in a country where suicide is identified as a national health crisis, but in the UK, there is little research regarding veterans from the British Armed Forces. METHODS: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Corresponding literature searches were conducted in PsychINFO, MEDLINE and CINAHL. Articles that discussed suicide, suicidal ideation, prevalence or risk factors among British Armed Forces veterans were eligible for review. A total of 10 articles met the inclusion criteria and were analysed. RESULTS: Veterans' suicide rates were found to be comparable to those of the general UK population. The method of suicide used was most commonly found to be hanging and strangulation. Firearms was recorded in 2% of suicide cases. Demographic risk factors were often contradictory with some research stating that there was risk in older veterans and some in younger. However, female veterans were found to be at higher risk than female civilians. Those who had deployed on combat operations were at lower risk of suicide, with research finding that veterans who took longer to seek help for mental health (MH) difficulties reported more suicidal ideation. CONCLUSIONS: Peer-reviewed research publications have revealed that UK veteran suicide prevalence is broadly comparable to the general population while highlighting differences across international armed forces. Veteran demographics, service history, transition and MH have all been identified as potential risk factors of suicide and suicidal ideation. Research has also indicated that female veterans are at higher risk than that of their civilian counterparts due to veterans being predominantly male; this could skew results and requires investigation. Current research is limited and further exploration of suicide prevalence and risk factors in the UK veteran population is required.

Critical analysis of the Armed Forces Covenant Fund Trust Aged Veterans Fund.

BACKGROUND: Relatively little research is available regarding the specific needs of older military veterans and the services introduced to support them. In 2016, the Armed Forces Covenant Fund Trust launched the Aged Veterans Fund (AVF), to understand the impact that military service may have on ageing, and to support initiatives targeting their health and well-being. This fund was financed for 5 years and included 19 UK portfolio projects. METHOD: The paper presents a retrospective evaluation on the processes and impact of the AVF, with the intent of informing policy, educational services, service providers and stakeholders of the lessons learnt. The inclusion criteria was veterans and their families aged 65 years of age or over. In 2019, data were drawn from documentary evidence related to the programmes. Qualitative analysis were performed on 78 eligible sources and 10 themes were identified. RESULTS: Programmes were rolled out via collaborative partnerships referrals, focusing on person-centred or skill-exchange approaches. Challenges were encountered, such as capacity and timelines issues. A limited amount of associated cost-savings was observed, even if examples of sustainability and high satisfaction were reported. Evidence was found of programmes boosting health and well-being outcomes, in raising awareness, and in positively impacting on clinical practice, such as re-admission rates. CONCLUSION: The AVF programmes were successful in their intent to provide support to older veterans and their families. The findings provide indicators of the next steps required for the support of ageing veterans. Further investigation of the cost-effectiveness of age-friendly veterans' services is needed.

Veteran help-seeking behaviour for mental health issues: a systematic review.

INTRODUCTION: Serving military personnel and veterans have been identified to have a high prevalence of mental health disorders. Despite this, only a significantly small number seek mental healthcare. With the UK beginning to invest further support to the armed forces community, identification of barriers and facilitators of help-seeking behaviour is needed. METHODS: Corresponding literature search was conducted in PsycINFO, PsycArticles, Medline, Web of Science and EBSCO. Articles which discussed barriers and facilitators of seeking help for mental health concerns in the veteran population were included. Those which discussed serving personnel or physical problems were not included within this review. A total of 26 papers were analysed. RESULTS: A number of barriers and facilitators of help-seeking for a mental health issue within the veteran population were identified. Barriers included stigma, military culture of stoicism and self-reliance, as well as deployment characteristics of combat exposure and different warzone deployments. Health service difficulties such as access and lack of understanding by civilian staff were also identified. Facilitators to help combat these barriers included a campaign to dispel the stigma, including involvement of veterans and training of military personnel, as well as more accessibility and understanding from healthcare staff. CONCLUSIONS: While some barriers and facilitators have been identified, much of this research has been conducted within the USA and on male veterans and lacks longitudinal evidence. Further research is needed within the context of other nations and female veterans and to further indicate the facilitators of help-seeking among veterans.

Caregiver self-efficacy to talk about sex predicts conversations about HIV transmission risk with perinatally infected young people in Zimbabwe.

Given advances in care and treatment for HIV, perinatally infected young people are surviving into adolescence. These young people are making decisions about engaging in sexual relationships and it is critical to ensure they have the information they need to engage responsibly in sexual activity, particularly in an era where adherence to treatment could make their virus undetectable. The main objective of this analysis was to examine whether an HIV-positive young person's knowledge about forward transmission is associated with caregiver self-efficacy to talk about sex and general caregiver communication. Using data from a 12-month prospective cohort of caregivers of HIV-positive children aged 9-15 on ART and pre-ART in rural Zimbabwe, we found that caregiver self-efficacy to talk about sex predicted whether conversations about HIV transmission would occur between caregiver and the young person. However, by the end of 12-months, nearly two-thirds of caregivers of HIV-positive teenagers in our sample had still not explained how their adolescents could spread the virus to others despite these caregivers saying their adolescent should know this information at baseline. We discuss the implications for designing sexual and reproductive health (SRH) programs among populations of young people perinatally infected with HIV to ensure that this breakthrough generation receives the SRH support they need.

Use of multiple markers demonstrates a cryptic western refugium and postglacial colonisation routes of Atlantic salmon (Salmo salar L.) in Northwest Europe.

Glacial and postglacial processes are known to be important determinants of contemporary population structuring for many species. In Europe, refugia in the Italian, Balkan and Iberian peninsulas are believed to be the main sources of species colonising northern Europe after the glacial retreat; however, there is increasing evidence of small, cryptic refugia existing north of these for many cold-tolerant species. This study examined the glacial history of Atlantic salmon in western Europe using two independent classes of molecular markers, microsatellites (nuclear) and mitochondrial DNA variation. Alongside the well-documented refuge in the Iberian Peninsula, evidence for a cryptic refuge in northwest France is also presented. Critically, methods utilised to estimate divergence times between the refugia indicated that salmon in these two regions had diverged a long time before the last glacial maximum; coalescence analysis (as implemented in the program IMa2) estimated divergence times at around 60 000 years before present. Through the examination of haplotype frequencies, previously glaciated areas of northwest Europe, that is, Britain and Ireland, appear to have been colonised from salmon expanding out of both refugia, with the southwest of England being the primary contact zone and exhibiting the highest genetic diversity.

Factors affecting front line casualty care in Afghanistan.

OBJECTIVE: Limited research has been undertaken to assess the effectiveness of pre-hospital care given at the point of wounding, nor how battlefield conditions affect the implementation of Battlefield Advanced Trauma Life Support (BATLS). This study examines the quality of care given at Role 1 and the psychological impact on clinical personnel of the application of current pre-hospital trauma management guidelines. METHOD: Data was collected through 17 digitally recorded semi-structured interviews with healthcare clinicians deployed in Role 1 medical facilities on OP HERRICK 14 following major medical incidents. Interview transcripts were subjected to content analysis based on a modified grounded theory approach. RESULTS: Triage was found to be done poorly with individuals treating patients as they were found rather than by identifying clinical priorities. Pain management was not always achieved. Fluid replacement was hampered with difficulty in obtaining parenteral access. Subsequently fluids were sometimes given in excess of protocols. Clinical documentation was not always completed even after a patient had been evacuated. Some interesting elements were noted, such as post incident reports being used as a reflective process which may be self-developmental and help clinicians deal psychologically with the incident. Clinical personnel carry out their duties, irrespective of personal injury or threats to their safety. However their performance may be tapered under such stress. Human factors training prior to deployment may help to ensure adherence to BATLS protocols despite the complexities of the battle space. CONCLUSIONS: The data identified a number of factors that affected clinicians ability to provide a high standard of casualty care. The general perception of this research cohort was that despite all the obstacles, the level of trauma care was of a high nature. However, the study provides pointers to a number of areas for future exploration where patient care was not BATLS protocol compliant.

Predisposing factors and associated symptomatology of British soldiers requiring a mental health assessment.

OBJECTIVES: To critically evaluate the predisposing factors and symptomatology that resulted in serving officers and soldiers requiring a Mental Health (MH) assessment. METHODS: 317 regular Army personnel who required a formal MH assessment completed a survey that detailed the predisposing factors and symptoms leading to the referral. SPSSv10 was used for data management and analysis of the data by descriptive and inferential statistical methods. RESULTS: Three quarter presented with at least two predisposing factors, the commonest being family issues (42%), relationship problems (40%) and general military stress (39%). Up to half of young male Soldiers required a MH assessment as a result of wanting to leave the Army, and were positively associated with self harming ideology. Female soldiers are significantly over represented. No-one reported feeling isolated. CONCLUSION: The majority of personnel accessing the Army MH Services present with multi-factorial problems and symptoms that should result in colleagues being aware of their distress, and every effort must be made to support these soldiers within unit lines. That no one reported feeling isolated, challenges the perception that soldiers with MH problems are stigmatised. In those young male soldiers who wish to leave the Army there are indicators that significant periods of notice to leave can have a negative impact on MH. It is unclear why females are more likely to require support. If the emerging themes noted in this study are addressed, and the lessons learnt encapsulated within a predictive theoretical model, then the result could be an improvement in operational capability through the early return of Army personnel and Officers to full duty.

Northern Uganda and paradigms of HIV prevention: the need for social analysis.

In settings of armed conflict, traditional HIV prevention programmes that promote risk avoidance via abstinence and fidelity and risk reduction via condom use and needle exchange are not viable. In such contexts, HIV risk depends less on personal choice than on exposure to physical, emotional and structural violence. War in northern Uganda has created three realities (internally displaced people's camps, night commuters and child abductions) which increase vulnerability to HIV transmission. Based upon this analysis of northern Uganda, we offer a conceptual framework for HIV transmission in conflict settings that recognizes the importance of local and global context in creating vulnerability to HIV infection. This framework is then used to delineate strategies for HIV prevention in northern Uganda, namely the provision of a safe physical environment and access to education, medical and psychological support, and the promotion of conflict resolution strategies and human rights law.

A review of one year of British Armed Forces mental health hospital admissions.

OBJECTIVES: The paper provides a review of one year of military Mental Health (MH) hospital admissions. This includes an exploration into demographic trends, differences in clinical opinion and how information gained is used to improve the service and ensure appropriate, cost effective care in the optimum environment. METHODS: The sample group is entitled military MH hospital admissions from 1 April 2005 to 31 March 2006. Data was collected on questionnaires with SPSS used for the management and analysis of the quantitative data, with the information exposed to descriptive and inferential statistical analysis. RESULTS: There were 344 admissions. The paper contains a detailed review of a number of variables. Depression was the most common diagnosis resulting in 112 (33%) hospital admissions and Post Traumatic Stress Disorder accounted for 23 (7%). There were statistically significant differences that may be attributable to gender with more women admitted with depression and more men with alcohol related disorders. The average length of stay was 21 days, with 48% of patients discharged within 3 weeks. 45% of all returns included significant events reporting that highlighted written evidence of good and poor practice. CONCLUSION: This study is part of an extensive monitoring programme of military MH hospital admissions. Depression is the most common MH problem leading to hospital admission. The results indicate that Service-personnel have access to a highly responsive service that provides brief assessment and treatment within a safe therapeutic environment. 45% of returns included significant event information that resulted in policy changes, leading to improved patient care and a better interface with the NHS. Bench-marking, both internally between military Departments of Community Mental Health and externally have improved visibility and self awareness leading to better GP induction programmes, PHC educational seminars and the establishment of MH web-pages. The Armed Forces need an effective MH service that is accessible, readily available, non-stigmatised and which positively advocates a duty of care. The results highlight the importance of further studies regarding depression to ensure that the Armed Forces are in a better position to maximise the use of MH resources.

Skeletal dysplasia and male infertility locus on mouse chromosome 9.

In mice and humans, growth insufficiency and male infertility are common disorders that are genetically and phenotypically complex. We describe a spontaneously arising mouse mutant, chagun, that is affected by both dwarfism and male infertility. Dwarfism disproportionately affects long bones and is characterized by a defect in the proliferative zone of chondrocytes in the growth plate. Gonads of mutant males are small, with apparent germ cell loss and no evidence of mature sperm. The locus responsible for chagun is recessive and maps to distal chromosome 9, in a region homologous to human chromosome 3. This location is consistent with chagun defining a novel locus. Identification of the mutant gene will uncover the basis for another type of skeletal dysplasia and male infertility.

Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis.

Two autoimmune murine models--proteoglycan (aggrecan)-induced arthritis (PGIA) and collagen-induced arthritis (CIA)--were developed in parent strains, F1 and F2 hybrids of major histocompatibility complex (MHC)-matched (H-2) BALB/c x DBA/2 and MHC-unmatched (H-2/H-2) BALB/c x DBA/1 intercrosses. The major goal of this comparative study was to identify disease (model)-specific (PGIA or CIA) and shared clinical and immunologic loci in 2 types of genetic intercrosses. Qualitative (binary/susceptibility) and quantitative (severity and onset) clinical trait loci were separated and analyzed independently or together with various pathophysiologic/immunologic traits, such as antigen-specific T- and B-cell responses and cytokine production. The major quantitative trait locus (QTL) was the MHC on chromosome 17, which was especially dominant in CIA. In addition, chromosomes 3, 5, 10, and X contained shared clinical loci in both models, and a total of 8 QTLs (clinical traits together with immunologic traits) were colocalized in PGIA and CIA.

Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis.

Proteoglycan (PG)-induced arthritis (PGIA) is a novel autoimmune murine model for rheumatoid arthritis induced by immunization with cartilage PG in susceptible BALB/c mice. In this model, hyperproliferation of peripheral CD4(+) T cells has been observed in vitro with Ag stimulation, suggesting the breakdown of peripheral tolerance. Activation-induced cell death (AICD) is a major mechanism for peripheral T cell tolerance. A defect in AICD may result in autoimmunity. We report in this study that although CD4(+) T cells from both BALB/c and B6 mice, identically immunized with human cartilage PG or OVA, express equally high levels of Fas at the cell surface, CD4(+) T cells from human cartilage PG-immunized BALB/c mice, which develop arthritis, fail to undergo AICD. This defect in AICD in PGIA may lead to the accumulation of autoreactive Th1 cells in the periphery. The impaired AICD in PGIA might be ascribed to an aberrant expression of Fas-like IL-1beta-converting enzyme-inhibitory protein, which precludes caspase-8 activation at the death-inducing signaling complex, and subsequently suppresses the caspase cascade initiated by Fas-Fas ligand interaction. Moreover, this aberrant expression of Fas-like IL-1beta-converting enzyme-inhibitory protein may also mediate TCR-induced hyperproliferation of CD4(+) T cells from arthritic BALB/c mice. Our data provide the first insight into the molecular mechanism(s) of defective AICD in autoimmune arthritis.

Variations in susceptibility to proteoglycan-induced arthritis and spondylitis among C3H substrains of mice: evidence of genetically acquired resistance to autoimmune disease.

OBJECTIVE: To identify and screen the level of arthritis susceptibility in C3H murine strains known to be resistant to proteoglycan (aggrecan)-induced arthritis, and to measure and correlate various immunologic and inflammatory parameters with susceptibility to either arthritis or spondylitis in various C3H substrains. METHODS: Mice of 10 C3H substrains (subcolonies) were immunized with cartilage proteoglycan (aggrecan) for induction of arthritis. Animals were assessed for clinical symptoms, and the peripheral joints and spine were studied by histologic methods. Proteoglycan-specific T cell responses (T cell proliferation and production of interleukin-2 [IL-2], interferon-y, and IL-4) and the B cell response to lipopolysaccharide (LPS) were measured in spleen cell cultures. Serum levels of heteroantibodies and autoantibodies as well as various cytokines (IL-6, IL-10, IL-12, and tumor necrosis factor alpha) and soluble CD44 were determined by enzyme-linked immunosorbent assay. RESULTS: Immunization with cartilage proteoglycan induced severe arthritis in the C3H/HeJCr substrain (95-100% incidence), whereas the original parent mice of the C3H/HeJ colony were resistant to proteoglycan (aggrecan)-induced arthritis. Furthermore, the progressive polyarthritis that is characteristic in susceptible C3H/HeJCr mice was accompanied by progressive inflammation around the spine. In subsequent experiments, 10 different C3H colonies with largely identical genetic backgrounds (all originating from the National Institutes of Health or Jackson Laboratory) exhibited extreme differences in susceptibility. Although none of the laboratory findings, including LPS hyporesponsiveness, immunologic parameters, and inflammatory markers, showed a correlation with susceptibility or resistance in the C3H/HeJCr and C3H/HeJ substrains, respectively, significant differences were found when all arthritic C3H mice were compared with all nonarthritic animals, regardless of their substrain origin. CONCLUSION: Because many of the C3H substrains lost arthritis susceptibility or acquired resistance, our results suggest that a preferred site for a mutation(s) in a gene(s) in a relatively upstream position of the inflammatory cascade is present. This is the first autoimmune model that exhibits extreme differences in arthritis susceptibility in the same murine strain, and is therefore a valuable tool for identification of arthritis-susceptible (or arthritis-suppressive) genes.

A genome scan using a novel genetic cross identifies new susceptibility loci and traits in a mouse model of rheumatoid arthritis.

Proteoglycan-induced arthritis (PGIA) is a murine model for rheumatoid arthritis (RA) both in terms of its pathology and its genetics. PGIA can only be induced in susceptible mouse strains and their F(2) progeny. Using the F(2) hybrids resulting from an F(1) intercross of a newly identified susceptible (C3H/HeJCr) and an established resistant (C57BL/6) strain of mouse, our goals were to: 1) identify the strain-specific loci that confer PGIA susceptibility, 2) determine whether any pathophysiological parameters could be used as markers that distinguish between nonarthritic and arthritic mice, and 3) analyze the effect of the MHC haplotype on quantitative trait loci (QTL) detection. To identify QTLs, we performed a genome scan on the F(2) hybrids. For pathophysiological analyses, we measured pro- and antiinflammatory cytokines such as IL-1, IL-6, IFN-gamma, IL-4, IL-10, IL-12, Ag-specific T cell proliferation and IL-2 production, serum IgG1 and IgG2 levels of both auto- and heteroantibodies, and soluble CD44. We have identified four new PGIA-linked QTLs (Pgia13 through Pgia16) and confirmed two (Pgia5, Pgia10) from our previous study. All new MHC-independent QTLs were associated with either disease onset or severity. Comprehensive statistical analysis demonstrated that while soluble CD44, IL-6, and IgG1 vs. IgG2 heteroantibody levels differed significantly between the arthritic and nonarthritic groups, only Ab-related parameters colocalized with the QTLs. Importantly, the mixed haplotype (H-2(b) and H-2(k)) of the C3H x C57BL/6 F(2) intercross reduced the detection of several previously identified QTLs to suggestive levels, indicating a masking effect of unmatched MHCs.

Spontaneous thymocyte apoptosis is regulated by a mitochondrion-mediated signaling pathway.

Most thymocytes that have not successfully rearranged their TCR genes or that express a receptor with subthreshold avidity for self-Ag/MHC enter a default apoptosis pathway, death by neglect. Spontaneous thymocyte apoptosis (STA), at least in part, may mimic this process in vitro. However, the molecular mechanism(s) by which thymocytes undergo this spontaneous apoptosis remains unknown. Here, we report that caspsase-1 and caspase-3 are activated during STA, but these caspases are dispensable for this apoptotic process. The inhibition of STA by a pan-caspase inhibitor, zVAD, suggests that multiple caspase pathways exist. Importantly, the early release of cytochrome c from mitochondria closely correlates with the degradation of Bcl-2 and Bcl-xL and a decrease in the ratios of Bcl-2 and Bcl-xL to Bax during STA. These findings suggest that the degradation of Bcl-2 and Bcl-xL may favor Bax to induce cytochrome c release from mitochondria, which subsequently activates downstream caspases in STA. Our data provide the first biochemical insight into the molecular mechanism of STA.

Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.

The central role of CD4+ T cells and the balance between T helper (Th) subpopulations in the pathogenesis of autoimmune diseases have been extensively studied. Proteoglycan (aggrecan)-induced arthritis (PGIA) is a murine model for rheumatoid arthritis (RA), which is characterized by a Th1 dominance at the onset of the disease. In addition to CD4+ T cells, antigen-presenting B cells and autoantibodies seem to play an important role in the development and regulation of PGIA. To identify proteoglycan-specific CD4+ T cell subsets and Th1- and Th2-supported antibody isotypes during the progression of PGIA, spleen cells of proteoglycan-immunized BALB/c mice were harvested at different times of immunization, and at different stages of the disease, and their cytokine production and antigen-specific antibody isotype profiles were determined by enzyme-linked immunospot (ELISPOT) assays. Both Th1 and Th2 cytokine-producing cells, with the predominance of IL-4/IL-5-secreting cells, were detected during the prearthritic stage, and a shift toward a Th1 dominance was observed at the time of onset of arthritis. Tissue homogenates of acutely inflamed joints contained significantly higher levels of interferon-gamma than IL-4. The prearthritic period and both the acute and chronic phases of joint inflammation were characterized by IgG1 dominance in the sera and this correlated with the number of IgG1-secreting B cells in the spleen. However, the ratio of autoreactive IgG1/IgG2a-secreting cells decreased in arthritic animals. These results indicate the activation and possible regulatory roles of both Th1 and Th2 subsets in the autoimmune process, with the necessity of a relative increase of autoreactive Th1 cells for the induction of joint inflammation.

Regulation of intercellular adhesion molecule-1 (CD54) gene expression.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is an inducible cell adhesion glycoprotein of the immunoglobulin supergene family expressed on the surface of a wide variety of cell types. ICAM-1 interactions with the beta2 integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (MAC-1) on the surface of leukocytes are important for their transendothelial migration to sites of inflammation and their function as costimulatory molecules for T cell activation. ICAM-1 is constitutively expressed on the cell surface and is up-regulated in response to a variety of inflammatory mediators, including proinflammatory cytokines, hormones, cellular stresses, and virus infection. These stimuli increase ICAM-1 expression primarily through activation of ICAM-1 gene transcription. During the past decade much has been learned about the cell type- and stimulus-specific transcription of ICAM-1. The architecture of the ICAM-1 promoter is complex, containing a large number of binding sites for inducible transcription factors, the most important of which is nuclear factor-kappa B (NF-kappaB). NF-kappaB acts in concert with other transcription factors and co-activators via specific protein-protein interactions, which facilitate the assembly of distinct stereospecific transcription complexes on the ICAM-1 promoter. These transcription complexes presumably mediate the induction of ICAM-1 expression in different cell types and in response to different stimuli. In this review, we summarize our current understanding of ICAM-1 gene regulation with a particular emphasis on the transcription factors and signal transduction pathways critical for the cell type- and stimulus-specific activation of ICAM-1 gene transcription.

Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.

In animal models of arthritis induced with Ags or infectious agents, disease severity correlates with a dominant Th1-type response characterized by a higher ratio of IFN-gamma to IL-4. Analysis of BALB/c mice revealed a genetic predisposition toward developing CD4+ Th2-type responses. The bias toward an IL-4-dominant response in BALB/c mice protects mice from severe Lyme-induced arthritis and spontaneous autoimmune disease. Since BALB/c mice immunized with proteoglycan develop severe arthritis, we were interested in testing whether arthritis is associated with a Th2-type response and thus is different from other arthritic models. BALB/c mice immunized with proteoglycan generated a higher ratio of IFN-gamma to IL-4 that peaks at the onset of arthritis. We investigated whether when Th1 cells were dominant, disease outcome could be modified with pharmacological amounts of Th2 cytokines. Treatment with IL-4 prevented disease and induced a switch from a Th1-type to a Th2-type response. Proinflammatory cytokine mRNA transcripts were reduced in joints of cytokine-treated mice. Th2 cytokine therapy at the time of maximum joint inflammation also suppressed symptoms of disease. Despite the predisposition of BALB/c mice to a Th2-type response, proteoglycan-induced arthritis is a Th1-type disease. The effectiveness of IL-4 treatment was particularly striking because in other models of arthritis, treatment in a similar manner with IL-4 was not sufficient to inhibit arthritis. The effective control of arthritis and the switch from a Th1 to Th2 response suggest that levels of endogenous IL-4 in BALB/c mice may increase their responsiveness to Th2 cytokine therapy.

Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells.

A novel type II integral membrane protein has been identified in the course of screening for genes overexpressed in a mouse model of chronic myelogenous leukemia blast crisis. This new protein, designated NKCL, consists of a 210-amino acid polypeptide with a short, NH2-terminal cytoplasmic tail of 17 amino acids preceding a transmembrane domain and a COOH-terminal extracellular region. The COOH-terminal 132 amino acids bear typical features of the C-type animal lectin carbohydrate-recognition domain. The Nkcl gene is unique in that it maps just proximal to the region of the genome that encodes group V members of the C-type animal lectin family near the natural killer gene complex on mouse chromosome 6, but its protein product also has features of several group II C-type animal lectins. Most notably, it has a complete Ca2+-binding site 2, which forms part of the sugar-binding site in other members of the family, and binds mannose in a Ca2+-dependent manner. Moreover, its expression is not restricted to natural killer cells, as reported for the majority of group V lectins. Nkcl is expressed in pluripotent myeloid precursors, precursor and mature macrophages, and neutrophils.