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Appendico-vesical fistula is a rare condition. In total, 109 cases, most secondary to appendicitis, have been reported in the English-language literature. We report the first case, to our knowledge, of appendico-ileo-vesical fistula secondary to appendiceal diverticulitis. An enterovesical fistula was diagnosed by urine culture, cystoscopy, and computed tomography. The locations of enteric opening sites were demonstrated by barium enema and colonoscopy. Ileocecal resection and fistulectomy with primary reconstruction were performed. We believe that accurate pre- and intra-operative diagnosis is essential for cure. This case demonstrates the importance of barium enema and colonoscopic examinations in the diagnosis and treatment of complicated enterovesical fistula. [ABSTRACT FROM AUTHOR]

Purpose: The Bayesian penalized likelihood (BPL) reconstruction algorithm, Q.Clear, can achieve a higher signal-to-noise ratio on images and more accurate quantitation than ordered subset-expectation maximization (OSEM). The reconstruction parameter (β) in BPL requires optimization according to the radiopharmaceutical tracer. The present study aimed to define the optimal β value in BPL required to diagnose Alzheimer disease from brain positron emission tomography (PET) images acquired using 18 F-fluoro-2-deoxy-D-glucose ([ 18 F]FDG) and 11 C-labeled Pittsburg compound B ([ 11 C]PiB)., Methods: Images generated from Hoffman 3D brain and cylindrical phantoms were acquired using a Discovery PET/computed tomography (CT) 710 and reconstructed using OSEM + time-of-flight (TOF) under clinical conditions and BPL + TOF (β = 20-1000). Contrast was calculated from images generated by the Hoffman 3D brain phantom, and noise and uniformity were calculated from those generated by the cylindrical phantom. Five cognitively healthy controls and five patients with Alzheimer disease were assessed using [ 18 F]FDG and [ 11 C]PiB PET to validate the findings from the phantom study. The β values were restricted by the findings of the phantom study, then one certified nuclear medicine physician and two certified nuclear medicine technologists visually determined optimal β values by scoring the quality parameters of image contrast, image noise, cerebellar stability, and overall image quality of PET images from 1 (poor) to 5 (excellent)., Results: The contrast in BPL satisfied the Japanese Society of Nuclear Medicine (JSNM) criterion of ≥55% and exceeded that of OSEM at ranges of β = 20-450 and 20-600 for [ 18 F]FDG and [ 11 C]PiB, respectively. The image noise in BPL satisfied the JSNM criterion of ≤15% and was below that in OSEM when β = 150-1000 and 400-1000 for [ 18 F]FDG and [ 11 C]PiB, respectively. The phantom study restricted the ranges of β values to 100-300 and 300-500 for [ 18 F]FDG and [ 11 C]PiB, respectively. The BPL scores for gray-white matter contrast and image noise, exceeded those of OSEM in [ 18 F]FDG and [ 11 C]PiB images regardless of β values. Visual evaluation confirmed that the optimal β values were 200 and 450 for [ 18 F]FDG and [ 11 C]PiB, respectively., Conclusions: The BPL achieved better image contrast and less image noise than OSEM, while maintaining quantitative standardized uptake value ratios (SUVR) due to full convergence, more rigorous noise control, and edge preservation. The optimal β values for [ 18 F]FDG and [ 11 C]PiB brain PET were apparently 200 and 450, respectively. The present study provides useful information about how to determine optimal β values in BPL for brain PET imaging., (© 2022 American Association of Physicists in Medicine.)

Competing Interests: No potential conflict of interest relevant to this article was reported.

We review the techniques and outcomes of the intragastric resection for gastric submucosal tumors (GSTs) using laparoscope and oral endoscope. In the literature, the mean operation time, intraoperative blood loss, pathological size of the tumor and postoperative hospital stay were 134 min, minimal, 31 mm and 6.4 d, respectively. There were no particular perioperative complications during the follow-up period (mean: 121.3 mo). Intragastric surgery using laparoscopy and oral endoscopy can be considerably beneficial for patients with GSTs locating in the upper third of the stomach between 2-5 cm in diameter and < 8 cm(2) in cross-sectional area and located in the upper third of the stomach.

A Gram-negative, magnetotactic bacterium, Magnetospirillum magneticum AMB-1 produces nano-sized magnetic particles (BacMPs) in the cytoplasm. Although various applications of genetically engineered BacMPs have been demonstrated, such as immunoassay, ligand-receptor interaction or cell separation, by expressing a target protein on BacMPs, it has been difficult to express disulfide-bonded proteins on BacMPs due to lack of disulfide-bond formation in the cytoplasm. Here, we propose a novel dual expression system, called in vitro docking, of a disulfide-bonded protein on BacMPs by directing an immunoglobulin Fc-fused target protein to the periplasm and its docking protein ZZ on BacMPs. By in vitro docking, an scFv-Fc fusion protein was functionally expressed on BacMPs in the dimeric or trimeric form. Our novel disulfide-bonded protein expression system on BacMPs will be useful for efficient screening of potential ligands or drugs, analyzing ligand-receptor interactions or as a magnetic carrier for affinity purification., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Paraesophageal hiatal hernia is often associated with a number of complications such as intestinal obstruction, gastric volvulus and acute pancreatitis, each of which can result in critical conditions requiring surgery. Herein, we report our surgical procedure for paraesophageal hiatal hernia., Methods: Since 2003, we have surgically treated hiatal hernia in 18 patients, including 2 men and 16 women, with a mean age of 73 years. Thirteen patients (72.2%) had a type-I hiatal hernia, two (11.1%) had type III and three (16.7%) had type IV. The operative procedure consisted of a crural repair and anti-reflux maneuver., Results: Laparoscopic procedures were completed in all patients. The mean operation time was 160.2 min for type I and 230.8 min for types III and IV. The mean postoperative hospital stay was 7.8 days, and there was no mortality. Three patients relapsed during the mean follow-up period of 74.9 months. Two of them were asymptomatic and one required laparoscopic reoperation., Conclusion: Laparoscopic surgery for paraesophageal hiatal hernia is safe and effective with minimal morbidity and early recovery. However, it is important to determine the appropriate timing of surgery based on the severity of the hernia and the patient's general status and comorbidities., (© 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

The measurement of autoantibodies to thyroid-stimulating hormone receptor (TSHR) is important for the diagnosis of autoimmune thyroid disease such as Graves' disease (GD). Although TSHR from porcine thyroid membrane is commonly used for the measurement of TSHR autoantibodies (TRAb), recombinant human TSHR (hTSHR) remains ideal in terms of stable supply and species identity. Here we set out to express recombinant hTSHR on the lipid-bilayer surface of magnetic nanoparticles from a magnetotactic bacterium, Magnetospirillum magneticum AMB-1. Using a tetracycline-inducible expression system, we successfully overexpressed functional hTSHR on bacterial magnetic particles (BacMPs) in AMB-1 via an anchor protein specific for BacMPs. The overexpressed hTSHR was membrane integrated and possessed both ligand and autoantibody binding activity. Our data suggest that hTSHR-displayed BacMPs have potential as novel tools for ligand-receptor interaction analysis or for TRAb immunoassay in GD patients.

IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.

Recent advances in chemotherapy and chemoradiation therapy for colorectal cancer have made neoadjuvant treatment an eligible therapeutic option for selected cases of marginally resectable colorectal cancer. However, marginally resectable colorectal cancer is not well defined. The authors suggest that a primary lesion is marginally resectable if extended resection such as pelvic exenteration and pancreaticoduedenectomy are not completely curative. Even if the lesion itself is resectable, it is marginally resectable if it has unfavorable prognostic factors such as numerous metastases to the regional lymph nodes. Rectal cancer invading beyond mesorectal fascia, or having bilateral or multiple lateral lymph node metastasis, may also be marginally resectable. All locally recurrent lesions may be marginally resectable because the prognosis after surgical resection is poor. Multiple liver metastases, liver metastasis for which resection requires vascular reconstruction, and technically resectable liver metastasis with unfavorable prognostic factors, are also thought to be marginally resectable. Neoadjuvant chemotherapy regimens including oxaliplatin and irinotecan combined with bevacizumab, cetuximab and panitumumab may be effective for hastening the curability of such marginally resectable tumors. For primary advanced rectal cancer and locally recurrent rectal cancer, neoadjuvant radiation combined with chemotherapy using oxaliplatin and irinotecan are being explored. A number of clinical trials are currently ongoing, and are expected to clarify the effectiveness of neoajuvant treatment for marginally resectable colorectal cancer.

Background: The aim was to considerably enhance the sensitivity of hepatitis B virus (HBV) surface antigen (HBsAg) detection and investigate whether the window period for HBV detection could be reduced., Study Design and Methods: A high-sensitivity chemiluminescent enzyme immunoassay (CLEIA) was developed for quantitative HBsAg detection by a combination of monoclonal antibodies, each one for a specific epitope of HBsAg, and by improving the conjugation technique. The sensitivity of the assay was compared with that of the existing chemiluminescent immunoassay (CLIA). Commercially available seroconversion panels and samples of HBV-infected chimpanzees were tested with the developed prototype to assess whether the window period for HBsAg detection could be reduced to that for DNA detection., Results: Compared to the existing CLIA, the CLEIA prototype detected HBsAg with approximately 230-fold higher sensitivity and showed a reduced window period. HBsAg detection by the CLEIA prototype and HBV DNA detection by polymerase chain reaction (PCR) occurred simultaneously. The mean time for the CLEIA prototype to first detect HBsAg was approximately 17.4 days less than that for the existing systems. Further, CLEIA prototype enabled HBsAg detection even in anti-HBs-positive seroconversion samples. In the inoculated chimpanzees the HBsAg and HBV DNA became detectable simultaneously and concentrations increased in parallel, whereas HBsAg remained detectable longer than HBV DNA in the declining phase of viremia., Conclusion: The CLEIA prototype yielded results comparable with those of HBV DNA PCR. This novel high-sensitivity assay may be useful for early detection of HBV infection and monitoring patients with a history of infection.

Serum amyloid A (SAA) is a sensitive marker of acute-phase responses and known as a precursor protein of amyloid fibril in amyloid A (AA) (secondary) amyloidosis. Since the serum SAA level is also closely related to activity of chronic inflammatory disease and coronary artery disease, it is important to clarify the exact induction mechanism of SAA from the clinical point of view. Here we provide evidence that STAT3 plays an essential role in cytokine-driven SAA expression, although the human SAA gene shows no typical STAT3 response element (RE) in its promoters. STAT3 and nuclear factor kappaB (NF-kappaB) p65 first form a complex following interleukin (IL)-1 and IL-6 (IL-1+6) stimulation, after which STAT3 interacts with nonconsensus sequences at a 3' site of the SAA gene promoter's NF-kappaB RE. Moreover, co-expression of p300 with STAT3 dramatically enhances the transcriptional activity of SAA. The formation of a complex with STAT3, NF-kappaB p65, and p300 is thus essential for the synergistic induction of the SAA gene by IL-1+6 stimulation. Our findings are expected to aid the understanding of the inflammatory status of AA amyloidosis to aid development of a therapeutic strategy for this disease by means of normalization of serum SAA levels.

Fusion proteins with an alpha-hemolysin (HlyA) C-terminal signal sequence are known to be secreted by the HlyB-HlyD-TolC translocator in Escherichia coli. We aimed to establish an efficient Hly secretory expression system by random mutagenesis of hlyB and hlyD. The fusion protein of subtilisin E and the HlyA signal sequence (HlyA(218)) was used as a marker protein for evaluating secretion efficiency. Through screening of more than 1.5 x 10(4) E. coli JM109 transformants, whose hlyB and hlyD genes had been mutagenized by error-prone PCR, we succeeded in isolating two mutants that had 27- and 15-fold-higher levels of subtilisin E secretion activity than the wild type did at 23 degrees C. These mutants also exhibited increased activity levels for secretion of a single-chain antibody-HlyA(218) fusion protein at 23 and 30 degrees C but unexpectedly not at 37 degrees C, suggesting that this improvement seems to be dependent on low temperature. One mutant (AE104) was found to have seven point mutations in both HlyB and HlyD, and an L448F substitution in HlyB was responsible for the improved secretion activity. Another mutant (AE129) underwent a single amino acid substitution (G654S) in HlyB. Secretion of c-Myc-HlyA(218) was detected only in the L448F mutant (AE104F) at 23 degrees C, whereas no secretion was observed in the wild type at any temperature. Furthermore, for the PTEN-HlyA(218) fusion protein, AE104F showed a 10-fold-higher level of secretion activity than the wild type did at 37 degrees C. This result indicates that the improved secretion activity of AE104F is not always dependent on low temperature.

Serum amyloid A (SAA) is known to be a precursor of amyloid A (AA) protein in AA (secondary) amyloidosis and SAA1 to be mainly involved in AA amyloidosis. We established an SAA isoform real-time quantitative RT-PCR assay and found that beta-2 microglobulin is more stable as an internal control than GAPDH and beta-actin for our system. Either IL-6 and IL-1beta or IL-6 and TNFalpha, but not IL-1beta and TNFalpha, induced the synergistic induction of SAA1 and SAA2 genes. Anti-IL-6 receptor monoclonal antibody completely inhibited the synergistic induction of SAA1 and SAA2 during triple stimulation with IL-6, IL-1beta, and TNFalpha, but, IL-1 receptor antagonist or anti-TNFalpha monoclonal antibody was only partially inhibited in HepG2, Hep3B, and PLC/PRF/5 cells. Although the SAA1 promoter has no STAT3 consensus sequence, the JAK2 inhibitor-AG490 reduced SAA1 gene expression to 30%, suggesting the involvement of STAT3. We were able to demonstrate that IL-6 plays a critical role in the synergistic induction of human SAA gene when stimulated with proinflammatory cytokines.

Background and Aims: Colonic J-pouch anastomosis after low anterior resection of the rectum has been reported to be associated with an increased risk of evacuation difficulty. Using scintigraphy we compared neorectal emptying after stapled low anterior resection between colonic J-pouch anastomosis and straight anastomosis., Patients and Methods: We studied 19 patients after colonic J-pouch anastomosis and 22 after straight anastomosis. After the introduction of an artificial stool containing (99m)Tc-DTPA into the neorectum sequential lateral gamma images were obtained. From the time activity curve of radioactivity in the whole pelvis the time taken to evacuate one-half of the introduced artificial stool ( t(1/2)) and the percentage of artificial stool evacuated in 1 min (Evac(1)) were calculated. Fourteen volunteers were also studied as the reference group., Results: The t(1/2) was significantly longer and Evac(1) significantly lower in patients after low anterior resection than in the reference group. t(1/2) was significantly longer in the pouch group than in the straight group. Anastomotic height was significantly correlated with both t(1/2) and Evac(1). Neither t(1/2) nor Evac(1) was correlated with the severity of impaired defecatory function., Conclusion: Although neither of the two parameters of neorectal emptying was correlated with the severity of impaired defecatory function, less effective neorectal emptying in patients after colonic J-pouch anastomosis than in those after straight anastomosis may be a factor causing evacuation difficulty after colonic J-pouch anastomosis.

Purpose: Patients who have undergone low anterior resection (LAR) of the rectum occasionally complain of symptoms related to impaired neorectal evacuation. Using scintigraphy, we assessed neorectal evacuation in 22 patients who underwent LAR and straight anastomosis, and correlated the results with clinical defecatory function, clinical factors, and anorectal manovolumetric parameters., Methods: After the introduction of an artificial stool containing 99mTc-DTPA into the neorectum, sequential lateral gamma images were obtained. From the time-activity curve of radioactivity in the whole pelvis, the time taken to evacuate half of the introduced artificial stool (T(1/2)) and the percentage of artificial stool evacuated in 1 min (Evac1) were calculated., Results: The Evac1 was significantly lower in the patients who had undergone LAR than in reference normal volunteers. A long T(1/2) was significantly associated with worse defecatory function. The Evac1 was also significantly lower in patients with a low anastomosis. The rectal sensory threshold was significantly greater in patients with a shorter T(1/2). The maximum tolerable volume of the neorectum was significantly greater in patients with a shorter T(1/2) and a higher Evac1., Conclusion: Poor neorectal evacuation is associated with impaired defecatory function after LAR. Therefore, it is suggested that optimizing both reservoir function and evacuation of the neorectum would improve defecatory function after LAR.

TAK1, a member of the MAPKKK family, is involved in the intracellular signaling pathways mediated by transforming growth factor beta, interleukin 1, and Wnt. TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1. The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1 interaction and activation. Analysis of various truncated versions of TAB1-C68 defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha-helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C-terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the conserved motif, is crucial for TAK1 binding and activation. The C. elegans homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4. These results suggest that the Phe or Ala residue within the conserved motif of the TAB1-related proteins is important for interaction with and activation of specific TAK1 MAPKKK family members in vivo.

HM1.24 antigen has been identified as a surface molecule preferentially expressed on terminally differentiated B cells, and its overexpression is observed in multiple myeloma cells. The HM1.24 antigen is, therefore, expected as a most potent target molecule for antibody-based immunotherapy for multiple myeloma. Here, we have identified the cDNA for human HM1.24 antigen and also analyzed its gene structure including the promoter region. The HM1.24 antigen is a type II membrane glycoprotein, which has been reported as a bone marrow stromal cell surface antigen BST2, and may exist as a homodimer on myeloma cell surface. Although a reason for the overexpression in myeloma cells is not understood, very interestingly, the promoter region of the HM1.24 gene has a tandem repeat of three cis elements for a transcription factor, STAT3, which mediates interleukin-6 (IL-6) response gene expression. Since IL-6 is a differentiation factor for B cells, and known as a paracrine/autocrine growth factor for multiple myeloma cells, the expression of HM1.24 antigen may be regulated by the activation of STAT3. Importantly, a humanized anti-HM1.24 antibody effectively lysed the CHO transformants which expressed HM1.24 antigen as high as human multiple myeloma cells, but not the cells with lower antigen expression. This evaluation shows that ADCC heavily depends on the expression level of target antigens and, therefore, the immunotherapy targeting the HM1.24 antigen should have a promising potential in clinical use., (Copyright 1999 Academic Press.)