Rectal leiomyoma with fibromuscular obliteration mimicking adematous lesion.
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Biomedical subjects
Publications and source records attributed to C Kawanami.
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It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.
The prevalence of Helicobacter pylori infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new H pylori acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with H pylori. Following acquisition of H pylori infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after H pylori acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus H pylori infection may have an inhibitory effect on the development of FGPs.
The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.
Recurrent intestinal ulcer is a frequent problem in the management of Behçet's disease. However, no standard therapy for intestinal Beheçt's disease has been established. We report two patients with intestinal Behçet disease and recurrent ileal ulcers who were treated successfuly with a lipid emulsion of dexamethasone. In one patient, the cecal ulcer did not relapse after the intravenous administration initiation of a lipid emulsion of dexamethasone once a week, despite the discontinuation of prednisolone. In the other patient, the cecal ulcer showed a healing tendency, and oral administration of prednisolone was reduced from 40 to 15 mg/day after intravenous administration of a lipid emulsion of dexamethasone. Both patients experienced no complications associated with the administration of the emulsion. These results suggest that an intravenous drug delivery system using a lipid emulsion of dexamethasone is useful for treatment of intestinal Behçet's disease.
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Immunological interaction between the host and Helicobacter pylori seems to play a critical role in follicular formation in gastric mucosa. We reported H. pylori-induced follicular gastritis model using neonatally thymectomized mice. In this study, we investigated the involvement of various cytokines in this model. BALB/c mice were thymectomized on the third day after birth (nTx). At 6 weeks old, these mice were orally infected with H. pylori. Histological studies showed that follicular formation occurred from 8 weeks after the infection and that most of the infiltrating lymphocytes were CD4(+) and B cells. Neutrophils increased transiently at 1 week after the infection. Gamma interferon, interleukin-7 (IL-7), and IL-7 receptor were expressed in the stomach of the nTx mice irrespective of the infection. In contrast, expressions of the tumor necrosis factor alpha, IL-4 and lymphotoxin-alpha genes were remarkably upregulated by the infection. Our findings suggest that follicular formation may require cooperative involvement of a Th2-type immune response, tumor necrosis factor alpha and lymphotoxin-alpha in addition to the Th1-type immune response in H. pylori-induced gastritis in nTx mice.
Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score, histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-kappaB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-kappaB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis. This drug delivery system could be an ideal therapy for human IBD.
Recently, several retrospective studies have shown an inverse association between appendectomy and development of ulcerative colitis. We describe a 21-year-old man with distal ulcerative colitis and appendiceal involvement. The patient passed bloody stools continually during the 3 years before admission. Macroscopic and microscopic findings showed chronic moderate inflammation of the appendix and rectum. The ratio of CD4 to CD8 lymphocytes isolated from rectal and appendiceal mucosa was increased (4.3 and 3.8, respectively) compared with controls (n = 11; 1.0 in the rectum and 1.4 in the appendix). Clinical symptoms and colonoscopic and microscopic findings improved significantly after appendectomy. In addition, the amount of interferon gamma secreted from rectal lymphocytes was reduced to 89 pg/mL after surgery (before appendectomy, 254 pg/mL). However, interleukin 4 production was below detectable levels both before and after appendectomy. These findings suggest that appendectomy resulted in altered T-helper (Th)1/Th2 balance in this patient. In the 3 years since surgery, the patient has been in good condition without recurrence of symptoms. This is the first report demonstrating therapeutic benefit of appendectomy in a patient with ulcerative colitis and potential mechanistic relationship.
Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these cells is considered a very important therapeutic strategy for patients with IBD. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with poly(DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodium sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally administered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxidase activity and nitric oxide production, and gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing (125)I-labeled Dx in inflamed colon was significantly higher than in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in mice treated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal repair in experimental colitis and could be an ideal agent for treatment of human IBD.
Therapy with oral 5-aminosalicylic acid (5-ASA) for ulcerative colitis has been reported to be effective and safe. We describe a case of biochemically proven mild acute pancreatitis occurring after 9 d of oral 5-ASA therapy for ulcerative colitis. A hypersensitivity mechanism seemed to be involved in the development of pancreatitis probably owing to erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for early diagnosis of pancreatitis in patients with ulcerative colitis receiving 5-ASA administration. This is the first report of acute pancreatitis developed by oral 5-ASA therapy for the treatment of ulcerative colitis in the literature of Japan.
Crohn's disease is associated with complications in multiple organs. However, there are very few reported cases of patients with Crohn's disease with muscle symptoms and/or high serum creatine phospho-kinase (CPK) levels. We report here a patient with Crohn's disease who experienced skeletal muscle damage with extremely high serum CPK level during treatment with an elemental diet. The non-parenteral administration of large amounts of carbohydrate and limited glycogen degradation capability may be a possible causative mechanism for this elemental diet-induced muscle damage.
BACKGROUND & AIMS: Gastrin stimulates acid secretion from parietal cells and histamine release from enterochromaffin-like (ECL) cells through identical gastrin receptors. However, gastrin has been shown to have a trophic effect only on ECL cells. The aim of this study was to compare gastrin-induced signal transduction pathways in the ECL and parietal cells of Mastomys natalensis, an African rodent. METHODS: Both ECL and parietal cells were isolated from the gastric mucosa of M. natalensis, and intracellular signal transduction events in response to gastrin were investigated. RESULTS: Gastrin elicited histamine release from ECL cells and acid secretion from parietal cells in association with enhanced inositol phospholipid turnover. Although gastrin increased [3H]thymidine incorporation into ECL cells, it had no effect on parietal cells. Moreover, tyrosine phosphorylation and activation of mitogen-activated protein (MAP) kinase as well as c-fos and c-jun gene expression were augmented only in ECL cells. In addition, gastrin increased the formation of guanosine triphosphate-Ras with a simultaneous decrease in guanosine diphosphate-Ras levels in ECL but not in parietal cells. CONCLUSIONS: Although gastrin receptors are present in both ECL and parietal cells, they activate the Ras-MAP kinase pathway only in ECL cells.
Adhesion molecules and cytokines are known to be involved in the formation of acute gastric mucosal injury. However, it is not clear whether the gastric mucosal cells express these molecules and modulate the inflammation. To clarify whether gastric mucosal cells express intercellular adhesion molecule-1 (ICAM-1) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), and cytokine-induced neutrophil chemoattractant-2-beta (CINC-2-beta)) in the formation of gastric mucosal injury, we have used rat indomethacin-induced gastric mucosal lesions as an in vivo model. The gene expression of all cytokines and ICAM-1 increases at the early stages of indomethacin-induced gastritis (TNF-alpha and IL-1-alpha gene expression began to increase earlier than that of ICAM-1 and CINC-2-beta) and can mainly be detected in the gastric epithelial layer. To further identify the source of those molecules, the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution. ICAM-1 and CINC-2-beta gene expressions are particularly enhanced in the middle-sized cell fractions that are rich in gastric mucous-producing cells. The effect of TNF-alpha or IL-1-alpha on the gene expression of ICAM-1 and cytokines was examined by using RGM-1 cells as a model for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and proinflammatory cytokine expression in response to TNF-alpha or IL-1-alpha stimulation. Moreover, immunohistochemical staining also reveals an increase in ICAM-1 and CINC protein production in RGM-1 cells in response to TNF-alpha stimulation. We conclude that gastric mucosal cells express various cytokines and an adhesion molecule during the formation of acute gastric mucosal injury and that they may modulate the inflammation.
Gastrin is a pivotal humoral factor which regulates gastric acid secretion through its receptors. There is no report, however, concerning the age-related changes of gastrin receptor gene expression in the stomach. Northern blot analysis and in situ hybridization were performed to clarify the changes of gastrin receptor expression during the aging. In situ hybridization clarified that gastrin receptor mRNA was expressed mainly in enterochromaffin-like (ECL) cells in adult rat gastric mucosa. With aging, gastrin receptor gene expression in the stomach increased with the concomitant increase in histidine decarboxylase mRNA. Since histidine decarboxylase is a marker of gastric ECL cells, the augmented gastrin receptor mRNA in aged rats may be caused by the increased ECL cells in gastric mucosa during the aging.
We examined 13 human gastric carcinoma cell lines for the expression of both c-kit and stem cell factor (SCF). Expression of mRNAs was detected by both Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), and expression of translated proteins was detected by western blotting. Using RT-PCR we confirmed the expression of c-kit in five (ECC12, TMK1, MKN7, GCIY, and HGC27) cell lines. Northern blot analysis showed coexpression of both c-kit and SCF in ECC12 and expression of SCF in five other (MKN74, MKN1 OKAJIMA, KATOIII, and TMK1) cell lines. SCF stimulated both tyrosine phosphorylation of c-kit and growth of ECC12, whereas it did not stimulate those of GCIY. The sizes of c-kit transcript and protein in GCIY were slightly smaller than those of the reported ones, suggesting the presence of a biologically inactive truncated form of c-kit in GCIY. The present study suggests that c-kit/SCF system might play an important role in the carcinogenesis and tumor growth of ECC12 and that the truncated form of c-kit in GCIY might not be associated with malignant transformation.
Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.
A 45-year-old woman with type IIIa glycogen storage disease (GSD IIIa) died of variceal hemorrhage secondary to liver cirrhosis. The postmortem examination disclosed increased intracellular glycogen in the liver as well as in the heart and skeletal muscle. Although most liver injuries in GSD IIIa have been considered to be non-progressive in adulthood, liver cirrhosis can be a cause of death in some patients.