A recently identified chemokine, fractalkine, is a member of the chemokine gene family, which consists principally of secreted, proinflammatory molecules. Fractalkine is distinguished structurally by the presence of a CX3C motif as well as transmembrane spanning and mucin-like domains and shows atypical constitutive expression in a number of nonhematopoietic tissues, including brain. We undertook an extensive characterization of this chemokine and its receptor CX3CR1 in the brain to gain insights into use of chemokine-dependent systems in the central nervous system. Expression of fractalkine in rat brain was found to be widespread and localized principally to neurons. Recombinant rat CX3CR1, as expressed in Chinese hamster ovary cells, specifically bound fractalkine and signaled in the presence of either membrane-anchored or soluble forms of fractalkine protein. Fractalkine stimulated chemotaxis and elevated intracellular calcium levels of microglia; these responses were blocked by anti-CX3CR1 antibodies. After facial motor nerve axotomy, dramatic changes in the levels of CX3CR1 and fractalkine in the facial nucleus were evident. These included increases in the number and perineuronal location of CX3CR1-expressing microglia, decreased levels of motor neuronexpressed fractalkine mRNA, and an alteration in the forms of fractalkine protein expressed. These data describe mechanisms of cellular communication between neurons and microglia, involving fractalkine and CX3CR1, which occur in both normal and pathological states of the central nervous system.Chemokines mediate the directed migration of a variety of leukocyte subsets and consist of at least four subfamilies based principally on the relative position of highly conserved cysteine residues in their amino acid sequences (1, 2). Most chemokine peptides are characterized as secreted proteins of Ϸ7-10 kDa. The recent discovery of a chemokine termed fractalkine has revealed additional distinctive structural features in this gene family. These features include a CX3C motif and a mucin-like stalk that tethers the chemokine domain to transmembrane (TM) spanning and short intracellular domains (3, 4). Evidence from transfected cell systems indicates that fractalkine can exist as membrane-anchored, pro-adhesive, and secreted, chemotactic forms. Furthermore, unlike most chemokine peptides, fractalkine expression is demonstrable in nonhematopoietic tissues including brain, kidney, lung, and heart. In particular, the relatively high levels of fractalkine in the brain raises questions related to the function of chemokines in the central nervous system (CNS).G-protein coupled receptors for chemokine peptides have been characterized extensively in transfected cells and peripheral leukocytes (2). However, very little is known regarding chemokine receptor expression and function in the CNS. Some chemokine receptors, including CCR5, CCR3 (5-7), CXCR4 (7-10), CXCR1, and DARC (11) have been demonstrated to be expressed in either normal brain tissue or cells derived from the...

Moderate-to-severe late-onset neonatal hypocalcemia is more common in Hispanic and male infants, is often a sign of coexistent vitamin D insufficiency or deficiency and hypomagnesemia, and is readily managed with therapy of limited duration. Neonates presenting with seizures who are found to be hypocalcemic are unlikely to benefit from neuroimaging evaluations.

No abstract

Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.

The genes encoding two functional human interleukin-8 (IL-8) receptors have been identified by molecular cloning techniques and they are members of the rhodopsin G-protein coupled receptor (GCR) superfamily. We report the molecular cloning of two rat GCR genes (rat CXCR1-like and rat CXCR2) whose conceptualized amino acid sequences are approximately 70% identical to the human IL-8 A and B receptor subtypes. The murine GRO-like peptide, macrophage inflammatory peptide-2 (MIP-2), elevates intracellular calcium levels in HEK293 cells expressing the rat CXCR2 receptor. Southern blot analysis of restriction-digested rodent and human genomic DNAs indicate that rat CXCR1-like and CXCR2 are: 1) each single copy genes in the rat genome; 2) most closely related to the human IL-8 receptor genes; and 3) orthologous to two previously identified murine genes. CXCR2 mRNA is detected in adult rat lung, spleen, and neutrophils. CXCR1-like mRNA can be detected in adult rat lung, native rat macrophages, and a rat alveolar macrophage cell line (NR8383). These data identify the rat orthologs of the human IL-8 receptors, and describe cellular and tissue targets of rat C-X-C chemokine peptides.

Introduction Despite recognition that childhood brain tumor survivors often suffer multiple late effects following therapy, little is known regarding the long‐term follow‐up (LTFU) programs for these patients. Methods A 16‐question survey was mailed to member institutions of the Children's Oncology Group in the United States. Institutions were asked about the size of their brain tumor program, activities of the LTFU programs and perceived barriers to follow‐up. Results One hundred forty‐five (74%) of 197 institutions returned surveys. Care for patients <21 years old at diagnosis who are >2 years following completion of therapy was provided at a designated neuro‐oncology LTFU clinic (31.2%), a general LTFU program for childhood cancer survivors (30.4%), or a general pediatric oncology program (29.7%). Institutions with a neuro‐oncology LTFU clinic were more likely to use neuro‐psychological testing following radiation therapy (P = 0.001), have longer duration of continued surveillance imaging (P = 0.02), use growth hormone replacement for medulloblastoma survivors (P < 0.001) and continue the use of growth hormone into adulthood (P = 0.05) than those with a general pediatric oncology program. Perceived barriers to care of brain tumor survivors included limited access and lack of insurance (32.1%), lack of funding or dedicated time for providers (22.9%), patients' uncertainty about need to follow‐up (20.6%), and patients' desire to not be followed in a pediatric cancer program (12.2%). Conclusions Considerable variation exists across institutions in the United States in the delivery of follow‐up care for survivors of childhood brain tumors. We encourage additional investigation to better define and implement optimal follow‐up care for childhood brain tumor survivors. Pediatr Blood Cancer 2009; 53:1295–1301. © 2009 Wiley‐Liss, Inc.

Recent reports have suggested an increased risk of QT prolongation and subsequent life-threatening ventricular arrhythmias, particularly torsade de pointes, in patients with coronavirus disease-2019 (COVID-19) treated with hydroxychloroquine and azithromycin. In this article, we report the case of a 75-year-old female with a baseline prolonged QT interval in whom the COVID-19 illness resulted in further remarkable QT prolongation (>700 ms), precipitating recurrent self-terminating episodes of torsade de pointes that necessitated temporary cardiac pacing. Despite the correction of hypoxemia and the absence of reversible factors, such as adverse medication effects, electrolyte derangements, and usage of hydroxychloroquine/azithromycin, the QT interval remained persistently prolonged compared with the baseline with subsequent degeneration into ventricular tachycardia and death. Thus, we highlight that COVID-19 illness itself can potentially lead to further prolongation of QT interval and unmask fatal ventricular arrhythmias in patients who have a prolonged QT and low repolarization reserve at baseline.

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.