Pediatric Pathology & Molecular Medicine 

About: Pediatric Pathology & Molecular Medicine is an academic journal. The journal publishes majorly in the area(s): Gene & Surfactant protein A. Over the lifetime, 189 publications have been published receiving 2530 citations.

Natural history and risk factors of atherosclerosis in children and youth: the PDAY study.

Abstract: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized to document the natural history of athersclerosis and to determine the relation of cardiovascular risk factors to atherosclerosis in young subjects. Pathology laboratories in 15 centers collected coronary arteries, aortas, and other tissues from over 3,000 subjects age 15 to 34 who died of external causes between 1987 and 1994. The extent, prevalence, and topography of arterial lesions were evaluated and risk factors were analyzed in a central laboratory. Postmortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus and body mass index (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. The PDAY study confirmed the origin of atherosclerosis in childhood, showed that progression toward clinically significant lesions may occur in young adulthood and demonstrated that the progression of atherosclerosis is strongly influenced by coronary heart disease (CHD) risk factors. Recent PDAY studies have shown that a significant number of advanced coronary artery lesions have microscopic qualities associated with susceptibility to rupture and that CHD risk factors are associated with the development of these characteristic microscopic qualities. The PDAY archive continues to provide an important resource for new investigators throughout the world that contribute to the understanding of atherosclerosis, the underlying cause of most cardiovascular disease and the leading cause of debilitating illness and death in this country. The PDAY findings emphasize the need to modify risk factors in young people to retard the development of atherosclerotic lesions, particularly clinically significant lesions. Thus, true primary prevention of atherosclerosis must being in childhood or early adolescence.

The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation, and repair in vitro

Abstract: Parathyroid hormone-related protein (PTHrP) expression is necessary for differentiation of mesenchymal lipofibroblasts, which induce epithelial type II (TII) cell differentiation, both of which are necessary for alveolarization. PTHrP deficiency may be associated with bronchopulmonary dysplasia (BPD), characterized by truncation of alveolarization among preterm infants. This is supported by the baboon model of BPD (failure of alveolarization) that manifests PTHrP deficiency. We provide evidence that TII cell PTHrP expression is downregulated by alveolar overdistension, resulting in the transdifferentiation of lipofibroblasts to myofibroblasts, characterized by progressive loss of PTHrP receptor expression and triglyceride content, and sequential upregulation of f -smooth muscle actin ( f SMA), typifying fibrosis. PTHrP reverses the downregulation of the PTHrP receptor and upregulation of f SMA, reverting myofibroblasts to a lipofibroblast genotype. When TII cells are co-cultured with lipofibro...

Surfactant regulation of host defense function in the lung: a question of balance.

Abstract: Although the lung is protected by classic innate and adaptive immune mechanisms, another unique local immunoregulatory system involving pulmonary surfactant is described in this review. Normal surfactant inhibits many immune cell functions including proliferation resulting from various stimuli and production of reactive oxidants, inflammatory mediators, and some cell surface markers. The predominant surfactant lipids appear to be responsible for these suppressive effects. Conversely, surfactant proteins SP-A and SP-D stimulate many aspects of immune cell behavior. These proteins are collagenous lectins or collectins that bind to glycoconjugates on many pathogens, enhancing phagocytosis and killing in some cases. SP-A and SP-D stimulate chemotaxis and reactive oxidant generation, particularly in macrophages, although other cells are probably affected as well. In some cases, SP-A also stimulates the expression of cell surface markers and is involved in the stimulation of inflammatory mediators. Under normal conditions, the inhibitory effects of the lipid prevail, but the collectins may provide focal activation and stimulate immune cells at sites where they are needed. However, in some types of lung disease or after certain insults or exposures, the balance between these inhibitory and stimulatory influences may be disrupted and result in inflammatory injury.

Integrins During Muscle Development and in Muscular Dystrophies

Abstract: Cellular interactions with the extracellular matrix (ECM) have been shown to be important for a number of developmental events from the time of fertilization up till the maturation of the organism. In the following review we will discuss what is currently known about these interactions with special emphasis on the role of integrins during the formation of skeletal muscle. The importance of cell-ECM interactions will also be illustrated by a discussion of what happens when these interactions to awry, as happens in muscular dystrophies.

Hemostatic Alterations in Sickle Cell Disease: Relationships to Disease Pathophysiology

Abstract: The protean manifestations of sickle cell disease (SCD), especially, microvessel involvement in the vasoocclusive process, is classically ascribed to the phenomena of erythrocyte sickling and enhanced red cell-endothelial adherence. Pertubations in various hemostatic systems occurs in SCD, both in steady state and during vasoocclusion, with the intravascular generation of thrombin. The etiology(s) of thrombin generation in SCD will be described. Whether the activation of the cellular and plasmatic phases of hemostasis is causative or occurs as a result of vascular injury will be discussed.