Differential involvement of GABA system in mediating behavioral and neurochemical effect of acupuncture in ethanol-withdrawn rats

In our previous study we demonstrated that acupuncture at Shenmen (HT7) points suppressed a decrease of accumbal dopamine (DA) release in ethanol-withdrawn rats. Furthermore, here we found that it inhibited behavioral withdrawal signs of ethanol. In an effort to better understand the mechanisms underlying this inhibition, the potential role of GABA receptor system in acupuncture was investigated. Male Sprague–Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 48 or 72 h of ethanol withdrawal, acupuncture was applied at bilateral HT7 for 1 min. The selective GABA_A antagonist bicuculline and the selective GABA_B antagonist SCH 50911 were injected intraperitoneally 20 min before acupuncture, respectively. Importantly, suppressive effects of acupuncture on DA deficiency were completely abolished by SCH 50911, but not by bicuculline, whereas ameliorating effects of acupuncture on ethanol withdrawal syndrome were completely blocked either by SCH 50911 or bicuculline. These results suggest that acupuncture at specific acupoint HT7 may normalize the DA release in the mesolimbic system and attenuate withdrawal syndrome through the GABA_B receptor system in ethanol-withdrawn rats.     

Characterization of Immunodominant Linear B-Cell Epitopes on the Carboxy Terminus of the Rinderpest Virus Nucleocapsid Protein

The nucleocapsid (N) protein of rinderpest virus (RPV) is one of the most abundant and immunogenic viral proteins expressed during natural or experimental infection. To identify immunogenic epitopes on the N protein, different forms of RPV N protein, including the full-length protein (N_1-525), an amino-terminal construct (N_1-179), and a carboxy-terminal construct (N_414-496), were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins. The antigenicity of each recombinant protein was evaluated by Western immunoblotting. All recombinants were recognized by hyperimmune RPV bovine antisera, indicating that immunoreactive epitopes may be present at both ends of the N protein. However, GST-N_414-496 was much more antigenic than GST-N_1-179 when tested with sera from vaccinated cattle, suggesting that an immunodominant or highly immunogenic epitope(s) may be located at the carboxy terminus of the N protein. Epitope mapping with overlapping peptides representing different regions of the carboxy terminus (amino acids 415 to 524) revealed three nonoverlapping antigenic sites in regions containing the residues ⁴⁴⁰VPQVRKETRASSR⁴⁵² (site 1), ⁴⁷⁹PEADTDPL⁴⁸⁶ (site 2), and ⁵²⁰DKDLL⁵²⁴ (site 3). Among these, antigenic site 2 showed the strongest reactivity with hyperimmune anti-RPV bovine sera in a peptide enzyme-linked immunosorbent assay but did not react with hyperimmune caprine sera raised against peste-des-petits-ruminants virus, which is antigenically closely related to RPV. Identification of an immunodominant linear antigenic site at the carboxy terminus of the N protein may provide an antigen basis for designing diagnostics specific for RPV.     

Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation

A dramatic form of experience-dependent synaptic plasticity is revealed in visual cortex when one eye is temporarily deprived of vision during early postnatal life. Monocular deprivation (MD) alters synaptic transmission such that cortical neurons cease to respond to stimulation of the deprived eye, but how this occurs is poorly understood. Here we show in rat visual cortex that brief MD sets in motion the same molecular and functional changes as the experimental model of homosynaptic long-term depression (LTD), and that prior synaptic depression by MD occludes subsequent induction of LTD. The mechanisms of LTD, about which there is now a detailed understanding, therefore contribute to visual cortical plasticity.     

Mast cell–derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

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Protective effect of retinoic acid on interleukin-1 beta-induced cytotoxicity of pancreatic beta-cells

Cytokines produced by immune cells in pancreatic islets infiltrating are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In this study, the effects of retinoic acid (RA) on cytokine-induced beta-cell dysfunction were examined. RA significantly protected interleukin-1 beta (IL-1) and interferon-gamma (IFN-gamma)-mediated cytotoxicity of rat insulinoma cell (RINm5F), and also reduced in IL-1 and IFN-gamma-induced nitric oxide (NO) production, which correlated well with reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein. The molecular mechanism, by which RA inhibited iNOS gene expression, appeared to involve the inhibition of NF-kappa B activation. Our results suggest possible therapeutic value of RA for the prevention of diabetes mellitus progression.     

Debate on annual influenza vaccination in healthcare workers for the same subtype under the vaccine shortage.

BACKGROUND: Influenza vaccination is the primary method for preventing influenza and its severe complications. Healthcare workers (HCWs) are one of the priority groups for the influenza vaccination. OBJECTIVES: To determine whether healthy HCWs, who were vaccinated with the same subtype for the two previous years, could be given less priority for influenza immunization under the vaccine shortage. STUDY DESIGN: We measured hemagglutination-inhibition antibody titers from sequential serum samples in 50 pre-immune subjects and 50 age-matched vaccine-naive subjects: immediately prior to the administration of the vaccine, 4-6 weeks, and 6 months after the vaccination. RESULTS: Prevaccination titers were maintained above protective level and high protection rates were observed for all three strains in pre-immune subjects: A/H1N1, A/H3N2, and B strains. As for the sequential changes, the protection rates for all three strains still remained above 70% until 6 months following the vaccination. CONCLUSION: Skipping influenza vaccination for a year could be considered in healthy pre-immune HCWs under the epidemic of the same subtype as two previous years.     

Villous adenoma of the bile ducts: a case report and a review of the reported cases in Korea

Villous adenomas are benign epithelial lesions with malignant potential which can occur at any site in the gastrointestinal tract. They are usually encountered in the rectum and colon, less frequently in the small bowel and very rarely in the biliary trees. Nine cases of bile duct villous adenomas have been reported in the literature. However, 4 cases of bile duct villous adenomas have been reported in the Korean literature. Recently, we experienced a case of villous adenoma in the common hepatic duct in a 77-year-old man presenting with obstructive jaundice in which preoperative histologic diagnosis of villous adenoma played a critical role in managing this patient. Herein, we present a case report of bile duct villous adenoma and a review of the reported cases in Korea to help define and manage this rare disease entity in the bile ducts. In addition, confusing nomenclature of bile duct adenomas is discussed.     

Activation of Src tyrosine kinase in microglia in the rat hippocampus following transient forebrain ischemia

To better understand the pathophysiological role of Src protein, a non-receptor protein tyrosine kinase of 60kDa, in the ischemic brain, we investigated the time course and regional distribution of active Src expression by using a specific antibody against Tyr416 phosphorylated Src (phospho-Src) in the rat hippocampus after transient forebrain ischemia. In the hippocampus of the control animals, active Src expression was too low to be detected by immunolabeling. Beginning 4h after reperfusion, active Src expression became evident and, after 1 day, had increased preferentially in the CA field of the hippocampus proper and the dentate gyrus. By day 3, active Src expression markedly increased in the pyramidal cell layer of CA1 and the dentate hilar region in temporal correlation with neuronal cell death occurring in these areas, where cells typical of phagocytic microglia showed phospho-Src immunoreactivity. Double-labeling experiments revealed that cells expressing active Src were microglia that stained for biotinylated lectin derived from Griffonia simplicifolia (GSI-B4). Active Src expression began to decline at day 7 and returned to the basal level by day 14 after reperfusion. These results demonstrate increased phosphorylation of Src in activated microglia of the post-ischemic hippocampus, indicating that Src signaling may be involved in the microglial reaction to an ischemic insult.     

PCR-RFLP based molecular typing of enteroviruses isolated from patients with aseptic meningitis in Korea

Summary.  We have evaluated PCR–RFLP as a practical method for rapid typing of enteroviruses causing aseptic meningitis in Korea. Through blind examination of 80 clinical isolates from patients with aseptic meningitis, we have compared the results of conventional serotyping with PCR–RFLP based genotyping, which was developed for this study. Among the 80 case isolates, which had been previously typed by routine neutralization test, only 42 cases (52.5%) were matched with typing by PCR–RFLP. The result clearly demonstrated that the enterovirus serotype does not coincide with the genotype. Therefore, the classification of enteroviruses by genotyping with PCR–RFLP, although rapid and simple, may be complicated by regional or seasonal differences. However, the PCR–RFLP method developed in this study is applicable to the epidemiological study of enteroviruses when regional or seasonal differences exist, and is useful in identifying the source of an infection. Received August 6, 2001; accepted April 15, 2002 Published online July 10, 2002     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.