Light microscopy of GTP-binding protein (Go) immunoreactivity within the retina of different vertebrates

To examine species differences in the distribution pattern of guanosine triphosphate (GTP)-binding protein (Go) within the vertebrate retina, paraffin-embedded retinae from a number of vertebrate species, including the goldfish, frog, turtle, chicken, monkey, and human, were immunohistochemically stained with affinity-purified antibody against the alpha-subunit of Go. Go-immunoreactive products were found to be located in the neuropil, but not in the cell bodies of neurons, in the retina of all these species. However, some species differences were observed. In the frog, monkey and human, the inner plexiform layer (IPL) was homogeneously stained with this antibody, but in the goldfish, turtle and chicken, the IPL was heterogeneously stained. In the frog, chicken, turtle and human, the outer plexiform layer (OPL) was densely stained with this antibody, but in the goldfish and monkey, the OPL was rather faintly immunoreactive to the antibody. In the goldfish, monkey and human, the outer nuclear layer (ONL) was not immunoreactive to the Go-antibody, whereas in the frog, turtle and chicken, the ONL was immunoreactive to it. The implications of these species differences in Go localization in the vertebrate retina are discussed.     

Alteration of epicardial lymphatics in lymphostatic canine hearts

Summary This study was conducted in an attempt to establish a method for evaluation of cardiac lymphostasis in autopsy cases and animal experiments. Ten mongrel dogs were operated on to induce cardiac lymphostasis in terms of ligation of coronary lymphatics. From the following day to 6 months after surgery, epicardial lymphatics were visualized to measure the volumes and densities of the lymphatics. The mean volume, measured after 1 week (0.27±0.09), 2 weeks (0.32±0.04), and 6 months (0.23±0.05) continued to be higher than that on the first day (0.16±0.04) (P<0.05). The density, measured after 1 week (2.6±0.3) and 2 weeks (3.7±0.7), also showed higher values, than that on the 1st day (1.7±0.7) (P<0.01). However, 6 months later, the measured value (1.9±0.03) showed no statistical difference compared to that of the 1st day. Observation under a binocular microscope revealed impressions of a progressive increase in both number and thickness of the lymphatics as late as 2 weeks after the induction. However, 6 months later, there was marked dilatation and a relative decrease in the number of lymphatics.     

Feeding Administration of Daikenchuto Suppresses Colitis Induced by Naive CD4+ T Cell Transfer into SCID Mice

Background and Aims

Daikenchuto, a traditional Japanese herbal medicine, suppresses bacterial translocation by improvement of gastrointestinal motility and blood flow. As Daikenchuto reportedly reduces gastrointestinal inflammatory activity by these mechanisms, we analyzed whether Daikenchuto suppresses experimental colitis and reduces inflammatory cytokine expression in a mouse model.

Methods

Colitis was induced by transfer of naive CD4⁺ T cells of BALB/c mice into SCID mice, and mice were given either control or 2.7?% Daikenchuto-containing feed. We investigated body weight, clinical symptoms, histological changes, and Th1- and Th17-cytokine expression. Cytokine mRNA expression was analyzed using real-time RT-PCR. The ratio of IL-17⁺ and IFN-γ⁺ CD4⁺ T cells were analyzed by flow cytometry.

Results

Daikenchuto delayed the development of colitis and significantly reduced the histological inflammation scores. Analyses of cytokine mRNA revealed that Th17 cytokines were significantly decreased in colons of mice that received Daikenchuto. Absolute numbers of IL-17⁺ or IFN-γ⁺ CD4⁺ T cells per colon were less in mice receiving Daikenchuto than in mice that received control feed, as both groups received naive CD4⁺ T cells to induce colitis.

Conclusions

We demonstrated that feeding administration of Daikenchuto suppresses colitis induced by naive CD4⁺ T cell transfer into SCID mice. Daikenchuto may show clinical benefit in the treatment of human inflammatory bowel disease and further studies are warranted.     

Improved techniques for double-balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography

AIM: To investigate the clinical outcome of double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) in patients with altered gastrointestinal anatomy.METHODS: Between September 2006 and April 2011, 47 procedures of DB-ERCP were performed in 28 patients with a Roux-en-Y total gastrectomy (n = 11), Billroth II gastrectomy (n = 15), or Roux-en-Y anastomosis with hepaticojejunostomy (n = 2). DB-ERCP was performed using a short-type DBE combined with several technical innovations such as using an endoscope attachment, marking by submucosal tattooing, selectively applying contrast medium, and CO₂ insufflations.RESULTS: The papilla of Vater or hepaticojejunostomy site was reached in its entirety with a 96% success rate (45/47 procedures). There were no significant differences in the success rate of reaching the blind end with a DBE among Roux-en-Y total gastrectomy (96%), Billroth II reconstruction (94%), or pancreatoduodenectomy (100%), respectively (P = 0.91). The total successful rate of cannulation and contrast enhancement of the target bile duct in patients whom the blind end was reached with a DBE was 40/45 procedures (89%). Again, there were no significant differences in the success rate of cannulation and contrast enhancement of the target bile duct with a DBE among Roux-en-Y total gastrectomy (88 %), Billroth II reconstruction (89%), or pancreatoduodenectomy (100%), respectively (P = 0.67). Treatment was achieved in all 40 procedures (100%) in patients whom the contrast enhancement of the bile duct was successful. Common endoscopic treatments were endoscopic biliary drainage (24 procedures) and extraction of stones (14 procedures). Biliary drainage was done by placement of plastic stents. Stones extraction was done by lithotomy with the mechanical lithotripter followed by extraction with a basket or by the balloon pull-through method. Endoscopic sphincterotomy was performed in 14 procedures with a needle precutting knife using a guidewire. The mean total duration of the procedure was 93.6 ± 6.8 min and the mean time required to reach the papilla was 30.5 ± 3.7 min. The mean time required to reach the papilla tended to be shorter in Billroth II reconstruction (20.9 ± 5.8 min) than that in Roux-en-Y total gastrectomy (37.1 ± 4.9 min) but there was no significant difference (P = 0.09). A major complication occurred in one patient (3.5%); perforation of the long limb in a patient with Billroth II anastomosis.CONCLUSION: Short-type DBE combined with several technical innovations enabled us to perform ERCP in most patients with altered gastrointestinal anatomy.     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Intestinal tuberculosis of the terminal ileum causing obstructive ileus and tuberculous peritonitis and presenting numerous peritoneal small red nodules: a case report

A 38-year-old woman suffering from lower abdominal pain was referred to our hospital. Abdominal computed tomography showed marked thickening of the terminal ileum to the cecum, localized collection of ascites, and multiple mesenteric lymphadenopathy. A barium contrast small bowel series showed solitary severe stenosis of the terminal ileum with marked swelling of the ileocecal valve, where colonoscopy could not pass through, suggesting that ileal stenosis was caused by intestinal tuberculosis. She also showed strongly positive tuberculin skin test. Laparoscopy-assisted ileocecal resection was performed for confirmation of diagnosis and removal of the stenotic intestinal lesion. Laparoscopically, numerous small red nodules scattered on the stenotic ileal serosa, peritoneum, and mesenterium. Histopathological examination revealed ileal tuberculosis causing ulcerative stricture, and mesenteric tuberculous lymphadenitis. The small red nodules were formed of hemorrhagic tuberculous nodules.     

Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled study

Bovine lactoferrin (bLF) has antibacterial activity against Helicobacter pylori in vitro and is effective to suppress bacterial colonization in mice. The aim of our study was to evaluate the efficacy of orally administered bLF on H. pylori colonization in humans by a randomized, double-blind, placebo-controlled study. Fifty-nine healthy subjects positive for H. pylori infection were recruited. Subjects were randomized into two groups. The bLF group received bLF tablets at a dosage of 200 mg b.i.d. for a period of 12 weeks, and the control group received placebo tablets without bLF. The ¹³C-urea breath test (UBT) was performed before, during, and at the end of administration, and again 4 weeks after administration. Positive response was defined as more than 50% decrease of the UBT value at the end of administration. Positive response was observed in 10 of 31 bLF-treated subjects (32.3%) and 1 of 28 control subjects (3.6%), indicating that the rate of positive response in the bLF group was significantly higher than that in the control group (bLF vs. control, P < 0.01). These results suggested that bLF administration is effective to suppress H. pylori colonization.     

Predictive factors for colonic diverticular rebleeding: a retrospective analysis of the clinical and colonoscopic features of 111 patients

Background/Aims

Colonic diverticular bleeding can stop spontaneously or be stopped by endoscopic hemostasis. We analyzed the clinical and colonoscopic features of patients with colonic diverticular bleeding to establish the predictive factors for rebleeding.

Methods

A total of 111 patients (median age, 72 years) with colonic diverticular bleeding in Aso Iizuka Hospital between April 2007 and July 2010 were enrolled. Age, sex, body mass index (BMI), comorbidity, medication, location of bleeding, colonoscopic findings and hemostatic methods were analyzed retrospectively from the hospital records.

Results

The most common sites of bleeding were the ascending (39.6%) and sigmoid (29.7%) colon. Overt rebleeding occurred in 30 patients (27.0%). Spontaneous hemostasis was seen in 81 patients (73.0%), and endoscopic hemostatic treatment was performed in 30 patients. The BMI in the patients with colonic diverticular rebleeding was significantly higher than in patients without rebleeding. Colonoscopic findings of actively bleeding or nonbleeding visible vessels in the responsible diverticula were more frequent in the group with rebleeding.

Conclusions

A higher BMI and colonoscopic findings of actively bleeding or nonbleeding visible vessels can be used as predictive factors for colonic diverticular rebleeding. Patients with such findings should be carefully followed up after hemostasis of the initial colonic diverticular bleeding.     

Gastric gastrointestinal stromal tumor smaller than 20 mm with liver metastasis

There have been no reports of gastric gastrointestinal stromal tumors (GISTs) <20 mm with distant metastasis. We report a case of a 15-mm gastric GIST with liver metastasis 1 year after surgical resection of the primary lesion. A 35-year-old man underwent routine esophagogastroduodenoscopy in July 2009. A submucosal tumor (SMT) <20 mm was incidentally detected at the posterior wall of the gastric body. Endoscopic ultrasound (EUS) indicated that it was a gastrointestinal mesenchymal tumor, including GIST, leiomyoma or schwannoma. He did not accept regular follow-up for this gastric SMT, therefore local laparoscopic excision was carried out in October 2009. The final pathological diagnosis after surgery was GIST, 15 mm in size, and a mitotic rate of 7/50 high-power fields, which did not indicate a high metastatic risk. The patient was followed up regularly without adjuvant chemotherapy. At 1 year after surgery, a space-occupying lesion ~15 mm was detected in the left lobe of the liver by abdominal ultrasound, where no mass lesion had been observed before surgery. To make a definite diagnosis of the hepatic mass lesion, EUS-guided fine-needle aspiration was performed, which demonstrated a metastatic liver tumor from a gastric GIST. Although this was a rare case, we should keep in mind that gastric GISTs do have a chance of malignant behavior, even if <20 mm.     

The effect of cholinergic antagonists on increases of spontaneous locomotor activity and body weight induced by the administration of morphine to tolerant rats

Increases both in spontaneous locomotor activity and in body weight were observed after the administration of morphine-HCl (100 mg/kg, i. p.) to tolerant rats. These signs were inhibited by pretreatment of the morphine-tolerant rats with cholinergic antagonists; the inhibition by scopolamine was greater than that by methscopolamine or atropine. These results suggest that both central and peripheral cholinergic mechanisms participate in the increases both in spontaneous locomotor activity and in body weight of tolerant rats after morphine administration.Portions of this work were presented at the 42nd and 43rd meeting of Japanese Pharmacological Society in Kanto district, May 23, 1970 and October 24, 1970 and in Jap. J. Pharmacol. 20, 455–457 (1970), as a preliminary report.