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J Spencer

Publications and source records attributed to J Spencer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Motion processing in autism: evidence for a dorsal stream deficiency.

We report that motion coherence thresholds in children with autism are significantly higher than in matched controls. No corresponding difference in form coherence thresholds was found. We interpret this as a specific deficit in dorsal stream function in autism. To examine the possibility of a neural basis for the perceptual and motor related abnormalities frequently cited in autism we tested 23 children diagnosed with autistic disorder, on two tasks specific to dorsal and ventral cortical stream functions. The results provide evidence that autistic individuals have a specific impairment in dorsal stream functioning. We conclude that autism may have common features with other developmental disorders and with early stages of normal development, perhaps reflecting a greater vulnerability of the dorsal system.

Adult↗
PubMed2000

Immunohistochemical analysis of ageing human B and T cell populations reveals an age-related decline of CD8 T cells in spleen but not gut-associated lymphoid tissue (GALT).

It is thought that senescence of the immune system is responsible, at least in part, for many health problems associated with ageing. Previous studies on changes in lymphocyte composition have used flow cytometry to study peripheral blood lymphocytes (PBL's), or cells isolated from rodent tissue, and have yielded conflicting results. We have used immunohistochemistry to determine whether the B and T cells in human tissue from spleen and gut are affected by age. Areas of germinal centre, mantle zone and marginal zone of B cell follicles were measured. In addition, CD4 and CD8 T cells in T cell areas and in B cell follicles were counted. We observed a striking age-related decrease in the proportion of CD8+ T cells in the T cell zones of the spleen. This decrease was not apparent in the T cell population that occupies splenic B cell areas, or in GALT. Further differences, in CD4+ cells, were seen between T cell populations in the T cell zones and those in B cell areas. These findings highlight differences between lymphocyte populations in different lymphoid tissues, and different compartments within each tissue, which may be of importance in future studies of the ageing immune system.

Adolescent↗
PubMed2000

Characteristics of human IgA and IgM genes used by plasma cells in the salivary gland resemble those used in duodenum but not those used in the spleen.

Immunologically, the parotid salivary gland is an effector site that secretes large quantities of polyspecific Abs into the saliva, mainly of the IgA isotype. It is considered to be part of the common mucosal immune system but the inductive site for the Ab-producing cells of the salivary gland has not yet been clearly identified. The origin and diversity of cells of B lineage can be investigated by analyzing their Ig heavy chain genes (IgH). We have obtained sequences of IgM and IgA VH4-34 genes from plasma cells in human salivary gland, duodenal lamina propria, and splenic red pulp. Related sequences were found in different areas sampled within each tissue studied, indicating that the plasma cells carrying these genes are widespread with limited diversity. Examples of related IgH genes that are isotype switched were also seen in the salivary gland. The genes from plasma cells of the salivary gland were highly mutated, as were duodenal plasma cell sequences. The level of mutation was significantly higher than that seen in splenic plasma cell sequences. Analysis of CDR3 regions showed that the sequences from salivary gland had significantly smaller CDR3 regions than sequences from spleen, due to differences in number and type of DH regions used. Sequences from duodenum also had smaller CDR3 regions. Therefore, plasma cells from human duodenum and salivary gland showed characteristics that differed from those of human splenic plasma cells.

Base Sequence↗
PubMed2000

Sequence analysis of light chain genes from human intestinal plasma cells demonstrates that lambda genes are almost all in-frame and highly mutated and most kappa genes are highly mutated when in-frame and minimally mutated when out-of-frame.

Around 80 % of immunoglobulin (Ig)-producing cells in man are located in the gut, with a preponderance of IgA- and IgM-producing cells that express heavily mutated IgVH genes. Here we describe the characteristics of Ig light chain genes isolated from human ileal and colonic lamina propria plasma cells. We focused on the properties of the two most commonly used light chain families, Vkappa1 and Vlambda2. Out-of-frame lambda rearrangements were very rare, suggesting that these lambda light chains may have undergone sequential rearrangements until successful conformation was achieved. This has not been observed in the human peripheral B cell population. The in-frame lambda gene rearrangements were highly mutated, with a frequency of mutation that was indistinguishable from that observed in many groups of heavy chain variable regions used by intestinal plasma cells. The in-frame kappac chain rearrangements were also highly mutated, but contained a subgroup of genes (27.3 %) that showed over 98 % homology with the germ-line gene. The majority of unused kappa chain genes were unmutated. A strong tendency for preferential mutation of G over C nucleotides was observed. Detailed analysis of the sequences in which the biases were observed suggested that this was likely to be due to selection, rather than a characteristic of the mechanism introducing the mutations.

Aged↗
PubMed2000

Ligation of alpha4ss1 integrin on human intestinal mucosal mesenchymal cells selectively Up-regulates membrane type-1 matrix metalloproteinase and confers a migratory phenotype.

Human intestinal lamina propria mesenchymal cells show high surface expression of the alpha4ss1 integrin. Ligation of alpha4ss1 on mesenchymal cell lines with an activating monoclonal anti-alpha4 antibody or vascular cell adhesion molecule-immunoglobulin (VCAM-IgG) leads to the appearance of activated forms of gelatinase A in culture supernatants, and the de novo expression of activated membrane type-1-matrix metalloproteinase (MT1-MMP). In functional assays, signaling through alpha4ss1 results in an increased capacity of mesenchymal cells to migrate through an artificial extracellular matrix, an effect inhibitable by excess tissue inhibitor of metalloproteinase-2. In organ cultures of human intestine, VCAM-IgG also up-regulates MT1-MMP, and in mucosal ulcers of inflammatory bowel disease patients, MT1-MMP transcripts are abundant, coincident with expression of VCAM-1 on cells at the ulcer margin. Collectively these results suggest that alpha4ss1-induced up-regulation of MT1-MMP may be a crucial factor in the migration of mesenchymal cells into ulcer beds during restitution of diseased gut mucosa.

Antibodies↗
PubMed2000

Clarifying the concepts of confidence and competence to produce appropriate self-evaluation measurement scales.

INTRODUCTION: This paper reviews the literature on self-evaluation and discusses the findings of a small-scale qualitative study which explored the terms 'confidence' and 'competence' as useful measures in a self-evaluation scale. Four pre-registration house officers took part in interviews and completed a provisional instrument to assess their perceived competence. FINDINGS: Competence and confidence are useful terms for house officers expressing beliefs about their ability to perform their job but the terms should not be used synonymously. In our study, 'competent' represented what individuals knew about their ability and was based on the individual's previous experience of the task. 'Confident' described a judgement which influenced whether an individual was willing or not to undertake an activity. Confidence was not necessarily based on known levels of competence and therefore performance of tasks which were unfamiliar to the house officer also involved the assessment of risk. The authors give examples of task and skill scales which may be useful in the process of self-evaluation by pre-registration house officers. CONCLUSIONS: The authors suggest that the process of assessing oneself is complicated, and by its very nature can never be objective or free from the beliefs and values individuals hold about themselves. Therefore self-evaluation instruments are best used to help individuals analyse their work practices and to promote reflection on performance. They should not be used to judge the 'accuracy' of the individual's evaluation.

Attitude↗
PubMed2000

Patient-oriented learning: a review of the role of the patient in the education of medical students.

AIM: To explore the contribution patients can make to medical education from both theoretical and empirical perspectives, to describe a framework for reviewing and monitoring patient involvement in specific educational situations and to generate suggestions for further research. METHODS: Literature review. RESULTS: Direct contact with patients can be seen to play a crucial role in the development of clinical reasoning, communication skills, professional attitudes and empathy. It also motivates through promoting relevance and providing context. Few studies have explored this area, including effects on the patients themselves, although there are examples of good practice in promoting more active participation. CONCLUSION: The Cambridge framework is a tool for evaluating the involvement of patients in the educational process, which could be used by curriculum planners and teachers to review and monitor the extent to which patients are actively involved. Areas for further research include looking at the 'added value' of using real, as opposed to simulated, patients; more work on outcomes for patients (other than satisfaction); the role of real patients in assessment; and the strengths and weaknesses of different models of patient involvement.

Clinical Competence↗
PubMed2000

Heartlift.

Explore the source record for details and available documents.

Anecdotes as Topic↗
PubMed2000

Immunohistochemical analysis of human CD5 positive B cells: mantle cells and mantle cell lymphoma are not equivalent in terms of CD5 expression.

CD5 is expressed by most T cells and a subset of B cells. Human CD5 positive B cells are present in fetal lymphoid tissue, their frequency decreasing with fetal age. In adult human tissues, CD5 positive B cells have been reported to be present in the germinal centre and mantle zone. Malignancies of CD5 positive B cells include mantle cell lymphoma and chronic lymphocytic leukemia. This report describes an immunohistochemical staining technique used to visualise the expression of CD5 by B cells in human fetal intestine, tonsil, and mantle cell lymphoma. B cells in fetal intestine, tonsillar epithelium, and mantle cell lymphoma all had a similar high intensity of CD5 expression. In contrast, CD5 B cells in the mantle and germinal centre expressed very small amounts of CD5, below the threshold of the technique. Therefore, mantle cells and mantle cell lymphoma are not equivalent in terms of CD5 expression.

Adult↗
PubMed1999

Characteristics of sequences around individual nucleotide substitutions in IgVH genes suggest different GC and AT mutators.

Somatic hypermutation affects Ig genes during T-dependent B cell responses and is characterized by a high frequency of single base substitutions. Hypermutation is not a completely random process; a study of mutations in different systems has revealed the presence of sequence motifs that target mutation. In a recent analysis of the sequences surrounding individual mutated bases in out-of-frame human IgVH genes, we found that the target motifs around mutated G's and C's are reverse complements of each other. This finding suggests that hypermutation acts on both strands of DNA, which contradicts evidence of a strand-dependent mechanism as suggested by an observed bias in A and T mutations and the involvement of transcriptional machinery. We have now extended our database of out-of-frame genes and determined the sequence motifs flanking mutated A and T nucleotides. In addition, we have analyzed the flanking sequences for different types of nucleotide substitutions separately. Our results confirm the relationship between the motifs for G and C mutations and show that the motifs surrounding mutated A's and T's are weaker and do not have the same relationship. Taken together with our observation of A/T strand bias in out-of-frame genes, this observation suggests that there is a semitargeted G/C mutator that is strand-independent and a separate A/T mutator that is strand-dependent and is less reliant on the local target sequence.

Adenine↗
PubMed1999

Human tonsillar germinal center T cells are a diverse and widely disseminated population.

Germinal center (GC) T cells are a poorly investigated population with a unique helper-inducer memory phenotype. Murine GC T cells have been demonstrated to be oligoclonal and antigen specific. The aim of this study was to investigate the diversity of human tonsillar GC T cells. Immunohistochemistry with a panel of different TCRVbeta family antibodies and sequencing of TCRgamma gene rearrangements obtained from individual microdissected GC demonstrated local diversity of human tonsillar GC T cells. No evidence of local clonal dominance or of a local migratory pathway from the T cell zone to adjacent GC was seen. Primers specific to the junctional region of the TCRgamma gene of individual GC T cell clones were designed, and used to trace the dissemination of the clones. One was found to be concentrated locally. Both clones studied were present in both of the patient's tonsils, suggesting widespread dissemination. In addition, no evidence of somatic hypermutation was found in the TCRgamma gene sequences, or in expressed TCRalpha and beta gene sequences obtained by reverse transcriptase-PCR from isolated tonsillar GC.

Child↗