Unique characteristics of community-onset healthcare- associated bloodstream infections: a multi-centre prospective surveillance study of bloodstream infections in Japan.

BACKGROUND: Analysis of bloodstream infections (BSIs) is valuable for their diagnosis, treatment and prevention. However, limited data are available in Japan. AIM: To investigate the characteristics of patients with bacteraemia in Japan. METHODS: This study was conducted in five hospitals from October 2012 to September 2013. Clinical, demographic, microbiological and outcome data for all blood-culture-positive cases were analysed. FINDINGS: In total, 3206 cases of BSI were analysed: 551 community-onset healthcare-associated (CHA)-BSIs, 1891 hospital-acquired (HA)-BSIs and 764 community-acquired (CA)-BSIs. The seven- and 30-day mortality rates were higher in patients with CHA- and HA-BSIs than in patients with CA-BSIs. The odds ratios (ORs) for seven-day mortality were 2.56 [95% confidence interval (CI) 1.48-4.41] and 2.63 (95% CI 1.64-4.19) for CHA- and HA-BSIs, respectively. The ORs for 30-day mortality were 2.41 (95% CI 1.63-3.57) and 3.31 (95% CI 2.39-4.59) for CHA- and HA-BSIs, respectively. There were 499 cases (15.2%) of central-line-associated BSI and 163 cases (5.0%) of peripheral-line-associated BSI. Major pathogens included coagulase-negative staphylococci (N = 736, 23.0%), Escherichia coli (N = 581, 18.1%), Staphylococcus aureus (N = 294, 9.2%) and Klebsiella pneumoniae (N = 263, 8.2%). E. coli exhibited a higher 30-day mortality rate among patients with HA-BSIs (22.3%) compared with patients with CHA-BSIs (12.3%) and CA-BSIs (3.4%). K. pneumoniae exhibited higher 30-day mortality rates in patients with HA-BSIs (22.0%) and CHA-BSIs (22.7%) compared with patients with CA-BSIs (7.8%). CONCLUSION: CHA- and HA-BSIs had higher mortality rates than CA-BSIs. The prognoses of E. coli- and K. pneumonia-related BSIs differed according to the category of bacteraemia.

Impact of bacterial contamination of the abdominal cavity during pancreaticoduodenectomy on surgical-site infection.

BACKGROUND: Several risk factors for complications after pancreaticoduodenectomy have been reported. However, the impact of intraoperative bacterial contamination on surgical outcome after pancreaticoduodenectomy has not been examined in depth. METHODS: This retrospective study included patients who underwent pancreaticoduodenectomy and peritoneal lavage using 7000 ml saline between July 2012 and May 2014. The lavage fluid was subjected to bacterial culture examination. The influence of a positive bacterial culture on surgical-site infection (SSI) and postoperative course was evaluated. Risk factors for positive bacterial cultures were also evaluated. RESULTS: Forty-six (21.1 per cent) of 218 enrolled patients had a positive bacterial culture of the lavage fluid. Incisional SSI developed in 26 (57 per cent) of these 46 patients and in 13 (7.6 per cent) of 172 patients with a negative lavage culture (P < 0.001). Organ/space SSI developed in 32 patients with a positive lavage culture (70 per cent) and in 43 of those with a negative culture (25.0 per cent) (P < 0.001). Grade B/C pancreatic fistula was observed in 22 (48 per cent) and 48 (27.9 per cent) respectively of patients with positive and negative lavage cultures (P = 0.010). Postoperative hospital stay was longer in patients with a positive lavage culture (28 days versus 21 days in patients with a negative culture; P = 0.028). Multivariable analysis revealed that internal biliary drainage, combined colectomy and a longer duration of surgery were significant risk factors for positive bacterial culture of the lavage fluid. CONCLUSION: Intraoperative bacterial contamination has an adverse impact on the development of SSI and grade B/C pancreatic fistula following pancreaticoduodenectomy.

Results of a national survey on laparoscopic bariatric surgery in Japan, 2000-2009.

INTRODUCTION: In Japan, laparoscopic bariatric surgery has not been popular until recently because morbidly obese patients were infrequently encountered previous and Japanese health insurance does not cover this type of surgery. In 2010, the Japan Research Society for Endoscopic and Laparoscopic Treatments of Obesity undertook the first nationwide survey on laparoscopic bariatric surgery to evaluate its current status and outcomes. METHODS: A mail survey was sent to the society's 64 member institutions, which included almost all institutions in Japan actively performing laparoscopic gastrointestinal surgery. RESULTS: From 2000 to 2009, 340 laparoscopic bariatric procedures, in total, were performed in nine of the 64 institutions (14%). The most popular procedure was laparoscopic Roux-en-Y gastric bypass (LRYGB, n=147), second was laparoscopic sleeve gastrectomy (LSG, n=102), and third was laparoscopic adjustable gastric banding (LAGB, n=55). However, the number of LRYGB procedures has decreased while the number of LSG procedures has rapidly increased. Total morbidity rates were 12.2% for LRYGB, 10.9% for LAGB, and 7.8% for LSG. Percent excess weight loss was 78% at 5 years after LRYGB, 52% at 4 years after LAGB, and 68% at 2 years after LSG. Although the bariatric procedures frequently resolved or improved obesity-related comorbidities, LRYGB appears to be superior to LAGB, as was previously reported. CONCLUSION: The first nationwide survey of laparoscopic bariatric surgery in Japan clearly showed the current status and outcomes of this group of procedures. The Japanese results appear to be comparable to similarly undertaken surveys in Europe and the USA.

Mechanism by which a novel non-thiazolidinedione peroxisome proliferator-activated receptor gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats.

AIM: The aim of this study was to examine the mechanism by which a novel non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR) gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats. METHODS: FK614 (1, 3.2 or 10 mg/kg) and a TZD PPARgamma agonist, pioglitazone (1, 3.2 or 10 mg/kg), were orally administered to Zucker fatty rats (genetically obese and insulin resistant) once a day for 14 days, and an oral glucose tolerance test was performed. The expression levels of various genes in the white adipose tissue (WAT) of Zucker fatty rats treated with FK614 (3.2 mg/kg), pioglitazone (10 mg/kg) and another TZD PPARgamma agonist, rosiglitazone (3.2 mg/kg), were determined using a real-time reverse transcription-polymerase chain reaction method. Morphometric analysis of the WAT of Zucker fatty rats treated with FK614 (3.2 mg/kg) and pioglitazone (10 mg/kg) was performed. Glucose transport activity in the isolated soleus muscle of FK614-treated Zucker fatty rats was also investigated. RESULTS: FK614 and pioglitazone both improved glucose tolerance in Zucker fatty rats. FK614 significantly increased the expression levels of acyl CoA oxidase, a PPAR-responsive gene, and adipocyte fatty acid-binding protein (aP2), an adipocyte differentiation marker gene, in epididymal WAT. It also significantly decreased the level of gene expression of tumour necrosis factor-alpha, an insulin resistance-inducing factor in retroperitoneal WAT, as did pioglitazone and rosiglitazone. FK614 and pioglitazone both significantly increased the total number of adipocytes and decreased their average size in WAT, mainly by increasing the number of small adipocytes. Additionally, administration of FK614 to Zucker fatty rats enhanced insulin sensitivity for glucose uptake in the soleus muscle. CONCLUSION: This study suggests the possibility that FK614 induces adipocyte differentiation in Zucker fatty rats by stimulating PPARgammain vivo, thereby changing the character of WAT and improving insulin sensitivity throughout the body.

Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands: involvement of mast cells and dendritic cells.

BACKGROUND: It has been suggested that airway bacterial infections exacerbate allergic disorders, and bacterial components in the air affect allergic inflammation via Toll-like receptors expressed on mast cells and dendritic cells in the airway mucosa. OBJECTIVE: Peptidoglycan (PGN) is a major component of the bacterial cell wall. We investigated the effect of PGN on the effector phase of allergic inflammation, in comparison with the effect of CpG-oligodeoxynucleotides (CpG), which is known to be a Th1 adjuvant. METHODS: Ovalbumin (OVA)-sensitized mice were challenged intranasally with OVA alone or OVA together with PGN or CpG. Nasal allergic symptoms and eosinophilia were scored, and the OVA-specific cytokine response was examined in the cells of cervical lymph nodes and nasal mucosa. Bone marrow-derived mast cells (BMMCs) and dendritic cells (BMDCs) were stimulated with PGN or CpG in vitro, and the expression level of cytokines and chemokines was examined by RT-PCR. In addition, the expression level of chemokines was examined by RT-PCR in mast cells of OVA-sensitized mice challenged with OVA alone or OVA together with PGN or CpG. RESULTS: PGN exposure exacerbated the nasal allergic symptoms and eosinophilia, whereas CpG exposure suppressed them. In addition, PGN exposure increased the OVA-specific IL-4 response in the cells, whereas CpG exposure decreased it. On the other hand, there were no significant differences in the OVA-specific IFN-gamma response. PGN but not CpG induced the expression of thymus and activation-regulated chemokine (TARC) and macrophage/monocyte-derived chemokine (MDC) in both BMMCs and mast cells of mice sensitized and challenged with OVA. CpG but not PGN induced the expression of IFN-beta and interferon-inducible protein-10 (IP-10) in BMDCs, and histamine did not influence this effect. CONCLUSION: These results demonstrate that PGN exposure exacerbates allergic inflammation mainly via mast cells, whereas CpG exposure suppresses allergic inflammation mainly via dendritic cells.

Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice.

Listeriolysin O (LLO) derived from Listeria monocytogenes is highly capable of inducing interleukin (IL)-12, IL-18 and interferon (IFN)-gamma, and facilitates the generation of Th1 cells. We have recently shown that recombinant LLO (rLLO) inhibits generation of ovalbumin (OVA)-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells. In the present study, we investigated the effect of rLLO on the effector phase of Th2-dependent allergic rhinitis in BALB/c mice sensitized with OVA. In mice sensitized intraperitoneally and challenged intranasally with OVA, nasal allergic symptoms such as sneezing and nose-scratching were observed at a high frequency. A high titre of anti-OVA IgE antibody was detected in sera and a large number of eosinophils migrated into the nasal tissue. However, rLLO treatment during the intranasal challenge inhibited the allergic symptoms, production of anti-OVA IgE antibody and eosinophil infiltration. Though rLLO did not affect antigen-specific cytokine production from splenic CD4(+) T cells, rLLO significantly suppressed OVA-specific IL-4 and IL-5 production from nasal mononuclear cells. We further found that rLLO inhibited the recruitment of CD4(+) T cells in nasal mucosa, and diminished the transcription and cell surface expression of CCR4 on splenic CD4(+) T cells. Moreover, rLLO was able to inhibit the passive cutaneous anaphylaxis reaction mediated by anaphylactic antibodies (IgE and IgG(1)) and mast cells. Taken together, these data showed that rLLO suppresses the effector phase of allergic rhinitis by inhibition of Th2 cell recruitment to nasal mucosa and type I allergic reaction.

Listeriolysin O, a cytolysin derived from Listeria monocytogenes, inhibits generation of ovalbumin-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells.

Listeriolysin O (LLO), a cholesterol-dependent cytolysin derived from Listeria monocytogenes, is a potent inducer of interleukin (IL)-12, IL-18 and interferon (IFN)-gamma. We have shown that LLO facilitates development of T cells mediating protective immunity against L. monocytogenes through the induction of IFN-gamma production at an early stage. Based on this finding, it is postulated that LLO inhibits differentiation of Th2 cells and the Th2 immune response. By using a murine model of ovalbumin (OVA)-induced allergic rhinitis, we investigated whether LLO has an ability to modulate the Th2-type immune disorder. In mice sensitized intraperitoneally with ovalbumin (OVA)/alum and challenged intranasally with OVA, a large number of eosinophils migrated into the nasal tissue, and high titres of anti-OVA IgE and IgG(1) antibodies were detected in sera. However, LLO treatment during sensitization markedly inhibited the eosinophil infiltration and production of these anti-OVA antibodies. A large number of T cells from mice sensitized and challenged with OVA produced high level of IL-4 and IL-5 but not IFN-gamma after stimulation with OVA. In contrast, OVA-specific IFN-gamma-producing T cells were preferentially induced in mice treated with LLO at the time of sensitization. In the absence of LLO administration, the expression level of GATA-3 and SOCS-3 in CD4(+) T cells was enhanced after sensitization with OVA. LLO treatment resulted in a reduction of GATA-3 and SOCS-3 expressions but induced the transcription of T-bet instead. Taken together, these data show clearly that LLO is capable of inhibiting Th2 immune response by skewing differentiation of antigen-specific T cells into Th1 cells.

Insulin-like growth factor-I enhances choleretic action of FK506 in rats.

FK506 is an immunosuppressant for organ transplantation in the same clinical settings as cyclosporine (CsA). In the management of liver transplantation, FK506 has advantages over CsA, in terms of rejection and corticosteroid requirements. Recent clinical findings in liver transplant patients indicate that FK506, but not CsA, stimulates choleresis, suggesting that FK506 treatment may accelerate recovery from cholestatic dysfunction through its choleretic action. Recently, we demonstrated in rats that exogenous treatment with insulin-like growth factor I (IGF-I) results in an increase in bile flow and also that FK506 has the potential to increase hepatic production of IGF-I. However, circulating levels of IGF-I in FK506-treated rats were only 30% higher than in nontreated rats. In this study, we evaluated the combined effect of treatment with both IGF-I and FK506 on bile flow in rats to explore the possibility that combination treatment in liver transplant patients could enhance the choleretic action of FK506, benefiting the transplanted liver. Combination treatment of IGF-I with FK506 resulted in a potent and long-lasting increase in bile flow. Overall, this study demonstrated that IGF-I treatment enhanced the choleretic action of FK506, providing potential clinical utility for combination therapy using these two drugs, in treatment after liver transplantation.

Induction of bone loss by bile duct ligation in rats.

Metabolic bone loss is the most common complication of chronic liver disease. However, there is little information available about bone loss in rats with a ligated bile duct, a biliary-type of experimental cirrhosis model. Therefore, in this study, the effect of bile duct ligation (BDL) on bone mineral density (BMD) and plasma insulin-like growth factor-I (IGF-I) levels was examined in rats. Two weeks after BDL operation, the rats with a ligated bile duct showed a pronounced and significant decrease in both trabecular and cortical BMD of the femur. In these rats, decreases in food intake and plasma IGF-I levels plus elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin were also observed. When the effect of dietary restriction (30% or 50%) over 2 weeks was then investigated in normal rats, 50% food restriction resulted in a significant decrease in femoral trabecular bone density although BMD was unchanged by 30% dietary restriction. The plasma levels of IGF-I were also decreased in food-restricted rats. Thus, the decrease in femoral bone density in 50% food-restricted rats was less potent compared with BDL rats; nevertheless, the decrease in plasma levels of IGF-I was almost equally potent in both BDL and food-restricted rats. Overall, this study showed that BDL operation resulted in a pronounced bone loss in rats, but also that this bone loss might not be merely due to the decreases in food intake and plasma IGF-I levels. These results suggest that BDL in rats is a useful experimental cirrhosis model for evaluating the bone loss associated with chronic liver disease.

Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in experimental diabetic neuropathy of rat.

The effects of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow (NBF) were explored in streptozotocin-induced diabetic rats. Rats were maintained on a diet of containing 0.09% zenarestat for 8 weeks, then NBF in the sciatic nerve was measured using microelectrode hydrogen polarography. NBF in the diabetic control rats was significantly lower than values in age-matched control rats, however, NBF was not significantly altered in diabetic rats treated with zenarestat. Direct application of nitric oxide synthase inhibitor, NG-nitro-L-arginine, did not affect NBF in diabetic control rats, whereas this application significantly reduced NBF both in age-matched control and zenarestat treated diabetic rats. Considerable levels of zenarestat were confirmed in the sciatic nerve in the drug treated rats. These data suggest that aldose reductase, such as zenarestat, might restore or prevent the alteration of endoneurial blood flow resulting from an impairment of nitric oxide function.

Difference in cholesterol-binding and cytolytic activities between listeriolysin O and seeligeriolysin O: a possible role of alanine residue in tryptophan-rich undecapeptide.

We have constructed recombinant listeriolysin O (rLLO) and seeligeriolysin O (rLSO) from Listeria monocytogenes and Listeria seeligeri, respectively. In hemolysis and cholesterol-binding assays, the specific activity of recombinant toxin was lower for LSO as compared to LLO. To understand the molecular basis of this difference, in particular with respect to the conserved Trp-rich undecapeptide, a naturally occurring Ala to Phe substitution in LSO was introduced into rLLO. The rLLO:A488F hemolysin exhibited a reduced activity in both hemolysis and cholesterol-binding. The reverse mutation, inserted into rLSO, also increased the hemolytic activity of this mutant LSO. These results suggested that the natural replacement of Ala to Phe is involved in the weak cytolytic activity of LSO.

Amelioration of insulin resistance in diabetic ob/ob mice by a new type of orally active insulin-mimetic vanadyl complex: bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) with VO(S(2)O(2)) coordination mode.

Recently, we have shown that a newly synthesized vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), VO(opt)(2), is a potent orally active insulin-mimetic in treating streptozotocin-induced diabetes in rats, with long-term action. In the present study, the anti-diabetic effect of VO(opt)(2) and its mechanism in ob/ob mice, an obese non-insulin-dependent diabetes mellitus (NIDDM) animal model, was investigated. In ob/ob mice, 15-day oral treatment with VO(opt)(2) resulted in a dose-dependent decrease in the levels of glucose, insulin and triglyceride in blood. VO(opt)(2) was also effective in ameliorating impaired glucose tolerance in ob/ob mice, when an oral glucose tolerance test was performed after treatment with VO(opt)(2). Tumor necrosis factor-alpha (TNF-alpha) is a key component of obesity-diabetes link, we therefore examined the attenuating effect of VO(opt)(2) on impaired insulin signal transduction induced by TNF-alpha. Elevated expression of TNF-alpha was observed in the epididymal and subcutaneous fat tissues of ob/ob mice. Incubation of 3T3-L1, mouse adipocytes, with TNF-alpha reduced the phosphorylation of insulin receptor substrate-1 (IRS-1), whereas VO(opt)(2) treatment resulted in an enhancement of IRS-1 phosphorylation, irrespective of the presence or absence of TNF-alpha. Overall, the present study demonstrates that VO(opt)(2) exerts an anti-diabetic effect in ob/ob mice by ameliorating impaired glucose tolerance, and furthermore, attenuates the TNF-alpha-induced decrease in IRS-1 phosphorylation in adipocytes. These results suggest that the anti-diabetic action of VO(opt)(2) is derived from an attenuation of a TNF-alpha induced impaired insulin signal transduction via inhibition of protein tyrosine phosphatase, providing a potential clinical utility for VO(opt)(2) in the treatment of NIDDM.

Intravenous injection of oligodeoxynucleotides to the NF-kappaB binding site inhibits hepatic metastasis of M5076 reticulosarcoma in mice.

We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo. In the present study, we employed decoy ODN targeting the transcription factor nuclear factor-kappaB (NF-kappaB) binding cis-elements to hepatic metastasis of murine reticulosarcoma M5076 in mice. Intravenous inoculation of M5076 into mice caused a marked increase in gene expression of interleukin-1beta, tumor necrosis factor-alpha and intercellular adhesion molecule-1 in the liver, whereas intravenous treatment with NF-kappaB decoy ODN reduced M5076-induced transactivation of these genes. Treatment with NF-kappaB decoy ODN, but not scrambled decoy ODN, significantly inhibited hepatic metastasis of M5076 in mice, and furthermore the combined treatment of NF-kappaB decoy ODN with an anti-cancer drug resulted in complete inhibition of hepatic metastasis in half of the mice, without affecting myelosuppression induced by the anti-cancer drug. Here, NF-kappaB decoy ODN inhibited hepatic metastasis of M5076 in mice possibly through a decrease in transactivation of important NF-kappaB-driven genes and also potentiated the anti-metastatic effect of an anti-cancer drug, demonstrating the first successful in vivo therapy for cancer metastasis using NF-kappaB decoy ODN as a novel molecular decoy approach.

The effects of zenarestat, an aldose reductase inhibitor, on minimal F-wave latency and nerve blood flow in streptozotocin-induced diabetic rats.

The effects of zenarestat, 3-(4-bromo-2-fluorobenzyl)-7-chloro-3,4-dihydro-2,4-dioxo-1(2H)-quinazolineacetic acid, an aldose reductase inhibitor (ARI), on F-wave conduction abnormalities, nerve blood flow (NBF) reduction and sorbitol accumulation were studied in streptozotocin-induced diabetic rats. Two weeks after the induction of diabetes, zenarestat was given once a day for two weeks. In diabetic control rats, marked accumulation of sorbitol, reduction of NBF and prolongation of minimal F-wave latency (FWL) were observed as compared to normal rats. Zenarestat, at a dose of 32 mg/kg, inhibited sorbitol concentration to nearly the normal rat level and significantly improved not only NBF but also minimal FWL. At a dose of 3.2 mg/kg, sorbitol accumulation was inhibited by approximately 40% and there was a tendency to increase in NBF; however, minimal FWL was not improved at all. These data suggest that a highly inhibition of the nerve sorbitol accumulation is requisite for the treatment of diabetic peripheral neuropathy.

Induction of choleresis by immunosuppressant FK506 through stimulation of insulin-like growth factor-I production in the liver of rats.

FK506 (Tacrolimus) is an effective immunosuppressant currently used worldwide in organ transplantation. Based on our recent findings that insulin-like growth factor-I (IGF-I) is important for the stimulation of choleresis in vivo, in this study we investigated the effect of FK506 on bile flow and the plasma and hepatic levels of IGF-I in rats. Intravenous treatment of rats with FK506 resulted in a significant increase in bile flow, whereas cyclosporin A induced a significant decrease. A significant increase in plasma levels of IGF-I was observed in rats 30 min after a single intravenous administration of FK506. Oral treatment of rats with FK506 for 1 week also resulted in an increase in both plasma and hepatic levels of IGF-I. Overall, this study showed that FK506 treatment increased bile flow and also induced an increase in the plasma and hepatic levels of IGF-I in rats, suggesting that a stimulation of hepatic IGF-I production by FK506 may contribute to its choleretic profile.

Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry.

The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.

[Indications for surgery for morbid obesity and effectiveness of bariatric surgery].

In this paper we describe a history and technical aspects of bariatric surgery. And surgical techniques of Divided Vertical Banded Gastroplasty and perioperative management are presented. Our indications for surgery for morbid obesity are almost equal to the guidelines for obesity surgery adopted by the American Society for Bariatric Surgery October 1986. From 1982 to 2000, 64 bariatric surgical procedures were performed at the author's institution. Vertical banded gastroplasty was performed in 45 patients, Horizontal gastric partitioning in 8 patients, Gastric bypass in 10 patients, and Divided vertical banded gastroplasty in 1 patient. The average weight loss one year after Vertical banded gastroplasty is 1/3 of the patient weight. Most of the preexisting comorbid conditions related to the obesity showed improvement or were completely resolved after surgery. No major complications were observed postoperatively. We concluded that surgical procedures for morbid obesity are very effective therapy.

Essential role of domain 4 of pneumolysin from Streptococcus pneumoniae in cytolytic activity as determined by truncated proteins.

Pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae, is one of the members of thiol-activated cytolysins (TACYs) consisting of four domains. TACYs commonly bind to membrane cholesterol and oligomerize to form transmembrane pore. We have constructed full-length and various truncated PLYs to study the role of domains of PLY in the cytolytic activity. Full-length PLY had binding ability to both cell membrane and immobilized cholesterol. A truncated PLY which comprised only domain 4 molecule, the C-terminal domain of PLY, sustained the binding ability to cell membrane and cholesterol, whereas domain 1-3 molecule had no binding ability to them. Furthermore, the domain 4 molecule inhibited both the membrane binding and the hemolytic activity of full-length PLY. Accordingly, the present results provided the direct evidence that domain 4 was essential for the initial binding to membrane cholesterol and the interaction led to the subsequent membrane damage process.

The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats.

We studied the effects of zenarestat, an aldose reductase inhibitor (ARI), on peripheral neuropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. ZDF rats and their lean rats counterparts were fed a sucrose-containing diet, and zenarestat was given orally once a day for 8 weeks. Motor nerve conduction velocity (MNCV), F-wave minimal latency (FML), and sorbitol concentrations in the sciatic nerve were measured. In ZDF control rats, a remarkable accumulation of sorbitol, a delay in FML, and a slowing of MNCV were observed compared with lean rats. At a dose of 3.2 mg/kg, zenarestat had no significant effect on the delay in FML and the slowing of MNCV, although the sorbitol accumulation in the sciatic nerve was partially inhibited in ZDF rats. On the other hand, 32 mg/kg zenarestat treatment improved these nerve dysfunctions in ZDF rats, along with a reduction of nerve sorbitol accumulation almost to the level of lean rats. These data showed that zenarestat improved diabetic peripheral neuropathy in ZDF rats, a type 2 diabetes model, providing evidence for the therapeutic potential of zenarestat for the treatment of diabetic neuropathy.