A large molecular form of glucagon-like peptide-1 (GLP-1) immunoreactivity is co-released with glucagon from pancreas by arginine in normal subjects

Plasma immunoreactivities of glucagon-like peptide-1 (GLP-1IR) in normal subjects were measured with a specific radioimmunoassay during the arginine tolerance test. Plasma GLP-1IR after arginine infusion showed a 3-fold increase in parallel to plasma glucagon immunoreactivity and plasma glucagon-like immunoreactivity, measured with a glucagon C-terminal specific antiserum (OAL 123) and an N-terminal and/or central region specific glucagon antiserum (OAL 196), respectively. This finding suggested that the increased immunoreactivities of GLP-1 as well as that of glucagon were of pancreatic origin. Upon gel chromatography, plasma at the basal state showed three GLP-1 immunoreactive peaks, eluted in the position of void volume, synthetic GLP-1(72-108), and a smaller molecular fraction. Gel chromatography of plasma after an arginine load showed an additional peak (Mr 13,000-15,000) with little change in other GLP-1 immunoreactive peaks. This large molecular form of GLP-1IR was also shown to exist in the human pancreatic extract. Moreover, the free GLP-1 concentrations in plasma before and after an arginine load were shown to be about equal by reverse phase HPLC. These data suggested that in normal subjects arginine stimulation co-releases GLP-1IR, predominantly large molecular form, with glucogen from the pancreas.     

Resistance of Helicobacter pylori to quinolones and clarithromycin assessed by genetic testing in Japan

Background and Aim: As bacterial resistance to clarithromycin limits the efficacy of clarithromycin‐based regimens for Helicobacter pylori infection, attention has turned to quinolone‐based rescue therapies. Resistance of H. pylori to both clarithromycin and quinolone can be predicted by genetic testing. Here, we used this approach to evaluate the prevalence of clarithromycin‐ and quinolone‐resistant strains of H. pylori in Japan. Methods: DNA was extracted from gastric tissue samples obtained from 153 patients infected with H. pylori (103 naive for eradication therapy and 50 with previous eradication failure following triple proton pump inhibitor/amoxicillin/clarithromycin therapy). Mutations in H. pylori 23S rRNA and gyrA genes associated with resistance to clarithromycin and quinolones, respectively, were determined. Results: Of 153 patients, 85 (55.6%) were infected with clarithromycin‐resistant strains. The prevalence of clarithromycin‐resistant strains in patients with previous eradication failure (90.0%, 45/50) was significantly higher than that (38.8%, 40/103) of those naive for eradication therapy (P < 0.001). Fifty‐nine patients (38.6%) were infected with strains resistant to quinolones. The incidence of quinolone‐resistant strains also appeared higher in patients with eradication failure (48.0%, 24/50) than in those who had not undergone therapy (34.0%, 35/103); however, the difference was not statistically significant (P = 0.112). The incidence of quinolone‐resistance in clarithromycin‐resistant strains (44/85, 51.8%) was significantly higher than that in clarithromycin‐sensitive strains (15/68, 22.1%) (P < 0.001). Conclusions: A high incidence of quinolone‐resistance was found in clarithromycin‐resistant strains of H. pylori, particularly in patients with previous eradication failure. Our results suggest that testing for susceptibility of H. pylori to quinolones is useful for determining the optimal rescue eradication regimen.     

Comparison of pain and dyspnea perceptual responses in healthy subjects

Dyspnea and pain have a number of similarities. Recent brain imaging experiments showed that similar cortical regions are activated by the perceptions of dyspnea and pain. We tested the hypothesis that an individual’s pain sensitivity might parallel the individual’s dyspnea sensitivity. Studies were carried out in 52 young healthy subjects. Each subject experienced experimentally induced pain and dyspnea. Pain was induced by a cold-pressor test and dyspnea was induced by breathholding while the unpleasant experience of pain and dyspnea was assessed by using a Visual Analogue Scale (VAS). The times from the start of cold stimulation and breathholding to the onset of uncomfortable sensation (pain threshold time and the period of no respiratory sensation, respectively) and to the limit of tolerance (pain endurance time and total breathholding time, respectively) were also measured. In response to cold pain stimulation, a behavioral dichotomy (pain-tolerant and pain-sensitive) was observed. The period of no respiratory sensation was significantly shorter in the PS (pain-sensitive) group than in the PT (pain-tolerant) group (16.9 ± 3.8 vs. 19.6 ± 5.3 s: P < 0.05), whereas no significant difference in the total breathholding time was found between the PT and PS groups. A significant correlation was observed between the pain threshold time and the period of no respiratory sensation in both the PT and PS groups. However, no significant association was observed between pain and dyspnea tolerance in both groups. In conclusion, an individual’s pain threshold is correlated to the individual’s dyspnea threshold, but the individual’s pain tolerance is not consistently correlated to the individual’s dyspnea tolerance.     

Cigarette smoking and the risk of colorectal cancer among men: a prospective study in Japan.

The association between cigarette smoking and the risk of colorectal cancer remains controversial. We examined this association using a population-based prospective cohort study in Miyagi, Japan. In 1990, we delivered a self-administered questionnaire on cigarette smoking and other health habits to 25 279 men who were 40-64 years of age and lived in 14 municipalities of Miyagi Prefecture. A total of 22 836 men responded (90.3% response rate). During 7 years of follow-up (158 376 person-years), we identified 188 patients of colorectal cancer. Relative risks and 95% confidence intervals were estimated by the Cox proportional-hazards regression analysis with adjustment for potential confounders. The multivariate-adjusted relative risks (95% confidence interval) of colorectal cancer for past smokers and current smokers compared with those who had never smoked were 1.73 (1.04-2.87) and 1.47 (0.93-2.34), respectively. Among current smokers, both a higher number of cigarettes smoked per day and an earlier age at which smoking had started were associated with a significant linear increase in risk (P for trend <0.05). Our findings are consistent with the hypothesis that cigarette smoking is associated with a higher risk of colorectal cancer in men.