bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Approaches for Validation of Lethal Phenotypes and Genetic Reversion in Helicobacter pylori
Authors: McDaniel Timothy K. , DeWalt Kevin C. , Salama Nina R. , Falkow Stanley 
Published: March 2003

AbstractBackground.Because of limited genetic tools for use in Helicobacter pylori, tests routinely applied in other bacteria for demonstrating a gene’s role in viability and other phenotypes have not been applied to this organism. In a mutational study of putative response regulator genes, we aimed to develop such tools for H. pylori.Materials and Methods.We attempted to mutate five response regulator genes by allelic exchange insertional mutagenesis. For genes that yielded no viable mutants, a second copy of the gene was inserted into the chromosome via a suicide vector, and it was seen if providing the second copy would permit the gene’s disruption. For genes that yielded mutants with selectable phenotypes, a strategy was developed for reversion whereby an intact copy of the gene is introduced to the organism by transformation with PCR products. Following this procedure, revertants were selected by phenotypic tests then tested for genetic reversion.Results.After failure to attain transformants upon attempted mutation of genes HP0166 and HP1365, we inserted a second copy of each gene within the H. pylori chromosome. In each case the second copy relieved the block of transformation. Mutation of genes HP0703 and HP1021 gave non‐motile and small‐colony phenotypes, respectively. Following transformation with PCR products containing intact copies of the genes, both phenotype and genotype had reverted following phenotypic selections.Conclusions.The methods used in this study provide new approaches for confirming suspected genotype/phenotype associations and should be widely applicable in the study of H. pylori.
CagA Status in Dyspeptic Patients With and Without Peptic Ulcer Disease in Turkey: Association With Histopathologic Findings
Authors: Demırtürk Levent , Özel A. Melih , Yazgan Yusuf , Solmazgül Emrullah , Yildirim Şükrü , Gültepe Mustafa , Gürbüz A. Kemal 
Published: March 2003

ABSTRACTBackground.CagA seropositivity is closely associated with that of vacuolating cytotoxin (VacA). Helicobacter pylori strains positive for both VacA and CagA were reported to be strongly associated with peptic ulcer disease. Different results reporting that cagA gene is not associated with more serious diseases, lowers the importance of CagA protein as a marker. In this study, CagA seropositivity is examined in Turkish peptic ulcer and nonulcer dyspepsia patients; histopathologic scores of CagA (+) and CagA (−) groups were compared.Materials and Methods.Sixty consecutive patients (one gastric ulcer, 13 duodenal ulcer and 46 nonulcer dyspepsia) (mean age 40.9 ± 14.7; 33 women, 27 men) with dyspeptic complaints who underwent upper gastrointestinal (GI) endoscopy were included. Biopsies from the antrum and corpus were used for histopathologic examination and for rapid urease test. H. pylori‐negative patients comprised the control group. Histopathologic findings were graded using a previously described grading system (for inflammation, activity, atrophy, intestinal metaplasia and H. pylori, grades from 0 to 3 were used to quantify the findings). In H. pylori‐positive patients, antibodies against CagA protein were determined using an ELISA method.Results. H. pylori was (+) in 46 patients. One duodenal ulcer and 13 nonulcer dyspepsia patients were negative for H. pylori. CagA positivity is significantly higher in peptic ulcer patients [12/12] than in nonulcer dyspepsia patients [25/33]. While inflammation, activity and atrophy scores were significantly higher in CagA positive patients, intestinal metaplasia and H. pylori load scores were not. Although the histopathologic scores in controls were lower than CagA (−) group, statistical significance was observed only in inflammation and intestinal metaplasia scores.Conclusion.Development of more prominent gastritis and severe atrophy in CagA (+) patients is an indicator of the importance of CagA rather than H. pylori load. Therefore, we suggest that nonulcer dyspepsia patients should also be tested for CagA status along with the tests for H. pylori status; and a positive CagA testing should be considered as an indication for eradication treatment. If CagA is negative, further assesment should be performed to decide whether or not to treat the patient.
The Pepsinogen Releasing Effect of Helicobacter pylori Lipopolysaccharide
Authors: Young G. O. , Brown S. , Stemmet N. , Lastovica A. J. , Marks I. N. , Modlin I. M. , Kidd M. 
Published: March 2003

ABSTRACTBackground. Helicobacter pylori lipopolysaccharide (LPS) affects pepsinogen release by a nontoxic mechanism. We hypothesized that this effect was characteristic of the organism and related to the clinical status of the strain.Materials and methods. LPS was isolated from 11 H. pylori strains whose pathogenic profile was known and four other nongastric bacteria. The effects of luminal LPS on guinea pig gastric mucosal pepsinogen release was evaluated using the Ussing chamber technique. CCK‐8 (10−9M) was used as a positive control.Results. H. pylori LPS dose‐dependently stimulated pepsinogen release with a maximal stimulation at 250 µg/ml (~4500%; p < .001 vs. control). LPS from other Helicobacter or Campylobacter species had no effect on pepsinogen release. ANOVA demonstrated significant differences in the efficacies of pepsinogen release between the 11 clinical H. pylori strains (p < .0001) despite the fact that they were all cagA+ and 90% had the cytotoxic vacA subtype s1. Physical and chemical disruption of the LPS suggested that both the structure and the carbohydrate composition of this molecule may play a critical role in pepsinogen release. Polymyxin B partly (p < .03) inhibited and dephosphorylation completely inhibited (p = .0002) LPS‐stimulated pepsinogen release.Conclusion. Pepsinogen release is an innate property of all cagA+H. pylori LPS. The structure of the molecule and composition of side‐chains are important in this response which appears to be partially lipid A driven.
Polaprezinc Attenuates Helicobacter pylori‐Associated Gastritis in Mongolian Gerbils
Authors: Ishihara Ryu , Iishi Hiroyasu , Sakai Noriko , Yano Hiroyuki , Uedo Noriya , Narahara Hiroyuki , Iseki Kazushige , Mikuni Tomiko , Ishiguro Shingo , Tatsuta Masaharu 
Published: March 2003

AbstractBackground. The ammonia‐monochloramine system plays an important role in Helicobacter pylori‐associated gastric mucosal injury. Polaprezinc, a new antiulcer agent, has a scavenging action against monochloramine. The aim of the experiment was to investigate the inhibitory effects of polaprezinc on the H. pylori‐induced gastritis in Mongolian gerbils.Materials and Methods. Mongolian gerbils fasting for 24 hours were orally given culture broth containing 2–4 × 108 colony‐forming units of H. pylori ATCC 43054 per milliliter. From 4 hours after inoculation until the end of the experiment, gerbils were given chow pellets with or without 0.02% polaprezinc. All gerbils were killed 12 weeks later. The grades of H. pylori density and histologic features of gastritis were evaluated in accordance with the Updated Sydney System. The scavenging effect of polaprezinc on monochloramine was investigated spectrophotometrically.Results. Polaprezinc had little or no influence on the H. pylori density in both pyloric and fundic mucosae. However, it significantly attenuated the development of polymorphonuclear neutrophil activity, mononuclear infiltration, and surface epithelial erosion in both pyloric and fundic mucosae compared with those of the control group. H. pylori inoculation significantly increased the heights of both pyloric and fundic mucosae (mainly due to the increased height of foveolar hyperplasia), but polaprezinc inhibited the increase of mucosal thickness in both pyloric and fundic mucasae. No intestinal metaplasia was detected in this study. Spectrophotometric examination revealed that polaprezinc scavenged monochloramine.Conclusions. Polaprezinc inhibited the development of H. pylori‐induced gastritis through its scavenging action against monochloramine.
Enterocromaffin‐Like Cell Tumor Induced by Helicobacter pylori Infection in Mongolian Gerbils
Authors: Kagawa Jiro , Honda Shoji , Kodama Masaaki , Sato Ryugo , Murakami Kazunari , Fujioka Toshio 
Published: March 2003

AbstractBackground. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori‐infected stomachs of Mongolian gerbils for a long time.Materials and Methods. Five‐week‐old‐male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals.Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes.Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin‐like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.
Statistical Model of the Interactions Between Helicobacter pylori Infection and Gastric Cancer Development
Authors: Welin Martin , Holmgren Noél M. A. , Nilsson Patric , Enroth Helena 
Published: March 2003

ABSTRACTBackground. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer.Methods. To find direct and indirect interactions between H. pylori and different histological variables, log‐linear analyses were used on a case–control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used.Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined.Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.
Helicobacter pylori Infection, Mucosal Atrophy and Intestinal Metaplasia in Asian Populations: A Comparative Study in Age‐, Gender‐ and Endoscopic Diagnosis‐Matched Subjects
Authors: Matsuhisa Takeshi M. , Yamada Nobutaka Y. , Kato Shunji K. , Matsukura Norio M. 
Published: March 2003

ABSTRACTBackground. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races.Materials and Methods. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori‐related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori‐positive cases (n = 120, 109, 145, 80, respectively) and H. pylori‐negative cases (n = 55, 66, 30, 95, respectively).Results. Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori‐positive Japanese subjects than in H. pylori‐positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori‐negative subjects belonging to the different Asian populations examined.Conclusions. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.
p16Ink4a is Overexpressed in H. pylori‐Associated Gastritis and is Correlated with Increased Epithelial Apoptosis
Authors: Shirin Haim , Hibshoosh Hanina , Kawabata Yuichi , Weinstein I. Bernard , Moss Steven F 
Published: March 2003

ABSTRACTBackground. Cell cycle regulatory proteins may be critical targets during carcinogenesis. We have previously shown that chronic H. pylori infection is associated with decreased expression of the cyclin dependent kinase inhibitor (CDI) p27kip1. Loss of p27kip1 and p16Ink4a (p16) expression, another CDI, has been reported during the progression of gastric tubular adenomas to advanced gastric cancer. The aim of the current study was to examine whether H. pylori infection also affects the expression of p16 in the gastric mucosa of H. pylori‐infected patients.Methods. p16 expression was evaluated in gastric antral biopsies by immunohistochemistry in 50 patients with nonulcer dyspepsia (n = 18 uninfected, n = 32 H. pylori infected, 24 by cagA+ strains). Adjacent sections were stained for proliferating epithelial cells (by Ki67) and for apoptotic cells (by TUNEL assay).Results. Both in H. pylori infected and uninfected patients the expression of p16 was higher in the neck and base of the gland than in the foveolar region. Epithelial staining for p16 was increased with H. pylori infection (31.3% vs. 11.1% in the foveolar region, 68.8% vs. 27.8% in the neck and 75% vs. 50% in the glandular base). There was no correlation between the expression of 16 and proliferation but there was a significant positive correlation between apoptosis and 16 immunostaining.Conclusions. The tumor suppressor gene 16 is over expressed in gastric epithelial cells of H. pylori infected patients and this is associated with an increase in apoptosis. These findings suggest a possible role for this cell cycle regulator in the increase in gastric cell turnover that is associated with H. pylori infection.
Success of the State Pain Initiatives
Authors: Dahl June L. , Bennett Mary E. , Bromley Matthew D. , Joranson David E. 
Published: March 2003

purpose: The purpose of this article is to describe the history of the State Cancer Pain Initiative (CPI) movement and current initiative activities that are directed at improving the management of cancer pain.overview: The undertreatment of pain is a major public health problem in the United States. State CPIs strive to remove the barriers to effective cancer pain management through the provision of innovative professional, patient, and public educational programs, through institutional change projects, and through public advocacy. Collaboration with organizations that share common goals is important in sustaining and maximizing the impact of the movement.clinical implications: Professionals, patients, and families benefit from the work of the State Initiatives. By enhancing the knowledge and skills of clinicians, supporting institutional change, and teaching patients and families the importance of effective pain control, the Initiatives help to improve the quality of life for all cancer survivors. Models of intervention that respond to local needs are discussed, and legislative and advocacy efforts that affect care also are noted.
Ensuring A Good Death
Authors: Lynch Maureen , Abrahm Janet 
Published: March 2003

purpose: The purpose of this article is to describe how the commitment of the Dana‐Farber Cancer Institute to pain management, quality of life, and optimal end‐of‐life care is operationalized through a comprehensive pain and palliative‐care program.overview: Institutional standards for pain management often address only the physical aspects of pain. Effective pain management requires assessment and interventions that address the multidimensional nature of pain, suffering, and quality of life throughout the cancer continuum. This approach seeks to lay the foundation of comfort and peace associated with a good death.clinical implications: Institutional pain management standards need to reflect the complexity of pain, especially cancer‐related pain, by emphasizing comprehensive, holistic assessment and multimodality approaches to pain control and quality‐of‐life issues.
Leptomeningeal Involvement in Chronic Lymphocytic Leukemia
Authors: Morrison Candis , Shah Surendra , Flinn Ian W. 
Published: March 2003

purpose
: This review and case report address the rare complication of leptomeningeal involvement in patients with chronic lymphocytic leukemia.
overview
: Chronic lymphocytic leukemia is the most common form of leukemia, with more than 200,000 cases reported in the past 20 years. An uncommon complication of the disorder is central nervous system invasion. To date, only 21 cases have been reported, and their presenting symptoms have been heterogeneous and often nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia, nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or radiation alone. Prognosis is improved by prompt and aggressive therapy. In this case report, a 61‐year‐old man developed severe ataxia, vertigo, and occipital headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic leukemia. After treatment with both radiation to the head and neck and intrathecal methotrexate the patient achieved complete symptom resolution. Thus far, no additional systemic cytotoxic chemotherapy has been necessary.
clinical implications
: Because central nervous system invasion is uncommon in chronic lymphocytic leukemia, it may go undiagnosed and under‐reported. Providers of patients with this disease need to be aware of possible central nervous system invasion when patients present with cranial nerve signs or symptoms and/or nonspecific neurologic manifestations. Early identification and prompt central nervous system‐directed chemotherapy can affect morbidity and quality of life positively.
Partner Abandonment of Women with Breast Cancer: Myth or Reality?
Authors: Taylor‐Brown Jill , Kilpatrick Marilyn , Maunsell Elizabeth , Dorval Michel 
Published: March 2003

Purpose: The purpose of this article is to determine the existing evidence related to marital breakdown after a breast cancer diagnosis by reviewing studies that highlight two current belief models: the lay belief model and the clinical belief model.Overview: The small number of studies conducted on this topic since 1988 revealed no data to confirm the lay belief model, which proposes that women with breast cancer are abandoned by their partners. The evidence appears to support the clinical belief model that the majority of marital relationships remain stable after breast cancer and that breakdown is most likely in those relationships with pre‐existing difficulties.Clinical implications: This review indicates that it may be important for clinicians to routinely ask about the quality of the marital relationship as part of the initial assessment, because it appears that this may be a main predictor of post‐diagnosis marital adjustment. In addition, greater dissemination of the findings of this review through the media and through cancer organizations is needed to more accurately reflect the experience of couples facing breast cancer and, thus, to begin to change the public perception of partner desertion after breast cancer. This could help both women with breast cancer and women from the general population who may one day confront a breast cancer diagnosis.
Problem‐Solving Cancer Care Education for Patients and Caregivers
Authors: Bucher Julia A. , Loscalzo Matthew , Zabora James , Houts Peter S. , Hooker Craig , BrintzenhofeSzoc Karlynn 
Published: March 2003

Purpose: A program evaluation was conducted to explore the potential effects of a 90‐minute problem‐solving education session for persons with advanced cancer and their families.Description of program: Patients with advanced cancer and their families, who were visiting a tertiary‐care outpatient setting, were invited to attend a 90‐minute individualized educational session that taught basic problem‐solving principles using a cognitive‐behavioral framework. Pre‐education and posteducation data were collected about the confidence of participants in providing care, their feelings about being informed about resources, and their perceptions of their problem‐solving ability.Results: At baseline, most participants reported low confidence about their ability to provide cancer care and felt uninformed about community resources, but they viewed themselves as moderate‐to‐good problem solvers. Forty‐two educational sessions were delivered to 49 caregivers and 40 patients. Two months later, participants reported feeling more informed about community resources and achieved higher posteducation scores for problem‐solving ability. More caregivers than patients reported that reading The Home Care Guide for Cancer made a great deal of difference in their approach to home care.Clinical implications: Most educational sessions for families affected by cancer focus on delivering information, not on building skills. These findings suggest that a one‐on‐one educational session that teaches problem‐solving skills can be successfully delivered in a busy clinic setting. Family caregivers are especially likely to benefit from this program.