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Biomedical subjects

J Reed

Publications and source records attributed to J Reed.

At least 73 records · Page 4Linked to original sources

Structure of the LAV6 peptide: a nucleation site for the correct receptor-induced refolding of the CD4-binding domain of HIV1 gp 120.

LAV44 and LAV15 (lymphadenopathy-associated virus) peptides of the CD4-binding region of gp 120 per se bind to the CD4 receptor (Reed and Kinzel, Biochemistry 30: 4521-4528, 1991; Lasky et al., Cell 50:975-985, 1987). Depending on the environment, the LAV peptides exhibit the ability to switch cooperatively between beta-sheet and helical conformation when solvent polarity is changed past a critical point. This property, which is dependent on the amino acid sequence LPCR, is crucial for receptor binding (Reed and Kinzel, Proc. Natl. Acad. Sci. U.S.A. 90:6761-6765, 1993). Structure determination with 2D-NMR-spectroscopy reveals that LAV6 peptide (sequence: TLPCRI) has a well-defined structure, partially exhibiting inverse gamma-turn conformation in aqueous solution. Quantitative evaluation of the NMR data discloses 90% trans-conformation for the peptide bond between leucine and proline. The psi- and phi-angles fall into the typical range for amino acids located in turns. On the other hand, the amino acid sequence C-terminal to the LPCR tetrad has been shown to fold atypically in the absence of these residues. All these results show that the short sequence of LAV6 peptide, with the central amino acids LPCR, displays a matrix-independent structure and may, therefore, act as a conformational template for forming secondary structure in the intact CD4-binding domain of gp 120.

CD4 Antigens↗

Distribution of prohormone convertase-6 expression in the gastrointestinal tract and effects of a fasting-refeeding regimen and a high-fat diet on ileal prohormone convertase-6 expression.

Proforms of gastrointestinal peptide hormones and neuropeptides are processed, in part, by prohormone convertases (PCs) to mature, biologically active peptides. The purpose of this study was to characterize the mRNA levels of PC-6 isoforms, PC-6A and PC-6B, in the gastrointestinal tract and pancreas of the rat, and to investigate the effects of a fasting and refeeding regimen, and a high-fat diet on ileal PC-6A expression. PC-6A mRNA is expressed throughout the entire gastrointestinal tract with the highest levels in the small intestine. Multiple-sized transcripts are present. PC-6B mRNA is expressed in the antrum and fundus of the stomach, in the small intestine, and colon. Ileal PC-6A mRNA expression increases significantly with fasting and then declines with refeeding toward control levels. Increased dietary fat increases PC-6A mRNA levels in the ileum. Since PC-6 is found throughout the entire gastrointestinal tract, it is likely that PC-6 participates in the processing of proforms of gastrointestinal peptides. The two isoforms of PC-6 have different patterns of distribution in the gastrointestinal tract and pancreas, suggesting that they process proforms of different gut peptides.

Animals↗

Focus groups: issues of analysis and interpretation.

Focus groups have become a popular method in nursing research. Their history can be traced back to marketing research methods, but they have also been used in qualitative, ethnographic research. Our study, which used this approach as part of data collection, raised many issues of analysis and interpretation: in particular, the importance of paying attention to the sequence of focus group discussions, the individuals involved, and the social context of the focus group. We conclude that focus groups are not a 'quick and easy' method of collecting data, and that issues of validity and the relationship between focus group data and other data require careful consideration.

Aged↗

Moving from hospital into a care home--the nurse's role in supporting older people.

Discharge planning has received much attention in the nursing literature over the past few years, and there has been particular concern over the discharge of older people back into their domestic environment. The practical and logistical problems of managing such a discharge are considerable, but in this paper we argue that discharging older people from hospital to care homes is equally problematic, though in different ways. This is a neglected area of research, perhaps because discharge into a care home seems to present fewer organizational problems. There is, however, an extensive body of literature from a range of different disciplines which suggests that the loss of home and entry into a strange environment can be very stressful. This paper outlines this literature and explores the implications for nursing practice.

Aged↗

From seed germination to flowering, light controls plant development via the pigment phytochrome.

Plant growth and development are regulated by interactions between the environment and endogenous developmental programs. Of the various environmental factors controlling plant development, light plays an especially important role, in photosynthesis, in seasonal and diurnal time sensing, and as a cue for altering developmental pattern. Recently, several laboratories have devised a variety of genetic screens using Arabidopsis thaliana to dissect the signal transduction pathways of the various photoreceptor systems. Genetic analysis demonstrates that light responses are not simply endpoints of linear signal transduction pathways but are the result of the integration of information from a variety of photoreceptors through a complex network of interacting signaling components. These signaling components include the red/far-red light receptors, phytochromes, at least one blue light receptor, and negative regulatory genes (DET, COP, and FUS) that act downstream from the photoreceptors in the nucleus. In addition, a steroid hormone, brassinolide, also plays a role in light-regulated development and gene expression in Arabidopsis. These molecular and genetic data are allowing us to construct models of the mechanisms by which light controls development and gene expression in Arabidopsis. In the future, this knowledge can be used as a framework for understanding how all land plants respond to changes in their environment.

Germination↗

Co-localization of the TSC2 product tuberin with its target Rap1 in the Golgi apparatus.

Tuberin is the protein product of the tuberous sclerosis-2 (TSC2) gene, which is associated with tuberous sclerosis (TSC), a human genetic syndrome characterized by the development of tumors in a variety of tissues. We have previously shown that tuberin is a widely expressed 180 kDa protein which exhibits specific GTPase activating activity in vitro towards the Ras-related Rap1 protein. In this study we have used affinity-purified antibodies against tuberin to analyse its expression in human and rat tissues and to examine its subcellular localization. Tuberin expression was detected in all adult human tissues tested, with the highest levels found in brain, heart and kidney, organs that are commonly affected in TSC patients. By contrast, in adult rats the highest levels of tuberin were found in brain, liver and testis. Indirect immunofluorescence of tuberin in various cultured cell lines revealed a punctate, mostly perinuclear staining pattern. Double-indirect immunofluorescence analysis with anti-tuberin sera and antisera against known Golgi markers (mannosidase-II and furin) revealed that the staining of tuberin was consistent with its localization in the stacks of the Golgi apparatus. In support of this, treatment of cells with brefeldin A, a drug known to cause disassembly of the Golgi apparatus, abolished the perinuclear staining of tuberin. Moreover, conventional and confocal immunofluorescence demonstrated co-localization of tuberin with Rap1, which has previously been localized to the Golgi apparatus. The co-localization of tuberin and Rap1 in vivo strengthens the likelihood that the in vitro catalytic activity of tuberin toward Rap1 plays a physiologically relevant role in the tumor suppressor function of tuberin.

Animals↗

Extension of the polarity-dependent "switch phenomenon" of the gp120 binding domain as a target for antiviral chemotherapy.

A 15-residue fragment within the major continuous domain of gp120 from HIV-1 that can bind independently to the CD4 receptor has been shown to have the property of behaving as a solvent polarity-dependent conformational switch. The switch behavior (cooperative transition from beta-sheet to helical conformation as a function of solvent polarity), which is conserved among strains with the widest sequence variability possible, appears to be a prerequisite for the CD4-binding ability. A number of switch inhibitors have been identified that destroy the conformational switch in the 15-residue fragment and concurrently its ability to bind to CD4-expressing cells. It can now be shown that the switch behavior and its inhibition by substances with certain shared structural characteristics are not restricted to the 15-residue subfragment, but are reflected by the behavior of the entire 44-residue binding domain. Further, substances active as switch inhibitors have an immediate effect on the conformation of the 44-residue fragment in aqueous buffer whereas inactive substances do not. The predictive value of this as a screening method is demonstrated in testing a number of new potential switch inhibitory compounds.

Amino Acid Sequence↗

Retinoblastoma protein in human breast carcinoma: immunohistochemical study using a new monoclonal antibody effective on routinely processed tissues.

Cyclic phosphorylation/dephosphorylation of the retinoblastoma gene product (pRB) has been found to play a central role in the progression of the normal cell cycle, through modulation of the activity of the E2F family of transcription factors. Mutations of the retinoblastoma gene have been described in a wide variety of human malignancies including carcinomas of the breast. The present investigation reports the production and application of a new monoclonal antibody in an immunohistochemical study of pRB expression in 233 primary breast carcinomas, allowing an assessment of the contribution made by this tumour suppressor gene to tumour development and progression. Overall, there was loss of pRB expression in 21 per cent of breast tumours. Although high-grade tumours were found to lack detectable pRB more frequently than low-grade tumours, the difference did not prove statistically significant. In addition, pRB immunostaining was not related significantly to relapse or survival. No significant correlations were observed between apparent loss of pRB and tumour size, parity, patient lymph-node status, p53, c-erbB-2, c-jun, EGFR or steroid hormone receptor expression. Preliminary findings, however, did suggest a relationship between pRB expression and response to endocrine therapy.

Adult↗

Differentiation of alpha coma from awake alpha by nonlinear dynamics of electroencephalography.

The electroencephalogram, as a probe of scalp-recorded electrical activity arising from the human cortex, provides useful information because of its temporal and spatial organization. Recent developments in nonlinear dynamics suggest that an object can be constructed in an n-dimensional space out of a temporal sequence of data such as an EEG signal and that its organization is characterized by the dimensionality of the object (in this case, human brain activity). We have carried out an analysis of a set of alpha coma EEG patterns in comparison to the awake alpha EEG patterns of normal volunteers and patients. Alpha coma recorded from a single channel is visually indistinguishable from normal resting alpha due to its similar frequency spectrum (a broad-band spectrum with 1/f characteristics). Our results show that alpha coma dimensionality, however, differs from that of normal alpha in that it has a greater variability over different temporal segments of EEG. Single channel recordings in 7 patients with alpha coma were differentiable from those of 10 subjects with "normal" EEGs. Through dynamic analysis of the EEG, novel methods of signal extraction from EEG may become evident and applicable to clinical practice.

Adult↗

Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography.

OBJECTIVES: This investigation sought to determine the relative prognostic value of coronary calcific deposits and coronary angiographic findings for predicting coronary heart disease-related events in patients referred for angiography. BACKGROUND: The relation among coronary calcification, coronary stenoses and coronary heart disease-related events is of interest on a clinical as well as a pathophysiologic basis. METHODS: Four hundred ninety-one symptomatic patients underwent coronary angiography and electron beam computed tomography at five different centers between April 1989 and December 1993. The electron beam computed tomograms were interpreted by a cardiologist with no knowledge of the coronary angiographic and clinical data. Receiver operating characteristic (ROC) curves were constructed to determine the relation between electron beam computed tomographic and coronary angiographic findings. A follow-up telephone survey was completed in 86% of patients. The records for all patients who died or were admitted to the hospital for chest pain or suspected myocardial infarction were reviewed by three other cardiologists with no knowledge of the coronary angiographic and electron beam computed tomographic study results. RESULTS: The mean (+/- SE) area under the ROC curve was 0.75 +/- 0.02 for the coronary calcium score, indicating moderate discriminatory power for this score for predicting angiographic findings. Thirteen coronary heart disease-related deaths and eight nonfatal acute infarctions occurred over 30 +/- 13 months. Scores were sorted in ascending order and divided into quartiles of equal size. One patient in the first quartile had a fatal myocardial infarction (coronary calcium score range 0 to 2.1); 2 in the second quartile (range 2.1 to 75.3), 8 in the third quartile (range 75.3 to 397.1) and 10 in the fourth quartile (> 397.1) had a coronary heart disease-related event. Application of bivariate logistic regression showed that log score but not number of angiographically diseased vessels significantly predicted the probability of a coronary heart disease-related event occurring during follow-up. CONCLUSIONS: Electron beam computed tomographic calcium scores correlate moderately well with angiographic findings. These scores predict coronary heart disease-related events in patients undergoing angiography as well as do the number of angiographically affected arteries.

Calcinosis↗

An investigation of the components used to calculate staff:student ratios in nursing and midwifery education.

This article describes the results of a census questionnaire sent to all colleges of nursing and midwifery and institutions of further and higher education undertaking English National Board for Nursing, Midwifery and Health Visiting (ENB) validated pre- and post-registration nursing and midwifery courses. The questionnaire was designed to identify the range of components, incorporated into formulae, used by the colleges and institutions to calculate staff:student ratios (SSRs), for each type of course. The results indicate that the majority of colleges and institutions use: [formula: see text] The definitions of staff and student within the formulae were either assumed or variously defined. A total of 17 different formulae for calculating SSRs were identified and 10 different formulae for calculating whole time equivalents. Each of these formulae are given in the article. The advantages and disadvantages for resourcing nurse education arising from the lack of definition surrounding the standardisation of formulae and the components within formulae are discussed. The discussion reflects both the responses given in the open-ended questions in the questionnaire and the debates surrounding the use of SSRs highlighted in the literature.

Education, Nursing, Baccalaureate↗

Solid phase synthesis of two phosphorylated peptides related to casein using allyl phosphate protection, and their CD spectra.

Phosphoserine peptides related to the casein kinase II substrate consensus sequence ESLSSSEE have been synthesized using N-Boc-O-diallylphosphono-L-serine by solid-phase methods. The allyl groups were removed, while the peptide was still attached to the solid support, by Pd0 with azide as the nucleophile. Far UV circular dichroism measurements indicate that peptides phosphorylated at Ser 4 or Ser 5 have a somewhat higher content of ordered structure than the non-phosphorylated peptide.

Allyl Compounds↗