bluuebunny/crossref_metadata_2025 huggingface dataset:
The Elimination of Lead in Gasoline
Authors: Thomas V. M.
Published: July 2003

Due to the health consequences of lead exposure, as well as to the introduction of catalytic converters, many countries have reduced or eliminated use of lead additives in motor gasolines. But in many other countries, leaded gasoline remains the norm. In these countries there is often confusion about the health significance of gasoline lead, the ability of cars to use unleaded gasoline, and the costs of unleaded gasoline. This chapter shows that leaded gasoline is a major source of human lead exposure. All cars, with or without catalytic converters, and with or without hardened exhaust valve seats, can use unleaded gasoline exclusively. Unleaded gasoline typically costs on the order of $0.01 more per liter than leaded gasoline to produce. Recent concerns about benzene exposure from unleaded gasoline have been addressed through choice of gasoline formulation and other measures.
Immunological Basis for Compatibility in Parasitoid-Host Relationships
Authors: Strand Michael R. , Pech Louis L.
Published: July 2003

The insect immune system serves as a key defense against attack by parasitoids. Incompatible hosts often eliminate parasitoids by encapsulation, a process in which hemocytes form a multilayered envelope around the invading organism. Capsule formation involves cooperation between one or more classes of hemocytes and is likely mediated by cytokines and adhesion molecules. Reciprocally, parasitoids have evolved a variety of strategies for overcoming host immune responses. Some parasitoids passively avoid elimination by developing in locations inaccessible to host hemocytes or by possessing surface features that fail to elicit an immune response. Other species actively disrupt the host immune system by injecting specific factors into the host at oviposition. In particular, polydnaviruses associated with several taxa of parasitoids disrupt capsule formation by killing hemocytes or altering their ability to adhere to foreign surfaces. These symbionts have likely played a critical role in evolution of host range and in defining parasitoid-host compatibility.
Butterfly Conservation Management
Authors: New T. R. , Pyle R. M. , Thomas J. A. , Thomas C. D. , Hammond P. C.
Published: July 2003

Butterflies are important flagship taxa for invertebrate conservation. Recent developments emphasizing species and habitat management based on sound ecological understanding exemplify progress in this emerging science. Studies in many countries show the complexity of management needs for single species, and examples of management and recovery plans demonstrate the worth of this approach. By contrast, in many tropical regions, where butterfly faunas are more diverse than in temperate zones and the resources for practical conservation are restricted, the major emphasis is on protection of habitats to safeguard relatively poorly documented assemblages, and on conservation measures that benefit local people. Aspects of butterfly ecology are discussed in relation to sound management of species and faunas, and selected examples from Europe, North America, and elsewhere exemplify increasing global interest in butterfly conservation.
Evolutionary Ecology and Developmental Instability
Authors: Markow Therese Ann
Published: July 2003

The past decade has seen a resurgence of interest in developmental instability, reflected in fluctuating asymmetry, as a concept in evolutionary ecology. Many investigations interpret fluctuating asymmetry in populations or subsets of populations as reflecting the existence of, or at least the potential for, natural or sexual selection. However, the biological and nonbiological factors underlying the appearance of developmental instability are not well understood. For example, the ability of heterozygosity vs genomic coadaptation to have an impact on development and cause fluctuating asymmetry is still debated, though each will have important, but different, implications for the genetic structure of populations and genetic architecture of various traits. These and other issues reviewed in this chapter must be clarified in order for the concept of developmental instability to be meaningful in evolutionary and ecological studies.
Culicoides Variipennis and Bluetongue-Virus Epidemiology in the United States
Authors: Tabachnick Walter J.
Published: July 2003

The bluetongue viruses are transmitted to ruminants in North America by Culicoides variipennis. US annual losses of approximately $125 million are due to restrictions on the movement of livestock and germplasm to bluetongue-free countries. Bluetongue is the most economically important arthropod-borne animal disease in the United States. Bluetongue is absent in the northeastern United States because of the inefficient vector ability there of C. variipennis for bluetongue. The vector of bluetongue virus elsewhere in the United States is C. variipennis sonorensis. The three C. variipennis subspecies differ in vector competence for bluetongue virus in the laboratory. Understanding C. variipennis genetic variation controlling bluetongue transmission will help identify geographic regions at risk for bluetongue and provide opportunities to prevent virus transmission. Information on C. variipennis and bluetongue epidemiology will improve trade and provide information to protect US livestock from domestic and foreign arthropod-borne pathogens.
Living on Leaves: Mites, Tomenta, and Leaf Domatia
Authors: Walter David Evans
Published: July 2003

Structures on the surfaces of leaves strongly affect phylloplane mites. Glandular trichomes defend against some plant parasites but can also mire predators. However, leaves with tomenta of nonglandular trichomes are often inhabited by large populations of predatory mites. Tufts of hairs and other minute structures in the vein axils are called leaf domatia. Comparative observations and experimental data demonstrate that leaves with domatia have enhanced levels of predatory mites. By accumulating predatory mites, leaf domatia act as a kind of constitutive defense against herbivores. Mites benefit from leaf domatia by securing a safe place for oviposition and molting. Like several other plant structures, leaf domatia are the manifestation of a long-term and mutually beneficial interaction between plants and arthropods.
Predatory Behavior of Jumping Spiders
Authors: Jackson R. R. , Pollard S. D.
Published: July 2003

Salticids, the largest family of spiders, have unique eyes, acute vision, and elaborate vision-mediated predatory behavior, which is more pronounced than in any other spider group. Diverse predatory strategies have evolved, including araneophagy, aggressive mimicry, myrmicophagy, and prey-specific prey-catching behavior. Salticids are also distinctive for development of behavioral flexibility, including conditional predatory strategies, the use of trial-and-error to solve predatory problems, and the undertaking of detours to reach prey. Predatory behavior of araneophagic salticids has undergone local adaptation to local prey, and there is evidence of predator-prey coevolution. Trade-offs between mating and predatory strategies appear to be important in ant-mimicking and araneophagic species.
Semiochemical Parsimony in the Arthropoda
Authors: Blum Murray S.
Published: July 2003

A wide variety of arthropods have adapted their own semiochemicals to subserve multiple functions in diverse contexts. Semiochemicals, the pheromones and allomones, have been detected in arthropod species in six orders, and it has been clearly established that these compounds are used with great parsimony. The versatility of these invertebrates in using these natural products for an incredible diversity of functions emphasizes the significance of semiochemicals in the evolutionary biology of the Arthropoda.

Multifunctional pheromones have proved to be especially characteristic of the queens of eusocial species. Compounds such as the queen substance of the honey bee, Apis mellifera, possess unrelated primer and releaser functions for the workers and act as a sex attractant for drones. Females of other hymenopterous species exploit the secretions of sting-associated glands as sex pheromones, whereas a variety of nonhymenopterous species have adapted components in diverse defensive secretions to function as sex pheromones.

The alarm pheromones of many arthropods are also used as defensive allomones, activity inhibitors, cryptic alarm pheromones, aggregative attractants, robbing agents, digging agents, trail pheromones, and antimicrobial agents. Defensive allomones also possess some of these parsimonious roles; in addition, however, some of these compounds possess highly distinctive roles, such as functioning as lethal attractants for prey or, in the aquatic milieu, cuticular wetting agents. Clearly, the availability of a variety of pheromones and allomones has enabled arthropods to evolve an elegant semiochemical parsimony with which to exploit the biological milieu.
Reproductive Traits and Male Fertility in Plants: Empirical Approaches
Authors: Snow Allison A. , Lewis Paul O.
Published: July 2003

Within-population variability in plant reproductive traits can influence both male and female fitness, but research on the male function of flowers has been hindered by the difficulty of measuring male fertility. Here we evaluate studies that employ paternity analysis to examine how specific plant traits affect male reproductive success (RS) in both natural and artificial populations. These studies illustrate the risks of assuming that male RS is correlated with female RS or with components of male fitness, such as the amount of pollen produced per plant. In some studies, paternity was assigned by simple genetic exclusion using unique multilocus allozyme profiles. More powerful methods involve statistical procedures that assign paternity to the most likely father of each offspring. Lack of genetic markers is a common problem in paternity analysis, and we discuss the types of molecular markers that may soon become more widely used in small, natural populations.
Sequences and Factors: A Guide to MHC Class-II Transcription
Authors: Glimcher Laurie H. , Kara Catherine J.
Published: July 2003

The expression of the class-II antigens of the major histocompatibility complex is tissue-specific, developmentally regulated in cells of the B lineage, and inducible by cytokine. Some of the molecular mechanisms that account for this regulation have recently been elucidated. DNA sequences upstream of human and mouse class-II genes that are critical for the transcription of these genes have been identified through transfection studies and transgenic analysis. Furthermore, a number of transcription factors that bind to important promoter motifs have recently been isolated. Examination of the class-II promoter in vivo both in the normal state and in patients with bare lymphocyte syndrome has further increased our understanding of class-II regulation.
Antigen Receptors on B Lymphocytes
Authors: Reth Michael
Published: July 2003

Recent studies on the structure of the B cell antigen receptor demonstrate that the membrane-bound and antigen-binding immunoglobulin molecules are noncovalently associated with a heterodimer of two novel transmembrane proteins. The B cell antigen receptor is thus a multicomponent receptor complex whose structural features are similar to those of the T cell antigen receptor complex. Cross-linking of the B cell antigen receptor results in rapid tyrosine phosphorylation of substrate proteins. This suggests that the B cell receptor belongs to a subgroup of the tyrosine kinase receptor family with a noncovalently associated src-like tyrosine kinase.
Immunological Aspects of Demyelinating Diseases
Authors: Martin Roland , McFarland Henry F. , McFarlin Dale E.
Published: July 2003

Primary demyelination in the central nervous system results from damage to the myelin sheath or oligodendroglia and can be produced by a variety of mechanisms, including metabolic disturbances, toxicities, infection, and autoimmunity. The major human demyelinating disease affecting the central nervous system is multiple sclerosis (MS). Although the etiology MS is not known, existing data indicate that both genetic and environmental factors contribute to pathogenesis. Experimental allergic encephalomyelitis (EAE) is induced by immunization of genetically susceptible animals with myelin proteins. This is mediated by autoimmune T cells. Characterization of MHC restriction, fine specificity of antigen recognition, and T cell receptor (TCR) usage by encephalitogenic T cells has resulted in highly specific immunotherapies. Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen. Because of the advances in the understanding and treatment of EAE, recent research in MS has been focused on the characterization of cellular immune responses against myelin components. The results of these studies are reviewed and the potential implications of these findings for the pathogenesis and future therapy of MS are examined.
In Vitro Antibodies: Strategies for Production and Application
Authors: Morrison Sherie L.
Published: July 2003

The approaches to the production of antibodies (Ab) using the techniques of genetic engineering and expression are reviewed. Genetic engineering facilitates the production of proteins tailormade for an intended use. Bacterial and mammalian expression systems are commonly used for the production of Ab and Ab-like molecules. While genomic or cDNA cloning can be used to obtain the relevant variable regions, PCR-based cloning approaches facilitate the acquisition of additional binding specificities. Large numbers of different chimeric Abs with murine variable regions joined to constant regions from human and other species have been expressed and found to exhibit the expected binding specificities and effector functions. These molecules have been used to study the structural basis of effector functions such as complement activation and Fc receptor binding, and potentially they may be used as therapeutic agents. Carbohydrate has been shown to influence both variable and constant region function. Single-chain Abs and fusion proteins with Ab binding specificities joined to nonimmunoglobulin sequences provide a source of Ab-like molecules with novel properties, and genetically engineered Ab-like molecules provide a source of useful antigens. Combinatorial libraries produced in bacteriophage present an alternative to hybridomas for the production of Abs with desired combining specifities. Issues of the immunogenicity of the recombinant molecules are addressed.
Apoptosis and Programmed Cell Death in Immunity
Authors: Cohen J. John , Duke Richard C. , Fadok Valerie A. , Sellins Karen S.
Published: July 2003

Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism ofapoptosis is currently under active investigation.
Structure of Peptides Associated with Class I and Class II MHC Molecules
Authors: Engelhard Victor H.
Published: July 2003

Class I and class II molecules encoded by genes within the major histocompatibility complex play a central role in regulation of immune responses through their ability to bind and display small peptides derived from foreign antigens. Within the last few years, considerable progress has been made in understanding the structures of class I and class II MHC molecules, as well as the features of the peptides that are their principal ligands. This review summarizes this information and describes how it accounts for both the specificity and degeneracy of peptide binding. It also considers how the origin and structural features of peptides that have been isolated from MHC molecules, so-called “naturally processed” peptides, have provided insight into the pathways through which the peptides are produced. Finally, the use of new structural information and techniques for peptide characterization for the identification of peptides that comprise epitopes for individual antigen-specific T cells are considered.
Lymphocyte Ontogeny and Activation in Gene Targeted Mutant Mice
Authors: Pfeffer K. , Mak T. W.
Published: July 2003

Gene targeting by homologous recombination in pluripotent embryonic stem cells enabled the systematic creation of mouse strains with defined genetic alterations. During the past few years a rapidly growing number of gene targeted mice has provided new insights into development, selection, activation, and signaling of T and B cells, as well as into the functions of cytokines. Here we discuss the present state of targeting technology and summarize the phenotypic changes observed in gene targeted mouse strains of immunological interest. These data allow us for the first time to define genetic checkpoints in lymphocyte development that are crucial for the orderly progression of T and B cells through ontogeny and for the generation of an immune response.
Positive Selection of Thymocytes
Authors: Jameson Stephen C. , Hogquist Kristin A. , Bevan Michael J.
Published: July 2003

Differentiation of αβ T cell receptor (TCR)-expressing T cells involves an obligatory interaction with self-major histocompatibility complex (MHC) molecules in the thymus. This process, called positive selection, both rescues thymocytes from programmed cell death and induces their differentiation into mature T cells. Another critical event in thymic development is to prevent maturation of hazardous autoreactive T cells; thus, mechanisms exist to eliminate T cells with self-reactive receptors (negative selection). How can these two pathways be distinguished? This question, which has long taxed immunologists, is more opposite because many features of the interactions in positive and negative selection are shared: Both processes are exquisitely MHC-allele specific, they involve MHC-bound peptide recognition, and employ at least some overlapping signal transduction pathways. However, resolution of this paradox has become much more feasible with the advent of powerful systems for withdrawing and reconstituting individual components involved in positive selection. This review describes recent advances in our understanding of the cells, receptors, ligands, and signaling pathways involved in this process. A pivotal part of this puzzle is the basis for discrimination between TCR ligands that induce positive vs negative selection. Recent work suggests that the peptide/MHC ligand for positive selection may bind with low avidity to the TCR. The implications of these data for the nature of T cell recognition during positive selection are discussed below.
Immunology of Reactive Arthritides
Authors: Burmester G. R. , Daser A. , Kamradt T. , Krause A. , Mitchison N. A. , Sieper J. , Wolf N.
Published: July 2003

Reactive arthritis (ReA) and Lyme arthritis together comprise a pair of chronic inflammatory diseases of the joints. Although differing in detail, these relatively rare diseases are related in their immunopathology to the much commoner rheumatoid arthritis (RA), for which they serve as both model and control. The trigger for rheumatoid arthritis is unknown, but for these rarer diseases triggering occurs by certain well-defined bacterial infections. Arthritis is an uncommon outcome of these infections, for reasons unknown, and the development of chronic, as distinct from brief, arthritis is even rarer; again, the reasons are unknown. Not only does knowing the trigger greatly assist us in understanding these diseases, so also does knowing the contrasting pattern of Th1 versus Th2 cytokines observed in RA and ReA. ReA and Lyme arthritis are here considered in the wider setting of infections where chronic morbidity arises first from hypersensitivity, and perhaps finally from autoimmunity, such as occurs in some of the major tropical diseases. The immunology of ReA and Lyme disease is surveyed in detail, concentrating on T cells and including an update on the Lyme vaccine(s). Additional sections deal with the enigma of HLA B27, with epidemiological findings relevant to the chronicity of ReA and to the need for enlarged prospective studies of ReA in the setting of a developing country.
Potassium and Calcium Channels in Lymphocytes
Authors: Lewis Richard S. , Cahalan Michael D.
Published: July 2003

Over the past decade, a variety of ion channels have been identified and characterized in lymphocytes by use of the patch-clamp technique. This review discusses biophysical and regulatory aspects of lymphocyte potassium and calcium channels with the aim of understanding the role of these channels in lymphocyte functions. Lymphocytes express both voltage-dependent potassium [K(V)] channels and calcium-activated potassium [K(Ca)] channels, and each is upregulated as cells progress toward division following mitogenic stimulation. The genes encoding two K(V) channels, Kv1.3 (type n) and Kv3.1 (type l), have cloned. Mutational analysis is revealing functionally important regions of these channel proteins. Exogenous expression studies and the use of highly specific channel blockers have helped to establish the roles of type n K(V) channels sustaining the resting membrane potential, in regulating cell volume, and in enabling lymphocyte activation. Blockade of K(V) and K(Ca) channels effectively inhibits the antigen-driven activation of lymphocytes, probably by inducing membraned epolarization and thereby diminishing calcium influx. A prolonged rise in intracellular calcium ([ Ca2+]i) is a required signal for lymphocyte activation by antigen or mitogens. Single-cell fluorescence measurements have revealed underlying [Ca2+]i oscillations that are linked closely to the opening and closing of Ca2+ and K+ channels. Sustained Ca2+ signaling and oscillations depend absolutely on plasma-membrane Ca2+ channels that are activated by the depletion of intracellular calcium stores. Under physiological conditions these channels open as a consequence of store depletion induced by inositol 1,4,5-trisphosphate (IP3), but they can also be activated experimentally by several agents that empty the stores without generating IP3, such as the microsomal Ca2+-ATPase inhibitor thapsigargin. The intricate causal relationships among ion channels, membrane potential, [Ca2+]i, and lymphokine gene expression can now be pursued at the single-cell level with patch-clamp recording, calcium-dependent dyes, reporter genes, and fluorescence video techniques. These approaches will help to clarify the essential roles of ion channels in the molecular pathways subserving activation and other lymphocyte behaviors.
Solid-State Reactivity at Heterophase Interfaces
Authors: Backhaus-Ricoult Monika
Published: July 2003

▪ Abstract  Chemical reactivity at heterophase interfaces is reviewed with a special focus on metal-oxide and oxide-oxide interfaces. Equilibrium chemistry of interfaces is discussed in terms of processes at the macroscopic and atomic level. The dependency on thermodynamic and crystallographic variables is described and illustrated by experimental results. Any reaction-related motion of an interface is associated with numerous transport and reaction steps that include not only atom transfer across the interface, chemical reactions between species and defects and phase transitions, but also steps accommodating lattice mismatch and volume changes. Faceting and morphology evolution of interfaces are included in the considerations.
Atomic Scale Investigation of Impurity Segregation to Crystal Defects
Authors: Cadel Emmanuel , Fraczkiewicz Anna , Blavette Didier
Published: July 2003

▪ Abstract  This paper presents a review of atomic-scale defects (planar defects and dislocations) analysis using atom probe (AP) and field ion microscopy (FIM). A large part of the discussion is dedicated to the first atomic-scale observation of a Cottrell atmosphere by a three-dimensional atom probe method (3DAP). The nanoscale boron segregation to line dislocations and planar defects in a B2-ordered FeAl (40 at.%Al) is imaged in three dimensions of the real space. The boron-enriched Cottrell atmosphere is imaged in the close vicinity of an edge 〈001〉 dislocation as a rod 3 nm in diameter, around to the dislocation line.
Proton Conduction Mechanisms at Low Degrees of Hydration in Sulfonic Acid–Based Polymer Electrolyte Membranes
Authors: Paddison S.J.
Published: July 2003

▪ Abstract  The need to operate polymer electrolyte membrane (PEM) fuel cells at temperatures above 100°C, where the amount of water in the membrane is restricted, has provided much of the motivation for understanding the mechanisms of proton conduction at low degrees of hydration. Although experiments have not provided any direct information, numerous theoretical investigations have begun to provide the basis for understanding the mechanisms of proton conduction in these nano-phase-separated materials. Both the hydrated morphology and the nature of the confined water in the hydrophilic domains influence proton dissociation from the acidic sites (i.e., −SO3H), transfer to the water environment, and transport through the membrane. The following molecular processes are discussed in connection to their role in the conduction of protons in sulfonic acid–based polymer electrolyte membranes (PEMs): (a) local chemistry of the hydrophilic side chains; its effect on the dissociation of the proton and eventual stabilization (separation) of the proton in the water; (b) the presence of neighboring sulfonic acid groups on proton transfer; and (c) the effect of the distribution of the sulfonate groups on the transport of protons in the channels/pores of the membrane.
Anhydrous Proton-Conducting Polymers
Authors: Schuster Martin F.H. , Meyer Wolfgang H.
Published: July 2003

▪ Abstract  Anhydrous proton-conducting polymers usually consist of a more or less inert polymer matrix that is swollen with an appropriate proton solvent (in most cases, phosphoric acid). An outline of the different materials is provided, with a focus on PBI/H3PO4 blends that are currently most suitable for fuel cell applications. Also discussed are alternative concepts for fully polymeric materials, which establish proton conductivity as an intrinsic property using amphoteric heterocycles such as imidazole as a proton solvent. The development of some of the first polymers is described, and the fundamental relations between their material properties and conductivity are discussed. Closely related to this relatively new concept are mechanistic investigations focusing on intermolecular proton transfer and diffusion of (protonated) solvent molecules, the contributions of both transport processes to conductivity, and the dependence of these ratios on composition, charge carrier density, etc. Although the development of fully polymeric proton conductors is inseparably related to mechanistic considerations, relatively little attention has been paid to these concepts in the field of conventional membranes (hydrated ionomers, H3PO4-based materials). Consequently, their general relevance is emphasized, and according investigations are summarized to provide a more comprehensive picture of proton transport processes within proton exchange membranes.
New Electrocatalysts by Combinatorial Methods
Authors: Smotkin Eugene S. , Díaz-Morales Robert R.
Published: July 2003

▪ Abstract  Combinatorial methods provide a means for accelerating the discovery of fuel cell catalysts. The first example of parallel fuel cell catalysts screening was an indirect method that used fluorescent chemosensors to detect changes in pH in proximity to electrocatalyst spots. Serial direct electrochemical methods have been developed that use voltammetry, chronoamperometry, and scanning electrochemical microscopy. An array fuel cell screens catalysts simultaneously, using high-performance fuel cell components. Heuristic models based on mechanistic and spectroscopic studies provide guidance for library development, and detailed studies of discovered catalysts can help to refine these models. The remaining challenges are the development of high throughput synthetic methods that can enable the use of discovery level and focus level screening. Until these synthetic methods are developed, a greater emphasis should be placed on smaller libraries with design of experiment strategies leveraged with informatics and data mining.
Solid Oxide Fuel Cell Cathodes: Polarization Mechanisms and Modeling of the Electrochemical Performance
Authors: Fleig Jürgen
Published: July 2003

▪ Abstract  Several recent experimental and numerical investigations have contributed to the improved understanding of the electrochemical mechanisms taking place at solid oxide fuel cell (SOFC) cathodes and yielded valuable information on the relationships between alterable parameters (geometry/material) and the cathodic polarization resistance. Efforts to reduce the polarization resistance in SOFCs can benefit from these results, and some important aspects of the corresponding studies are reviewed. Experimental results, particularly measurements using geometrically well-defined Sr-doped LaMnO3 (LSM) cathodes, are discussed. In regard to simulations, the different levels of sophistication used in SOFC electrode modeling studies are summarized and compared. Exemplary simulations of mixed conducting cathodes that show the capabilities and limits of different modeling levels are described.
Methanol-Resistant Oxygen-Reduction Catalysts for Direct Methanol Fuel Cells
Authors: Shukla A.K. , Raman R.K.
Published: July 2003

▪ Abstract  Methanol oxidation in the cathode compartment of the fuel cell, which occurs during the oxygen-reduction reaction on Pt-based cathodes, constitutes a significant performance loss in the direct methanol fuel cells. Over the past decade, four types of methanol-resistant oxygen-reduction catalysts have been developed to circumvent this problem. Among these, transition-metal chalcogenides, and in particular RuSe, have shown effective selectivity to oxygen-reduction reaction in the presence of methanol. These catalysts not only can enhance the performance of the conventional direct methanol fuel cells but also could provide a route to develop mixed-reactants direct methanol fuel cells, which could be highly cost-effective in comparison with the conventional direct methanol fuel cells. This article is a brief update on the preparation, characterization, and implications of methanol-resistant oxygen-reduction catalysts.
Prostaglandins, Glucose Homeostasis, and Diabetes Mellitus
Authors: Robertson R. Paul
Published: July 2003

Prostaglandins of the E series are implicated as regulators of glucose homeostasis because of their effects on glucose production and secretion of insulin and glueagon. PGE is postulated to play a role in the pathophysiology of insulin secretion in adult-onset (Type II) diabetes mellitus. Evidence supporting this hypothesis includes the demonstration that PGE inhibits glucose-induced acute insulin responses in normal humans. Moreover, drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus.
Etiology of Type I Diabetes Mellitus: Heterogeneity and Immunological Events Leading to Clinical Onset
Authors: Doniach D. , Bottazzo G. F. , Path M. R. C. , Cudworth A. G.
Published: July 2003

Type I diabetes is a heterogeneous disorder and the causes of pancreatic beta-cell destruction are unknown. In 1-2% of all cases, viruses (e.g. coxsackie, rubella, mumps, or beta-cell poisons) have been implicated. Twin studies suggest at most 50% of genetic predisposition.

In this review we describe the autoimmune components which, in association with inheritance of HLA-haplotypes in susceptible families, allow the future selection of predisposed sibs for possible preventive therapy to retard loss of insulin secretion. The known association of the endocrine autoimmune organ-specific disorders in 10% of Type I diabetics is the extreme expression of the other main genetic ingredient in the development of insulitis in this disease, irrespective of the triggering environmental components. In this “polyendocrine” subgroup and in the “juvenile-onset” cases there is a prolonged latency period during which pancreatic autoimmunity markers are present before clinical expression of the disease.
Iron Absorption
Authors: Charlton Robert W. , Bothwell Thomas H.
Published: July 2003

The rate of absorption of iron is adjusted according to body iron requirements, but the virtual absence of heme and the poor bioavailability of the nonheme iron in the diets of many people, especially in developing countries, means that the amount that can be absorbed is limited. Those whose requirements are increased by growth, menstruation, or pregnancy frequently cannot absorb enough. Sufficient is now known about the factors in food that increase or diminish the bioavailability of nonheme iron to permit the effective fortification of dietary staples, although the application of this information has proved difficult particularly in the Third World where nutritional iron deficiency is most prevalent. Effective fortification may lead to iron overload in those whose control of iron absorption is genetically defective, and recent evidence that the HLA-linked recessive gene for idiopathic hemochromatosis may occur much more commonly than hitherto suspected makes it imperative that an effective monitoring system should form a part of every fortification program.
Alcohol and Pregnancy: A Clinical Perspective
Authors: Rosett Henry L. , Weiner Lyn
Published: July 2003

Exposure of the fetus at any gestational stage to high concentrations of alcohol can adversely affect growth, morphology, and neurophysiologic development. Sustained heavy drinking can result in the fetal alcohol syndrome. Cessation of heavy drinking during pregnancy will benefit both mother and child. Primary health care providers can effectively identify and treat women at risk.
Psychological Dysfunction Accompanying Subcortical Dementias
Authors: Cummings Jeffrey L. , Benson D. Frank
Published: July 2003

Subcortical dementia occurs both in disorders affecting the basal ganglia (for example, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy) and in a variety of subcortical vascular, infectious, inflammatory, neoplastic, and traumatic conditions. The principal features of subcortical dementia include bradyphrenia, impairment of executive function, recall abnormalities, visuospatial disturbances, depression, and apathy. The syndrome contrasts with dementia of the Alzheimer type in which cortical involvement produces aphasia, combined recall and recognition deficits, and indifference. Electrophysiologic, biochemical, and metabolic studies support a distinction between subcortical and cortical dementias.
Dyspnea: Physiological and Pathophysiological Mechanisms
Authors: Wasserman Karlman , Casaburi Richard
Published: July 2003

Dyspnea, the sensation of feeling breathless, is a symptom experienced under conditions in which there is an inordinately high ventilatory demand relative to the ability to breathe. Its major physical sign is tachypnea. New developments in monitoring ventilation during exercise have improved our ability to evaluate the symptom of dyspnea and to understand pathophysiological mechanisms contributing to the symptom. We briefly describe the range of mechanisms that determine exercise ventilation and their possible relationship to dyspnea. Questionnaires and psychophysical testing have been used to quantify dyspnea, but there is variability in dyspnea grade from these methods. Dyspnea-producing stimuli and the mechanisms by which they act are reviewed. Disorders producing dyspnea and the pathophysiological mechanisms underlying each are discussed. Perception of dyspnea is obviously through the central nervous system, where dyspnea-producing stimuli are integrated. The specific integration site is probably in the region of the brain stem, since occasional patients with brain stem lesions do not experience dyspnea despite the presence of a number of dyspnea-producing stimuli.
Pathogenesis of Membranous Nephropathy
Authors: Couser William G. , Abrass Christine K.
Published: July 2003

Membranous nephropathy is the most common cause of idiopathic nephrotic syndrome in adults. Recent studies of the pathogenesis of the sub-epithelial glomerular immune deposits that characterize this disease have revealed new mechanisms of glomerular immune deposit formation involving cell surface antigens and have documented the role of the C5b-9 membrane attack complex of complement in mediating renal injury. Understanding these mechanisms may help us understand the pathogenesis of several other immune-mediated diseases and has implications for possible therapeutic interventions in MN.
Systemic Effects of Vitamin D
Authors: Reichel Helmut , Norman Anthony W.
Published: July 2003

Traditionally perceived as a seco-steroid hormone involved in the regulation of calcium metabolism, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is now known also to be active in tissues not directly contributing to mineral metabolism. New data show that 1α,25(OH)2D3 is produced by and interacts with hematopoietic cells. The hormone promotes myeloid differentiation and modulates the function of activated lymphocytes. Another new target tissue for 1α,25(OH)2D3 is the skin, where 1α,25(OH)2D3 enhances differentiation of epidermal cells. Therapeutic application of 1α,25(OH)2D3 or suitable analogues in differentiation disorders of hematopoietic and skin cells is currently under investigation.
The Pathophysiology of Pleural Effusions
Authors: Sahn Steven A.
Published: July 2003

Two features of human parietal pleura explain its role in the formation and removal of pleural liquid and protein in the normal state: the proximity of the microvessels to the pleural surface and the presence of stomata situated between mesothelial cells. For pleural fluid to accumulate in disease, there must be increased production from increased hydrostatic pressure, decreased oncotic or pleural pressure, increased microvascular permeability, or peritoneal-pleural movement. The rate of formation must overwhelm lymphatic clearance, which may be decreased by hydrostatic forces or blocked by malignant infiltration.
Neurologic Consequences of Cocaine Use
Authors: Rowbotham M. C. , Lowenstein D. H.
Published: July 2003

Neurologic consequences of cocaine use frequently present as medical emergencies in the form of stroke, repeated seizures, encephalopathy, acute headache, and unusual transient neurological deficits. The often fatal or disabling neurologic syndromes have only recently been recognized but are now well documented. Cocaine use is a significant cause of stroke in young adults, and the full, long-term ramifications of maternal cocaine use on the fetus will not be known for years to come. Unfortunately, there is not effective treatment other than abstinence, and our understanding of the pathophysiology of cocaine-associated neurologic illness remains limited.
Growth Factors and Cytokines in Bone Cell Metabolism
Authors: Canalis Ernesto , McCarthy Thomas L. , Centrella Michael
Published: July 2003

Growth factors regulate the growth and differentiated function of cells. Skeletal cells synthesize fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor β, and additional cytokines. Some of the growth factors produced by bone cells primarily stimulate bone cell replication, whereas others also affect the differentiated function of the osteoblast. Skeletal growth factors also may play a role in the pathogenesis and therapy of metabolic bone disease.
Cell-Mediated Immunity in Glomerular Disease
Authors: Rovin Brad H. , Schreiner George F.
Published: July 2003

Our understanding of the role of the immune system in modulating glomerular injury continues to evolve. The participation of antibody, complement, and neutrophils alone cannot completely explain many aspects of the pathways of experimental and human glomerulonephritis. The elements of the immune system that mediate cellular immunity, T lymphocytes and monocytes, also appear to be important effectors of glomerulonephritis. An understanding of the role of cell-mediated immunity in renal disease is essential in designing therapies to interrupt immunologically sustained glomerular damage.
Growth Factors and Wound Healing: Platelet-Derived Growth Factor as a Model Cytokine
Authors: Deuel Thomas F. , Kawahara Rodney S. , Mustoe Thomas A. , Pierce Glenn F.
Published: July 2003

Cytokines such as the platelet-derived growth factor (PDGF) have the potential to initiate and mediate many if not all of the complex biological responses associated with inflammation and wound healing. PDGF is a potent cytokine that may be used to illustrate the diverse activities initiated by the interactions of PDGF with its receptor relevant to the inflammatory response and subsequent wound repair. Because PDGF can chemotactically attract, activate, and initiate new expression of quiescent genes (e.g. the small inducible gene, SIG, family), it fulfills the predictions anticipated of a candidate wound hormone. PDGF added directly to experimental wounds in animals enhances wound healing, which suggests that cytokines will become increasingly important as therapeutic agents in the treatment of wounds in humans.
Antithrombins: Their Potential as Antithrombotic Agents
Authors: Weitz Jeffrey I. , Hirsh Jack
Published: July 2003

The inhibition of thrombin is the key to the prevention and treatment of thrombotic disorders. Although heparin is an extremely effective anticoagulant, it has certain limitations that are not shared by newer thrombin inhibitors. As a result, these novel inhibitors may have advantages over heparin in certain clinical settings.
Suicide: Risk Factors and Prevention in Medical Practice
Authors: Buzan Randall D. , Weissberg Michael P.
Published: July 2003

Suicide is a preventable cause of death that increasingly affects younger age groups. We review the epidemiology of suicide in the general population, in psychiatric patients, and in medical/surgical patients. The essential role of the primary care physician in preventing suicide is examined.
The Molecular Biology of G6PD Variants and Other Red Cell Enzyme Defects
Authors: Beutler Ernest
Published: July 2003

Modern techniques of molecular biology have made it possible to identify mutations in a number of different hereditary red cell enzyme defects. Most of the studies have been performed in glucose-6-phosphate dehydrogenase deficiency, where a large number of point mutations have been identified. The same mutations are encountered repeatedly, even in patients with defects that were thought, on the basis of biochemical properties of the residual enzyme, to be distinct. A beginning has been made in identifying mutations in a few other red cell enzyme defects.
The Molecular Basis of Colon Cancer
Authors: Rustgi Anil K. , Podolsky Daniel K.
Published: July 2003

There are approximately 160,000 new cases of colon cancer every year in the United States. Colon carcinoma results from the aggregate effects of multiple genetic alterations. Some genetic alterations may be inherited, while others reflect somatic mutations. The latter may themselves be the indirect result of environmental factors such as diet. It is the total accumulation of these genetic changes, combining the activation of oncogenes with the inactivation of tumor suppressor genes, that is responsible for determining the biologic properties of colon cancer.
A Putative Role of Hypercholesterolemia in Progressive Glomerular Injury
Authors: Diamond Jonathan R. , Karnovsky Morris J.
Published: July 2003

Recently, much experimental evidence has accumulated contending that hypercholesterolemia is an aggravating factor in the progression of initial glomerular injury to glomerulosclerosis. Many of the features of progressive glomerular disease share biological properties with those of atherosclerosis, and data suggesting a noxious role for oxidized low-density lipoprotein in the glomerulosclerosis process are emerging. This review discusses these issues and examines the pathobiology of cholesterol-induced glomerular injury.
Biological Regulation of Factor VIII Activity
Authors: Kaufman Randal J.
Published: July 2003

Factor VIII, the plasma protein deficient in hemophilia A, is a crucial cofactor for regulation of hemostasis. Our understanding of factor VIII increased tremendously once it became possible to isolate homogeneous preparations of this protein from plasma. In addition, the isolation of the factor VIII gene has provided new means of exploring the structure and function of factor VIII. This increasing knowledge also sheds light on the genetic alterations resulting in hemophilia as well as in thrombophilia. This chapter summarizes our current understanding of the regulation of factor VIII function and raises questions to be answered in the years to come.
Kidney Preservation Ex Vivo for Transplantation
Authors: Bonventre Joseph V. , Weinberg Joel M.
Published: July 2003

Ischemic injury to the renal allograft, prior to implantation, is an important cause of delayed graft function. With improved understanding of the pathophysiological mechanisms involved, strategies have been devised to minimize ischemic injury during preservation ex vivo. It is clear that reducing the warm ischemic time, flushing the kidney with hypothermic solution containing cell-impermeant compounds, and maintaining the organ at low temperature ex vivo have increased the duration that the kidney can be preserved. The effectiveness of a number of other components of preservation solutions, as well as the relative merits of continuous perfusion of the organ ex vivo, is more controversial. In this chapter, we review the mechanistic features of ischemic acute renal failure and discuss various preservation strategies and their success in the context of these basic principles of ischemic pathophysiology.
Antibiotic Therapy for Chronic Infection of Pseudomonas in the Lung
Authors: Høiby N.
Published: July 2003

Chronic Pseudomonas aeruginosa lung infection is an endobronchiolitis characterized by the microcolony mode of growth (biofilm). Early colonization is treated with oral ciprofloxacin combinedw ith colistin inhalation. Chronic infection is treated with “maintenance chemotherapy” consisting of β-lactam antibiotics and tobramycin intravenously in combination with colistin inhalation four times yearly.
Role of Bacterial Cytotoxins in Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
Authors: Ashkenazi Shai
Published: July 2003

Bacterial cytotoxins, which are produced by Shigella dysenteriae 1 and certain E. coli serotypes, kill mammalian cells by inhibiting protein synthesis. They have been related to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, probably by initial insult to vascular endothelial cells. This insight opened new avenues of research and possible interventions.
Diagnosis and Treatment of Obsessive Compulsive Disorder
Authors: De Veaugh-Geiss Joseph
Published: July 2003

Obsessive compulsive disorder (OCD) is a common anxiety disorder that appears to be due to a disturbance in central serotonergic functioning. Drugs, such as clomipramine, that inhibit neuronal reuptake of serotonin are effective in treating OCD. Behavioral therapy techniques are also effective.