Pseudotype hepatitis C virus enters immature myeloid dendritic cells through the interaction with lectin

Dendritic cells (DC) are the most potent antigen-presenting cells that regulate immune responses. One of the mechanisms for hepatitis C virus (HCV) persistence is the ability of HCV to suppress DC function. Direct HCV infection to blood DC has been implicated for DC dysfunction. To clarify the susceptibility of each DC subset to HCV, we used pseudotype vesicular stomatitis virus (VSV) coated with chimeric HCV envelope glycoproteins (E1 and E2). We demonstrate that pseudotype VSV enters myeloid DC (MDC) but not plasmacytoid DC (PDC). The highest efficiency of pseudotype VSV entry to MDC was observed when MDC were cultured with GM-CSF. Such efficiency decreased when MDC are matured with the treatment of IL-4, CpG oligodeoxynucleotide, or CD40 ligand. Mannan inhibited pseudotype VSV entry to MDC, but Ca(2+) chelators failed to do so. These results show that pseudotype VSV possessing HCV-E1 and E2 enters immature MDC through the interaction with lectins in a Ca(2+)-independent manner.     

Role of ventricular assist devices in the German heart allocation system

The Eurotransplant (ET) allocation algorithm, newly implemented in 2000, gives priority for heart transplantation (HTx) to patients with high urgency (HU) status, but now this status is rescinded upon ventricular assist device (VAD) implantation and only regained if severe complications occur during mechanical circulatory support (MCS). We studied the effects of this change on the patients in our institute who were waiting for HTx with MCS. The median duration of MCS until HTx in adult patients gradually increased from 3.1 months in 1994, reaching a peak of 16.7 months in 2000, and then gradually decreased to 6.0 months in 2003. Among the patients with VAD implantation as a bridge to HTx, two patients were on MCS for more than 1 year (the longest duration of MCS being 1.6 years) at the end of 1999, and this figure increased to nine patients and a maximum MCS duration of 3.7 years at the end of 2003. These data imply that the patients in whom a complication occurred in the early phase of MCS and who had overcome this complication underwent HTx early with HU status, and those who were stable during MCS waited a long time for HTx. Furthermore, the number of patients in the latter group is increasing. The new allocation algorithm imposes on patients with MCS waiting for HTx who are relatively young and free from complications and serious coexisting disease, very long-term MCS without an end to VAD bridging, which is almost equivalent to destination therapy. Part of this paper was presented at the 42nd JSAO Conference (Tokyo, October 5–7, 2004)     

Three-dimensional imaging of mitral and tricuspid annuli for total artificial heart implantation

The establishment of a method to clarify the three-dimensional interrelations among the mitral annulus, tricuspid annulus, ascending aorta, and main pulmonary artery, which constitute the interface between the human and total artificial heart (TAH), is essential to the design of the TAH. In a previous study based on transverse magnetic resonance (MR) images of a live human heart, reconstructed images of mitral and tricuspid annuli were found to be deformed. The present study of cadaver and beating hearts revealed that the optimal conditions for atrioventricular annular reconstruction of a beating heart with electrocardiogram-gated MR imaging include use of four-chamber imaging, 5 mm slice thickness, and a slice interval ranging from 5 to 7 mm. Under these conditions, the mitral and tricuspid annuli of 3 beating hearts were reconstructed successfully. It was recognized that during the systolic phase the mitral and tricuspid annuli move anteriorly, leftward and downward, and that in late systole the right lateral margin of the tricuspid annulus is close to the sternum.     

Differential sleep-promoting effects of five sleep substances nocturnally infused in unrestrained rats.

Sleep-inducing and sleep-maintaining effects of five different putative sleep substances were compared by the same nocturnal 10-hr intracerebroventricular infusion technique in otherwise saline-infused, freely moving male rats. Delta-sleep-inducing peptide (2.5 nmol), which induces electroencephalogram delta (slow)-wave patterns, was rapidly effective in increasing both slow-wave sleep and paradoxical sleep but the effects were not long-lasting. Muramyl dipeptide (2 nmol) induced excessive slow-wave sleep in the middle of the infusion period, accompanying a simultaneous elevation of brain temperature. However, paradoxical sleep was not affected. Component B of sleep-promoting substance (2 brainstem equivalents), a partially purified extract from rats deprived of sleep for 24-hr, was markedly effective in inducing and maintaining both kinds of sleep. Prostaglandin D2 (0.36 nmol) was more effective in enhancing sleep at the later period of the infusion period. Uridine (10 pmol) caused a mild but long-lasting increase in sleep, especially in paradoxical sleep. Thus, each substance exhibited compound-specific sleep-modulating properties.     

Oenothein B,dimeric hydrolysable tannin inhibiting HCV invasion from Oenothera erythrosepala

The envelope proteins of the hepatitis C virus (HCV), E1 and E2, have been revealed to be essential for invasion of HCV. Thus, we were engaged in the search for the inhibitors against HCV invasion through the assay system using the model virus expressing recombinant HCV envelopes, E1 and E2. Now, we disclosed dimeric hydrolysable tannin oenothein B (1) from MeOH extract of Oenothera erythrosepala as an active principle for inhibition of HCV invasion and its potency was almost the same as that of monomeric hydrolysable tannin, tellimagrandin I (2). Furthermore, by use of stereoselectively prepared 1-β- and 1-α-O-methyl tellimagrandin Is (4 and 5), the introduction of methyl moiety into 1-hydroxy group of 2 was clarified to result in slightly reduction of activity and β-isomer was revealed to exhibit a little stronger activity than α-one.

     

Pharmacokinetics of ivermectin applied topically by whole‐body bathing method in healthy volunteers

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a “whole‐body bathing method (WBBM)”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole‐body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole‐body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.     

Completely Laparoscopic Total Colectomy for Chronic Constipation: Report of a Case

Laparoscopic surgery has had a remarkable impact on the practice of colorectal surgery. However, most operations are performed using a technique of laparoscopic assistance, whereby extracorporeal bowel division and anastomosis are made following laparoscopic mobilization of the bowel. To our knowledge, this is the first report to describe a case of chronic constipation managed by total colectomy with ileorectal anastomosis, performed completely laparoscopically. The diagnosis of slow transit constipation was made by a transit time study. After dissection of the entire colon, the colon to be resected was delivered through the open rectal stump and brought out transanally. The anvil of an intraluminal circular stapler was passed through the rectum into the peritoneal cavity and the end of the open distal rectum was closed with a linear cutting stapler. The anvil of the circular stapler was inserted into the end of the open terminal ileum and fixed with an Endo-Loop, following which an intracorporeal double-stapling anastomosis was performed. By 3 months following surgery, the patient was passing 3–4 stools a day. Thus, we highly recommend this technique as it eliminates the need for a small incision to deliver the resected colon, thereby minimizing the operative time and risk of wound infection. Received: August 23, 2001 / Accepted: January 8, 2002     

The potent role of graft-derived NKR-P1+TCRalphabeta+ T (NKT) cells in the spontaneous acceptance of rat liver allografts

BACKGROUND: The mechanism involved in the spontaneous acceptance of liver allografts in some rat strain combinations remains unclear. Immunoregulatory NKR-P1TCRalphabetaT (NKT) cells primarily produce IL-4 and IFN-gamma, and enhance the polarization of immune responses to Th2 and Th1, respectively. The aim of this study was to clarify the role of graft-derived NKT cells in inducing the spontaneous acceptance of rat orthotopic liver transplantation (OLTx) METHODS: The experimental groups were divided as follows: Group 1, BN to LEW "low responder (acceptor)" combination; Group 2, DA to LEW "high responder (rejector)" combination; na?ve BN (Group 3) or LEW recipients (Group 4) with liver allografts from irradiated BN donors. The recipients had liver allografts from irradiated donors reconstituted from the following cell populations 24 hr before harvesting, spleen cells (SPCs, Group 5), IgSPCs (Group 6), IgNKR-P1SPCs (Group 7), and IgTCRabSPCs (Group 8) RESULTS: In Group 1, the percent of graft-derived NKT cells harvested on day 7 posttransplant were significantly higher than in Group 2. In the case of BN liver allografts that had been irradiated and reconstituted with cell populations including NKT cells (Groups 5 and 6), the mean graft survival (MST) was extended to 39.2+/-5.7 and 38.8+/-8.0 days, respectively. In contrast, when NKT cells were excluded (Groups 7 and 8), the grafts were acutely rejected within MST of 17.8+/-4.0 and 18.8+/-7.7 days, respectively. The concentrations of IL-10 and TGF-beta, but not IL-4 in IgGICs culture supernatants were predominant in the acceptor, whereas those with IFN-gamma predominated in the rejector. CONCLUSIONS: Graft-derived NKT cells might be responsible for spontaneous acceptance in the rat OLTx.     

Surgically repaired bilateral giant bullae after long-time follow-up; report of a case

A 44-year-old male was admitted to our hospital owing to severe dyspnea of sudden onset. Chest X-ray disclosed bilateral giant bullae. His pulmonary function was severely depressed. VC (%) was 2.61 l (66.3%) and FEV1% (%) was 1.47 l (64.5%). Indication of surgical repair of giant bullae are; space occupying lesion more than 25-50% in 1 thorax, progressive dyspnea, enlargement over time irrespective of symptoms, and expectation that re-expand the normal lung. He was conducted two-staged bullectomy using video-assisted thoracoscopic surgery (VATS) with small incisions. First operation was performed to left lung. Pulmonary function improved. VC (%) increased 3.02 l (76.8%) and FEV1% (%) 2.36 l (76.6%). After second operation, which was performed to right lung, VC (%) was 2.40 l (60.5%) and FEV1% (%) was 2.21 l (92.1%). Hugh-Jones grade improved class IV to class I. Postoperative course was uneventful and he was discharged 15 days after second operation. Two-staged bullectomy was appropriate in this case, because he might have suffered from re-expansion pulmonary edema after first surgery. The extent of recovery of pulmonary function was unpredictable. And performing right lung bullectomy just after the left bullectomy may be dangerous, because the patient have to receive anesthesia with his resected left lung. There is some possibility that patient who has bilateral giant bullae shows severe dyspnea during the progress, care should be taken to conduct operation as soon as possible.