bluuebunny/crossref_metadata_2025 huggingface dataset:
CD45: An Emerging Role as a Protein Tyrosine Phosphatase Required for Lymphocyte Activation and Development
Authors: Trowbridge Ian S. , Thomas Matthew L.
Published: July 2003

CD45 is one of the most abundant leukocyte cell surface glycoproteins and is expressed exclusively upon cells of the hematopoietic system. Different isoforms of CD45 are generated by alternative splicing and are expressed in cell type-specific patterns on functional subpopulations of lymphocytes. In a major advance, CD45 was identified as one of the first members of a novel class of enzymes, the protein tyrosine phosphatases (PTPs). This serendipitous discovery linked CD45 to the process of reversible protein tyrosine phosphorylation, a key regulatory mechanism for controlling the growth and division of eukaryotic cells, and provided the impetus for most of the studies described in this review. CD45 is now established as a critical component of the signal transduction machinery of lymphocytes. In particular, evidence from genetic experiments indicates that CD45 plays a pivotal role in antigen-stimulated proliferation of T lymphocytes and in thymic development. Two members of the Src-family of protein tyrosine kinases (PTKs), the p56lck and p59fyn proteins, have been implicated as physiological substrates of CD45, providing an important clue to how the action of this leukocyte-specific PTP might influence signaling by the T cell antigen receptor. Structure-function analysis of CD45 and other PTPs has identified structural features of PTP catalytic domains required for enzymatic activity. However, despite intensive efforts, little is known about how the activity of CD45 is regulated. The external domain of CD45 does not appear to be absolutely required for signal transduction by the T cell receptor, and there is currently no evidence that ligand binding modulates CD45 activity. Analysis of CD45 isoform expression has revealed a hitherto unrecognized plasticity in isoform usage by T cells and other leukocytes, adding to the regulatory complexity of isoform expression.
Lymphokine Production by Human T Cells in Disease States
Authors: Romagnani Sergio
Published: July 2003

A large body of evidence suggests the existence of polarized human T cell responses, reminiscent of Th1 and Th2 subsets described for mouse T cells. Human Th1-like cells preferentially develop during infections by intracellular bacteria, protozoa, and viruses, whereas Th2-like cells predominate during helminthic infestations and in response to common environmental allergens. The cytokine profile of “natural immunity” evoked by different offending agents in the context of different host genetic backgrounds appears to be a critical factor in determining the phenotype of the subsequent specific response.

Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, they can also promote different immunopathological reactions. Th1-type responses appear to be involved in organ specific autoimmunity, in contact dermatitis, and in some chronic inflammatory disorders of unknown etiology. In contrast, in genetically predisposed hosts, Th2-type responses against common environmental allergens are responsible for triggering of allergic atopic disorders. Altered profiles of lymphokine production may account for immune dysfunctions in some primary or acquired immunodeficiency syndromes. The role of lymphokines produced by T cells in the pathogenesis of systemic autoimmune disorders is less clear. Further work is also required to better clarify the role of T cell-derived lymphokines in protecting against tumors or in favoring their development.
Choices Following Antigen Entry: Antibody Formation or Immunologic Tolerance?
Authors: Nossal G. J. V.
Published: July 2003

The research briefly summarized here covers 38 years of work in cellular immunology, briefly devoted to understanding how antigen subserves the antithetical functions of stimulating antibody formation and inducing tolerance. The three interlocking themes running through the work are the development of methods to beat the problem of heterogeneity among lymphocytes by studying single cells and single clones; critical pursuit of antigen-trapping patterns within lymphoid tissues and analysis of consequent cellular events; and construction of models of tolerance that permit the detection of events subtler than direct purging of the B cell repertoire. One of the best features of this adventure has been its international character, the interaction with colleagues in many countries, and the influence that this work, despite its entirely fundamental character, has exerted in the practical world of preventive and clinical medicine.
Interleukin-12: A Proinflammatory Cytokine with Immunoregulatory Functions that Bridge Innate Resistance and Antigen-Specific Adaptive Immunity
Authors: Trinchieri Giorgio
Published: July 2003

Interleukin-12 (IL-12) is a heterodimeric cytokine produced mostly by phagocytic cells in response to bacteria, bacterial products, and intracellular parasites, and to some degree by B lymphocytes. IL-12 induces cytokine production, primarily of IFN-γ, from NK and T cells, acts as a growth factor for activated NK and T cells, enhances the cytotoxic activity of NK cells, and favors cytotoxic T lymphocyte generation. In vivo IL-12 acts primarily at three stages during the innate resistance/adaptive immune response to infection: 1. Early in the infection, IL-12 is produced and induces production from NK and T cells of IFN-γ , which contributes to phagocytic cell activation and inflammation; 2. IL-12 and IL-12- induced IFN-γ favor Thl cell differentiation by priming CD4+ T cells for high IFN-γ production; and 3. IL-12 contributes to optimal IFN-γ production and to proliferation of differentiated Th l cells in response to antigen. The early preference expressed in the immune response depends on the balance between IL-12, which favors Thl responses, and IL-4, which favors Th2 responses. Thus,IL-12 represents a functional bridge between the early nonspecific innate resistance and the subsequent antigen-specific adaptive immunity.
Principles for Adoptive T Cell Therapy of Human Viral Diseases
Authors: Riddell Stanley R. , Greenberg Philip D.
Published: July 2003

The development of successful adoptive immunotherapy for human virus infections is predicated on an understanding of the effector cells and mechanisms essential for providing the host with a protective response to acute infection and the requirements for long-term in vivo survival of transferred cells that will be necessary to provide memory responses to persistent and latent viral infections. In this review, we discuss the results of recent studies examining the effector mechanisms mediated by virus-specific αβ+ T cells and the strategies viruses have evolved to evade recognition by such T cells and/or to interfere with the expression of T cell effector functions. The evasion strategies employed by individual viruses can render T cell subsets or T cells of particular specificities less effective in eliminating virally infected cells, and consequently they are less desirable choices for use in adoptive therapy. Insights derived from described studies of the pathogenesis and immunobiology of virus infections have resulted in the development of clinical adoptive immunotherapy studies for infections with CMV, EBV, and HIV. Although the results from such studies are preliminary, the principle that virus-specific T cells can be successfully transferred and can mediate therapeutic efficacy in humans has already been affirmed. The use of recently developed methods, such as retroviral-mediated gene transfer, to genetically modify antigen-specific T cell clones provides a novel approach to overcome limitations and improve on the safety and efficacy observed in these initial studies, suggesting that more widespread use of adoptive transfer of specific T cells as a therapeutic regimen should be feasible in the near future.
New Material Needs for Hydrocarbon Fuel Processing: Generating Hydrogen for the PEM Fuel Cell
Authors: Farrauto R. , Hwang S. , Shore L. , Ruettinger W. , Lampert J. , Giroux T. , Liu Y. , Ilinich O.
Published: July 2003

▪ Abstract  The hydrogen economy is fast approaching as petroleum reserves are rapidly consumed. The fuel cell promises to deliver clean and efficient power by combining hydrogen and oxygen in a simple electrochemical device that directly converts chemical energy to electrical energy. Hydrogen, the most plentiful element available, can be extracted from water by electrolysis. One can imagine capturing energy from the sun and wind and/or from the depths of the earth to provide the necessary power for electrolysis. Alternative energy sources such as these are the promise for the future, but for now they are not feasible for power needs across the globe. A transitional solution is required to convert certain hydrocarbon fuels to hydrogen. These fuels must be available through existing infrastructures such as the natural gas pipeline. The present review discusses the catalyst and adsorbent technologies under development for the extraction of hydrogen from natural gas to meet the requirements for the proton exchange membrane (PEM) fuel cell. The primary market is for residential applications, where pipeline natural gas will be the source of H2used to power the home. Other applications including the reforming of methanol for portable power applications such as laptop computers, cellular phones, and personnel digital equipment are also discussed. Processing natural gas containing sulfur requires many materials, for example, adsorbents for desulfurization, and heterogeneous catalysts for reforming (either autothermal or steam reforming) water gas shift, preferential oxidation of CO, and anode tail gas combustion. All these technologies are discussed for natural gas and to a limited extent for reforming methanol.
Understanding Materials Compatibility
Authors: Yokokawa Harumi
Published: July 2003

▪ Abstract  The use of chemical potential diagrams to examine interface chemistry is discussed in terms of the chemical reactions among oxides and associated interdiffusion across the interface. The driving force for both processes can be determined from the chemical potential values. The geometrical features of the chemical potential diagrams can be related to the valence stability of binary oxides and the stabilization energy of double oxides from the constituent oxides. The materials compatibility in solid oxide fuel cell materials is discussed with a focus on a lanthanum manganite cathode and a yttria-stabilized zirconia (YSZ) electrolyte. Emphasis is placed on the valence numbers of manganese in the fluorite solid solution and the perovskite oxides, which have been derived by thermodynamic analysis of the magnitude of the stabilization energy/interaction parameters as a function of ionic size for respective valence numbers. The change of manganese valence on La2Zr2O7 formation and Mn dissolution in YSZ are discussed in relation with the oxygen evolution/adsorption process. Oxygen flow associated with electrochemical reactions exhibits markedly different features depending on the direction of the polarization, which can lead to drastic changes in the interface chemistry (precipitation or interdiffusion).
Applications and Limitations of Hemapheresis
Authors: Silvergleid Arthur J.
Published: July 2003

Hemapheresis is the selective collection of any blood component. With the use of automated equipment, hemapheresis has become practical both for procuring specific components for transfusion and for removing specific components considered pathogenic factors in clinical disease. This review considers all aspects of hemapheresis, including its role in blood component procurement and its potential therapeutic applications. Attention is focused on the clinical indications for the use of apheresis-harvested components, and on the rationale for the effectiveness of therapeutic cytapheresis and plasma exchange.
Identification and Significance of Cell Markers in Leukemia and Lymphoma
Authors: Warnke Roger A. , Link Michael P.
Published: July 2003

The identification of markers of human hematopoietic cell differentiation and function has revealed the nature of the proliferating cell in many lymphoid neoplasms and demonstrated marked phenotypie heterogeneity in traditional subgroups. Selected markers are described that define common subgroups of lymphoid leukemia and non-Hodgkin’s lymphoma. The identification of cell markers has significant implications for accuracy of diagnosis, for predicting clinical characteristics, and for understanding the biology of these diseases.
Congestive Heart Failure in the Diabetic
Authors: Regan Timothy J.
Published: July 2003

Heart failure seems to occur in adult-onset diabetics with a greater frequency than in the nondiabetic population, particularly in women. A number of such patients do not have significant occlusive disease of the major coronary arteries, or convincing small-vessel disease. A subclinical abnormality of myocardium in experimental diabetes and asymptomatic human diabetics supports the concept of a diabetic cardiomyopathy.
The Diagnosis and Treatment of Major Depressive Disorder in Childhood
Authors: Puig-Antich Joaquim , Weston Burt
Published: July 2003

The authors review the evidence supporting the hypothesis of similarity or identity of prepubertal and adult major depressive disorders and give a state-of-the-art account of current assessment techniques, diagnosis, and treatment methods of prepubertal major depression. This is an area of child psychiatry where recent psychobiological research advances are fueling profound changes in traditional nosology and therapeutics. In addition, further understanding of early onset major depression is likely to throw considerable light on the nature and pathophysiology of depressive illness across ages.
Localization of Parathyroid Glands
Authors: Levin Kenneth E. , Clark Orlo H.
Published: July 2003

Parathyroid localization tests are helpful for all patients with primary hyperparathyroidism before parathyroid exploration, and they are essential for patients who have had previous parathyroid or thyroid operations. The selection of specific localization tests depends on whether the patient is undergoing an initial or a reoperative procedure, as well as on the availability of the specialized equipment and expertise of the physicians and technicians performing and interpreting these studies.
Oral Antibiotic Therapy for Serious Infections
Authors: Smith Arnold L.
Published: July 2003

After a pathogen has been identified and the antibiotic susceptibility determined, parenteral antibiotic administration can be replaced by the oral route for certain patients with meningitis, brain abscess, endocarditis, and skeletal infections. Antibiotics should be administered with the stomach empty and accompanied by 3 ml/kg of water. Direct instillation into the lumen of the small intestine may be advantageous with selected patients. Documenting adequate antibiotic absorption and ensuring compliance are essential to efficacious therapy.
Evaluation of Brain Imaging Techniques in Mental Illness
Authors: Andreasen Nancy C.
Published: July 2003

Brain imaging is increasingly applied in psychiatry, both for clinical evaluation and as a research tool. Computerized tomography (CT) and magnetic resonance imaging (MRI) have documented that structural brain abnormalities occur in some types of psychiatric patients, particularly those who suffer from schizophrenia. Dynamic imaging techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have documented decreased temporoparietal activity in Alzheimer’s disease, hypofrontality in schizophrenia, and a variety of abnormalities in affective and anxiety disorders. These techniques promise to teach us a great deal about the underlying neural mechanisms in mental illness.
The Pathobiology of Alzheimer's Disease
Authors: Glenner George G.
Published: July 2003

The discovery of β protein, the major component of the amyloid fibrils of the plaques and cerebral vessels and of the paired helical filaments of the neurofibrillary tangles, has provided a means to decipher the pathogenesis of Alzheimer's disease. The same lesions in aged Down's syndrome individuals have also been shown to be composed of β protein. Gene probes localize the gene for β protein, as well as that for familial Alzheimer's disease, to chromosome 21, but these genes are not linked. A study of posttranslational modifications of the 695-amino-acid β-protein gene precursor, with specific reference to abnormal proteolysis, may provide insights into the cause of the amyloidotic lesions of Alzheimer's disease and the means of arresting them.
Molecular Pathogenesis of Ph-Positive Leukemias
Authors: Clark Steven S. , Crist William M. , Witte Owen N.
Published: July 2003

The strong association between the Philadelphia chromosome (Ph) and chronic myelogenous leukemia (CML) suggests that the Ph translocation plays a significant role in CML pathogenesis. For this reason, Ph-positive leukemias have been well studied from the molecular, clinical, and cell biological perspective. We attempt to integrate these data in order to better our understanding of the role of the Ph chromosome in human leukemia.
Guillain-Barré Syndrome
Authors: England John D.
Published: July 2003

Guillain-Barre syndrome is an acute inflammatory demyelinative neuropathy usually presenting as a symmetric areflexic paralysis. An immunologic pathogenesis is likely. Early diagnosis is important since good supportive care and plasmapheresis can decrease morbidity and hasten recovery.
Modulation of Endothelial Hemostatic Properties: An Active Role in the Host Response
Authors: Gerlach Herwig , Esposito Ciro , Stern David M.
Published: July 2003

As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose-modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state.
Insulin Receptor Structure and Function in Normal and Pathological Conditions
Authors: Becker Andrew B. , Roth Richard A.
Published: July 2003

The insulin receptor is a large cell surface glycoprotein that concentrates insulin at the site of action and also initiates responses to insulin. The receptor is a disulfide-linked oligomer comprised of two α and two β subunits. Signal transduction through the insulin receptor appears to require the activation of an intrinsic tyrosine-specific protein kinase activity. A variety of disorders, both acquired and genetic, are associated with the development of insulin resistance and are frequently the result of cellular defects in insulin receptor structure, function, and action. The recent cloning of several mutant receptors from patients with genetic forms of extreme insulin resistance has increased our understanding of insulin resistance on the molecular level.
Pathophysiology of Hashimoto's Thyroiditis and Hypothyroidism
Authors: Rapoport Basil
Published: July 2003

Autoimmune Hashimoto's thyroiditis, the most common endocrine disorder, is primarily a subclinical disease. Whether or not subclinical hypothyroidism should be treated remains controversial. Recent advances have been made in understanding the molecular nature of the antigens that are the target of the immune system in Hashimoto's thyroiditis. The “microsomal antigen” is now recognized to be thyroid peroxidase.
Genetics of Major Psychiatric Disorders
Authors: Ciaranello Roland D. , Ciaranello Andrea L.
Published: July 2003

We review recent studies on the inheritance of affective disorders and schizophrenia. Both groups of diseases have substantial genetic and nongenetic components, and their inheritance does not fit simple Mendelian models. Linkage studies implicate the Xp28 and 11p15 regions as potential disease loci in affective illness, and the 5q11-q13 region in schizophrenia. These conclusions are highly controversial, however, and must be viewed as extremely tentative.
Epidemiology and Outcome of Child Abuse
Authors: Rosenberg Donna A. , Krugman Richard D.
Published: July 2003

Maltreatment in childhood can result in problems that eventually present to the internist. The common somatic, psychosomatic, and psychiatric presentations in adults are reviewed. Mental health referral is often appropriate. When a case of child abuse is reported to the physician by a patient, the physician's legal responsibilities and protections are summarized.
Resistance of Viruses to Antiviral Drugs
Authors: Freifeld A. G. , Ostrove J. M.
Published: July 2003

In recent years, substantial advances in antiviral therapy have been made; however, in the immunocompromised host, antiviral drug resistance is becoming an issue of increasing clinical importance. Understanding the mechanism of action of antiviral agents, especially those used to treat herpesvirus infections, may enable us to design new therapeutic agents and better treatment regimens to deal with antiviral drug resistance.
Unusual Forms of Insulin Resistance
Authors: Taylor Simeon I. , Accili Domenico , Cama Accili , Imano Eiichi , Kadowaki Hiroko , Kadowaki Takashi
Published: July 2003

Insulin resistance is an important feature in the pathogenesis of noninsulin-dependent diabetes mellitus. Some rare patients have syndromes associated with a severe form of insulin resistance, usually involving acanthosis nigricans and, in premenopausal females, hyperandrogenism. This review discusses two of the causes of insulin resistance: mutations in the insulin receptor gene and autoantibodies directed against the insulin receptor.
Hypothalamic-Pituitary-Adrenal Axis in Psychiatric Disorders
Authors: Stokes Peter E. , Sikes Carolyn R.
Published: July 2003

Hypothalamic-pituitary-adrenocortical (HPA) physiology is complex, and dysregulation of this neuroendocrine axis cannot be characterized adequately by isolated or unintegrated measures. Repeated assessments over time, involving multiple measures of axis activity (basal and dynamic tests), have furthered our understanding of the character of the HPA abnormalities reported in various psychiatric disorders. We review the nature and clinical significance of these HPA disturbances in the affective disorders and other psychiatric illnesses.
Pathophysiology and Management of Hypertension in Diabetes
Authors: Tuck Michael L. , Corry Dalila B.
Published: July 2003

Arterial hypertension is more common in diabetes mellitus than in nondiabetic subjects, and many metabolic and hemodynamic features of diabetes mellitus contribute to the etiology of hypertension. Control of hypertension in diabetes mellitus is extremely important as high blood pressure accelerates both macrovascular and microvascular complications of this disease. Most classes of antihypertensive agents are effective in blood pressure control in diabetes mellitus, so the choice of antihypertensive therapy is based on the differences in adverse effects of these agents on metabolic control and other cardiovascular risks.
Acute Progressive Epstein-Barr Virus Infections
Authors: Straus Stephen E.
Published: July 2003

A few Epstein-Barrvirus (EBV) infections result in progressive, potentially fatal disease. Nearly all of these progressive EBV infections occur in individuals known or suspected to be immunodeficient. Diagnosis and treatment are difficult.
Therapeutic Approaches to Hemoglobin Switching in Treatment of Hemoglobinopathies
Authors: Stamatoyannopoulos J. A. , Nienhuis A. W.
Published: July 2003

The past decade has witnessed profound increases in knowledge of the structure, function, and developmental regulation of the human globin genes. This information has deepened our understanding of the molecular and cellular mechanisms underlying inherited disorders affecting hemoglobin, and it has provided a new perspective for attaining meaningful increases in fetal hemoglobin synthesis in the management of sickle cell anemia and beta thalassemia. Efforts to provide therapy for these disorders are based on three factors: an understanding of their pathophysiology; the potential for fetal hemoglobitno alter its manifestation; and the concept that developmental changes in globin gene expression might be reversed by manipulating cellular and molecular regulatory mechanisms. In this review we discuss these topics and examine critically recent efforts to apply various pharmacological agents to in vitro, animal, and human models with the goal of increasing HbF synthesis. Several agents have demonstrated activity in patients with hemoglobin disorders. One such agent, hydroxyurea, has been shown to be potentially efficacious in phase II clinical trials in patients with sickle cell anemia and awaits testing in a placebo-controlled phase III study.
Serum Transferrin Receptor
Authors: Cook J. D. , Skikne B. S. , Baynes R. D.
Published: July 2003

The transferrin receptor plays a critical role in iron metabolism by precisely contrOlling the flow of transferrin iron into body cells. A soluble truncated form of the receptor can be detected in human serum using sensitive immunoassays, and the initial clinical experience with this new measurement indicates that it reflects the total body mass of tissue receptor. Serum receptor levels rise significantly with tissue iron deficiency and the heightened demand for iron associated with expansion of the erythroid marrow. The serum receptor provides a quantitative measure of functional iron deficiency and distinguishes the associated anemia from that of chronic disease. If iron deficiency is excluded, the serum receptor provides a quantitative measure of total erythropoiesis that is more sensitive and less invasive than bone marrow examination currently used to assess red cell precursor mass. Performed in conjunction with serum ferritin measurements, the serum receptor will be useful in establishing the true prevalence of iron deficiency anemia in population studies.
GENETICS OF RIBOSOMALLY SYNTHESIZED PEPTIDE ANTIBIOTICS
Authors: Kolter Roberto , Moreno Felipe
Published: July 2003

In recent years many peptide antibiotics have been shown to be ribosomally synthesized. Among these are many microcins, produced by diverse strains of gram-negative bacteria. While the structures and modes of action of these peptide antibiotics vary widely, many of them  share several important features. Their synthesis is often induced by the cessation of growth. In addition, many of them undergo unusual posttranslational modifications to yield the mature molecule, which is often exported from the cell by a dedicated export apparatus. The genes involved in modification and export of the peptide antibiotics are generally found adjacent to the structural gene and are under the same regulation. The results supporting these conclusions are reviewed and discussed in this chapter.
Developmental Neurobiology and the Natural History of Nerve Growth Factor
Authors: Levi-Montalcini Rita
Published: July 2003

I was invited to write about the discovery of Nerve Growth Factor and its relationship to developmental neurobiology. Rather than detail the life of NGF over the past 30 years, I wish to concentrate on what was the most attractive and also the most unusual feature in the investigation of NGF: that each finding has signaled a new turning point and opened up a new perspective. The story of NGF is therefore more like a detective story than a scientific enterprise, since science usually unfolds according to well-defined rules, along the route paved by previous findings. In retrospect, the previous experience with NGP holds out the promise that as many turning points still await us on the road ahead as we experienced on the road we have traveled so far. To me this is an encouraging rather than a depressing thought; the abrupt end of a scientific pursuit is more often synonymous with an intellectual dead end than with a goal successfully achieved. By way of introduction, I shall recount the early beginnings of this research, which are well known to old-timers but probably not to biochemically trained newcomers who were lured to take part in this game by the molecule itself and who are only vaguely acquainted with its natural history and with its problems.
Apolipoprotein E and Alzheimer's Disease
Authors: Strittmatter Warren J. , Roses Allen D.
Published: July 2003

The apolipoprotein E locus (APOE) is associated with variations in the age of onset and risk of Alzheimer's disease. The APOE4 allele increases the probability of disease at an earlier age. In contrasL the APOE3 and APOE2 alleles decrease the probability of disease and increase the age of onset. Therefore the metabolism of apolipoprotein E is relevant to Alzheimer's disease. Isoform-specific interactions of apolipoprotein E with other molecules may determine the rate of disease expression through molecular pathways that appear unique to the disease. In addition, some isoform-specific interactions of apolipoprotein E have been demonstrated with the defining pathological lesions of Alzheimer's disease, the neurofibrillary tangle and neuritic plaque. Several hypotheses of disease pathogenesis are now based on the relevance of apolipoprotein E.
Lactoferrin: Molecular Structure and Biological Function
Authors: Lönnerdal B. , Iyer S.
Published: July 2003

Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
Energy Partitioning and Modeling in Animal Nutrition
Authors: Baldwin R. L. , Sainz R. D.
Published: July 2003

We first present a brief discussion of early and current models (feeding systems) used to estimate animal energy and protein requirements and to predict performance based on feed composition and intake. We then touch on some limitations inherent in these systems. Next, we propose that dynamic (i.e. time-variant) models and mechanistic models (i.e. equations based on knowledge of physiological functions) are superior to earlier systems for both practical and research applications. Finally, we describe a number of applied and research models of animal growth and lactation to illustrate how biological concepts may be represented in equation form. Equations that represent current knowledge of underlying functions can be used to improve predictions of animal requirements and performance and to evaluate hypotheses about nutritional and physiological mechanisms that influence animal performance.
Trans Fatty Acids and Their Effects on Lipoproteins in Humans
Authors: Katan Martijn B. , Zock Peter L. , Mensink Ronald P.
Published: July 2003

Trans fatty acids raise plasma low-density lipoprotein (LDL) cholesterol levels in volunteers when exchanged for cis unsaturated fatty acids in the diet. In addition, trans fatty acids may lower high-density lipoprotein (HDL) cholesterol levels and raise triglyceride and lipoprotein(a) levels in plasma. Trans and cis unsaturated fatty acids are thus not equivalent, and diets aimed at reducing the risk of coronary heart disease should be low in both trans and saturated fatty acids.
Apolipoprotein E and the Apolipoprotein E-Deficient Mouse
Authors: Plump Andrew S. , Breslow Jan L.
Published: July 2003

Apolipoprotein E (apoE) is one of several lipoprotein transfer genes. A primary function of this protein is the mediation of receptor-mediated lipoprotein removal from the blood. Several studies have demonstrated that genetic variation at the apoE locus is associated with an increased risk of developing atherosclerosis, and recent studies implicate this same genetic variation in determining susceptibility to Alzheimer's disease. An apoE-deficient mouse has been created to further understand the role of apoE in these areas. This review briefly discussed the biological and clinical importance of this protein and describes the early experiments performed in the apoE-deficient mouse.
On the Making of a Clinical Nutritionist
Authors: Olson Robert E.
Published: July 2003

Clinical nutrition may be defined as the application of the principles of nutrition science and medical practice to the diagnosis, treatment, and prevention of human disease caused by the deficiency, excess, or metabolic imbalance of nutrients. At present, many physicans do not appreciate the great traditions established by their forebears in this field (Hippocrates, Lind, Eijkman, Glisson, Casal, Livingstone, Hopkins, and Goldberger). They have tended to avoid nutritional problems, plead ignorance of nutrition principles, and delegate the nutritional care of their patients to paramedical personnel. Only by changing this situation can members of the medical profession offer adequate care to their patients. In this chapter, I have attempted to present the duties and responsibilities of a clinical nutritionist in an academic environment. A well-trained academician in such a position can improve the education of medical students in nutrition, attract well-motivated graduates into nutrition training programs, and establish clinical nutrition as a bona fide subspecialty of medicine.
Zonation of Parenchymal and Nonparenchymal Metabolism in Liver
Authors: Jungermann Kurt , Keitzmann Thomas
Published: July 2003

The enormous number of different liver functions are carried out by parenchymal and four main types of nonparenchymal cells, either alone or in cooperation. Although the liver tissue is uniform on the level of histology, it is heterogenous on the level of morphometry and histochemistry. This heterogeneity is related to the blood supply; cells located in the upstream or periportal zone differ from those in the downstream or perivenous zone in their equipment with key enzymes, translocators, receptors, and subcellular structures and therefore have different functional capacities. This is the basis of the model of metabolic zonation, according to which glucose release from glycogen and via gluconeogenesis, amino acid utilization and ammonia detoxification, protective metabolism, bile formation, and the synthesis of certain plasma proteins such as albumin and fibrinogen occur mainly in the periportal area, whereas glucose utilization, xenobiotic metabolism, and the formation of other plasma proteins such as α1-antitrypsin or α-fetoprotein occur predominantly in the perivenous zone. The morphologic and functional heterogeneity is the result of zonal differences in the activation of the cellular genome caused by gradients in oxygen, substrate, hormone, and mediator levels, in innervation, as well as in cell-to-cell and cell-to-biomatrix interactions.
Structure/Function of Cytoplasmic Vitamin A-Binding Proteins
Authors: Li Ellen , Norris Andrew W.
Published: July 2003

Two cytoplasmic retinol-binding proteins, CRBP and CRBP II, and two cytoplasmic retinoic acid-binding proteins, CRABP-I and CRABP-II, have been well characterized. There has been significant progress in the structural analysis of these four proteins with X-ray crystallography, nuclear magnetic resonance, mutagenesis, and binding studies. In contrast, the cellular functions of these cytoplasmic vitamin A-binding proteins are less well understood. Since these proteins bind their respective ligands with high affinity, they are likely to influence retinoid signaling pathways. Analysis of retinoid metabolism in the presence or absence of these proteins provides support for the hypothesis that these proteins are involved in modulating intracellular retinoid metabolism. Molecular genetic approaches to alteration of the levels of these proteins in tissue culture cells and in whole animals have provided a powerful means toward defining the physiological roles of the cytoplasmic vitamin A-binding proteins in vivo.
Control of Human Appetite: Implications for The Intake of Dietary Fat
Authors: Bludell J. E. , Lawton C. L. , Cotton J. R. , Macdiarmid J. I.
Published: July 2003

The human appetite system contains central and peripheral mechanisms that interact with environmental features, especially with the physical and nutrient composition of the food supply. Foods varying in nutrient composition exert different physiologic effects, some of which function as satiety signals. High-fat diets (low food quotient) lead to high levels of energy intake. This effect is termed passive overconsumption and overcomes fat-induced physiological satiety signals. High-fat foods exert a weak effect on satiation (intra-meal satiety), and fat has a weaker effect, joule for joule, on postingestive satiety than do other macronutrients. The frequency of obesity is greater among high-fat than low-fat consumers. However, the development of obesity on a high-fat diet is not a biological inevitability. The investigation of people who resist the weight-inducing properties of high-fat diets is a key research strategy. Understanding the appetite control system suggests behavioral, nutritional, and pharmacologic strategies for modifying dietary fat intake.
DIET ANDNUTRITION INPOOR ANDMINORITYCOMMUNITIES INTHEUNITEDSTATES100 YEARSAGO
Authors: Dirks Robert
Published: July 2003

▪ Abstract  Atwater and his colleagues began studying food consumption in the closing years of the nineteenth century and from the very start devoted much effort to collecting data from poor and minority households. This paper reviews some of the fruits of these labors, particularly from the standpoint of what they contribute toward a better historical understanding of American food habits and nutrition. It surveys dietary data from African American, Appalachian white, Mexican American, native-born poor, and immigrant households. These data shed light on several areas of historical concern, including rural versus urban nutrition, seasonal hunger, class disparities, and food-habit change. I suggest the economically and culturally diverse sample of dietary patterns that comes to us as a legacy of the Atwater era sets the stage for a history of American food habits considerably more sophisticated than has been realized to date.
Effects of Drugs on the Electrical Activity of the Brain: Anesthetics
Authors: Winters Wallace D.
Published: July 2003

The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states—some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperexcite the system resulting in a function disorganization (stage II-C). 3. Some agents traverse both excitation and depression, diethyl ether (I, II, III). 4. Others induce only stage II—catalepsia, e.g. nitrous oxide, ketamine, gamma-hydroxybutyrate, alpha-chloralose, phencyclidine, trichlorethylene, and enflurane. 5. Others induce no stage II but progress directly from stage I stage III, e.g. halothane and barbiturates. 6. Cataleptic agents may induce further CNS excitation manifested by seizures, e.g. gamma-hydroxybutyrate, phencyclidine, ketamine, alpha-chloralose, trichlorethylene, and enflurane. 7. The functional definition of surgical anesthesia is: a stage induced by a drug that makes the subject relatively unresponsive to painful stimuli and amnestic. Thus, the subject does not respond during surgery and cannot recall what happened afterwards. This state can be achieved by functional disruption of CNS systems by marked stimulation or depression.
Fifty Years of Physical Chemistry in Berkeley
Authors: Hildebrand Joel H.
Published: July 2003

This is to be a reminiscence rather than a history. By the time it is published fifty years will have passed since I joined the little band of young iconoclasts in Berkeley that Gilbert Lewis took there with him in 1912. Much that might be said about my exciting half century has been published in the Biographical Memoirs that I wrote for the National Academy of Sciences on the careers of Gilbert N. Lewis, William C. Bray, and Wendell M. Latimer. A labor of love in each case. What follows will include items from these memoirs.
Heteronuclear NMR Pulse Sequences Applied to Biomolecules
Authors: Pelton Jeffrey G. , Wemmer David E.
Published: July 2003

Current concepts in heteronuclear multidimensional NMR spectroscopy are reviewed. Methods to improve the sensitivity and the efficiency of data collection include constant time, compression through the overlap of chemical shift evolution and dephasing and rephasing periods, and dual or time-shared evolution. Two classes of three-dimensional and fourdimensional triple-resonance experiments applied to proteins are considered. The first class correlates 1H, 15N, and 13C signals of the protein backbone. The second class correlates both backbone and side-chain signals. Application of triple resonance to RNA is also discussed. Heteronuclear cross polarization (HCP) is considered as an alternative to INEPT transfer, and its application to nucleic acids is presented. Finally, two methods of employing pulsed field gradients (PFGs) are reviewed.
Theoretical Studies of Polyatomic Bimolecular Reaction Dynamics
Authors: Bowman Joel M. , Schatz George C.
Published: July 2003

We describe recent advances in the theoretical description of bimolecular reactions involving four or more atoms based on quantum scattering theory and quasiclassical trajectory methods. The application of these methods to several reactions is described in detail along with relevant experimental results. The discussion emphasizes the use of reduced dimensionality quantum scattering methods and quasiclassical trajectory methods to describe quantum state-resolved effects, including state-specific reaction rate enhancements and product state distributions. Also considered are thermal rate constants, the lifetimes of intermediate complexes, and the branching between multiple reaction pathways.
Photoassociative Spectroscopy of Laser-Cooled Atoms
Authors: Lett P. D. , Julienne P. S. , Phillips W. D.
Published: July 2003

Advances in laser cooling of neutral atoms have made possible a new form of high-resolution laser spectroscopy: photoassociation of ultracold atoms. Colliding neutral atoms, confined in a laser trap, are photoassociated to bound excited states of the dimer molecule by absorbing a photon from a tunable laser. The technique can probe long range and “purely long range” molecular states that are difficult or impossible to detect by traditional means and, because of the extremely low energy of the colliding atoms (<1 mK), is capable of high resolution (<0.001 cm-1). The spectra are useful for atomic lifetime measurements, determination of atomic ground-state scattering information, and measurement of curve-crossing probabilities. Theoretical and experimental work in the field, including multiple resonance techniques and photo association line shapes, are reviewed.
Design and Regulation of Efficient Photoinduced Electron Transfer in Macromolecular and Photosynthetic Systems
Authors: Franzen Stefan , Martin Jean-Louis
Published: July 2003

The factors that govern efficient electron transfer in the initial steps of photosynthetic charge separation are discussed. The dependence of the electron transfer rate constant on free energy, temperature, and distance are described both in theory and in numerous experiments on photosynthetic and macromolecular systems, with particular attention to those aspects of macromolecular charge transfer systems that show strong analogy to characteristics of photosynthetic charge transfer reactions. The unique features of the primary charge separation reaction in photosynthesis are emphasized in light of recent experimental data, including time-resolution of excited state vibrational motion, the electric field dependence of the quantum yield, and resonance Raman and hole-burning experiments that probe the nature of the initially formed excited state. The experimental results indicate the need for further development of electron transfer theory to include nonequilibrium vibrational populations and more explicit models of higher-order electronic coupling.
Orientation and Alignment in Reactive Beam Collisions: Recent Progress
Authors: Loesch H. J.
Published: July 2003

The concept of directional axis distributions and orientation-dependent reaction cross sections is used to describe the effect of the mutual orientation of reagents on the outcome of reactive beam collisions. The axis distributions and cross sections are expanded in series of Legendre polynomials and real spherical harmonics, respectively, and characterized by the expansion coefficients (moments). The interrelations between the moments of the cross sections and the directionally dependent experimental data (steric effects) on the one hand and the anisotropic properties of the potential energy surfaces on the other hand are presented. Recent progress in the field of dynamical stereochemistry results from the prep­ aration of molecular orientation and alignment by using the novel brute force technique and an optical method, respectively. The theories of both methods are summarized, and typical experimental arrangements are presented. All experimental results based on these techniques are reviewed. Among the most important ones are the first orientation effects observed in a reaction with a 1Σ: molecule (K + ICl) and the alignment effects found in the bench mark reaction Li + HF → LiF + H.
Density-Functional Theory of the Electronic Structure of Molecules
Authors: Parr Robert G. , Yang Weitao
Published: July 2003

Recent fundamental advances in the density-functional theory of electronic structure are summarized. Emphasis is given to four aspects of the subject: (a) tests of functionals, (b) new methods for determining accurate exchange-correlation functionals, (c) linear scaling methods, and (d) developments in the description of chemical reactivity.