In situ visualization of plasma cells producing antibodies reactive to Porphyromonas gingivalis in periodontitis: the application of the enzyme-labeled antigen method.

Porphyromonas gingivalis is a keystone periodontal pathogen. Histologocally, the gingival tissue in periodontitis shows dense infiltration of plasma cells. However, antigens recognized by antibodies secreted from the immunocytes remain unknown. The enzyme-labeled antigen method was applied to detecting plasma cells producing P. gingivalis-specific antibodies in biopsied gingival tissue of periodontitis. N-terminally biotinylated P. gingivalis antigens, Ag53 and four gingipain domains (Arg-pro, Arg-hgp, Lys-pro and Lys-hgp) were prepared by the cell-free protein synthesis system using wheatgerm extract. With these five labeled proteins as probes, 20 lesions of periodontitis were evaluated. With the AlphaScreen method, antibodies against any one of the five P. gingivalis antigens were detected in 11 (55%) serum samples and 17 (85%) tissue extracts. Using the enzyme-labeled antigen method on paraformaldehyde-fixed frozen sections of gingival tissue, plasma cells were labeled with any one of the five antigens in 17 (94%) of 18 specimens, in which evaluable plasma cells were detected. The positivity rates in periodontitis were significantly higher than those found previously in radicular cysts (20% in sera and 33% in tissue extracts with the AlphaScreen method, and 25% with the enzyme-labeled antigen method). Our findings directly indicate that antibodies reactive to P. gingivalis are locally produced in the gingival lesions, and that inflammatory reactions against P. gingivalis are involved in periodontitis.

Histopathological diagnosis of Japanese spotted fever using formalin-fixed, paraffin-embedded skin biopsy specimens: usefulness of immunohistochemistry and real-time PCR analysis.

Japanese spotted fever (JSF) is caused by Rickettsia japonica, and lethal cases are reported yearly in southwest Japan. We thus established the method of diagnosing JSF by immunohistochemistry (IHC) and real-time PCR (RT-PCR) using formalin-fixed, paraffin-embedded skin biopsy specimens. Two monoclonal antibodies were used for IHC, and the 17k genus common antigen gene served as the target of RT-PCR. We collected skin biopsy (n = 61) and autopsy (n = 1) specimens from 50 patients clinically suspected of JSF. Immunohistochemically, the rickettsial antigens were localized as coarse dots in the cytoplasm of endothelial cells and macrophages. Thirty-one seropositive cases plus one autopsy case (group A) and nine seronegative cases but with positive IHC and/or RT-PCR (group B) were judged as JSF. Nine cases were regarded as non-JSF disorders based on negative serology, IHC and RT-PCR (group C). Of 50 biopsies (eschar 34, eruptions 10, and scabs 6) from groups A and B, IHC and RT-PCR positivities were 94% (32/34) and 62% (21/34) for eschar, 80% (8/10) and 30% (3/10) for eruptions, and 33% (2/6) and 50% (3/6) for scabs. For IHC, eschar was most suitable, and scabs were insufficient. Unexpectedly, 18 biopsies happened to be fixed in 100% formalin, and this lowered the detection rate by RT-PCR, but IHC was tolerant. Sequence analysis using five skin biopsy specimens confirmed a 114 bp DNA stretch homologous to that reported for the target gene of R. japonica. In 26 (84%) of the 31 seropositive patients, the diagnosis was made by IHC and/or RT-PCR earlier than serology.

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

RUNX3 expression correlates with chief cell differentiation in human gastric cancers.

RUNX3 is a novel tumor suppressor in gastric carcinogenesis and an important factor for differentiation of chief cells in the normal gastric fundic mucosa. In this study, we confirmed RUNX3 immunolocalization in the fundic gland (bottom part) but minimum in surface mucous cell epithelium (top part) in the isolated gland from fundic mucosa. We also analyzed RUNX3 expression by immunohistochemistry in 102 gastric cancers and made a histological assessment of the expression of differentiation markers to evaluate interrelations. Among them, 45 and 57 cases were judged to be RUNX3 positive and negative, respectively, and 33 and 69 cases were pepsinogen I positive and negative, with no link to histological types. RUNX3 expression was significantly associated with that of pepsinogen I (P<0.001), but not mucins, including MUC5AC and MUC6, or the parietal or intestinal phenotypes. In conclusion, the present study showed, for the first time to our knowledge, a relation between RUNX3 and pepsinogen I expression in human gastric cancers. RUNX3 is strongly associated with chief cell phenotypic expression in human gastric cancers, as well as in normal gastric mucosa, and could be considered to play an important role in maintaining the chief cell phenotype.

Assessment of NMDA receptor activation in vivo by Fos induction after challenge with the direct NMDA agonist (tetrazol-5-yl)glycine: effects of clozapine and haloperidol.

Induction of Fos protein by the potent and direct NMDA agonist (tetrazol-5-yl)glycine (TZG) was examined in mice. Effects of antipsychotic drugs were assessed on this in vivo index of NMDA receptor activation. TZG induced the expression of Fos in a neuroanatomically selective manner, with the hippocampal formation showing the most robust response. In mice genetically altered to express low levels of the NR1 subunit of the NMDA receptor, TZG-induced Fos was reduced markedly in comparison to the wild type controls. TZG-induced Fos was also blocked by the selective NMDA antagonist MK-801. Pretreatment of mice with clozapine (3 and 10 mg/kg) reduced TZG-induced Fos in the hippocampal formation but not in other brain regions. Haloperidol at a dose of 0.5 mg/kg did not antagonize TZG induced Fos in any region. Haloperidol at a dose of 1.0 mg/kg did attenuate the induction of Fos by TZG in the hippocampus but not in other brain regions. The relatively high dose (1 mg/kg) of haloperidol required to block effects of TZG suggests that this action may not be related to the D(2) dopamine receptor-blocking properties, since maximal D(2) receptor blockade was probably achieved by the 0.5 mg/kg dose of haloperidol. The antidepressant drug imipramine (10 or 20 mg/kg) did not antagonize TZG induced Fos in any brain region. The data suggest that clozapine can reduce excessive activation of NMDA receptors by TZG administration in vivo at doses relevant to the drugs' actions in rodent models of antipsychotic activity. Whether or not this action of clozapine contributes to its therapeutic properties will require further study.

Loss of MUC2 expression correlates with progression along the adenoma-carcinoma sequence pathway as well as de novo carcinogenesis in the colon.

AIMS: We have previously demonstrated links between clinicopathological findings and phenotypes using several gastric and intestinal phenotypic markers in stomach and pancreatic cancers. However, the clinicopathological significance of the phenotype and Cdx2 expression has hitherto remained unclear in colorectal carcinogenesis. METHODS AND RESULTS: We examined the correlation between gastric and intestinal phenotypic expression in 91 primary early carcinomas of the colon. MUC2 expression demonstrated a significant decrease from tubular/tubulovillous adenomas with moderate atypia, through intramucosal carcinomas, to cancers with submucosal invasion (P<0.0001). Intramucosal de novo carcinomas (flat type carcinomas without adenomatous components) exhibited a greater decrease of MUC2 than intramucosal lesions with adenomatous components. Expression of MUC5AC also decreased significantly with progression according to the tubular/tubulovillous adenoma-carcinoma sequence, carcinomas with villous adenomatous components having a higher level compared with their tubular adenomatous counterparts, suggesting differences in the pathway of malignant transformation. Cdx2 nuclear expression was maintained in all of the adenomas and early carcinomas examined. CONCLUSIONS: Our data suggest that the reduction of MUC2 expression may be associated with the occurrence and progression of colorectal carcinomas in both adenoma-carcinoma sequence pathway and de novo carcinogenesis. Tumor-suppressive effects of Cdx2 may be preserved during early stages of colorectal carcinogenesis.

Mutations and nuclear accumulation of beta-catenin correlate with intestinal phenotypic expression in human gastric cancer.

AIMS: Abnormal localization of beta-catenin is frequently observed in human gastric cancers. The aim of the present study was to evaluate relationships among gastrointestinal differentiation phenotypes, beta-catenin localization and mutations of Wnt signalling genes. METHODS AND RESULTS: Seventy-seven regions in 39 gastric adenocarcinomas were classified according to beta-catenin localization and gastric and intestinal phenotypes. Cases with membranous beta-catenin localization showed a gradual decrease from gastric (G) (55% = 6/11) and gastric-and-intestinal-mixed (GI) (17% = 5/29) to intestinal (I) (0% = 0/21) phenotypes, while those with nuclear localization showed a concomitant increase: 18% (2/11), 41% (12/29), 95% (20/21) and 63% (10/16) for G, GI, I and null type (N), respectively (P < 0.001, membranous versus nuclear localization in G, GI through I). Mutations in exon 3 of the beta-catenin gene were found in G (50% = 1/2), GI (67% = 8/12), I (45% = 9/20) and N (0% = 0/10) regions with nuclear beta-catenin localization (GI versus N, P < 0.01; I versus N, P < 0.05). Adenomatous polyposis coli (APC) gene mutations were demonstrated only in GI, I and N types, irrespective of beta-catenin localization. Molecular analysis of these genes revealed 10 tumours to be heterogeneous out of 16 informative cases (62.5%). CONCLUSION: Intestinal phenotypic expression is accompanied by a shift from membranous to cytoplasmic/nuclear accumulation of beta-catenin. In contrast, N-type regions may progress along a different pathway.

Perioperative serum procalcitonin concentrations in patients with acute aortic dissection.

We investigated the perioperative serum procalcitonin (PCT) concentrations in 5 consecutive patients who underwent surgery for acute aortic dissection (2 men, 3 women; mean age 72 +/- 9 years, age range 52-81 years). Surgery used cardiopulmonary bypass with deep hypothermic circulatory arrest. Blood samples were taken prior to surgery, upon arrival in the intensive care unit, and 6, 12, 18, 24, and 48 h after intensive care unit arrival. Prior to surgery, the PCT level was 4.2 +/- 3.4 (range 0.8-8.3) ng/ml. The PCT increase was greatest at 24 h (5.8 +/- 4.5 ng/ml). Preoperatively, the C-reactive protein concentration was 8.0 +/- 8.3 (range 0.9-23.8) mg/dl, and the white blood cell count was 8.5 +/- 3.1 x 10(3). C-reactive protein continued to increase at 48 h, while the white blood cell count peaked at 24 h. In spite of no symptoms of infectious diseases or septicemia, all patients had a significant preoperative PCT elevation. This finding may have something to do with the specific preoperative condition of acute aortic dissection. However, more clinical investigation is needed to clarify the PCT changes during and after surgery for acute aortic dissection.

Cellular differentiation status of epithelial polyps of the colorectum: the gastric foveolar cell-type in hyperplastic polyps.

AIMS: The 'metaplastic' polyp of the colorectum, a synonym for the hyperplastic polyp, was named based only on features of the crypt epithelium. It is considered non-neoplastic, but the precise cellular differentiation status remains to be proven. METHODS AND RESULTS: Forty-eight hyperplastic polyps, 12 serrated adenomas, 45 tubular adenomas and five juvenile polyps were studied for their phenotypic expression using gastric (foveolar or pyloric gland cell), small intestinal (goblet cell), and colonic (goblet cell) cellular markers by immunohistochemical and mucin histochemical techniques. Gastric foveolar cell-type differentiation was significantly expressed in hyperplastic polyps, while colonic differentiation was also consistently preserved. Neither gastric pyloric-type nor small intestinal differentiation was observed. The same cell differentiation status as hyperplastic polyps was observed in serrated adenomas but not in tubular adenomas or juvenile polyps. CONCLUSIONS: A large proportion of hyperplastic polyps are composed of hybrid epithelium, with bidirectional differentiation to both gastric foveolar and colonic epithelial cells in the same crypt. Therefore hyperplastic polyps might be interpreted as the outcome of abnormal cell differentiation of stem cells. The same phenotypic expression suggests that hyperplastic polyps and serrated adenomas share the same cell lineage.

Real time reverse transcriptase polymerase chain reaction of urinary cytokeratin 20 detects transitional cell carcinoma cells.

PURPOSE: We evaluate the diagnostic use of cytokeratin 20 messenger (m) RNA quantitation in urine as a marker of urothelial transitional cell carcinoma using the real time reverse transcriptase polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: Spontaneously voided urine was obtained from 47 patients with urothelial transitional cell carcinoma (carcinoma group), 19 other urological diseases (noncarcinoma group) and 27 healthy volunteers (control group). Quantification of cytokeratin 20 was performed with mRNA extracted from urine samples with primers and hybridization probes specific for cytokeratin 20 on a LightCycler instrument (Roche Diagnostics Corp., Indianapolis, Indiana). RESULTS: This method allowed reproducible quantitation of 10 to 106 cytokeratin 20 expressing colon carcinoma cells per 107 peripheral blood leukocytes, comparable to the sensitivity of conventional RT-PCR with a wide linear measuring range. Cytokeratin 20 mRNA values in the carcinoma group (mean 35,850) were significantly higher than noncarcinoma (171) and control groups (4.55, p <0.0001 and <0.0001, respectively). Urinary cytokeratin 20 mRNA values significantly correlated with tumor grade, urinary cytological class, immunostaining pattern and depth of tumor invasion. Sensitivity and specificity of real time RT-PCR with a cutoff value of 15 were 81% and 83%, whereas those of conventional cytology were 28% and 100%, respectively. CONCLUSIONS: These results indicate that real time cytokeratin 20 RT-PCR is a sensitive, quantitative, rapid and specific method to detect free cancer cells in the urine, with good potential for monitoring recurrence of urothelial transitional cell carcinoma.

Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody.

Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and Lewis (Le) gene are involved in type I Le antigen synthesis. The present study was performed to investigate the possibility that Se and Le gene polymorphisms alter the risk of H. pylori infection. Two hundred thirty-nine participants were genotyped for Se and Le and tested for the presence of anti-H. pylori IgG antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we assessed immunohistochemically whether type I Le antigen expression depended on the Se and Le genotypes. The H. pylori infection rate was positively associated with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se group, 73.3%) and negatively associated with the number of Le alleles (le/le group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were classified into three groups [low risk, (se/se, Le/Le) genotype; high risk, (Se/Se, le/le), (Se/Se, Le/le), and (Se/se, le/le) genotypes; moderate risk, other than low- or high-risk group], the odds ratio relative to the low-risk group was 3.30 (95% confidence interval, 1.40-7.78) for the moderate-risk group and 10.33 (95% confidence interval, 3.16-33.8) for the high-risk group. Immunohistochemical analysis supported the finding that Se and Le genotypes affected the expression of H. pylori adhesin ligands. We conclude that Se and Le genotypes affect susceptibility to H. pylori infection.

Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach.

We have proposed that intestinal metaplasia (IM) of the human stomach be divided into two types on the basis of cell differentiation status: a gastric and intestinal (GI) mixed type and a solely intestinal (I) type. In the GI mixed type, gastric (foveolar epithelial and pyloric gland cells) and intestinal (goblet, intestinal absorptive, and Paneth cells) phenotype cells coexist in the same intestinalized gastric glands in various combinations and degrees. Consequently, intestinalized gastric glands are hybrids. Although we have described the rare appearance of Paneth-like cells in pyloric glands of GI mixed-type IM, the absence of an appropriate Paneth cell marker leaves room for doubt as to their true character. The purpose of this study was to clearly identify Paneth cells in pyloric glands in IM lesions using a new Paneth cell marker, a polyclonal antibody human defensin (HD)-5, raised against HD-5, which is included in granules of Paneth cells. A total of 105 gastric samples (4 biopsy and 101 surgical resected specimens) were examined. In only nine cases (8.6%), the antibody allowed demonstration of Paneth cells in pyloric glands in GI mixed-type IM, confirming our previous finding. Analysis of the proliferative cell (P) zone indicated that a common stem cell might generate both GI phenotype cells by upward and downward migration. No Paneth cells were found above the P zone. The results suggest that the stem cells show abnormal cell differentiation in IM lesions but preserve their normal direction of migration.

Sequential histopathological changes in vivo after suicide gene therapy of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

Gastrointestinal cancer is the most important clinical target of gene therapy. Suicide gene therapy, such as with the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene, has been shown to exert antitumor efficacy in various cancer models in vitro. We previously reported in situ gene transfer and gene therapy for gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in dogs. Here, we describe the sequential histopathological changes after suicide gene therapy of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer in rats. Gastric tumors were induced by MNNG in 38 / 73 (52%) of Wistar strain rats. The suicide gene therapy group (14 rats) was subjected to in situ gene transfer with a recombinant adenovirus vector carrying the HSV-TK gene driven by CAG promoter (Ad.CAGHSV-TK) in gastric tumor, followed by the antiviral drug ganciclovir (GCV). To observe the histopathological changes at various times after HSV-TK / GCV gene therapy, groups of animals were sacrificed at 3, 8, and 30 days after gene transfer. Apoptosis in the gastric tumors was detected by the TUNEL method to assess the efficacy of HSV-TK / GCV gene therapy, and it was marked in the 8- and 30-day treatment groups compared to the sham operation controls (P < 0.001). Various histopathological changes, degeneration of cancer tissue and fibrosis after necrosis and apoptosis were significantly greater in the 30-day treatment group. The HSV-TK gene was detectable in peripheral blood by PCR until 30 days after gene transfer. These results may be useful in devising a method of suicide gene therapy for humans.

Interleukin 18 levels reflect the severity of acute pancreatitis.

The serum interleukin 18 (IL-18) levels were significantly increased in cases of acute pancreatitis, corresponding to the severity of the disease. The IL-18 levels were also significantly correlated with the serum tumor necrosis factor alpha (TNF-alpha) and bilirubin levels. The possible involvement of IL-18 in the development of liver dysfunction in acute pancreatitis is suggested.

Involvement of soluble adhesion molecules in acute pancreatitis.

The relationship between inflammatory cytokines and adhesion molecules in cases of acute pancreatitis was studied. Twenty-five patients were divided into three groups based on the severity of their disease as rated by the Ranson score. They were also divided into two groups according to the presence or absence of the complications of the multiorgan dysfunction syndrome (MODS) and the prognosis. As the severity of acute pancreatitis increased, the plasma levels of TNF-alpha, slCAM-1, sE-selectin, and sVCAM-1 also increased. The levels of all of these soluble adhesion molecules were significantly higher in the MODS-complicated group than in the non-MODS-complicated group. The levels of TNF-alpha, slCAM-1, and sVCAM-1 were significantly higher in patients who eventually died than in patients who survived. Significant correlations were observed between the levels of TNF-alpha and slCAM-1, between those of TNF-alpha and sVCAM-1, and between the levels of slCAM-1 and sVCAM-1. These results suggest that inflammatory cytokines stimulate the expression of adhesion molecules on the vascular endothelium and that mediators, including these adhesion molecules, are closely involved in the pathogenesis of acute pancreatitis. The plasma levels of these soluble adhesion molecules reliably reflected the severity of the disease.

Plasma type II phospholipase A2 levels in patients with acute pancreatitis.

Changes in the blood levels of type II phospholipase A2 (PLA2) were investigated over time in patients with acute pancreatitis from an early stage after manifestation of the disease. The serum level of type II PLA2 at the first examination and the maximum level during the course of illness were both correlated with the severity of the disease. Serum levels of type II PLA2 were significantly higher in patients with acute pancreatitis complicated by multiple organ failure (349.1 +/- 146.6 ng/ml) than in those with acute pancreatitis not complicated by multiple organ failure (66.9 +/- 50.1 ng/ml). The serum levels of type II PLA2 were also significantly higher in patients who eventually died (316.8 +/- 150.5 ng/ml) than in those who survived (148.9 +/- 167.9 ng/ml). There was a significant correlation between the serum levels of type II PLA2 and those of TNF-alpha during the course of illness (r = 0.8037, p < 0.0001). The serum levels of type II PLA2 reliably reflected the severity of acute pancreatitis even in the early stages of the disease. These results suggest that type II PLA2 may be closely involved in the pathophysiology of acute pancreatitis.

Mediastinal liposarcoma appearing as a tumor arising in the esophageal wall.

We report a case of mediastinal liposarcoma, a relatively uncommon neoplasm, in which the mass also appeared as a tumor arising in the esophageal wall. A 76-year-old man diagnosed with a posterior mediastinal mass had the tumor extirpated in local esophageal myectomy due to its unclear margin on the esophageal wall. The resected specimen was diagnosed as well-differentiated liposarcoma. Preoperative angiography showed the tumor received its blood supply from a branch of the left gastric artery, suggesting it arose in the lower esophageal segment close to the hiatus and extended to the mediastinum. Since this tumor's growth pattern differed completely from esophageal liposarcoma described in previous case reports, we concluded that it was mediastinal liposarcoma.

Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach.

BACKGROUND: The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. The aims of this study were: (1) to assess the normal tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach associated with gastritis. METHODS: Fresh human tissues were collected by surgical resection from 39 patients after informed consent had been received. RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), and Northern hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM, confirmed histopathologically. Reverse-transcriptase polymerase chain reaction (RT-PCR) was then carried out for Cdx1 and Cdx2. RESULTS: The expression of Cdx1 mRNA increased gradually from the duodenum to the distal colon, with no expression detected in the stomach. Compared with the distribution of Cdx1 mRNA in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human gastrointestinal tract showed greater predominance in the jejunum and ileum. The expression of Cdx2 mRNA increased gradually from the duodenum to the proximal colon and decreased from the ascending colon to the rectum. Compared with the expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the expression of Cdx2 mRNA in the human gastrointestinal tract showed greater predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in the mild and severe types of IM. However, neither of these mRNAs was identified in normal gastric mucosa without IM. CONCLUSIONS: Cdr1 and Cdx2 mRNAs are widely present in the human intestinal and colonic mucosae, but not in the gastric mucosa, suggesting that their expression may contribute to the intestinal phenotype. The high levels of these mRNAs in IM mucosa associated with chronic atrophic gastritis point to an association with this phenotypic shift in the gastric mucosa.

Interleukin 18 (IL-18) levels in patients with sepsis.

IL-18 levels in the blood of 13 sepsis patients were assessed. The IL-18 values were significantly correlated with their Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and they were a good reflection of the severity of the disease. There was also a strong correlation between the IL-18 values and the patients' inflammatory cytokine levels. The results suggested strong involvement of IL-18 in the pathogenesis of sepsis.