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Biomedical subjects

G M Barton

Publications and source records attributed to G M Barton.

At least 19 recordsLinked to original sources
PubMed2002

Toll-like receptors and their ligands.

The Toll-like receptors (TLRs) are key molecules involved in the recognition of pathogens by the innate immune system. This family of germ line-encoded receptors has evolved to recognize conserved features of microbes. Currently, 10 TLR family members have been identified in mammals. The number of ligands for these receptors continues to grow, and it seems clear that multiple ligands exist for each receptor. Whether engagement of different TLRs leads to differences in gene expression and thereby differences in the immune response remains to be seen. However, recent work has demonstrated that activation of TLRs is required for initiation of only certain adaptive immune responses.

Animals↗
PubMed2001

Dynamic tuning of T cell reactivity by self-peptide-major histocompatibility complex ligands.

Intrathymic self-peptide-major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4(+)CD8(+) thymocytes. By analyzing the development of MHC class II-restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide-MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.

Animals↗
PubMed2001

TIRAP: an adapter molecule in the Toll signaling pathway.

Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial metabolism and activate NF-kappa B and other signaling pathways through the adapter protein MyD88. Although some cellular responses are completely abolished in MyD88-deficient mice, TLR4, but not TLR9, can activate NF-kappa B and mitogen-activated protein kinases and induce dendritic cell maturation in the absence of MyD88. These differences suggest that another adapter must exist that can mediate MyD88-independent signaling in response to TLR4 ligation. We have identified and characterized a Toll-interleukin 1 receptor (TIR) domain-containing adapter protein (TIRAP) and have shown that it controls activation of MyD88-independent signaling pathways downstream of TLR4. We have also shown that the double-stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and MyD88-dependent signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Toll-like receptors control activation of adaptive immune responses.

Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Private psychiatric practice in an era of managed care.

Managed care is a given for private practice right now. It is important to develop a practice you can be proud of and be comfortable to work in by practicing ethically, with high standards for quality. Be persistent in expecting the same from the managed care companies, your colleagues, and your patients. Solid clinical and business principles are the backbone of private practice.

Attitude of Health Personnel↗
PubMed1999

Requirement for diverse, low-abundance peptides in positive selection of T cells.

Whether a single major histocompatibility complex (MHC)-bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide-MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.

Animals↗
PubMed1999

Evaluating peptide repertoires within the context of thymocyte development.

The process of antigen presentation by MHC molecules allows T cells to sample the proteins expressed within a particular cell. This sampling is in the form of short peptides bound within the grooves of MHC molecules displayed on the surface of cells. In the context of immune surveillance, this presentation allows the identification of infected cells by displaying peptides originating from foreign proteins within the cell. However, MHC-bound peptides play additional roles beyond serving as antigenic stimuli during an immune response. In fact, it has become clear that MHC-bound peptides derived from self proteins are critically involved in the development of T cells during selective events in the thymus. In this review we will discuss the nature of the population of MHC-bound peptides as it relates to thymocyte development, with particular emphasis on the recent finding that peptide-MHC complexes present at low levels can drive the positive selection of thymocytes.

Animals↗
PubMed1998

An altered invariant chain protein with an antigenic peptide in place of CLIP forms SDS-stable complexes with class II alphabeta dimers and facilitates highly efficient peptide loading.

We report an experimental system for abundant expression of specific peptide-class II complexes in vivo and in vitro. We have constructed a cassette which allows for the replacement of the CLIP region of invariant chain (Ii) with an antigenic peptide. In fibroblasts expressing an altered Ii protein, in which CLIP has been replaced with peptide 52-68 from the class II I-E alpha chain (pEalpha), pEalpha-I-Ab complexes are formed with high efficiency. This peptide loading occurs in the endoplasmic reticulum (ER) when the Ii:pEalpha fusion protein associates with the I-Ab alpha and beta chains. The trimeric complexes of Ii:pEalpha and I-Ab molecules are stable in SDS and can be detected by the pEalpha-I-Ab-specific mAb, YAe, indicating that pEalpha is bound in the class II groove in the context of full-length Ii. These data strongly suggest that the CLIP region of intact Ii prevents peptide loading in the ER by binding in the peptide binding groove of newly synthesized class II alphabeta dimers.

Amino Acid Sequence↗
PubMed1991

Gastric villous adenoma: radiologic features.

The high incidence of malignant transformation of gastric villous adenoma requires prompt diagnosis of this rare tumor. We have reported the case of such a tumor in a 29-year-old man. The radiologic appearance of a gastric soft tissue mass with a reticular pattern is highly diagnostic.

Adenoma↗
PubMed1988

Combined Escherichia coli and Staphylococcus aureus thyroid abscess in an asymptomatic man.

Patients with acute suppurative thyroiditis usually have pain or tenderness in the anterior part of the neck associated with erythema and dysphagia. An elderly man with none of these symptoms presented with fever and a urinary tract infection. When his systemic infection failed to respond to antibiotics, a search for an occult abscess was undertaken. An 111Indium leukocyte scan indicated a localized abscess in the right lobe of his thyroid from which Escherichia coli and Staphylococcus aureus coagulase positive were isolated. This case demonstrates that a thyroid abscess can occur in a completely asymptomatic patient without a clinically enlarged thyroid.

Abscess↗
PubMed1976

Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.

Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.

Antipsychotic Agents↗
PubMed1976

Group care for psychiatric patients.

The family physician and one or two office staff members or associates can conveniently and effectively provide ongoing care for a large group of reasonably stable, yet severely disturbed, psychiatric patients. The main goal is to promote successful integration into meaningful family and community relationships. In many cases, the family physician is the most appropriate health professional to provide this care, due to his knowledge of the patient's family, community situation and physical health.

Family Therapy↗