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PubMed2001

Current concepts in lymphocyte homing and recirculation.

The immune system consists of a complex collection of leukocytes and dendritic cells that surveys most tissues in the body for the appearance of foreign antigens. For an efficient immune response, the interaction and co-localization of antigen-presenting cells, costimulatory helper cells and effector cells are crucial parameters. Therefore, the migration routes of antigen-presenting cells and potential antigen-specific lymphocytes merge in secondary lymphoid organs in order to increase the likelihood and speed of a lymphocyte finding its cognate antigen. Additionally, antigen-primed effector cells are directed to the tissue where they are most likely to encounter their cognate antigen. This highly organized and efficient antigen encounter is based on a continuous recirculation of antigen-specific lymphocytes between blood, peripheral tissue, and secondary lymphoid organs. Moreover, the efficacy of the immune system is further increased by the ability of different lymphocyte subsets to recirculate only through distinct tissues. The scope of this review is to outline the concept and mechanisms of lymphocyte homing and recirculation and to discuss the significance for the immune defense. Current models in leukocyte homing and recirculation and the underlying molecular functions of implicated cell adhesion molecules, chemokines, and chemokine receptors are discussed.

Animals↗

PubMedDate not supplied

Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection.

Heme oxygenase (HO)-1, involved in the heme degradation process, is an important antioxidant enzyme. The induction of HO-1 gene expression, in response to diverse oxidative stimuli, represents a critical event in adaptive cellular response. Experimental models of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis, have demonstrated that the induction of HO-1 can prevent or mitigate the symptoms associated with these ailments. Recent progress in our understanding of cellular signaling networks as critical modulators of gene transcription sheds light on the molecular basis of HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor- kappaB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as regulators of HO-1 gene induction. The scope of this review is limited to focus on molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a strategy to achieve chemoprevention and chemoprotection.

Animals↗

PubMed2004

Vaccinia virus recombinants as a model system to analyze interferon-induced pathways.

The interferons (IFNs) are a family of cytokines with broad antiviral activities that also control cell proliferation and modulate immune responses. IFNs exert their pleiotropic actions through the regulation of multiple pathways that have been subjected to extensive study using diverse approaches. The scope of this review is to show how we can take advantage of vaccinia virus (VV) to study IFN-related pathways. We summarize and present the different VV models available for studying IFN function and the possibilities that they offer to analyze IFN-induced pathways, IFN modulators, and the biologic effects at the molecular and cellular levels. Emphasis is given to studies of dsRNA-activated signaling with VV lacking E3L (VV DeltaE3L) and in RNA-activated protein kinase (PKR)-related pathways, through the use of VV recombinants (VVr) with inducible PKR (VV PKR). The latest system is versatile, as expression of PKR can be regulated and induced at different times; similarly, VVr can be generated expressing other PKR modulators. As an example of the utility of VVr, we describe how this model has been used to analyze the antiviral and proapoptotic functions of PKR, the impact of PKR on translation, and the PKR-induced activation of the nuclear factor-kappaB (NF-kappaB) pathway.

Animals↗

PubMed1977

Magnitude of the host nutritional responses to infection.

This review describes the scope, complexity, and magnitude of host nutritional responses throughout the course of an infectious process. These responses include prominent changes in nitrogen and protein metabolism, altered rates of carbohydrate and lipid production and utilization, and changes in mineral, electrolyte, trace element, and vitamin metabolism. It is postulated that these responses develop in a relatively predictable sequence which is influenced by the adequacy of host antimicrobial defense mechanisms, the severity and duration of illness, and specific localization of an infectious process within the body. In addition to hormonal regulatory effects, the metabolic and nutritional responses of the host are also influenced by biologically active substances released when host cells participate in phagocytic activity and local inflammatory responses.

Carbohydrate Metabolism↗

PubMed2004

The effect of stress on genome regulation and structure.

BACKGROUND: Stresses exert evolutionary pressures on all organisms, which have developed sophisticated responses to cope and survive. These responses involve cellular physiology, gene regulation and genome remodelling. SCOPE: In this review, the effects of stress on genomes and the connected responses are considered. Recent developments in our understanding of epigenetic genome regulation, including the role of RNA interference (RNAi), suggest a function for this in stress initiation and response. We review our knowledge of how different stresses, tissue culture, pathogen attack, abiotic stress, and hybridization, affect genomes. Using allopolyploid hybridization as an example, we examine mechanisms that may mediate genomic responses, focusing on RNAi-mediated perturbations. CONCLUSIONS: A common response to stresses may be the relaxation of epigenetic regulation, leading to activation of suppressed sequences and secondary effects as regulatory systems attempt to re-establish genomic order.

Climate↗

PubMed2005

Plant DNA flow cytometry and estimation of nuclear genome size.

BACKGROUND: DNA flow cytometry describes the use of flow cytometry for estimation of DNA quantity in cell nuclei. The method involves preparation of aqueous suspensions of intact nuclei whose DNA is stained using a DNA fluorochrome. The nuclei are classified according to their relative fluorescence intensity or DNA content. Because the sample preparation and analysis is convenient and rapid, DNA flow cytometry has become a popular method for ploidy screening, detection of mixoploidy and aneuploidy, cell cycle analysis, assessment of the degree of polysomaty, determination of reproductive pathway, and estimation of absolute DNA amount or genome size. While the former applications are relatively straightforward, estimation of absolute DNA amount requires special attention to possible errors in sample preparation and analysis. SCOPE: The article reviews current procedures for estimation of absolute DNA amounts in plants using flow cytometry, with special emphasis on preparation of nuclei suspensions, stoichiometric DNA staining and the use of DNA reference standards. In addition, methodological pitfalls encountered in estimation of intraspecific variation in genome size are discussed as well as problems linked to the use of DNA flow cytometry for fieldwork. CONCLUSIONS: Reliable estimation of absolute DNA amounts in plants using flow cytometry is not a trivial task. Although several well-proven protocols are available and some factors controlling the precision and reproducibility have been identified, several problems persist: (1) the need for fresh tissues complicates the transfer of samples from field to the laboratory and/or their storage; (2) the role of cytosolic compounds interfering with quantitative DNA staining is not well understood; and (3) the use of a set of internationally agreed DNA reference standards still remains an unrealized goal.

Cell Nucleus↗

PubMed2005

pH regulation in anoxic plants.

BACKGROUND: pH regulation is the result of a complex interaction of ion transport, H+ buffering, H+-consuming and H+-producing reactions. Cells under anoxia experience an energy crisis; an early response thereof (in most tissues) is a rapid cytoplasmic acidification of roughly half a pH unit. Depending on the degree of anoxia tolerance, this pH remains relatively stable for some time, but then drops further due to an energy shortage, which, in concert with a general breakdown of transmembrane gradients, finally leads to cell death unless the plant finds access to an energy source. SCOPE: In this review the much-debated origin of the initial pH change and its regulation under anoxia is discussed, as well as the problem of how tissues deal with the energy crisis and to what extent pH regulation and membrane transport from and into the vacuole and the apoplast is a part thereof. CONCLUSIONS: It is postulated that, because a foremost goal of cells under anoxia must be energy production (having an anaerobic machinery that produces insufficient amounts of ATP), a new pH is set to ensure a proper functioning of the involved enzymes. Thus, the anoxic pH is not experienced as an error signal and is therefore not reversed to the aerobic level. Although acclimated and anoxia-tolerant tissues may display higher cytoplasmic pH than non-acclimated or anoxia-intolerant tissues, evidence for an impeded pH-regulation is missing even in the anoxia-intolerant tissues. For sufficient energy production, residual H+ pumping is vital to cope with anoxia by importing energy-rich compounds; however it is not vital for pH-regulation. Whereas the initial acidification is not due to energy shortage, subsequent uncontrolled acidosis occurring in concert with a general gradient breakdown damages the cell but may not be the primary event.

Acclimatization↗

PubMed2005

Nitrogen regulation of root branching.

BACKGROUND: Many plant species can modify their root architecture to enable them to forage for heterogeneously distributed nutrients in the soil. The foraging response normally involves increased proliferation of lateral roots within nutrient-rich soil patches, but much remains to be understood about the signalling mechanisms that enable roots to sense variations in the external concentrations of different mineral nutrients and to modify their patterns of growth and development accordingly. SCOPE: In this review we consider different aspects of the way in which the nitrogen supply can modify root branching, focusing on Arabidopsis thaliana. Our current understanding of the mechanism of nitrate stimulation of lateral root growth and the role of the ANR1 gene are summarized. In addition, evidence supporting the possible role of auxin in regulating the systemic inhibition of early lateral root development by high rates of nitrate supply is presented. Finally, we examine recent evidence that an amino acid, L-glutamate, can act as an external signal to elicit complex changes in root growth and development. CONCLUSIONS: It is clear that plants have evolved sophisticated pathways for sensing and responding to changes in different components of the external nitrogen supply as well as their own internal nitrogen status. We speculate on the possibility that the effects elicited by external L-glutamate represent a novel form of foraging response that could potentially enhance a plant's ability to compete with its neighbours and micro-organisms for localized sources of organic nitrogen.

Arabidopsis↗

PubMed2006

Sensitivity of rice to ultraviolet-B radiation.

BACKGROUND: Depletion of the stratospheric ozone layer leads to an increase in ultraviolet-B (UVB: 280-320 nm) radiation reaching the earth's surface, and the enhanced solar UVB radiation predicted by atmospheric models will result in reduction of growth and yield of crops in the future. Over the last two decades, extensive studies of the physiological, biochemical and morphological effects of UVB in plants, as well as the mechanisms of UVB resistance, have been carried out. SCOPE: In this review, we describe recent research into the mechanisms of UVB resistance in higher plants, with an emphasis on rice (Oryza sativa), one of the world's most important staple food crops. Recent studies have brought to light the following remarkable findings. UV-absorbing compounds accumulating in the epidermal cell layers have traditionally been considered to function as UV filters, and to play an important role in countering the damaging effects of UVB radiation. Although these compounds are effective in reducing cyclobutane pyrimidine dimer (CPD) induction in plants exposed to a challenge exposure to UVB, certain levels of CPD are maintained constitutively in light conditions containing UVB, regardless of the quantity or presence of visible light. These findings imply that the systems for repairing DNA damage and scavenging reactive oxygen species (ROS) are essential for plants to grow in light conditions containing UVB. CONCLUSION: CPD photolyase activity is a crucial factor determining the differences in UVB sensitivity between rice cultivars. The substitution of one or two bases in the CPD photolyase gene can alter the activity of the enzyme, and the associated resistance of the plant to UVB radiation. These findings open up the possibility, in the near future, of increasing the resistance of rice to UVB radiation, by selective breeding or bioengineering of the genes encoding CPD photolyase.

DNA, Plant↗

PubMed2006

Could heat shock transcription factors function as hydrogen peroxide sensors in plants?

BACKGROUND: Heat shock transcription factors (Hsfs) are modular transcription factors encoded by a large gene family in plants. They bind to the consensus sequence 'nGAAnnTCCn' found in the promoters of many defence genes, and are thought to function as a highly redundant and flexible gene network that controls the response of plants to different environmental stress conditions, including biotic and abiotic stresses. Hsf proteins encoded by different genes exhibit a high degree of complexity in their interactions. They can potentially bind and activate their own promoters, as well as the promoters of other members of their gene family, and they can form homo- or heterotrimers resulting in altered nuclear localization, as well as enhanced or suppressed transcription. SCOPE: In this review, we summarize recent studies on Hsf function in Arabidopsis and tomato and present evidence obtained from microarray expression studies in Arabidopsis that the Hsf gene network is highly flexible and specialized, with specific members and/or member combinations controlling the response of plants to particular stress conditions. In addition, we describe recent studies that support the hypothesis that certain Hsfs function as molecular sensors that directly sense reactive oxygen species (ROS) and control the expression of oxidative stress response genes during oxidative stress.

Arabidopsis↗

PubMed1988

The natural history of human immunodeficiency virus infection.

Although much is known about the natural history of HIV infection, many issues remain unresolved and require additional study. At least four major questions require further investigation. (1) Current data suggest that most HIV-infected persons will eventually develop AIDS. The proportion of all infected persons who will eventually develop AIDS, as well as the average and maximum incubation periods, have not yet been conclusively defined. (2) Certain clinical signs (such as oral candidiasis) or laboratory test results (such as a depressed T4 count) may indicate a poorer prognosis. However, the predictive value of such indicators for a specific patient and in an individual situation varies. Combinations of clinical and laboratory data may help refine estimates of the likelihood of developing AIDS or other HIV-related diseases. (3) Why some HIV-infected persons develop disease and others do not is not completely understood. The role of cofactors for disease progression needs additional investigation. There may be no one universal cofactor for progression but, rather, various agents that cause immune stimulation and reactivation of latent HIV. Therefore, exposure to a variety of infectious or environmental agents (such as through sexually transmitted diseases or injection of iv drugs) may accelerate progression to disease in HIV-infected persons. (4) It is not established whether antiviral agents will prevent or reduce the likelihood of disease progression in asymptomatic HIV-infected persons. If beneficial, should they be given to all HIV-infected persons or only to those whose clinical and laboratory evaluation suggests an increased likelihood of progression? Given these uncertainties, how should the physician or other health care worker evaluate, treat, and counsel the HIV-infected patient? Such patients should receive a comprehensive medical evaluation for both diagnostic and staging purposes; the details of such an evaluation are beyond the scope of this review and have been well described. A few brief points, however, should be emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1988

Institutional animal care and use committees: a new set of clothes for the emperor?

According to some proponents and critics of research using animals, the greatest hope for improved conditions for laboratory animals is to be found in the system of self-regulation called for by recent legislation and the NIH's revised policy. This article explores advantages and disadvantages of relying on "Institutional Animal Care and Use Committees" to subject research proposals to ethical scrutiny. Among the advantages discussed are: institutional dialogue concerning the ethics of research; inclusion of perspectives of non-scientists in such dialogues; and the possibility of improved research proposals. Despite these advantages, I argue that serious problems with the committee system may limit the degree to which conditions for animals are actually improved. Disadvantages discussed include: limitations in the scope of the review process, and built-in bias in favor of certain philosophical stances in the composition of the committees.

Animal Care Committees↗

PubMed1998

The Internet for the medical and scientific community.

With the explosion of data coming out from the international scientific community, researchers can now locate and manipulate data of interest quickly and easily on the Internet. The scope of this review is to focus on some of the recent developments of the Internet that are specially relevant to health scientists. The review also provides the medical and scientific community with a selection of sites to visit on the Internet, dealing with clinical and laboratory aspects of science.

Bibliographies as Topic↗

PubMed1994

The ubiquitin-mediated proteolytic pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins.

Ubiquitin modification of a variety of protein targets within the cell plays important roles in many cellular processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, import of proteins into mitochondria, uptake of precursors into neurons, and biogenesis of mitochondria, ribosomes, and peroxisomes. The best studied modification occurs in the ubiquitin-mediated proteolytic pathway. Degradation of a protein via the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP-dependent mode to the protein substrate. The targeted protein is then degraded by a specific and energy-dependent high molecular mass protease into free amino acids, and free and reutilizable ubiquitin is released. In addition, stable mono-ubiquitin adducts are also found in the cell, for example, those involving nucleosomal histones. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, little is known on the signals that target proteins for degradation. Although mechanistic aspects of recognition via the N-terminal residue have been studied thoroughly, it is clear that the vast majority of cellular proteins are targeted by other signals. The identity of the native cellular substrates of the system is another important, yet unresolved, problem: only few proteins have been recognized so far as substrates of the system in vivo. The scope of this review is to discuss the mechanisms involved in ubiquitin activation, selection of substrates for conjugation, and degradation of ubiquitin-conjugated proteins in the cell-free system. In addition, we shall summarize what is currently known of the physiological roles of ubiquitin-mediated proteolysis in vivo.

Amino Acid Sequence↗

PubMed1991

Catheter ablation.

Catheter ablation is gaining increasing interest for the therapy of symptomatic, sustained arrhythmias of various origins. The scope of this review is to give an overview of the biophysical aspects and major characteristics of some of the most widely used energy sources in catheter ablation, e.g., the discharge of conventional defibrillators, modified defibrillators, laser light, and radiofrequency current application. Results from animal studies are considered to explain the basic mechanisms of catheter ablation. The recent achievements with the use of radiofrequency current to modify or ablate cardiac conduction properties are outlined in more detail.

Animals↗

PubMed2001

Class A scavenger receptors, macrophages, and atherosclerosis.

The scope of this review is to discuss the new advances in our understanding of the role of scavenger receptor class A in the initiation and modulation of the atherosclerotic process. Through the approaches of gene manipulation in the mouse model, a substantial body of literature has accumulated that depicts scavenger receptor class A as a central player in atherogenesis. In studies of scavenger receptor class A overexpression in macrophages through bone marrow transplantation using transgenic donor material, recipient mice with hyperlipidemia caused either by apolipoprotein E or LDL receptor deficiency did not show convincing changes in the degree of atherosclerosis development compared with controls. Conversely, the deletion of the scavenger receptor class A gene in the mouse has shown, in a consistent and significant fashion, that this receptor serves a pro-atherogenic function under hyperlipidemic conditions, as both apolipoprotein E and LDL receptor-deficient mice had reduced atherosclerosis in the absence of scavenger receptor class A. In addition, we have recently shown that C57BL/6 mice are protected from diet-induced atherosclerosis when they lack scavenger receptor class A, and that the macrophage is the cell type responsible for the effect of scavenger receptor class A deficiency in reducing lesion formation in C57BL/6 and LDL receptor null mice. Together, these results demonstrate that macrophage scavenger receptor class A contributes significantly to atherosclerotic lesion formation, and suggest that the uptake of oxidized or modified lipoproteins by vessel wall macrophages is a central process in atherogenesis.

Animals↗

PubMed1996

Chronic rejection.

The pathogenesis of chronic rejection is a complex network of immunological, metabolic and haemodynamic events leading to a cascade of cellular and molecular events with a subsequent remodelling of the graft. Evidence suggests that the frequency and intensity of acute rejection episodes strongly correlate with graft loss as a result of chronic rejection. The most characteristic feature of chronic rejection, shared by all organs, is concentric generalized arteriosclerosis with low-grade perivasculitis affecting all intragraft arteries of the transplant. In-vitro studies have demonstrated that a variety of cells and molecules may regulate smooth muscle cell replication in the vascular wall, the migration of smooth muscle cells from the media into the intima, and the development of arteriosclerotic lesions throughout the entire length of the vessel wall. These molecules include peptide growth factors, cytokines, vasoactive hormones, and lipid mediators of inflammation (eicosanoids), and they are secreted in situ by inflammatory, endothelial and smooth muscle cells in the vascular wall. In order to prevent chronic rejection it is necessary to optimize immunosuppression, possibly by the use of new immunosuppressive drugs that also seem to have direct inhibitory effect on smooth muscle cells and on transplant arteriosclerosis. The scope of this review is to highlight our current understanding of the risk factors, pathogenesis and prevention of chronic renal allograft rejection. This review will also briefly discuss present animal models used to investigate chronic rejection at the cellular and molecular level.

Animals↗

PubMed2000

Prostate specific antigen and benign prostatic hyperplasia.

Benign prostatic hyperplasia is a common condition in males over 50 years, but prostate cancer can develop in the same population. Prostate specific antigen, the best marker for prostate cancer, is also produced by benign epithelial cells, and there is an overlapping phenomenon between both conditions. The better we understand the relationships between benign prostatic hyperplasia and prostate specific antigen, the higher will be the discrimination power of prostate specific antigen measurement as a marker for prostate cancer. Our scope includes a review of the latest published material to date on this subject.

Age Factors↗