Antibodies to histones H1 and H5 in sera of patients with juvenile rheumatoid arthritis

The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular-onset JRA sera, 4 of 19 polyarticular-onset JRA sera, and 2 of 11 systemic-onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age-matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.     

Five-year effect of medical and surgical therapy on resting left ventricular function in stable angina: Veterans administration cooperative study

The effect of coronary artery bypass grafting (CABG) and medical therapy on 5-year resting left ventricular (LV) function was studied in 194 randomized patients with stable angina in the Veterans Administration Study of Coronary Artery Bypass Surgery. LV ejection fraction (EF) was determined in a central laboratory. The 92 medical and 102 surgical patients were comparable at entry with respect to historic, angiographic and electrocardiographic prognostic indicators. Twenty-eight percent of the medical and 30% of the surgical patients had a baseline EF of < 50%. There was no significant change in mean EF between baseline and 5-year values in either treatment group. The base-line and 5-year values were 56 and 58% in each treatment group. Intervening myocardial infarction (MI) had an adverse effect in medically treated patients (59 to 46%, p < 0.01) and in surgically treated patients with late Ml (58 to 47%, difference not significant). Perioperative MI was not associated with a decrease in EF (56 to 58%, difference not significant). These findings extend the similar results of previous short-term studies of the effect of coronary bypass surgery on resting LV function to 5 years, and provide data in a comparable medical control group.     

How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative

Immunologic Research - Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a...     

Human pancreatic precursor cells secrete FGF2 to stimulate clustering into hormone-expressing islet-like cell aggregates

Development of the endocrine pancreas includes a series of early events wherein precursor cells cluster, that is migrate to form cell aggregates, which subsequently differentiate into islets of Langerhans. We show that PANC-1 cells, a human pancreatic cell line, differentiates into hormone-producing islet-like cell aggregates after exposure to a defined serum-free medium. These cells were used to provide the following evidence that fibroblast growth factor (FGF)2 is a paracrine chemoattractant during PANC-1 cell clustering: (i) FGF2 is secreted and remains bound to the extracellular matrix from where it may diffuse to form chemoattractive gradients; (ii) a subset of cells expresses FGF receptors (FGFRs) -1, -2, -3, and -4; (iii) inhibition of FGFR tyrosine kinase inhibits cell clustering; and (iv) FGF2 neutralizing antibody inhibits clustering. In addition, adult human islet-derived precursor cells, which cluster and differentiate in a manner similar to PANC-1 cells, also secrete FGF2 and express FGFRs. We conclude that FGF2, acting as a paracrine chemoattractant, stimulates clustering of precursor cells, an early step leading to islet-like cell aggregate formation. Similar processes may occur during development of the islet of Langerhans in humans.     

Anorectal Physiology and Pathophysiology

The anatomy and physiology of the external anal sphincter, puborectalis muscle, internal anal sphincter, and rectum are described. Measurement techniques are reviewed emphasizing those which can be carried out by the gastroenterologist in independent office practice, and the range of normal values for each test is given. A protocol for diagnostic evaluation of anorectal disorders is recommended which includes testing for rectal prolapse and for descent of the perineum by having the patient strain while seated on a commode chair, evaluating the external and internal anal sphincters by recording EMG with an anal plug, or recording pressures with a perfused catheter or balloon probe, using a rectal balloon to evaluate the maximum tolerable volume of rectal distension and the minimum (threshold) volume of a bolus injection which can be subjectively perceived, and arranging with a radiologist to perform a proctogram--a radiograph of the rectum and anal canal during rest and when the patient strains to defecate--in order to evaluate the anorectal angle (puborectalis muscle) and to detect rectocele and intussusception. These objective tests should be supplemented by a careful clinical history and physical examination.     

Esthesioneuroblastoma: An Update on the UCLA Experience, 2002–2013

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems.