سبد خرید

The Eye in Pediatric Systemic Disease

Perhaps the most frequent question which parents ask pertaining to their infant’s eyes is “What does my baby see?” The answer to this question depends in part on the type of method used to assess visual acuity. The majority of babies should show some fxational behavior at term birth. At 4 weeks, the baby looks at their mother’s face while breast feeding . When the mother moves her face, the child will follow it visually. This movement is interrupted if the mother turns her face away so that only her profle is presented . By 2 months the baby is following better but the pursuit movements tend to be jerky rather than smooth . Smooth pursuit eye movements show the most maturation from 2 to 6 months old, and reaching almost an adult-like gain by 18 months old . Pieh and coworkers found that tracking time was highest when a larger stimulus of 4.78° of visual angle was applied (p<0.022) and when the stimulus was moved at a medium stimulus velocity of 15 degree/s (p<0.0002) . Often, the human face is a better stimulus of fxation than a light source . Goren et al. were able to show that 9 min old infants had a preference for a face-like stimulus over a scrambled face image. Both of these were preferred by the infant over a blank face image.

Vascular Smooth Muscle Structure and Function in Health and Disease

This book covers core concepts in the structure and function of vascular smooth muscle cells in health and disease. Supplemental reading may be drawn from the extensive number of references listed at the end of each chapter. Vascular smooth muscle cell is the major cell type in blood vessels. Dysfunction of vascular smooth muscle cells is an important cause of vascular diseases — for example, atherosclerosis, hypertension, and circulatory shock. Vascular smooth muscle cells are phenotypically plastic, capable of switching between two major phenotypes — contractile/differentiated phenotype and invasive/ proliferative phenotype — in response to environmental clues. This book is organized in three sections. Section I (chapters 2 to 4) addresses the structure and function of the contractile/differentiated phenotype of vascular smooth muscle cell. Section II (chapters 5 and 6) addresses the developmental basis of vascular smooth muscle cell phenotype and structure and function of podosomes (invasive organelles) in the invasive/proliferative phenotype of vascular smooth muscle cell. Section III (chapters 7 to 9) addresses the role of vascular smooth muscle cell dysfunction in three vascular diseases — atherosclerosis, hypertension, and circulatory shock.

Vascular Smooth Muscle Structure and Function in Health and Disease

This book covers core concepts in the structure and function of vascular smooth muscle cells in health and disease. Supplemental reading may be drawn from the extensive number of references listed at the end of each chapter. Vascular smooth muscle cell is the major cell type in blood vessels. Dysfunction of vascular smooth muscle cells is an important cause of vascular diseases — for example, atherosclerosis, hypertension, and circulatory shock. Vascular smooth muscle cells are phenotypically plastic, capable of switching between two major phenotypes — contractile/differentiated phenotype and invasive/ proliferative phenotype — in response to environmental clues. This book is organized in three sections. Section I (chapters 2 to 4) addresses the structure and function of the contractile/differentiated phenotype of vascular smooth muscle cell. Section II (chapters 5 and 6) addresses the developmental basis of vascular smooth muscle cell phenotype and structure and function of podosomes (invasive organelles) in the invasive/proliferative phenotype of vascular smooth muscle cell. Section III (chapters 7 to 9) addresses the role of vascular smooth muscle cell dysfunction in three vascular diseases — atherosclerosis, hypertension, and circulatory shock.

Atlas of Graft-versus-Host Disease

Allogeneic hematopoietic stem cell transplantation (HSCT) is a form of immune therapy used to treat a variety of malignant and nonmalignant diseases. The procedure involves transfusion of multipotent hematopoietic stem cells derived from bone marrow, peripheral blood, or umbilical cord blood from a donor, usually matched in human leukocyte antigens (HLA). Immediately prior to HSCT, patients receive conditioning chemoradiotherapy to eliminate underlying hematologic malignant cells, and to suffciently suppress the host’s immune functions for successful engraftment of donor hematopoietic cells. Following the conditioning regimen and HSCT, donor-derived hematopoietic recovery and immune reconstitution occur, during which patients require intensive supportive care, including prevention and treatment of complications such as infections and acute or chronic graftversus-host disease (GVHD). Currently, between 55,000 and 60,000 HSCTs are performed worldwide each year, including approximately 8000 in the United States alone . With the use of alternative donor strategies, reduced intensity conditioning (RIC) regimens, and greater availability of donors, the application of this form of immunotherapy is set to increase in the coming years (Fig. 1.1). Although allogeneic HSCT is the most effective and intensive therapy for hematologic disorders, there are signifcant barriers towards improving outcomes of HSCT, including transplant-related morbidity and mortality associated with acute and chronic GVHD, infection or delayed immune reconstitution, and regimen-related organ toxicities. In addition, despite intensive conditioning regimens and potent graft-versus-leukemia (GVL) effects, posttransplant relapse remains a signifcant cause of treatment failure. Thus, ongoing efforts are focused on improving patient selection criteria, preventing and treating GVHD and infection, and devising methods to reduce post-HSCT relapse of the underlying disease.

Vascular Disease in Older Adults

Abdominal Aortic Aneurysms (AAAs) represent a signifcant vascular health problem. In the United States alone, an estimated 1.5 million people have AAAs, with 200,000 more diagnosed each year, and associated with at least 15,000 annual deaths . AAAs account for 4–5% of sudden deaths and represent the 13th most
common cause of death overall .An aneurysm is defned as an abnormal focal dilation of a blood vessel where the minimum diameter exceeds 3.0 cm in any perpendicular plane; this generally accepted threshold equates to 1.5 times the normal juxta-renal diameter . As aneurysms grow, the vessel wall weakens, increasing the risk of rupture. AAA rupture is a life-threatening event with a high mortality rate due to the rapidity with which exsanguination occurs, often prior to the patient arriving at a medical facility for treatment. Thus, there is a rationale for screening to diagnose AAA and institute measures to reduce the growth of the aneurysm, as well as to stratify those who may need surgical treatment.

Protein Deimination in Human Health and Disease

Autoimmune diseases represent a long-standing puzzle. In an incompletely understood series of steps, the immune system loses immune tolerance to self and acquires the ability to recognize and respond to defined and characteristic autoantigens . The involvement of an infectious agent has been suspected to trigger this transition, but a specific etiologic stimulus has not been identified. Recent years have seen an evolution in the understanding of events that lead to autoimmunity . A central role has been assigned to posttranslational modifications of autoantigens during the initial, preclinical phase of autoimmune syndromes. In response to various infections or even under sterile inflammatory conditions, the innate immune system activates a characteristic set of enzymatic reactions, including the regulated conversion of certain arginine residues to citrulline residues. The conversion, carried out by the peptidylarginine deiminases (PADs), results in the conversion of arginine residues to citrulline residues in many notable autoantigens . In turn, an important category of autoantibodies, referred to as anti-citrullinated protein antibodies (ACPA) , specifically recognizes the citrullinated form of these autoantigens. Thus, the concept is gaining acceptance that diverse infections (or sterile inflammation ) result in the citrullination of selfproteins, which—given genetic predisposition or a conducive infectious microenvironment—break tolerance and trigger a self-perpetuating autoimmune process. This chapter highlights aspects of PAD regulation and the development of ACPA in order to propose a unifying principle for the induction of autoimmune disorders.

Pulmonary Vasculature Redox Signaling in Health and Disease

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature, which is characterized by sustained pulmonary arterial pressure, resulting in increased pulmonary vascular resistance, with eventual right heart failure . Vascular remodeling caused by the medial hyperplasia of pulmonary artery (PA) smooth muscle cells is a hallmark feature of PAH , which causes occlusion of the vessels . In most forms of PAH, muscularization of small distal PA occurs , and is further characterized by excessive vascular cell proliferation, inward remodeling, rarefaction, and a loss of compliance of the pulmonary blood vessels . Increased resistance to blood flow and more rigid blood vessels (loss of vascular compliance) leads to failure of the right ventricle and eventual death. PAH is more frequent in women than men, and left untreated has a survival time of 5–7 years post diagnosis . From a therapeutic standpoint, there are a number of vasodilator drugs that are indicated for the treatment of PAH, but none of the current therapeutics offers long-term success for survival due to limited effectiveness and unwanted side effects , and more importantly, do not address the underlying causes of the disease.

Human Retrotransposons in Health and Disease

Retrotransposons are a class of mobile genetic elements that make up around 40% of the sequenced mammalian genome (Chinwalla et al. 2002; Lander et al. 2001). Retrotransposons contribute to genomic instability in mammalian genomes by providing interspersed repeats of homologous sequences that can act as substrates for recombination causing deletions, duplications and structural rearrangements in the genome (Romanish et al. 2010). Retrotransposons are thought to be the only active class of mobile genetic element in most mammalian genomes, and can also cause genome instability through jumping to new locations in the genome. These de novo retrotransposon insertions have been reported as the causal mutation in various human genetic diseases (Crichton et al. 2014; Hancks and Kazazian 2012). The copy-and-paste mechanism that retrotransposons use to jump to new locations in the genome involves reverse-transcription of retrotransposon RNA, and integration of the resulting cDNA into new locations in the genome. There are typically a few hundred different types of retrotransposon annotated in each mammalian genome, with each type of retrotransposon being present in up to 10,000 copies. However, the types of retrotransposon, their copy numbers and their genomic locations vary signifcantly between species.

Neuroepigenomics in Aging and Disease

From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/ hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners. The fnal outcome is a highly specialized chromatin organization wherein linker histones (histones of the H1 family) and MeCP2 share an organizational role that dynamically changes during neuronal development andthat it is still poorly understood. MeCP2 mutations alter its chromatin-binding dynamics and/or impair the ability of the protein to interact with some of its partners, resulting in Rett syndrome (RTT). Therefore, deciphering the molecular details involved in the MeCP2 neuronal chromatin arrangement is critical for our understanding of the proper and altered functionality of these cells.

THE ROLES OF HORMONES IN DEFENSE AGAINST INSECTS AND DISEASE

Jasmonic acid (JA1) and its volatile methyl ester, MeJA, are fatty acidderived cyclopentanones that occur ubiquitously in the plant kingdom. Since the discovery of jasmonates (JAs) in plants over 40 years ago, our understanding of the biosynthesis and physiological function of these compounds has been marked by several major developments. Experiments performed in the 1980s elucidated the JA biosynthetic pathway and demonstrated that exogenous JAs exert effects on a wide range of physiological processes. The discovery in the early 1990s that JAs act as potent signals for the expression of defensive proteinase inhibitors (PIs) aroused intense interest in the function of hormonally active JAs in plant defense. Research in the past decade has led to several key developments, including identification of genes encoding most of the JA biosynthetic enzymes and discovery of novel biologically active JAs. Identification of a large collection of JA biosynthesis and response mutants has provided important tools to assess the role of JAs in plant developmental and defenserelated processes. The widespread occurrence of JAs in plants and somelower eukaryotes, together with their capacity to regulate physiological processes in animals (e.g., insects), reinforces the notion that JAs are of general biological interest.

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