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Biomedical subjects

Kentaro Sugano

Publications and source records attributed to Kentaro Sugano.

At least 73 records · Page 4Linked to original sources

Systematic review for evaluation of tolerability of nonsteroidal antiinflammatory drugs in osteoarthritis patients in Japan.

To evaluate the gastrointestinal tolerability of nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis patients in Japan, a systematic review of Japanese randomized controlled trials was performed. This study consisted of double-blind, randomized, controlled clinical trials with 4-week NSAID treatment of osteoarthritis patients in Japan. The analysis included 4725 patients from 25 trials. On average the cumulative incidences of patients who had experienced any adverse reaction and any adverse digestive reaction were 14.3% [95% confidence interval (CI) 13.3%-15.3%] and 10.4% (95% CI 9.4%-11.4%), respectively. The cumulative incidence for the upper gastrointestinal (GI) symptoms such as abdominal pain, nausea/vomiting, and dyspepsia was estimated to be approximately 10.9%. When the risk of upper GI symptoms was compared between males and females, the summary odds ratio was 1.71 (95% CI 1.11-2.65). Comparing the risk of upper GI symptoms between patients 59 years of age and younger and those 60+ years old, the summary odds ratio was 1.07 (95% CI 0.75-1.52). Despite the incidence of adverse reactions varying across the drugs being used, there was an obvious increased risk of GI symptoms.

Anti-Inflammatory Agents, Non-Steroidal↗

Proteasome is required for class I-restricted presentation by Fcgamma receptor-mediated endocytosis in primary biliary cirrhosis.

There is a considerable database on the effector mechanisms for CD8 recognition of PDC-E2 in primary biliary cirrhosis (PBC). In particular, the specific roles of MHC class I, the mitochondrial autoepitope, and the liver-specific T cell precursor frequency, are defined for HLA-A2.1 patients. There is evidence for a role of MHC class I-mediated presentation of exogenous antigens, or cross-presentation, in the development of the antimitochondrial response and a contributory role of Fcgamma receptor-mediated uptake of autoantigen-autoantibody complexes for the induction of a PDC-E2 specific autoreactive CTL response. Based on this background, we examined potential intracellular pathways for processing the immunodominant mitochondrial autoantigen, PDC-E2, by dendritic cells (DC). In particular, we studied the effects of the proteasome inhibitor lactacystin and the endosomal acidification inhibitor bafilomycin on the induction of PDC-E2-specific CTL response in PBC. Importantly, our data indicate that pre-treatment with either lactacystin or bafilomycin inhibits the PDC-E2 immune complex-induced CTL response. The processing and presentation of PDC-E2 by CD8(+)T cells is mediated by proteasomes and facilitated by Fcgamma receptor-mediated endocytosis. This data reflects another layer of interaction between components of the immune system in the development of autoimmunity. Further characterization of autoantigen uptake and processing may lead to potential therapeutic intervention.

Acetylcysteine↗

Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus.

We encountered a patient with sporadic acute hepatitis E who had not traveled to areas endemic for hepatitis E virus (HEV) infection and may have been infected in Japan. The patient was a 47-year-old male who had no history of blood transfusion or contact with travelers to hepatitis E-endemic regions or unspecified individuals. The disease presented with general malaise, fever, and brown urine as chief complaints in April 2002. Various hepatitis virus markers were negative, but IgM class antibodies to hepatitis E virus (anti-HEV) and HEV RNA were positive, and the patient was diagnosed with acute hepatitis E. The entire nucleotide sequence (7240 bases) of HEV (HE-JK4) isolated from this patient was determined and compared with known HEV strains. HE-JK4 belonged to genotype IV and exhibited higher similarities to genotype IV HEV strains previously isolated in Japan than to those isolated in China, Taiwan, and Vietnam. The patient's family members living with him were negative for anti-HEV IgG and IgM, but their pet cat was anti-HEV IgG-positive. This finding suggests a potential route of infection of sporadic cases of hepatitis E in Japan. Since the presence of HEV indigenous to Japan is predicted, HEV infection should be considered in the diagnosis of acute hepatitis of unknown cause, even for patients who have not traveled abroad.

Journal Article↗

A new method of enteroscopy--the double-balloon method.

The diagnosis and treatment of diseases of the small intestine have been impeded by difficult technical challenges. Traditionally, endoscopic evaluation of this organ has required open laparotomy with the surgically assisted passage of the scope through the intestine. Nonsurgical endoscopic techniques have been developed, including push enteroscopy, passage of a scope over a guide-string, and a method that depends on peristalsis to advance the instrument, but each of these is subject to severe limitations. A novel procedure has been devised, whereby an endoscope and a soft flexible overtube, each of which has an inflatable balloon attached to its distal end, are employed together. The technique is described in detail in the present article. Double-balloon enteroscopy allows visualization of the entire small intestine, to and fro examination of an area of interest, and the taking of biopsy specimens in a manner that is safer, quicker and less painful than previous techniques. It constitutes an important advance in the diagnosis and management of bleeding and other small intestinal disorders.

Catheterization↗

Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice.

Gastric intestinal metaplasia occurs as a pathological condition in the gastric mucosa. To clarify how an intestine-specific homeobox gene, Cdx2, affects the morphogenesis of gastric mucosa, we generated transgenic mice expressing Cdx2 in parietal cells. Until Day 18 after birth, the number of parietal cells inthegastric mucosa of transgenic mice was the same as for their normal littermates. However, at Day 19, we detected several glands in which parietal cells disappeared and the proliferating zone moved from the isthmus to the base of the glands. Thereafter, parietal cells decreased gradually and disappeared at Day 37. All of the gastric mucosal cells, except for enterochromaffin-like (ECL) cells, were completely replaced by intestinal metaplasia, consisting of goblet cells, enteroendocrine cells, and absorptive cells expressing alkaline phosphatase. Pseudopyloric gland metaplasia was also formed. The transgenic mouse is a very useful model for clarifying physiological differentiation of gastric and intestinal cell lineages and analyzing the molecular events from intestinal metaplasia to adenocarcinoma.

Aging↗

Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia.

BACKGROUND: The CDX1 and CDX2 genes are intestinal transcription factors that may be involved in the regulation of proliferation and differentiation of intestinal epithelial cells. There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in chronic gastritis and intestinal metaplasia. Accordingly, we examined the expression of CDX1/2 and its association with the expression of other intestinal metaplasia-associated genes during the development of intestinal metaplasia. METHODS: The expression of CDX1/2 genes was analyzed, using the reverse transcriptase-polymerase chain reaction, in 44 human gastric tissue samples obtained endoscopically. The expressions of mucin markers (MUC2, MUC5AC), intestine-specific genes (sucrase-isomaltase, human defensin-5, alkaline phosphatase), a gene marker for fundic gland area (H+/K+ATPase beta subunit), and a gene for entire gastric glands (pepsinogen C) were also comparatively analyzed. RESULTS: There was no expression of CDX1/2 in gastric mucosa not infected by Helicobacter pylori. The prevalence of CDX1 mRNA expression was significantly higher in mucosa with intestinal metaplasia than in mucosa without intestinal metaplasia. It is noteworthy that CDX2 was expressed in the antral and fundic mucosa in the absence of the expression of CDX1 and gene markers for intestinal metaplasia. CONCLUSIONS: The expression of CDX2 precedes those of CDX1, sucrase-isomaltase, other intestine-specific genes (human defensin-5, alkaline phosphatase), and MUC2 during the progression of intestinal metaplasia. These findings imply that the expression of CDX2 may trigger the initiation and development of intestinal metaplasia.

Adult↗

Biliary guidewire facilitates bile duct biopsy and endoscopic drainage.

BACKGROUND: The introduction of a guidewire through bile duct strictures may facilitate transpapillary bile duct biopsy and subsequent biliary drainage. METHODS: Endoscopic bile duct biopsy was attempted in 61 patients with bile duct strictures. After the introduction of a guidewire into the bile duct, biopsy forceps were inserted via the papilla. Both devices were inserted through the working channel (3.2 mm in diameter) of a conventional duodenoscope. After the procedure, an endoscopic naso-biliary drainage catheter was advanced along the guidewire. The success rate of inserting the biopsy forceps, the sensitivity of the biopsy, and the success rate of endoscopic biliary drainage after the biopsy were analyzed prospectively. RESULTS: The final diagnosis was malignant strictures in 50 patients and benign strictures in 11. The success rate of inserting biopsy forceps without performing endoscopic papillary balloon dilation was 85%. The sensitivity of the biopsy for primary bile duct cancer (83%) was significantly higher (P < 0.05) than that of pancreatic cancer (47%). All patients had successful endoscopic biliary drainage after the procedure. CONCLUSION: A previously placed guidewire facilitates insertion of biopsy forceps and endoscopic biliary drainage. The histological diagnosis of cancer is more likely with bile duct cancer than with pancreatic cancer.

Bile Duct Neoplasms↗