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Biomedical subjects

Ian Brown

Publications and source records attributed to Ian Brown.

At least 19 recordsLinked to original sources
PubMed2007

Two high-amylose maize starches with different amounts of resistant starch vary in their effects on fermentation, tissue and digesta mass accretion, and bacterial populations in the large bowel of pigs.

Four groups of young pigs (n 6) were fed a diet containing 50% maize starch as either a highly digestible waxy starch (control; 0% amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85% amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85% amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS(88%) than for HTHAMS (70%; P<0.05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P<0.05) and digesta pH lower (by about 1 unit, all P<0.001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0.5-0.9 m longer (19-35%) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P<0.05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P< 0.05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

Amylose↗
PubMed2006

T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha.

T cell anergy has been correlated with defective signaling by the GTPase Ras, but causal and mechanistic data linking defective Ras activity with T cell anergy are lacking. Here we used adenoviral transduction to genetically manipulate nonproliferating T cells and show that active Ras restored interleukin 2 production and mitogen-activated protein kinase signaling in T cells that were made anergic in vitro or in vivo. Diacylglycerol kinases (DGKs), which negatively regulate Ras activity, were upregulated in anergic T cells, and a DGK inhibitor restored interleukin 2 production in anergic T cells. Both anergy and DGK-alpha overexpression were associated with defective translocation of the Ras guanine nucleotide-exchange factor RasGRP1 to the plasma membrane. Our data support a causal function for excess DGK activity and defective Ras signaling in T cell anergy.

Animals↗
PubMed2006

Eosinophilic angiocentric fibrosis: an unusual entity producing complete lacrimal duct obstruction.

Eosinophilic angiocentric fibrosis is an unusual fibrotic condition of unknown aetiology that tends to affect the upper respiratory tract. Twenty-one cases have been reported in the literature and only three have had ocular adnexal involvement. Despite characteristic histopathological and clinical findings, the diagnosis remains a challenge. Furthermore, its progressive nature with potential to invade adjacent structures and the lack of response to current treatment modalities make management difficult. We describe a case of sinonasal eosinophilic angiocentric fibrosis that presented with bilateral nasolacrimal duct obstruction.

Adult↗
PubMed2006

Nurses' attitudes towards adult patients who are obese: literature review.

AIMS: This paper presents a review of all empirical studies focusing on nurses' attitudes towards adult overweight or obese patients, with the aim of clarifying the dimensions and patterns of these attitudes and the methods by which they have been studied. BACKGROUND: Obesity has become a common condition and a major public health concern, but it is often associated with negative attitudes and discrimination. Nurses play a key role in providing support and care to patients who are obese. METHODS: Electronic searches were carried out on seven databases from inception to December 2004, along with hand-searching of references in relevant studies. The search terms were built around obesity (and related terms), nursing (and its branches) and attitudes (and related terms). Eleven studies met the inclusion criteria. Data were extracted and summarized in tabular form and analysed in relation to the aims of this review during January 2005. FINDINGS: There is relatively little research about nurses' attitudes towards obese patients, and the studies reviewed mostly have weaknesses of sampling and measurement. However, they do consistently suggest that a proportion of nurses have negative attitudes and beliefs, reflecting wider stereotypes within Western cultures. There is also a hint of a more complex mix of attitudes among nurses, some of which may counter the consequences of negative attitudes, but these have not been adequately investigated. A number of variables that influence attitudes of nurses can be identified, including age, gender, experience and the weight/body mass index of the nurse. CONCLUSION: Further research (both qualitative and quantitative) is needed with more rigorous sampling and, where appropriate, more consistency of measurement. A shift in focus towards the sets of attitudes (positive as well as negative) and behaviours that influence health service quality and outcomes for obese persons would be useful.

Attitude of Health Personnel↗
PubMed2006

Immune resistance orchestrated by the tumor microenvironment.

It is now little disputed that most if not all cancer cells express antigens that can be recognized by specific CD8(+) T lymphocytes. However, a central question in the field of anti-tumor immunity is why such antigen-expressing tumors are not spontaneously eliminated by the immune system. While in some cases, this lack of rejection may be due to immunologic ignorance, induction of anti-tumor T-cell responses in many patients has been detected in the peripheral blood, either spontaneously or in response to vaccination, without accompanying tumor rejection. These observations argue for the importance of barriers downstream from initial T-cell priming that need to be addressed to translate immune responses into clinical tumor regression. Recent data suggest that the proper trafficking of effector T cells into the tumor microenvironment may not always occur. T cells that do effectively home to tumor metastases are often found to be dysfunctional, pointing toward immunosuppressive mechanisms in the tumor microenvironment. T-cell anergy due to insufficient B7 costimulation, extrinsic suppression by regulatory cell populations, inhibition by ligands such as programmed death ligand-1, metabolic dysregulation by enzymes such as indoleamine-2,3-dioxygenase, and the action of soluble inhibitory factors such as transforming growth factor-beta have all been clearly implicated in generating this suppressive microenvironment. Identification of these downstream processes points to new therapeutic targets that should be manipulated to facilitate the effector phase of anti-tumor immune responses in concert with vaccination or T-cell adoptive transfer.

Animals↗
PubMed2006

Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis.

CONTEXT: An increased intraepithelial lymphocyte density in an architecturally normal proximal small intestinal mucosal biopsy is a common finding facing surgical pathologists dealing with gastrointestinal biopsy specimens. Approximately 1% to 2% of all proximal small intestinal biopsies will show this change. It is increasingly recognized by surgical pathologists that gluten-sensitive enteropathy is an important cause of this pattern; however, gluten-sensitive enteropathy accounts for the minority of all cases. A wide variety of immunologic stimuli can raise intraepithelial lymphocyte numbers. Among the other common associations are enteric infection, autoimmune disease, drugs, and gastric Helicobacter infection. OBJECTIVE: To outline the causes of intraepithelial lymphocytosis, to highlight the importance and the difficulties faced in establishing gluten-sensitive enteropathy as the cause, and to aid the surgical pathologist in the routine sign out of these cases. DATA SOURCES: A review of the literature detailing the causes or associations of proximal small intestinal intraepithelial lymphocytosis is presented. CONCLUSIONS: Increased lymphocyte numbers in the epithelium of architecturally preserved proximal small intestinal biopsies is a morphologic feature associated with a broad differential diagnosis.

Autoimmune Diseases↗
PubMed2006

A visual graphic/haptic rendering model for hysteroscopic procedures.

Hysteroscopy is an extensively popular option in evaluating and treating women with infertility. The procedure utilises an endoscope, inserted through the vagina and cervix to examine the intra-uterine cavity via a monitor. The difficulty of hysteroscopy from the surgeon's perspective is the visual spatial perception of interpreting 3D images on a 2D monitor, and the associated psychomotor skills in overcoming the fulcrum-effect. Despite the widespread use of this procedure, current qualified hysteroscopy surgeons have not been trained the fundamentals through an organised curriculum. The emergence of virtual reality as an educational tool for this procedure, and for other endoscopic procedures, has undoubtedly raised interests. The ultimate objective is for the inclusion of virtual reality training as a mandatory component for gynaecologic endoscopy training. Part of this process involves the design of a simulator, encompassing the technical difficulties and complications associated with the procedure. The proposed research examines fundamental hysteroscopy factors, current training and accreditation, and proposes a hysteroscopic simulator design that is suitable for educating and training.

Computer Graphics↗
PubMed2006

Haptic rendering for VR laparoscopic surgery simulation.

This project concerns the application of haptic feedback to a VR laparoscopic surgery simulator. Haptic attributes such as mass, friction, elasticity, roughness and viscosity are individually modeled, validated and applied to the existing visual simulation created by researchers at Monash University. Haptic feedback is an essential element in an immersive and realistic virtual reality laparoscopic training simulator. The haptic system must display stable, continuous and realistic multi-dimensional force feedback, and its inclusion should enhance the simulators training capability. Stability is a recurring concern throughout haptic history, and will be tackled with the implementation of a stable control algorithm and a passive environment model. Haptic force feedback modeling, systems implementation and validation studies form the principal areas of new work associated with this project.

Computer Graphics↗
PubMed2006

Atypical prostatic glandular proliferations on needle biopsy: Diagnostic implications, use of immunohistochemistry, and clinical significance.

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.

Adenocarcinoma↗
PubMed2006

Primary care support for tackling obesity: a qualitative study of the perceptions of obese patients.

BACKGROUND: Obesity has become a major public health issue and there is concern about the response of health services to patients who are obese. The perceptions of obese patients using primary care services have not been studied in depth. AIM: To explore obese patients' experiences and perceptions of support in primary care. DESIGN OF STUDY: Qualitative study with semi-structured interviews conducted in participants' homes. SETTING: Five general practices contrasting in socioeconomic populations in Sheffield. METHOD: Purposive sampling and semi-structured interviewing of 28 patients with a diverse range of ages, backgrounds, levels of obesity and experiences of primary care services. RESULTS: Participants typically felt reluctance when presenting with concerns about weight and ambivalence about the services received. They also perceived there to be ambivalence and a lack of resources on the part of the health services. Participants showed a strong sense of personal responsibility about their condition and stigma-related cognitions were common. These contributed to their ambivalence about using services and their sensitivity to its features. Good relationships with primary care professionals and more intensive support partly ameliorated these effects. CONCLUSION: The challenges of improving access to and quality of primary care support in tackling obesity are made more complex by patients' ambivalence and other effects of the stigma associated with obesity.

Adolescent↗
PubMed2005

ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo.

ICAM-1 has been described to provide both adhesion and costimulatory functions during T cell activation. In the setting of antitumor immunity, ICAM-1/LFA-1 interactions could be important at the level of T cell priming by APCs in draining lymph nodes as well as for transendothelial migration and tumor cell recognition at the tumor site. To determine the contribution of ICAM-1 to tumor rejection in vivo, we performed adoptive transfer of 2C TCR-transgenic/RAG2(-/-) T cells into TCRalpha(-/-) vs ICAM(-/-)/TCRalpha(-/-) recipient animals. ICAM-1-deficient mice successfully rejected HTR.C tumors expressing Ld recognized by the 2C TCR, albeit with a kinetic delay. Inasmuch as HTR.C tumor cells themselves express ICAM-1, a second model was pursued using B16-F10 melanoma cells that lack ICAM-1 expression. These cells were transduced to express the SIYRYYGL peptide recognized by the 2C TCR in the context of Kb, which is cross-presented by APCs in H-2b mice in vivo. These tumors also grew more slowly but were eventually rejected by the majority of ICAM-1(-/-)/TCRalpha(-/-) recipients. Delayed rejection in ICAM-1(-/-) mice was associated with diminished T cell priming as assessed by ELISPOT. In contrast, T cell penetration into the tumor was comparable in wild-type and ICAM-1(-/-) hosts, and adoptively transferred primed effector 2C cells rejected normally in ICAM-1(-/-) recipients. Our results suggest that ICAM-1 contributes to but is not absolutely required for CD8+ T cell-mediated tumor rejection in vivo and dominantly acts at the level of priming rather than the effector phase of the antitumor immune response.

Adoptive Transfer↗
PubMed2005

Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients.

PURPOSE: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. METHODS: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control. RESULTS: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival. CONCLUSIONS: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Adolescent↗
PubMed2004

PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells.

Although increased circulating tumor antigen-specific CD8(+) T cells can be achieved by vaccination or adoptive transfer, tumor progression nonetheless often occurs through resistance to effector function. To develop a model for identifying mechanisms of resistance to antigen-specific CTLs, poorly immunogenic B16-F10 melanoma was transduced to express the K(b)-binding peptide SIYRYYGL as a green fluorescent protein fusion protein that should be recognized by high-affinity 2C TCR transgenic T cells. Although B16.SIY cells expressed high levels of antigen and were induced to express K(b) in response to IFN-gamma, they were poorly recognized by primed 2C/RAG2(-/-) T cells. A screen for candidate inhibitory ligands revealed elevated PD-L1/B7H-1 on IFN-gamma-treated B16-F10 cells and also on eight additional mouse tumors and seven human melanoma cell lines. Primed 2C/RAG2(-/-)/PD-1(-/-) T cells showed augmented cytokine production, proliferation, and cytolytic activity against tumor cells compared with wild-type 2C cells. This effect was reproduced with anti-PD-L1 antibody present during the effector phase but not during the priming culture. Adoptive transfer of 2C/RAG2(-/-)/PD-1(-/-) T cells in vivo caused tumor rejection under conditions in which wild-type 2C cells or CTLA-4-deficient 2C cells did not reject. Our results support interfering with PD-L1/PD-1 interactions to augment the effector function of tumor antigen-specific CD8(+) T cells in the tumor microenvironment.

Animals↗
PubMed2004

Effects of neck extensor muscles fatigue on balance.

OBJECTIVE: Measure the effects of cervical extensor muscle isometric contraction on cervical surface electromyographic spectral shift and balance in healthy subjects. DESIGN: Experimental within-subject design. BACKGROUND: Postural instability can be induced by mechanically stimulating cervical muscle spindles. Postural changes are also observed in individuals who suffer from chronic neck pain or whiplash injury. Furthermore these subjects appear to experience neck musculature fatigue more quickly, which in turn not only affects the neck function but also seems to affect the balance in a standing posture. METHODS: Using a force platform, balance was measured, in 10 blindfolded college students before and after isometric voluntary contraction in neck extension at 5% and 25% maximum voluntary isometric contraction for a period of 5, 10 and 15 min. Paired posturographic data were analysed for differences. Control measurements were performed on the same subjects by measuring balance before and after subjects sitting quietly for 5, 10 and 15 min without performing isometric contraction. RESULTS: The results indicate that a 25% maximal isometric contraction of the neck extensors for 10 and 15 min duration produced significant changes in some posturographic parameters in young healthy males. Furthermore, this contraction also produced a significant cervical muscle electromyography median frequency spectrum shift of the lower frequencies. CONCLUSIONS: Balance was affected by 15 min of 25% maximal isometric contraction of the extensor cervical muscles. Posturographic parameters affected are similar to parameters observed in subjects that have suffered a whiplash injury. RELEVANCE: This study contributes to our understanding of functional aspects of cervical muscle fatigue. The similarity of results with other studies performed on subjects suffering from chronic neck pain and from whiplash injuries may suggest a similar cause for loss of postural control. Ultimately, this may help us in developing objective evaluation procedures for subjects suffering from neck complaints.

Adult↗
PubMed2004

Restored immune response to an MHC-II-Restricted antigen in tumor-bearing hosts after elimination of regulatory T cells.

BACKGROUND/PURPOSE: Pediatric sarcomas have a poor prognosis, recur frequently, and are not effectively treated by currently available therapy. Immunotherapy is a promising treatment modality; however, to be successful, immune tolerance must be overcome. CD4+CD25+ T cells are immunosuppressive. The authors hypothesize that immune tolerance may be overcome by eliminating the regulatory CD4+CD25+ T cells, which are induced by tumor. METHODS: A murine fibrosarcoma (MF), which expresses an MHC-II-restricted tumor antigen (mL26), was injected subcutaneously. CD4+ T cells were isolated and CD25+ population examined. Monoclonal antibody was used to deplete CD25+ T cells. Proliferation to mL26 was used to determine CD4+ T cell response to tumor-associated antigen (TAA). RESULTS: Depletion of CD25+ cells prevented tumor establishment. Tumor-infiltrating CD25+ T cells, which made up 48% of CD4+ T cells in tumors, suppressed proliferation in allogeneic mixed lymphocyte reactions. Draining lymph node cells from tumor-bearing (TB) mice did not proliferate in response to mL26, whereas those from naive mice responded vigorously. Depletion of CD25+ cells before immunization restored response to mL26 in TB mice. CONCLUSIONS: CD4+CD25+ T cells induced by MF facilitate tumor establishment and maintain immune tolerance. Depletion of CD4+CD25+ T cells may be an effective means for reversing tumor tolerance and enhancing cancer vaccines.

Amino Acid Sequence↗