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At least 217 records · Page 12Linked to original sources
PubMed2003

HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection.

All primate lentiviruses (HIV-1, HIV-2, SIV) encode Nef proteins, which are important for viral replication and pathogenicity in vivo. It is not known how Nef regulates these processes. It has been suggested that Nef protects infected cells from apoptosis and recognition by cytotoxic T lymphocytes. Other studies suggest that Nef influences the activation state of the infected cell, thereby enhancing the ability of that cell to support viral replication. Here we show that macrophages that express Nef or are stimulated through the CD40 receptor release a paracrine factor that renders T lymphocytes permissive to HIV-1 infection. This activity requires the upregulation of B-cell receptors involved in the alternative pathway of T-lymphocyte stimulation. T lymphocytes stimulated through this pathway become susceptible to viral infection without progressing through the cell cycle. We identify two proteins, soluble CD23 and soluble ICAM, that are induced from macrophages by Nef and CD40L, and which mediate their effects on lymphocyte permissivity. Our results reveal a mechanism by which Nef expands the cellular reservoir of HIV-1 by permitting the infection of resting T lymphocytes.

B-Lymphocytes↗
PubMed2003

Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1.

The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, providing an integral link between XBP-1, the UPR and plasma cell differentiation. Signals involved in plasma cell differentiation, specifically interleukin-4, control the transcription of XBP-1, whereas its post-transcriptional processing is dependent on synthesis of immunoglobulins during B cell differentiation. We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR.

Animals↗
PubMed2001

Mitogenesis and endocytosis: What's at the INTERSECTIoN?

Endocytosis is a regulated physiological process by which cell surface proteins are internalized along with extracellular factors such as nutrients, pathogens, peptides, toxins, etc. The process begins with the invagination of small regions of the plasma membrane which ultimately form intracellullar vesicles. These internalized vesicles may shuttle back to the plasma membrane to recycle the membrane components or they may be targeted for degradation. One role for endocytosis is in the attenuation of receptor signaling. For example, desensitization of activated membrane bound receptors such as G-protein coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs) occurs, in part, through endocytosis of the activated receptor. However, accumulating evidence suggests that endocytosis also mediates intracellular signaling. In this review, we discuss the experimental data that implicate endocytosis as a critical component in cellular signal transduction, both in the initiation of a signal as well as in the termination of a signal. Furthermore, we focus our attention on a recently described adaptor protein, intersectin (ITSN), which provides a link to both the endocytic and the mitogenic machinery of a cell. Thus, ITSN functions at a crossroad in the biochemical regulation of cell function.

Adaptor Proteins, Vesicular Transport↗
PubMed2000

Knowledge management in the NHS: positioning the healthcare librarian at the knowledge intersection.

This paper defines what is meant by Knowledge Management, investigates how it interlinks with new ways of delivering health care and gives a synopsis of a study that investigated issues around implementation of Knowledge Management across a sample of healthcare librarians. Areas of investigation that are related to Knowledge Management include: HSG(97)47, evidence-based medicine, clinical governance, information and communication technologies, and the changing role of the healthcare librarian. A diagram is included in this paper which illustrates how the healthcare librarian interacts with resources, staff and practices, so contributing to the knowledge base of health care. The paper concludes that Government policy, new technologies and the push towards the practice of information age medicine are forcing changes throughout the NHS. Recognition of Knowledge Management is still in its infancy in the NHS--it calls for major change in organizational thinking and acceptance by the librarian that their service must also be subject to continuous improvement.

Humans↗
PubMed2002

The nature of psychiatric nursing: the intersection of paradigm, evolution, and history.

Psychiatric nursing, while vibrant and applicable once, is predicated on an approach to care and an understanding of mental illness that reflects an older time. Psychiatric nursing is in the precarious position of having an aging paradigm of practice, rooted in older knowledge and beliefs and recalcitrant to new knowledge and new realities of clinical practice. This article highlights paradigmatic assumptions and identifies the two dominant knowledge structures that struggle to coexist within that paradigm. Practical consequences of practicing psychiatric nursing with an aging paradigm are reviewed and a beginning point for the development of a new paradigm is presented.

Forecasting↗
PubMed2003

[Health services research: subject matter and objectives of a field at the intersection of economics, medicine and ethics].

In analogy to the famous saying that war is too serious to leave it to the generals, one could say that the provision of medical care is too serious and too costly to leave it to doctors. This, however.would give the impression of an incongruity which does not exist as an actual factor or as a standpoint in research on the healthcare system. Having said that, there are differences in the methods of observation used: doctors always base their observations on their experiences at the doctor/patient level. In these situations, they are influenced by the therapeutic imperative of wanting to help and their convictions do not allow them to take into account competing requirements or to feel dependent on the higher-level conditions; and the realm of research on the health care system bases its observations more or less on findings derived by means of analysing what is often highly aggregated data, be it of a medical, economic or epidemiological nature. Even though the insights gained at the macrolevel ultimately have to be applied at the microlevel of the doctor/patient relationship, there remains an internal distance from the problems of care which is conducive to proper judgement. From this distant vantage point, researchers attempt to prove the relationship between effort and yield, to indicate weak spots which individual doctors cannot recognise and to define capacity, structure and incentive conditions which guarantee maxi-mum medical care quality. There is, for instance, evidence of astonishing dependence between the medical care provided and incentives for the number of doctor/patient contacts, use of medicines, surgery rates and number of diagnoses. This evidence can be used to draw up recommendations for self-governing bodies in the health care sector and for the political sphere as to how the health care system could be enhanced to achieve a high level of efficiency and quality.

Adolescent↗
PubMed1994

Intersecting epidemics--crack cocaine use and HIV infection among inner-city young adults. Multicenter Crack Cocaine and HIV Infection Study Team.

BACKGROUND AND METHODS: The smoking of "crack" cocaine is thought to be associated with high-risk sexual practices that accelerate the spread of infection with the human immunodeficiency virus (HIV). We studied 2323 young adults, 18 to 29 years of age, who smoked crack regularly or who had never smoked crack. The study participants, recruited from the streets of inner-city neighborhoods in New York, Miami, and San Francisco, were interviewed and tested for HIV. This report presents the findings for the 1967 participants (85 percent) who had never injected drugs. RESULTS: Of the 1137 crack smokers, 15.7 percent were positive for HIV antibody, as compared with 5.2 percent of the 830 nonsmokers (prevalence ratio adjusted for the city, 2.4; 99 percent confidence interval, 1.7 to 3.6). The prevalence of HIV was highest among the crack-smoking women in New York (29.6 percent) and Miami (23.0 percent). Of the 283 women who had sex in exchange for money or drugs, 30.4 percent were infected with HIV as compared with 9.1 percent of the 286 other women (prevalence ratio, 3.1; 99 percent confidence interval, 1.9 to 5.1); of the 91 men who had anal sex with other men, 42.9 percent were infected with HIV as compared with 9.3 percent of the 582 men who did not have anal sex with other men (prevalence ratio, 4.7; 99 percent confidence interval, 3.0 to 7.4). In multivariable analyses, these high-risk sexual practices accounted for the higher prevalence of HIV infection among the crack smokers, as compared with those who did not smoke crack. Women who had recently had unprotected sex in exchange for money or drugs were as likely to be infected as men who had had sex with men (40.9 percent vs. 42.9 percent). CONCLUSIONS: In poor, inner-city communities young smokers of crack cocaine, particularly women who have sex in exchange for money or drugs, are at high risk for HIV infection. Crack use promotes the heterosexual transmission of HIV.

Adolescent↗
PubMed2003

M. M. House mental classification revisited: Intersection of particular patient types and particular dentist's needs.

Fifty-three years ago, M. M. House devised a classification of patients on the basis of how they behaved in response to the prospect of becoming edentulous and on how they subsequently adapted to wearing complete dentures. Although House's system was an important contribution, it failed to consider the dentist's emotional reaction to a patient's behavior as part of an understanding of how the patient and doctor cope with the dental treatment. This article presents an expansion of the House classification to include the behavior of the dentist as a codeterminer of the patient's behavior. This expanded classification system is based on empiricism and awaits scientific validation or clinical application to determine its ultimate validity, reliability, and effectiveness.

Adaptation, Psychological↗
PubMed1980

The effect of blurring on intersecting-line illusions.

It was observed by chance that illusions in patterns consisting of criss-crossing lines, such as the Orbison and Hering illusions, are markedly reduced when the patterns are blurred. In the first of two experiments the reduction with blurring was confirmed for four patterns but failed to occur in patterns lacking criss-crossing lines. In the second experiment the reduction was shown to be due mainly to the reduced luminance contrast in blurred patterns, thus confirming earlier findings on the effect of contrast of this group of illusions. Theoretical implications are discussed.

Adolescent↗
PubMed1996

Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain.

Paraneoplastic neurologic disorders (PNDs) are believed to be autoimmune neuronal degenerations that develop in some patients with systemic cancer. A series of genes encoding previously undiscovered neuronal proteins have been cloned using antiserum from PND patients. Identification of these onconeural antigens suggests a reclassification of the disorders into four groups: those in which neuromuscular junction proteins, nerve terminal/vesicle-associated proteins, neuronal RNA binding proteins, or neuronal signal-transduction proteins serve as target antigens. This review considers insights into basic neurobiology, tumor immunology, and autoimmune neuronal degeneration offered by the characterization of the onconeural antigens.

Antigens, Neoplasm↗
PubMed2000

BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins.

Two major pathways for induction of apoptosis have been identified-intrinsic and extrinsic. The extrinsic pathway is represented by tumor necrosis factor family receptors, which utilize protein interaction modules known as death domains and death effector domains (DEDs) to assemble receptor signaling complexes that recruit and activate certain caspase-family cell death proteases, namely procaspases-8 and -10. The intrinsic pathway for apoptosis involves the participation of mitochondria, which release caspase-activating proteins. Bcl-2 family proteins govern this mitochondria-dependent apoptosis pathway, with proteins such as Bax functioning as inducers and proteins such as Bcl-2 and Bcl-X(L) serving as suppressors of cell death. An apoptosis regulator, BAR, was identified by using a yeast-based screen for inhibitors of Bax-induced cell death. The BAR protein contains a SAM domain, which is required for its interactions with Bcl-2 and Bcl-X(L) and for suppression of Bax-induced cell death in both mammalian cells and yeast. In addition, BAR contains a DED-like domain responsible for its interaction with DED-containing procaspases and suppression of Fas-induced apoptosis. Furthermore, BAR can bridge procaspase-8 and Bcl-2 into a protein complex. The BAR protein is anchored in intracellular membranes where Bcl-2 resides. BAR therefore may represent a scaffold protein capable of bridging two major apoptosis pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Cross-induction of glc and ace operons of Escherichia coli attributable to pathway intersection. Characterization of the glc promoter.

The metabolic pathways specified by the glc and ace operons in Escherichia coli yield glyoxylate as a common intermediate, which is acted on by two malate synthase isoenzymes: one encoded by glcB and the other by aceB. Null mutations in either gene exhibit no phenotype, because of cross-induction of the ace operon by glycolate and the glc operon by acetate. In this study, the regulation of the glc operon, comprising the structural genes glcDEFGB, was analyzed at the molecular level. This operon, activated by growth on glycolate, is transcribed as a single message and is under the positive control of GlcC encoded by a divergent gene. Expression of the glc operon is strongly dependent on the integration host factor (IHF) and is repressed by the global respiratory regulator ArcA-P. In vitro gel-shift experiments demonstrated direct binding of the promoter DNA to IHF and ArcA-P. Mutant analysis indicated that cross-induction of the glc operon by acetate is mediated by the GlcC protein that recognizes the compound as an alternative effector. The similar pattern of regulation of the Glc and Ace systems by IHF and ArcA-P ensures their effective cross-induction.

Acetic Acid↗
PubMed2003

Protein kinase A intersects SRC signaling in membrane microdomains.

Regulation of Src kinase activity is tightly coupled to the phosphorylation status of the C-terminal regulatory tyrosine Tyr(527), which, when phosphorylated by Csk, represses Src. Here, we demonstrate that activation of Csk through a prostaglandin E(2)-cAMP-protein kinase A (PKA) pathway inhibits Src. This inhibitory pathway is operative in detergent-resistant membrane fractions where cAMP-elevating agents activate Csk, resulting in a concomitant decrease in Src activity. The inhibitory effect on Src depends on a detergent-resistant membrane-anchored Csk and co-localization of all components of the inhibitory pathway in membrane microdomains. Furthermore, epidermal growth factor-induced activation of Src and phosphorylation of the Src substrates Cbl and focal adhesion kinase are inhibited by activation of the cAMP-PKA-Csk pathway. We propose a novel mechanism whereby G protein-coupled receptors inhibit Src signaling by activation of Csk in a cAMP-PKA-dependent manner.

CSK Tyrosine-Protein Kinase↗
PubMedDate not supplied

A heroin epidemic at the intersection of histories: the 1960s epidemic among African Americans in Baltimore.

In the drug field the fundamental epidemiological question-why illicit drug use, here, now, among these people-has still not been adequately answered. Drawing on the work of colleagues in medical anthropology, we attempt to move closer to an answer by developing a "trend theory." In this article we analyze a single case: the increase in heroin use and addiction among African Americans in the City of Baltimore in the 1960s. We found that the two most important historical processes behind the epidemic were (1) a changing distribution/supply system and (2) the mix of hope and despair that was part of the early civil rights movement.

Black or African American↗