A case of fulminant amebic colitis that could be saved

An 80-year-old man was admitted to a neighboring hospital with severe diarrhea and bloody stools. He did not have a remarkable medical history, was not homosexual, and had not traveled outside the country for several years. Colonoscopy was performed on the day of admission and revealed multiple ulcerations with edematous mucosa throughout the colorectum. Histopathological findings of biopsy specimen could not identify the reason for the inflamed colon. On postadmission day 6, the patient developed severe abdominal pain and underwent an emergent surgery for pan-peritonitis due to bowel perforation. The laparotomy revealed glossy fecal pan-peritonitis with perforation of the sigmoid colon; necrosis was observed through the entire length of the colon. The colonic tissue was extremely fragile and exhibited a blotting paper-like appearance. Total colectomy, sigmoid mucous fistula, ileostomy, and intraperitoneal drainage were performed. On postadmission day 12, histopathological findings of resected specimen raised the suspicion of amebic dysentery, and we accordingly treated him with metronidazole (2,250 mg/day) administered orally. Abdominal CT images taken on days 12 and 20 postadmission showed multiple liver abscesses, which improved following metronidazole administration. Metronidazole was discontinued 14 days after initiation as the patient’s general condition improved. His condition remained stable thereafter, and he was transferred two months after admission

Derivation of a Myeloid Cell-Binding Adenovirus for Gene Therapy of Inflammation

The gene therapy field is currently limited by the lack of vehicles that permit efficient gene delivery to specific cell or tissue subsets. Native viral vector tropisms offer a powerful platform for transgene delivery but remain nonspecific, requiring elevated viral doses to achieve efficacy. In order to improve upon these strategies, our group has focused on genetically engineering targeting domains into viral capsid proteins, particularly those based on adenovirus serotype 5 (Ad5). Our primary strategy is based on deletion of the fiber knob domain, to eliminate broad tissue specificity through the human coxsackie-and-adenovirus receptor (hCAR), with seamless incorporation of ligands to re-direct Ad tropism to cell types that express the cognate receptors. Previously, our group and others have demonstrated successful implementation of this strategy in order to specifically target Ad to a number of surface molecules expressed on immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid cell-binding peptide (MBP), with the sequence WTLDRGY, and demonstrated that MBP can be successfully incorporated into a knob-deleted Ad5. The resulting virus, Ad.MBP, results in specific binding to primary myeloid cell types, as well as significantly higher transduction of these target populations ex vivo, compared to unmodified Ad5. These data are the first step in demonstrating Ad targeting to cell types associated with inflammatory disease

HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach

Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response

Correlation Index-Based Responsible-Enzyme Gene Screening (CIRES), a Novel DNA Microarray-Based Method for Enzyme Gene Involved in Glycan Biosynthesis

BACKGROUND: Glycan biosynthesis occurs though a multi-step process that requires a variety of enzymes ranging from glycosyltransferases to those involved in cytosolic sugar metabolism. In many cases, glycan biosynthesis follows a glycan-specific, linear pathway. As glycosyltransferases are generally regulated at the level of transcription, assessing the overall transcriptional profile for glycan biosynthesis genes seems warranted. However, a systematic approach for assessing the correlation between glycan expression and glycan-related gene expression has not been reported previously. METHODOLOGY: To facilitate genetic analysis of glycan biosynthesis, we sought to correlate the expression of genes involved in cell-surface glycan formation with the expression of the glycans, as detected by glycan-recognizing probes. We performed cross-sample comparisons of gene expression profiles using a newly developed, glycan-focused cDNA microarray. Cell-surface glycan expression profiles were obtained using flow cytometry of cells stained with plant lectins. Pearson's correlation coefficients were calculated for these profiles and were used to identify enzyme genes correlated with glycan biosynthesis. CONCLUSIONS: This method, designated correlation index-based responsible-enzyme gene screening (CIRES), successfully identified genes already known to be involved in the biosynthesis of certain glycans. Our evaluation of CIRES indicates that it is useful for identifying genes involved in the biosynthesis of glycan chains that can be probed with lectins using flow cytometry

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京都大学0048新制・課程博士博士(医学)甲第8866号医博第2369号新制||医||769(附属図書館)UT51-2001-F196京都大学大学院医学研究科婦人科学産科学専攻(主査)教授 今村 正之, 教授 小川 修, 教授 藤井 信吾学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Reduced-port surgery for rectal cancer

Laparoscopic surgery for rectal cancer has short-term and long-term oncological outcomes similar to those of open surgery. Conventional multiport laparoscopic surgery (CMLS) for rectal cancer requires four or five abdominal incisions for trocars, each of which could lead to complications and/or pain. Single-incision laparoscopic surgery (SILS) would reduce the incidence of such wound-related complications and achieve better cosmetic outcomes relative to CMLS. The potential advantages of SILS are less pain and more rapid recovery than achieved with CMLS. However, SILS is rarely used for rectal cancer because of the high-level technical expertise required. Reduced-port laparoscopic surgery (RPS), which involves one additional port, may bridge the technical gap between CMLS and SILS and has a less steep learning curve. RPS for rectal cancer has a short history, and its usefulness has not yet been fully established. Here, we review the present situation, challenges, and future prospects for RPS for rectal cancer