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PubMedDate not supplied

Resistance to re-infection after exposure to normal and attenuated schistosome parasites in the baboon model.

The baboon model of schistosomiasis has been used extensively to study parasite biology, immune responses and pathological manifestations after natural and experimental infections. The body of knowledge accumulated so far has placed this animal model at the pinnacle in the continuing search for new interventions and might hold the key to the development of new anti-schistosome vaccines. In this review paper, we highlight previous and recent studies that have elevated the baboon to be the model of choice for schistosomiasis research. In particular, the long-term studies of re-infection after chemotherapy as well as the interaction between vaccination, chemotherapy and infection are highlighted.

Animals↗
PubMed2006

Pediatric bipolar disease: current and future perspectives for study of its long-term course and treatment.

AIM AND METHODS: Findings from recent long-term, prospective longitudinal studies of the course, outcome and naturalistic treatment of adults with bipolar illness are highlighted as background for long-term developmental study of pediatric bipolar illness. RESULTS: Accumulating knowledge of bipolar illness in adults underscores a high risk for multiple recurrences through the lifespan, significant medical morbidity, high rates of self-harm, economic and social burden and frequent treatment resistance with residual symptoms between major episodes. At present, there is no empirical foundation to support any assumption about the long-term course or outcome of bipolar illness when it arises in childhood or adolescence, or the effects of conventional pharmacotherapies in altering its course and limiting potentially adverse outcomes. The proposed research articulates specific descriptive aims that draw on adult findings and outlines core methodological requirements for such an endeavor. CONCLUSIONS: Innovations in the description and quantitative analysis of prospective longitudinal clinical data must now be extended to large, systematically ascertained pediatric cohorts recruited through multicenter studies if there is to be a meaningful scientific advance in our knowledge of the enduring effects of bipolar illness and the potential value of contemporary approaches to its management.

Age of Onset↗
PubMed1997

Leukocyte adhesion--structure and function of human leukocyte beta2-integrins and their cellular ligands.

Leukocyte adhesion is of pivotal functional importance and this has resulted in extensive research and rapid development in the field. Leukocyte adhesion involves members of three molecular families: integrins, members of the immunoglobulin superfamily and carbohydrate binding selectins and sialoadhesins. Recently, considerable structural information on leukocyte integrins and members of the immunoglobulin superfamily of adhesion molecules has been obtained. This fact, combined with the identification of several novel adhesion molecules, has increased our understanding of how they function at the molecular level. Furthermore, the important issue of how integrins are activated to become adhesive is rapidly advancing. It is clearly evident that the knowledge accumulated from basic research will increasingly be applied in clinical medicine. In this review we focus on two important families of adhesion molecules, the leukocyte-specific beta2-integrins and their ligands, the intercellular adhesion molecules. Emphasis is put on their structural/functional relationships, their mode of regulation and on novel adhesion molecules recently discovered.

Amino Acid Sequence↗
PubMed2006

Brief report: lack of a race effect in primary care ratings among women veterans.

OBJECTIVE: To explore the effect of race on primary care quality and satisfaction among women in the Department of Veterans Affairs (VA). METHODS: We used a mail survey to measure primary care quality and satisfaction. We focused on 4 primary care domains: patient preference for provider, interpersonal communication, accumulated knowledge, and coordination. We performed univariate analyses to compare variables by race and multiple logistic regression analysis to examine the effect of race on the probability of reporting a perfect score on each domain, while adjusting for patient characteristics and site. RESULTS: Black women were younger, unmarried, educated, of higher income, and reported female providers and gynecological care in VA more often. In regression analysis, race was not significantly associated with any primary care domain or satisfaction. Gynecological care from VA provider was associated with perfect ratings on patient preference for provider (odds ratio [OR] 2.0, 95% confidence intervals [CI] 1.3, 3.1), and satisfaction (OR 1.6, 95% CI 1.2, 2.3), while female provider was associated with interpersonal communication (OR 1.9, 95% CI 1.4, 2.6). CONCLUSIONS: While demographics and health experiences vary by race among veterans, race had no effect on primary care ratings. Future studies need to determine whether this racial equity persists in health outcomes among women veterans.

Adolescent↗
PubMed1977

Mission of the National Institute on Aging.

The National Institute on Aging (NIA), the newest of the eleven National Institutes of Health, is dedicated to improving the quality of life of the old in America through biomedical, social, and behavioral research. Aging is reviewed as more than just decline and deterioration; it is also a process of continued development and accumulated knowledge. The NIA will encourage innovative research, but will not support the delivery of health services, as that is the domain of other agencies. In areas of overlap, such as diseases common to the old, the NIA will collaborate with other Institutes. A good target area for collaboration is senile dementia. Other areas of interest to the NIA are: encouraging the incorporation of geriatric medicine as a subspecialty, developing retirement test patterns, and investigating drug-drug and drug-age interactions, personality and social processes, and immunocompetence.

Adaptation, Psychological↗
PubMed1996

Long reflections on the QT interval: the sixth annual Gordon K. Moe Lecture.

This review of accumulated knowledge about the long QT syndromes begins with an iteration of the original papers and then proceeds to a broader historic reflection that includes my personal work as well as many studies by others. Next come reflections upon the current status of knowledge on the subject, combined with comments about remaining challenges and questions grouped as follows: (1) morphologic abnormalities of the cardiac conduction system and their pathophysiologic significance in the long QT syndromes; (2) cardioneuropathy in the pathogenesis of long QT syndromes; (3) variability of QT prolongation, including consideration of peripheral and central dysautonomic conditions with certain diagnostic and therapeutic implications; (4) some caveats about the popular use of left cervical sympathectomy to treat symptomatic individuals with long QT syndrome, emphasizing hazards for future electrical instability of the heart; (5) consideration of genetic influences in the long QT syndromes, a field holding great promise as well as fraught with many puzzling dilemmas; and (6) apoptosis and the pathogenesis of the long QT syndromes, based upon personal observations previously made with electron microscopic studies of the sinus node and now including new immunohistochemical evidence expanding the relevance of this novel view-point. These intentionally provocative presentations are made to stimulate physicians and other scientists to consider these several different perspectives in planning future studies aimed at better understanding of one of the most challenging medical entities facing cardiology today.

Apoptosis↗
PubMed2002

Current understanding of food allergens.

Food allergies are IgE-mediated immunological reactions; this distinguishes them from other adverse reactions to foods. Most (>90%) of the recognized food allergies are generally thought to be caused by eight foods or food groups. A number of factors can affect food allergy development, including diet and culture, route of exposure, processing, cooking, and digestion. In addition, it is thought that the properties of certain food proteins render them more likely to be allergenic than other proteins. Most food allergens are major proteins, polyvalent molecules with at least two or more IgE-binding sites, and are recognized as foreign molecules (hence immunogenic). A number of major food allergens have been recently characterized, and amino acid sequences determined. Tropomyosin is the only major allergen of shrimp. A number of IgE-binding epitopes have been identified in this molecule, though they may vary from one shrimp-allergic individual to another. Single amino acid substitutions within epitopes based on that of homologous, nonreactive tropomyosins can substantially enhance or abolish IgE antibody binding. Using the accumulated knowledge of food allergen protein structure, the allergenicity of novel proteins to which there has been no prior human exposure has been assessed. This has been based primarily on the lability or resistance of a protein to enzymatic degradation. Clearly, further criteria must be developed to refine this process. In this regard, the development of animal models that have been sufficiently validated as surrogates of human IgE antibody responses is needed for more precise assessment of the allergenic potential of proteins.

Allergens↗
PubMed1971

Sex and population differences in the incidence of a plasma cholinesterase variant.

Accumulating knowledge of polymorphic enzyme systems poses intriguing possibilities of anthropologic genetics. Development of an automated procedure for determination of heterozygosity or homozygosity of the atypical plasma cholinesterase allele (E(1)(a)) permitted screening of 2317 individuals during a national Preschool Nutrition Survey and several smaller population studies. Frequencies of the allele (E(1)(a)) closely parallel those previously reported. Caucasians manifested a heterozygote male preponderance of 1.85: 1.

Africa↗
PubMed1994

Biology of parainfluenza viruses.

Parainfluenza virus types 1 to 4 (PIV1 to PIV4) are important human pathogens that cause upper and lower respiratory tract infections, especially in infants and children. PIV1, PIV2, and PIV3 are second only to respiratory syncytial virus as a cause of croup in young children. Although some clinical symptoms are typical of PIVs, etiologic diagnosis always requires detection of infectious virus, viral components, or an antibody response. PIVs are typical paramyxoviruses, causing a syncytial cytopathic effect in cell cultures; virus growth can be confirmed either by hemadsorption or by using immunological reagents. Currently, PIV is most often diagnosed by demonstrating viral antigens in clinical specimens by rapid and highly sensitive immunoassays. More recently, PCR has been used for the detection of PIVs. Serological diagnosis is made by detecting a rising titer of immunoglobulin G or by demonstrating immunoglobulin M antibodies. PIVs infect species other than humans, and animal models are used to study the pathogenesis of PIV infections and to test candidate vaccines. Accumulating knowledge on the molecular structure and mechanisms of replication of PIVs has accelerated research on prevention and treatment. Several strategies for vaccine development, such as the use of live attenuated, inactivated, recombinant, and subunit vaccines, have been investigated, and it may become possible to prevent PIV infections in the near future.

Genome, Viral↗
PubMed2000

Fundamentals of impact biomechanics: Part I--Biomechanics of the head, neck, and thorax.

This is the first of two chapters dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in this first chapter are the head, neck, and thorax. The next chapter will discuss the abdomen, pelvis, and the lower extremities. Although the principal thrust of the research has been toward the mitigation of injuries sustained by automotive crash victims, the results of this research have applications in aircraft safety, contact sports, and protection of military personnel and civilians from intentional injury, such as in the use of nonlethal weapons. The reader should be keenly aware of the wide variation in human response and tolerance data in the cited results. This is due primarily to the large biological variation among humans and to the effects of aging. Average values are useful in design but cannot be applied to individuals.

Animals↗
PubMed2001

Fundamentals of impact biomechanics: Part 2--Biomechanics of the abdomen, pelvis, and lower extremities.

This is the second of two chapters (the first chapter appeared in the Annual Review of Biomedical Engineering, 2000, 2:55-81) dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in the first chapter were the head, neck, and thorax. In this chapter, the abdomen, pelvis, and lower extremities are discussed. The thoracolumbar spine is not covered because of length limitations and the low frequency of injury to this area from automotive accidents. Again, in the cited results, the reader needs to be keenly aware of the wide variation in human response and tolerance. This is due primarily to the large biological variations among humans and to the effects of aging. Average values that are useful in design cannot be applied to individuals.

Abdomen↗
PubMed2000

Trinucleotide repeats: mechanisms and pathophysiology.

Within the closing decade of the twentieth century, 14 neurological disorders were shown to result from the expansion of unstable trinucleotide repeats, establishing this once unique mutational mechanism as the basis of an expanding class of diseases. Trinucleotide repeat diseases can be categorized into two subclasses based on the location of the trinucleotide repeats: diseases involving noncoding repeats (untranslated sequences) and diseases involving repeats within coding sequences (exonic). The large body of knowledge accumulating in this fast moving field has provided exciting clues and inspired many unresolved questions about the pathogenesis of diseases caused by expanded trinucleotide repeats. This review summarizes the current understanding of the molecular pathology of each of these diseases, starting with a clinical picture followed by a focused description of the disease genes, the proteins involved, and the studies that have lent insight into their pathophysiology.

Female↗
PubMed1998

Regulation of immune responses by TGF-beta.

The transforming growth factor beta (TGF-beta) family of proteins are a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties. TGF-beta 1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these immune cells. TGF-beta can modulate expression of adhesion molecules, provide a chemotactic gradient for leukocytes and other cells participating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-beta have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to the fibrotic complications associated with chronic inflammatory conditions. In addition to these roles in disease pathogenesis, TGF-beta is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cells that are induced in this process. The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-beta gene knockout and transgenic mice, supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function.

Animals↗
PubMed2005

Severe acute respiratory syndrome (SARS): a year in review.

Severe acute respiratory syndrome (SARS) emerged from China as an untreatable and rapidly spreading respiratory illness of unknown etiology. Following point source exposure in February 2003, more than a dozen guests infected at a Hong Kong hotel seeded multi-country outbreaks that persisted through the spring of 2003. The World Health Organization responded by invoking traditional public health measures and advanced technologies to control the illness and contain the cause. A novel coronavirus was implicated and its entire genome was sequenced by mid-April 2003. The urgency of responding to this threat focused scientific endeavor and stimulated global collaboration. Through real-time application of accumulating knowledge, the world proved capable of arresting the first pandemic threat of the twenty-first century, despite early respiratory-borne spread and global susceptibility. This review synthesizes lessons learned from this remarkable achievement. These lessons can be applied to re-emergence of SARS or to the next pandemic threat to arise.

Anti-Inflammatory Agents↗
PubMed2001

The multifunctional capsid proteins of plant RNA viruses.

This article summarizes studies of viral coat (capsid) proteins (CPs) of RNA plant viruses. In addition, we discuss and seek to interpret the knowledge accumulated to data. CPs are named for their primary function; to encapsidate viral genomic nucleic acids. However, encapsidation is only one feature of an extremely diverse array of structural, functional, and ecological roles played during viral infection and spread. Herein, we consider the evolution of viral CPs and their multitude of interactions with factors encoded by the virus, host plant, or viral vector (biological transmission agent) that influence the infection and epidemiological facets of plant disease. In addition, applications of today's understanding of CPs in the protection of crops from viral infection and use in the manufacture of valuable compounds are considered.

Biotechnology↗
PubMed2005

Dynamic and static baroreflex control of muscle sympathetic nerve activity (SNA) parallels that of renal and cardiac SNA during physiological change in pressure.

Despite accumulated knowledge on human baroreflex control of muscle sympathetic nerve activity (SNA), whether baroreflex control of muscle SNA parallels that of other SNAs, in particular renal and cardiac SNAs, remains unclear. Using urethane and alpha-chloralose-anesthetized, vagotomized and aortic-denervated rabbits (n = 10), we recorded muscle SNA from tibial nerve by microneurography, simultaneously with renal and cardiac SNAs by wire electrode. To produce a baroreflex open-loop condition, we isolated the carotid sinuses from systemic circulation and altered the intracarotid sinus pressure (CSP) according to a binary white noise sequence of operating pressure +/- 20 mmHg (for investigating dynamic characteristics of baroreflex) or in stepwise 20-mmHg increments from 40 to 160 mmHg (for investigating static characteristics of baroreflex). Dynamic high-pass characteristics of baroreflex control of muscle SNA, assessed by the increasing slope of transfer gain, showed that more rapid change of arterial pressure resulted in greater response of muscle SNA to pressure change and that these characteristics were similar to cardiac SNA but greater than renal SNA. However, numerical simulation based on the transfer function shows that the differences in dynamic baroreflex control at various organs result in detectable differences among SNAs only when CSP changes at unphysiologically high rates (i.e., 5 mmHg/s). On the other hand, static reverse-sigmoid characteristics of baroreflex control of muscle SNA agreed well with those of renal or cardiac SNAs. In conclusion, dynamic-linear and static-nonlinear baroreflex control of muscle SNA is similar to that of renal and cardiac SNAs under physiological pressure change.

Animals↗
PubMed2005

Renewal of the neurophysiology of language: functional neuroimaging.

Functional neuroimaging methods have reached maturity. It is now possible to start to build the foundations of a physiology of language. The remarkable number of neuroimaging studies performed so far illustrates the potential of this approach, which complements the classical knowledge accumulated on aphasia. Here we attempt to characterize the impact of the functional neuroimaging revolution on our understanding of language. Although today considered as neuroimaging techniques, we refer less to electroencephalography and magnetoencephalography studies than to positron emission tomography and functional magnetic resonance imaging studies, which deal more directly with the question of localization and functional neuroanatomy. This review is structured in three parts. 1) Because of their rapid evolution, we address technical and methodological issues to provide an overview of current procedures and sketch out future perspectives. 2) We review a set of significant results acquired in normal adults (the core of functional imaging studies) to provide an overview of language mechanisms in the "standard" brain. Single-word processing is considered in relation to input modalities (visual and auditory input), output modalities (speech and written output), and the involvement of "central" semantic processes before sentence processing and nonstandard language (illiteracy, multilingualism, and sensory deficits) are addressed. 3) We address the influence of plasticity on physiological functions in relation to its main contexts of appearance, i.e., development and brain lesions, to show how functional imaging can allow fine-grained approaches to adaptation, the fundamental property of the brain. In closing, we consider future developments for language research using functional imaging.

Aphasia↗
PubMed1998

Inhibition of dentin demineralization by fluoride in vitro.

Compared with the knowledge accumulated on enamel-fluoride interactions, relatively little data is available regarding fluoride effects on dentin. This applies to both laboratory and clinical studies into the efficacy of fluoride schemes for the prevention of root surface caries. This study aimed to determine the effects of fluoride and pH on the demineralization of dentin, such as to provide information necessary to develop preventive programmes. Bovine dentin blocks were subjected to undersaturated calcium- and phosphate-containing solutions in the pH range 4.0-6.0 with fluoride added at concentrations between 0.5 and 10 ppm. Non-fluoride solutions served as controls. Mineral loss was assessed chemically and by transversal microradiography. Comparisons were made with similar studies on enamel demineralization. The results showed that demineralization of dentin depends on both pH and fluoride concentration in the demineralizing solution. Inhibition of demineralization that could be relevant from a clinical point of view was found at fluoride values 5-10 times the corresponding values for enamel. Also rapid depletion of fluoride from the solutions was observed, indicating the high uptake capacity of dentin for fluoride. Lesion depth depended on pH of the solution while the fluoride levels were associated with the surface layer, both in mineral content and depth. For dentin we propose a demineralization mechanism where acid penetrates rapidly into the tissue, presumably through the tubules, after which the released calcium and phosphate is partly trapped by the inward diffusing fluoride. This leads to the formation of a surface layer, which may even be hypermineralized compared to sound dentin.

Animals↗