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PubMed2006

Operon prediction in Pyrococcus furiosus.

Identification of operons in the hyperthermophilic archaeon Pyrococcus furiosus represents an important step to understanding the regulatory mechanisms that enable the organism to adapt and thrive in extreme environments. We have predicted operons in P.furiosus by combining the results from three existing algorithms using a neural network (NN). These algorithms use intergenic distances, phylogenetic profiles, functional categories and gene-order conservation in their operon prediction. Our method takes as inputs the confidence scores of the three programs, and outputs a prediction of whether adjacent genes on the same strand belong to the same operon. In addition, we have applied Gene Ontology (GO) and KEGG pathway information to improve the accuracy of our algorithm. The parameters of this NN predictor are trained on a subset of all experimentally verified operon gene pairs of Bacillus subtilis. It subsequently achieved 86.5% prediction accuracy when applied to a subset of gene pairs for Escherichia coli, which is substantially better than any of the three prediction programs. Using this new algorithm, we predicted 470 operons in the P.furiosus genome. Of these, 349 were validated using DNA microarray data.

Algorithms↗
PubMed1990

Regulation of proteolytic activity of complement factor I by pH: C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) have different pH optima for factor I-mediated cleavage of C3b.

C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) are integral membrane glycoproteins with factor I-dependent cofactor activity. They bind to C3b, allowing factor I to cleave C3b at two sites (first and second cleavage), which results in the generation of C3bi, a hemolytically inactive form which is a ligand for complement receptor type three (CR3). C3bi is further degraded by factor I and CR1 (third cleavage) to C3dg (a ligand for complement receptor type two, CR2) and C3c. Using two different substrates, fluid-phase C3b and cell-bound C3b, the cleavage of C3b by MCP and factor I was compared to that by CR1 and factor I under various conditions. The optimal pH for the first and second cleavage of either substrate was 6.0 for MCP and 7.5 for CR1. The third cleavage was mediated only by CR1 and factor I, the optimal pH being 8.0. Low ionic conditions enhanced the C3b binding and cofactor activity of both CR1 and MCP. The efficiency of binding C3b to CR1 or MCP was maximal at pH 6.2. The isoelectric point (pI) of MCP was acidic (approximately 4.0), while that of CR1 was 6.8. Therefore, compared to CR1, MCP possesses distinct functional profiles relative to C3b-binding and factor I-cofactor activity.

Antigens, CD↗
PubMed2004

Lupus nephritis: treatment with mycophenolate mofetil.

OBJECTIVE: To evaluate the safety and efficacy of mycophenolate mofetil (MMF) treatment in patients with lupus nephritis. METHODS: Eighteen patients with biopsy-proven lupus nephritis (17 females, one male; mean age 31.6 yr; mean lupus duration 92 months; mean duration of nephritis 57 months; nine with focal proliferative glomerulonephritis, three with diffuse proliferative glomerulonephritis, six with membranous nephropathy) were included. With five exceptions, all patients had been treated previously with cyclophosphamide and were selected because of either toxicity or inadequate clinical response to treatment. MMF was given at 2 g daily in combination with steroids for up to 31 months (mean 15.3 months). The side-effects of MMF were recorded and efficacy was assessed as the renal function profile. RESULTS: Complete remission was observed in 10/18 patients and another 4/18 went into partial remission. Both creatinine clearance and proteinuria were significantly improved during MMF treatment in patients with the proliferative forms of nephritis. MMF demonstrated a steroid-sparing effect in the whole population. Treatment failure was recorded in 4/18 patients, all with membranous nephropathy. Two patients developed gastrointestinal complaints and infectious meningitis occurred in one patient. CONCLUSION: MMF appears to be an efficacious and safe treatment in patients with proliferative forms of lupus nephritis who do not respond to or cannot tolerate conventional treatment. The efficacy of MMF in lupus membranous nephropathy remains unclear.

Adult↗
PubMed2001

In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated.

J-113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one) is a recently developed antagonist of the opioid receptor-like 1 (ORL1) receptor. We compared the in vitro functional profile J-113397 on [35S]guanosine 5'-O-(gamma-thio)triphosphate (GTPgammaS) binding to mouse brain with that of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 and naloxone benzoylhydrazone (NalBzoH). J-113397 antagonized nociceptin/orphanin FQ-stimulated [35S]GTPgammaS binding to mouse brain with an IC50 value of 7.6 nM, but had no effect on basal [35S]GTPgammaS binding by itself. [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 partially antagonized nociceptin/orphanin FQ-stimulated [35S]GTPgammaS binding but showed agonistic activity on ORL1 by itself. NalBzoH showed antagonistic activity on ORL1 receptor but had significant agonistic activity on other opioid receptors at lower doses. Schild plot analysis demonstrated competitive antagonism of J-113397 on ORL1 receptor in mouse brain. A [35S]GTPgammaS binding study using ORL1 receptor-deficient mice confirmed the selective antagonism of J-113397 on ORL1 receptor. These data indicate that J-113397 is the most potent and selective antagonist of ORL1 receptor in mouse brain that has yet been reported, and therefore will be a useful tool for characterization of ORL1 receptors in the brain.

Animals↗
PubMed2002

Pure severe dyslexia after a perinatal focal lesion: evidence of a specific module for acquisition of reading.

A child with a small, residual "localized" perinatally acquired left hemisphere temporal tip lesion is described. He presents with pure and severe dyslexia and average to high-average cognitive skills, which are usually in the low-average range in patients with developmental dyslexia. A highly circumscribed deficit of rote auditory verbal memory was the only deficit other than the dyslexia; his verbal semantic memory and visuospatial memory were intact. Two previously reported cases present a similar functional profile and lesion locus. This profile indicates that there may exist, at birth, a localized neural network dedicated to "reading acquisition" and that the layout of this network may differ from the systems identified as defective in developmental dyslexia, as well as in cases of acquired dyslexia in adults.

Atrophy↗
PubMed2000

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood.

BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Adolescent↗
PubMed2002

Nursing case management in the 21st century: intervening where margin meets mission.

Case management, the basic process of matching key resources to individual's needs, often carried out across time and place, has been a relatively low-profile function (under various levels) within society, business, and health care for many years. Nurses have been involved in case management since its beginnings in social service and public health. However, nurses only became prominent as case managers during the last half of the 20th century because of the need to establish medical necessity for health care payments and, eventually, the need to provide discharge planning. The 21st century begins with an evolving core for case management functions in health care, the specific models dictated by the margins and missions of the employing organization. Case management, in fact, is the nursing process applied at a system level. However, if case management is to remain an adaptable yet powerful strategy for patients and organizations across the continuum of health care, it will have to move beyond access and medical necessity functions to those functions that demand advanced nursing experience and skills.

Case Management↗
PubMed2000

Global spectral-kinetic analysis of room temperature chlorophyll a fluorescence from light-harvesting antenna mutants of barley.

This study presents a novel measurement, and simulation, of the time-resolved room temperature chlorophyll a fluorescence emission spectra from leaves of the barley wild-type and chlorophyll-b-deficient chlorina (clo) f2 and f104 mutants. The primary data were collected with a streak-camera-based picosecond-pulsed fluorometer that simultaneously records the spectral distribution and time dependence of the fluorescence decay. A new global spectral-kinetic analysis programme method, termed the double convolution integral (DCI) method, was developed to convolve the exciting laser pulse shape with a multimodal-distributed decay profile function that is again convolved with the spectral emission band amplitude functions. We report several key results obtained by the simultaneous spectral-kinetic acquisition and DCI methods. First, under conditions of dark-level fluorescence, when photosystem II (PS II) photochemistry is at a maximum at room temperature, both the clo f2 and clo f104 mutants exhibit very similar PS II spectral-decay contours as the wild-type (wt), with the main band centred around 685 nm. Second, dark-level fluorescence is strongly influenced beyond 700 nm by broad emission bands from PS I, and its associated antennae proteins, which exhibit much more rapid decay kinetics and strong integrated amplitudes. In particular a 705-720 nm band is present in all three samples, with a 710 nm band predominating in the clo f2 leaves. When the PS II photochemistry becomes inhibited, maximizing the fluorescence yield, both the clo f104 mutant and the wt exhibit lifetime increases for their major distribution modes from the minimal 205-500 ps range to the maximal 1500-2500 ps range for both the 685 nm and 740 nm bands. The clo f2 mutant, however, exhibits several unique spectral-kinetic properties, attributed to its unique PS I antennae and thylakoid structure, indicating changes in both PS II fluorescence reabsorption and PS II to PS I energy transfer pathways compared to the wt and clo f104. Photoprotective energy dissipation mediated by the xanthophyll cycle pigments and the PsbS protein was uninhibited in the clo f104 mutant but, as commonly reported in the literature, significantly inhibited in the clo f2; the inhibited energy dissipation is partly attributed to its thylakoid structure and PS II to PS I energy transfer properties. It is concluded that it is imperative with steady-state fluorometers, especially for in vivo studies of PS II efficiency or photoprotective energy dissipation, to quantify the influence of the PS I spectral emission.

Chlorophyll↗
PubMed2006

Quantitative analysis of photon density of states for a realistic superlattice with omnidirectional light propagation.

Omnidirectional light propagation in a realistic superlattice is investigated. This work complements two previous articles [Phys. Rev. E 59, 3624 (1999); 61, 5802 (2000)] that analyzed the cases of transverse electric (TE) and transverse magnetic (TM) polarization modes, respectively, of the dielectric superlattice modeled by means of Dirac delta functions. We present a quantitative analysis of the transmission functions, the band structures, the equifrequency surfaces, and the photon density of states (PDOS) for both TE and TM modes of the real superlattice without any approximations on the given dielectric function profiles. One of the advantages is that the Brewster effect can be manifested via our approach. In addition, the modes corresponding to TM evanescent waves that are absent from the Dirac comb model can be predicted. Finally, the exact PDOS of the realistic superlattice for the TE and TM modes can be obtained, respectively. These results are relevant to the spontaneous emission by an atom or to dipole radiation in one-dimensional periodic structures.

Journal Article↗
PubMed2002

Whole powder pattern modelling.

A new approach for the modelling of diffraction patterns without using analytical profile functions is described and tested on ball milled f.c.c. Ni powder samples. The proposed whole powder pattern modelling (WPPM) procedure allows a one-step refinement of microstructure parameters by a direct modelling of the experimental pattern. Lattice parameter and defect content, expressed as dislocation density, outer cut-off radius, contrast factor, twin and deformation fault probabilities), can be refined together with the parameters (mean and variance) of a grain-size distribution. Different models for lattice distortions and domain size and shape can be tested to simulate or model diffraction data for systems as different as plastically deformed metals or finely dispersed crystalline powders. TEM pictures support the conclusions obtained by WPPM and confirm the validity of the proposed procedure.

Journal Article↗
PubMed2005

Intestinal macrophages: unique effector cells of the innate immune system.

The gastrointestinal mucosa is the largest reservoir of macrophages in the body. These important effector cells are derived from blood monocytes that are recruited to the lamina propria by endogenous chemoattractants in the non-inflamed mucosa and by inflammatory chemokines and bacterial products during inflammation. In the non-inflamed mucosa, newly recruited pro-inflammatory monocytes are exposed to lamina propria stromal (extracellular matrix) factors that induce phenotypic and functional differentiation into non-inflammatory macrophages. As a consequence of this differentiation, resident lamina propria macrophages are strikingly downregulated for the expression of innate response receptors, such as the receptors for lipopolysaccharide, immunoglobulin G (IgG), and IgA, and the production of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-alpha. Despite downregulated pro-inflammatory function, strong phagocytic and bactericidal activities remain intact. Thus, in the non-inflamed intestinal mucosa, lamina propria macrophages are non-inflammatory but retain avid scavenger and host defense functions, a unique but ideal phenotype and functional profile for effector cells in close proximity to immunostimulatory microorganisms and products.

Animals↗
PubMed1997

Cholinesterase. Its significance in anaesthetic practice.

Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its role in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.

Anesthesia↗
PubMed2006

Lower urinary tract dysfunction in type 1 familial amyloidotic polyneuropathy in Kumamoto, Japan.

OBJECTIVE: To evaluate lower urinary tract dysfunction of type 1 familial amyloidotic polyneuropathy (FAP) patients in Kumamoto, Japan. METHODS: Lower urinary tract symptoms were evaluated in FAP patients. Urodynamic studies were evaluated in FAP patients as compared to those in control subjects. The location and distribution of amyloid deposits were evaluated in the urinary bladder in an autopsy case. RESULTS: In lower urinary symptoms, 86%, 19% and 38% patients showed difficulty in urination, urinary frequency and urinary incontinence. In detrusor function during filling cystometry, 14% patients showed detrusor overactivity. Moreover, 43% patients showed low compliance bladder, 62% and 38% patients showed normal and reduced bladder sensation, respectively. First desire to void (FDV), strong desire to void (SDV) and post-voided residual urine (PVR) were increased in FAP patients as compared to those in control subjects. In the urethral pressure profilometry, 71%, 10% and 19% patients showed incompetent, normal functional and overactive urethral closure mechanism, respectively. Maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP) and functional profile length (FPL) were decreased in FAP patients compared to those in control subjects. CONCLUSION: Autonomic, somatic nerve systems and bladder detrusor musculature might be impaired in lower urinary tract of type 1 FAP patients in Kumamoto, Japan.

Adult↗
PubMed1999

Large animal models of heart failure.

Congestive heart failure (HF) is a major focus of medical research. Its incidence has greatly increased in recent decades because of an aging population base and the increasingly successful treatment of other forms of chronic cardiac disease. Relevant large animal models of HF should reflect the complex interactions of cardiac dysfunction, neurohumoral dynamics and peripheral vascular abnormalities found in human HF. A number of large animal models have been developed, especially in dogs, sheep and swine, using naturally occurring HF, or single or combinations of interventions, as instruments to trigger the development of HF. Naturally occurring HF models are not commonly used because of ethical or perceived ethical grounds, however, King Charles Cavalier Spaniel and Yucatan Mini Pig models have been described. Tachycardia induced HF is the most commonly used HF model. Ventricular pacing at 220-240 bpm results in profound low output, biventricular, oedematous failure in two to three weeks. Lower pacing rates result in a more stable, sustainable, lesser degree of failure. Positive features of this model include 'acceptance', aetiological relevance to patient tachycardia induced HF, neurohumoral and functional profile similar to most human HF, relatively low cost simple preparation, ability to manipulate the degree of failure with pacing rate, reversibility, reliability and a large amount of published multi species data. Limitations to the use of the model are the rapid onset, the fact that reversibility is only relevant to the tachycardia induced patient HF, the absence of hypertrophy in failure, the diminished plasma atrial natriuretic peptide (ANP) levels, absence of ANP of ventricular origin, and the interference between rapid pacing and therapeutic interventions. Myocardial damage models of HF include those models induced by ischaemia, eg due to coronary occlusion (ligation or aneroid) or intracoronary microembolism, transmyocardial DC shock, toxic cardiomyopathy from adriamycin, doxorubicin or catecholamines. Overload models of HF may be induced by high pressure from aortic constriction, aortic regurgitation, renal artery constriction, pulmonary stenosis or aortocaval shunts, or by induction of mitral regurgitation from chordae or leaflet damage. No single, all-encompassing, large animal model of HF exists to date. Selection of the type of model to be used should be based primarily on the hypotheses to be tested and secondarily on the available resources and facilities.

Animals↗
PubMed1988

Urodynamic findings following radiotherapy for cervical carcinoma.

Forty patients were assessed urodynamically 5 to 11 years after radiotherapy for cervical carcinoma and compared with 27 patients prior to treatment. The mean volume of first bladder sensation after radiotherapy was significantly lower than the mean volume before treatment, as was the mean maximum cystometric capacity. The mean filling detrusor pressure was higher after radiotherapy than before treatment. Unstable detrusor contractions were found only in the 12 symptomatic patients. There was a significant reduction in maximal urethral closure pressure and functional profile length in the post-radiotherapy group. Detrusor instability was a common finding following radiotherapy. The reduction in bladder capacity alone was not sufficient to account for the symptoms of frequency, urgency and urge incontinence.

Female↗
PubMedDate not supplied

The performance of three measures of health status in an outpatient diabetes population.

Both the late complications of diabetes and the means used to prevent them have a significant impact on the lives of people with the condition. Measuring quality of life is therefore important in assessing clinical need and evaluating the success of management. Three approaches to measuring health status were therefore compared in 284 randomly selected out-patients attending a hospital diabetes service. The measures used were the Nottingham Health Profile (NHP), four categories of an anglicized version of the Sickness Impact Profile (the Functional Limitations Profile (FLP)), and a scale of Positive Well-being (PWB). The results were found to be independent of questionnaire order and place of completion. The distributions of scores on the NHP and FLP scales were highly skewed, with a majority of cases scoring zero. NHP and FLP scores were related (p < 0.001) to age, but not otherwise to type of diabetes. Patients with angina, circulatory problems, and neuropathy scored significantly higher (up to p < 0.001) on several dimensions/categories of the NHP and FLP, but not the PWB scale. Severe visual impairment (worse than 6/36) was only related (p < 0.005) to NHP 'Mobility' and FLP 'Ambulation' and 'Home management'. Validation of scores by interview gave satisfactory results on all dimensions of the NHP except 'Energy', and all FLP categories except 'Recreations and pastimes'. No statistically significant association was observed between the PWB and the interviewer's assessments, but it did correlate (up to tau = 0.45, p < 0.001) with some social and psychological dimensions/categories of the NHP/FLP. In conclusion the PWB scale is independent of physical disability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Nicotinic acetylcholine currents of cultured Kkenyon cells from the mushroom bodies of the honey bee Aapis mellifera.

1. Acetylcholine-induced currents of mushroom body Kenyon cells from the honey bee Apis mellifera were studied using the whole-cell configuration of the patch clamp technique. Pressure application of 1 mM acetylcholine (ACh) induced inward currents with amplitudes between -5 and -500 pA. 2. The cholinergic agonists ACh and carbamylcholine had almost equal potencies of current activation at concentrations between 0.01 and 1 mM; nicotine was less potent. The muscarinic agonist oxotremorine did not elicit any currents. 3. Approximately 80 % of the ACh-induced current was irreversibly blocked by 1 microM alpha-bungarotoxin. Atropine (1 mM) did not block the ACh-induced current. 4. Upon prolonged ACh application the current desensitized with a time course that could be approximated by the sum of two exponentials (tau1 = 276 +/- 45 ms (mean +/- s.e.m. ) for the fast component and tau2 = 2.4 +/- 0.7 s for the slow component). 5. Noise analyses of whole-cell currents yielded elementary conductances of 19.5 +/- 2.4 pS for ACh and 23.7 +/- 5.0 pS for nicotine. The channel lifetimes, calculated from the frequency spectra, were tauo = 1.8 ms for ACh and tauo = 2.5 ms for nicotine. 6. Raising the external calcium concentration from 5 to 50 mM shifted the reversal potential of the ACh-induced current from +4. 6 +/- 0.9 to +37.3 +/- 1.3 mV. The calcium-to-sodium permeability ratio (PCa : PNa) was 6.4. 7. In high external calcium solution (50 mM) the ACh-induced current rectified in an outward direction at positive membrane potentials. 8. We conclude that Kenyon cells express nicotinic ACh receptors with functional profiles reminiscent of the vertebrate neuronal nicotinic ACh receptor subtype.

Animals↗
PubMed2004

The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia.

OBJECTIVES: (1) To investigate the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function. DESIGN: Analysis of the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation, and the effects of MMP inhibition on these parameters. SETTING: University of Alberta, Edmonton, Alberta, Canada. SAMPLES: Pooled plasma from non-pregnant (n= 9), normal pregnant (n= 6) and pre-eclamptic women (n= 12). METHODS: Mesenteric arteries from virgin female C57BL/6J mice were exposed to pooled plasma from non-pregnant, normal pregnant and pre-eclamptic women in the absence and presence of GM6001 (5 microM; MMP inhibitor), and arterial function was assessed. MAIN OUTCOME MEASURES: Myogenic tone and endothelium-dependent relaxation. RESULTS: Plasma of women with pre-eclampsia, and interestingly, plasma of non-pregnant women, significantly enhanced myogenic tone at pressures > or =70 mmHg (P < 0.001) and blunted the maximum relaxation to methacholine (P < 0.001; P < 0.005) in isolated arteries. GM6001 altered response only in vessels exposed to the plasma of women with pre-eclampsia; however, contrary to our hypothesis, this further enhanced myogenic tone and further abrogated relaxation. CONCLUSIONS: The strikingly similar vascular function profiles of vessels incubated in the plasma of non-pregnant and pre-eclamptic women suggest that pre-eclampsia may be due, in part, to the lack of a necessary adaptation to pregnancy. Despite these similarities, however, there are differential effects of MMP inhibition, suggesting that MMPs play a greater role in the vasculature of women with pre-eclampsia compared with non-pregnant and normal pregnant women.

Adult↗