Impact of esophageal bile exposure on the genesis of reflux esophagitis in the absence of gastric acid after total gastrectomy

OBJECTIVE: The role of duodenal contents refluxing into the esophagus in producing reflux esophagitis (RE) remains unclear. We aimed to assess the impact of esophageal bile exposure on the genesis of RE in reference to esophageal pH changes in the absence of gastric acid after total gastrectomy. METHODS: Thirty patients having undergone total gastrectomy were studied with concurrent 24-h esophageal pH and bilimetric monitoring, and were divided into two groups based on endoscopic esophageal mucosal findings: without RE, group 1 (n = 24) and with RE, group 2 (n = 6). Esophageal bile exposure was defined as bilirubin absorbance >0.14 detected in the esophagus. RESULTS: 1) The percentage total time of esophageal bilirubin absorbance >0.14 was not correlated with that of esophageal pH >7.0, >7.4, and >8.0. 2) All parameters for esophageal bilirubin absorbance >0.14 in group 2 were significantly higher than those in group 1, whereas none of the parameters for esophageal pH >7.0, >7.4, and >8.0 showed a significant difference between the two groups. 3) The percentage total time of esophageal bilirubin absorbance >0.14 was over 50% in all subjects with RE, and six of seven subjects with that over 50% had RE. CONCLUSIONS: Esophageal bile exposure plays an important role in the genesis of RE in the absence of gastric acid, which is assessed better with the measurement of esophageal bilirubin absorbance than that of esophageal pH.     

Role of the short isoform of myosin light chain kinase in the contraction of cultured smooth muscle cells as examined by its down-regulation

GbaSM-4 cells, smooth muscle cells derived from brain basilar artery, which express both 210-kDa long and 130-kDa short isoforms of myosin light chain kinase (MLCK), were infected with an adenovirus vector carrying a 1.4-kb catalytic portion of MLCK-cDNA in an antisense orientation. Western blot analysis showed that the expression of short MLCK was depressed without affecting long MLCK expression. The contraction of the down-regulated cells was measured by the cell-populated collagen-fiber method. The tension development after stimulation with norepinephrine or was depressed. The additional infection of the down-regulated cells with the adenovirus construct containing the same insert in a sense direction rescued not only the short MLCK expression but also contraction, confirming the physiological role of short MLCK in the contraction. To examine the role of long MLCK in the residual contraction persisting in the short MLCK-deficient cells, long MLCK was further down-regulated by increasing the multiplicity of infection of the antisense construct. The additional down-regulation of long MLCK expression, however, did not alter the residual contraction, ruling out the involvement of long MLCK in the contractile activity. Further, in the cells where short MLCK was down-regulated specifically, the extent of phosphorylation of 20-kDa myosin light chain (MLC20) after the agonist stimulation was not affected. This finding suggests that there are additional factors to MLC20 phosphorylation that contribute to regulate smooth muscle contraction.     

Basic studies on a labeled anti-mucin antibody detectable by infrared-fluorescence endoscopy

Background. We developed a fluorescent dye, indocyanine green (ICG)-sulfo-OSu, which was excited by infrared rays and conjugated to various antibodies. We attempted to clarify the staining patterns of anti-sulfomucin and anti-MUC1 antibodies in gastrointestinal cancer. We then evaluated the potential of the dye as a fluorescent label for antibodies specific to cancer, to be used as a diagnostic method for microcancer, with infrared fluorescence endoscopy. Methods. Paraffin sections of samples collected from 10 patients with esophageal cancer, 30 patients with gastric cancer, and 20 patients with colorectal cancer were immunohistologically stained using an anti-sulfomucin antibody and an anti-MUC1 antibody, and the staining patterns were examined. If a section had a high staining intensity, it was reacted with the ICG-suflo-OSu-labeled antibody and evaluated with infrared fluorescence imaging. Results. The staining patterns with the antibodies varied depending on the organs and the histological types and depth of the cancers, but the staining was generally good and the staining on the mucosal surface of cancer tissues was retained. Good images of cancer cells could be obtained by infrared fluorescence observation using the ICG-sulfo-OSu-labeled anti-MUC1 antibody. Conclusions. The anti-MUC1 antibody stained gastrointestinal cancer cells well, and nearly specific infrared fluorescence in cancer tissues was observed using the labeled anti-MUC1 antibody. The ICG-sulfo-OSu-labeled anti-MUC1 antibody has possible usefulness for the screening of cancer via infrared fluorescence endoscopy. Received: December 8, 2000 / Accepted: September 28, 2001     

Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D(2) and prostaglandin E(2) spontaneously or in response to A23187 (10 microM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.     

Prevalence of Helicobacter pylori infection and its link to coronary risk factors in Japanese patients with acute myocardial infarction.

The association between Helicobacter pylori (H. pylori) infection and coronary artery disease, as well as the association between H. pylori infection and classic coronary risk factors, is controversial in patients from Western countries. The high prevalence of H. pylori infection in Japanese subjects enables an examination of these associations in a large population, especially in young patients, because coronary risk factors may be more strongly associated with younger individuals than with older individuals. The IgG seropositivity to H. pylori was assessed in 618 cases with acute myocardial infarction (AMI) and in 967 controls. The prevalence of seropositivity to H. pylori was similar between cases and controls, but in subjects younger than 55 years, the rate was significantly higher in cases than in controls (58.7% vs 43.3%, p = 0.009). After adjustment for age, gender, diabetes mellitus, hypertension, smoking, body mass index, total cholesterol, and high density lipoprotein cholesterol, the odds ratio for acute myocardial infarction was 2.97 (95% confidence interval, 1.37-6.41; p = 0.006). Worsening of classic coronary risk factors was not associated with H. pylori infection in subjects younger than 55 years. These results suggest that in younger individuals in Japan, H. pylori infection is significantly associated with AMI independent of the classic coronary risk factors.     

Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers

Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (Bcl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CIP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis.     

Two Independent Clones in Myelodysplastic Syndrome Following Treatment of Acute Myeloid Leukemia

We describe a 55-year-old Japanese woman with therapy-related myelodysplastic syndrome (t-MDS) with 2 independent clones, t(1;2)(p36;p21) and t(11;12)(pl5;ql3). She was diagnosed with acute myeloid leukemia (AML) with cytological features of the bone marrow and peripheral blood. Cytogenetic evaluation revealed a 46,XX karyotype. She received chemotherapy and achieved complete remission (CR). Despite maintenance chemotherapy, she suffered a relapse. Chromosomal analysis showed t(1;2)(p36;p21) in 2 of 20 metaphases. At second CR, this clone transiently disappeared. Nine months later, t(1;2) (p36;p21) was detected again in 3 of 20 metaphases while the patient remained in CR. Six months later, bone marrow examination disclosed trilineage dysplasia without an excess of blasts, suggesting MDS. t(1;2)(p36;p21) was observed in 16 of 20 metaphases. The clinical course and serial cytogenetic findings were diagnostic of t-MDS. The duration of t-MDS was 6 years. During this period, persistent t(1;2)(p36;p21) and transient t(11;12)(p15;q13) were found. When t-MDS evolved toAML, cytogenetic evaluation revealed 46,XX,t(1;2)(p36;p21),del(7)(q22),add(19)(p13).     

Bone loss in men under androgen-deprivation therapy for prostate cancer

Bone is a major target tissue for sex hormones and hypogonadism is a known cause of male osteoporosis. Androgen-deprivation therapy (ADT) for prostate cancer yields hypogonadotropic status and accelerates age-related decrease in bone mineral density. The risk for osteoporotic fractures is also increased which may lead to a shorter life expectancy for prostatic cancer patients. Baseline and follow up bone density measurement is desired for all men beginning ADT and it is advisable to take calcium and vitamin D as well as maintain a moderate exercise. Bisphosphonate is a possible treatment for those in whom osteoporosis develops. More data are desirable to make a guideline to prevent and treat male osteoporosis under ADT.     

Relationship of forces acting on implant rods and degree of scoliosis correction

Background

Adolescent idiopathic scoliosis is a complex spinal pathology characterized as a three-dimensional spine deformity combined with vertebral rotation. Various surgical techniques for correction of severe scoliotic deformity have evolved and became more advanced in applying the corrective forces. The objective of this study was to investigate the relationship between corrective forces acting on deformed rods and degree of scoliosis correction.

Methods

Implant rod geometries of six adolescent idiopathic scoliosis patients were measured before and after surgery. An elasto-plastic finite element model of the implant rod before surgery was reconstructed for each patient. An inverse method based on Finite Element Analysis was used to apply forces to the implant rod model such that it was deformed the same after surgery. Relationship between the magnitude of corrective forces and degree of correction expressed as change of Cobb angle was evaluated. The effects of screw configuration on the corrective forces were also investigated.

Findings

Corrective forces acting on rods and degree of correction were not correlated. Increase in number of implant screws tended to decrease the magnitude of corrective forces but did not provide higher degree of correction. Although greater correction was achieved with higher screw density, the forces increased at some level.

Interpretation

The biomechanics of scoliosis correction is not only dependent to the corrective forces acting on implant rods but also associated with various parameters such as screw placement configuration and spine stiffness. Considering the magnitude of forces, increasing screw density is not guaranteed as the safest surgical strategy.