bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and velocity clumping in a Sloan Digital Sky Survey blue horizontal branch star catalogue
Authors: Clewley L. , Kinman T. D.
Published: June 2006

We present evidence for eight new clumps of blue horizontal branch stars discovered in a catalogue of these stars compiled from the Sloan Digital Sky Survey by Sirko et al. and published in 2004. Clumps are identified by selecting pairs of stars separated by distances ⩽2 kpc and with differences in galactocentric radial velocities <25 km s−1. Each clump contains four or more stars. Four of the clumps have supporting evidence: two of them also contain overdensities of RR Lyrae stars which makes their reality very likely. At least one of the clumps is likely to be associated with the tidal debris of the Sagittarius dwarf spheroidal galaxy. We emphasize that more accurate observations of the radial velocities or proper motions of the stars in the clumps, as well as the identification of other halo stars in these regions, are required to establish the reality of the remaining clumps.
Significance of activated mast cells in submucosa and muscularis propria of patients with Crohn's disease detected by a novel antimast cell surface molecule antibody
Authors: OSHITANI N. , KAMATA N. , INAGAWA M. , YAMAGAMI H. , WATANABE K. , FUJIWARA Y. , HIGUCHI K. , ARAKAWA T. , OKADA T.
Published: June 2006

Background

Degranulated mast cells may be missed by histochemical and immunohistological techniques, making the histological assessment of activated mast cells difficult.

Aim

To use a novel mast cell surface antigen 1 (MASA‐1) to detect activated mast cells.

Methods

Surgical samples of human intestine were obtained from 15 patients with ulcerative colitis (UC), 14 patients with Crohn's disease (CD) and 11 controls. Frozen sections were cut and MASA‐1 was detected and quantified by enzyme immunohistology. Immunohistological double staining with anti‐MASA‐1 and either anti‐CD68 or anti‐c‐Kit antibody was also performed.

Results

The number of MASA‐1‐positive cells was significantly higher in the submucosal layer and muscularis propria in patients with CD than in patients with UC or controls. The number of MASA‐1‐positive cells was significantly higher in the muscularis propria in patients with UC in highly inflamed colon compared with controls and less inflamed colon. Human intestinal MASA‐1‐positive cells are not from the macrophage lineage and showed heterogeneous expression of c‐Kit.

Conclusion

The increased number of mast cells in the submucosa and muscularis propria in patients with CD suggests that the involvement of activated mast cells in transmural inflammatory responses possibly including tissue remodelling.
Correlation of serum pepsinogen with histological atrophy following successful Helicobacter pylori eradication
Authors: KAWAI T. , KAWAKAMI K. , KATAOKA M. , TAKEI K. , TAIRA S. , ITOI T. , MORIYASU F. , TAKAGI Y. , AOKI T. , SERIZAWA H. , RIMBARA E. , NOGUCHI N. , SASATSU M.
Published: June 2006

Background

Levels of pepsinogen have been reported to correlate with the degree of gastric atrophy in Helicobacter pylori‐infected gastric mucosa.

Aim

To investigate the relationship between PG levels and histological atrophy before and after H. pylori eradication.

Methods

Eradication therapy was conducted on 180 H. pylori‐positive patients with upper gastrointestinal conditions. Endoscopy was performed prior to and at 2, 12 and 24 months after successful eradication therapy. Histological findings were scored using the updated Sydney System in the antrum and the corpus of the stomach. Pepsinogen was measured.

Results

Pepsinogen I levels dropped significantly at 2 months after the eradication. By 12 months and 24 months post‐eradication they had risen again. Histological improvement was seen in atrophy at all sites at 24 months after the eradication. A significant correlation between atrophy and pepsinogen I was seen from prior to eradication. The correlation coefficient was greater at 2 months post‐eradication, decreased again at 12 months and was no longer significant at 24 months.

Conclusions

Our results suggest that pepsinogen levels correlate with the degree of gastric mucosal atrophy prior to and soon after successful eradication therapy, but that the degree of correlation subsequently declines over time.
Changes in biochemical parameters related to atherosclerosis after Helicobacter pylori eradication
Authors: ANDO T. , MINAMI M. , ISHIGURO K. , MAEDA O. , WATANABE O. , MIZUNO T. , FUJITA T. , TAKAHASHI H. , NOSHIRO M. , GOTO H.
Published: June 2006

Background

Recent evidence suggests that Helicobacter pylori infection is involved in the pathogenesis of extra‐gastrointestinal diseases such as coronary heart disease.

Aim

To determine the association of H. pylori infection with biochemical parameters of atherosclerosis in the serum.

Methods

One hundred and fifty‐nine patients with H. pylori‐positive peptic ulcer (duodenal ulcer, n=89; gastric ulcer, n=70) receiving triple therapy were studied prospectively for up to 3 years for clinical parameters associated with inflammation and cardiovascular events. Blood was tested at the time of annual check‐up.

Results

Eradication was successful in 137 patients (86%), and body weight, body mass index (BMI) and TG levels increased gradually each year. No significant hanges were seen in plasma levels of total cholesterol, interleukin‐6 or interleukin‐8, whereas those of HDL‐C increased significantly, and those of C‐reactive protein, fibrinogen and LDL‐C decreased.

Conclusion

There is evidence for the possible implication of H. pylori infection in the etiology of cardiovascular events via its exacerbation of or influence on risk factors of atherogenesis.
Infliximab regulates lamina propria T lymphocytes in patients with Crohn's disease
Authors: WATANABE O. , ANDO T. , FURUTA R. , MAEDA O. , ISHIGURO K. , TAKAHASHI H. , INA K. , KUSUGAMI K. , GOTO H.
Published: June 2006

Background and Aims

The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohn's disease. Cytokines such as tumour necrosis factor‐alpha are well‐known mediators of the immune system, and treatment with a chimeric anti‐tumour necrosis factor‐alpha antibody (infliximab) has been shown to be highly effective in patients with Crohn's disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximab's effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes.

Methods

Thirteen patients with Crohn's disease were treated with infliximab at a dosage of 5‐mg/kg body weight. Clinical response was evaluated using the Crohn's Disease Activity Index, and serum soluble interleukin‐2 receptor, interleukin‐6, tumour necrosis factor‐alpha levels were analysed by enzyme‐linked immunosorbent assay at 0 and 2 weeks after treatment. Apoptosis of peripheral and lamina propria T lymphocytes after culture with infliximab was detected by flow cytometry.

Results

Crohn's Disease Activity Index decreased in 12 of 13 patients, and serum soluble interleukin‐2 receptor, interleukin‐6 and tumour necrosis factor‐alpha levels decreased in most patients after treatment with infliximab. Tumour necrosis factor‐alpha level before treatment in the six patients in whom Crohn's Disease Activity Index decreased by more than 70 was <5 ng/mL. Infliximab induced the apoptosis of lamina propria but not of peripheral T lymphocytes.

Conclusion

These findings suggest that a low level of serum tumour necrosis factor‐alpha is an indicator for infliximab treatment. The induction of apoptosis of lamina propria T lymphocytes by infliximab may be an important mechanism of its anti‐inflammatory effect in patients with Crohn's disease.
Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance?
Authors: MASAOKA T. , SUZUKI H. , KURABAYASHI K. , NOMOTO Y. , NISHIZAWA T. , MORI M. , HIBI T.
Published: June 2006

Background

Although resistance of Helicobacter pylori to metronidazole had been reported to be associated with mutations in the rdxA or the frxA gene, recent studies have indicated that they may contribute little to metronidazole resistance.

Aim

To clarify the roles of these genes in metronidazole resistance, we examined them in strains that were not eradicated by first‐line eradication therapy.

Patients and methods

A total of 132 patients (92 males, 40 females, average age: 53.8 years old) who underwent upper gastrointestinal endoscopy after unsuccessful first‐line H. pylori eradication were enrolled. Antibiotic susceptibility to metronidazole was investigated using the agar dilution method. The H. pylorirdxA and frxA genes were then sequenced.

Results

In the metronidazole‐resistant strains, the sensitivity of detection of frameshift mutations in the rdxA gene was 44%. A significant association between the presence of frameshift mutations in the rdxA gene and resistance to metronidazole was observed. No significant association between frameshift mutations in the frxA gene and resistance to metronidazole was observed.

Conclusion

Mutation in the rdxA gene was sufficient, but not necessary to confer resistance to metronidazole in H. pylori. Mutation in the frxA gene was not necessary for resistance to metronidazole in H. pylori.
Intravenous ghrelin administration enhances gastric acid secretion – evaluation using wireless pH capsule
Authors: MORI M. , SUZUKI H. , MASAOKA T. , IMAEDA H. , NOMOTO Y. , HOSODA H. , NISHIZAWA T. , KANGAWA K. , HIBI T.
Published: June 2006

Background

Ghrelin, a recently discovered peptide hormone, has been shown to be produced mainly by the A‐like cells of the gastric mucosa. Ghrelin not only stimulates growth hormone (GH) release but also promotes gastric motility. While the effect of ghrelin on the gastric acid secretion in rats has been reported, no such reports appeared to date from studies in humans.

Aim

To investigate the effect of ghrelin administration on the gastric pH in humans, using a novel wireless pH capsule (Bravo, Medtronic, Shoreview, MN, USA).

Methods

Four healthy volunteers (male; average age, 35.0 years; Helicobacter pylori‐negative) were enrolled. The pH capsule was attached endoscopically to the gastric mucosa and the data were transmitted to a portable receiver. Thirty minutes after a stabilization period, synthetic ghrelin (5 μg/kg body weight) was injected intravenously into the subjects and the data were monitored for more than 120 min while the subjects lay supine.

Results

The average minimum gastric pH in four cases (1.2 ± 0.10) was significantly decreased after injection of ghrelin, as compared with the basal pH value (1.8 ± 0.06). The serum gastrin level, however, showed no change after the ghrelin injection.

Conclusion

These results suggest that exogenous ghrelin could enhance gastric acid secretion in humans.
Increased levels of plasma ghrelin in peptic ulcer disease
Authors: SUZUKI H. , MASAOKA T. , NOMOTO Y. , HOSODA H. , MORI M. , NISHIZAWA T. , MINEGISHI Y. , KANGAWA K. , HIBI T.
Published: June 2006

Background

Ghrelin is a novel appetite‐promoting peptide secreted primarily from the A‐like cells in the gastric fundic mucosa. As gastric inflammation caused by Helicobacter pylori infection extends, the number of ghrelin‐producing A‐like cells is diminished and gastric ghrelin content decreases significantly. We previously reported that plasma levels of ghrelin, which correlated well with the serum levels of pepsinogen (PG) I and PG I/II ratio, decreased as gastric mucosal atrophy increased in non‐ulcerogenic conditions and that plasma ghrelin level increased in rats with cysteamine‐induced duodenal ulcer.

Aim

To investigate the plasma levels of ghrelin in patients with peptic ulcer disease.

Patients and Methods

Two hundred and eighty‐six patients with epigastric symptoms, who underwent upper gastrointestinal endoscopy, were enrolled. Blood samples were collected after a 12‐h fast before endoscopy. Patients were divided into four groups, namely chronic gastritis with high PG (n = 197), chronic gastritis with low PG (n = 58), duodenal ulcer (n = 14) and gastric ulcer (n = 17) and plasma concentrations of total and active ghrelin as well as serum concentrations of PG I and PG II were measured by radioimmunoassay. Six patients with duodenal ulcer and seven with gastric ulcer were also examined after ulcer healing.

Results

Plasma ghrelin levels were significantly higher in patients with duodenal ulcer or gastric ulcer than in those without ulcers. Elevated plasma total ghrelin levels did not significantly change after the healing of ulcers.

Conclusions

Plasma ghrelin levels were significantly higher in patients with peptic ulcer than in those with gastritis without ulcer. This finding suggests a possible relationship between mucosal injury susceptibility and elevated fasting plasma ghrelin.
Gastric motility and autonomic activity during obstructive sleep apnea
Authors: URATA M. , FUKUNO H. , NOMURA M. , OGATA T. , ITO S. , NAKAYASU K. , NAKAYA Y.
Published: June 2006

Background

Patients with Obstructive Sleep Apnea Syndrome (OSAS) often experience gastroesophageal reflux disease (GERD).

Aim

To investigate gastric motility and autonomic nervous activity during sleep apnea.

Methods

The subjects of this study were 20 individuals with OSAS who experienced 10 or more sleep apnoea events per hour, as measured with a portable sleep polygraph. A percutaneous electrogastrography (EGG) and fast Fourier transformation analysis was carried out on the results. The mean amplitude was compared for bradygastria, normogastria and tachygastria. Spectral analysis of heart rate variability was performed, and low‐frequency (LF) power, high‐frequency (HF) power and the LF/HF ratio were measured. Oesophagogastroduodenal endoscopy was performed on each subject, and the presence of reflux oesophagitis (RE) was diagnosed according to the Los Angeles (LA) grade classification. Moreover, questionnaire for the diagnosis of reflux disease (QUEST) was carried out.

Results

Normogastria was significantly decreased, and brady‐, tachygastria, or both were increased during sleep apnea (P < 0.01). There was no significant relation between LA grade classification of RE and severity of OSAS. The LF/HF ratio was significantly higher during sleep apnea for patients with RE and OSAS, but the opposite for those with RE without OSAS. Decreased percutaneous arterial oxygen saturation and normogastria were independent risk factors for the severity of RE.

Conclusions

The present study suggested that, in addition to decreased pressure on the pleural cavity, factors affecting the development of RE might include abnormal gastric motility, low oxygen, and increased sympathetic nervous activity during sleep apnea.
Efficacy and endoscopic prediction of cytapheresis therapy in patients with refractory and steroid‐dependent ulcerative colitis
Authors: WATANABE K. , OSHITANI N. , KAMATA N. , INAGAWA M. , YAMAGAMI H. , HIGUCHI K. , ARAKAWA T.
Published: June 2006

Background

Recently, it has been proved in Japan that granulocyte and monocyte adsorption apheresis (GCAP) and leukocytapheresis (LCAP) are effective and safe for patients with moderate to severe ulcerative colitis (UC).

Aim

To investigate the efficacy of GCAP and LCAP in patients with active UC, and the use of endoscopic findings in predicting efficacy, especially in refractory and steroid‐dependent cases.

Subjects and methods

Thirty‐four patients with active UC (24 refractory to conventional therapy and 10 steroid‐dependent) were treated with GCAP (n = 21) or LCAP (n = 13). The patients received one or two GCAP or LCAP sessions per week for 5 consecutive weeks, with colonoscopy before and after each session.

Results

About 70% of the patients achieved a clinical response, and no severe adverse effects were observed. Most steroid‐dependent patients or patients who had side effects due to steroids were controlled successfully. Endoscopically, 14 of 16 cases with shallow ulcers and erosion throughout the colon and 10 of 15 with deep ulcerations responded to treatment. However, three with massive ulceration of the whole mucosa did not respond.

Conclusions

GCAP or LCAP are valuable therapies for refractory or steroid‐dependent UC, and endoscopic findings are helpful in predicting clinical effectiveness.
Differential expression of cyclo‐oxygenase‐2 and nuclear β‐catenin in colorectal cancer tissue
Authors: TATSUGUCHI A. , KISHIDA T. , FUJIMORI S. , TANAKA S. , GUDIS K. , SHINJI S. , FURUKAWA K. , TAJIRI T. , SUGISAKI Y. , FUKUDA Y. , SAKAMOTO C.
Published: June 2006

Background

Both adenomatous polyposis coli (APC) gene mutation and cyclo‐oxygenase (COX)‐2 are thought to play key roles in colorectal carcinogenesis. Nuclear accumulation of β‐catenin results from APC gene mutation, which leads to enhanced transcription and activation of target genes, including cyclin D1. In vitro studies suggest that Cox‐2 transcription is directly regulated by β‐catenin/TCF complexes.

Aim

To investigate the relationship between cellular localization of β‐catenin and COX‐2 in colorectal cancer.

Methods

We performed immunohistochemical analysis of β‐catenin, cyclin D1 and COX‐2 expression in 50 resected colorectal cancer cases.

Results

The proportion of cases positive for cyclin D1 was higher in nuclear β‐catenin‐positive cases than in negative cases (P < 0.001). Serial sections revealed that the co‐localization of cyclin D1 and nuclear β‐catenin was most frequently evident in the tumour cells at the advancing margin of invasive carcinoma. Conversely, there was no association between COX‐2 and nuclear β‐catenin expression, either topographically or statistically. The staining patterns for COX‐2 and nuclear β‐catenin differed; COX‐2 was diffuse and homogeneous, whereas nuclear β‐catenin was focal and preferentially distributed at the invasive margin of cancer cells.

Conclusions

These two important modulators of colorectal tumourigenesis are differentially expressed. Cox‐2 and β‐catenin transcription may be activated by different pathways.
Relationship between ghrelin and Helicobacter pylori infection in Polish adult shepherds and their children
Authors: PLONKA M. , KONTUREK P. C. , BIELANSKI W. , PAWLIK T. , BRZOZOWSKI T. , KONTUREK S. J.
Published: June 2006

Background

Ghrelin stimulates food intake and body weight gain. The stomach is the major source of circulating ghrelin, but controversy exists over the relationship between ghrelin release and Helicobacter pylori infection.

Aim

To assess the relationship between H. pylori infection and ghrelin, leptin and gastrin release in adult shepherds and their children, and to measure the effect of H. pylori eradication on gastric ghrelin content.

Methods

H. pylori prevalence was compared in 42 shepherds with full contact with sheep, 148 farmers without sheep contact and in 61 age‐matched urban adult controls as well as in 58 shepherd children with sheep contact, 88 mountain children without contact and 141 urban children controls. Serum levels of ghrelin, leptin and gastrin in adult shepherds and their children with and without H. pylori infection were measured.

Results

The major source of circulating ghrelin was gastric corpus mucosa, as ghrelin content was severalfold higher than that in antral mucosa and was significantly higher in the H. pylori‐eradicated than that in H. pylori‐infected mucosa. Serum levels of ghrelin were greatly increased, while gastrin levels were significantly decreased in H. pylori‐negative as compared with H. pylori‐positive subjects. In mountain children, serum levels of ghrelin and leptin were about twofold higher in H. pylori‐negative than in H. pylori‐positive children, whereas gastrin levels were significantly reduced in H. pylori‐negative children.

Conclusions

The high incidence of H. pylori infection in shepherds and their children seems to contribute to the decreased serum levels of ghrelin and increased levels of gastrin in H. pylori‐infected mountain children and to their decreased appetite and dyspeptic symptoms.
High prevalence of Helicobacter pylori infection in Japanese patients with membranous nephropathy
Authors: MORIYAMA T. , KANEKO T. , FUJII M. , TSUBAKIHARA Y. , KAWANO S. , IMAI E.
Published: June 2006

Background

Membranous nephropathy is the most common cause of nephrotic syndrome in Japanese adults, and is often precipitated by systemic diseases such as infection, neoplasm, and autoimmune conditions. Recently, the Helicobacter pylori antigen was detected histochemically in the glomeruli of membranous nephropathy patients, raising the possibility that H. pylori may be the pathogen that causes.

Aim

To reveal the p1revalence of H. pylori infection in the Japanese membranous nephropathy population and to test the therapeutic efficacy of H. pylori eradication on the course of disease in membranous nephropathy patients.

Methods

The prevalence of H. pylori infection was investigated by the HM‐CAP method in 32 membranous nephropathy patients and an age‐matched control group (C: n = 243).

Results

A significantly higher H. pylori infection rate was found in membranous nephropathy patients than in the control group (positive/total: membranous nephropathy 21/32 vs. C 108/243, P < 0.05 by chi‐squared test). Eradication of H. pylori was achieved in four membranous nephropathy patients with proteinuria who were receiving glucocorticoid therapy, three of whom experienced a reduction of proteinuria after eradication.

Conclusions

We found a higher prevalence of H. pylori infection in Japanese membranous nephropathy patients than in age‐matched control subjects, which suggests the possible involvement of H. pylori infection in the pathogenesis of membranous nephropathy.
Helicobacter pylori eradication prevents the development of gastric cancer – results of a long‐term retrospective study in Japan
Authors: KATO M. , ASAKA M. , NAKAMURA T. , AZUMA T. , TOMITA E. , KAMOSHIDA T. , SATO K. , INABA T. , Shirasaka D. , OKAMOTO S. , TAKAHASHI S. , TERAO S. , SUWAKI K. , ISOMOTO H. , YAMAGATA H. , NOMURA H. , YAGI K. , SONE Y. , URABE T. , AKAMATSU T. , OHARA S. , TAKAGI A. , MIWA J. , INATSUCHI S.
Published: June 2006

Aim

This large‐scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan.

Methods

This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow‐up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection.

Results

Three‐thousand twenty‐one patients were enrolled. The median follow‐up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62).

Conclusion

This large‐scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.
Helicobacter pylori eradication and metachronous gastric cancer after endoscopic mucosal resection of early gastric cancer
Authors: NAKAGAWA S. , ASAKA M. , KATO M. , NAKAMURA T. , KATO C. , FUJIOKA T. , TATSUTA M. , KEIDA K. , TERAO S. , TAKAHASHI S. , UEMURA N. , KATO T. , AOYAMA N. , SAITO D. , SUZUKI M. , IMAMURA A. , SATO K. , MIWA H. , NOMURA H. , KAISE M. , OOHARA S. , KAWAI T. , URABE K. , SAKAKI N. , ITO S. , NODA Y. , YANAKA A. , KUSUGAMI K. , GOTO H. , FURUTA T. , FUJINO M. , KINJYOU F. , OOKUSA T.
Published: June 2006

Aim

To conduct a retrospective multicentre study at 31 medical centres in Japan, to investigate the association between the eradication of Helicobacter pylori and the development of new gastric cancer after endoscopic mucosal resection (EMR) for early gastric cancer.

Methods

Patients included those in whom early gastric cancer had been removed by EMR, and who had received follow‐up endoscopic treatment. All patients underwent follow‐up endoscopic treatment at least once a year after the initial EMR. The rate of new gastric cancer development was compared among those patients for whom H. pylori had been successfully eradicated and those with persistent H. pylori infection.

Results

The study included 2835 patients with a median follow‐up period of 2 years (range 0.5–12 years). Helicobacter pylori was eradicated in 356 patients (13%). Metachronous gastric cancers developed in eight (2%) patients among those who had been successfully treated for H. pylori, compared with 129 patients (5%) among those with persistent H. pylori infection (P = 0.021; OR = 0.42; 95% CI = 0.20–0.86).

Conclusion

Although longer term, prospective randomized controlled trials are needed to better estimate the extent and sustainability of possible benefits, this study suggests that the eradication of H. pylori may help reduce the incidence of metachronous gastric cancer.
Distribution comparison of depressed vs. non‐depressed early colorectal cancers
Authors: SAKAMOTO N. , TERAI T. , OHKUSA T. , ABE S. , BEPPU K. , KOBAYASHI O. , HIRAI S. , KONNO A. , NAMIHISA A. , OGIHARA T. , FUJII H. , MIWA H. , SATO N.
Published: June 2006

Background

Colorectal depressed tumours have a tendency to invade deeper mucosal layers and metastasize in the lymph nodes, despite their small size.

Aim

To investigate the clinical and endoscopic characteristics of depressed early colorectal cancers (intramucosal and submucosal adenocarcinoma) compared with non‐depressed early cancers.

Methods

Five hundred and seventy consecutive early colorectal cancers obtained through endoscopic resection or surgical operation were studied. Early cancers were endoscopically classified as either the depressed or non‐depressed type. The age and gender of the patients as well as the size and distribution of the cancers were compared between types. The tumour locations were classified into three groups: caecum to transverse colon (right colon), descending to sigmoid colon (left colon) and rectum.

Results

Patients were similar with respect to age and gender. The mean size of the depressed type was smaller than that of the non‐depressed type (mean 8.4 mm vs. 13.3 mm; P < 0.0001). The rate of occurrence of depressed type in the right colon was higher than that of non‐depressed type (49% vs. 23%) (P = 0.0006). Among the early cancers, the incidence of the depressed type in the right colon was higher than that in the left colon and rectum (15% in the right colon, 7% in the left colon and 4% in the rectum; P < 0.01).

Conclusions

Compared with non‐depressed early colorectal cancers, depressed cancers were smaller in size and more likely to be distributed in the right colon.
Increased intestinal luminal carbon monoxide gas in patients with ulcerative colitis
Authors: TAKAGI T. , NAITO Y. , TSUBOI H. , ISOZAKI Y. , KATADA K. , SUZUKI T. , TERAO K. , HANDA O. , KOKURA S. , ICHIKAWA H. , YOSHIDA N. , OKUYAMA Y. , YAGI N. , UEDA H. , YOSHIKAWA T.
Published: June 2006

Background

Recent studies in models of inflammatory bowel disease have demonstrated that heme oxygenase‐1 (HO‐1) induction, or its by‐products in this process such as carbon monoxide (CO), plays an important role in the intestinal inflammation. However, the distribution of HO‐1 in intestinal mucosa and the concentration of intestinal luminal CO in humans have not yet been investigated.

Aim

To detect the HO‐immunopositive cells in the intestine of normal subjects and in patients with ulcerative colitis (UC) and to measure intestinal luminal CO gas contents using gas chromatography.

Materials and Methods

The expression of HO‐1 in the intestine was determined using immunohistochemistry. Human colonic gas was collected using colonoscopy from healthy volunteers and patients with UC. Analysis of intestinal luminal gas was performed using a newly developed portable gas chromatograph.

Results

Immunopositive staining for HO‐1 was localized in the inflammatory cells, mainly mononuclear cells, and the number of cells that accepted stain was greater in patients with UC. CO level in the intestinal lumen significantly increased in patients in the active stage of UC.

Conclusion

These findings indicate that the HO‐CO system is induced in UC.
Host serological response to Helicobacter pylori after successful eradication: long‐term follow‐up in patients with cured and persistent infection
Authors: TANAKA J. , OHKUSA T. , YOKOYAMA T. , MATSUHISA T. , KAWAI T. , HASHIMOTO H. , TOMITA T. , HORI K. , NAKAJIMA K. , MATSUMOTO T. , MIWA H.
Published: June 2006

Aim

To systematically determine the usefulness of Helicobacter pylori IgG antibody titer decline as a predictor of treatment success after H. pylori eradication in large patient samples.

Patients and Methods

Serum samples from 258 H. pylori positive patients (52.8 yrs, 65% males) were retrospectively collected from five medical centers, and H. pylori titers were quantitatively determined by ELISA. Serial serum samples were collected at baseline and for up to 4.9 years after treatment. 169 patients underwent successful eradication while 89 remained infected. The median total observation period was 635 days (range, 51 to 1,800 days). Chronological changes in H. pylori titers were analyzed and compared between cured and infection persistent subjects.

Results

The proportion of infection persistent patients who developed negative H. pylori IgG antibody titers was below 5%. A receiver operating characteristic (ROC) curve for the confirmation of successful eradication according to the percent decline over baseline at each time‐point showed that a 60% decline at 1 year or more after eradication treatment strongly correlated with successful eradication (sensitivity = 90% and specificity = 87%).

Conclusion

A 60% decline in H. pylori IgG titers (HEL‐p kit) from baseline to one year or greater is a reliable predictor of successful H. pylori eradication.
Enhancement of cytoprotective ability and cell restoration in 70‐kDa heat shock protein gene‐transfected rat gastric mucosal cells
Authors: OTAKA M. , MATSUHASHI T. , ODASHIMA M. , ITOH H. , JIN M. , WADA I. , KOMATSU K. , HORIKAWA Y. , OHBA R. , OYAKE J. , HATAKEYAMA N. , WATANABE S.
Published: June 2006

Background

Many recent studies have indicated the importance of heat shock proteins for cell survival under stress conditions. Some heat shock proteins are known to be involved in cytoprotection against environmental stresses, through their function as ‘molecular chaperones’.

Aim

To examine the biological characteristics of HSP70 gene‐transfected gastric mucosal cells.

Materials and methods

Complimentary DNA of human HSP70 gene was transfected to RGM‐1 cells (rat gastric mucosal cell line) and HSP70 highly‐expressing cells were selected and cloned. A single clone (7018‐RGM‐1), which highly expressed HSP70 compared with RGM‐1, was used in this study. Cytoprotective ability against H2O2 or ethanol was analysed by WST‐assay and LDH‐release. Wound restoration of artificially created wounds was also compared between RGM‐1 and 7018‐RGM‐1 cells.

Results

We successfully cloned HSP70 highly‐expressing gastric mucosal cells, which expressed a level of HSP70 equal to 350% of that of RGM‐1 cells. Over‐expression of HSP70 clearly enhanced cytoprotective ability against H2O2 or ethanol‐induced cell damage. Wound restoration was enhanced in 7018‐RGM‐1 cells compared with RGM‐1 cells.

Conclusion

Our results suggested that expression of HSP70 might play important roles not only in cytoprotection but also in mucosal wound restoration, mediated by the molecular chaperone function of HSP70.
Helicobacter pylori eradication therapy modulates acidity and interleukin‐1β mRNA levels in un‐operated stomach and in remnant stomach after gastrectomy in gastric cancer patients
Authors: KATO S. , MATSUKURA N. , MATSUDA N. , TSUKADA K. , NAITO Z. , TAJIRI T.
Published: June 2006

Background

A number of studies have indicated that Helicobacter pylori eradication therapy helps prevent secondary cancers in the stomach.

Aim

To investigate the risk of secondary cancer in the residual stomach after gastrectomy by comparing molecular biomarkers from stomach mucosa biopsies and the pH of gastric juice between H. pylori patients with and without gastrectomy.

Methods

Conventional H. pylori eradication therapy was administered to 22 patients who had undergone gastrectomy and to 37 un‐operated patients. We measured pH levels of gastric juice, and collected stomach mucosa biopsy specimens by gastrointestinal fiberscopy. The mRNA expression levels of interleukin‐1β, interleukin‐8 and cyclo‐oxygenase 2 in the biopsy tissues were measured by real‐time polymerase chain reaction.

Results

Interleukin‐1β levels in the antrum of un‐operated H. pylori‐positive patients showed a reverse correlation with pH levels in the gastric lumen (correlation coefficient: −0.50, P = 0.007). After eradication, pH levels were strongly associated with interleukin‐1β mRNA levels, r = 0.83, P = 0.01, which, in the remnant stomach mucosa, decreased from 22.5 to 4.6 in the anastomosis and from 3.1 to 2.4 in the upper corpus, with a simultaneous and statistically significant decrease in pH.

Conclusions

Interleukin‐1β mRNA levels correlated with pH levels in the remnant stomach. This indicates that eradication therapy may contribute not only to a reduction in these cancer‐associated cytokines, but also to an improvement in the internal environment of the remnant stomach.
Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells
Authors: FUJII Y. , SHIMADA T. , KOIKE T. , HOSAKA K. , TABEI K. , NAMATAME T. , TAJIMA A. , YONEDA M. , TERANO A. , HIRAISHI H.
Published: June 2006

Trefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.

Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach.

TFF1 was originally discovered as an oestrogen‐inducible gene in MCF‐7 breast cancer cells, and its expression is dependent on oestrogen in MCF‐7 and other hormone‐dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis‐regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL‐6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.

Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue‐specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.
Review article: fast acid control and rapid symptom relief for patients with gastro‐oesophageal reflux disease – the evidence from proton pump inhibitor studies
Authors: BYTZER P.
Published: June 2006

Because of their potent, rapid antisecretory effects, proton pump inhibitors (PPIs) are the mainstay of treatment for patients with gastro‐oesophageal reflux disease (GERD), providing fast symptom relief and increased mucosal healing.

A review of the clinical data suggests that subpopulations of patients with GERD – non‐erosive symptomatic GERD (NERD), and erosive oesophagitis (EO) – derive significant benefits from fast‐acting PPIs. Patients with EO receiving fast‐acting PPIs experienced rapid relief of daytime and night‐time heartburn and related symptoms, with associated increases in quality of life (QoL). Similar benefits were observed for patients with NERD. Patients with EO and NERD showed significant symptom relief within the first day of treatment, which was most evident following lansoprazole, esomeprazole and rabeprazole. When used as long‐term on‐demand/intermittent therapy, fast‐acting PPIs significantly improved symptom relief and patient's QoL by reducing treatment discontinuation rates.

In conclusion, fast‐acting antisecretory PPIs should be considered as optimal therapy for rapid symptom relief in different patient subpopulations with GERD.
Effects of Multiple Reflections on Hole Formation During Short-Pulsed Laser Drilling
Authors: Modest Michael F.
Published: June 2006

Beam guiding effects during laser drilling due to multiple specular reflections inside the hole are analyzed for the case of very short laser pulses (nanosecond range). Specular reflections are valid for materials that retain a smooth surface during laser evaporation (small optical roughness compared to the laser wavelength). The problem is assumed to be two-dimensional axisymmetric (unpolarized laser), with the hole geometry defined by nodal values connected through a cubic spline. The net radiative flux onto a surface node is determined through ray tracing methods. The resulting absorbed laser flux is combined with a simple quasi-one-dimensional conduction model (to assess the minor conduction losses) and an Arrhenius evaporation rate model, to predict hole development as a function of time through iteration. To stabilize this highly nonlinear and thus unstable problem (in numerical analysis as well as in experiments) the laser beam is diffused a small amount from the specular direction (to also account for the limitation that no beam can be focused down to a point), and by periodic slight smoothing of the irradiation levels. Results show that drilling rates are increased dramatically due to beam trapping for highly reflective materials, resulting in a more pointed hole profile.
Population Pharmacokinetic Assessment of a New Regimen of Mefloquine Used in Combination Treatment of Uncomplicated Falciparum Malaria
Authors: Ashley Elizabeth A. , Stepniewska Kasia , Lindegårdh Niklas , McGready Rose , Hutagalung Robert , Hae Rae , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: June 2006

A fixed artesunate-mefloquine combination, comprising three daily doses of 8 mg of mefloquine/kg of body weight and 4 mg of artesunate/kg, has been developed recently. This study was designed to construct a population pharmacokinetic model describing this new dosage regimen of mefloquine given as loose tablets together with artesunate. In two randomized trials in Thailand which evaluated the efficacy, safety, and tolerability of this new regimen, the members of a subgroup of 50 patients were randomized to have capillary blood sampling before treatment and at five randomly assigned time points during the 63-day follow-up period. Mefloquine levels in capillary whole blood were assayed by liquid chromatography with UV detection. A pharmacokinetic model for mefloquine was constructed using mixed-effects modeling. A one-compartment model with first-order absorption and elimination was selected to describe the kinetic properties of mefloquine. For capillary whole-blood mefloquine, the area under the concentration curve (AUC) was 40% higher than previous estimates for patients given the equivalent conventional-dose regimen (mefloquine given as 15 mg/kg and then 10 mg/kg on the second and third days of treatment). The half-life (
t
1/2
) of the carboxylic acid metabolite was estimated as 26 days, and the metabolite was eliminated more slowly than the parent drug (population
t
1/2
estimate, 10.5 days). Splitting the 25 mg/kg dose of mefloquine into three doses of 8 mg/kg each resulted in improved oral bioavailability compared to the conventional split-dose regimen results. This new regimen is well tolerated and results in an equivalent therapeutic response.
Effect of a Selective Decontamination of the Digestive Tract Regimen Including Parenteral Cefepime on Establishment of Intestinal Colonization with Vancomycin-Resistant
Enterococcus
spp. and
Klebsiella pneumoniae
in Mice
Authors: Paterson David L. , Stiefel Usha , Donskey Curtis J.
Published: June 2006

In mice, a selective decontamination of the digestive tract regimen consisting of orogastric tobramycin, polymyxin E, and amphotericin B in combination with subcutaneous cefepime inhibited gram-negative bacilli, including
Klebsiella pneumoniae
, and did not promote vancomycin-resistant
Enterococcus
spp. (VRE) colonization. However, concurrent administration of subcutaneous ampicillin-sulbactam resulted in promotion of VRE.
In Vivo Survival of Teicoplanin-Resistant
Staphylococcus aureus
and Fitness Cost of Teicoplanin Resistance
Authors: McCallum N. , Karauzum H. , Getzmann R. , Bischoff M. , Majcherczyk P. , Berger-Bächi B. , Landmann R.
Published: June 2006

Glycopeptide resistance, in a set of in vitro step-selected teicoplanin-resistant mutants derived from susceptible
Staphylococcus aureus
SA113, was associated with slower growth, thickening of the bacterial cell wall, increased
N
-acetylglucosamine incorporation, and decreased hemolysis. Differential transcriptome analysis showed that as resistance increased, some virulence-associated genes became downregulated. In a mouse tissue cage infection model, an inoculum of 10
4
CFU of strain SA113 rapidly produced a high-bacterial-load infection, which triggered MIP-2 release, leukocyte infiltration, and reduced leukocyte viability. In contrast, with the same inoculum of the isogenic glycopeptide-resistant derivative NM67, CFU initially decreased, resulting in the elimination of the mutant in three out of seven cages. In the four cages in which NM67 survived, it partially regained wild-type characteristics, including thinning of the cell wall, reduced
N
-acetylglucosamine uptake, and increased hemolysis; however, the survivors also became teicoplanin hypersusceptible. The elimination of the teicoplanin-resistant mutants and selection of teicoplanin-hypersusceptible survivors in the tissue cages indicated that glycopeptide resistance imposes a fitness burden on
S. aureus
and is selected against in vivo, with restoration of fitness incurring the price of resistance loss.
Antimicrobial Activity and Spectrum of Cefovecin, a New Extended- Spectrum Cephalosporin, against Pathogens Collected from Dogs and Cats in Europe and North America
Authors: Stegemann M. R. , Passmore C. A. , Sherington J. , Lindeman C. J. , Papp G. , Weigel D. J. , Skogerboe T. L.
Published: June 2006

Cefovecin is a new extended-spectrum semisynthetic cephalosporin indicated for the treatment of bacterial infections in dogs and cats. This study evaluated the in vitro activity and spectrum of cefovecin against 2,641 recent clinical isolates (1,660 canine and 981 feline isolates) from Europe and the United States. MIC determinations against cefovecin and other reference antimicrobials were performed by broth microdilution methods recommended by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS). Cefovecin demonstrated bactericidal activity against both gram-positive and gram-negative pathogens. Cefovecin exhibited in vitro activity against all major aerobic and anaerobic bacterial pathogens associated with skin, urinary tract, and periodontal infections in dogs and cats. The MIC
90
values of cefovecin against
Staphylococcus intermedius
,
Escherichia coli
, and
Pasteurella multocida
were 0.25 μg/ml, 1.0 μg/ml, and 0.06 μg/ml, respectively. No significant differences were observed in terms of the activities of cefovecin against pathogens from different European countries and against pathogens of European and U.S. origin.
Activity of LBM415 Compared to Those of 11 Other Agents against
Haemophilus
Species
Authors: Bogdanovich Tatiana , Smith Kathy A. , Clark Catherine , Pankuch Glenn A. , Lin Gengrong , McGhee Pamela , Dewasse Bonifacio , Appelbaum Peter C.
Published: June 2006

When tested against 254
Haemophilus influenzae
strains, LBM415, a peptide deformylase inhibitor, gave MIC
50
and MIC
90
values of 2.0 μg/ml and 8.0 μg/ml, respectively. The MICs were independent of β-lactam or quinolone susceptibility and the presence or absence of macrolide efflux or ribosomal protein mutations. The MICs of LBM415 against 23
H. parainfluenzae
strains were similar to those against
H. influenzae
. In contrast, erythromycin, azithromycin, and clarithromycin gave unimodal MIC distributions, and apart from β-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the β-lactams tested. Apart from selected quinolone-resistant strains, all strains were susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The potencies of all drugs against 23
H. parainfluenzae
strains were similar to those against
H. influenzae
. Time-kill studies with 10
Haemophilus
strains showed LBM415 to be bactericidal at 2× the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and β-lactams were bactericidal against 8 to 10 strains each at 2× the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2× the MIC after 24 h. Against six
H. influenzae
strains, postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep resistance selection studies, LBM415 produced resistant clones in 7 of the 10 strains tested, with MICs ranging from 4 to 64 μg/ml. No mutations in deformylase (
def
) and formyltransferase (
fmt
) genes were detected in any of the LBM415-resistant mutants.
Absorption, Metabolism, and Excretion of [
14
C]Viramidine in Humans
Authors: Lin Chin-chung , Xu Christine , Zhu Nanqun , Yeh Li-Tain
Published: June 2006

Absorption, metabolism, and excretion of [
14
C]viramidine, a prodrug of ribavirin, were studied in humans following a single oral dose (600 mg). Viramidine was rapidly absorbed, with a time to maximum concentration of the drug in plasma of 1.5 h. Viramidine and ribavirin accounted for only 4.3% and 42% of plasma area under the concentration-time curve (AUC) for radioactivity, respectively, indicating extensive conversion of viramidine to ribavirin, followed by further metabolism of ribavirin. The drug was largely trapped in red blood cells (RBC), with an RBC-to-plasma radioactivity AUC
0-∞
ratio of 108. Excretion of total radioactivity in urine and feces accounted for 50.8% and 26.1% of the dose, respectively. The metabolic profile in urine (0 to 24 h) indicated that viramidine was excreted primarily as triazole carboxamide (TCONH
2
), triazole carboxylic acid nucleoside (TCOOH), and ribavirin with a small amount of unchanged viramidine, which each accounted for 64.1%, 17.0%, 15.7%, and 3.2% of urinary radioactivity, respectively. The amounts of unchanged viramidine (3.4% of dose) and ribavirin (10% of dose) in urine were small after oral administration of viramidine.