Antiviral Activity of Innate Immune Protein ISG15

The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part, as a modifier of protein function. Evidence implicating ISG15 as an innate immune protein with broad-spectrum antiviral activity continues to accumulate rapidly. This review will summarize recent findings on the innate antiviral activity of ISG15, with a focus on the interplay between ubiquitination and ISGylation pathways resulting in modulation of RNA virus assembly/budding. Indeed, ubiquitination is known to be proviral for some RNA viruses, whereas the parallel ISGylation pathway is known to be antiviral. A better understanding of the antiviral activities of ISG15 will enhance our fundamental knowledge of host innate responses to viral pathogens and may provide insight useful for the development of novel therapeutic approaches designed to enhance the immune response against such pathogens

Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-sensitive idiopathic left ventricular tachycardia

AbstractOBJECTIVESWe characterized pharmacologically the slow conduction zone of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) with regard to the late diastolic potential (LDP).BACKGROUNDWe showed that the slow conduction zone of ILVT could be divided into two components by LDP; that is, the distal component with a tachycardia-dependent conduction delay property and the proximal one without it.METHODSElectrophysiologic studies were performed in eight consecutive patients. The LDP was recorded during left ventricular (LV) mapping during ILVT. Entrainment was performed from the right ventricular outflow tract while recording LDP. The effects of lidocaine (1 mg/kg body weight) and verapamil (0.5 or 1.0 mg) were examined during entrainment.RESULTSThe LDPs preceding the Purkinje potential (PP) were serially recorded from the upper third to the middle of the LV septum along the narrow longitudinal line. The ventricular tachycardia (VT) cycle length increased after lidocaine (p < 0.05), and further after verapamil (p < 0.05). The increments in the VT cycle length after administration of the drugs strongly correlated with those in LDP-PP (r > 0.9 for both drugs). The interval from the ventricular potential to LDP was unchanged after administration of the drugs. In one patient, verapamil terminated VT by local conduction block between LDP and PP. The LDP-PP measured during entrainment increased after lidocaine, and further after verapamil, whereas the interval from the stimulus to LDP remained unchanged.CONCLUSIONSThe component distal to LDP is mainly calcium channel-dependent and partly depressed sodium channel-dependent. The proximal component is considered to be sodium channel-dependent (normal)

THE INCIDENCE OF PEPTIC ULCER SURGERY BEFORE AND AFTER THE INTRODUCTION OF H2-RECEPTOR ANTAGONISTS

Since the introduction of H2-receptor antagonists, the incidence of ulcer surgery has decreased markedly. Based on the number of patients who underwent ulcer surgery and upper gastrointestinal endoscopy in our hospital, the number of operations for peptic ulcer disease has decreased, although the number of peptic ulcer patients diagnosed by endoscopy has increased after the introduction of cimetidine (the first H2-receptor antagonist in Japan). The decreasing rate of surgical therapy before and after the administration of H2-receptor antagonists was 49.1%. The number of emergency operations has also decreased among ulcer patients diagnosed by endoscopy although the number of perforated and bleeding ulcer patients has increased. It is also reported that the most common operative procedure for both gastric and duodenal ulcer was distal gastrectomy reconstructed by gastroduodenostomy (Billroth Ⅰ)

Intra-Day Variation of Sagittarius A* at Short Millimeter Wavelengths

We have performed the monitoring observations of flux density of Sagittarius A* at short millimeter wavelengths (100 and 140 GHz bands) on seven years in the period from 1996 to 2003 using the Nobeyama Millimeter Array (NMA). We found intra-day variation of Sgr A* in March 2000 flare. The flux density at the peak of the flares increases 100-200 % at 100 GHz and 200-400 % at 140 GHz ($?Delta S/S$), respectively. The two-fold increase timescale of the flare is estimated to be about 1.5 hours at 140 GHz. The intra-day variation at mm-wavelengths has similar increase timescale as those in the X-ray and infrared flares but has smaller amplitude. This short timescale variability suggests that the physical size of the emitting region is smaller than 12 AU $?approx$ 150 Rs). The decay timescale of the flare was at most 24 hours. Such a light curve with rapid increase and slow decay is similar to that often observed in outburst phenomena with ejections.Comment: 13 pages, 3 figures, Accepted for publication in ApJ