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The neurologic complications of human immunodeficiency virus infection.

The physician caring for HIV-1-infected patients must have a good working knowledge of the broad spectrum of neurologic diseases that occur in association with this infection. As with any other neurologic disorder, the site of the neuraxis that is affected must be properly identified. In HIV-1-infected persons, more than one site may be involved simultaneously, such as the coexistence of myelopathy and peripheral neuropathy, often resulting in a confusing array of neurologic signs and symptoms. The frequent occurrence of two or more diseases affecting the neuraxis, such as progressive multifocal leukoencephalopathy and toxoplasmosis, further complicates the picture. With the AIDS patient, the physician cannot rely on the clinical adage that all attempts should be made to ascribe the patient's problems to one disease. Often, it is not the case. As with other illnesses, the approach to the HIV-1-infected person with neurologic disease needs to be thorough and fluid. After rendering a diagnosis and embarking on therapy, the physician needs to be open minded about the possibility of an incorrect or additional diagnosis not previously considered. Lastly, despite all the knowledge that has been accumulated in the first decade of the AIDS epidemic, new illnesses occurring with HIV-1 infection are recognized with regularity. The physician must always bear in mind that the illness with which he or she is confronted may be one that has not been previously described.

AIDS-Related Opportunistic Infections↗

Ice (photo)chemistry. Ice as a medium for long-term (photo)chemical transformations--environmental implications.

This review accounts for the current knowledge about the distribution, accumulation, and chemical/photochemical transformations of persistent, bioaccumulative, and toxic compounds (PBTs) in water ice, especially in the connection with polar regions and atmospheric cloud particles. (Photo)reactions on/in ice are discussed in terms of photochemistry, photobiology, paleochemistry, as well as astrophysics. Authors propose a model, in which a significant amount of some PBTs are generated by (photo)chemistry of primary pollutants in ice, which may subsequently be released to the environment. It is argued that ice photochemistry might play an important role in the chemical transformations in cold ecosystems and in the upper atmosphere, particularly now when the ozone layer is partially depleted.

Air Pollutants↗

Endogenous opiates: 1980.

Vast amounts of research have been done that have attempted to delineate the pharmacological and physiological effects of the endogenous opiate peptides. A great deal of knowledge has also been accumulated in a limited time span concerning the types and locations of the opiate receptors and peptides, as well as their functions. In 1980, reports were made concerning the effects of these peptides on analgesia, on tolerance and dependence, on activity, on learning and memory, on schizophrenia and other types of emotional disturbances, and on physiological responses such as eating and drinking, cardiovascular responses, and sexual function. Additional understanding was also gained concerning their interactions with neurotransmitters, other neuropeptides, and hormones. These and other studies published only in 1980 are reviewed in this paper, which is the third of an annual series.

Animals↗

Glycosylation of hepatitis C virus envelope proteins.

Enveloped viruses are surrounded by a membrane derived from the host-cell that contains proteins called "envelope proteins". These proteins play a major role in virus assembly and entry. In most of the enveloped viruses, they are modified by N-linked glycosylation which is supposed to play a role in their stability, antigenicity and biological functions. Glycosylation is also known to play a major role in the biogenesis of proteins by being directly and/or indirectly involved in protein folding. Recent studies on hepatitis C virus (HCV) envelope proteins have revealed a complex interplay between cleavage by signal peptidase, folding and glycosylation. The knowledge that has been accumulated on the early steps of glycosylation of these proteins is presented in this review.

Binding Sites↗

Rudolf Virchow and modern aspects of tumor pathology.

Rudolf Virchow (1821-1902), the great German pathologist of the 19th century, founder of the "Zellularpathologie", also dealt with principal problems of tumor pathology. His theoretical concepts concern the definition and characterization of the tumor process, the dignity and diagnosis, published especially in his 3 monographs "Die Entwicklungsgeschichte des Krebses" (1847), "Handbuch der speciellen Pathologie und Therapie" (1854) and "Die krankhaften Geschwülste" (1863-65). The achievements of Rudolf Virchow are not related to the description and diagnosis of specific tumors together with their genesis and interpretation. There have been quite a few errors and false concepts which can longer be accepted today. The timeless modernity and topicality of Rudolf Virchow's postulations on tumor pathology is based on his general conclusions which as key propositions have retained general validity throughout more than a century. They have been confirmed and further interpreted by knowledge which has been accumulated largely over the past one or two decades in the fields of tumor research, electron microscopy, molecular biology, genetics, and immunology.

Germany↗

Impact of aging on DNA methylation.

The biochemistry of aging is complex, with biologically significant changes occurring in proteins, lipids and nucleic acids. One of these changes is in the methylation of DNA. DNA methylation is a mechanism modifying gene expression. The methylation of sequences in or near regulatory elements can suppress gene expression through effects on DNA binding proteins and chromatin structure. Both increases and decreases in methylation occur with aging, depending on the tissue and the gene. These changes can have pathologic consequences, contributing to the development of malignancies and autoimmunity with aging, and possibly to other disorders as well. Thus, while aging can impact on DNA methylation, the changes in DNA methylation can also impact on aging. This review summarizes current evidence for changes in the methylation status of specific genes with aging, their impact on diseases that develop with aging, and mechanisms that may contribute to the altered DNA methylation patterns. As this field is still developing, it is anticipated that new knowledge will continue to accumulate rapidly.

Aging↗

Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device.

Although a wealth of knowledge about chemotaxis has accumulated in the past 40 years, these studies have been hampered by the inability of researchers to generate simple linear gradients instantaneously and to maintain them at steady state. Here we describe a device microfabricated by soft lithography and consisting of a network of microfluidic channels that can generate spatially and temporally controlled gradients of chemotactic factors. When human neutrophils are positioned within a microchannel, their migration in simple and complex interleukin-8 (IL-8) gradients can be tested. The cells exhibit strong directional migration toward increasing concentrations of IL-8 in linear gradients. Neutrophil migration halts abruptly when cells encounter a sudden drop in the chemoattractant concentration to zero ("cliff" gradient). When neutrophils are challenged with a gradual increase and decrease in chemoattractant ("hill" gradient), however, the cells traverse the crest of maximum concentration and migrate further before reversing direction. The technique described in this paper provides a robust method to investigate migratory cells under a variety of conditions not accessible to study by earlier techniques.

Biological Assay↗

The problem and management of sickness absence in the NHS: considerations for nurse managers.

AIM: This paper examines the topic of sickness absence management in the context of the healthcare sector. BACKGROUND: National Health Service (NHS) employee absenteeism is an expensive and difficult problem. Nurse managers need to assess the extent and characteristics of absenteeism, be aware of their organization's sickness policies, evaluate the effectiveness of these policies and contribute to the development of related initiatives to ensure prudent management of sickness absence. METHOD: A literature review has been undertaken, providing a broad conceptual context by which the problem of sickness absence in the NHS can be examined. The focus of this paper is to examine the accumulation of research based knowledge to provide a healthcare perspective on the problem of sickness absence management. CONCLUSION: Sickness absence management within the NHS is challenging but provides opportunities to improve the working lives of NHS employees. Sickness absence cannot be eradicated but it can be reduced by a selection of measures that reflect the uniqueness of the NHS. The many and diverse causes of sickness absence need acknowledgement, when devising strategies that can effectively provide solutions to the problems of sickness absence.

Absenteeism↗

Design of integrated practice for learning professional competences.

To acquire professional competences that entail performance of complex skills, an authentic learning environment is required focused on the integration of all aspects of competences. However, most educational programmes offer separate building blocks, such as separate modules for knowledge and skills. Students accumulate what they have learned in these modules as they progress through the curriculum. In this paper the authors advocate the Four-Component Instructional Design model (4C/ID), which offers a whole-task approach to course design for programmes in which students learn complex skills. The four core components of this approach are: learning tasks, supportive information, just-in-time information and part-task practice. A concrete example from medical education will be presented to clarify both the general ideas behind this approach and the differences between the whole-task approach and conventional educational designs.

Education, Medical↗

Etiologic evidence and primary prevention of cancer.

For many decades, primary prevention of cancer was implemented on the basis of evidence for a causal relationship between exposure and human cancer that took into consideration biological plausibility, but did not depend on the degree of understanding of the underlying mechanisms. One of the credos of public health is that primary prevention can be implemented before reaching a complete understanding of mechanisms that could confirm/explain causality. Measures of primary prevention are taken on the basis of what is recognized as causative factors of human cancer. The most authoritative lists of recognized human carcinogens are those compiled from the evaluations of carcinogenic risk carried out by the International Agency for Research on Cancer (IARC) and the evaluations that the U.S. National Toxicology Program (NTP) publishes in its periodical Report on Carcinogens. Knowledge of mechanisms is accumulating at a fast pace, and although it has not yet led to the definition of an efficient strategy for primary prevention for the majority of cancer cases, it may drive the scientific establishment toward a high-risk approach to prevention. The most reasonable and socially acceptable development of primary prevention should be the blending of a population approach; that is, the shifting of the distribution of risk factors across an entire population in a favorable direction (e.g., a general decrease of the levels of exposure to environmental carcinogens) with the high-risk approach that will concern individuals with extreme values of genetically determined weaknesses in the interactions with the environment.

Carcinogens↗

Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young.

Pediatric bipolar disorder is commonly mixed with co-occurring symptoms of major depression and mania. Knowledge has begun to accumulate on the treatment of the mania component, but limited information is available to guide the therapeutic approach to bipolar depression. To this end, we reviewed the medical charts of 59 patients with diagnosis of DSM-III-R bipolar disorder from an outpatient pediatric psychopharmacology clinic. Multivariate methods were used to model the probability of improvement and relapse at each visit of clinical follow-up. Serotonin-specific antidepressants were significantly associated with both an increased rate of improvement of bipolar depression-relative risk = 6.7 (1.9-23.6); p = 0.003-and a significantly greater probability of relapse of manic symptomatology-relative risk = 3.0 (1.2-7.8); p = 0.02. Although mood stabilizers improved manic symptomatology, they had no demonstrable effect on the symptoms of bipolar depression. Despite the increased risk of mood destabilization, serotonin-specific antidepressants did not interfere with the antimanic effects of mood stabilizers. Because bipolar youth commonly come to clinical practice with depression, these results underscore the importance of assessing a lifetime history of bipolar disorder in making treatment decisions in depressed youth.

Adolescent↗

Proteasome function in aging and oxidative stress: implications in protein maintenance failure.

Damage to cellular components by reactive oxygen species is believed to be an important factor contributing to the aging process. Likewise, the progressive failure of maintenance and repair is believed to be a major cause of biological aging. Cellular aging is characterized by the accumulation of oxidatively modified proteins, a process that results, at least in part, from impaired protein turnover. Indeed, oxidized protein buildup with age may be due to increased protein damage, decreased elimination of oxidized protein (i.e., repair and degradation), or a combination of both mechanisms. Since the proteasome has been implicated in both general protein turnover and the removal of oxidized protein, the fate of the proteasome during aging has recently received considerable attention, and evidence has been provided for impaired proteasome function with age in different cellular systems. The present review will mainly address age-related changes in proteasome structure and function in relation to the impact of oxidative stress on the proteasome and the accumulation of oxidized protein. Knowledge of molecular mechanisms involved in the decline of proteasome function during aging and in oxidative stress is expected to provide new insight that will be useful in defining antiaging strategies aimed at preserving this critical function.

Aging↗

New developments in aetiological mechanisms of inflammatory bowel disease.

This review in depth considers the new knowledge and some hypotheses accumulated during the last few years regarding the aetiology of inflammatory bowel disease. The role of genetic susceptibility, in particular the first gene where a mutation is responsible for part of patients with Crohn's disease, is discussed. The consequence for phenotype variability and the environmental influences regarding manifestation of the disease are analysed by experts. Finally, alternative hypotheses including an immune deficiency and defective local bacterial response are demonstrated.

Carrier Proteins↗

Ruth Ann Sanger.

Ruth Ann Sanger's scientific career was concerned with the delineation and mapping of human blood group genes by simple manual methods using, as tools, blood group antibodies and the agglutination reaction followed by statistical analysis of the results. Her active period coincided with the flowering of the whole subject of blood groups, which was initiated by the recognition of the clinical significance of the Rh antigens and the rediscovery of the antiglobulin reaction by Coombs, Mourant and Race (Coombs et al. 1945). In these days of 'high-technology' research, it is salutary to recognize that the complex body of knowledge that has been accumulated about blood groups has been derived by using the very simple technique of the visible cross-linking of red cells by antibodies specific for the blood group antigens present on the red cell surface. Ladsteiner had by chance discovered the ABO blood group system in 1900 with the use of the agglutination reaction, but little progress was made in the next 45 years and we know that the main reason for this is that most blood group antibodies are not physically capable of bringing about the cross-linking and agglutination of red cells on their own. This problem was solved by the introduction of the antiglobulin reaction, which uses a secondary antibody to bring about the cross-linking of blood group antibodies already attached to red cells.

Australia↗

A unified framework for image retrieval using keyword and visual features.

In this paper, a unified image retrieval framework based on both keyword annotations and visual features is proposed. In this framework, a set of statistical models are built based on visual features of a small set of manually labeled images to represent semantic concepts and used to propagate keywords to other unlabeled images. These models are updated periodically when more images implicitly labeled by users become available through relevance feedback. In this sense, the keyword models serve the function of accumulation and memorization of knowledge learned from user-provided relevance feedback. Furthermore, two sets of effective and efficient similarity measures and relevance feedback schemes are proposed for query by keyword scenario and query by image example scenario, respectively. Keyword models are combined with visual features in these schemes. In particular, a new, entropy-based active learning strategy is introduced to improve the efficiency of relevance feedback for query by keyword. Furthermore, a new algorithm is proposed to estimate the keyword features of the search concept for query by image example. It is shown to be more appropriate than two existing relevance feedback algorithms. Experimental results demonstrate the effectiveness of the proposed framework.

Algorithms↗

Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis.

Malignant transformation is associated with abnormal glycosylation, resulting in the synthesis and expression of altered carbohydrate determinants including sialyl Lewisa and sialyl Lewisx. The sialyl Lewisa and sialyl Lewisx determinants appear in the sera of patients with cancer, and are extensively utilized for serum diagnosis of cancers in Japan. Sialyl Lewisa and sialyl Lewisx are involved in selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants are thought to be closely associated with hematogenous metastasis of cancers. Recent progress in this area includes the following: 1. Substantial increases in solid clinical statistics that further confirm the contribution of these determinants in the progression of a wide variety of cancers; 2. Elucidation of the ligand specificity of the three family members of selectins and evaluation of the roles of these molecules in cancer cell adhesion; and 3. Advances in the study of the mechanism that leads to the enhanced expression of the sialyl Lewis(a/x) determinants in malignant cells. These recent results have confirmed that these determinants are not merely markers for cancers, but are functionally implicated in the malignant behavior of cancer cells. The results also suggested that the increase of these determinants in malignant cells is an inevitable consequence of the malignant transformation of cells. Considerable new knowledge has also been accumulated regarding the therapeutic implications for suppression of hematogenous metastasis targeting this cell adhesion system.

Antigens, Tumor-Associated, Carbohydrate↗

Expression of cyclin E in resting and activated B-chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target.

Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E-cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E-cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL.

Aged↗

The changing nature of fatherhood: the nurse and social policy.

Fathers, fathering and fatherhood are topics which receive little attention throughout the world's professional literature. Only recently has there been increased interest and research on the changing roles of men with particular emphasis on nurturing and parenting. A body of knowledge has started to accumulate which investigates the role of fathers with their families. The purpose of this article is to summarize the research literature about fatherhood in the United States of America today and to discuss the implications of this research for the practice of nursing. This analysis synthesizes the literature using two different perspectives. The developmental perspective traces the role of fathers from family planning through the family life cycle to grandfatherhood. The social contextual perspective summarizes the literature related to fathers for three common variations in society today: single custodial fathers, fathers in dual earner families, and adolescent fathers. Lastly, implications for nursing practice and social policy are discussed.

Family↗