Novel image enhancement technology that helps find bleeding points during endoscopic submucosal dissection of gastric neoplasms.

BACKGROUND AND AIM: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology. METHODS: Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE-L*a*b* color space were calculated in the original and enhanced images. RESULTS: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36). CONCLUSION: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.

Thermoreversible gelation with ion-binding cross-links of variable multiplicity.

Thermoreversible gelation and liquid-liquid phase separation are theoretically studied for the gels of polyfunctional molecules (polymers) whose network junctions are formed by complexation of functional groups on the polymer chains with added metal ions. Phase diagrams on the polymer/ion/solvent concentration plane, including both sol-gel transition lines and liquid-liquid phase separation lines (spinodals), are derived as functions of the polymer functionality, molecular weight, maximum coordination number of ions, and temperature. Binding isotherms of ions are also calculated as functions of the ion concentration. Results of the calculated sol-gel transition lines are compared with our recent experimental data on gelation of star block and telechelic, acrylic copolymers cross-linked by iron ions. It is shown that, owing to reaction stoichiometry, there is an optimal ion concentration at which the solution gels for the lowest polymer concentration and also that a re-entrant sol phase appears in the ion concentrations higher than the optimal one. The effect of stepwise complex formation constants on the re-entrant phase is studied in detail.

Extended Release of Native Drug Conjugated in Polyketal Microparticles.

Polyketals, which can be biodegradable, have good biocompatibility, and are pH-sensitive, could have broad applicability in drug delivery and other biomedical applications. However, facile synthesis of high molecular weight polyketals is challenging, and short durations of drug release from polyketal particulate formulations limit their application in drug delivery. Here we report the synthesis of a di-isopropenyl ether monomer and its use to synthesize high molecular weight estradiol-polyketal conjugates by addition polymerization. Microparticles were prepared from the estradiol-polyketal conjugate, where estradiol was incorporated into the polymer backbone. The particles had high drug loading and significantly prolonged drug release. Release of estradiol from the drug-polyketal conjugate microparticles was acid-responsive, as evidenced by faster drug release at low pH and with co-incorporation of PLGA. Tissue reaction to the microparticles was benign in vivo. Polyketal drug conjugates are promising candidates for long-acting drug delivery systems to treat chronic diseases.

Large Inflammatory Myofibroblastic Tumor of the Esophagus: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of myofibroblasts with inflammatory blood cell infiltration. It commonly occurs in the lungs and rarely in the esophagus. We herein report a valuable case of IMT originating in the esophagus. A 60-year-old Japanese woman with dysphagia had a large subepithelial lesion in the cervical esophagus, which was 15 cm in length. Surgical resection was performed to confirm the pathological diagnosis and improve the symptoms. The postoperative diagnosis was IMT composed of multiple nodules. There was no recurrence or metastasis within one year after surgery.

Usefulness of ultrasound in diagnosing long head of the biceps tendon malposition in patients with rotator cuff tears.

PURPOSE: This study aimed to determine the role of preoperative shoulder ultrasonography (SUS) in detecting positional abnormalities of the long head of the biceps tendon (LHBT) and predicting subscapularis (SSC) tears in patients with rotator cuff injuries. METHODS: A total of 331 patients (365 shoulders) who had undergone arthroscopic shoulder surgery for the treatment of rotator cuff tears were included in the study. Their preoperative SUS and magnetic resonance imaging (MRI) findings were examined retrospectively to assess the presence of LHBT abnormalities at the bicipital groove. Using arthroscopic findings as the standard of reference, the sensitivity, specificity, and diagnostic accuracy of SUS and MRI were calculated for detection of LHBT malposition. Furthermore, the correlation between SSC rupture and preoperative LHBT condition was evaluated by MRI and SUS. RESULTS: LHBT malposition was preoperatively diagnosed with a sensitivity of 92%, specificity of 90%, and accuracy of 91% with SUS, and a sensitivity of 74%, specificity of 84%, and accuracy of 80% with MRI. Preoperative SUS was significantly superior to MRI in terms of sensitivity, specificity, and accuracy (p < 0.001 each). Further, the preoperative SUS LHBT findings could predict well the presence or absence of intraoperative SSC rupture (odds ratio: 1.73, p < 0.001). CONCLUSION: SUS is a useful diagnostic modality for preoperative detection of LHBT malposition and prediction of SSC tears in patients with rotator cuff tears.

The Influence of Posture on Instability Evaluation Using Flexion-Extension X-Ray Imaging in Lumbar Spondylolisthesis.

STUDY DESIGN: Prospective clinical study. PURPOSE: To determine the optimal posture for instability evaluation using flexion-extension X-ray imaging in patients with lumbar spondylolisthesis. OVERVIEW OF LITERATURE: Currently, flexion-extension X-ray imaging is the most practical approach for the evaluation of lumbar instability. In flexion-extension X-ray imaging, achievement of the greatest segmental motion with flexion-extension movement is necessary. However, to our knowledge, currently, there is no standardized posture for determining lumbar instability. METHODS: Twenty-three individuals with lumbar spondylosis related to the fourth vertebra underwent flexion-extension X-ray imaging in different postures (standing, sitting, and lateral decubitus positions), lumbar magnetic resonance imaging (MRI), and low back pain Visual Analog Scale (VAS) evaluation on the same day. Intervertebral angle, percent slippage, and intervertebral disc area ratio for different postures during flexion and extension were compared using Tukey's method. The effect of low back pain and the association between MRI facet effusion and these measurements were investigated according to posture. RESULTS: The percent slippage during extension (p=0.036), change in the percent slippage between flexion and extension (p=0.004), and change in the intervertebral angle (p=0.042) were significantly different between the sitting and lateral decubitus positions. There were also significant differences between the standing and lateral decubitus positions in the change in intervertebral angle (p=0.010). In patients with VAS score <40, there were significant differences in the intervertebral angle (p=0.011) between the standing and lateral decubitus positions, percent slippage (p=0.048), and intervertebral disk ratio (p=0.008) between the sitting and lateral decubitus positions. We found no relationship between MRI facet effusion and posture in terms of instability. CONCLUSIONS: In this study, intervertebral instability was best evaluated in the lateral decubitus position when using flexion-extension X-ray imaging for patients with fourth lumbar vertebral spondylolisthesis.

New System for the Classification of Epiphyseal Separation of the Coracoid Process: Evaluation of Nine Cases and Review of the Literature.

Objectives and Design. Epiphyseal separation of the coracoid process (CP) rarely occurs in adolescents. In this retrospective case series, we reviewed the data of nine patients treated at our center and those of 28 patients reported in the literature. This injury can be classified into three types according to the injured area: Type I, base including the area above the glenoid; Type II, center including the coracoclavicular ligament (CCL); and Type III, tip with the short head of the biceps and coracobrachialis, as well as the pectoralis minor. Patients/Participants. A total of 37 patients were included in the analysis. Data on sex, age, cause and mechanism of injury, separation type, concomitant injury around the shoulder girdle, treatment, and functional outcomes were obtained. Main Outcome Measurements and Results. Type I is the most common type. The cause of injury and associated injury around the shoulder girdle were significantly different between Type I, II, and III fractures. The associated acromioclavicular (AC) dislocation and treatment were significantly different between Type I and III fractures. Our new classification system reflects the clinical features, imaging findings, and surgical management of epiphyseal separation of the CP. Type I and II fractures are mostly associated with AC dislocation and have an associated injury around the shoulder girdle. Type III fractures are typically caused by forceful resisted flexion of the arm and elbow. Although the latter are best managed surgically, whether conservative or surgical management is optimal for Type I and II fractures remains controversial. Conclusions. We noted some differences in the clinical characteristics depending on the location of injury; therefore, we aimed to examine these differences to develop a new system for classifying epiphyseal separation of the CP. This would increase the clinicians' awareness regarding this injury and lead to the development of an appropriate treatment.

Evaluating Cervical Sagittal Alignment in Cervical Myelopathy: Are Sitting Cervical Radiographs and Standing Whole-Spine Radiographs Equally Useful?

STUDY DESIGN: Retrospective review of medical charts and radiographic data. OBJECTIVES: We aimed to clarify the differences in cervical alignment findings between sitting cervical lateral radiographs and standing whole-spine lateral radiographs with clavicle positioning in cervical spondylotic myelopathy (CSM) patients. METHODS: We retrospectively evaluated the radiographs of 50 consecutive patients who underwent cervical surgery for CSM in our hospital. Cervical sagittal alignment was evaluated based on the C0-2 angles and C2-7 Gore and Cobb angles. Head position was evaluated in terms of the center of gravity of the head to C7 (CGH-C7) angle and the McGregor angle (ie, the angle between the McGregor line and a horizontal line). The T1-slope was also evaluated. RESULTS: The mean values of the CGH-C7 angle and T1-slope were significantly lower, while the mean value of the McGregor angle was significantly higher on whole-spine lateral radiographs with clavicle positioning than on sitting cervical lateral radiographs. The mean values of the C0-2 and C2-7 angles did not differ significantly between the 2 radiographic positioning approaches. CONCLUSIONS: Using whole-spine lateral radiographs with clavicle positioning may result in a significantly lower T1-slope and a posterior tilt of the head. In the absence of a compensatory change in cervical alignment, clavicle positioning may force patients to adopt an upward gazing position of the head. These compensatory mechanisms should be considered while evaluating cervical alignment on whole-spine lateral radiographs with clavicle positioning. Surgical planning should take into account the effect of posture on the radiographic appearance of cervical alignment.

Prevention of Peritoneal Adhesions by Ferric Ion-Cross-Linked Hydrogels of Hyaluronic Acid Modified with Iminodiacetic Acids.

We fabricated ferric ion-cross-linked hydrogels of a chelating hyaluronic acid (HA) derivative. HA was conjugated with iminodiacetic acid (IDA) at 22% of a modification degree to its disaccharide unit of HA. This conjugate (HA-IDA) showed degradability by hyaluronidase even after the IDA modification, and its degradation rate was almost the same as that of HA. HA-IDA and HA formed hydrogels (FeHA and FeHA-IDA) by cross-linking with ferric ions (Fe3+). The storage modulus of FeHA-IDA was ca. 100 Pa, which was higher than ca. 10 Pa of FeHA. FeHA-IDA showed excellent biocompatibility to a mesothelium cell line as well as rapid degradation. Above all, FeHA-IDA showed efficacy in reducing adhesion formation in a rat sidewall defect-bowel abrasion model.

Genotype analysis of Candida albicans isolates obtained from different body locations of patients with superficial candidiasis using PCRs targeting 25S rDNA and ALT repeat sequences of the RPS.

BACKGROUND: Several molecular biology-based genotyping techniques have been adapted for studying the molecular characteristics of Candida albicans strains, which constitute the majority of the etiologic agents in candidiasis. Recently, we reported a PCR system targeting 25S rDNA and ALT repeat sequences in the repetitive sequence (RPS) for genotyping of C. albicans. OBJECTIVE: To assess the potential of 25S rDNA and RPS-based genotyping for studying the molecular epidemiology of C. albicans, and define the genotypic relationship of C. albicans between invasive and non-invasive lesions in the same individual. METHODS: C. albicans strains were isolated from infected lesions and commensal sites, such as oral mucosa and/or feces, of patients with superficial candidiasis. The genomic DNAs were amplified by PCRs using P-I and P-II to determine the 25S rDNA- and RPS-based genotypes of the isolates. RESULTS: Genotype A:3 C. albicans constituted the majority of the isolates, followed by A:3/4 and B:3 C. albicans. There was usually one genotype of C. albicans per person. The genotypes of infected lesion isolates and non-infected oral mucosa and/or feces isolates were identical in the same individual, even in serially isolated C. albicans. CONCLUSION: The results indicate that our combined PCR technique using P-I and P-II is a potential tool for molecular typing of C. albicans, and reveal that the genotypes of isolates are identical in the same individual, independent of the infective and non-infective phases or the body location.

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome complicated by IgA nephropathy with nephrotic syndrome.

A 62-year-old man visited our hospital with a mild sore throat, high-grade fever, and clavicular pain. Seven years earlier, he had been diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. His clavicles were tender and remarkably swollen. Also noted was marked pitting edema in the lower extremities and pustulosis on the palms and soles of the feet. Laboratory studies on admission showed an elevated white cell count (23,400/µl) and serum C-reactive protein level (24.4 mg/dl). Urinalysis revealed proteinuria (2+) and occult blood (3+) with numerous dysmorphic red blood cells and hyalin casts. The patient was diagnosed with recurrence of his SAPHO syndrome and started on oral glucocorticoid therapy. By day 9 after admission, he had gained 16 kg in body weight, and his proteinuria (6.4 g/day) and serum creatinine level (2.3 mg/dl) were elevated. Renal biopsy revealed mesangial proliferative glomerulonephritis with deposition of IgA and C3 in the mesangial area and along the capillary walls. The patient was diagnosed with IgA nephropathy accompanied by nephrotic syndrome. With oral prednisolone therapy, his fever, clavicular pain, and proteinuria were gradually relieved. The clinical course in this case suggests the onset of nephrotic syndrome with IgA nephropathy was associated with the recurrence of the patient's SAPHO. To our knowledge, this is the first reported case of SAPHO-associated IgA nephropathy.

The nucleotide sequence determination of catalases of three medically important yeasts using newly designed degenerated primers.

We have developed degenerated primers for the isolation of several fungal species catalases, based on the known catalase genes of several yeast species. Using a combination of degenerated primers and the nested polymerase chain reaction (PCR) method, we were able to obtain PCR products from Candida dubliniensis, C. tropicalis, and C. glabrata. The nucleotide sequence of the PCR products amplified showed that those fragments contained sequences homologous with the known Candida catalases, indicating the usefulness of the designed primers. We determined the nucleotide sequences of the open reading frames and respective 5' untranscribed regions of these yeasts and compared each sequence with that of the respective related species. The difference between the deduced amino acid sequence of catalase of C. dubliniensis and C. albicans was 5 in 485 amino acids. The nucleotide sequence of C. glabrata catalase was identical to the sequence results from the genome sequence project which was recently released, whereas that of the catalase of the C. tropicalis clinical isolate was not the same as the strain Pk233, n-alkane-utilizing C. tropicalis. The catalase activities of all the strains tested so far were activated by short-term hydrogen peroxide treatment, suggesting that common mechanisms were involved in the induction of catalase activity, although the nucleotide sequences of the 5' untranscribed region of these yeasts were diversified.

A biocompatible calcium salt of hyaluronic acid grafted with polyacrylic acid.

We have synthesized hyaluronic acid (HA) grafted with polyacrylic acid (PAA) via controlled radical polymerization (CRP) in aqueous media. The grafted HA (HA-g-PAA) showed slow degradation by hyaluronidase compared with unmodified HA as a result of the steric hindrance produced by grafted PAA, and PAA was detached by hydrolysis and enzymatic degradation by lipase. It formed an insoluble salt immediately after mixing with Ca(2+) by the binding between grafted PAA and Ca(2+). Both HA-g-PAA and its salt showed good biocompatibility, especially to mesothelial cells in vitro. Finally, they were administered into mice subcutaneously and intraperitoneally. The residue of the material was observed 7 days after subcutaneous administration, while the material was almost cleared from the peritoneum 7 days after intraperitoneal administration with or without Ca(2+). HA-g-PAA is expected to be applicable to medical uses such as drug delivery in the peritoneum and for materials preventing peritoneal adhesion.

Biocompatible Star Block Copolymer Hydrogel Cross-linked with Calcium Ions.

Hydrogels cross-linked with calcium ions (Ca2+) have various potential medical applications. A star block copolymer with a dendritic polyester (DPE) core and double hydrophilic block copolymer arms composed of oligo(ethylene glycol) methyl ether acrylate (OEGA) and acrylic acid (AA) has been synthesized for the first time. This star block copolymer showed a spherical morphology with an average diameter of 62 nm and rapidly formed a hydrogel in normal saline under physiological conditions when it was mixed with Ca2+. Furthermore, the star block copolymer and its hydrogel cross-linked by Ca2+ showed excellent biocompatibility both in vitro and in vivo.

Histological observation for needle-tissue interactions.

We histologically investigated tissue fractures and deformations caused by ex vivo needle insertions. The tissue was formalin-fixed while the needle remained in the tissue. Following removal of the needle, the tissue was microtomed, stained, and observed microscopically. This method enabled observations of cellular and tissular conditions where deformations caused by needle insertions were approximately preserved. For this study, our novel method presents preliminary findings related with tissue fractures and the orientation of needle blade relative to muscle fibers. When the needle blade was perpendicular to the muscle fiber, transfiber fractures and relatively large longitudinal deformations occurred. When the needle blade was parallel to the muscle fiber, interfiber fractures and relatively small longitudinal deformations occurred. This made a significant difference in the resistance force of the needle insertions.

PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

Translesion DNA synthesis (TLS) involves PCNA mono-ubiquitination and TLS DNA polymerases (pols). Recent evidence has shown that the mono-ubiquitination is induced not only by DNA damage but also by other factors that induce stalling of the DNA replication fork. We studied the effect of spontaneous DNA replication errors on PCNA mono-ubiquitination and TLS induction. In the pol1L868F strain, which expressed an error-prone pol alpha, PCNA was spontaneously mono-ubiquitinated. Pol alpha L868F had a rate-limiting step at the extension from mismatched primer termini. Electron microscopic observation showed the accumulation of a single-stranded region at the DNA replication fork in yeast cells. For pol alpha errors, pol zeta participated in a generation of +1 frameshifts. Furthermore, in the pol1L868F strain, UV-induced mutations were lower than in the wild-type and a pol delta mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol eta) suppressed this defect. These data suggest that nucleotide misincorporation by pol alpha induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.

Catalase gene disruptant of the human pathogenic yeast Candida albicans is defective in hyphal growth, and a catalase-specific inhibitor can suppress hyphal growth of wild-type cells.

Although the catalase gene (CAT1) disruptant of the human pathogenic yeast Candida albicans was viable under ordinary growth conditions, we previously found that it could not grow on YPD (yeast extract/peptone/dextrose) containing SDS or at higher growth temperatures. To investigate the pleiotrophic nature of the disruptant, we examined the effect of the catalase inhibitor 3-AT on the growth of wild-type strains. Surprisingly, the addition of 3-AT and SDS caused the wild-type cells to be non-viable on YPD plates. We found an additional phenotype of the catalase gene disruptant: it did not produce normal hyphae on Spider medium. Hyphal growth was observed in a CAP1 (Candida AP-1-like protein gene) disruptant, a HOG1 (high-osmolarity glycerol signaling pathway gene) disruptant, and the double CAP1/HOG1 disruptant, suggesting that the defect in hyphal formation by the catalase disruptant was independent of these genes. Addition of 3-AT and SDS to hyphae-inducing media suppressed growth of normal hyphae in the wild-type strain. The potential necessity for catalase action upon exposure to hyphae-inducing conditions was confirmed by the immediate elevation of the catalase gene message. In spite of the requirement for catalase during hyphal growth, the catalase gene disruptant was capable of forming germ tubes in medium containing serum.

Disruption of the human pathogenic yeast Candida albicans catalase gene decreases survival in mouse-model infection and elevates susceptibility to higher temperature and to detergents.

Catalase-deficient strains of the human pathogenic yeast Candida albicans were constructed using the URA-blaster method. The disruptant was viable and grew normally in an ordinary culture condition, but became extremely sensitive to treatment with hydrogen peroxide. No catalase activity was observed in a catalase (CCT)-gene-disrupted strain, 1F5-4-1, suggesting that there were no other catalase or catalase-like enzymes in this yeast. The disruptant was shown to be sensitive to higher temperature and to low concentrations of SDS, NP-40, or Triton X-100. After a wild-type CCT gene was reintroduced into the disruptant, catalase activity was restored and the strain became moderately sensitive to treatment with hydrogen peroxide. However, neither the temperature sensitivity nor the susceptibility to SDS observed in the disruptant was restored in the CCT-reintroduced strain. A model infection experiment using wild-type and dCCT strains showed that the disruptants disappeared more rapidly than the wild-type strain in mouse liver, lung, and spleen. These results suggest that the catalase plays a significant role in survival in the host immune system and thus leads this organism to establish infection in the host.