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Biomedical subjects

E Baxter

Publications and source records attributed to E Baxter.

At least 19 recordsLinked to original sources

Proviral insertions induce the expression of bone-specific isoforms of PEBP2alphaA (CBFA1): evidence for a new myc collaborating oncogene.

The til-1 locus was identified as a common retroviral integration site in virus-accelerated lymphomas of CD2-myc transgenic mice. We now show that viral insertions at til-1 lead to transcriptional activation of PEBP2alphaA (CBFA1), a transcription factor related to the Drosophila segmentation gene product, Runt. Insertions are upstream and in the opposite orientation to the gene and appear to activate a variant promoter that is normally silent in T cells. Activity of this promoter was detected in rodent osteogenic sarcoma cells and primary osteoblasts, implicating bone as the normal site of promoter activity. The isoforms encoded by the activated gene all encompass the conserved runt DNA-binding domain and share a novel N terminus different from the previously reported PEBP2alphaA products. Minor products include isoforms with internal deletions due to exon skipping and a novel C-terminal domain unrelated to known runt domain factors. The major isoform expressed from the activated til-1 locus (G1) was found to account for virtually all of the core binding factor activity in nuclear extracts from its corresponding lymphoma cell line. Another member of this gene family, AML1(CBFA2), is well known for its involvement in human hemopoietic tumors. These results provide evidence of a direct oncogenic role for PEBP2alphaA and indicate that the Myc and Runt family genes can cooperate in oncogenesis.

Amino Acid Sequence↗

Patients, caregivers, and managing care.

Providing care to patients who have Alzheimer's disease requires that professional care providers have an understanding not only of the disease and its progression, but also of informal caregivers, their roles, capabilities, and needs. Using experience from the Medicare Alzheimer's Demonstration Project and subsequent work of the Legacy Health System in Portland, OR, this paper reviews the perspectives of case managers and caregivers regarding a variety of strategies that have been implemented.

Alzheimer Disease↗

A supportive partnership for CAPD patients.

CAPD patient education is a continuous process. The renal training centre maintains close relationships with patients' community CAPD nurses. A high nurse/patient ratio allows time to deal with individual problems.

Clinical Competence↗

Assaults by patients: the experience and attitudes of psychiatric hospital nurses.

Four hundred and twenty-five nurses working in a 420 bed metropolitan psychiatric hospital were asked to complete a questionnaire about their experience of physical assault by patients and their attitude toward the problem. 61% returned the questionnaire. The overall mean annual rate of assault per nurse was 2.0, with student psychiatric nurses (mean 6.7) significantly more at risk than any other group. Nurses working in the psychogeriatric area reported more than double the rate of assaults reported by nurses working in rehabilitation services. 60% of respondents were female; there were very few sex differences in attitudes to assault. Overall, nurses reported a high tolerance for assault, although they recognised it as an experience that was often very traumatic psychologically. Views about managing assaultiveness differed widely, and this lack of consensus probably hinders the development of optimal strategies to deal with what is a major problem in many psychiatric units.

Adaptation, Psychological↗

Breastfeeding. Setting a standard: the challenge for health visiting.

Health visitors agree that breast is best. But how far is this principle translated into practice? Copious evidence exists of conflicting advice and views on breastfeeding among health professionals and even between health visitors themselves. Marianne Cowpe, Ann MacLachlan and Elizabeth Baxter describe how north east Fife health visitors drew up an agreed standard of practice to boost local breastfeeding rates.

Breast Feeding↗

Origin of segmental identity in the development of the leech nervous system.

The leech embryo develops its segmental body plan by means of a stereotyped cell lineage. Each hemilateral segment arises from a small set of embryonic blast cells via a comparable sequence of formative cell divisions, and for the most part, lineally homologous cells manifest similar patterns of differentiation in the various hemisegments. Nonetheless, some identified central neurons undergo segment-specific or laterally asymmetric patterns of neuropeptide expression and/or cell death. Certain aspects of this regional diversification result from competitive cell interactions which occur at the level of the postmitotic neuron. However, the neuron's segmental identity is lineally determined, being inherited from its blast cell progenitor over several intervening rounds of mitosis. To learn more about the molecular basis of this phenomenon, we have isolated and begun to characterize leech homeobox genes which are related to the genes that govern segmental identity in other organisms.

Amino Acid Sequence↗

Use of seclusion in a psychiatric intensive care unit.

OBJECTIVE: To evaluate the use in a psychiatric intensive care unit of a newly introduced seclusion room for the management of acutely disturbed and/or violent patients. METHOD: A specially designed seclusion chart was used to document fully events immediately before, during, and immediately after seclusion. Data from the charts over a 6-month period provided the basis for the study. RESULTS: The seclusion rate of about 2% of all admissions is less than that reported in the UK and the USA, suggesting that the facility is not used exclusively. Nursing staff welcomed seclusion as a means of reducing levels of dangerousness in the unit, but emphasized that it should be monitored carefully in order to prevent inappropriate use.

Clinical Protocols↗

Leucine metabolism as a source of acetate in the synthesis of hyaluronic acid.

Synovial fibroblasts were incubated in nutrient medium with either L-[U-14C]leucine or L-[4,5-3H]leucine to reveal peptides associated with hyaluronic acid. Isotope was found in hyaluronic acid extracted from culture medium by repeated density gradient ultracentrifugation, but 76-98% of the labelled hyaluronic acid fraction was recovered as oligosaccharide by Sephadex G-25 gel chromatography after digestion with protease-free staphylococcal hyaluronidase (EC 4.2.99.1). Radioactivity in acid digests of the oligosaccharide fractions (i) was volatile, (ii) separated similarly to acetate in Biogel P2 chromatography, and (iii) was identified as acetate by melting point after conjugation as a p-phenylphenacyl ester crystallized to constant specific activity. The synovial fibroblast thus possesses metabolic pathways for complete transformation of leucine to acetylCoA, which operate freely in adequate nutrient medium and are a significant source of acetyl groups in hyaluronic acid synthesis.

Acetates↗

Activation of human synovial cells by cholera enterotoxin: correlation of morphological responses with adenylate cyclase activities, and the reversing effects of hyaluronidase.

Previously described morphological changes in human synovial cell cultures due to cholera enterotoxin (CT) were studied in relation to activation of adenylate cyclase. A single pulse of CT at nanomolar concentration or less induced at least two-fold activation of adenylate cyclase, which persisted for 7 days or more. The enzyme hyaluronidase was found to cause a rapid reversal of the morphological effects of CT. There was also a reduction in adenylate cyclase activity but only with hyaluronidase concentrations greater than those required to produce maximum reversal of the CT-induced morphological changes. Removal of hyaluronidase was followed by reappearance of the CT-associated morphological effects and a slower reactivation of adenylate cyclase. The mechanism by which hyaluronidase produces the observed changes in synovial cells is not known, but might be related to the dispersal of hyaluronic acid gels bound to the surface of these cells.

Adenylyl Cyclases↗

Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit.

The plasma clearance, tissue distribution and metabolism of hyaluronic acid were studied with a high average molecular weight [3H]acetyl-labelled hyaluronic acid synthesized in synovial cell cultures. After intravenous injection in the rabbit the label disappeared from the plasma with a half-life of 2.5--4.5 min, which corresponds to a normal hyaluronic acid clearance of approx. 10 mg/day per kg body weight. Injection of unlabelled hyaluronic acid 15 min after the tracer failed to reverse its absorption. Clearance of labelled polymer was retarded by prior injection of excess unlabelled hyaluronic acid. The maximum clearance capacity was estimated in these circumstances to be about 30 mg/day per kg body wt. The injected material was concentrated in the liver and spleen. As much as 88% of the label was absorbed by the liver, where it was found almost entirely in non-parenchymal cells. Degradation was rapid and complete, since volatile material, presumably 3H2O, appeared in the plasma within 20 min. Undegraded [3H]hyaluronic acid, small labelled residues and 3H2O were detected in the liver, but there was little evidence of intermediate oligosaccharides. No metabolite except 3H2O was recognized in plasma or urine. Two-thirds of the radioactivity was retained in the body water 24 h later, and small amounts were found in liver lipids. Radioactivity did not decline in the spleen as rapidly as in the liver. The upper molecular weight limit for renal excretion was about 25 000. Renal excretion played a negligible part in clearance. It is concluded that hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver.

Animals↗

Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells.

In contrast with newly isolated cells or early primary cultures, synovial cell lines in standardised growth conditions assume a rather uniform fibroblast-like appearance. However, 2 distinct variations in the cytological pattern can be induced at this stage. The first is characterised primarily by increased numbers of small phase-dense organelles that show the distinctive fluorescence of lysosomes after supravital staining, and are interspersed with vacuoles. The associated functional changes include increased enzyme activity and decreased net synthesis of hyaluronic acid. This variation can be induced by exposure to indigestible neutral sugars, adenosine, or its 5' nucleotides. The second variation consists of a striking reorganisation of cytoplasm by condensation into dense ridges or a dendritic network of processes. It is accompanied by increased hyaluronic acid secretion and is induced by agents that enhance intracellular activity of cyclic adenosine monophosphate, such as dibutyryl cyclic adenosine monophosphate and cholera enterotoxin. It appears possible to direct differentiation in synovial cell lines to correspond at least in part with the presumed functions of the different cell types in the parent tissue. The 2 patterns may be useful markers to correlate with other aspects of synovial cell function in vitro.

Acetylglucosaminidase↗

Effects of carrageenin on human synovial cells in vitro: morphology, hyaluronic acid production, growth, and the lysosomal system.

Some in-vitro effects of the arthritogenic polysaccharide carrageenin were studied on cells from human synovium. Synovial cells were isolated from intact human knee joints, and cell lines were developed by passaging with trypsin. Carrageenin was ingested by the cells but did not significantly affect cell growth, numbers of lysosomes, intracellular lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase), or release of lysosomal enzyme from cells. Carrageenin produced a reduction in net hyaluronic acid synthesis. It also induced a striking morphological change in a high proportion of synovial cells, characterised by increased spreading over the culture surface and apparent condensation of the cytoplasm into a pattern of ridges. Nonrheumatoid and rheumatoid synovial cells behaved similarly to one another.

Acetylglucosaminidase↗

The nature of the protein moieties of cartilage proteoglycans of pig and ox.

Proteoglycans extracted with 4M-guanidinium chloride from pig laryngeal cartilage and bovine nasal septum were purified by density-gradient centrifugation in CsCl under 'associative' followed by 'dissociative' conditions [Hascall & Sajdera (1969) J. Biol. Chem. 244, 2384-2396]. Proteoglycans were then digested exhaustively with testicular hyaluronidase, which removed about 80% of the chondroitin sulphate. The hyaluronidase was purified until no proteolytic activity was detectable under the conditions used for digestion. The resulting 'core' proteins of both species were fractionated by a sequence of gel-chromatographic procedures which gave four major fractions of decreasing hydrodynamic size. Those that on electrophoresis penetrated 5.6% (w/v) polyacrylamide gels migrated as discrete bands whose mobility increased with decreasing hydrodynamic size. The unfractionated 'core' proteins had the same N-terminal amino acids as the intact proteoglycan, suggesting that no peptide bonds had been cleaved during hyaluronidase digestion. Alanine predominated as the N-terminal residue in all the fractions of both species. Fractions were analysed for amino acid, amino sugar, uronic acid and neutral sugar compositions. In pig 'core' proteins, the glutamic acid content increased significantly with hydrodynamic size, but in bovine 'core' proteins this trend was less marked. Significant differences in amino acid composition between fractions suggested that in each species there was more than one variety of proteoglycan. The molar proportions of xylose to serine destroyed on alkaline beta-elimination were equivalent in most fractions, indicating that the serine residues destroyed were attached to the terminal xylose of chondroitin sulphate chains. The ratio of serine residues to threonine residues destroyed on beta-elimination, was similar in all fractions of both species. Since the fractions of smallest hydrodynamic size contained less keratan sulphate than those of larger size, it implies that in the former the keratan sulphate chains were shorter than in the latter.

Amino Acids↗