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At least 811 records · Page 45Linked to original sources
PubMed2003

Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations.

PURPOSE OF REVIEW: Apolipoprotein A-I is the major structural protein of HDL. Its physicochemical properties maintain a delicate balance between maintenance of stable lipoproteins and the ability to associate with and dissociate from the lipid transported. Here we review the progress made in the last 2-3 years on the structure-function relationships of apolipoprotein A-I, including elements related to the ATP binding cassette transporter A1. RECENT FINDINGS: Current evidence now supports the so-called 'belt' or 'hairpin' models for apolipoprotein A-I conformation when bound to discoidal lipoproteins. In-vivo expression of apolipoprotein A-I mutant proteins has shown that both the N- and C-terminal domains are important for lipid association as well as for the esterification reaction, particularly binding of cholesteryl esters and formation of mature alpha-migrating lipoproteins. This property is apparently quite distinct from the activation of the enzyme lecithin cholesterol acyl transferase, which requires interaction with the central helix 6. The interaction of apolipoprotein A-I with the ATP binding cassette transporter A1 has been shown to require the C-terminal domain, which is proposed to mediate the opening of the helix bundle formed by lipid-free or lipid-poor apolipoprotein A-I and allow its association with hydrophobic binding sites. SUMMARY: Significant progress has been made in the understanding of the molecular mechanisms controlling the folding of apolipoprotein A-I and its interaction with lipids and various other protein factors involved in HDL metabolism.

Apolipoprotein A-I↗
PubMed2004

Is perception of handicap related to functional performance in persons with vestibular dysfunction?

OBJECTIVE: The purpose of this study was to determine if scores between 0 and 30 (mild), 31 and 60 (moderate), and 61 and 100 (severe) on the Dizziness Handicap Inventory (DHI) differentiated a person's functional abilities. STUDY DESIGN: Retrospective case series. SETTING: Tertiary balance outpatient center. PATIENTS: Patients (n = 85; mean age, 61 years) with a variety of vestibular diagnoses participated. INTERVENTIONS: Patients completed the DHI, the Dynamic Gait Index (DGI), the 5 times sit to stand test (FTSST), the Activities-specific Balance Confidence (ABC) scale, gait speed, and the Timed "Up & Go" (TUG) during the same session. Reported numbers of falls within the last 4 weeks were recorded. MAIN OUTCOME MEASURES: The DGI, FTSST, ABC, gait speed, TUG, and gait speed were compared among DHI groups. RESULTS: Significant differences were identified using an analysis of variance between DHI groups on the DGI, the FTSST, ABC, and number of falls (p < 0.05). A significant difference was found between DHI groups (mild vs. severe and moderate vs. severe) on the DGI (p < 0.05) with greater DHI scores exhibiting more impaired walking. The FTSST was different between DHI groups mild and severe and DHI groups moderate and severe (p < 0.05), with slower FTSST scores with higher DHI scores. Reported falls were higher among the severe DHI group and the other 2 DHI groups (p < 0.05). All 3 DHI groupings were different from each other on the ABC (p < 0.001). CONCLUSION: Patients who perceive a greater handicap as a result of dizziness demonstrate greater functional impairment than patients who perceive less handicap from dizziness.

Adolescent↗
PubMed1992

Myelomeningocele: a review of the orthopaedic aspects of 206 patients treated from birth with no selection criteria.

Two hundred and six consecutive children with spina bifida who have been treated since the first day of life were analysed in terms of walking ability, motor level, orthopaedic deformities, operative procedures and balance deficit. The authors found that: (1) ambulation was quite delayed compared with the normal population; (2) sitting balance was a useful predictor of future walking; (3) almost all patients with quadriceps function were able to walk and were community ambulators; and (4) a significant number of congenital and acquired orthopaedic deformities required surgical intervention.

Adolescent↗
PubMed1999

The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem.

The calcium channel blocker diltiazem lowers heart rate in man and this property probably contributes to its clinical effectiveness in ischaemic heart disease and hypertension. This review examines the pharmacological basis of diltiazem's heart rate-lowering activity and considers its pathophysiological significance. The points discussed include the potent direct inhibitory effect of diltiazem on the sinus node and the frequency-dependence of this action. In addition, the well-balanced tissue selectivity profile of diltiazem and its ability to modulate cardiac reflex responsiveness contribute by counteracting the potential for reflex tachycardia.

Calcium Channel Blockers↗
PubMed1987

Thromboembolic and infectious complications of total artificial heart implantation.

Thromboembolic and infectious events were found to be major complications of long-term total artificial heart implantation in two patients. Similar complications have been reported in other patients, as well as in animal studies. The thromboembolic events and the infectious complications appear to be interrelated. On the one hand, thrombi located on the valves and at the vascular anastomoses of the artificial heart were found to be infected at autopsy; such infections are known to exacerbate formation of thromboemboli. On the other hand, the generation of microthrombi may have contributed to the RES blockade seen in our patients. We hypothesize that this RES blockade led to a progressive decrease in lymphoid system function and impaired the patients' capacity to clear microorganisms from the circulation. These phenomena arose, in part, from the design of the artificial heart and were exacerbated by associated therapy, such as blood transfusions. Our data suggest several measures that might be taken in order to reduce the severity of both the thrombogenic and infectious complications. Improved anticoagulation regimens, which increase the ability of the physician to maintain the proper balance between thrombotic and hemorrhagic potential, are needed. This may require not only improved methods of monitoring anticoagulation and predicting changes in the effectiveness of various agents as other events supervene, but also new anticoagulant and antithrombotic drugs, for example, low molecular weight heparins and prostacyclin derivatives. It is also clear that the design of the artificial heart should be modified in order to improve fluid dynamics so that they will approximate as closely as possible those of the natural heart. This includes redesigning the mounting of the valves to eliminate crevices and discontinuities that allow stagnant flow and predispose to thrombus formation as well as imposing a dP/dt that minimizes shear-related hemolysis, thereby minimizing the need for blood transfusions. Prevention of infections presents a more difficult problem. Transcutaneous lines (regardless of their use) are an obvious route for infection, and attention should be given to minimizing the number and length of use of monitoring lines. However, until a totally implantable drive system is available, the drive lines will remain a potential avenue for the introduction of infections. The risk may be minimized by rigorous attention to care of the exit sites and by improved designs that will provide a better mechanical barrier by, for example, enhancing epithelial ingrowth into the materials of the drive line.(ABSTRACT TRUNCATED AT 250 WORDS)

Candidiasis↗
PubMed1997

Interferon-gamma differentially regulates interleukin-12 and interleukin-10 production in leprosy.

The ability of monocytes to influence the nature of the T cell response to microbial pathogens is mediated in part by the release of cytokines. Of particular importance is the release of IL-12 and IL-10 by cells of the monocyte/macrophage lineage upon encountering the infectious agent. IL-12 promotes cell mediated immunity (CMI) to intracellular pathogens by augmenting T-helper type 1 responses, whereas IL-10 downregulates these responses. The ability of IFN-gamma to modulate the balance between IL-12 and IL-10 production was examined by studying leprosy as a model. In response to Mycobacterium leprae stimulation, IFN-gamma differentially regulated IL-12 and IL-10 production resulting in upregulation of IL-12 release and downregulation of IL-10 release. Furthermore, we determined that the mechanism by which IFN-gamma downregulates IL-10 was through the induction of IL-12. The data suggest a model of lymphocyte-monocyte interaction whereby the relative presence or absence of IFN-gamma in the local microenvironment is a key determinant of the type of monocyte cytokine response, and hence the degree of CMI in the host response to infection.

Down-Regulation↗
PubMed2003

Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha.

Monocyte-derived dendritic cells (DCs) generated in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4-DCs) are used to enhance antitumor immunity in cancer patients, although recent evidence suggests that their functional repertoire may be incomplete; in particular, IL-4-DCs appear unable to induce type 2 cytokine-producing T helper (Th) cells. To assess whether type 1 interferon (IFN) could replace IL-4 and generate DCs with a more complete repertoire, we characterized in detail DCs generated from human monocytes cultured with GM-CSF and IFN-alpha (IFN-DCs). We found that IFN-alpha induces DC differentiation more efficiently than IL-4, yielding similar numbers of DCs in a shorter time and that this differentiation persists upon removal of cytokines. Although IFN-DCs had a more mature immunophenotype than IL-4-DCs, showing higher expression of CD80, CD86, and CD83, they still preserved comparable endocytic and phagocytic capacities and responsiveness to maturation stimuli. IFN-DCs had strong antigen-presenting capacity, inducing intense proliferation of T cells to alloantigens or influenza virus. Moreover, IFN-DCs produced lower levels of IL-12p70 and higher levels of IFN-alpha, IL-4, and IL-10 than IL-4-DCs. As a consequence of this different pattern of cytokine secretion, IFN-DCs induced T cells to produce type 1 (IFN-gamma) and type 2 (IL-4 and IL-10) cytokines, and as expected, IL-4-DCs induced only Th1 differentiation. As immune responses with extreme Th1 bias are considered inadequate for the induction of optimal, systemic antitumor immunity, the ability of IFN-DCs to promote more balanced cytokine responses may suggest the advisability to consider these cells in the development of future, DC-based immunotherapy trials.

Cell Adhesion↗
PubMed1992

Postural stability in patients with Huntington's disease.

We characterized postural stability in patients with Huntington's disease (HD) by examining their ability to use different sensory cues to maintain balance and by recording their automatic postural responses to externally applied perturbations. Our HD patients, like normal subjects, depended more on proprioceptive than on visual cues to maintain balance. HD patients, however, developed more sway than normal subjects when proprioceptive cues, or when proprioceptive cues and vision, were altered. Thus, HD patients showed a defect in using vestibular information alone to maintain normal postural stability. The onset of compensatory motor responses in the lower extremities following sudden translations of the support surface was delayed by 30 to 60 msec in HD patients as compared with normal subjects. HD patients also had more sway and falls during unexpected rotations of the support surface, although they could appropriately reduce their motor responses on the next trial.

Adult↗
PubMed2005

Hemodynamic effects of portal triad clamping with and without pneumoperitoneum: an echocardiographic study.

The decrease of cardiac index observed during portal triad clamping (PTC) with and without pneumoperitoneum has been studied only with right heart catheterization. To better understand this decrease of cardiac index, we investigated the balance between the adequacy of preload and the ability of the heart to pump against an increased afterload, by using transesophageal echocardiography. Ten patients with PTC performed during laparoscopy and 10 with PTC performed during laparotomy were studied. Five minutes after PTC, the stroke volume, the left ventricular (LV) fractional area change (FAC), and the LV end-systolic wall stress (LVESWS) were measured as the conventional hemodynamic variables. Regional wall motion abnormalities (RWMA) were also recorded. In the laparotomy group, LV end-diastolic area decreased, and LVESWS did not increase significantly. FAC remained stable, and one patient developed RWMA. In the laparoscopic group, LV end-diastolic area remained stable, and LVESWS increased. FAC decreased significantly, and five patients developed RWMA. A decrease in preload was the main important change in the laparotomy group, and in the laparoscopic group a decrease in LV function was demonstrated that was likely a consequence of decreased LV preload and increased LV afterload. However, these did not necessitate stopping the procedure or releasing PTC in these study patients without cardiac disease.

Adult↗
PubMed1996

Hepatotoxic effects of SH-reagents in human and rat hepatocyte cultures and in situ perfused rat livers.

Effects organic mercurials (PCMBS, PCMB, mersalyl) an alkylating reagent (NEM), disulphide reagents (DTP, CPDS) and the dithiocarbamate agent DSF (disulfiram) were studied in hepatocyte culture. Cytotoxicity, was on a high level (organic mercurials), moderate (NEM, DTP), or none (DSF, CPDS). The organic mercurials and NEM induced glutathione depletion. Disulphide compounds were detoxified by metallothionein binding. Organic mercurials inhibited the cellular glucose uptake. The most prominent effect of NEM, DTP and DSF was an inhibition of the TCA-cycle. The hepatocellular BSP metabolism was delayed by all tested compounds. Albumin synthesis was stimulated by pyruvate and blocked by PCMB and PCMBS, by inhibiting the hepatocellular amino acid uptake. Phase I and II biotransformation reactions were inhibited by PCMBS and PCMB by direct binding to Cyt. P450 cysteinyl-residues and active sites of UDP-glucuronyltransferases. DSF probably reacts by diminishing the availability of the cofactor NADPH. Isolated ALDH (EC 1, 2, 1.3) was inhibited by all studied compounds. In cellular systems, DSF and the organomercurials inhibited ALDH, thereby reducing the cell's capacity of ethanol catabolism. All tested compounds showed, in low doses, the anabolic ability of insulin mimicking, as demonstrated in a balanced endocrine in vitro testsystem. Morphology, Exposure to NEM, DTP, CPDS, DSF did not result in any morphological alterations in the cell cultures. However, an exposure to PCMBS and PCMB, resulted in extensive bleb-formation, as a result of SH group blocking at the cell's outer membrane. It can be concluded, that cultured hepatocytes from human or rat origin, resist an exposure to alkylating and disulphide SH-reagents up to relatively high dose (1.0 mM). However, organic mercury compounds triggered an extensive bleb formation, as a result of SH-blocking, thereby disturbing the osmotic balance by blocking Na+/K+ carriers. Of all tested reagents, organic mercury compounds arose as the most toxic reagents.

2,2'-Dipyridyl↗
PubMed2002

Health human resources: can present trends be altered?

Predicting the need for health human resources and ensuring an adequate supply continues to confound those with a stake in health services. The many interrelated factors that influence the demand and supply of health professionals seem to exceed our ability to develop strategies that ensure a healthy balance between the size of the health services workforce and the needs of Canadians. We continue to focus on specific health disciplines rather than considering alternatives and implementing policy options that recognize the interdependence of health professionals.

Canada↗
PubMed2000

Echocardiographic evaluation of left ventricular function in critically ill patients: dynamic loading challenge using medical antishock trousers.

STUDY OBJECTIVE: We hypothesized that a dynamic left ventricular (LV) evaluation during a loading challenge might enhance diagnostic capabilities of routine transesophageal echocardiography in critically ill patients and selection of therapeutic options against circulatory failure, particularly the choice between volume expansion and vasoactive agent infusion. DESIGN: Prospective clinical study in a group of 26 patients requiring hemodynamic support by vasoactive infusion because of low systemic arterial pressure (< 90 mm Hg by invasive monitoring) during mechanical ventilation. SETTING: University hospital ICU. PATIENTS: Patients required respiratory support for an episode of acute respiratory failure of various causes or for an episode of coma. They were studied by transesophageal echocardiography during mechanical ventilation in the controlled mode, before and during a loading challenge made using the legs compartment of medical antishock trousers inflated at 80 mm Hg. MEASUREMENTS: A short-axis view of the left ventricle was obtained by a transgastric approach, and end-diastolic and end-systolic areas were measured. LV stroke area (LVSA) and LV fractional area contraction (LVFAC) were calculated. RESULTS: Changes in LV echocardiographic measurements permitted separation of the patients into two groups. In nine patients (group 1), LVSA, used as an index of stroke output, was significantly increased during the challenge, together with a significant increase in LV end-diastolic area, suggesting preload improvement by the challenge. Conversely, in 17 patients (group 2), LVSA was significantly reduced by the challenge, together with a significant decrease in LVFAC, suggesting a negative effect of increased afterload by the challenge. CONCLUSION: Study of the changes in LV dimensions during loading challenge in hemodynamically unstable patients was used to evaluate the balance between the adequacy of preload and the ability of the heart to pump against an increased load, and might thus guide hemodynamic support.

Critical Illness↗
PubMedDate not supplied

[The movement for reassessing education and research in nursing history].

The thematic focus of this work is a call for reconsidering Education and Research on Nursing History (NH). Such movement is deemed a late manifestation in a process of improvement in Nursing knowledge, mediated by the development of stricto sensu Postgraduate programs, by the end of the 20th century, when a wakening of the Nursing area was seen due to a need to search for balance between technical and scientific competence and the ability for social criticism and professional self-assessment. An analysis of the possibilities and limitations of education and research in NH is presented, as well as its contribution to the advancement of the profession, and implications from understanding NH as an interdisciplinary field are discussed.

Education, Nursing↗
PubMed2005

Feature selection and the class imbalance problem in predicting protein function from sequence.

When the standard approach to predict protein function by sequence homology fails, other alternative methods can be used that require only the amino acid sequence for predicting function. One such approach uses machine learning to predict protein function directly from amino acid sequence features. However, there are two issues to consider before successful functional prediction can take place: identifying discriminatory features, and overcoming the challenge of a large imbalance in the training data. We show that by applying feature subset selection followed by undersampling of the majority class, significantly better support vector machine (SVM) classifiers are generated compared with standard machine learning approaches. As well as revealing that the features selected could have the potential to advance our understanding of the relationship between sequence and function, we also show that undersampling to produce fully balanced data significantly improves performance. The best discriminating ability is achieved using SVMs together with feature selection and full undersampling; this approach strongly outperforms other competitive learning algorithms. We conclude that this combined approach can generate powerful machine learning classifiers for predicting protein function directly from sequence.

Algorithms↗
PubMed2001

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian BP variation has been proposed, but data have been conflicting. The aim of the present study was to describe associations between QT dispersion and circadian BP variation as well as autonomic function in type 1 diabetic patients. In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three times in 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (deep breathing test, postural heart rate, and BP response). No patient had received (or had earlier received) antihypertensive or other medical treatment apart from insulin. In a resting 12-lead electrocardiogram, the QT interval was measured by the tangent method in all leads with well-defined T-waves. The measurement was made by one observer blinded to other data. The QT interval was corrected for heart rate using Bazett's formula. The QTc dispersion was defined as the difference between the maximum and the minimum QTc interval in any of the 12 leads. When comparing patients with QTc dispersion below and above the median (43 ms), the latter had significantly higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the group with QTc dispersion >43 ms with significantly higher night/day ratio, both for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01) BP. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated with reduced nocturnal fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters to predict cardiovascular events.

Adult↗
PubMed1998

[Effects of the microwave radiation from the cellular phones on humans and animals].

Biological effects of the mobile phone microwave radiation were shown to depend on many factors: the duration of the irradiation, individual characteristics of the CNS and immune systems, and others. The cellular phone microwave radiation can induce reversible unspecific adaptive responses if it is short and the organism is very radiosensitive. A long-term exposure (over one year) combined with the organism weakened immune system may produce a cumulative effect in the form of stress responses, various damages and, in some cases, even cancer. The ultimate result of the microwave exposure depends on the balance between induced damage and the organism reparative ability.

Animals↗