Neurogenic regulation of basal tone of coronary artery with mild atherosclerosis in humans: observation using two-dimensional intravascular ultrasound

The purpose of this study was to assess the role of the autonomic nervous system in the regulation of basal coronary artery tone in normal and atherosclerotic plaque segments by using intravascular ultrasound in humans. In each of 21 patients, a short-axis image at one site of coronary artery was imaged by means of a 3.2F, 30-MHz intravascular ultrasound before and after intracoronary administration of 2 mg isosorbide dinitrate (ISDN). The authors identified the perimeters of the vessel wall segments with normal or atherosclerotic plaque on ultrasound images and evaluated the basal tone in each segment as a percent increase in each perimeter produced by ISDN. Using heart rate variability analysis for 512 seconds recorded immediately before ISDN administration, they evaluated cardiac sympathetic and vagal activities at rest as the integrated power of fast Fourier transform (FFT) spectrum for the low-frequency (LF: 0.04 to 0.15 Hz), and high-frequency (HF: 0.15 to 0.4 Hz) components, respectively. Of 29 segments examined by ultrasound, 16 were normal and 13 were atherosclerotic plaque. In all 29 segments, ISDN produced an increase in the perimeter of the vessel wall. At the normal 16 segments, the increase in perimeter by ISDN exhibited a significant correlation to the power of HF (r = 0.749, p = 0.0008) but no significant correlation to LF. At 13 plaque segments, however, no significant correlation between the response to ISDN and autonomic nerve activity was observed. In conclusion, the basal tone of normal coronary arterial wall segment is closely related to parasympathetic nerve, whereas the relation is impaired in mild atherosclerotic segments.     

Application of the Human Hepatitis B Virus Core Antigen from Transgenic Tobacco Plants for Serological Diagnosis

Background and objectives: The aim was to produce HBcAg from plants more cheaply than can be done by other currently available means, and to apply such antigen to immunoassay procedures for pretransfusion testing of donor blood. Materials and methods: Transgenic Nicotiana tabacum cv. SR-1 plants expressing the human hepatitis B virus (HBV) core antigen (HBcAg) gene were generated by Agrobacterium-mediated transformation. The recombinant product, called tHBcAg, can assemble itself into a spherical particle with a diameter of 25 to 30 nm, and can maintain two antigenic determinants of HBcAg, namely HBc/α and HBc/β. Partly purified tHBcAg was used in the hemagglutinationinhibition (HI) test, as routinely used by the Japanese Blood Center, to test a panel of 524 blood units taken from HBV-positive donors. Results: In the HI test, tHBcAg showed serologic properties comparable to that from Escherichia coli, the standard antigen used in the Japanese Blood Center. Conclusions: Transgenic plants can produce reagents for serologic testing and perhaps even such medical materials as oral vaccines.     

Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival

We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus.     

Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes

As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia.     

Difference in CD22 molecules in human B cells and basophils

OBJECTIVE: CD22 is believed to be restricted to normal and neoplastic B cells. Human basophils were found to express CD22 molecules. Among the antibodies against CD22, Leu14, which recognized the ligand binding domain, reacted to basophils, and B3 and 4KB128, which recognized the amino terminus side and carboxy terminus side of the ligand binding epitope, respectively, did not. To clarify the difference of CD22 antigenicity in human B cells and basophils, we investigated RNA sequence and structures of CD22 molecules. MATERIALS AND METHODS: Purified B cells and basophils were obtained from normal human volunteers by using a MACS magnetic cell sorting system and anti-CD19 and anti-Fc epsilon R1 antibodies, respectively. RT-PCR and sequencing of CD22 mRNA were performed in the exons 3 to 8. Western blotting analysis of CD22 was also performed. RESULTS: The sequence of CD22 mRNA extracted from the basophils was the same as that of B cells in exons 3 to 8 (epitopes recognized by Leu14, B3, and 4KB128 were translated from exons 4 and 5). Reduced CD22 peptide extracted from the basophils reacted to Leu14 as well as B3 and 4KB128, and the molecular size of the reduced and nonreduced products was 130 kDa as expected. CONCLUSION: Disulfide bonds and the resulting 3D conformation of the CD22 molecules may have important roles in the difference of antigenicity of CD22 beta in B cells (CD22 beta 1) and basophils (CD22 beta 2). The difference in molecular structure surrounding the ligand-binding domain of CD22 may imply a specialization of the conformational forms of CD22 according to the ligand isoforms.     

Fenofibrate,a peroxisome proliferator-activated receptor alpha activator,suppresses experimental autoimmune myocarditis by stimulating the interleukin-10 pathway in rats

Experimental autoimmune myocarditis (EAM) in rats is an animal model of human giant cell myocarditis and postmyocarditis dilated cardiomyopathy. As the heart consumes large amounts of energy, heart diseases such as myocarditis and dilated cardiomyopathy are associated with abnormal fatty acid metabolism. Peroxisome proliferator-activated receptor alpha (PPARalpha) is a regulator of the oxidative degradation of fatty acids. To investigate the role of PPARalpha in EAM, fenofibrate (a PPARalpha activator) was administered to rats with EAM for 4 weeks. Reductions in the ratios of both ventricular weight to body weight and the area of inflammatory lesions to the total area of heart sections were observed in fenofibrate-treated rats when compared with controls. Fenofibrate ameliorated changes in serum albumin and sialic acid, which are markers of inflammation. Cardiac expression of interleukin-10 (IL-10) mRNA was more pronounced in the fenofibrate group than in the control group (1.3 +/- 0.2 vs 0.7 +/- 0.1; p < 0.01), and the area of intact myocardium correlated with the IL-10 mRNA level (p = 0.0297, r = 0.620). We suggest that PPARalpha activators may prevent the progression of myocarditis through increased expression of the gene encoding the anti-inflammatory cytokine IL-10, although the mechanisms involved remain to be determined.     

Electron microscopic identification of histidine decarboxylase-containing endocrine cells of the rat gastric mucosa. An immunohistochemical analysis

The localization of histidine decarboxylase-like immunoreactive structures in the mucosal cells of the rat stomach was studied by the peroxidase-antiperoxidase method. At the light microscopic level, histidine decarboxylase-like immunoreactivity-containing cells were concentrated in the basal part of the oxyntic region, whereas in other areas no immunoreactive cells were seen. Ultrastructural study showed that reaction end products were diffusely distributed within the cytoplasm of the enterochromaffinlike cells but other cell types such as A cells, G cells, and enterochromaffin cells were not labeled. These findings suggest that enterochromaffinlike cells synthesize histamine.