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OBJECTIVE: Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication.METHODS: Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted.RESULTS: The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9;p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects.CONCLUSION: The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.(Am J Gastroenterol 2005;100:1–8) [ABSTRACT FROM AUTHOR]

Background We investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of 13-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD). Methods. The expression of IL-15 and IL-15Rα mRNA and protein in inflamed colonic mucosal tissues with IBD), and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Rα on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues. Results. The intensity of IL-15 and IL-15Rα mRNA was greater in the mucosal tissues of patients with IBD), especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to con- trol tissues, mononuclear cells positive for IL-15Rα protein were observed in greater proportions in tissue sections from patients with IBD), especially in those from patients with UC, where IL-15Rα protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Rα-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination. Conclusions. These data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD), especially in those with UC. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) have intestinal and extraintestinal symptoms that can greatly impair their quality of life. They must rely on multiple medications with aminosalicylates, corticosteroids, and purine analogues to control these symptoms. Although decades of clinical experience in IBD management has led to optimized approaches for achieving the induction and maintenance of remission, the disease in some patients is still refractory to conventional medical treatment, or the effectiveness of these drugs can be limited by treatment-related side effects. Significant progress in our understanding of the pathogenesis of IBD has yielded several immunomodulatory approaches with novel biological agents or apparatus, such as cyclosporine, cytoprotective agents, infliximab, and leukocytapheresis. Further immunomodulatoy therapy, aiming at the inhibition of molecular and cellular mediators, is anticipated, in parallel with the clarification of im-munoinflammatory pathways in IBD. An additional goal will be to identify factors predictive of response to treatment with each novel immunomodulatory agent or apparatus. This will help provide each patient with optimized and individualized therapy, thereby increasing therapeutic efficacy and reducing possible side effects. [ABSTRACT FROM AUTHOR]

ß-Catenin is an essential element for the transcriptional activation of target genes in the Wnt signaling cascade and is also a cell adhesion molecule that couples with cadherins. Although plakoglobin (?-catenin), a closely related homologue of ß-catenin, is also known to be a cell adhesion molecule, its function as a transcriptional factor has not been revealed in detail. Using a human malignant mesothelioma cell line, NCI-H28, in which we have identified a homozygous deletion of the ß-catenin gene, we studied whether plakoglobin has a T-cell factor/lymphocyte enhancer factor (TCF/LEF) family-dependent transcriptional activity. Transfection with the wild-type plakoglobin expression vector induced accumulation of plakoglobin in the nucleus. Immunoprecipitation assay with cotransfection of plakoglobin and either TCF-4 or LEF-1 detected binding of plakoglobin to TCF-4 or LEF-1. Luciferase reporter assay demonstrated transcriptional activity of the wild-type plakoglobin when transfected with TCF/LEF, although plakoglobin showed less activity than ß-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous ß-catenin into the nuclei. Furthermore, small interfering RNA directed against plakoglobin suppressed expression of endogenous plakoglobin and its transcriptional activity, suggesting that endogenous plakoglobin has a weak transcriptional activity. These results suggest that plakoglobin can activate the Wnt signaling cascade directly without interaction of ß-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like ß-catenin.Oncogene (2004) 23, 964-972. doi:10.1038/sj.onc.1207254 Published online 8 December 2003 [ABSTRACT FROM AUTHOR]

Background. No effective treatment for advanced esophageal cancer extending to adjacent organs or associated with distant metastasis is known. We prospectively analyzed the efficacy of concurrent chemoradiotherapy with uracil plus tegafur (UFT) and cisplatin (CDDP) for such cases of advanced esophageal cancer. Methods. Patients with advanced cancers received 60 to 70 Gy of radiotherapy given during a period of 7 weeks, concurrently with daily oral UFT (200 mg/m2 per day), and a 24-h infusion of CDDP (70 mg/m2) on days 8 and 36. After chemoradiotherapy, UFT (250 mg/m2/per day) was administered daily for 1 year, while CDDP (80 mg/m2) was administered twice every 4 weeks. Results. Patients with stage III disease numbered 31, while 24 had stage IV disease according to the tumor-node-metastasis (TNM) staging. Including all patients, complete response (CR) occurred in 20% and partial response (PR) in 51%. In stage III patients, CR, PR, and CR+PR rates were 29%, 48%, and 77%, respectively. In stage IV patients, CR, PR, and CR+PR rates were 8%, 54%, and 63%. Grade 4 leukocytopenia occurred in 22% of patients, and grade 3 pain, nausea/vomiting, and oral mucositis occurred in 7%, 9%, and 4% of patients respectively, but resolved after the reduction or discontinuation of chemoradiotherapy. Median survival in stage III patients was 415 days (range, 3 to 3046 days), and in stage IV patients, it was 187 days (range, 75 to 764 days). The 2-year survival rate in stage III patients was 25% and it was 4% in stage IV patients. The 5-year survival rate in stage III patients was 7%, while in stage IV patients it was 0%. Conclusion. This combined treatment may be a promising nonsurgical management option for locally advanced esophageal cancer, and can achieve good palliative effects in patients with distant metastasis. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the precise mechanisms leading to the development of acute gastric mucosal lesions (AGMLs). We investigated whether the pathologic mechanism of AGMLs resulting in damage to epithelial cells is associated with cytotoxic molecules expressed by activated intraepithelial lymphocytes (IELs). Methods: The expression of the lymphocyte markers, CD3, CD4, CD8, CD20, T-cell-restricted intracellular antigen (TIA)-1, and granzyme B (GrB)-7 in IELs and that of single-stranded DNA (ssDNA) in apoptotic epithelial cells were evaluated by immunohistochemistry, using endoscopic biopsy specimens from 20 patients with AGMLs and 20 controls. Results: The number of CD3- and CD8-positive IELs increased in AGML specimens when compared with controls, and this increase was accompanied by a concomitant increase in TIA-1-positive cells. The epithelial cell layers of AGML specimens contained more GrB-7-positive phenotypically activated cytotoxic T cells than those in controls. Apoptotic ssDNA-positive epithelial cells were detected more frequently in AGML specimens than in controls, a feature which was paralleled by an increase in GrB-7-positive IELs in the former group of specimens. Conclusions: The present study showed that activated cytotoxic IELs and apoptotic epithelial cells are increased in number in gastric mucosa affected with AGMLs. These results provide evidence that this condition could be categorized as apoptotic gastritis with activation of the innate immune response. [ABSTRACT FROM AUTHOR]

Bacterial diarrhea can be classified into two clinical entities, noninflammatory diarrhea and inflammatory diarrhea syndromes. The latter type of diarrhea is characterized by bloody and puruloid mucus stool, and is often accompanied by fever, tenesmus, and severe abdominal pain. Pathogenic bacteria causing the inflammatory diarrhea syndrome include Salmonella, Vibrio, Shigella, enteroinvasive and enterohemorrhagic Escherichia coli, Campylobacter, Yersinia, Chlamydia, and Clostridium difficile. The pathologic changes in the inflammatory diarrhea syndrome range from a superficial exudative enterocolitis to a transmural enterocolitis with overt ulceration. This syndrome is also designated as bacterial hemorrhagic enterocolitis because of its usual manifestation by bloody diarrhea. The diagnostic approach needs information on the patient's age, travel history, epidemiological associations, sexual practice, and medical history, including usage of antibiotics. Bacterial information can be obtained by microscopic study, culture, and the identification of specific bacterial toxins. Flexible colonoscopy with biopsy is useful for the differentiation of bacterial hemorrhagic enterocolitis from idiopathic ulcerative colitis and ischemic colitis. Physicians should be familiar with the diagnostic modalities used to detect the specific pathogens causing hemorrhagic bacterial enterocolitis; namely, bacterial culture, serology, histology, and nucleic acid technologies. [ABSTRACT FROM AUTHOR]

Cold restraint stress (CRS) induced vagal-dependent corpus mucosal erosions with hemorrhage in rats. Aggressive factors such as gastric acid, pepsin, and high-amplitude contractions have been reported to be responsible for inducing the formation of gastric lesions. Thyrotropin-releasing hormone (TRH) microinjected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus induced similar vagally mediated gastric injuries as CRS, and both were prevented by immunoneutralization with TRH antibody injected centrally. These findings indicated that TRH action in the DMN may contribute to CRS-induced gastric mucosal lesions. However, either exogenous or endogenous TRH at a subthreshold dose, which did not increase gastric acid secretion, alleviated gastric injury induced by intragastric administration of a strong irritant in rats. Previous studies have shown that the vagus participates in adaptive cytoprotection. Vagotomy or intracisternal injection of TRH-antibody completely abolished the protective effect of a mild irritant pretreatment in rats. The number of c-Fos protein-positive cells in the DMN increased in the process of adaptive cytoprotection. These results suggest that vagal afferent nerves activated by a topical gastric irritant influence DMN activity by releasing endogenous TRH, leading to protection against injury induced by a subsequent strong irritant. The dual vagally mediated action of TRH in the medulla to regulate the gastric mucosa's response to injury reflects the balance between the aggressive (acid, pepsin, motility) and protective (prostaglandin, calcitonin gene-related peptide, nitric oxide) factors recruited by the level of vagal activation. These data indicate a crucial role of medullary TRH and gastric vagal efferent and afferent circuits in the modulation of gastric integrity. [ABSTRACT FROM AUTHOR]

Background. Little information is available on the relative contribution of peptide growth factors and leukocyte-derived proteinases to the repair processes in inflammatory bowel disease (IBD). We investigated their possible roles in epithelial cell restitution and proliferation in patients with IBD. Methods. The expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor-β (TGF-β), and neutrophil elastase (NE) was examined in colonic mucosal tissues. The effects of organ culture supernatants of mucosal tissues on epithelial cell restitution and proliferation were analyzed in vitro using an intestinal cell line, IEC-6 cells. Results. Most organ cultures detected the presence of measurable levels of HGF, with a relative paucity of KGF and TGF-β activity. Greater levels of HGF were obtained in the mucosa involved with IBD, especially in patients with ulcerative colitis (UC). The mucosa involved with UC also showed higher amounts of NE. The supernatants from the mucosa involved with UC possessed a prominent stimulatory effect on the restitution of IEC-6 cells. By contrast, significant suppression beyond baseline levels was observed for the proliferation of IEC-6 cells when they were incubated with recombinant HGF plus the supernatants from the mucosa involved with UC. This suppression was diminished considerably by preincubation of the supernatants with the anti-NE antibody. Conclusions. HGF produced in the intestinal mucosa may be an important stimulator acting on epithelial cell restitution in patients with IBD. However, NE released in situ may impair mucosal repair through inhibiting epithelial cell proliferation in patients with UC. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection has been found to de-crease the expression of antral somatostatin and to in-crease the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or ex-posed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of li-popolysaccharide from H. pylori on somatostatin recep-tor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is de-creased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent devel-opment of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physi-ological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastri-tis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones. [ABSTRACT FROM AUTHOR]

We performed this study to analyze the endoscopic findings, dissecting microscopic features, and p53 immunostaining in superficial depressed-type (depressed) colorectal neoplastic lesions. METHODS: Dissecting stereomicroscopy was used to ascertain the size and pit pattern of lesions removed by endoscopic snare polypectomy. Immunohistochemical staining of p53 was performed with an antigen retrieval system using a monoclonal antibody to p53. RESULTS: All depressed neoplastic lesions (submucosal carcinoma, n = 6; high-grade dysplasia, n = 14; and adenoma, n = 30) were small (< 1 cm in diameter) and were detected as a depression with or without a marginal elevation on colonoscopic examination. In the dissecting microscopic study, submucosal carcinomas and lesions of high-grade dysplasia almost exclusively showed irregular small pits, with the exception of four malignant lesions with moderate submucosal invasion in which the pit structure was absent. In contrast, adenomas had either regular small (29/30 lesions) or oval pits (1/30 lesions). Rates of p53 positivity were 100%, 64%, and 7% in depressed submucosal carcinomas, lesions of high-grade dysplasia, and adenomas, respectively, thus the prevalence of p53 positivity was significantly higher in the former two groups than in the adenoma group. CONCLUSIONS: The high frequency of invasive carcinoma and high-grade dysplasia found in depressed colorectal neo-plastic tumors, despite their small size, indicates that these lesions may be a subtype of colorectal tumor with more aggressive malignant potential at an earlier stage. [ABSTRACT FROM AUTHOR]

The neuropeptides beta-endorphin (BE), thyrotropin-releasing hormone (TRH), and somatostatin (SOM) in the gastric mucosa have the capacity to regulate gastric function. To clarify the possible role of BE in the interactions of neuropeptides and gastric acid secretion we investigated the effect of the intragastric administration of BE on TRH and SOM release into the gastric lumen. BE (100ng/kg) induced an immediate decrease in TRH release and a reciprocal increase in SOM release into the gastric lumen, followed by the suppression of gastric acid secretion. When various doses of BE (0-500ng/kg) were administered, changes in TRH and SOM occurred in a dose-dependent manner. Pretreatment with naloxone dihydrochloride (5 mg/kg, intraperitoneally) completely inhibited the BE-induced changes in the release of these peptides. These findings suggest that BE has a paracrine effect on TRH and SOM release into the gastric lumen through opioid receptors, and that these interactions may be involved in the regulation of gastric acid secretion. [ABSTRACT FROM AUTHOR]

Objectives: In this study, our purpose was to determine whether locally generated interleukin-8 (IL-8) is involved in neutrophil migration and binding to extra-cellular matrix, using the colonic mucosal specimens obtained from patients with inflammatory bowel disease (IBD). Methods: Levels of IL-8 secreted in the organ cultures were measured by enzyme-linked immunosorbent assay. Chemotactic activity and binding capacity of neutrophils were induced by the organ culture supernatants. Results: Significantly higher levels of IL-8 were secreted in patients with IBD, and its elevation was more prominent in patients with active ulcerative colitis. The organ culture supernatants induced higher chemotactic activity and binding capacity of neutrophils in patients with IBD, especially in those with active ulcerative colitis, compared with controls. These effects were inhibited significantly when the supernatants were submitted to preincubation with neutralizing anti-IL-8 antibody. Conclusions: Increased mucosal generation of IL-8 may attract neutrophils from the circulation into the inflammatory site and induce binding of neutrophils in the interstitial tissue, contributing to accumulation and activation of neutrophils in the affected mucosa with IBD. [ABSTRACT FROM AUTHOR]

Objectives; To examine the background histology, interleukin-8 (IL-8) secretion, and expression of IL-8 mRNA and protein, using the gastric antral mucosa infected with Helicobacter pylori. Methods: The antral biopsies were obtained from an area of endoscopically intact mucosa in 147 patients whose endoscopic diagnoses were normal (n = 41), duodenal ulcer (n = 58), gastric ulcer (n = 21), or gastritis (n = 27). Levels of IL-8 secreted in the organ cultures of mucosal biopsies were measured by an ELISA assay, and the expression of IL-8 mRNA and protein was analyzed in fresh biopsy tissues with RT-PCR and immunofluorescent microscopy, respectively. Results: Significantly greater levels of IL-8 were secreted in patients with H. pylori infection, and its elevation was more prominent in duodenal ulcer patients than in those with gastric ulcer or endoscopically defined gastritis. There was an association among H. pylori density, IL-8 activity, and histological severity of activity and inflammation of gastritis in the Sydney system. Consistent with enhanced IL-8 activity in the organ cultures, IL-8 mRNA was detected in 16 of 23 fresh biopsy tissues studied in H. pylori-positive patients. In contrast, IL-8 transcript was detected in only one of 12 H. pylori-negative cases. Immunofluorescent microscopy showed localization of IL-8 protein in the gastric epithelial cells and lamina propria cells, primarily CD68+ macrophages in specimens with H. pylori infection. Conclusions: This study indicates that a strong correlation exists between mucosal IL-8 activity and histological severity in H. pylori-associated antral gastritis. Further studies will be necessary to determine the mechanisms involved in elevated mucosal IL-8 activity in H. pylori infection. [ABSTRACT FROM AUTHOR]

Phenotypic and functional analysis was performed with lamina propria mononuclear cells (LPMCs) isolated from colonoscopic biopsies in 27 patients with ulcerative colitis (UC). The proportion of T lymphocytes displaying HLA-DR antigens, interleukin 2 (IL-2) receptor, and transferrin receptor was greater in active UC than in control diseases. When LPMCs were cultured with IL-2 or phytohemagglutinin for 72 h, there were no significant differences in the proportion of cells bearing these activation markers between active UC and controls. The proportion of CD56+ cells and lymphokine-activated killer (LAK) cell activity was lower in LPMCs from active UC than in control cells, and depletion of CD56+ cells from control lamina propria cells essentially eliminated LAK cell activity. Mucosal T lymphocytes may be activated in vivo during active inflammation in UC, and lower levels of intestinal LAK cell activity may be related to the decrease of CD56+ cells under these conditions. [ABSTRACT FROM AUTHOR]

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), beta-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4-5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6-12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

The phenotypes and ultrastructure of macrophages and dendritic cells in aphthoid lesions of the colon were immunocytochemically observed in patients with Crohn's disease. Biopsy specimens were endoscopically obtained from both aphthoid and advanced lesions in Crohn's disease patients. Biopsy specimens obtained from patients with infectious colitis and from normal individuals served as controls. Aphthoid lesions contained densely aggregated CD68+ macrophages, which were surrounded by numerous ID-1+ dendritic cells. In the normal controls and infectious colitis patients, however, a few scattered CD68+ macrophages and ID-1+ dendritic cells were noted beneath the surface epithelium. CD3+ lymphocytes were significantly increased in both aphthoid and advanced lesions of Crohn's disease, but the CD4/CD8 ratio was similar in all groups studied. The double immunoperoxidase staining method revealed that both CD68+ macrophages and ID-1+ dendritic cells in the aphthoid lesions simultaneously expressed ICAM-1 and HLA-DR antigens. Electronmicroscopic observation revealed that CD68+ macrophages had numerous vesicles and lysosomal granules and few projections, and that ID-1+ dendritic cells had appreciable cytoplasmic protrusions with a few vacuoles. These findings suggested that the colonic mucosa in Crohn's disease contained two types of macrophage/dendritic cells in the same lineage that expressed intercellular adhesion molecules and class-II MHC antigens. It also appeared that the aphthoid lesions of Crohn's disease featured an increase in macrophages and dendritic cells consistent with immunological activation. [ABSTRACT FROM AUTHOR]

The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E (PGE) were studied in the rat stomach. Water-immersion caused a significant decrease in immunoreactive-TRH (irTRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE were significantly increased at 0.5-4hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of irTRH in the stomach was significantly decreased after VIP injection,whereas it was significantly increased after β-endorphin injection. The concentration of PGE was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after β-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE and that these interrelations between neuropeptides and PGE may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat. [ABSTRACT FROM AUTHOR]

Immunoglobulin (Ig) synthesis, natural killer (NK) cell activity, and lymphokine production by peripheral blood mononuclear cells (PBMC) were studied in 34 patients with ulcerative colitis (UC). Levels of Ig produced by PBMC were significantly higher in patients with active UC as compared to controls. However, there were no significant differences in Ig-synthesis between patients with inactive UC and controls. NK cell activity was significantly decreased in patients with active UC as compared to controls, and a significant negative correlation was observed between the level of IgA and NK cell activity in patients with UC. Reconstitution experiments demonstrated that CD56 cells from controls suppressed the levels of IgA, when added to the culture containing a constant number of B cells and CD4 cells. In contrast, CD56 cells from patients with active UC completely lacked the capacity to suppress IgA production. In addition, the activities of interleukin-2 and interferon-γ were significantly decreased in patients with active UC. The present study suggests that immunoregulatory abnormality of NK cells exists in patients with UC and impaired NK cell activity may be related to increased Ig-synthesis observed in these patients. [ABSTRACT FROM AUTHOR]

The interleukin 2 (IL-2) and interferon-γ (IFN-γ) activities of regional lymph node mononuclear cells (LNMC) were studied in 22 patients with gastric cancer. Regional LNMC could produce high levels of IL-2 and IFN-γ independent of the disease extension or the location of the lymph nodes. The activities of peripheral blood mononuclear cells (PBMC) from cancer patients were decreased especially in advanced disease compared to controls. The lymph node CD4 cells were responsible for the bulk of IL-2 activity, whereas both CD4 and CD8 cells were equally capable of producing IFN-γ. The proportion of T cells in LNMC was similar to that seen in PBMC, however, CD4 cells predominated over CD8 cells in the lymph nodes, contributing to higher activities of IL-2 and IFN-γ in LNMC. Furthermore, significant cytotoxic activity could be induced from PBMC using the culture supernatant derived from autologous LNMC in cancer patients. This study suggests that regional lymph nodes are strategically located near the tumor and the local cells are capable of producing high levels of IL-2 and IFN-γ. [ABSTRACT FROM AUTHOR]

Natural killer (NK) activity, lymphokine-activated killer (LAK) activity and interferongamma (IFN-γ) producing activity of peripheral blood mononuclear cells (PBMC) and regional lymph node mononuclear cells (LNMC) were studied in 23 previously untreated cases of colorectal cancer. NK and LAK activities were significantly lower in LNMC than in PBMC. Patients showed depressed NK and LAK activities in PBMC. In the Dukes C group, especially, both NK activity and LAK activity decreased compared to control patients. NK and LAK activities of PBMC decreased as the grade of invasion to lymphatic channels progressed. LAK activity positively correlated with NK activity in PBMC. Patients with high LAK activity showed high IFN-γ production in both controls and Dukes A · B patients. However, in Dukes C patients, no relationship between LAK activity and IFN-γ production was observed. We conclude that the depressed NK and LAK activities of PBMC reflect the local lymphatic invasion and that IFN-γ involvement in LAK cell generation is impaired in advanced cancer patients. More fundamental studies should be carried out before clinical trials of adoptive immunotherapy using LAK cells, because LAK activity is not induced sufficiently in advanced cancer. [ABSTRACT FROM AUTHOR]

We investigated the effect of recombinant interferongamma (rIFN-gamma) in vitro on natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) in patients with gastric cancer. Thirty untreated patients with gastric cancer and eleven healthy donors were studied. NK cell activity in healthy donors was 38.6 ± 5.2%. In patients with gastric cancer, NK cell activity was 32.4 ± 3.9% in stage I, 35.5 ± 7.1% in stages II and III, and 22.4 ± 3.9% in stage IV. NK cell activity in stage IV patients was significantly lower than in healthy controls or gastric cancer patients in stages I-III. After stimulation by rIFNgamma, NK cell activity increased in all groups, and in stage IV patients NK cell activity recovered to normal levels. However, there was no significant increase in the proportion of Leu 7 positive or Leu 11 positive cells in PBL. In conclusion rIFNgamma enhances the activity of NK cells, but does not increase the number of active NK cells. [ABSTRACT FROM AUTHOR]

Two cases of minute carcinoid tumor of the stomach were reported and 167 cases of gastric carcinoid in Japan up to December 1984 were reviewed. In Case 1, two carcinoid tumors of the body were found as sessile polyps of 4.2 and 4.8 mm in diameter, respectively, the latter having been detected two years previously. Case 2 had 60 polypoid lesions on the body and the fundus, ranging from 1.0 to 4.5 mm in diameter. In both cases the tumor invasion was limited to the mucosa and submucosa, although many micronests were found around the polypoid lesions. Among 167 cases of gastric carcinoid in Japan, 12 were 5 mm or less in size and 12 were 6 to 10 mm in size. In the former cases, there was no metastasis while in the latter, metastasis to the lymph nodes was found in 25.0%. We propose that the minute gastric carcinoid should be defined as a tumor not exceeding 5 mm in size with the invasion limited to the mucosa or submucosa. In addition, we emphasized that radical gastrectomy should be performed even for the minute carcinoid tumor because of its multicentricity and invasiveness. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on the study demonstrating tissue distribution of matrix metalloproteinase (MMP) and their tissue inhibitors in ulcerative colitis patients. Increase in the expression of MMP compared to their inhibitors; Correlation between the histological degree of inflammation and the frequency of epithelial expression of MMP-7 at the edge of ulcerative lesions.

Discusses the usefulness of Doppler ultrasonography for the detection of gastric varices. Use of angiography or computed tomography in the diagnosis of gastric varices; Description of how transcutaneous sonography is used to identify gastric varices.

Editorial. Discusses the differences in clinical features of ulcerative colitis (UC) in the elderly. Variety of diseases of the elderly with UC; Controversies on the clinical investigations of UC; Study of late-onset UC.