Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis.

BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and non-inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t-test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real-time ploymerase chain reaction. RESULTS: We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non-inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.

Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.

This study aims at clarifying whether the humoral immune response to the tandem repeat domain of MUC1 can be induced or not in vivo. The expression of MUC1 mRNA in the colon was revealed by Northern blot analysis, and cDNA cloning of an extracellular tandemly repeated domain of MUC1 was then performed to prepare the recombinant MUC1 protein. A cDNA clone coding for ten repeat domains was ligated into an expression vector in prokaryotes, resulting in a recombinant protein which could react with the MAb MUSE11 against an adenocarcinoma-associated antigen whose epitope has been shown to be localized in the tandem repeat domain on MUC1. The reactivity of sera from patients with ulcerative colitis with the recombinant protein was evaluated by SDS-PAGE and Western blot analysis to detect the antibodies against this tandem repeat domain. Five out of 19 serum samples tested positive, and these reactions were totally inhibited by MAb MUSE11, suggesting that the epitope recognized by these antibodies in sera is almost identical to that recognized by MAb MUSE11. The data represent the first demonstration of antibody production against a peptide epitope of the tandem repeat domain of MUC1.

Gastric antral vascular ectasia causing severe anemia.

Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal bleeding is reported in a 76-year-old woman who had been treated with repeated blood transfusions because of severe anemia. Endoscopic examination was performed and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory data showed SGOT > SGPT, decreased chE level and the increased levels of serum gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination revealed splenomegaly. There was no family history of telangiectasia, and no telangiectasia was found in other organs. The diagnosis was established as GAVE with liver cirrhosis. Surgical resection of the distal stomach resulted in termination of the bleeding, and the cirrhotic changes of the surface of the liver were revealed at that time, providing further evidence of liver cirrhosis. Although the pathogenesis of GAVE is unknown, liver cirrhosis and hypergastrinemia are thought to be associated with the condition. Importantly, this condition is a cause of severe gastrointestinal bleeding in elderly patients.

The effect of the immune response to Helicobacter pylori in the development of intestinal metaplasia.

AIM: To determine whether cytotoxic Helicobacter pylori antibodies occur in gastric mucosa, and whether these antibodies contribute to the development of intestinal metaplasia. MATERIALS AND METHODS: The number of mononuclear inflammatory cells, which specifically produce immunoglobulin (Ig)G and IgA antibodies, was investigated by using an enzyme-linked immunospot assay and the fraction of mononuclear inflammatory cells determined in gastric biopsy specimens from 34 subjects with H. pylori infection. Assays for the cytotoxicity of H. pylori antibodies were performed on cultured Japanese green monkey kidney (Vero) cells and by in vitro tests. RESULTS: The number of IgG and IgA antibody-producing cells was positively correlated with the degree of inflammation of the gastric mucosa. However, the number of IgG antibody-producing cells was lower in subjects with intestinal metaplasia than in those without. This was not the case for IgA. Significant cytotoxic damage was observed in Vero cells in vitro when incubated in a solution containing the H. pylori IgG antibody, antigen and polymorphonuclear leukocytes. No cytotoxicity was seen with the IgA antibody or with the antigen or polymorphonuclear leukocytes alone. CONCLUSIONS: H. pylori infection is associated with the appearance of immunocompetent mononuclear cells in gastric mucosa. These cells produce H. pylori antibodies of the IgG class which are capable of causing cytotoxic damage in the epithelial cells, obviously through activation of polymorphonuclear leukocytes by antibody-antigen complexes. The occurrence of these cells is inversely related to intestinal metaplasia, suggesting that they may be involved in the processes of epithelial damage leading to the appearance of intestinal metaplasia.

Further immunohistochemical study of Crooke's hyalin.

For analysis of the cytokeratin (CK) of Crooke's cells, 28 post-mortem pituitary glands with unequivocal Crooke's hyaline change were investigated immunohistochemically using monoclonal antibodies for CK subfamilies. Crooke's hyalin was positive for CK 8 [molecular weight 52.5 kilodalton (KD)] and 18 (45 KD) but negative for skin-, cornea- and esophageal-typed CKs.

Reliability of cytological grading of prostatic carcinoma compared with histological grading.

Thirty prostatic carcinomas diagnosed simultaneously by fine needle aspiration cytology and punch biopsy were graded into three groups according to their cytological and histological appearances. Among them 23 carcinomas were graded equally by both methods. Cytological examination appears to be suitable for grading prostatic carcinoma, thus being a possible indicator of the patient's prognosis and response to hormonal therapy. In addition to the results obtained here, fine needle aspiration cytology has many advantages such as simplicity, quickness and safety. With increase of attention of urologists and pathologists to fine needle aspiration cytology, this evaluation will become comparable to the histological examination not only as a routine diagnostic tool.

Malignant Zollinger-Ellison syndrome. Stabilization of liver metastasis after gastrectomy with resection of primary tumor.

A case of malignant gastrinoma of the jejunum and jejunal mesentery, with findings of metastasis in the liver was studied. Tumor resection and remnant gastrectomy, as well as liver biopsy, were performed. Of all the tumors removed, the metastatic tumor had the lowest gastrin content, which was 1.5 times that found in normal human antral mucosa. The gastrin distribution was of four peaks and one peak for the main tumor, versus two peaks for the metastatic tumor in which G17 was the main component. Seven years after the operation, computed tomography (CT) scan indicated there was stabilization of the liver metastasis, and now, ten years after the total gastrectomy, the patient is well and working full-time. Such an analysis can be of value in determining the prognosis in cases of malignant gastrinoma with liver metastasis.

Gastric non-Hodgkin's lymphoma associated with Behçet's disease.

The first case of primary gastric lymphoma associated with Behçet's disease is reported. A 43-year-old woman, who had been treated for Behçet's disease for 15 years, was diagnosed as low-grade and small lymphocytic malignant lymphoma of the stomach. Although the patient had been treated for Behçet's disease, chemotherapy was performed and a complete remission of gastric lymphoma was achieved. The literature regarding the association of malignant diseases with Behçet's disease is briefly reviewed.

Chronic encapsulated intracerebral hematoma associated with angiographically occult arteriovenous malformation--case report.

A 34-year-old female presented with a rare chronic encapsulated intracerebral hematoma associated with an angiographically occult arteriovenous malformation. A neovascularized fibrous capsule containing various stages of intracerebral hematoma formation was removed. These unusual entities mimic brain tumors or abscesses because of gradual growth and slowly progressive neurological deficits. Repeated bleeding or exudation from the capillaries of the capsule may allow expansion of the chronic encapsulated intracerebral hematoma.

[Comparison of three methods for detecting Campylobacter pylori and measurement of human antibody titers against the whole organisms].

In order to detect Campylobacter pylori in the gastric mucosa, three different methods as 1) culture of the organisms, 2) immunostaining by monoclonal antibody against the cells, and 3) urease test were compared. In the disease group, positive % of each methods was 64, 75 and 74. However, positive % common to the three methods was only 48. The corresponding rate of culture and urease tests, and that of culture and staining methods was 81% and 60%, respectively. Therefore, it was concluded that urease test was a useful method, and that the three methods were necessary to confirm the existence of the organisms in the gastric mucosa. Total positive % of culture and staining methods in disease and control groups was 77 and 31, respectively, indicating that positive % of the disease group was much higher than that of the control group. Anti C. pylori titer was compared between culture-positive and culture-negative patients by ELISA. The titer of the former was significantly higher than that of the latter.

[Atypical hyperplasia and latent carcinoma of the prostate as an early stage of carcinoma].

The prostate gland exhibits various borderline lesions and latent prostatic carcinoma is important as a preceding lesion of clinically manifest carcinoma. In this report, we describe a study of these lesions which was carried out using preparations from five different races. Atypical hyperplasia (AH) is the most important of these borderline lesions. Histologically, latent carcinoma exhibits a wide range, from poorly to well differentiated types, and is widely accepted to be the preceding state of clinically manifest carcinoma. Both lesions were common in all five races with a frequency several hundred times greater than the mortality rate for prostatic carcinoma. A significant correlation was found between the prevalences of AH and latent carcinoma, both of which had a tendency to show multifocal growth. Although there were many latent carcinoma cases exceeding 130 mm3 in size and poorly or moderately differentiated, rare cases would advance to clinically manifest carcinoma. Since the formation of tiny carcinomas and progression to clinically manifest carcinoma are two different phenomena, it is considered important to study the factors affecting the latter phenomenon.

[Weekly low-dose CPT-11 and HCFU for advanced colorectal cancer on an outpatient treatment basis].

We attempted a new outpatient treatment using weekly low-dose CPT-11 for advanced colorectal cancer patients. A 73-year-old female with para-aortic lymph node metastases from advanced rectal cancer was given outpatient treatment for more than 5 months with weekly low-dose CPT-11 and HCFU. CPT-11 was given intravenously at a dose of 20 mg/m2 on day 1 every week. On days 2-7, she was treated by oral administration of HCFU (600 mg). Her serum CEA level decreased and continued to do so for more than 5 months. The size of the para-aortic lymph node was reduced by approximately 40%. There were no adverse effects except leukopenia (grade 2). These results suggest that weekly low-dose CPT-11 and oral HCFU may be an effective therapy on an outpatient basis in cases of advanced colorectal cancer.

Mucosal immune response to Helicobacter pylori and cytotoxic mechanism.

BACKGROUND: Helicobacter pylori is widely accepted as a major pathogen in gastritis. The histologic features of H. pylori gastritis are the numerous infiltrating mononuclear cells (MNCs) and neutrophils. It is not clear what role the infiltrating MNCs and neutrophils play in H. pylori gastritis. METHODS: In this study, we have established enzyme-linked immunospot (ELISPOT) assay for the measurement of H. pylori antibody-producing cells in gastric mucosa. RESULTS: Using ELISPOT assay, we found that H. pylori-specific IgA-producing cells as well as IgG-producing cells were distributed in gastric mucosa. These H. pylori-specific antibodies in gastric mucosa and neutrophils are responsible for the induction of cytotoxic effect to cultured Vero cells. CONCLUSIONS: These observations suggest that a mucosal immune response specific to H. pylori is closely associated with the pathogenesis of gastritis.

[Quantitative X-ray computed tomography].

Quantitative X-ray Computed Tomography (QCT) has an advantage to be able to determine three-dimensional bone density of lumbar vertebral body compared with dual energy X-ray absorptiometry (DXA) method. We introduced the high reproductable QCT method as a simplified manual operation avoiding simultaneous imaging of both patients and bone mass phantoms. The coefficient of variation of values measured by phantom study was 0.6% for 7 years in our hospital. In measuring of 144 healthy Japanese women, the bone mineral density of lumbar spine was most likely to be decreased linealy with age.

[Inhalant abusers and psychiatric symptoms].

There are different opinions about the cause of chronic psychiatric symptoms observed in drug abusers between Japanese and foreign psychiatrists. The Japanese seem to recognize the chronic psychosis as the result of drug abuse. In the other hand, foreigners diagnose these cases as dual diagnosis of drug abuse and psychosis. Authors studied the problem in this research. One of the authors has examined 120 inhalant abusers of all, in- and out-patients in Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital from 1991 to 1995. These patients were classified into three groups: psychosis group (23 patients), dependence group (51 patients) and abuse group (46 patients) according to their clinical courses and psychiatric symptoms. The psychosis group consists of patients who showed psychiatric symptoms such as hallucination, delusion and thought disturbance for long time after detoxification. The dependence group contains patients whose inhalant dependence was severe and met DSM-4 Diagnostic Criteria for Substance Dependence, but manifested no chronic psychiatric symptoms after detoxification. The patients belonging to abuse group were at the earlier stages of inhalant abuse and had no chronic psychiatric symptoms. The average age of the first inhalant abuse was 14.7 years old in the psychosis group, 14.8 years in the dependence group and 14.7 years in the abuse group. The average years of abuse was 9.0 years in the psychosis group, and 8.5 years in the dependence group. There was little difference between these two groups. The psychosis patients manifested chronic symptoms 5.7 years on average after the first abuse of inhalants. About one forth (26.1%) of the psychosis patients and only 5.9% of the dependence patients had family history of schizophrenia. The difference was statistically significant. These results suggest that chronic psychiatric symptoms are caused not only by inhalant abuse, but also by the genetic factors of psychosis of each patient. There have been several reports that many patients with dual diagnosis of substance dependence and other mental disorders are poly-drug abusers. In our study, 43.4% of the psychosis group patients and 19.6% of the dependence group patients had the past history of abuse of other drugs including methamphetamine and marijuana. The difference was, however, not statistically significant.