bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Recombinant Baculoviruses for Insect Control
Authors: Bonning Bryony C. , Hammock Bruce D.
Published: July 2003

In this review, we provide an overview of the current status of recombinant baculoviruses, describe the development of genetically engineered baculoviruses for use as rapid-action biological insecticides, and provide more detailed information on one particular set of recombinant viruses. The advantages and disadvantages of recombinant baculovirus insecticides, and the importance of risk-assessment studies of these genetically modified organisms, are reviewed. Finally the importance of sensible regulatory strategies to the success and future prospects of this technology is discussed.
Sexual Selection in Relation to Pest-Management Strategies
Authors: Boake Christine R. B. , Shelly Todd E. , Kaneshiro Kenneth Y.
Published: July 2003

The application of principles derived from the sexual selection literature can assist attempts to subvert the normal mating behavior of pests. Sexual selection encompasses both intermale competition for access to females and female choice of mates. It can operate during long-range attraction and short-range courtship, as well as after copulation. We review the major aspects of sexual selection and illustrate their application to pheromonal and SIT pest-management programs. Pheromones are important both in long-range attraction and in close-range mate choice; parapheromones may be very useful in pest management because of their influence on male mating success. Sexual selection theory provides a scheme for studying the normal mating behavior of a pest species and thus determining which attributes of the mass-reared sterile males are critical to their success with wild females. We hope that our review will suggest novel ways of attacking pests as well as encourage behavioral ecologists to study pest species.
Floral Resource Utilization by Solitary Bees (Hymenoptera: Apoidea) and Exploitation of Their Stored Foods by Natural Enemies
Authors: Wcislo William T. , Cane James H.
Published: July 2003

Bees are phytophagous insects that exhibit recurrent ecological specializations related to factors generally different from those discussed for other phytophagous insects. Pollen specialists have undergone extensive radiations, and specialization is not a always a derived state. Floral host associations are conserved in some bee lineages. In others, various species specialize on different host plants that are phenotypically similar in presenting predictably abundant floral resources. The nesting of solitary bees in localized areas influences the intensity of interactions with enemies and competitors. Abiotic factors do not always explain the intraspecific variation in the spatial distribution of solitary bees. Foods stored by bees attract many natural enemies, which may shape diverse facets of nesting and foraging behavior. Parasitism has evolved repeatedly in some, but not all, bee lineages. Available evidence suggests that cleptoparasitic lineages are most speciose in temperate zones. Female parasites frequently have a suite of characters that can be described as a masculinized feminine form. The evolution of resource specialization (including parasitism) in bees presents excellent opportunities to investigate phenotypic mechanisms responsible for evolutionary change.
The Role of Nourishment in Oogenesis
Authors: Wheeler Diana
Published: July 2003

Sexual receptivity is female behavior that allows or helps a male to fertilize her eggs; through this behavior, females play an active role in reproduction. Multiple signals may be used for receptivity or unreceptivity. Insect species exhibit three ontogenetic patterns of receptivity: cyclic, in which females alternately become receptive and unreceptive; brief, in which females mate during one short developmental period; and continuous. Primary (initial) receptivity may be stimulated or inhibited by diet, ovarian development, or juvenile hormone. In species with cyclic receptivity, remating may be inhibited by copulation itself, the presence of eggs, sperm stored in spermathecae, or seminal factors—usually peptides—secreted by the male accessory glands. In many species, there is substantial genetic variation for both primary receptivity and speed of remating. Several single-gene mutations reduce female receptivity; most of these mutations also impair sensory functioning.
Bacillus Sphaericus Toxins: Molecular Biology and Mode of Action
Authors: Charles J.-F. , Nielson-LeRoux C. , Delécluse A.
Published: July 2003

Bacillus sphaericus is a spore-forming aerobic bacterium, several strains of which are pathogenic for mosquito larvae. During sporulation, the most active strains produce a crystal toxin with a high degree of larvicidal activity. The toxin is composed of two proteins of 5 1.4 and 41.9 kDa, which are encoded by highly conserved chromosomal genes. After B. sphericus is ingested, these proteins are released in the larva’s midgut, and, in susceptible mosquito species, bind to a specific receptor present on midgut brush-border membranes. The resulting damages to the midgut cells leads to the mosquitoes’ death. During vegetative growth, some B. sphericus strains also synthesize mosquito larvicidal proteins of 100 and 30.8 kDa (Mtx toxins), the mode of action of which is still unknown. The mechanism of acquisition of the recessive mosquito resistance to the crystal toxin vanes with selection conditions.
Sexual Receptivity in Insects
Authors: Ringo John
Published: July 2003

Sexual receptivity is female behavior that allows or helps a male to fertilize her eggs; through this behavior, females play an active role in reproduction. Multiple signals may be used for receptivity or unreceptivity. Insect species exhibit three ontogenetic patterns of receptivity: cyclic, in which females alternately become receptive and unreceptive; brief, in which females mate during one short developmental period; and continuous. Primary (initial) receptivity may be stimulated or inhibited by diet, ovarian development, or juvenile hormone. In species with cyclic receptivity, remating may be inhibited by copulation itself, the presence of eggs, sperm stored in spermathecae, or seminal factors—usually peptides—secreted by the male accessory glands. In many species, there is substantial genetic variation for both primary receptivity and speed of remating. Several single-gene mutations reduce female receptivity; most of these mutations also impair sensory functioning.
Genetics and Evolution of Phenotypic Plasticity
Authors: Scheiner Samuel M.
Published: July 2003

To achieve a coherent evolutionary theory, it is necessary to account for the effects of the environment on the process of development. Phenotypic plasticity is the change in the expressed phenotype of a genotype as a function of the environment. Various measures of plasticity exist, many of which can be united within the framework of a polynomial function. This function is the norm of reaction. For the special case of a linear reaction norm, genetic variation can be partitioned into portions that are independent and dependent on the environment. From this partition two heritability measures are derived which can be used, alternatively, to compare populations or make predictions about the response to selection. Genetically, plasticity is likely due both to differences in allelic expression across environments and to changes in interactions among loci; plasticity is not a function of heterozygosity. Plasticity responds to both artificial and natural selection. The evolution of plasticity is modeled in three ways: optimality models, quantitative genetic models, and gametic models. All models make similar predictions about the conditions that will favor plasticity. In need of further development are the extension of quantitative genetic models, and structured population models; also needed are data on the true shapes of reaction norms and genetic variation and covariation for nonlinear reaction norm parameters and multiple environments.
Population Genetic Consequences of Small Population Size: Implications for Plant Conservation
Authors: Ellstrand Norman C. , Elam Diane R.
Published: July 2003

Although the potential genetic risks associated with rare or endangered plants and small populations have been discussed previously, the practical role of population genetics in plant conservation remains unclear. Using theory and the available data, we examine the effects of genetic drift, inbreeding, and gene flow on genetic diversity and fitness in rare plants and small populations. We identify those circumstances that are likely to put these plant species and populations at genetic risk. Warning signs that populations may be vulnerable include changes in factors such as population size, degree of isolation, and fitness. When possible, we suggest potential management strategies.
HUMAN ECOLOGY AND RESOURCE SUSTAINABILITY: The Importance of Institutional Diversity
Authors: Becker C. Dustin , Ostrom Elinor
Published: July 2003

We define the concept of a common-pool resource based on two attributes: the difficulty of excluding beneficiaries and the subtractability of use. We present similarities and differences among common-pool resources in regard to their ecological and institutional significance. The design principles that characterize long-surviving, delicately balanced resource systems governed by local rules systems are presented, as is a synthesis of the research on factors affecting institutional change. More complex biological resources are a greater challenge to the design of sustainable institutions, but the same general principles appear to carry over to more complex systems. We present initial findings from pilot studies in Uganda related to the effects of institutions on forest conditions.
G. W. BEADLE
Authors: Srb Adrian M.
Published: July 2003

George Wells Beadle was born in 1903 and died in 1989. During his lifetime, the science of genetics changed dramatically. Beadle contributed definitively to that change. Perhaps more than that of any other investigator, his work prepared the way for the transition from neoclassical to molecular genetics. His contributions were recognized with a Nobel Prize and many other high honors.
DNA REPAIR IN HUMANS
Authors: Sancar Aziz
Published: July 2003

DNA repair is an important molecular defense system against agents that cause cancer, degenerative diseases, and aging. Several repair systems in humans protect the genome by repairing modified bases, DNA adducts, cross links, and double strand breaks. These repair systems, base excision, nucleotide excision, and recombination, are intimately connected to transcription and to cell cycle checkpoints. In addition, genotoxic stress induces a set of cellular reactions mediated by the p53 tumor suppressor and the Ras oncogene. These genotoxic response reactions may help the cell survive or enter apoptosis. Damage-response reactions may be utilized as targets of anticancer chemotherapy.
MEMBRANE PROTEIN ASSEMBLY: GENETIC, EVOLUTIONARY AND MEDICAL PERSPECTIVES
Authors: Manoil Colin , Traxler Beth
Published: July 2003

Lipid bilayers are delicate structures that are easily disrupted by a variety of amphipathic molecules. Yet the viability of a cell requires the continued assembly of large amphipathic proteins within its membranes without damage. The need to minimize bilayer disruption may account for a number of fundamental features of membrane protein assembly. These include the use of redundant sequence information to establish the topologies and folded structures of membrane proteins and the existence of efficient mechanisms to rid cells of misassembled proteins. Most missense mutations that inactivate a membrane protein probably do so by altering the folding of the membrane-inserted structure rather than by rearranging the topology or by changing key residues involved directly in function. Such misfolded membrane proteins may be toxic to cells if they escape cellular safeguards. This toxicity may underlie some human degenerative diseases due to mutant membrane proteins.
Biology of Hematopoietic Stem Cells and Progenitors: Implications for Clinical Application
Authors: Kondo Motonari , Wagers Amy J. , Manz Markus G. , Prohaska Susan S. , Scherer David C. , Beilhack Georg F. , Shizuru Judith A. , Weissman Irving L.
Published: July 2003

▪ Abstract  Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases.
Lpr and gld: Single Gene Models of Systemic Autoimmunity and Lymphoproliferative Disease
Authors: Cohen Philip L. , Eisenberg Robert A.
Published: July 2003

The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes. The clinical syndromes and immune abnormalities associated with these two nonallelic genes are nearly identical and are also highly dependent on background genes. MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE). Abnormal cell marker expression in the aberrant lpr T lymphocytes includes surface antigens normally associated with activated T cells or even with B cells, and it occurs along with enhanced expression of certain oncogenes. The lpr gene results in intrinsic abnormalities of both T and B lymphocytes, yet its location and product are unknown. The gld gene is located on chromosome 1; its product is also unknown. Although many immunological abnormalities are known, the mechanism whereby these two genes induce autoimmunity and lymphoproliferation remains obscure. Further studies of mice bearing these mutant genes are certain to yield insights into systemic autoimmunity and the control of lymphocyte proliferation.
Specialization, Tolerance, Memory, Competition, Latency, and Strife among T Cells
Authors: Mitchison N. A.
Published: July 2003

Over the last four decades much insight has been gained into the working of T cells. This survey offers an interpretation of regulatory T-cell function in terms of epitope linkage and the need to free B cells of responsibility for self-tolerance. These functions dictate specialized forms of antigen presentation, by separate populations of dendritic cells. Tolerance induction among T cells occurs at a threshold of antigen concentration which is close to that required for positive stimulation, as would be expected for the efficient workingo f the immunsey stem. Certain self-proteins, especially those located on cell surfaces, also induce tolerance among B cells, thus reducing the danger of activating latent epitopes. Memory among T cells is attributed to two components, one of hyperreactivity of activated cells, and the other of clonal expansion. Examples of competition and buffering between T-cell activities are given. A brief discussion of autoimmune disease focusses on the importance of disease remission, protective HLA genes, and immunoinhibitory genes in animal models. The mechanism underlying all three may be a balance between competing subsets of T cells.
Peripheral T Cell Tolerance
Authors: Miller Jacques F. A. P. , Morahan Grant
Published: July 2003

The most efficient way to ensure self-tolerance in the T-cell repertoire is by intrathymic deletion of self-reactive clones. Antigens not present intrathymically may, however, influence the peripheral T-cell pool in various ways. They may of course activate T cells, provided that these have the correct specificity and affinity and that the antigens are presented in sufficient amounts on professional antigen-presenting cells. They may be ignored by T cells if some of these conditions are not met. In some forms, the antigen may be toleragenic for mature T cells. If the antigens persist in an immunogcnic form, unresponsiveness may eventually be imposed as the end result of a powerful immune response. Extrathymic self-antigenic components are generally encountered early in development, and the way in which these influence peripheral T lymphocytes has been studied by transgenic technology. They may be ignored by T cells if they are sequestered from the immune system, or if they are present in low amounts or on nonprofessional antigen-presenting cells which lack the appropriate accessory molecules or signals needed to activate the relevant T-cell subset. On the other hand, some of these self-antigens readily induce anergy in peripheral T cells, which may or may not involve downregulation of antigen receptors and coreceptors. Tolerance in the T-cell repertoire is therefore achieved not only by intrathymic deletion of self-reactive clones but also by several postthymic mechanisms
The Human T Cell Receptor in Health and Disease
Authors: Moss Paul A. H. , Rosenberg William M. C. , Bell John I.
Published: July 2003

The T cell antigen receptor (TCR) recognizes antigen in the form short peptides bound to a major histocompatibility (MHC) molecule. This review provides a synopsis of the current state of knowledge of the structure and function of the receptor and its possible role in human disease. Analysis of the T cell receptor usage of T-cell lines and clones recognizing the same peptide-MHC complex is beginning to shed light onto the structural basis of the TCR-peptide-MHC complex. Also, it is now apparent that there are two mechanisms by which the TCR can interact with the MHC molecule, either through classical peptide interactions or through superantigens. Finally, we review the role of specific TCRs in human disease. Current evidence in this area is difficult to interpret; however, it is likely that TCR-mediatedi sease susceptibility exists, and its basis at either a germline or somatic level will soon be clarified.
Roles of alphabeta and gammadelta T Cell Subsets in Viral Immunity
Authors: Doherty Peter C. , Allan William , Eichelberger Maryna , Carding Simon R.
Published: July 2003

The current status of T-cell subset involvement in viral immunity is summarized for experimental studies in mice. The immunobiology of the normal host response is discussed, with particular reference to lymphocytic choriomeningitis (LCM) and influenza. The general impression is that CD8+ cytotoxic T lymphocytes, CD4+ TH1 cells, γ interferon, and IL-2 are of major importance, with these different components of the immune system interacting to promote an optimal response. However, experiments with a variety of virus systems indicate that there is considerable plasticity, at least in young, adult mice. Other mechanisms often compensate if a key lymphocyte subset is absent throughout the development of the immune response. Influenza-infected mice depleted of either CD4+ or CD8+ T cells clear virus and recover, though the latter may not be true for the elimination of LCM Virus. Emerging information on the involvement of γδ T cells in viral pneumonia is summarized, but there is as yet no understanding of the biological significance (if any) of these lymphocytes in viral immunity. The point is made that αβ T-cell memory to viruses is long-lived, and the need for antigen persistence to maintain such memory is questioned.
Murine Natural Killer Cells and Marrow Graft Rejection
Authors: Yu Y. Y. L. , Kumar V. , Bennett M.
Published: July 2003

Rejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3-, NK1.1+), cytotoxic T cells (CD3+, CD8+), and T cells with natural killer cell markers (CD3+, NK1.1+) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented.
Molecular Approaches to Analysis of X-Linked Immunodeficiencies
Authors: Conley Mary Ellen
Published: July 2003

Although the X-linked immunodeficiencies—X-linked agammaglobulinemia (XLA), X-linked severe combined immunodeficiency (XSCID), Wiskott-Aldrich syndrome (WAS), X-linked lymphoproliferative syndrome and X-linked hyper IgM syndrome—have been mapped to loci distributed throughout the X chromosome, they have several features in common that suggest that they might be members of a gene family: (i) all are maintained in the population at approximately the same gene frequency; (ii) expression of each defect is limited to the hematopoieticsy stem; (iii) atypical forms of each disorder have been described; and (iv) obligate carriers of these disorders are normal by all immunologic criteria. The failure of carriers of XLA, XSCID, and WAS to show signs of their gene defects can be explained by the preferential use of the normal, nonmutant X as the active X in the cell lineages affected by the gene defects. These three disorders also share an additional feature; in boys with XLAX, SCID, or WAS there is asynchronous expression of cell surface markers of differentiation or activation. If some or all of the genes that are abnormal in the X-linked immunodeficiencies are members of a gene family, then isolation of one gene may lead to the others.
Germinal Centers
Authors: MacLennan Ian C. M.
Published: July 2003

Germinal centers develop in the B cell follicles of secondary lymphoid tissues during T cell-dependent (TD) antibody responses. The B cells that give rise to germinal centers initially have to be activated outside follicles, in the T cell-rich zones in association with interdigitating cells and T cell help. After immunization with a single dose of protein-based antigen, the germinal centers formed are oligoclonal; on average three B blasts colonize each follicle. These blasts undergo massive clonal expansion and activate a site-directed hypermutation mechanism that acts on their immunoglobulin-variable (Ig-v)-region genes. Mature germinal centers are divided into dark and light zones. The proliferating blasts, centroblasts, occupy the dark zone and give rise to centrocytes that are not in cell cycle and fill the light zone. The light zone contains a rich network of follicular dendritic cells (FDC) that have the capacity to take up antigen and hold this on their surface for periods of more than a year. The antigen is held as an immune complex in a native unprocessed form; but the antigen may be taken up from FDC by B cells, which can process this and present it to T cells. Centrocytes appear to be selected by their ability to interact with antigen held on FDC. There is a high death rate among centrocytes in vivo, and when these cells are isolated in vitro, they undergo apoptosis within hours on culture. The onset of apoptosis can be delayed by cross-linking centrocytes' surface Ig, and long-term survival is achieved by signalling through their surface CD40. After activation through CD40 the centrocytes increase their surface Ig and acquire characteristics of memory and processing of antigen held on FDC and its presentation to T cells that can be induced to express CD40 ligand at the point of cognate interaction. Other signals that induce a proportion of germinal center cells to become plasma cells have also been described. Germinal centers persist for about 3 weeks following immunization, but after this, memory B blasts continue to proliferate in follicles throughout the months of T cell-dependent antibody responses. These cells are probably the source of plasma cells and memory cells required to maintain long-term antibody production and memory after the first 3 weeks of T cell-dependent antibody responses.
Assembly, Transport, and Function of MHC Class II Molecules
Authors: Cresswell Peter
Published: July 2003

MHC class II molecules assemble in the endoplasmic reticulum in a chaperone-mediated fashion to form a nine-chain structure consisting of three alpha beta dimers associated with an invariant chain trimer. This complex is transported through the Golgi apparatus and into the endosomal system. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. Current evidence argues that the segregation of the class II-invariant chain complex from the constitutive pathway of membrane protein transport occurs in the trans-Golgi network. However, class II-invariant chain complexes that reach the cell surface are also rapidly internalized into endosomes. Within the endosomal system, probably in a late endosome/pre-lysosome, the invariant chain is degraded, releasing alpha beta dimers that bind peptides predominantly derived from endocytosed proteins. Evidence suggests that many of these peptides are actually generated in lysosomes. The precise mechanisms involved in forming class II-peptide complexes are unclear, although the existence of antigen-processing mutants argues that additional gene products, at least one of which is encoded in the MHC, are involved. After binding peptides, class II molecules are transported by an unknown route to the cell surface, where their primary function of presenting antigenic peptides to CD4+ T cells is carried out.
Antigen Analogs/MHC Complexes as Specific T Cell Receptor Antagonists
Authors: Sette Alessandro , Alexander Jeff , Ruppert Jörg , Snoke Ken , Franco Alessandra , Ishioka Glenn , Grey Howard M.
Published: July 2003

Recent studies demonstrated that antigen analogs can act as powerful and specific inhibitors of T cell activation, leading to the formulation of the concept that antigen analog/MHC complexes may act as antagonists of the T cell receptor (TCR). TCR antagonism appears to be associated with engagement of the TCR below a crucial affinity threshold necessary for full T cell activation. Studies addressing the molecular mechanism of this effect suggest that TCR antagonists could act by interfering with membrane-related events (such as proper receptor clustering) that might precede intracellular signaling. Discovery of the TCR antagonism phenomenon also suggested a possible rational approach to antigen-specific immunointervention in allergies and autoimmune diseases. The feasibility of such an approach is now being actively investigated. Finally, TCR antagonist peptides may provide a useful tool to probe TCR-peptide/MHC interactions involved in the process of thymic education.
Hepatitis B Virus Immunopathogenesis
Authors: Chisari Francis V. , Ferrari Carlo
Published: July 2003

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) that causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid, and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal, and multispecific in acutely infected patients who successfully clear the virus, and the responses are relatively weak and more narrowly focused in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a posttranscriptional mechanism mediated by interferon gamma, tumor necrosis factor alpha, and interleukin 2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult-onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete downregulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
The Three-Dimensional Structure of Peptide-MHC Complexes
Authors: Madden Dean R.
Published: July 2003

The ability of MHC molecules to present a broad spectrum of peptide antigens for T cell recognition requires a compromise between high affinity and broad specificity. Three-dimensional atomic structures of several class I and class II MHC molecules reveal a unique structural solution to this problem: Tight binding to the peptide main chain is supplemented by more or less restrictive interactions with peptide side chains. In spite of these contacts, peptide side-chain and conformational variability ensures that the resulting peptide-MHC complex presents an antigenically unique surface to T cell receptors.

Extension of this understanding to other peptide-MHC complexes, including agonist/antagonist peptides and the identification of antigenic peptides within protein sequences, however, requires a detailed analysis of the interactions that determine both peptide-MHC binding affinity and the conformations of bound peptides. While many of these interactions can be modeled by homology with known structures, their specificity can depend sensitively on subtle and long range structural effects. Structurally and immunologically important distinctions are also found between the class I and class II peptide-binding strategies. Taken together, these interactions ultimately determine the ability of an individual to respond successfully to immune challenges.
T Cell-Independent Antigens Type 2
Authors: Mond James J. , Lees Andrew , Snapper Clifford M.
Published: July 2003

In this review we have attemped to define the characteristics of TI-2 antigens that enable them to stimulate antibody production in the absence of T cell help. One of the most critical properties of this group of antigens is their ability to deliver prolonged and persistent signaling to the B cell. This by itself is not however sufficient to stimulate Ig synthesis, and they mus therefore stimulate non-T cells to interact with the B cells either directly or indirectly via cytokine production. There is evidence implicating the NK cell and T cell as playing this important role in response to TI antigens. Furthermore, we discuss the importance of cytokines such as IL-3, GMCSF and IFN-γ, which significantly enhance antibody production by these antigens. Finally, we present evidence demonstrating that B cell activation via TI stimuli does not play merely a permissive role in allowing for cell cycle entry and enhanced responsiveness to other stimuli. Rather, the nature of the B cell activating signal is critical in determining the quantitative and qualitative profile of Ig isotype production.
Interface Fracture
Authors: Lane Michael
Published: July 2003

▪ Abstract  Interfacial adhesion plays a central role in a number of technologically important applications. Quantitatively measuring the adhesion of an interface and understanding the processes and controlling mechanisms of energy dissipation is not always a straightforward task, however. It is often not enough to know that an interface in a particular application is weak and prone to failure because it can be difficult to accurately recreate that interface with a bulk specimen and derive a meaningful adhesion value. Rather, a fundamental knowledge of the processes that actually contribute to the interfacial strength is important, so that, when bulk specimens are prepared, care can be taken to eliminate energy-absorbing processes that are not present in the actual application. Accordingly, this paper reviews some of the literature highlighting the contributing factors that control interfacial adhesion. The focus is on those models that describe the detailed mechanisms of the energy-absorbing processes and on some of the experimental data that illustrates those models.
Science and Technology of the Twenty-First Century: Synthesis, Properties, and Applications of Carbon Nanotubes
Authors: Terrones Mauricio
Published: July 2003

▪ Abstract  This account reviews the discovery, synthesis, properties, and the latest research advances of carbon nanotubes developed over the past 12 years. Because of their remarkable electronic and mechanical properties, carbon nanotubes are unique and exciting. The field has been developed rapidly, and the number of publications per year is increasing almost exponentially. Various technological applications are likely to arise using nanotubes for fabrication of flat panel displays, gas storage devices, toxic gas sensors, Li+ batteries, robust and lightweight composites, conducting paints, electronic nanodevices, etc. Further experimental and theoretical research is still necessary so that novel technologies will become a reality in the early twenty-first century.
Oxide-Ion Electrolytes
Authors: Goodenough John B.
Published: July 2003

▪ Abstract  The performance of the oxide-ion electrolyte of a solid oxide fuel cell (SOFC) is critical to the development of an intermediate-temperature system. Although yttria-stabilized zirconia is the electrolyte used in SOFCs under commercial development, other candidate materials are now available, and there remains a strong motivation to search for new, improved oxide-ion electrolytes. The leading contenders are discussed not only with respect to their oxide-ion conductivity, but also with respect to mechanical and chemical compatibility with the electrodes and the working environment at each electrode.
Conversion of Hydrocarbons in Solid Oxide Fuel Cells
Authors: Mogensen Mogens , Kammer Kent
Published: July 2003

▪ Abstract  Recently, a number of papers about direct oxidation of methane and hydrocarbon in solid oxide fuel cells (SOFC) at relatively low temperatures (about 700°C) have been published. Even though the conversion of almost dry CH4 at 1000°C on ceramic anodes was demonstrated more than 10 years ago, the reports about high-current densities for methane oxidation at such low temperatures are indeed surprising. Several papers indicate that a catalytic effect (due to the mixed ionic and electronic conductivity) of CeO2-x is partially responsible for this effect. However, this seems to contradict previous reports, and thus this issue deserves further analysis.
Recent Advances in Materials for Fuel Cells
Authors: Brandon N.P. , Skinner S. , Steele B.C.H.
Published: July 2003

▪ Abstract  After a brief survey of fuel cell types, attention is focused on material requirements for SOFC and PEMFC stacks, with an introductory section on materials technology for reformers. Materials cost and processing, together with durability issues, are emphasized as these now dominate materials selection processes for prototype stack units. In addition to optimizing the cell components, increasing attention is being given to the composition and processing of the bipolar plate component as the weight and volume of the relevant material has a major influence on the overall power density and cost of the fuel cell stack. It is concluded that the introduction of alternative materials/processes that would enable PEMFC stacks to operate at 150–200°C, and IT-SOFC stacks to operate at 500–700°C, would have a major impact on the successful commercialization of fuel cell technology.
Management of Children with Progressive Renal Failure
Authors: Herrin John T.
Published: July 2003

The strategy of management in childhood renal failure is to integrate available therapeutic modalities with the natural history of the disease in such a manner that linear growth is preserved. Attention to psychosocial growth is necessary for full rehabilitation. Treatment is ordered to provide hope and confidence to family and patient. Conservative medical therapy provides chemical stabilization and prophylaxis against bone disease and growth retardation. Planned progression to replacement of renal function by dialysis or renal transplant is made when growth or control of bone disease is no longer possible, but before complications occur. Therapy is effective; 90% of patients survive 5-10 years with 65% retaining a functioning allograft. Full rehabilitation is attained in 85-90% of post-transplant and 50% of dialysis patients. Technical advances now allow safe dialysis for all age groups. Although growth maintenance remains a major problem, it is possible that earlier metabolic control and transplantation to protect growth in the critical early years, together with improved control of rejection, may allow close approximation to optimal growth potential.
Chemotherapy and Cognitive Defects in Cancer Patients
Authors: Silberfarb Peter M.
Published: July 2003

The cognitive functions are defined and discussed. Factors that place cancer patients at high risk for disorders of cognition are presented along with the problem of semantic confusion in this area. The cognitive impairment found in cancer patients receiving chemotherapy is reviewed, as is the importance of the mental status examination and the treatment of delirium in cancer patients. Several illustrative case reports are presented.
Infections and Hypocomplementemia
Authors: Goldstein Ira M. , Marder Shelley R.
Published: July 2003

The complement system, phagocytic leukocytes, and antibodies constitute the “department of defense” in the battle against infections caused by pyogenie microorganisms. Complement components are capable of directly killing (by lysis) certain susceptible bacteria and are the source of chemotactic peptides and heat-labile opsonin, which facilitate recognition and killing of microbes by phagocytic cells. When these vital functions are compromised, as in individuals with inherited deficiencies of complement components, the result is unusual susceptibility to severe infections.
Acyclovir and Other Chemotherapy for Herpes Group Viral Infections
Authors: Balfour H. H.
Published: July 2003

The recent profusion of antiviral research has resulted in significant advances toward prevention and treatment of herpes group virus infections. The most promising new agent is acyclovir, which is available in topical, intravenous, and oral formulations. Results of clinical trials of acyclovir for prevention and treatment of herpes simplex, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus infections are discussed, and the potential problem of antiviral resistance considered. Vidarabine therapy is reviewed briefly, and future new drugs with activity against herpesviruses are mentioned.
Epidemiology of Alcoholism and Prospects for Treatment
Authors: Nace Edgar P.
Published: July 2003

This chapter reviews current American drinking patterns and the prevalence of problems resulting from alcohol use. The general population is discussed first. Then a look at five subgroups within the population is presented. These groups are older adults, adolescents, women, Blacks, and Hispanics. For the general population as well as each of the five subgroups, the prospects regarding treatment outcome are discussed.
Understanding and Promoting Smoking Cessation: Overview and Guidelines for Physician Intervention
Authors: Orleans C. Tracy
Published: July 2003

This chapter outlines requirements for quitting smoking successfully, and for effective treatments. It presents practical guidelines for physicians and allied health care providers with specific recommendations for how to motivate and help patients quit “on their own” and how to select more intensive backup treatment if needed. Useful guides, references, and resources are suggested, with recommendations concerning optimal use of nicotine chewing gum.
Medical Implications of Shift-Work
Authors: Moore-Ede Martin C. , Richardson Gary S.
Published: July 2003

The circadian pacemakers, which time the approximately 24-hour rhythms in sleep and wakefulness, neuroendocrine, thermoregulatory, and other body functions, resynchronize only slowly after an abrupt phase shift in environmental time cues. While the symptoms of jet-lag are transient, the kinds of repeated shifts over a number of years experienced by shift-workers on rotating schedules induce sleep-wake disorders, gastrointestinal pathology, and an increased risk of cardiovascular disease. There is significant interindividual variation in the ability to adapt and also a deterioration with age. Evidence is accumulating that poor adapters present with a Shift Maladaption Syndrome with characteristic pathological manifestations.
Colonic Polyps
Authors: Ackroyd Frederick W. , Hedberg Stephen E.
Published: July 2003

Carcinoma of the large bowel arises almost exclusively in neoplastic polyps, which are present in 5-10% of the population over age 40. These polyps may be of three histologic types: (a) tubular adenoma (adenomatous polyp), (b) tubulovillous adenoma (villoglandular polyp), and (c) villous adenoma. The tendency for malignant change is greatest in the villous adenoma (41%) and in tubulovillous (villoglandular polyps–23%). In tubular adenomas (simple adenomatous polyps), the incidence of malignancy is 5% over all. The tendency toward malignant change is determined by histologic type, size, and degree of atypicality of adenoma. Early detection and complete removal of neoplastic polyps of the colon are essential to the prevention of cancer of the large bowel, and this may usually be done in most cases with the colonoscope.
Swallowing Disorders
Authors: Merlo Angela , Cohen Sidney
Published: July 2003

Swallowing is a coordinated activity that enables solids and liquids to pass uninterruptedly from the mouth to the stomach. Dysphagia occurs when this process is disrupted by organic or functional alterations at the level of swallow initiation or esophageal emptying. The differential diagnosis includes obstructive lesions and motility disorders. Symptoms and clinical features help distinguish these diseases.
Atrial Fibrillation: Natural History, Complications, and Management
Authors: Alpert Joseph S. , Petersen Palle , Godtfredsen John
Published: July 2003

Atrial fibrillation is a clinically important arrhythmia that carries important prognostic and therapeutic implications. Hypertension, ischemic heart disease, and rheumatic valvular disease are the commonest causes of atrial fibrillation. The presence of chronic or paroxysmal atrial fibrillation places the patient at increased risk for embolic stroke and/or death. When atrial fibrillation develops, there is loss of the atrial transport factor (“atrial kick”), with consequent decrease of cardiac output. Stroke output declines by 20-30% in normal individuals with loss of atrial kick; the decline in stroke output is considerably larger in patients with heart disease. Atrial fibrillation can be electrically or pharmacologically reverted to sinus rhythm. Even patients with refractory atrial fibrillation can be reverted to sinus rhythm with amiodarone.
Tumors of the Immunocompromised Patient
Authors: Penn Israel
Published: July 2003

Immunocompromised patients are prone to develop certain malignancies, particularly involving cells of the immune system itself (1-3). In this chapter we describe the various neoplasms, note the differences between these and similar cancers in the general population, emphasize similar tumor patterns in different types of immunodeficiency, and discuss possible etiologic factors.
Evaluation of Asymptomatic Solitary Hepatic Lesions
Authors: Foster James H.
Published: July 2003

Clinical judgment and noninvasive radiologic imaging are the keystones to decision-making in the management of most patients with asymptomatic liver lesions. A knowledge of the natural history of the common lesions suggests a conservative approach to those that are benign and an aggressive approach to those that are malignant and still localized.
Treatment of Sensorineural Hearing Loss by Cochlear Implantation
Authors: Nadol Joseph B. , Eddington Donald K.
Published: July 2003

Cochlear implantation, a form of neural prosthesis, is now being employed for some profoundly deaf individuals. The pathophysiology of profound deafness, the strategies inherent in cochlear implantation, the differences between various cochlear implant strategies and designs, medical and otologic evaluation of implant candidates, and the surgical procedure are each discussed. The results in speech recognition and speech reading that have been obtained with four commonly used cochlear implant systems are also presented.
Operations for Duodenal Ulcer Disease
Authors: Jordan Paul H.
Published: July 2003

Operative treatment of duodenal ulcer has been restricted to the small proportion of ulcer patients who have complications of ulcers or to those patients who do not respond to medical treatment. The principal surgical procedures that have been used include different types of gastric drainage, gastric resection, gastric denervation, or various combinations of these principles. Initially, the primary objective of ulcer surgery was to prevent recurrent ulcer. Currently, the objectives of operation are to cure an ulcer without a recurrent ulcer or any undesirable sequelae developing as a result of altered gastric physiology. Perhaps no operation will satisfy each of these conditions for every patient. Parietal cell vagotomy without a drainage procedure, the latest contribution to ulcer surgery, has been intensively studied for 19 years. The operative mortality of 0.26%, the recurrence rate of 4 to 11%, and virtually no significant side effects have caused the operation to become the procedure of choice for an increasingly large number of gastric surgeons.