Seisuke Okamura

Development of fluorescence-emitting antibody labeling substance by near-infrared ray excitation

Abstract Indocyanine green succinimidyl esters, near-infrared labeling dyes, were synthesized. These reagents were indocyanine green derivatives possesing N-hydroxysuccinimidyl groups capable of reacting with proteins. The absorption maximum of indocyanine green-labeled human IgG was 785 nm, and its fluorescent excitation and emission maxima were 768 nm and 807 nm, respectively.

Relationship among gastric motility, autonomic activity, and portal hemodynamics in patients with liver cirrhosis

We examined the effects of the autonomic nervous function and the volume of portal blood flow to clarify the mechanism of the abnormal gastric motility in patients with liver cirrhosis.

Colorectal xanthomas with polypoid lesion: Report of 25 cases

Little attention has been paid to colorectal xanthoma. To clarify the clinical and pathological features of colorectal xanthoma, we report 28 colorectal xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells and showed polypoid configuration. Median age of the patients was 64 years and there were 15 men and 10 women. Diabetes mellitus, constipation, and hyperlipidemia were found in two, one, and seven patients, respectively. Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the remaining 11 in the rectum. Twenty‐three polyps (82.1%) were sessile. Twelve (60.0%) of twenty polyps that were recorded were reddish in color. Only two polyps revealed a yellowish tone. Microscopically, foamy cells were present in the lamina propria, but the submucosa did not contain foamy cells. Immunohistochemically, the foamy cells invariably expressed extensive positivity for CD68. The colonic glands showed a deformity in the case with moderate to intense density of the foamy cells. The surface epithelium showed a hyperplastic change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also associated with hyperplastic changes. The basement membrane of the surface epithelium was often thickened. Cell debris and proliferation of the capillaries were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%) xanthomas, respectively. Previous mucosal minute injury was suggested as the pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the term “xanthomatous polyp” rather than xanthoma in the colorectal region. They may be regarded as a novel type of colorectal non‐neoplastic polyp.

Ultrasonographic assessment of gastric motility in diabetic gastroparesis before and after attaining glycemic control.

BackgroundGlycemic control is important for maintaining gastric motility in diabetic patients, but gastric motility has not yet been studied ultrasonographically in relation to glycemic control.MethodsWe made such observations before and after establishing glycemic control in diabetic patients with gastroparesis. We studied 30 diabetic patients with upper abdominal digestive symptoms who were hospitalized for correction of poor blood sugar control and who underwent upper digestive tract endoscopy to rule out structural causes such as gastric/duodenal lesions. Gastric motility was evaluated by transabdominal ultrasonography, using a test meal, before and after attainment of glycemic control (within 3 days after admission and 3 days before discharge). Also, upper abdominal digestive symptoms present on admission and at discharge were compared.ResultsAfter glycemic control was established, contractions of the antral region were more frequent than before the attainment of control (8.93 ± 1.17/3 min vs 7.63 ± 2.22/3 min, respectively; P < 0.001). Glycemic control also significantly improved gastric emptying (before glycemic control, 49.2 ± 14.8%; after, 67.1 ± 11.5%; P < 0.001). This was also true for the motility index, concerning antral gastric contractility (before control, 2.97 ± 1.57; after, 3.75 ± 1.09; P < 0.05). Upper abdominal symptom scores were also significantly lower after attainment of control than before (0.47 ± 0.78 vs 3.17 ± 2.00, respectively; P < 0.001).ConclusionsThese findings suggest that attaining glycemic control improves gastric motility and attainments upper abdominal symptoms in diabetic patients with gastroparesis.

A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors

BackgroundRadiation proctitis is an increasingly prevalent problem, with many patients being treated with radiotherapy for pelvic cancers. However, the mechanisms by which radiation proctitis develops in humans are not well understood. In this study, the expression profiles of angiogenic factors were analyzed to clarify their role in the etiology of radiation proctitis.MethodsRectal biopsies were taken from 8 patients with radiation proctitis and 8 normal subjects. Protein lysates of the tissues were applied to an antibody array for angiogenesis-related factors. The mRNA level of each factor was evaluated by Taqman real-time PCR. Immunohistochemistry was performed using the labeled streptavidin biotin method.ResultsAntibody array analysis revealed 2.12- to 7.31-fold higher expression levels of angiogenin, fibroblast growth factor 1 (FGF1), endoglin, matrix metalloproteinase (MMP)-8, urokinase-type plasminogen activator (uPA) and maspin in radiation proctitis tissues compared with normal rectal mucosa. The mRNA level of each factor in radiation proctitis tissue was significantly higher than in normal rectal mucosa, suggesting their transcriptional activation. Immunohistochemical staining showed strong expression of angiogenin and maspin in rectal epithelia, MMP-8 and uPA in infiltrating lymphocytes, FGF1 in fibroblasts and endoglin in endothelial cells. The expression of VEGF was not evident.ConclusionsOur results suggest that in radiation proctitis, MMP-8 and uPA cooperatively degrade the extracellular matrix and basement membrane to provide space for angiogenesis. Simultaneously, angiogenin and FGF1 promote endothelial cell proliferation, and endoglin induces vessel formation, culminating in angiogenesis. Inhibitors of angiogenic factors such as angiogenin and FGF1 may be effective for treating radiation proctitis.

Development of agents for reinforcement of fluorescence on near-infrared ray excitation for immunohistological staining

Fluorescence intensity of indocyanine green (ICG) derivative (ICG-sulfo-OSu) was too low for its use to detect microlesions. Therefore, we examined the effects of reinforcement agents on ICG-sulfo-OSu labeled antibodies. Solutions of distearoylphosphatic acid sodium salt (DSPA) and octylglucoside (OG) in physiological phosphate buffered saline (PBS) were found to increase the intensity of fluorescence of ICG-sulfo-OSu labeled antibodies, with shift in the fluorescence peak wavelength from 804 to 821 nm.

Lymphoepithelioma-like carcinoma of the esophagus: Report of a case with non-progressive behavior

Lymphoepithelioma‐like carcinoma (LELC) of the esophagus is extremely rare and the prognosis has been described to be favorable. Herein, the case is reported of esophageal LELC showing non‐progressive course for 1 year. The patient was a 70‐year‐old Japanese man with a submucosal tumor in the lower esophagus. The tumor was endoscopically regarded as a benign leiomyoma. One year after the first endoscopic examination, the size of the lesion remained unchanged despite no treatment. Histologically, the tumor showed undifferentiated carcinoma associated with dense lymphocytic and plasma cell infiltration. Lymphoid follicles surrounded the tumor cell nests. Immunohistochemically, Ki‐67 labeling index of the tumor cells were 76.0%, and there were few single‐strand DNA‐positive apoptotic cells. In situ hybridization using a digoxigen‐labeled Epstein–Barr virus (EBV)‐encoded small RNA (EBER)‐1 riboprobe failed to detect the presence of EBV infection. Physicians should be aware that esophageal LELC endoscopically mimics benign submucosal tumor. This case may demonstrate that esophageal LELC is a slow‐growing tumor and it is related to immune reaction.

Endoscopic sonography in the diagnosis of xanthogranulomatous cholecystitis

Xanthogranulomatous cholecystitis (XGC) is an unusual inflammatory disease of the gallbladder that may simulate gallbladder cancer. We report the findings with conventional sonography, endoscopic sonography (EUS), and CT in 3 cases of XGC. EUS could visualize hyperechoic nodules in the gallbladder wall, probably representing xanthogranulomas, but loss of the multilayered structure of the gallbladder wall and infiltration into adjacent organs make differentiating XGC from gallbladder cancer difficult with EUS alone.

Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: A multicenter study of 2283 cases

The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured.

Colonic pseudolipomatosis, microscopically classified into two groups

Background:  Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology.