Clonal T cell responses reflect the expression of multiple DQ genes in cattle.
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Biomedical subjects
Publications and source records attributed to A Gallagher.
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OBJECTIVE: To determine the views of doctors and nurses about two recent innovations in the structure of case notes: the use of preprinted prompts and the use of joint medical and nursing notes. DESIGN: Questionnaire survey of all doctors and nurses working on the children's wards. SETTING: Children's wards in a district general hospital. MAIN OUTCOME MEASURES: Whether or not respondents wanted to return to traditional notes; positive and negative aspects of the two innovations. RESULTS: There was an 81% response rate. 45 of 48 respondents (94%) did not want to return to traditional notes. Positive features of joint notes that were identified included: promotes team work (21/48 respondents), improves access to information (14/48), and reduces duplication (14/48). Negative features included uncertainty about identity of writer (8/48) and incompletely filled in sheets (7/48). Positive features of preprinted prompts included: less information omitted (29/48), easier to read and find information (28/48), and quicker to write (21/48). Negative features included: not enough space (19/48) and clerking too mechanical (16/48). CONCLUSION: Advantages of both innovations outweighed their disadvantages to the extent that only three out of 48 respondents wanted to return to writing traditional notes.
RAS genes have been implicated in several different malignancies. The mechanism of activation in most cases has been due to point mutations at critical domains responsible for guanine nucleotide binding. These changes alter the conformation of the protein resulting in insensitivity of the protein to the GTPase activating protein which normally hydrolyses the active p21RAS GTP-bound form to the inactive GDP-bound form. RAS genes have potent effects on the differentiation and proliferation program of cells. The mechanism induced depends on the context in which RAS is found as well as its mutational status and indeed which RAS gene family member is involved. RAS mutations have been described early in the disease process in haematologically normal individuals at risk of mutations induced by either occupational hazard exposure, such as benzene, or of secondary disease after chemotherapy for a previous malignancy. It also been associated with disease progression from myelodysplasia (MDS) to acute myelogenous leukaemia (AML), but it has also been described to be lost upon disease progression, thus showing that RAS mutations are unlikely to be initiating events or at least not required for maintenance of disease. As RAS appears to be involved in primary and secondary myeloid leukaemias, it is a good candidate for gene targeted therapeutic intervention. Studies to target RAS either directly or indirectly by interfering in the RAS pathway are underway. Clinical trials with a peptide RAS vaccine are also ongoing in solid tumours. This report seeks to review the evidence for RAS involvement as oncogenes, focusing on MDS, the reasons as to why the hot spots of codons 12/13 and 61 are particularly potent in activating the transformation potential of RAS and the different approaches being undertaken to translate laboratory findings into therapeutic reality.
Protein glycosylation has an important influence on a broad range of molecular interactions in eukaryotes, but is comparatively rare in bacteria. Several antigens from Mycobacterium tuberculosis, the causative agent of human tuberculosis, have been identified as glycoproteins on the basis of lectin binding, or by detailed structural analysis. By production of a set of alkaline phosphatase (PhoA) hybrid proteins in a mycobacterial expression system, the peptide region required for glycosylation of the 19 kDa lipoprotein antigen from M.tuberculosis was defined. Mutagenesis of two threonine clusters within this region abolished lectin binding by PhoA hybrids and by the 19 kDa protein itself. Substitution of the threonine residues also resulted in generation of a series of smaller forms of the protein as a result of proteolysis. In a working model to account for these observations, we propose that the role of glycosylation is to regulate cleavage of a proteolytically sensitive linker region close to the acylated N-terminus of the protein.
A rhyming and short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca's area during the rhyming task, temporo-parietal cortex during the short- term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.
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The prediagnosis period of 74 children with primary brain tumours was assessed to examine their presentation and reasons for any delay in diagnosis. Medical case notes were reviewed and parents were interviewed and asked to complete psychological questionnaires. Mean (SD) duration of clinical history was 20.0 (29.1) weeks. Most common symptoms were vomiting (65%) and headache (64%). Only 34% of headaches were always associated with vomiting and only 28% occurred 'early morning'. Changes in the child's personality (47%) were also common. The average number of consultations before diagnosis was 4.6. Migraine was diagnosed in 24% of children and a psychological aetiology in 15%. One quarter of the children had altered levels of consciousness on arrival at the unit. Results indicate that delay in diagnosis still occurs, despite strong parental concern. The nonspecificity of symptoms and a high incidence of psychological symptoms may confound the clinical picture and are considered along with other possible contributory factors.
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Polymorphism of expressed bovine major histocompatibility complex (MHC) class II DQB genes was investigated in a group of nine MHC-homozygous Kenya Boran cattle (Bos indicus). DQB second exon fragments were amplified by reverse transcription-polymerase chain reaction of total mononuclear cell RNA, cloned and sequenced. While a single DQB sequence was obtained from some animals, two DQB exon 2 sequences were found in others, implying expression of duplicated DQB genes. Two pairs of duplicated DQB genes were found in this group of homozygotes, and sequence analysis showed that both pairs contained distinct DQB alleles. One DQB duplication was observed in two related animals with the same MHC haplotype (F100 and F188), while the second was detected in three animals (F187, G166 and G277) that expressed the same class II DRB3 and DQB alleles but had different class I (BoLA-A) types, suggesting that this DR/DQ haplotype may be widespread in Boran cattle.
In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.
Since the publication of Carol Gilligan's In a different voice in 1982, there has been much discussion about masculine and feminine approaches to ethics. It has been suggested that an ethics of care, or a feminine ethics, is more appropriate for nursing practice, which contrasts with the 'traditional, masculine' ethics of medicine. It has been suggested that Nel Noddings' version of an 'ethics of care' (or feminine ethics) is an appropriate model for nursing ethics. The 'four principles' approach has become a popular model for medical or health care ethics. It will be suggested in this article that, whilst Noddings presents an interesting analysis of caring and the caring relationship, this has limitations. Rather than acting as an alternative to the 'four principles' approach, the latter is necessary to provide a framework to structure thinking and decision-making in health care. Further, it will be suggested that ethical separatism (that is, one ethics for nurses and one for doctors) in health care is not a progressive step for nurses or doctors. Three recommendations are made: that we promote a health care ethics that incorporates what is valuable in a 'traditional, masculine ethics', the why (four principles approach) and an 'ethics of care', the 'how' (aspects of Noddings' work and that of Urban Walker); that we encourage nurses and doctors to participate in the 'shared learning' and discussion of ethics; and that our ethical language and concerns are common to all, not split into unhelpful dichotomies.
The RAS gene family encodes signal transducing proteins which are involved in the regulation of cell growth and differentiation. Constitutively 'activating' point mutations of RAS have been detected at high frequency in preleukaemia and acute leukaemia, however, the distribution of expression of p21RAS in normal or preleukaemic primary haematopoietic cells has not been studied. We have examined the expression of p21RAS and its negative regulator/downstream effector, p120GAP, in combination with lineage-specific cluster of differentiation markers in normal and preleukaemic myeloid bone marrow cells using flow cytometry. Normal bone marrow was characterized by low and uniform levels of p21RAS expression throughout all lineages analysed. In contrast, 28% (9/32) of patients with myelodysplastic syndrome (MDS) over-expressed p21RAS. In three of these patients a single over-expressing peak of p21RAS expression was observed, with no evidence of a population exhibiting expression within the normal range. In 6/32 MDS patients over-expression of p21RAS was observed only in a subpopulation of the myeloid cells. Follow-up samples were analysed in three of these six patients; over-expression was confirmed in each patient and in two patients a relative expansion of the over-expressing cell population was observed. Eight out of nine of the patients with aberrant p21RAS expression were diagnosed with low-risk MDS. From 21 MDS patients screened for p120GAP expression, no reduction or loss of expression was observed, however, one AML patient demonstrated a heterogeneous pattern of expression. p120GAP expression was lower (P < 0.05) in the AML group than in normals. The results of the study suggest that over-expression of the RAS gene product, p21RAS, may represent an alternative or additional mechanism of activation of the RAS signalling pathway and that this may play a role in leukaemogenesis, however, there is no evidence from this study that loss of p120GAP expression is a feature of myelodysplasia.