No abstract

Gold nanoparticles (AuNPs) provide excellent platforms for the development of colorimetric biosensors as they can be easily functionalised, displaying different colours depending on their size, shape and state of aggregation. In the last decade, a variety of biosensors have been developed to exploit the extent of colour changes as nano-particles (NPs) either aggregate or disperse, in the presence of analytes. Of critical importance to the design of these methods is that the behaviour of the systems has to be reproducible and predictable. Much has been accomplished in understanding the interactions between a variety of substrates and AuNPs, and how these interactions can be harnessed as colorimetric reporters in biosensors. However, despite these developments, only a few biosensors have been used in practice for the detection of analytes in biological samples. The transition from proof of concept to market biosensors requires extensive long-term reliability and shelf life testing, and modification of protocols and design features to make them safe and easy to use by the population at large. Developments in the next decade will see the adoption of user friendly biosensors for point-of-care and medical diagnosis as innovations are brought to improve the analytical performances and usability of the current designs. This review discusses the mechanisms, strategies, recent advances and perspectives for the use of AuNPs as colorimetric biosensors.

No abstract

No abstract

SummaryResting autoreactive T cells are present in the circulation ofnormal individuals without pathologic consequences . In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity . Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry . In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression ofB7-1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions ofvaried time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation ofMS involves upregulation o£ B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses .A utoimmune disease is presumably mediated by activated, autoantigen-reactive T cells (1-8) . Two distinct signals are required to induce differentiation of naive to activated, effector T cells : an antigen-specific signal mediated through the T cell receptor, and a second non-antigenspecific "costimulatory" signal (9, 10) . Interactions between CD28 and its counterreceptors, B7-1 (CD80) and B7-2 (CD86), are important T cell-costimulatory signals (11, 12) . Essentially all CD4 + and most CD8+ T cells express CD28 constitutively, and CD28-deficient T cells show a markedly reduced response to antigen stimulation (13) . A second ligand for B7 is CTLA-4, which is expressed on T cells after activation (14) and also may regulate T cell function (15) . The B7 molecules regulate IL-2 secretion and costimulate T cell proliferation (16)(17)(18) . Blocking of the B7-CD28 pathway in vitro results in T cell anergy (19-21) whereas in vivo blocking of the B7-CD28 pathway results in immunosuppression (22)(23)(24) .Aberrant expression of B7-costimulatory molecules is important in experimental autoimmune diabetes . Doubletransgenic mice with T cell receptors recognizing a viral antigen expressed on pancreatic islet cells do not develop diabetes . Triple-transgenic mice that additionally expressed B7-1 on pancreatic islet cells, however, developed massive tissue destruction and diabetes (25) . Moreover, double transgeni...

Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.

We previously have described a group of patients with gluten sensitivity presenting with ataxia (gluten ataxia) and suggested that this disease entity may account for a large number of patients with sporadic idiopathic ataxia. We have therefore investigated the prevalence of gluten sensitivity amongst a large cohort of patients with sporadic and familial ataxia and looked at possible genetic predisposition to gluten sensitivity amongst these groups. Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.

Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.