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PubMed1983

Reconstitution of a functional beta-adrenergic receptor using cholate and a novel method for its functional assay.

Solubilization of purified turkey erythrocyte membranes at increasing cholate to protein ratios and in the presence of salt, extracts up to 20% of the beta-adrenergic receptor together with the GTP stimulatory protein (Ns) of adenylate cyclase. Upon removal of the cholate, by active absorption on Bio-beads, the functional interaction between the beta-receptor and the GTP regulatory protein Ns is quantitatively restored. The receptor (R) in the presence of l-isoproterenol and p[NH]ppG is able to catalyze the activation of Ns to its permanently active state, N's p[NH]ppG, with a rate constant (kon) identical to that of the native membrane. Reconstitution of the R/Ns mixture using poly(ethyleneglycol)-6000 restores the receptor binding properties as effectively as SM-2 Bio-beads. Unlike SM-2 Bio-beads, however, poly(ethyleneglycol) is not as efficient in restoring the R to Ns functional coupling. In this communication we also report on the ability to monitor quantitatively N's . p[NH]ppG, using native turkey erythrocyte membranes in the presence of Lubrol-PX as the source of the catalytic unit (c) of adenylate cyclase. The latter method is as efficient as using S49 AC- lymphoma cell membranes but much less expensive. Using this technique, we also demonstrate that when the Ns to C interaction is nullified, employing treatment with N-ethylmaleimide, the parameters which characterize R to Ns coupling remain unchanged.

Adenylyl Cyclases↗

PubMed1998

Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific Working Party on Functional Dyspepsia.

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2-4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.

Antiemetics↗

PubMed2006

Residual renal function and dialysis modality: is it really beneficial to preserve residual renal function in dialysis patients?

Residual renal function (RRF) contributes to the achievement of treatment adequacy in stage 5 chronic kidney disease (CKD-5) patients. It may facilitate patients' acceptance of renal replacement therapy (RRT) in allowing reduction of treatment time duration and minimising dietary and fluid restriction. It has been confirmed to improve dialysis patient outcomes. Attempts to preserve RRF in incident Stage 5 chronic kidney disease patients are still subject to intense controversies in the nephrology community. The aim of this review is to analyse the role of renal replacement modalities in the maintenance of RRF in dialysis patients. Under the scope of this manuscript, four questions are explored: Is the preservation of residual renal function an objective for dialysis adequacy? Does dialysis modality affect the decline of RRF? What are the factors implicated by this loss of RRF? At what expense can the maintenance of RRF be achieved in dialysis patients? Preservation of RRF is undoubtedly an interesting means to enhance the efficacy of renal replacement therapy and reduce dietary fluid restriction but it should not be considered as a goal of dialysis adequacy in dialysis patients. Further, preservation of RRF must be considered as a permanent trade-off between patient comfort and chronic fluid volume overload.

Chronic Disease↗

PubMed2002

Inferring Function from Structure: Relationship of Magnetic Resonance Imaging-Detected Hippocampal Abnormality and Memory Function in Epilepsy.

Although temporal lobectomy is an effective alternative treatment for many patients with medication-resistant epilepsy, the risk of cognitive morbidity is not inconsequential. The ability to predict cognitive outcome is increasingly dependent on convergent information from multiple sources, including direct (e.g., Wada test) and indirect (e.g., psychometric testing) functional assessments along with magnetic resonance imaging studies that detect structural abnormalities. This brief review summarizes the relationship between imaging and function at baseline and predicting cognitive outcome following temporal lobectomy.

Journal Article↗

PubMed1988

Functional illness and family functioning: a comparison of healthy and somaticizing adolescents.

This study examined the usefulness of the Circumplex Model of Marital and Family Functioning for discriminating between families of healthy adolescents and families of adolescents with functional somatic complaints. The findings did not support the expected curvilinear relationship between symptomatology and the FACES II family dimensions of cohesion and adaptability. Questions are raised regarding the degree of correspondence between the constructs of enmeshment and rigidity as assessed clinically and as measured by the Circumplex Model.

Adaptation, Psychological↗

PubMed2002

Does esophageal function vary at the striated and smooth muscle segments in functional chest pain?

OBJECTIVE: Hypersensitivity of the esophageal wall may contribute to the pathogenesis of functional chest pain. Whether the hypersensitivity is more uniformly distributed along the esophageal wall or is segmental is not known. METHODS: Graded balloon distentions were performed randomly at the smooth muscle as well as at the striated muscle portions of the esophagus in 20 patients with functional chest pain and in 15 healthy volunteers, using impedance planimetry. Sensory thresholds and cross-sectional area were examined in relation to the esophageal wall tension, and the results were compared between two levels as well as the two groups of subjects. RESULTS: During balloon distention, 17 (85%) patients reported typical chest pain, 11 (55%) at both levels, four (20%) at the smooth muscle level, and two (10%) at the striated muscle level only. The sensory thresholds for perception, discomfort, or pain were lower in patients than in controls (p < 0.05). The cross-sectional area and the esophageal wall stiffness at the smooth muscle level were lower than those obtained at the striated muscle level both in controls and in patients (p < 0.01). The wall tension at which moderate discomfort and pain were reported was lower in patients than controls (p < 0.05). CONCLUSIONS: Although in most patients the esophagus is uniformly hypersensitive, in some either the smooth muscle or the striated muscle segment can be hypersensitive. If considering balloon distention at only one level, we recommend balloon placement at 10 cm above the lower esophageal sphincter because of a higher yield of hypersensitivity.

Adult↗

PubMed1979

Dissimulation function in some functional psychoses.

Dissimulation function as estimated by means of Lie-Scale scores can be used as a pointer towards the impaired self-appraising ability of the individuals in relation to others. Sixty non-psychiatric normal persons and 133 psychiatric cases, representing two major psychotic groups, were investigated for the dissimulation function. The results show a significant difference between the two groups of normal and abnormal individuals, the abnormal group dissimulating distinctively more than the other. However, this impaired self-appraising ability does not seem to relate to the chronicity of the illness but only partly with the typology of illness.

Adult↗

PubMed1988

Neuropsychological assessment of functional central nervous system disorders. I. Hemispheric functioning characteristics in schizophrenia and affective illness.

The neuropsychological characteristics of a group of schizophrenic and affective patients were assessed by mean of a comprehensive neuropsychological tool, the Luria-Nebraska Neuropsychological Batter (LNNB), to determine the lateralized hemispheric neurofunctional characteristics in major functional central nervous system disorders. The results showed that schizophrenics had more right-hemisphere impairment than affectives. They do not substantiate the hypothesis of right hemisphere-lateralized malfunctioning in functional mood disorders. Psychopharmacological treatment influences neuropsychological test performance, neuroleptics having the greatest effects. Pharmacological effects other than anticholinergic ones are responsible for the negative influence on neuropsychological test performance.

Adolescent↗

PubMedDate not supplied

Calculation of ocular single-pass modulation transfer function and retinal image simulation from measurements of the polarized double-pass ocular point spread function.

The single-pass modulation transfer function (MTF(sgl)) is an important numerical parameter that can help elucidate the performance and some processes of the human visual system. In previous studies, the MTF(sgl) was calculated from double-pass point spread function (PSF) measurements. These measurements include a depolarized reflection component from the retina that introduces a measurement artifact, and they require long acquisition times to allow averaging to reduce speckle. To solve these problems, we developed a new ocular PSF analysis system (PSFAS) that uses polarization optics to eliminate the depolarized retinal reflection component, and a rotating prism to increase measurement speed. Validation experiments on one patient showed that the MTF(sgl) measured by PSFAS agrees closely with the MTF calculated from contrast sensitivity measurements. A simulated retinal image was calculated by convolution of Landolt rings with the calculated single-pass PSF provided by the PSFAS. The contrast characteristic then was calculated from the simulated retinal images. These results indicate that the MTF(sgl) obtained using the PSFAS may be a reliable measure of visual performance of the optics of the eye, including the optical effects of the retina. The simulated retinal images and contrast characteristics are useful for evaluating visual performance.

Adult↗

PubMedDate not supplied

The line spread function and modulation transfer function of a computed tomographic scanner.

A simple method to measure the line spread function of computed tomographic scanners has been developed. The line spread function of the EMI-Scanner was measured and the MTF of the scanner was calculated. The reproducibility of the method indicated this technique could be utilized to compare the spatial resolution of various computed tomographic scanners.

Diagnosis, Computer-Assisted↗

PubMed2004

Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains.

In Escherichia coli, the ribosome-associated chaperone Trigger Factor (TF) promotes the folding of newly synthesized cytosolic proteins. TF is composed of three domains: an N-terminal domain (N), which mediates ribosome binding; a central domain (P), which has peptidyl-prolyl cis/trans isomerase activity and is involved in substrate binding in vitro; and a C-terminal domain (C) with unknown function. We investigated the contributions of individual domains (N, P, and C) or domain combinations (NP, PC, and NC) to the chaperone activity of TF in vivo and in vitro. All fragments comprising the N domain (N, NP, NC) complemented the synthetic lethality of Deltatig DeltadnaK in cells lacking TF and DnaK, prevented protein aggregation in these cells, and cross-linked to nascent polypeptides in vitro. However, DeltatigDeltadnaK cells expressing the N domain alone grew more slowly and showed less viability than DeltatigDeltadnaK cells synthesizing either NP, NC, or full-length TF, indicating beneficial contributions of the P and C domains to TF's chaperone activity. In an in vitro system with purified components, none of the TF fragments assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in a manner comparable to that of wild-type TF, suggesting that the observed chaperone activity of TF fragments in vivo is dependent on their localization at the ribosome. These results indicate that the N domain, in addition to its function to promote binding to the ribosome, has a chaperone activity per se and is sufficient to substitute for TF in vivo.

Escherichia coli↗

PubMed1994

Serum response factor has functional roles both in indirect binding to the CArG box and in the transcriptional activation function of human T-cell leukemia virus type I Tax.

We previously reported that Tax1 of human T-cell leukemia virus type I interacts directly with serum response factor (SRF) and that Tax1 activates the transcription of several cellular immediate-early genes through the SRF binding site (CArG box). This activation required the transcriptional activation function of Tax1, identified as an activity of GALTax (a chimeric Tax1 with the yeast transcription factor GAL4) at the GAL4-binding site. In this study, we examined whether SRF plays a role in the transcriptional activation function of Tax1. Expression of Tax1 suppressed the GALTax activity at the GAL4 site as a result of squelching, and the suppressed activity was recovered by the overexpression of SRF, suggesting that SRF is a factor that is required for GALTax activity and that is inhibited by competition with Tax1. The expression of antisense SRF RNA specifically inhibited GALTax activity to less than 20%. Deletion of the Tax1 interaction domain of SRF at its C terminus converted SRF from an activator of GALTax to an inhibitor. These results suggest that SRF is an essential component of the transcriptional activation of Tax1 in addition to a mediator of CArG box binding.

3T3 Cells↗

PubMed2002

Pestivirus internal ribosome entry site (IRES) structure and function: elements in the 5' untranslated region important for IRES function.

The importance of certain structural features of the 5' untranslated region of classical swine fever virus (CSFV) RNA for the function of the internal ribosome entry site (IRES) was investigated by mutagenesis followed by in vitro transcription and translation. Deletions made from the 5' end of the CSFV genome sequence showed that the IRES boundary was close to nucleotide 65: thus, the IRES includes the whole of domain II but no sequences upstream of this domain. Deletions which invaded domain II even to a small extent reduced activity to about 20% that of the full-length structure, and this 20% residual activity persisted with more extensive deletions until the whole of domain II had been removed and the deletions invaded the pseudoknot, whereupon IRES activity fell to zero. The importance of both stems of the pseudoknot was verified by making mutations in both sides of each stem; this severely reduced IRES activity, but the compensating mutations which restored base pairing caused almost full IRES function to be regained. The importance of the length of the loop linking the two stems of the pseudoknot was demonstrated by the finding that a reduction in length from the wild-type AUAAAAUU to AUU almost completely abrogated IRES activity. Random A-->U substitutions in the wild-type sequence showed that IRES activity was fairly proportional to the number of A residues retained in this pseudoknot loop, with a preference for clustered neighboring A residues rather than dispersed As. Finally, it was found that the sequence of the highly conserved domain IIIa loop is, rather surprisingly, not important for the maintenance of full IRES activity, although amputation of the entire domain IIIa stem and loop was highly debilitating. These results are interpreted in the light of recent models, derived from cryo-electron microscopy, of the interaction of the closely related hepatitis C virus IRES with 40S ribosomal subunits.

5' Untranslated Regions↗

PubMed1999

Genetics of synaptic vesicle function: toward the complete functional anatomy of an organelle.

Synaptic transmission starts with the release of neurotransmitters by exocytosis of synaptic vesicles. As a relatively simple organelle with a limited number of components, synaptic vesicles are in principle accessible to complete structural and functional genetic analysis. At present, the majority of synaptic vesicle proteins has been characterized, and many have been genetically analyzed in mice, Drosophila, and Caenorhabditis elegans. These studies have shown that synaptic vesicles contain proteins with diverse structures and functions. Although the genetic studies are as yet unfinished, they promise to lead to a full description of synaptic vesicles as macromolecular machines involved in all aspects of presynaptic neurotransmitter release.

Animals↗

PubMed2005

Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function.

Angiotensin-converting enzyme 2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the COOH-terminus of its substrates. Because ACE2 efficiently hydrolyzes the potent vasoconstrictor angiotensin II to angiotensin (1-7), this has changed our overall perspective about the classical view of the renin angiotensin system in the regulation of hypertension and heart and renal function, because it represents the first example of a feedforward mechanism directed toward mitigation of the actions of angiotensin II. This paper reviews the new data regarding the biochemistry of angiotensin-(1-7)-forming enzymes and discusses key findings such as the elucidation of the regulatory mechanisms participating in the expression of ACE2 and angiotensin-(1-7) in the control of the circulation.

Angiotensin I↗

PubMed1986

Structural-functional relationships along the distal nephron.

The distal tubule, which includes the thick ascending limb (TAL), the macula densa, and the distal convoluted tubule (DCT), and the collecting duct are structurally heterogeneous, thus reflecting the functional heterogeneity that is also present. As the TAL ascends from medulla to cortex, the surface area of the apical plasma membrane increases while that of the basolateral membrane decreases. The structure of the DCT resembles that of the medullary TAL. An excellent correlation exists between structure, Na-K-ATPase activity, and NaCl reabsorptive capacity in the distal tubule. The collecting duct is subdivided into the initial collecting tubule (ICT), and cortical (CCD), outer medullary (OMCD), and inner medullary (IMCD) collecting ducts. Between the distal tubule and the collecting duct is a transition region termed the connecting segment or connecting tubule (CNT). Considerable structural heterogeneity exists along the collecting duct within the two major cell populations, the intercalated cells and the principal cells. In the CNT, the ICT, and the CCD, potassium loading and mineralocorticoids stimulate Na-K-ATPase activity and cause proliferation of the basolateral membrane of CNT cells and principal cells, thus identifying the cells responsible for mineralocorticoid-stimulated potassium secretion in these regions. Finally, at least two morphologically distinct populations of intercalated cells exist, types A and B. In the rat, type A predominates in the CNT and the OMCD and is believed to be responsible for H+ secretion, at least in the OMCD. Type B predominates in the CCD, where it may be involved in bicarbonate secretion.

Animals↗

PubMedDate not supplied

A prospective, randomized study of shunt function and infections as a function of shunt placement.

Much controversy still exists about the relative advantages and disadvantages of anteriorly vs. posteriorly placed shunts in terms of infection rate and duration of function. During a 27-month period, all 121 patients seen requiring new shunt insertions were prospectively randomized to anterior or posterior placement. The mean duration of follow-up was 15 months. 70% of the shunts in the posteriorly placed group vs. 59% of the shunts in the anteriorly placed group did not require further surgery during the study period. In a life-table analysis of shunt survival as a function of placement, the shunts in the posteriorly placed group 'survived' slightly longer without malfunctioning or becoming infected than the anteriorly placed shunts. Therefore, the authors conclude that anteriorly placed shunts offer no advantage over posteriorly placed shunts in terms of shunt malfunction or infection.

Adolescent↗

PubMed1991

Effects of exercise on renal function in patients with moderate impairment of renal function compared to normal men.

The renal excretory and haemodynamic responses to sustained moderate exertion were investigated in normotensive humans with impaired renal function and normal volunteers. The heart rate increase with exercise was similar in each group. Subjects with impaired renal function showed a significant fall in glomerular filtration rate on exertion, while normals did not. In the presence of renal disease, urine osmolality did not rise with exertion, although it rose markedly in the normal group. Free water clearance became negative after exercise in the normal group only. The diseased kidney is unable to maintain glomerular filtration rate or conserve water under the stress of exertion as well as the normal kidney.

Adult↗