Erratum: Intracellular amyloid ß oligomers impair organelle transport and induce dendritic spine loss in primary neurons.

The original version of this article unfortunately contained a mistake in the presentation of Fig. 1 in both the PDF and HTML versions of this manuscript [1]. In the right panel of the corrected Fig. 1d, the images of Mock cells, which were visualized with GFP and stained with Abeta oligomer-specific antibody 11A1, were replaced with those of APPWT cells, and instead the images of APPWT cells were replaced with those of Mock cells. These images had been incorrectly placed in the original Fig. 1. The correct version of Fig. 1 is presented below.

Immunological potential of cytotoxic T lymphocyte antigen 4 immunoglobulin in murine autoimmune cholangitis.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig) is an important regulator of T cell activation and a fusion protein directed at CD80 and CD86; it blocks co-stimulatory signalling and T cell activation. We have taken advantage of a murine model of human primary biliary cirrhosis (PBC), mice expressing a transforming growth factor (TGF)-ß receptor II dominant negative (dnTGF-ßRII) transgene to address the potential therapeutic efficacy of CTLA-4 Ig. To mimic patients with PBC at different stages or duration of disease, we treated mice with either CTLA-4 Ig or control IgG three times weekly from 3 to 12 or 24 weeks of age, or from 12 to 24 weeks of age. CTLA-4 Ig treatment from 3 weeks of age significantly reduced liver inflammation to 12 weeks of age. Treatment initiated at 12 weeks of age also ameliorated the autoimmune cholangitis at 24 weeks of age. However, in mice treated at 3 weeks of age, suppression of liver inflammation was not sustained and colitis was aggravated when treatment was extended to 24 weeks of age. Our data indicate that, in dnTGF-ßRII mice, CTLA-4 Ig treatment has short-term beneficial effects on autoimmune cholangitis, but the effect varies according to duration of treatment and the time in which therapy was initiated. Further dissection of the events that lead to the reduction in therapeutic effectiveness of CTLA-4 Ig will be critical to determining whether such efforts can be applied to human PBC.

Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg ) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8(+) T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-ßRII) mice to recombination-activating gene (Rag)1(-/-) recipients. We then used this robust established adoptive transfer system and co-transferred CD8(+) T cells from dnTGF-ßRII mice with either C57BL/6 or dnTGF-ßRII forkhead box protein 3 (FoxP3(+) ) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-ßRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-ßRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-ßRII mice. Our data reflect the therapeutic potential of wild-type CD4(+) FoxP3(+) Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC.

Sexual dimorphism in scales of marbled flounder Pseudopleuronectes yokohamae (Pleuronectiformes: Pleuronectidae), with comments on the relevance to their spawning behaviour.

Variation of scales on the blind side of Pseudopleuronectes yokohamae in relation to sex, maturity and body size was examined. Immature males often have cycloid scales, while mature males have mostly ctenoid scales. Large females also often have ctenoid scales (but with fewer spines compared with males), and small females have mostly cycloid scales. The number of spines (ctenii) on the blind-side scale increases with body size in both sexes, indicating an ontogenetic change in scale morphology. As P. yokohamae spawn demersal eggs with males positioning themselves above the females on the ocular side, it is hypothesized that ctenoid scales on the blind side in mature males function for maintaining contact with females during spawning.

Seasonal and ontogenetic diet shift in juvenile stone flounder Platichthys bicoloratus.

The diet of juvenile (0 year old) stone flounder Platichthys bicoloratus after settlement was investigated in an estuarine habitat. The principal prey items included harpacticoids and palps of polychaetes in February and March and thereafter shifted to siphons of the bivalve Nuttallia olivacea from April to June. This seasonal change in diet occurred irrespective of body size, suggesting that other factors, such as morphological development of the predator or vulnerability of prey, induced the diet shift.

Immune responses to porphyromonas gingivalis infection suppress systemic inflammatory response in experimental murine model.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), and the severity correlates to significance of immune responses. Recently, it has been reported that periodontitis is associated with the development of systemic disease such as diabetes and atherosclerosis because of increasing invasion of oral pathogens to the circulation. However, the association between local and systemic infectious responses is still unclear. In the present study, we examined the differences of biological responses in animals with or without bacterial infection. After Balb/c mice were infected subcutaneously with live P. gingivalis W83, serum, skin and liver were collected according to experimental protocol. The skin and liver tissues were observed pathologically by haematoxylin-eosin staining, and serum IL-6 levels were measured using ELISA method. Throughout the experimental period, conditions of the mice were observed continuously. As expected, severe infiltration of leukocytes were observed at inflamed skin corresponding to the number of bacterial challenges. Although no inflammatory appearance of skin was observed, serum IL-6 levels were increased dramatically (P <0.01, Student's t-test) and liver tissues were injured in the mice without bacterial challenge. Interestingly, although severe inflammatory appearance of the skin was observed, serum IL-6 levels were not increased and no inflammatory responses were observed in the liver of the 3-times bacterially challenged group. Importantly, immunoglobulin G against P. gingivalis W83 was detected in the blood of mice with 3-times bacterial challenge corresponding to improvement of weight loss and survival. In conclusion, although multiple infections develop severe localized inflammation, the immune system should be sufficient to protect the systemic inflammatory responses.

Post-release feeding and growth of hatchery-reared Japanese flounder Paralichthys olivaceus: relevance to stocking effectiveness.

The feeding and growth of hatchery-reared (HR) Japanese flounder Paralichthys olivaceus of c. 100 mm total length (L(T) ) released off the coast of Fukushima, Japan, were investigated. From 2 to 15 days after release, the HR P. olivaceus frequently exhibited high empty-stomach frequency (>40%), low stomach-content mass (<1% of body mass), reduced somatic condition from release (c.-10%) and negligible growth. Thereafter, empty-stomach frequency decreased, the stomach-content mass of HR fish increased to 2-8% of body mass, the somatic condition recovered and growth rate increased to 0·5-1·5 mm day(-1) . Prey items were initially mysids, shifting thereafter to fishes such as the Japanese anchovy Engraulis japonica, as observed similarly in wild counterparts. The proportion of mysids decreased with time after release irrespective of size at release, indicating the importance of mysids for adaptation to natural food. Recapture rates at age 1 year, derived from fish market surveys, varied greatly among release years (4-11%). The variation in the recapture rates was largely accounted for by the post-release growth rates (r(2) = 0·5), suggesting a relationship between the post-release growth of HR fish and their survival and subsequent stocking effectiveness.

Heel movement in horses: comparison between glued and nailed horse shoes at different speeds.

REASONS FOR PERFORMING STUDY: It has been suggested that the heel of the horse's hoof expands in the stance phase and this reduces the concussion at impact and helps pump blood into the hoof. Therefore, farriers usually leave a gap in the heel region when using the traditional nailed shoe. Recently glued shoes which are attached firmly to the heel have been developed and these could restrict heel movement. OBJECTIVE: To compare the degree of mediolateral heel movement between glued and nailed shoes. METHODS: Seven Thoroughbreds were used. Either their fore- or hind hooves were shod with plain aluminium shoes, attached first with glue and later with nails. Measurements were collected continuously with a displacement sensor fixed between the medial and lateral hoof walls at the heel. The horses ran on a treadmill at a walk (1.8 m/s), trot (3.5 m/s), canter (8 m/s) and gallop (12 m/s). The mediolateral heel movement in a nonweightbearing position was set at zero for each hoof and thus positive and negative numbers represented expansion and contraction, respectively. Average values of 10 consecutive strides at each speed were compared between the 2 shoeing methods by paired t test. RESULTS: At all running speeds, the heels expanded in the first 70-80% of the stance phase and contracted at breakover. The total heel movement calculated as the sum of the maximum expansion and contraction value was less with glued shoeing than with nailed shoeing for walking (all limbs), trotting (all limbs), cantering (leading forelimb and both hindlimbs) and galloping (both hindlimbs). CONCLUSIONS: Glueing restricted heel movement, suggesting possible interference with shock absorption and blood pumping in the hoof. Further study is needed to evaluate the influence of glued shoeing on hoof mechanics.

Rapid fluctuation in infection levels of Neoheterobothrium hirame (Monogenea) in Japanese flounder Paralichthys olivaceus in the Joban area, Japan.

Neoheterobothrium hirame a haematophagous monogenean parasite on Japanese flounder Paralichthys olivaceus occurred at high prevalences (> 70%) from 1999 to 2002 but thereafter declined and remained low (< 20%) from 2003 to 2005 in the Joban area, Japan. In 2006, N. hirame became abundant again reaching a prevalence of 63%. Generalized linear models explained these rapid fluctuations in infection in relation to inshore water temperature, which affected the reproductive success of the parasite, and also the encounter rate between host and parasite through changes in their respective population densities. Severely anaemic fish were few, 2.4% even in 1999-2002 and 2006, suggesting that the effect of N. hirame infection on the P. olivaceus population was small in this area.

Post-release predation on hatchery-reared Japanese flounder Paralichthys olivaceus in the coast of Fukushima, Japan.

To determine the predators of 100 mm total length hatchery-reared juvenile Japanese flounder Paralichthys olivaceus, fishes and crabs were collected using gillnets and a small trawl net off the coast of Fukushima Prefecture, Japan. Predation on juvenile P. olivaceus by older conspecifics, the snailfish Liparis tanakai, ocellate spot skate Okamejei kenojei and the swimming crab Ovalipes punctatus, was detected based on analogical observation and molecular techniques. These predators are nocturnal feeders except for P. olivaceus. Liparis tanakai with body sizes large enough to consume juveniles only appeared in winter, whereas the large O. punctatus was abundant in early summer and in late autumn. Such seasonal variation in predator abundance indicates that the release season can be optimized for reducing predation mortality.

Pericryptal fibroblast sheath in intestinal metaplasia and gastric carcinoma.

BACKGROUND AND AIMS: In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype which is closely related to gastric carcinoma. However, to date, it has not been elucidated whether the intestinal metaplasia is merely a change in the epithelium or whether the underlying mesenchyme also changes from gastric type to intestinal type. We have investigated the relationship between intestinal metaplasia and the pericryptal fibroblast sheath (PCFS) in the mesenchyme. In addition, we also examined PCFS in gastric carcinoma. METHODS: We determined the existence of PCFS in the intestinal metaplastic mucosa and carcinoma of both human and Cdx2 transgenic mouse stomach. PCFS was determined using the antibody against alpha-smooth muscle actin and electron microscopic observations. RESULTS: PCFS formed an almost complete layer around the small and large intestinal crypts while it did not exist around the normal gastric glands in both mice and humans. PCFS was seen around the glands of intestinal metaplastic mucosa in both Cdx2 transgenic mouse and human stomachs. However, PCFS was virtually absent in the intestinal-type gastric adenocarcinoma area. CONCLUSION: We successfully demonstrated that the epithelium as well as the mesenchyme changed from the gastric type to the intestinal type in intestinal metaplasia and that PCFS disappeared in intestinal-type gastric carcinoma.

Two states of the triple helix in the thermal transition of the collagen model peptide (Pro-Pro-Gly)10.

The collagen model peptide (Pro-Pro-Gly)10 is known to fold into a triple helix in solution. So far, the triple helix has been considered to exist as a single state. However, our previous study of (Pro-Pro-Gly)10 in solution has indicated the presence of two different states of the triple helix, a lower (HL) and a higher temperature state (HH). In the present study, these triple-helical states were investigated in more detail by NMR. Complete stereospecific assignments of the methylene protons of the proline residues were accomplished by the use of NOESY and TOCSY spectra. The temperature dependence of the 1H chemical shifts showed that the HL-to-HH thermal transition can be attributed to a conformational change of the first proline (Pro1) residues of the (Pro-Pro-Gly) triplets. Since TOCSY spectra with a 10 ms mixing-time confirmed a down puckering of these Pro residues in the HL state, but interconverting down and up puckerings in the HH state, the HL-to-HH thermal transition corresponds to conformational changes of the pyrrolidine rings of the Pro1 residues from an uniform down puckering to a more flexible state. The results confirm that thermal unfolding of the triple helix proceeds through the intermediate HH state.

Vitrification of human blastocysts using cryoloops: clinical outcome of 223 cycles.

BACKGROUND: The need to cryopreserve human blastocysts is increasing. The successful birth has been reported of a baby from a blastocyst vitrified using the cryoloop technique. The present study expands on this earlier report to confirm the effectiveness of this vitrification procedure. METHODS: In patients undergoing IVF at one of three clinics, supernumerary blastocysts on day 5 or 6 at various stages of development were vitrified using cryoloops. RESULTS: Of 725 vitrified blastocysts, 583 (80.4%) survived. After the transfer of 493 blastocysts in 207 cycles, 76 women (37%) became clinically pregnant. Among these women, 21 pregnancies ended in miscarriage, 23 healthy babies were born in 18 deliveries, and 37 pregnancies are ongoing. The survival rate of day 5 blastocysts (87%) was higher than that of day 6 blastocysts (55%), but implantation rates and pregnancy rates were not statistically significantly different. CONCLUSIONS: Clinical outcomes with 725 blastocysts and 207 transfers showed that vitrification using cryoloops is effective and practical for the cryopreservation of human blastocysts. Early blastocysts on day 5 seem to be the most suitable in terms of stage and age for cryopreservation, but developed and day 6 blastocysts can also be cryopreserved.

Enhanced Abeta40 deposition was associated with increased Abeta42-43 in cerebral vasculature with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D).

Cerebrovascular deposition of the amyloid beta-protein (Abeta) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders. Such an Abeta vascular deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses, including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Abeta deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. We analyzed cerebral Abeta deposition in brains with AD and Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) on the basis of two amyloid species of Abeta(40) and Abeta(42/43) using specific monoclonal antibodies. Compared to Abeta deposition in senile plaques, the molecular composition of Abeta was distinguishable, indicating that the Abeta(40) species is the main component for vascular amyloid. Furthermore, we found Abeta(42/43) immunoreactivity was also much increased in amyloid angiopathy of all cases with HCHWA-D. Taken together, amyloid angiopathy in HCHWA-D may share an Abeta(42)-driven deposition mechanism with plaque amyloid, resulting in enhanced Abeta(40) deposition.

Safe percutaneous canalization of the biliary tree using a sheath in patients with malignant biliary stenosis.

BACKGROUND: Percutaneous canalization of the bile duct is essential for radiologic interventions of the biliary tract. This study discusses technical considerations for safe approaches for canalization of the bile duct when using a sheath. METHODS: During early and late periods, percutaneous canalization was performed in 104 patients and 79 patients with malignant biliary stenosis, respectively. The late period differed from the early period in that the bile duct was canalized with a previously placed sheath to prevent catheter dislodgement during the procedure. RESULTS: During the early and late periods, catheter dislodgement during canalization occurred in three of 104 patients (3%) and none of 79 patients (0%), respectively. The success rate of canalization without cholangioscopy in the late period (99%) was better than that in the early period (89%; p < 0.05). CONCLUSION: Placement of a sheath into the biliary tree increases the safety and success of canalization in patients with malignant stenosis.

Endoscopic transpapillary bile duct biopsy with the combination of intraductal ultrasonography in the diagnosis of biliary strictures.

BACKGROUND: When endoscopic retrograde cholangiopancreatography (ERCP) guided bile duct biopsy fails to demonstrate malignancy, it remains unclear how to manage patients with presumably malignant strictures. AIMS: To evaluate the value of intraductal ultrasonography (IDUS) when bile duct biopsy is negative. METHODS: Sixty two patients with strictures of the bile duct were studied prospectively. During ERCP, IDUS was performed using an ultrasonic probe (diameter 2.0 mm; frequency 20 MHz). Following IDUS, a bile duct biopsy was performed using forceps (diameter 1.8 mm). The IDUS images of the tumour were classified as polypoid lesions, localised wall thickening, intraductal sessile tumours, sessile tumour outside of the bile duct, or absence of apparent lesion. The bile duct wall structures at the site of the tumour as well as the maximum diameter of the tumour were also analysed. The IDUS findings were compared with the histological findings or clinical course. RESULTS: When the IDUS images showed a polypoid lesion (n=19), localised wall thickening (n=8), intraductal sessile tumour (n=13), and sessile tumour outside of the bile duct (n = 20), the sensitivities of the biopsy were 80%, 50%, 92%, and 53%, respectively. Multiple regression analysis showed that the presence of sessile tumour (intraductal or outside of the bile duct: p<0.05), tumour size greater than 10.0 mm (p<0.001), and interrupted wall structure (p<0.05) were independent variables that predicted malignancy. CONCLUSION: When biopsy fails to demonstrate evidence of malignancy, the presence of sessile tumour (intraductal or outside of the bile duct), tumour size greater than 10.0 mm, and interrupted wall structure on IDUS images are factors that can predict malignancy.

Successful birth after transfer of vitrified human blastocysts with use of a cryoloop containerless technique.

OBJECTIVE: Clinical application of vitrification for the cryopreservation of human blastocysts. DESIGN: Clinical trial of vitrification of human blastocysts. SETTING: Private assisted reproductive technology clinic. PATIENT(S): Supernumerary blastocysts after fresh blastocyst transfer were vitrified for subsequent transfer. INTERVENTION(S): Culture of pronuclear embryos to the blastocyst stage in sequential media and subsequent vitrification of supernumerary blastocysts using a cryoloop technique. MAIN OUTCOME MEASURE(S): Clinical outcome after transfer of vitrified blastocysts. RESULT(S): A total of 60 vitrified blastocysts from 21 patients were warmed, and the survival rate at 2 hours after warming was 63%. Six clinical pregnancies were achieved after 19 transfers. One healthy baby was born, four pregnancies are ongoing, and one ended in miscarriage. CONCLUSION(S): Human blastocysts can be successfully vitrified by suspension on a small nylon loop and a direct plunge into liquid nitrogen. A delivery and ongoing pregnancies prove the safety of this method. This report documents the first successful pregnancy and delivery achieved by blastocyst vitrification using the cryoloop containerless technique.

Endoscopic partial resection of a duodenal duplication cyst.

A case of symptomatic duodenal duplication cyst is reported. The patient underwent endoscopic partial resection of the cystic wall using the O-ring ligation kit. After resection, the abdominal pain disappeared. Endoscopic partial resection is useful for diagnosis and treatment of duodenal duplication cyst.

Looping technique for transpapillary selective biopsy of the left hepatic duct.

PURPOSE: Because biopsy forceps tend to turn towards the right hepatic duct during endoscopic retrograde cholangiopancreatography (ERCP), selective access to the left hepatic duct is difficult. METHODS: In this study, we managed to insert biopsy forceps selectively into the left hepatic duct, by using a looping technique, in three patients. Biopsy forceps were inserted into the right hepatic duct by the conventional method. The elevator of the endoscope was kept down, and the shaft of the biopsy forceps was then advanced to the duodenal cavity until it formed a loop between the endoscope and the papilla. During the procedure, the tip of the forceps was kept at the hepatic hilus. RESULTS: In this condition, we were able to slowly rotate the tip of the forceps and direct the forceps towards the left. Sufficient material from the left hepatic duct was obtained in all patients. CONCLUSIONS: The looping technique was useful for selective access to the left hepatic duct.