Pericardial fluid level of heart-type cytoplasmic fatty acid-binding protein (H-FABP) is an indicator of severe myocardial ischemia

BACKGROUND: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or pericardial fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. METHODS: A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A (n=17), and those without these symptoms and changes into group B (n=17). Blood and pericardial fluid samples were obtained immediately after median sternotomy, and serum and pericardial fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. RESULTS: Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5+/-1.0 vs. 7.1+/-0.7 ng/ml, P=0.25), pericardial fluid levels of H-FABP were significantly higher in group A than in group B (16.3+/-2.0 vs. 9.6+/-1.0 ng/ml, P=0.0046). H-FABP showed a weak correlation between its serum levels and pericardial fluid levels (r=0.40). CONCLUSIONS: Pericardial fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, pericardial fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.     

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of > 8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).     

The dominant negative effect of a kinase-defective insulin receptor on insulin-like growth factor-I-stimulated signaling in Rat-1 fibroblasts

To study the interaction between insulin receptor (IR) and insulin-like growth factor-I (IGF-I) receptor (IGF-IR) tyrosine kinases, we examined IGF-I action in Rat-1 cells expressing a naturally occurring tyrosine kinase-deficient mutant IR (Asp 1048 IR). IGF-I normally stimulated receptor autophosphorylation, IRS-I phosphorylation, and glycogen synthesis in cells expressing Asp 1048 IR. However, the Asp 1048 IR inhibited IGF-I-stimulated thymidine uptake by 45% to 52% and amino acid uptake (aminoisobutyric acid [AIB]) by 58% in Asp 1048 IR cells. Furthermore, IGF-I-stimulated tyrosine kinase activity toward synthetic polymers, Shc phosphorylation, and mitogen-activated protein (MAP) kinase activity was inhibited. The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild-type IGF-IR in Asp 1048 IR cells. These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF-IR in transmitting signals to Shc and MAP kinase activation, which leads to decreased IGF-I-stimulated DNA synthesis, and that the kinase-defective insulin receptor does not affect IGF-I-stimulated IRS-I phosphorylation, which leads to the normal IGF-I-stimulated glycogen synthesis.     

Drug-induced pneumonitis associated with imatinib mesylate in a patient with idiopathic pulmonary fibrosis

A 74-year-old man with idiopathic pulmonary fibrosis (IPF) developed severe dyspnea on exertion after the readministration of imatinib mesylate for chronic myeloid leukemia. Chest X-ray and CT showed ground-glass opacities in both lungs in addition to preexisting honeycombing. Discontinuation of imatinib and methylprednisolone pulse therapy followed by administration of oral prednisolone resulted in improvement in both symptoms and radiographic findings. Imatinib-induced pneumonitis was diagnosed based on the clinical course and findings. Only five previous reports of imatinib-induced pneumonitis have been published in the literature, and this is the first case reported in a patient with IPF.     

Down syndrome candidate region 1,a downstream target of VEGF, participates in endothelial cell migration and angiogenesis

Vascular endothelial growth factor (VEGF) is a principal stimulator of angiogenesis. However, the downstream targets of VEGF in endothelial cells (ECs) are not entirely clarified. Survey of downstream targets of VEGF in human ECs identified a number of genes, including Down syndrome candidate region 1 (DSCR1). Here, we confirmed the inducible expression of DSCR1 in ECs by Northern and Western blottings. Moreover, VEGF-stimulated induction of DSCR1 was blocked by anti-VEGF receptor-2 monoclonal antibody (mAb), or the specific calcineurin inhibitors cyclosporin A and FK506. The expression of DSCR1 in ECs of neovessels was further shown by immunohistochemical analysis. We therefore examined whether DSCR1 played any roles in angiogenesis. The specific downregulation of DSCR1 expression by antisense oligonucleotide (AS-ODN) inhibited VEGF-stimulated migration of ECs as well as angiogenesis in vivo. AS-ODN inhibited the spreading of ECs on vitronectin, as well as on the immobilized anti-alphavbeta3 mAb, but not on anti-alphavbeta5 mAb. Moreover, AS-ODN inhibited tyrosine phosphorylation of focal adhesion kinase when ECs were plated on a vitronectin-coated dish. Immunoprecipitation followed by Western blotting showed the coimmunoprecipitation of DSCR1 and integrin alphavbeta3. These results suggest that DSCR1 is involved in angiogenesis by regulating adhesion and migration of ECs via the interaction with integrin alphavbeta3.     

Comparison of the performance of zotarolimus- and everolimus-eluting stents by optical coherence tomography and coronary angioscopy

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.     

Beneficial effect of candesartan treatment on cardiac autonomic nervous activity in patients with chronic heart failure: simultaneous recording of ambulatory electrocardiogram and posture

BACKGROUND: Reclining in the right lateral decubitus position in chronic heart failure (CHF) is a self-protective mechanism for normalizing impaired cardiac autonomic nervous activity (CANA). HYPOTHESIS: Candesartan, an angiotensin II receptor blocker, exerts beneficial effects on CANA and postural preferences in patients with CHF. METHODS: We studied 15 patients with CHF due to coronary artery disease. Cardiac autonomic nervous activity was assessed using spectral heart rate variability (HRV) analysis based on 24-h ambulatory electrocardiogram monitoring before and after an 8-week treatment with candesartan. The patients' posture was simultaneously recorded using a specially devised detector, as the right (R) or left (L) lateral decubitus or supine (S) positions, to evaluate postural modulations of CANA. Normalized high-frequency (0.15 to 0.40 Hz) power (nHF) and the low-frequency (0.04 to 0.15 Hz)/high-frequency power ratio (LF/HF) were used as indices of vagal activity and sympathovagal balance, respectively. RESULTS: When HRV was analyzed in each position, CANA was changed in L and S, but not in R, from sympathetic to parasympathetic prevalence by the treatment (R, nHF, 50 +/- 20 vs. 52 +/- 19 nu, p = 0.87; LF/HF, 1.39 +/- 1.11 vs. 1.32 +/- 1.32, p =0.93; L, nHF, 28 +/- 13 vs. 47 +/- 19 nu, p = 0.019; LF/HF, 3.34 +/- 2.48 vs. 1.56 +/- 1.39, p = 0.029; S, nHF, 38 +/- 17 vs. 53 +/- 16 nu, p = 0.0023; LF/HF, 2.43 +/- 2.21 vs. 1.03 +/- 0.59, p = 0.025). The fractions of the time in R and L were decreased and increased, respectively, by the treatment (R, 40 +/- 30 vs. 18 +/- 24%, p = 0.0018; L, 11 +/- 20 vs. 27 +/- 26%, p = 0.025). CONCLUSIONS: In patients with CHF, candesartan treatment improves cardiac autonomic balance, and the preference for the right lateral decubitus position disappears after the treatment.     

Inhibition of intestinal sodium-dependent inorganic phosphate transport by fibroblast growth factor 23

The mechanisms by which fibroblast growth factor 23 (FGF23) alters inorganic phosphate (Pi) homeostasis is not entirely clear. In the present study, we examined the effect of FGF23 on intestinal sodium-dependent Pi transport in mice. Injection of FGF23(R179Q) markedly reduced serum Pi and 1,25(OH)2D3 levels in normal mice. Those animals show the reduction of intestinal sodium-dependent Pi transport activity and the amount of type IIb sodium-dependent Pi cotransporter (type IIb NaPi) protein in the brush border membrane vesicles. In vitamin D receptor null mice (VDR-/-), FGF23(R179Q) had no effect on intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels. The present study suggests that FGF23(R179Q) reduces intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels by a mechanism that is dependent on VDR.