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At least 1,423 records · Page 79Linked to original sources
PubMed2002

GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway.

Endocytosis of cell-surface proteins via specific pathways is critical for their function. We show that multiple glycosylphosphatidylinositol-anchored proteins (GPI-APs) are endocytosed to the recycling endosomal compartment but not to the Golgi via a nonclathrin, noncaveolae mediated pathway. GPI anchoring is a positive signal for internalization into rab5-independent tubular-vesicular endosomes also responsible for a major fraction of fluid-phase uptake; molecules merely lacking cytoplasmic extensions are not included. Unlike the internalization of detergent-resistant membrane (DRM)-associated interleukin 2 receptor, endocytosis of DRM-associated GPI-APs is unaffected by inhibition of RhoA or dynamin 2 activity. Inhibition of Rho family GTPase cdc42, but not Rac1, reduces fluid-phase uptake and redistributes GPI-APs to the clathrin-mediated pathway. These results describe a distinct constitutive pinocytic pathway, specifically regulated by cdc42.

Animals↗
PubMed2005

Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis.

Highly activated neutrophils play a critical role in mediating organ injury in sepsis by releasing neutrophil elastase (NE). Toll-like receptors (TLRs) play an important role in the host defense against invading microbes, and their signaling pathway is critical to the activation of the proinflammatory response. However, the relationship between TLR expression and the host defense mechanism during sepsis has not been fully elucidated. In this paper, we investigated the relationships among chemokine (MIP-2), TLR-4, and NE expression in human sepsis and murine peritonitis (CLP). TLR-4 expression on monocytes/macrophages was examined in patients with sepsis and in murine peritonitis and was markedly increased in both populations. LPS-induced MIP-2 production by bronchoalveolar cells and liver mononuclear cells in mice with peritonitis was also significantly increased compared with sham-operated mice. Pretreatment of the macrophage cell line, RAW 264.7 cells, with a NE inhibitor before their exposure to LPS resulted in a significant dose-dependent decrease in MIP-2 production, which was comparable to that seen following pretreatment with TLR-4 antibody. Furthermore, NE and LPS both up-regulated TLR-4 expression on human peripheral blood monocytes. Thus, chemokine-induced recruitment of neutrophils in sepsis may result in further increased chemokine production and increased expression of TLR-4. Neutrophil-derived NE may be associated with increased expression of monocyte/macrophage TLR-4, thereby serving as a positive feedback loop for the inflammatory response among the different cell populations.

Animals↗
PubMed2005

PKC-mediated survival signaling in breast carcinoma cells: a role for MEK1-AP1 signaling.

The ability of peptide hormones, as well as the protein kinase C (PKC)-activating phorbol ester (PMA), to protect cells from apoptosis has been demonstrated to occur through activation of cellular signaling pathways such as the mitogen-activated protein kinase (MAPK) and phosphatidyl-inositol-3 kinase (PI3K) families. Here we demonstrate that tumor necrosis factor alpha (TNF)-induced apoptosis is suppressed by treatment with PMA in MCF-7 breast carcinoma cells. Reversal of the PMA survival effect with the classical isoform-specific PKC inhibitor, Go 6976, or the selective mitogen-activated protein kinase kinase (MEK) inhibitor, PD 098059, suggested a partial requirement for PKCalpha and the Erk cascade in MCF-7 cell survival. The ability of these agents to block PMA-mediated cell survival was also correlated with a suppression of PMA-induced AP-1 activity. Some naturally occurring flavonoid compounds such as apigenin can function to block cell signaling cascades such as MAPK. The ability of apigenin to block PMA-mediated cell survival was similarly correlated with suppression of PMA-stimulated AP-1 activity. Our results strongly suggest that PKC- and Erk-dependent pathways are critical components of the cell survival cascade function in suppression of TNF-induced apoptosis in MCF-7 cells. The ability of natural dietary flavonoids such as apigenin to affect cell survival pathways may represent an important aspect of the proposed anti-tumor effects of these compounds.

Apigenin↗
PubMed1996

Clinical pathway implementation in the acute care hospital setting.

A study was conducted to assess the current status of clinical path implementation for acute care cases and to explore implementation issues related to defining discharge outcomes and measuring variances in clinical paths. Results indicated that documentation, identification of critical indicators and discharge outcomes, and variance detection and correction are three core issues that must be addressed by institutions that implement clinical paths. A discussion of each of these areas is provided.

Critical Pathways↗
PubMed2006

[Clinical pathways in endocrinology and diabetology].

Endocrinology and diabetology are disciplines with an interdisciplinary approach. Patients with diabetes or endocrine disorders are diagnosed and treated by multiple disciplines both in an outpatient or in-hospital setting. Additional diabetes-specific professions also participate in the care of diabetic patients. The development of clinical pathways and case-management in institutionalized "Diabetes Centers" and "Endocrinology Centers" as platforms of cooperation is one way to improve patient care and to pool resources. In such centers an interdisciplinary decision support within the diagnostic and therapeutic process is important. E. g., interdisciplinary case conferences expediate and intensify the necessary flow of information. This guarantees the implementation of a rational and concerted treatment according to guidelines and finally optimize the clinical pathways in a continuous process improvement.

Communication↗
PubMed2003

The Drosophila IgC2 domain protein Friend-of-Echinoid, a paralogue of Echinoid, limits the number of sensory organ precursors in the wing disc and interacts with the Notch signaling pathway.

The Notch signaling pathway is critical in cell fate specification throughout development. In the developing wing disc, single sensory organ precursors (SOPs) are selected from proneural clusters via a process of lateral inhibition mediated by the Notch signaling pathway. The epidermal growth factor receptor (EGFR) pathway has also been implicated in SOP formation. Here, we describe the Drosophila melanogaster gene friend of echinoid (fred), a paralogue of echinoid (ed), a gene recently identified as a negative regulator of the EGFR pathway. fred function was examined in transgenic flies by using inducible RNA interference (RNAi). Suppression of fred in developing wing discs results in specification of ectopic SOPs, additional microchaeta, and cell death. In eye-antennal discs, fred suppression causes a rough eye phenotype. These phenotypes are suppressed by overexpression of Notch, Suppressor of Hairless [Su(H)], and Enhancer of split m7. In contrast, overexpression of Hairless, a negative regulator of the Notch pathway, and decreased Su(H) activity enhance these phenotypes. Thus, fred acts in close concert with the Notch signaling pathway. Dosage-sensitive genetic interaction also suggests a close relationship between fred and ed.

Amino Acid Sequence↗
PubMed2006

Cardiac hypertrophy: a risk factor for QT-prolongation and cardiac sudden death.

Cardiac hypertrophy was viewed as a compensatory response to hemodynamic stress. However, cumulative evidence obtained from studies using more advanced technologies in human patients and animal models suggests that cardiac hypertrophy is a maladaptive process of the heart in response to intrinsic and extrinsic stimuli. Although hypertrophy can normalize wall tension, it is a risk factor for QT-prolongation and cardiac sudden death. Studies using molecular biology techniques such as transgenic and knockout mice have revealed many important molecules that are involved in the development of heart hypertrophy and have demonstrated signaling pathways leading to the pathogenesis. With the same approach, the consequence of heart hypertrophy has been examined. The significance of hypertrophy in the development of overt heart failure has been demonstrated and several critical molecular pathways involved in the process were revealed. A comprehensive understanding of the threats of heart hypertrophy to patients has helped to develop novel treatment strategies. The recognition of hypertrophy as a major risk factor for QT-prolongation and cardiac sudden death is an important advance in cardiac medicine. Cellular and molecular mechanisms of this risk aspect are currently under extensively exploring. These studies would lead to more comprehensive approaches to prevention of potential life threatening arrhythmia and cardiac sudden death. The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy.

Adaptation, Physiological↗
PubMed1998

The effects of clinical pathways for renal transplant on patient outcomes and length of stay.

OBJECTIVES: Clinical pathways have been implemented nationwide but little is understood about their effects on efficiency of care and patient outcomes. The present study examined the effects of both development and implementation of two renal transplant pathways. METHODS: Cohorts of patients at a university hospital were compared before, during, and after the development and implementation of two renal transplant clinical pathways: isolated renal transplant from cadaveric donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric and living related donor renal transplants were developed and implemented. Hospital length of stay and complications and infections after renal transplant were determined. RESULTS: Mean length of hospital stay decreased after development and implementation of the cadaveric donor pathway (11.8 days after implementation versus 17.5 days before development). Cadaveric kidney recipients also had statistically fewer complications and infections after both guideline development and guideline implementation (57.1% before, 24.5% during, 18.5% after), but the greatest effect occurred during development. All of these findings persisted after control for demographic and comorbid factors. There were no changes in hospital stay, complications, or infections in the patients who received kidneys from living donors. CONCLUSIONS: The development and use of a clinical pathway for cadaveric donor renal transplant patients was associated with a significant decline in length of stay, complications, and infections, but much of the effect was seen during development rather than during implementation, and a closely related pathway for living related donor patients had no effect. Further understanding of what factors predict an effective pathway and what elements (ie, development or implementation) have an effect should be undertaken.

Adult↗
PubMed1997

Managed care and the cystic fibrosis patient.

Since the first published report of mortality in cystic fibrosis in 1969, the median survival among cystic fibrosis patients has risen from 14 to 31 years. The reasons for this improved survival are complex and include earlier diagnosis; improved control of pulmonary infection; aggressive nutritional intervention; and enhanced monitoring of patients in peer-reviewed, accredited centers for cystic fibrosis care, teaching, and research. Emphasis on the importance of research on changing and improved treatment has been effectively communicated to patients and families. As a result, a group of highly educated medical consumers has been created. During the last decade, another focus of rapid change has appeared, that of cost containment in the medical profession, creating the field of managed care. Practicing medical professionals perceive the need for reduction in excessive spending in medicine and have taken a variety of approaches to balance better the value and cost of medical care while maintaining superb quality. Physicians and consumers continue to have concerns about the potential negative impact of managed care on a relatively rare, specialized, and chronic illness such as cystic fibrosis if managed care concepts are applied without proper understanding of the disease. A great concern is that managed care in cystic fibrosis may cause reversal of trends in improved quality and length of survival. The increased length of survival places an increasing demand on the already stressed system of health care financing. Understanding the changing area of managed care is therefore of paramount importance to clinicians involved in cystic fibrosis care. The Cystic Fibrosis Foundation has presented symposia on managed care at each of the last three annual meetings, including the North American Cystic Fibrosis Meeting, October 1996. The following issues were addressed by speakers and panel discussants, with portions excerpted for this review: trends in managed care, measures and guidelines useful in managed care, Medicaid managed care and cystic fibrosis, and practical aspects of using pathways in caring for patients with cystic fibrosis.

Critical Pathways↗
PubMed1995

Following pathways in pursuit of excellence. Discusses the patient-focused approach of Cheviot and Wandbeck NHS Trust.

Presents Cheviot and Wansbeck NHS Trust's strategy for quality improvement with a patient-focused approach. Describes the development and implementation of multidisciplinary pathways of care. Discusses the benefits of using the pathways. Proposes that multidisciplinary pathways of care are the ideal method of reviewing and coordinating the care process.

Attitude of Health Personnel↗
PubMed1997

Clinical pathways can help manage managed care.

Clinical pathways are designed to map the course of medical or surgical interventions and their expected outcomes. They take into account standards of care and the human and material resources needed to provide specific services. Clinical pathways promote cost-effective, high-quality care and thereby help to standardize practice protocols and coordinate care. Healthcare organizations can decrease lengths of stay, reduce costs, and win more managed care contracts by developing and implementing comprehensive clinical pathways. Pathways can also make carve-outs and other specialty contract services easier to manage.

Contract Services↗
PubMed1999

Flexible rehab path wins wide physician support.

A joint replacement pathway developed at DuBois (PA) Regional Medical Center has made fans out of patients and orthopedic surgeons like, thanks to its extremely flexible approach, which accommodates all the varying practice patterns of the referring physicians. The pathway's designer, himself a physician, devised the pathway to be so flexible because he realized that the orthopedic physicians would never be persuaded to standardize their practice patterns. Even with the designer's attempts at accommodation, many orthopedic physicians held off endorsing the pathway until patients began sharing their enthusiasm for it. The pathway has served as a useful training tool for young physical therapists.

Arthroplasty, Replacement, Hip↗
PubMed2001

Pathway achieves first steps toward improvement.

In 1999, Pomona Valley Hospital in Claremont, CA, saw a real need to revise its treatment of community-acquired pneumonia. After a thorough chart review and development of a new pathway, the case management team has taken an important step toward a standard of care.

California↗
PubMed2001

CM cooperation skills help doctors to 'buy in'.

Physicians play a key role in making your care pathways successful, says Maria Brillant, RN, coordinator of case management at NYU Medical Center. Case managers at her facility have a philosophy of cooperation that encourages the right doctors to champion the right pathways. Using a step-by-step pathway for getting buy-in can help case managers and physicians foster cooperation.

Attitude of Health Personnel↗
PubMed2001

Stroke pathways.

Stroke pathways are task-orientated structured multidisciplinary care plans which detail essential steps and interventions during the period of care of a "typical" stroke patient. Pathway development and implementation are best achieved by an appointed champion leading a multidisciplinary team of health care workers and administrators, who will also be the end users of the pathway. Pathway development involves reviews of existing clinical practice guidelines and pathways, followed by documentation, interdigitation and prioritization of care requirements at different time points in the various spheres, taking into consideration local philosophies and practices. These spheres could include investigations, pharmacologic treatment, rehabilitative therapy, nursing measures, and patient education. This would result in evidence-based holistic quality care, wide support base, efficient service provision, reduced costs and length of stay, less practice variation, improved communication among disciplines, enhanced patient-staff relationship, ease of audit and research opportunities. Components of the pathway could include a patient summary sheet, multidisciplinary record of the various activities structured on a day-to-day basis, sign-off columns for staff responsible for performing those activity, variance sheet, and separate protocols for specific issues. Implementation requires training of users, pilot runs, feedback, regular revisions, monitoring of compliance, and analysis of variances. Widespread implementation of pathways may be hindered by lack of support, and concerns about increased time requirements and costs, stifling of innovation, restriction of application of clinical judgement, lack of applicability to all patients, misuse and legal issues. However, a well-designed pathway will ensure quality care in a cost-efficient manner, benefiting the patient, carer and the health care service.

Critical Pathways↗
PubMed2000

A care pathway for COPD.

Nurses can have a major impact on the management of patients with COPD. A carefully planned care pathway can improve patient and staff satisfaction. The BTS COPD guidelines provided the impetus for improving levels of care.

Critical Pathways↗
PubMedDate not supplied

Cancer care. Part 1. Mental health care for women with breast cancer.

Women with breast cancer often experience anxiety and depression related to their diagnosis, treatment and prognosis. A collaborative project was set up by a breast care nurse and a liaison psychiatric nurse after they detected a gap in the services on offer to these women. Their initiative uses an established assessment tool to detect potential mental health problems and a patient pathway to ensure that the women's needs are monitored and met throughout their illness.

Anxiety↗
PubMed2003

Molecular genetic perspectives on cross-talk and specificity in abiotic stress signalling in plants.

The perception of abiotic stresses and signal transduction to switch on adaptive responses are critical steps in determining the survival and reproduction of plants exposed to adverse environments. Plants have stress-specific adaptive responses as well as responses which protect the plants from more than one environmental stress. There are multiple stress perception and signalling pathways, some of which are specific, but others may cross-talk at various steps. Recently, progress has been made in identifying components of signalling pathways involved in salt, drought and cold stresses. Genetic analysis has defined the Salt-Overly-Sensitive (SOS) pathway, in which a salt stress-induced calcium signal is probably sensed by the calcium-binding protein SOS3 which then activates the protein kinase SOS2. The SOS3-SOS2 kinase complex regulates the expression and activity of ion transporters such as SOS1 to re-establish cellular ionic homeostasis under salinity. The ICE1 (Inducer of CBF Expression 1)-CBF (C-Repeat Binding Protein) pathway is critical for the regulation of the cold-responsive transcriptome and acquired freezing tolerance, although at present the signalling events that activate the ICE1 transcription factor during cold stress are not known. Both ABA-dependent and -independent signalling pathways appear to be involved in osmotic stress tolerance. Components of mitogen-activated protein kinase (MAPK) cascades may act as converging points of multiple abiotic as well as biotic stress signalling pathways. Forward and reverse genetic analysis in combination with expression profiling will continue to uncover many signalling components, and biochemical characterization of the signalling complexes will be required to determine specificity and cross-talk in abiotic stress signalling pathways.

Abscisic Acid↗