bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide Mediators of Hypercalcemia in Malignancy
Authors: Strewler G. J. , Nissenson R. A.
Published: July 2003

A parathyroid hormone-like peptide that probably causes hypercalcemia associated with solid tumors was recently characterized. It is a potent hypercalcemic and hypophosphatemic factor whose production is strongly associated with hypercalcemia and whose properties account for most aspects of the clinical syndrome. Diagnostic tests for this peptide have been developed. The parathyroid hormone-like peptide as well as other cytokines, such as tumor necrosis factor-alpha, likely play a role in causing hypercalcemia in multiple myeloma and lymphomas.
Pathophysiologic Strategies in the Management of Congestive Heart Failure
Authors: Brozena Susan , Jessup Mariell
Published: July 2003

The management of patients with congestive heart failure is based upon an understanding of the pathogenetic mechanisms. Therapy aimed at optimizing preload, decreasing afterload, and improving contractility can improve symptoms, and in some instances, improve survival.
Physiology of Thrombospondin
Authors: Mosher Deane F.
Published: July 2003

Thrombospondin is a large, multifunctional glycoprotein released from activated platelets and secreted by growing cells. It binds to components of the cell surface and extracellular milieu. Thrombospondin probably modulates a number of processes, including aggregation of platelets, formation and lysis of fibrin, adhesion and migration of cells, and progression of cells through the growth cycle. Studies relating thrombospondin to disease processes are just beginning.
Infections in Child Day Care Centers as they Relate to Internal Medicine
Authors: Reves Randall R. , Pickering Larry K.
Published: July 2003

Internists should be aware of the increased frequency of most communicable diseases among parents and child care providers exposed to children attending child day care centers. Episodes of shigellosis and hepatitis A among adults in contact with children in day care centers should be promptly reported to public health authorities, since they may indicate the presence of a day care center outbreak for which effective control measures are available. Although effective treatment or intervention is limited or not available for many other infections acquired by adults from children in day care centers, significant illness may result in a minority of individuals at increased risk for infection with agents such as cytomegalovirus and varicella. Acute infectious diseases of children caused by organisms transmitted from day care center staff are less common and largely preventable by ensuring that staff are appropriately immunized and screened for tuberculosis.
The Diagnosis and Treatment of Prostate Cancer
Authors: Andriole Gerald L. , Catalona William J.
Published: July 2003

Prostate cancer is the most common cancer among American men and is the third leading cause of cancer death in the United States. Over the past few years, significant advances (e.g. improved prostatic ultrasonography and the discovery of serum prostate-specific antigen) have made it possible to detect prostate cancer at an early stage. In addition, refinements in the treatment both of localized disease (by nerve-sparing radical prostatectomy) and of advanced disease (by novel forms of hormonal therapy) have improved the outlook and quality of life for men with prostate cancer.
Latency of the Human Herpesviruses
Authors: Croen Kenneth D.
Published: July 2003

The herpesviruses are ubiquitous pathogens that establish latent infections and can reactivate to produce recurrent disease. The fact that clinical recurrences are infrequent in most healthy individuals indicates that potent regulatory mechanisms must exist to ensure viral latency. Rapid progress is being made toward understanding the pathogenesis of latency and reactivation and is the subject of this review.
Detection of Microbial Nucleic Acids for Diagnostic Purposes
Authors: Engleberg N. Cary , Eisenstein Barry I.
Published: July 2003

The last decade has seen an explosion of interest in the use of molecular genetic techniques to diagnose infectious diseases. Specific molecular probes have been developed for nearly all of the significant, known microbial pathogens. The evolution of incrementally more powerful technologies, particularly gene amplification, has made it possible to detect pathogens with exquisite sensitivity, as well as specificity, based on their nucleic acids. As increasingly rapid and automated methods have become incorporated into successive generations of probe tests, these diagnostics have gained increasing acceptance for routine clinical use.
Pulmonary Complications of Transplantation
Authors: Robbins Richard A. , Floreani Anthony A. , Buchalter Scott E. , Spurzem John R. , Sisson Joseph H. , Rennard Stephen I.
Published: July 2003

Improved immunosuppressive regimens, advances in surgical proficiency and techniques, and improved supportive medical care have translated into dramatic increases in graft survival in organ transplantation and in patient outcome in bone marrow transplantation. Though effective immunosuppression has also led to an increase in infectious complications, several recent advances, including the development of effective surveillance protocols and antiviral therapy and the use of prophylactic antibiotics, appear to have made a significant positive impact on the management of infections and survival of transplant recipients. In addition, a clearer understanding of noninfectious pulmonary complications, such as bronchiolitis obliterans, and continued improvement in techniques for evaluating a host of posttransplant pulmonary disorders will likely further enhance posttransplant therapy and survival.
The Resurgence of Measles in the United States, 1989-1990
Authors: Atkinson William L. , Orenstein Walter A. , Krugman Saul
Published: July 2003

After almost a decade of relatively few reported cases, a major resurgence of measles occurred in the United States in 1989-1990. The increase primarily involved unvaccinated racial and ethnic minority children less than five years of age residing in inner-city areas. Outbreaks of measles among vaccinated school-aged children continued to occur but had less impact than outbreaks among preschool-aged children. Efforts to prevent measles must be aimed at improving age-specific measles vaccination coverage among preschool-aged children, and implementation of a two-dose measles strategy among school-aged children.
Quinolone Antimicrobial Agents
Authors: Neu Harold C.
Published: July 2003

This chapter reviews the chemistry, microbiology, pharmacology, and clinical use of the fluoroquinolone antimicrobial agents. The molecular and clinical problems of bacterial resistance are reviewed. The clinical areas in which fluoroquinolones have been investigated are detailed, with particular attention to areas of appropriate and inappropriate use.
Management of Primary Hyperparathyroidism
Authors: Deftos L. J. , Parthemore J. G. , Stabile B. E.
Published: July 2003

Primary hyperparathyroidism is a common disease that can be accurately diagnosed and effectively treated in most patients. The diagnosis is established by a persistent elevation of serum calcium and parathyroid hormone and by clinical evaluation. Surgery is the appropriate treatment, and preoperative localization procedures are seldom indicated. Selected patients with mild disease may be followed by procedures devised to identify deterioration of skeletal, neurological, and renal function. The accurate diagnosis and effective treatment of primary hyperparathyroidism are rewarding clinical experiences for the endocrinologist and surgeon.
Cellular Mechanisms of Acute Ischemic Injury in the Kidney
Authors: Brezis Mayer , Epstein Franklin H.
Published: July 2003

Hypoxic injury to tubular cells represents an early event in acute renal failure. Although important advances have been made in the understanding of hypoxic injury at the cellular level (e.g. loss of cell polarity, production of free radicals, calcium entry, and the activation of genes for protection or regeneration), the basic mechanisms responsible for organ failure remain elusive. The renal medulla, working on the brink of anoxia and being the site of concentration for many toxins, may be an important target for the synergistic events of hypoperfusion and nephrotoxic exposure that often precede human acute renal failure.
The Diagnosis and Treatment of Panic Disorder
Authors: Agras W. Stewart
Published: July 2003

Panic attacks and panic disorder often first present in the emergency room or to the family practitioner. The presentation and differential diagnosis of this disabling disorder are described in this review, together with the etiology and health effects of the syndrome. Both medication and psychological treatments are described, as are the indications, side effects, and expected outcome for each therapy alone and in combination.
Pathogenesis and Pathophysiology of Bacterial Meningitis
Authors: Tunkel Allan R. , Scheld W. Michael
Published: July 2003

Despite the availability of bactericidal antibiotics with potent in vitro activity against the major meningeal pathogens, the morbidity and mortality from bacterial meningitis remains unacceptably high. Animal models have proven to be extremely valuable in the study of the pathogenesis and pathophysiology of bacterial meningitis, with the hopes of providing new information that may lead to an improved outcome from this disorder.

Bacterial meningitis usually begins with nasopharyngeal colonization by a new organism, followed by invasion and bacteremia. Subsequently there is central nervous system invasion, although the exact site and mechanism of meningeal invasion are unknown. The generation of an intense subarachnoids pace inflammatory response, induced by release of bacterial virulence factors and/or inflammatory cytokines, contributes to many of the pathophysiologicc onsequences of bacterial meningitis, including cerebral edema, increased intracranial pressure, and alterations of cerebral blood flow. Attenuation of this inflammatory response ( e.g. by co-administration of antiinflammatory agents) may diminish many of these pathophysiologic consequences of meningitis, and perhaps improve morbidity and mortality from this disorder
Role of Insulin Resistance in Human Disease (Syndrome X): An Expanded Definition
Authors: Reaven Gerald M.
Published: July 2003

Resistance to insulin-mediated glucose uptake is characteristic of individuals with impaired glucose intolerance or non-insulin-dependent diabetes, and it also occurs commonliyn patients with high blood pressure. The physiological response to a decrease in insulin-mediated glucose uptake is an increase in insulin secretion, and as long as a state of compensatory hyperinsulinemia can be maintained, frank decompensation of glucose tolerance can be prevented. However, it is likely that the defect in insulin action and/or the associated hyperinsulinemia will lead to an increase in plasma triglyceride and a decrease in high density lipoprotein-cholesterol concentration, and high blood pressure. It seems likely that the cluster of changes associated with resistance to insulin-mediated glucose uptake comprise a syndrome, which plays an important role in the etiology and clinical course of patients with non-insulin-dependent diabetes, high blood pressure, and coronary heart disease.
Primary Sclerosing Cholangitis
Authors: Martin Maureen
Published: July 2003

Primary sclerosing cholangitis (PSC) is an inflammatory disease of unknown etiology. It affects the biliary system and is characterized by fibrosis and progressive obliteration of extrahepatic and intrahepatic bile ducts. Its frequent coexistence with antibody-mediated diseases, certain human leukocyte antigens, and altered lymphocyte mechanisms suggests a strong autoimmune and genetic etiology. Other conditions such as recurrent cholangitis, acquired immunodeficiency syndrome, previous bile duct surgery, bile duct anomalies, or biliary stone disease may result in similar clinical patterns and radiologic profiles. PSC can be asymptomatic and slowly progressive over years, or it may develop rapidly with an inexorable progression to cirrhosis and portal hypertension. Clinical and biochemical abnormalities may suggest PSC, but it is the characteristic radiological pattern that secures the diagnosis. Once viewed as a rare entity, the widespread use of radiological and endoscopic methods have increased physician awareness. There is no successful medical treatment for PSC. While traditional surgical approaches have been directed at the relief of cholangitis and biliary obstruction, liver transplantation has emerged as definitive therapy for patients with PSC complicated by cirrhosis or recurrent bouts of cholangitis.
Special Aspects of Neuropsychiatric Illness in Women: With a Focus on Depression
Authors: Hamilton Jean A. , Halbreich Uriel
Published: July 2003

Many depressive disorders predominate in women. Other psychiatric disorders more prevalent in women than men often occur concomitantly with depression. A variety of these disorders show a premenstrual patterning of symptoms and are responsive to antidepressants. Migraine headaches are also more common in women, show a premenstrual patterning, and are responsive to antidepressants. Other neuropsychiatric and endocrine-related disorders predominating in women are discussed in this review. Greater attention to the special aspects of neuropsychiatric disorders in women may improve diagnosis and treatment.
Endothelial Dysfunction in Coronary Artery Disease
Authors: Lüscher Thomas F. , Tanner Felix C. , Tschudi Marcel R. , Noll Georg
Published: July 2003

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle cells.

Monoaminooxidasc deactivates catecholamines and serotonin. Angiotensin converting enzyme transforms angiotensin I into angiotensin II and breaks down bradykinin into inactive products. Nitric oxide is a potent vasodilator and inhibitor of platelet function that under most circumstances is released together with prostacyclin, which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2, and endoperoxides. Endothelium-derived growth inhibitors include heparin (sulfates) and transforming growth factor β1, while basic fibroblast growth factors and platelet- derived growth factor and possibly endothelin promote proliferation. Because of its strategic anatomic position, the endothelium is a primary target for injuries and cardiovascular risk factors. In particular, aging, low density lipoproteins, hypertension, diabetes, and ischemia alter endothelium function. In arterial coronary bypass grafts, the release of nitric oxide is more pronounced than in vein grafts. Alterations of endothelial function may contribute to vasospasm, thrombus formation, and vascular proliferation and in turn myocardial ischemia, all commone vents in patients with coronary artery disease.
Aging—Causes and Defenses
Authors: Martin George R. , Danner David B. , Holbrook Nikki J.
Published: July 2003

Recent studies have shown that chromosomes shorten as cells divide and become senescent. Also, deletions in mitochondrial DNA increase markedly with advancing age, presumably secondary to damage from oxygen radicals. Since host defenses against environmental factors also become attenuated, the molecular damage associated with aging may increasingly perturb normal homeostasis and increase the susceptibility to disease and disability. Such age-associated dysfunctions can be targeted and interrupted.
Antioncogenes and Human Cancer
Authors: Carbone David P. , Minna John D.
Published: July 2003

Multiple genetic lesions are thought to transform a normal cell into a malignant one, and both dominant and recessive genetic effects have been identified in this process. Antioncogenes (or tumor suppressor genes) act in a recessive manner, in which both maternal and paternal alleles need to be inactivated to abrogate normal function. The identification of these lesions is giving us insight into the regulatory pathways in the cell and may translate into future improvements in prevention, diagnosis, prognosis, and therapy of human cancer.
Angioplasty for Acute Coronary Syndromes
Authors: Tenaglia Alan N. , Stack Richard S.
Published: July 2003

The acute ischemic syndromes (unstable angina and acute myocardial infarction) are often treated with percutaneous transluminal coronary angioplasty. Angioplasty should be considered in patients with unstable angina refractory to medical therapy and in those with evidence for ischemia after medical stabilization. Direct or primary angioplasty is indicated in patients with acute myocardial infarction with contraindications to thrombolytic therapy and is a reasonable alternative even in those eligible for thrombotytics. While there is no role for immediate angioplasty of a patent infarct-related artery following thrombolysis, rescue angioplasty of persistently occluded arteries may be beneficial, although further studies are needed.
Methods, Successes, and Failures of Smoking Cessation Programs
Authors: Fisher Edwin B , Lichtenstein Edward , Haire-Joshu Debra , Morgan Glen D. , Rehberg Heather R.
Published: July 2003

Addictive and conditioning processes interact to make cigarette smoking a common, lethal behavior that is highly resistant to change. In addition to addiction and conditioning, smoking is maintained by a wide range of forces, ranging from social modeling and advertising to the politics and economics of international trade. Parallel to this wide range of causes of smoking, interventions to encourage smoking cessation range from simple information and suggestions to smoking cessation classes, to nicotine replacement, to community or national campaigns that promote nonsmoking. Clinicians can make contributions throughout this range of activities, from the consulting room to political advocacy. While no one of these is highly successful on its own, together they have prompted almost 50% of smokers to quit, an impressive accomplishment.
REGULATION OF SULFUR AND NITROGEN METABOLISM IN FILAMENTOUS FUNGI
Authors: Marzluf George A.
Published: July 2003

In the filamentous fungi, N. crassa and A. nidulans, complex regulatory circuits control nitrogen metabolism and sulfur metabolism. The expression of entire sets of unlinked structural genes that encode metabolic enzymes is repressed when favored sulfur or nitrogen sources are available. These structural genes are coregulated by global positive-acting regulatory proteins and often are also controlled by metabolic inducers and pathway-specific regulatory proteins. The recent isolation of regulatory genes and representative structural genes of these circuits has provided significant new insight into the operation of both the nitrogen and the sulfur regulatory circuits, which involve sequence-specific DNA binding proteins, promoter control elements, metabolic inducers and repressors, and autogenous regulation.
DISSIMILATORY METAL REDUCTION
Authors: Lovley Derek R.
Published: July 2003

Microorganisms can enzymatically reduce a variety of metals in metabolic processes that are not related to metal assimilation. Some microorganisms can conserve energy to support growth by coupling the oxidation of simple organic acids and alcohols, H2, or aromatic compounds to the reduction of Fe(III) or Mn(IV). This dissimilatory Fe(III) and Mn(IV) reduction influences the organic as well as the inorganic geochemistry of anaerobic aquatic sediments and ground water. Microorganisms that use U(VI) as a terminal electron acceptor play an important role in uranium geochemistry and may be a useful tool for removing uranium from contaminated environments. Se(VI) serves as a terminal electron acceptor to support anaerobic growth of some microorganisms. Reduction of Se(VI) to Se(O) is an important mechanism for the precipitation of selenium from contaminated waters. Enzymatic reduction of Cr(VI) to the less mobile and less toxic Cr(lll), and reduction of soluble Hg(lI) to volatile Hg(O) may affect the fate of these compounds in the environment and might be used as a remediation strategy. Microorganisms can also enzymatically reduce other metals such as technetium, vanadium, molybdenum, gold, silver, and copper, but reduction of these metals has not been studied extensively.
Human Immunodeficiency Virus and the Brain
Authors: Glass Jonathan D. , Johnson Richard T.
Published: July 2003

Human immunodeficiency virus (HIV) infects the nervous system in the majority of patients, causing a variety of neurological syndromes throughout the course of the disease. This review focuses on the effects of HIV in the central nervous system, with an emphasis on HIV-associated dementia. HIV-associated dementia occurs in a subset of patients with AIDS; it is unclear why these patients and not all patients develop the disease. Several factors are likely to be involved in the pathogenesis of HIV-associated dementia, including neurotoxins released from the virus and/or infected macrophages and microglia, immunologic dysregulation of macrophage function, and specific genetic strains of HIV. These factors, and their possible interactions, are discussed.
RNA Editing
Authors: Simpson Larry , Emeson Ronald B.
Published: July 2003

RNA editing is a term describing a variety of novel mechanisms for the modification of nucleotide sequences of RNA transcripts in different organisms. These editing events include (a) the U-insertion and -deletion type of editing found in the mitochondrion of kinetoplastid protozoa, (b) the C-insertion editing found in the mitochondrion of Physarum, (c) the C-to-U substitution editing of the mammalian apoB mRNA, (d)a similar C-to-U substitution editing of mRNAs in higher plant mitochondria and chloroplasts and in tRNAs of marsupials and rats, (e) a diverse nucleotide substitution editing of tRNAs in Acanthomoeba mitochondria, and (f) the A-to-I type of editing found in the mammalian glutamate receptor subunits. These diverse phenomena involve several different enzymatic mechanisms. In several cases, duplex RNAs with internal or external guide sequences help determine the site specificity of editing. The A-to-I editing observed in RNAs encoding non-NMDA glutamate receptor subunits may be due to the actions of a double-stranded RNA-specific adenosine deaminase that is widespread in higher organisms. Although the function of many RNA editing events is unclear, the biological importance of RNA editing in other systems may prove as significant as the nucleotide modifications regulating the cation selectivity and electrophysiological profiles elaborated by non-NMDA glutamate receptors in the mammalian brain.
Sodium Channel Defects in Myotonia and Periodic Paralysis
Authors: Cannon Stephen C.
Published: July 2003

Myotonias and periodic paralyses constitute a diverse group of inherited disorders of muscle in which the primary defect is an alteration in the electrical excitability of the muscle fiber. The ion channel defects underlying these excitability derangements have recently been elucidated at the molecular and functional levels. This review focuses on sodium channel mutations that disrupt inactivation and thereby cause both the enhanced excitability of myotonia (muscle stiffness due to repetitive discharges) and the inexcitability resulting from depolarization during attacks of paralysis.
Physiology of the Neurotrophins
Authors: Lewin Gary R. , Barde Yves-Alain
Published: July 2003

The neurotrophins are a small group of dimeric proteins that profoundly affect the development of the nervous system of vertebrates. Recent studies have established clear correlations between the survival requirements for different neurotrophins of functionally distinct subsets of sensory neurons. The biological role of the neurotrophins is not limited to the prevention of programmed cell death of specific groups of neurons during development. Neurotrophin-3 in particular seems to act on neurons well before the period of target innervation and of normally occuning cell death. In animals lacking functional neurotrophin or receptor genes, neuronal numbers do not seem to be massively reduced in the CNS, unlike in the PNS. Finally, rapid actions of neurotrophins on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.
Long-Term Depression in Hippocampus
Authors: Bear Mark F. , Abraham Wickliffe C.
Published: July 2003

Long-term depression (LTD) is a lasting decrease in synaptic effectiveness that follows some types of electrical stimulation in the hippocampus. Two broad types of LTD may be distinguished. Heterosynaptic LTD can occur at synapses that are inactive, normally during high-frequency stimulation of a converging synaptic input. Homosynaptic LTD can occur at synapses that are activated, normally at low frequencies. Here we discuss the mechanisms of LTD and their possible relevance to hippocampal function.
The Neurotrophins and CNTF: Two Families of Collaborative Neurotrophic Factors
Authors: Ip Nancy Y. , Yancopoulos George D.
Published: July 2003

Because the actions of neurotrophic factors appear distinct from those of traditional growth factors and cytokines, it was long assumed that the neurotrophic factors utilized receptors and signaling systems fundamentally different from those used by growth factors operating elsewhere in the body. Recent advances in the understanding of the structure of the receptors for neurotrophic factors have unexpectedly revealed that they are in fact similar to the receptors used by the traditional growth factors and cytokines. The expression of the receptors for the neurotrophic factors is exclusively or predominantly in the nervous system; activation of these receptors in the context of the neuron allows these factors to display distinctive actions. While the precise roles of the neurotrophic factors and their therapeutic potential in various disease states still remain to be elucidated, this review describes studies on their receptor systems, their notable biological activities in the nervous system, and recent insights provided by targeted gene disruptions.
DECIPHERING THE GENETIC BASIS OF SPEECH AND LANGUAGE DISORDERS
Authors: Fisher Simon E. , Lai Cecilia S.L. , Monaco Anthony P.
Published: July 2003

▪ Abstract  A significant number of individuals have unexplained difficulties with acquiring normal speech and language, despite adequate intelligence and environmental stimulation. Although developmental disorders of speech and language are heritable, the genetic basis is likely to involve several, possibly many, different risk factors. Investigations of a unique three-generation family showing monogenic inheritance of speech and language deficits led to the isolation of the first such gene on chromosome 7, which encodes a transcription factor known as FOXP2. Disruption of this gene causes a rare severe speech and language disorder but does not appear to be involved in more common forms of language impairment. Recent genome-wide scans have identified at least four chromosomal regions that may harbor genes influencing the latter, on chromosomes 2, 13, 16, and 19. The molecular genetic approach has potential for dissecting neurological pathways underlying speech and language disorders, but such investigations are only just beginning.
Whole-Body Protein Turnover in Humans—Past, Present, and Future
Authors: Waterlow J. C.
Published: July 2003

Protein turnover is a fundamental biological process in all living organisms. The study of protein turnover in human subjects, and in the body as a whole, is of relatively recent origin. In this review, I summarize briefly how this field of work has expanded over the past 25 years, with emphasis on conceptual problems and controversies, particularly those related to methods of measurement. We cannot be certain that our estimates are accurate because no method of verification exists, but progress will be made through successive approximations. Some of the applications are described in different physiological and pathological states such as growth and trauma, and possible directions for fruitful future research are indicated.
Regulation of Pigeon Cropmilk Secretion and Parental Behaviors by Prolactin
Authors: Horseman Nelson D. , Buntin John D.
Published: July 2003

Prolactin stimulates the growth and development of specialized epithelial cells lining the cropsac of pigeons and doves (family Columbidae), leading to formation of “cropmilk,” which is fed to the newly hatched squab. This system of milk feeding is unique among birds. To support the feeding of cropmilk, a complex array of behavioral adaptations are also supported by high levels of prolactin secretion in columbids during parenting. These specializations include elevated food intake (hyperphagia), nest attendance, and regurgitation feeding of the squab. Although prolactin is clearly important for these behavioral adaptations, the precise physiological and mechanistic bases for these behavioral effects remain controversial. The molecular mechanisms of prolactin action in the cropsac epithelium have been studied by cloning prolactin-induced genes, by cloning and expressing the pigeon prolactin receptor, and by analyzing the transcription factors that are activated after prolactin treatment. The avian (pigeon) prolactin receptor is a member of the cytokine receptor superfamily and uniquely contains a complete duplication of the extracellular ligand-binding domain. One of the early signal­transducing actions of prolactin in cropsac epithelium is the activation of signal transducer and activator of transcription (STAT) proteins via tyrosine phosphorylation. This fundamental signaling pathway is shared with mammalian prolactin target tissues. The convergent evolution of milk feeding and the behaviors that support parenting in columbids and mammals has depended on adaptation of both conserved mechanisms and divergent physiological processes.
Folic Acid and the Prevention of Birth Defects
Authors: Butterworth C. E. , Bendich Adrianne
Published: July 2003

Thirty years ago, it was suggested that maternal intake of certain vitamins during pregnancy affected the incidence of serious fetal malformations. Subsequent research has revealed that folate (folic acid), a B vitamin, plays a crucial role in the development of the central nervous system during the early weeks of gestation, which is generally before the pregnancy is confirmed. In a significant number of embryos, an inadequate supply of folate at this time leads to a failure of the primitive neural tube to close and differentiate normally and results in neural tube birth defects (NTD). Numerous studies have confirmed the importance of an adequate intake of folate during the weeks just before and after conception. Overall, the data predict that if women consume multivitamin supplements containing folic acid during the periconceptional period, the number of children born with serious malformations (such as spina bifida and anencephaly) could be reduced by half. Although programs to increase dietary folate intake of potential mothers may be effective in reducing NTD, the only proven and practical preventive measure currently available is to take oral multivitamin supplements containing folic acid. Multivitamin supplementation has also been associated with reduced incidence of other congenital malformations.

Current research is focusing on the role of micronutrients in embryogenesis, and on methods to identify prospective mothers at increased risk for bearing a child with NTD or with other major malformations shown to occur at reduced frequency with multivitamin supplementation. Of equal importance is the development of methods to communicate current knowledge as a public health measure.
ROUGH AND ROCKY ROAD TO THE RETINOID REVOLUTION
Authors: Chytil Frank
Published: July 2003

▪ Abstract  Some of us who were born in the middle of Europe between World Wars I and II had to face quite a few unusual challenges that we all met in different ways. I was born and raised in Prague, Czechoslovakia, a country at the time of my birth that was governed by a Western style of democracy, which was later destroyed by the occupation by Nazi Germany and subsequently by the takeover by the equally cruel Communists. Life required special means of adaptation to the changing living conditions and a great deal of luck to survive. After graduating from the School of Technology, I started working in the Department of Medicine at Charles University in Prague as a clinical chemist in endocrinology. This work was followed with training in basic biochemistry and the study of metabolic changes in stress. This rather diversified research, due to my changing of workplaces, led to the findings that diet can change enzymatic activity of liver tryptophan oxygenase. For a short time I worked on the metabolism of cyclic AMP in Escherichia coli, and at the age of 41, I made a risky move and succeeded in escaping with my family from the “paradise of communism.” The reasons for this decision will become clear. After settling in the United States, I worked on the mechanism of activation of liver tryptophan oxygenase by cyclic AMP and eventually moved to the Vanderbilt University School of Medicine. There I initially worked on the mechanism of action of steroid hormones and finally on the molecular mechanism of action of retinoids, retinol, and retinoic acid. Also in cooperation with neonatologists, I initiated studies on prematurely born human neonates which led to successful supplementation of these patients with vitamin A. The work from my laboratory and my coworkers eventually became recognized.

“Who does not remember the past, is condemned to repeat it.”

     George Santayana (1863–1952)
Pathophysiological Basis of Vulnerability to Drug Abuse: Role of an Interaction Between Stress, Glucocorticoids, and Dopaminergic Neurons
Authors: Piazza Pier Vincenzo , Le Moal Michel
Published: July 2003

Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some individuals to respond in a pathophysiological way to drugs.
Chemistry in the Interstellar Medium
Authors: Herbst Eric
Published: July 2003

Over the past 25 years, astronomers have discovered a large number of gas-phase molecules in space, ranging in size up to more than 10 atoms. The molecules, which are mainly organic in nature and comprise both normal and abnormal species, are located between stars, in regions known as interstellar clouds, which contain both gaseous material and material in the form of dust particles. The gas is well characterized by high-resolution spetroscopy, whereas the dust is less well characterized by low-resolution infrared spectroscopy and the scattering of visible radiation. The gaseous molecules are synthesized in situ from precursor atomic material, which derives from the mass loss of previous generations of stars. The chemical reactions involved in this synthesis are discussed in some detail as are the models that seek to reproduce the observed abundances of molecules.
Gas-Phase Reactions and Energy Transfer at Very Low Temperatures
Authors: Sims Ian R. , Smith Ian W. M.
Published: July 2003

Experimental studies of gas-phase chemical reactions and molecular energy transfer at very low temperatures and between electrically neutral species are reviewed. Although work of collisionally induced vibrational and rotational transfer is described, emphasis is placed on very recent results on the rates of free radical reactions obtained by applying the pulsed laser photolysis (PLP)–laser-induced fluorescence (LIF) technique in a CRESU (Cinétique de Réactions en Ecoulement Supersonique Uniforme) apparatus at temperatures as low as 13 K. These measurements demonstrate that quite a wide variety of reactions—including those between two radicals, those between radicals and unsaturated molecules, and even some of those between radicals and saturated molecules—remain rapid at very low temperatures. Theoretical efforts to explain some of these results are described, as is their impact on attempts to model the synthesis of molecules in interstellar clouds.
Collective Variable Description of Native Protein Dynamics
Authors: Hayward Steven , Go Nobuhiro
Published: July 2003

The importance of collective motions in proteins, such as hinge-bending motions or motions involving domains, has been recognized. Occurrence of such motions and their experimental and theoretical studies are reviewed. Normal-mode analysis and principal component analysis are powerful theoretical tools for studying such motions. The former is based on the assumption of harmonicity of the dynamics, while the latter is valid even when the dynamics is highly anharmonic. The results of the latter analysis indicate that most important conformational events are taking place in a conformational subspace spanned by a rather small number of principal modes, and this important subspace is also spanned by a small number of normal modes. The normal-mode refinement method of protein X-ray crystallography, which is developed based on the concept of the above important subspace, is discussed.
High-Resolution Photoelectron Spectroscopy of Molecules
Authors: Wang Kwanghsi , McKoy Vincent
Published: July 2003

Rotationally resolved photoelectron spectra can provide significant insight into the underlying dynamics of molecular photoionization. Here, we discuss and compare results of recent theoretical studies of rotationally resolved photoelectron spectra with measurements for molecules such as HBr, OH, NO, N2, CO, H20, H2CO, and CH3. These studies reveal the rich dynamics of quantum-state-specific studies of molecular photoionization and provide a robust description of key spectral features resulting from Cooper minima, autoionization, alignment, partial-wave mixing, and interference in related experimental studies.
Algebraic Methods in Spectroscopy
Authors: Kellman Michael E.
Published: July 2003

At present, two main types of algebraic methods are employed for analysis of molecular spectra. The first goes back to the early days of molecular spectroscopy. The second, developed recently by Iachello and coworkers, grew out of nuclear physics and makes use of classical Lie algebras such as SU(4). In this review, the standard spectroscopic fitting Hamiltonian for molecular vibrations, including resonance interactions, is first described. Then, new developments in the application of the standard approach are surveyed. In particular, the question of how one determines the true nature of molecular motions in highly excited spectra is investigated. Next, the recent algebraic approach of Iachello and coworkers is discussed. Application of ideas of molecule-like modes and algebraic methods to the analysis of the electronic spectra of atoms is discussed. Finally, prospects for future development of algebraic methods are discussed.
Nucleation: Measurements, Theory, and Atmospheric Applications
Authors: Laaksonen Ari , Talanquer Vicente , Oxtoby David W.
Published: July 2003

New experiments have succeeded in measuring actual rates of nucleation and are revealing the shortcomings of classical nucleation theory, which assumes that the molecular-scale regions of the new phase may be treated using bulk thermodynamics and planar surface free energies. In response to these developments, new theories have been developed that incorporate information about molecular interactions in a more realistic fashion. This article reviews recent experimental and theoretical advances in the study of nucleation of liquids from the vapor and of crystals from the melt, with particular emphasis on phenomena that relate to particle formation in the atmosphere.
Salt-Nucleic Acid Interactions
Authors: Anderson Charles F. , Record M. Thomas
Published: July 2003

Coulombic interactions of salt ions with polymeric and oligomeric nucleic acids in solution have large and distinctive effects on ion distributions, on thermodynamic coefficients, and hence on equilibrium processes involving nucleic acids, such as their conformational transitions and binding interactions. In experimental or theoretical studies where an oligonucleotide is taken to represent the corresponding polynucleotide, the impact of coulombic end effects on molecular and thermodynamic properties must be taken into account. Observable consequences of coulombic interactions in nucleic acid solutions have been calculated by using models with varying degrees of detail and methods formulated at varying levels of rigor. From comparisons of experimental results with predictions of the prevalent theoretical approaches, this review concludes that the more rigorous methods have proved capable of accounting for thermodynamic (and some molecular) consequences of coulombic interactions with a minimal number of preaveraged parameters that represent the most important structural features of the nucleic acid solution.
THEMEDIA ANDDEMOCRACY: Beyond Myths and Stereotypes
Authors: Graber Doris
Published: July 2003

▪ Abstract  This essay's point of departure is the hallowed belief that democracy requires active citizens and news media that supply them with information they need to participate effectively in politics. The main features of this model of a functioning democracy, including the underlying assumptions, are tested and found wanting. Neither citizens nor media are capable of performing the roles expected of them. The appropriateness of these roles for life in modern societies is also open to question, as are the many myths and stereotypes that obscure the interface between media and democracy. The fact that democracy can persist despite citizens and media that fall short of the expected performance suggests that political culture may be more important than citizen wisdom and media excellence. Rallies in civic activism during crises may also be a major factor in the durability of democratic governance in the United States.
Regulation of Metabolism in Transgenic Plants
Authors: Stitt Mark , Sonnewald Uwe
Published: July 2003

This review discusses how genetically manipulated plants are being used to study the regulation of metabolism in plants, using carbohydrate metabolism as an example. The molecular tools required are introduced, including the history of Agrobacterium tumefaciens-mediated gene transfer and other transformation techniques, the availability of promoters to achieve a specific or induced expression, strategies to target proteins to subcellular compartments of the cell, and the use of antisense or cosuppression to inhibit expression of endogenous genes. A discussion then follows of how such plants can be used in biochemical and physiological experiments to identify and quantify the importance of enzymes and processes that control metabolic fluxes, storage, and growth. These results are leading to a reassessment of ideas about metabolic regulation and have consequences for design of bioengineering strategies in plants. Emerging commercial applications are also surveyed.
Starch Synthesis in Maize Endosperms
Authors: Nelson Oliver , Pan David
Published: July 2003

Research over the past three decades has greatly increased our understanding of starch biosynthesis in storage tissues, but our knowledge is still incomplete. Advances and areas of uncertainty are discussed with a focus on the maize mutants that have been useful in elucidating the process. This emphasis on mutant genes promises additional insights when we discover the role of several mutants known to affect starch synthesis and when we isolate mutations in genes encoding enzymes that have important roles in the process. The goal is a complete understanding of starch synthesis. This understanding will also facilitate the design of transgenic plants that might produce unique starches with promise as raw materials for industrial processes.
Women, Work, and Health
Authors: Sorensen Glorian , Verbrugge Lois M.
Published: July 2003

The majority of women today simultaneously occupy demanding work and family roles. In 1980, 60 percent of women between 16 and 64 years of age were employed (76). Yet women continue to shoulder the main responsibilty for household tasks and childcare. It is often suggested that women's multiple responsibilities and attendant role conflicts will have negative consequences for their health. Despite the rising concern and considerable speculation surrounding this subject, little is known about the implications of women's rising employment for changes in women's physical and mental well-being. In this article, we describe the main theoretical models and pertinent research about work and health among women. It is likely that all of the models contain some truth and that no single model can encompass the ways employment affects women's health. The scientific task therefore is to identify the job conditions and role configurations that lead to positive, or negative, health consequences and then to distill the many empirical results.
Exposure Assessment Error and its Handling in Nutritional Epidemiology
Authors: Kohlmeier Lenore , Bellach Bärbel
Published: July 2003

Exposure assessment is the weakest element in nutritional epidemiologic studies. In the absence of an adequate arsenal of biomarkers of intake in the United States, food frequency questionnaires are widely used to assess habitual frequency of consumption of foods. These tools need to be designed for the population under study, based on prior information on the eating behavior of the population. The questions to be addressed to insure appropriate application of these tools are presented. The influence of various sources and types of measurement error on various scientific hypotheses is addressed. In assessment of nutrient adequacy, information on intra- to interindividual variation of the nutrient or substance of interest is essential. Risk assessment requires examination of sources and extent of bias and differential and nondifferential measurement error within the study. The theory required for error correction is well developed, but rarely carried out because of lack of software and lack of information needed to calibrate the measures.