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Biomedical subjects

Mitsuhiro Fujishiro

Publications and source records attributed to Mitsuhiro Fujishiro.

At least 19 recordsLinked to original sources
PubMed2025

CRISPR-mediated proximity labeling unveils ABHD14B as a host factor to regulate HBV cccDNA transcriptional activity.

BACKGROUND: The long-term goal of chronic hepatitis B research is a functional cure (HBsAg seroclearance). Although currently used nucleos(t)ide analogs can efficiently inhibit viral replication, they do not reduce viral RNAs or proteins produced from covalently closed circular DNA (cccDNA), and rarely achieve a functional cure. To overcome this situation, revealing the mode of the existence of cccDNA is required, including identifying the interreacting proteins with cccDNA. Here, we aimed to identify novel proteins that interact with cccDNA. METHODS: Using an in vitro HBV infection model and a sequence-specific proximity labelling method consisting of dead Cas9 and biotin identification (BioID2), we comprehensively determined proteins that possibly interact with cccDNA. After identifying the candidate proteins, the HBV RNA transcription levels were examined by knocking out the associated genes. RESULTS: We identified ABHD14B as a protein that interacts with cccDNA and inhibits HBV RNA transcription from cccDNA. ABHD14B decreases the acetylation levels of histone proteins that control the transcription levels of HBV RNA in cccDNA. Moreover, ABHD14B interacts with TFII-I, which binds directly to cccDNA in a sequence-dependent manner. These results suggest that the host protein, ABHD14B, is recruited to cccDNA via the TFII-I protein, inhibiting HBV RNA transcription from cccDNA by deacetylating cccDNA histones. CONCLUSIONS: ABHD14B was newly identified as a suppressor of HBV RNA transcription from cccDNA, which may improve our understanding of the mode of existence of cccDNA, providing a basis for development of a functional cure.

Humans↗
PubMed2006

Endoscopic submucosal dissection for stomach neoplasms.

Recent advances in techniques of therapeutic endoscopy for stomach neoplasms are rapidly achieved. One of the major topics in this field is endoscopic submucosal dissection (ESD). ESD is a new endoscopic technique using cutting devices to remove the tumor by the following three steps: injecting fluid into the submucosa to elevate the tumor from the muscle layer, pre-cutting the surrounding mucosa of the tumor, and dissecting the connective tissue of the submucosa beneath the tumor. So the tumors are resectable in an en bloc fashion, regardless of the size, shape, coexisting ulcer, and location. Indication for ESD is strictly confined by two aspects: the possibility of nodal metastases and technical difficulty, which depends on the operators. Although long-term outcome data are still lacking, short-term outcomes of ESD are extremely favourable and laparotomy with gastrectomy is replaced with ESD in some parts of therapeutic strategy for early gastric cancer.

Endoscopy, Gastrointestinal↗
PubMed2006

Endoscopic submucosal dissection of esophageal squamous cell neoplasms.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) has recently been developed for en bloc resection of stomach neoplasms, which results in high tumor eradication rates as well as a modality for the precise histologic assessment of the entire lesion. Application of the technique is desirable for esophageal squamous cell neoplasms (SCNs), but there have been no reports on the use of this procedure in the esophagus. METHODS: An ESD with methods similar to those used for resections of early gastric cancer was performed on 58 consecutive esophageal SCNs with preoperative diagnoses of intraepithelial neoplasm or intramucosal invasive carcinoma occurring in 43 enrolled patients. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The rate of en bloc resection was 100% (58/58), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 78% (45/58). There was no evidence of significant bleeding. Perforation occurred in 4 (6.9%) patients during the ESD, who were managed by conservative medical treatments after endoscopic closure of the perforation. Removal of 9 (16%) lesions resulted in esophageal stricture requiring balloon dilation after ESD. Of 40 lesions occurring in 31 patients fulfilling the criteria of node-negative tumors (mean follow-up, 17 months), 1 lesion resected by en bloc resection with nonevaluable tumor-free lateral margins (Rx [lateral] resection) recurred locally 6 months after ESD, which was treated successfully by a second ESD procedure. CONCLUSIONS: The ESD is applicable to the esophagus with promising results, but notification of risk is essential.

Coloring Agents↗
PubMed2006

Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar.

BACKGROUND: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation is to create a sufficient submucosal fluid cushion (SFC). The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol). METHODS: Sixty-seven consecutive GI tumors in 54 patients who met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1:3 for esophageal/colorectal tumors and stomach tumors with scar, and 1:7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. The clinical outcomes were investigated. RESULTS: Mean resected and tumor sizes were 38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with severe fibrosis (1.5%), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. In one stomach and in one rectal tumor (3%), endoscopic hemostasis was necessary because of postoperative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow-up of 1 year. CONCLUSIONS: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD.

Adjuvants, Immunologic↗
PubMed2006

Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection.

Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR.

Animals↗
PubMed2006

En bloc resection of a large semicircular esophageal cancer by endoscopic submucosal dissection.

A semicircular esophageal cancer, approximately 7 cm wide, was detected in the middle to lower esophagus of an 81-year-old gentleman during an esophagogastroduodenoscopy. Thorough examinations using chromoendoscopy and endoscopic ultrasonography led to preoperative diagnosis of an intramucosal tumor. With informed consent, the patient underwent endoscopic submucosal dissection (ESD), a novel endoscopic treatment. A successful en bloc resection by ESD was completed without complications. The resected specimen measured 72 mm by 35 mm, and the cancer was contained in an area of 66 mm by 32 mm. Histologic assessment revealed squamous cell carcinoma, microinvasive into the mucosal layer, but without vessel infiltration. Six months after ESD, mild stenosis remained, but dilation was no longer needed, and esophagogastroduodenoscopy with chromoendoscopy and biopsy revealed no residual or recurrent cancer.

Aged, 80 and over↗
PubMed2006

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Animals↗
PubMed2006

Helicobacter pylori status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal dissection.

BACKGROUND: Eradication therapy for Helicobacter pylori is effective in preventing peptic ulcer recurrence, but its efficacy in ulcer healing is still controversial. The effect of H. pylori on artificial ulcers after endoscopic resection is not known. The purpose of the present study was therefore to evaluate the influence of H. pylori infection on ulcer healing after endoscopic submucosal dissection (ESD). METHODS: One hundred and 10 patients who underwent ESD for gastric tumors, and for whom the infection status of H. pylori was confirmed before treatment, were included. The healing stage was studied by endoscopy performed at 8 weeks after ESD. In addition, 73 patients whose serum pepsinogen (PG) was evaluated before ESD, were divided into three groups: PG positive (PGI<or=70 ng/mL and I/II<or=3 ng/mL), strongly positive (PGI<or=30 ng/mL and I/II<or=2 ng/mL) and negative, to study the influence of atrophic gastritis on ulcer healing. RESULTS: Ulcer healing was observed in 85 patients (93%) who were H. pylori positive, and in 19 patients (100%) in whom H. pylori had been eradicated previously. Serum PG level had no influence on the healing process. Among 15 patients with ulceration or ulcer scar with the lesion, ulcer healing was observed in nine patients (60%), which was significantly low. CONCLUSIONS: Infection status of H. pylori and the extent of gastric atrophy do not affect ulcer healing after ESD. Preoperative existence of fibrotic change in the submucosal layer may delay the healing process.

Female↗
PubMed2005

Tissue damage of different submucosal injection solutions for EMR.

BACKGROUND: When choosing submucosal injection solutions for EMR, tissue damage should be considered, as well as the lesion-lifting ability. The objective of the study was to find out the potential tissue damage of submucosal injection solutions. METHODS: The submucosal injection solutions examined were the following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5% fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and 0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable concentration without tissue damage. A total of 2 mL of each solution per stomach were injected by endoscopy into the submucosal layer at the separate sites of 4 living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic observations, and the others were euthanized after additional endoscopic observations a week after injection. RESULTS: There was no apparent tissue damage in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic solutions, except Glyceol and 10% DW, have more or less potency of tissue damage. In 3.75% NaCl and DW with concentrations of >or=20%, considerable tissue damage was observed, which might affect resected EMR specimens and ulcer healing. CONCLUSIONS: Use of hypertonic solutions except Glyceol is not recommended with respect to tissue damage. A combination of HA and Glyceol is the most favorable submucosal injection solution, considering tissue damage and lesion-lifting ability.

Animals↗
PubMed2004

Percutaneous traction-assisted EMR by using an insulation-tipped electrosurgical knife for early stage gastric cancer.

BACKGROUND: EMR now is accepted as a minimally invasive treatment for early stage gastric cancer. However, the endoscopic approach sometimes is limited by the size and location of the tumor. The technique and early results of percutaneous, traction-assisted EMR for resection of larger early stage gastric cancers is described. METHODS: EMR, by using an insulation-tipped electrosurgical knife, was performed with the simultaneous assistance of laparoscopy devices. A small snare was introduced into the gastric lumen through a gastric port (2-mm diameter) to grasp and pull the EGC away from the muscularis propria to facilitate resection. RESULTS: The technique was performed successfully in our endoscopic suite in the first patient under general anesthesia and the remaining seven under conscious sedation. Tumors situated in any part of the stomach could be reached with percutaneous assistance, and this facilitated en bloc resection of large specimens (mean size 50 mm). The procedure was performed in about 60 minutes. Seven patients (88%) resumed eating 1 or 2 days after surgery. All patients were discharged after 1 week without complication. CONCLUSIONS: Percutaneous, traction-assisted EMR is useful for resection of large lesions en bloc and can be performed easily and safely under direct vision.

Adult↗
PubMed2004

[Endoscopic hemostasis using high-frequency hemostatic forceps for hemorrhagic gastric ulcer].

Gastric ulcer is a major responsible lesion for upper gastrointestinal bleeding. Several methods for endoscopic hemostasis are widely used throughout Japan to treat the ulcerative lesion. High-frequency hemostatic forceps is one of the endoscopic coagulation devices developed solely for hemostasis. Unlike biopsy forceps, it has narrow opening angle, a small cup and a dull edge to make pinpoint holding of the target lesion possible. We applied high-frequency hemostatic forceps for eleven cases of hemorrhagic gastric ulcer with exposed vessels. All of the cases were treated by endoscopic hemostasis with the device. Initial hemostasis obtained in all of the cases(100%), and no rebleeding was observed. Additional treatment, however, was necessary in four cases(36%). No serious complication, like perforation, was observed. We concluded that endoscopic hemostasis using high-frequency hemostatic forceps for hemorrhagic gastric ulcer is safe and effective method.

Hemostasis, Endoscopic↗