Serum hepatocyte growth factor and cancer mortality in an apparently healthy Japanese population

Background: In patients with cancer, hepatocyte growth factor (HGF) is elevated and is a predictor of prognosis. We investigated whether serum HGF was a predictive marker for cancer death in a population of community-dwelling Japanese.Methods: We studied 1492 apparently healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of liver disease or malignancy on a baseline questionnaire were excluded, and plasma HGF was measured in the remaining 1470 participants, who were followed periodically for 10 years. Multivariate proportional hazards regression was used to estimate cancer mortality.Results: A total of 169 participants died during follow-up (61 from cancer, 32 from cerebrocardiovascular disease, and 76 from other diseases). Mean HGF at baseline was significantly higher among decedents than among survivors (0.26 ± 0.11 vs 0.23 ± 0.09 ng/ml, respectively; P < 0.01). The Cox proportional hazards model showed that age, systolic blood pressure, HGF (hazard ratio, 1.27; 95% CI, 1.06-1.52; P = 0.009), albumin level, smoking status, and creatinine were independent predictors of all-cause death. Age, HGF (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = 0.02), and total cholesterol were independent predictive markers for cancer death.Conclusions: Serum HGF was a predictor of cancer death in an apparently healthy population of community-dwelling Japanese.     

Effect of eicosapentaenoic acid on the platelet aggregation and composition of fatty acid in man. A double blind study

Twelve volunteers (mean age, 60.7 +/- 4.2 years) were treated with placebo for the first week and then given partially purified eicosapentaenoic acid (EPA, 67% purity) at 2 g per day for 4 weeks. Significant decreases in ADP-, collagen- and adrenalin-induced platelet aggregation were observed at 2 and 4 weeks after EPA treatment, together with an increase in the plasma ratio of EPA to arachidonic acid and in platelet phospholipids. It was concluded that the administration of partially purified EPA was effective in decreasing platelet aggregation, possibly by changing the platelet ratio of EPA to arachidonic acid.     

Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated

BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial. OBJECTIVE: To determine whether H. pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. DESIGN: Single-blind, uncontrolled prospective trial. SETTING: Academic gastroenterology clinic in Japan. PATIENTS: 163 consecutive patients with dyspepsia and H. pylori infection. INTERVENTION: One-week course of a proton-pump inhibitor and antibiotic therapy. MEASUREMENTS: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment. Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. RESULTS: In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. CONCLUSION: In the year after successful H. pylori eradication, precancerous lesions improved in most patients.     

Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system

OBJECTIVE: Our aim was to identify endoscopic features associated with Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: A total of 50 infected patients with nonulcer dyspepsia who underwent endoscopy with antral and corporal biopsies and 50 patients matched for age and sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively by three endoscopists blinded to the H. pylori status and the patient's history. The endoscopic findings of gastritis, classified by a modification of the Sydney system as present or absent, were evaluated, and the histological severity was graded by the updated Sydney system. RESULTS: For endoscopic features, the odds ratio was 53.1 (95% confidence interval, 6.8-414.9) for edema, 18.8 (5.8-60.5) for erythema with reddish streaks excluded, 0.0275 (0.0002-0.477) for reddish streaks, 17.4 (0.97-313.7) for friability, 14.2 (5.1-40.0) for exudate, 17.2 (2.2-137.6) for flat erosions, 2.54 (0.81-7.94) for raised erosions, 40.1 (2.3-694.5) for rugal hypertrophy, 19.1 (2.4-151.6) for rugal atrophy, 96.2 (23.4-395.9) for a vascular pattern, 0.125 (0.010-1.06) for bleeding spots, and 21.0 (2.6-166.5) for nodularity. The histological severity of inflammation, neutrophil activity, and atrophy in the antrum and corpus and of metaplasia in the antrum was greater in the infected patients than in the noninfected patients. CONCLUSIONS: Endoscopic features associated with H. pylori were a vascular pattern, edema, rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks excluded, flat erosions, and exudate. These endoscopic features were associated with the histological findings of inflammation, neutrophil activity, atrophy, and metaplasia.     

Attenuation of graft injury in porcine liver transplantation from non-heart beating donor by FR167653

BACKGROUND/AIMS: Orthotopic liver transplantation (OLTx) from non-heart beating donor (NHBD) often involves hepatic warm ischemia and reperfusion injury which is triggered by the inflammatory cytokines. This study was carried out to investigate whether a newly synthesized cytokine suppressive anti-inflammatory agent, FR167653, attenuates graft injury in OLTx from NHBD. METHODOLOGY: Porcine OLTx from NHBD was performed. No-heart beating time was scheduled to be 60 minutes. Animals were divided into two groups: no treatment control (CT) group (n=5), and FR167653 treated (FR) group (n=5), in which FR167653 was administered intravenously before the aortic cross clamp in the donor, and before and after the hepatic allograft reperfusion in the recipient continuously. RESULTS: Four out of five pigs died within 24 hours and one on postoperative day 1 from graft liver failure in the CT group, while two pigs died on day 3, and three survived more than 7 days in the FR group (p<0.05). Microcirculatory disturbance was attenuated, liver injury was lessened, and ATP resynthesis was enhanced in the FR group. Additionally, FR167653 inhibited neutrophils infiltration in the liver tissue, and suppressed release of inflammatory cytokines after OLTx from NHBD. CONCLUSIONS: The treatments with FR167653 successfully prevented graft injury after OLTx from NHBD by means of improvement of liver microcirculation, and attenuation of neutrophils activation. The inhibitory effect of FR167653 on the release of inflammatory cytokines played an important role in the liver graft protection.     

Development of a New Device for Diagnosis of Hypoxemia and Arrhythmia by SaO2 ECG Holter Monitoring

Background: We have developed a system to monitor, simultaneously and continuously, ambulatory SaO₂ measured using a pulse-oximeter and ECG data for 24 hours. Methods: The ambulatory SaO₂-ECG monitoring system consisted of a portable monitoring device (SM50) with two channels for ECG data and one channel for SaO₂ data input; a sensor for SaO₂ recording; and a pulse-oximeter. An ambulatory monitoring analyzer was used. The SaO₂ report from the present analyzer included two types of data (i.e., a profile of heart rate [HR], pulse rate [PR], and SaO₂ value per min), and a trend graph of HR, arrhythmia, ST level and slope, PR, and SaO₂ per minute. We also designed and produced an analytical program to automatically remove noise errors relating to the SaO₂ measurement. Results: Using this system, we performed a clinical study on ten healthy volunteers (Group N) and seven patients with chronic pulmonary diseases (Group CPD) to evaluate the usefulness of the system as a diagnostic means for respiratory failure and arrhythmia. Group N showed a stable value of 90% or over in SaO₂ during the 24-hour monitoring while Group CPD showed values under 90% SaO₂ in all patients at rest during the night or after a 15-minute walk. Transient atrial tachycardia (TAT) was observed in 3 of 7 CPD patients, and each episode was preceded by a decrease of SaO₂. The occurrence of a single or double ventricular extrasystole was high in Group CPD compared with Group N (1.21 ± 0.89 vs 0.6%± 0.3%, P < 0.05), its occurrence was not associated with a decrease in SaO₂. Conclusions: In outpatients, especially patients who are taken care of at home, the present system will certainly contribute greatly to the diagnosis of respiratory failure and arrhythmia as well as to evaluate the effects on these diseases of therapy. In addition it is suggested that in CPD, patients’hypoxemia may induce TAT.     

Induction of mucosal immunity by pulmonary administration of a cell-targeting nanoparticle

We previously found that a nanoparticle constructed with an antigen, benzalkonium chloride (BK) and γ-polyglutamic acid (γ-PGA) showed high Th1 and Th2-type immune induction after subcutaneous administration. For prophylaxis of respiratory infections, however, mucosal immunity should be induced. In this study, we investigated the effect of pulmonary administration of a nanoparticle comprising ovalbumin (OVA) as a model antigen, BK, and γ-PGA on induction of mucosal immunity in the lungs and serum. The complex was strongly taken up by RAW264.7 and DC2.4cells. After pulmonary administration, lung retention was longer for the OVA/BK/γ-PGA complex than for OVA alone. OVA-specific serum immunoglobulin (Ig)G was highly induced by the complex. High IgG and IgA levels were also induced in the bronchoalveolar lavage fluid, and in vivo toxicities were not observed. In conclusion, we effectively and safely induced mucosal immunity by pulmonary administration of an OVA/BK/γ-PGA complex.     

Detection of Mycoplasma hyopneumoniae DNA by the polymerase chain reaction

DNA amplification by the polymerase chain reaction (PCR) was examined to detect DNA of Mycoplasma hyopneumoniae, an etiological agent of porcine pneumonia. A pair of synthetic primers was selected that specify the amplification of a 520-basepair DNA fragment in a reiterative sequence of M. hyopneumoniae genome. The PCR product was detected by direct gel electrophoresis or by blot hybridization to a synthetic oligonucleotide probe. The specificity of PCR for M. hyopneumoniae was confirmed by lack of cross-reactivity to DNA from other porcine mycoplasmas.