Interferon-inducible gene family 1-8U expression in colitis-associated colon cancer and severely inflamed mucosa in ulcerative colitis

Persistent severe inflammation in colonic mucosa is thought to cause the development of colon cancer in patients with ulcerative colitis (UC). However, predisposing genetic abnormalities have not been identified in this sequence. Using differential display PCR, we isolated cDNA fragments corresponding to mRNAs that were differentially expressed in colitis-associated cancer tissues and mucosa with mild inflammation in the colon of five UC patients. This molecular screening approach identified 60 cDNA fragments, and we sequenced 34 fragments. One cDNA fragment, which is identical to IFN-inducible gene family 1-8U, was strongly expressed in all five UC-associated cancers. 1-8U was also expressed in sporadic colon cancer tissues and colon cancer cell lines, but not in normal mucosa. This gene was strongly expressed in severely inflamed colonic mucosa of UC without colitis-associated colon cancer, although 1-8U expression was not related to the extent and duration of the disease. However, 1-8U was expressed in the colonic mucosa of all patients with chronic, continuously severe inflammation. These results indicated that IFN-inducible gene family 1-8U expression in inflamed colonic mucosa might be used as a preferential marker of colitis-associated colon cancer in UC.     

Post-endsystolic active shortening in the non-ischemic region impairs left ventricular pressure fall in acute ischemic heart

To investigate the relation between the impairment of isovolumic relaxation and the regional wall motion in acute ischemia, the left ventricular pressure fall and regional myocardial motion were examined in the relaxation phase in dogs during both acute coronary artery occlusion (n = 12) and a regional coronary flow reduction (n = 6). Fifteen to 40 seconds after complete coronary artery occlusion or in the stable state after a regional coronary flow reduction by 70 to 90% of the control state, a shortening of the non-ischemic region at the early isovolumic relaxation phase (the post-endsystolic shortening) appeared, combined with lengthening of the ischemic region. In these situations, the logarithmic plots of the left ventricular pressure fall was composed of two components (time constant of early part [Ta] and at latter part [Tb]). Ta was greater than Tb (64.3 +/- 13.8 milliseconds vs. 36.6 +/- 10.4 milliseconds at 15 seconds after coronary occlusion, p < 0.01; 67.6 +/- 22.9 milliseconds vs. 45.1 +/- 17.5 milliseconds at flow reduction, p < 0.01) and the time constant at control (p < 0.01). These findings suggested that post-endsystolic shortening in the non-ischemic region played a role in a the non-uniformity of the left ventricular contraction and contributed to the impairment of the left ventricular pressure fall in acute regional ischemia, especially in early isovolumic relaxation.     

Varieties of right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy

We examined whether differences in the location of myocardial hypertrophy influence the right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy using cineangiography. Biplane right ventriculography was performed in 34 subjects (normal = 14, asymmetric septal hypertrophy = 9, apical hypertrophy = 11) during cardiac catheterization. In patients with asymmetric septal hypertrophy, compared with apical hypertrophy and normal groups, the indices of the right ventricular diastolic function including right ventricular peak filling rate and filling fraction of rapid filling phase were lower and the time to peak filling rate was prolonged. But in patients with apical hypertrophy, these indices were not significantly different compared with normal. There were no differences in right ventricular ejection fraction and cardiac index among the three groups. These data suggest that the location of the myocardial hypertrophy of the left ventricle is a significant factor affecting the right ventricular diastolic filling in non-obstructive hypertrophic cardiomyopathy.     

Dopamine does not correct oxygen consumption/oxygen delivery relation abnormality during vasomotor shock induced by interleukin-1beta

We previously showed that interleukin 1beta (IL-1beta) induces vasomotor shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. In the present study, we investigated the inotropic effect of dopamine on the VO2/DO2 abnormality induced by IL-1beta. Twelve rabbits were divided into two groups (n = 6, each) and were given 10 microg/kg of IL-1beta or saline (control) intravenously. After baseline measurements were obtained, dopamine was infused continuously at a rate of 20 microg/kg/min throughout the study in both groups. All rabbits were subjected to stepwise cardiac tamponade to reduce the DO2 to <5 mL/min/kg by inflation of a handmade balloon placed into the pericardial sac. The VO2/DO2 relation was then analyzed by the dual-line method. Dopamine failed to correct the IL-1beta-induced decrease in mean arterial pressure to the baseline level. Dopamine significantly increased cardiac index in both groups, resulting in significant increases in DO2 (IL-1beta, 28.5 +/- 6.0 mL/min/kg from baseline 24.1 +/- 3.5 mL/min/kg; control, 27.7 +/- 2.9 mL/min/kg from baseline 22.9 +/- 2.9 mL/min/kg), but did not affect VO2 (IL-1beta, 10.0 +/- 0.5 mL/min/kg from baseline 9.9 +/- 0.7 mL/min/kg; control, 10.2 +/- 0.4 mL/min/kg from baseline 10.2 +/- 0.2 mL/min/kg). The IL-1beta group showed a significantly greater supply-independent line slope than that of controls (IL-1beta, y = 0.14x + 6.3; control, y = 0.06x + 8.6) during stepwise decreases in DO2. These results indicate that continuous infusion of dopamine at 20 microg/kg/min increases DO2 but does not correct the vasomotor disturbance or VO2/DO2 abnormality caused by IL-1beta.     

Gemcitabine as first-line chemotherapy in elderly patients with unresectable pancreatic carcinoma

Background  

Gemcitabine (GEM) is the key drug for the chemotherapy of unresectable pancreatic cancer. However, the efficacy and safety of GEM has not been established in elderly patients. We retrospectively examined the prognosis of elderly pancreatic cancer patients treated with GEM.     

gamma-Glutamyltransferase predicts cardiovascular death among Japanese women

The clinical importance of gamma-glutamyltransferase (GGT) has recently been debated. Although some studies have suggested that the relationship between GGT and cardiovascular disease (CVD) mortality is independent of alcohol consumption, to our knowledge no studies have reported the relationship between GGT and CVD mortality in never-drinker subgroups. Since Japanese women are known to have a lower prevalence of alcohol consumption, we examined whether GGT predicts CVD mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82 CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive relationship was unchanged in the never-drinkers subgroup (HR for log-transformed continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were observed in men. GGT displays a strong positive association with CVD mortality among Japanese women, for whom the prevalence of ever-drinkers is very low. Exploring the significance and biological mechanisms of GGT might provide useful insights into CVD prevention.     

Visualization of hepatic lymphatic vessels during transcatheter arterial chemoembolization for hepatocellular carcinoma

PURPOSE: To analyze visualization of hepatic lymphatic vessels during transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Retrospective review was conducted of 255 tumors in 161 patients treated by TACE with catheterization of the most distal portion of the tumor-feeding branches. All TACE procedures were performed with use of a mixture of iodized oil and anticancer drugs followed by gelatin sponge particles. Arteriograms and spot radiographs obtained during TACE were reviewed to determine whether hepatic lymphatic vessels appeared. Serial computed tomography (CT) images after TACE were evaluated along with clinical symptoms in cases that exhibited lymphatic vessel visualization. RESULTS: Hepatic lymphatic vessels were demonstrated in eight tumors (3.1%) in eight patients during TACE. The mean tumor diameter was 1.7 cm +/- 0.7 (range, 1.0-3.3 cm), and mean volume of injected iodized oil was 1.7 mL +/- 1.0 (range, 1-4 mL). Lymphatic vessels were demonstrated followed by marked portal vein visualization (n = 5) or extravasation of a small amount of contrast material (n = 2). In the remaining patient, these were depicted during the early stage of the TACE procedure. On CT after 1 week, iodized oil in the lymphatic systems in the hepatoduodenal ligament was seen in six patients, and it was shown to have been retained in four of these patients on follow-up CT performed 2, 7, 11, and 21 months later, respectively. None of these patients presented any clinical symptom other than postembolization syndrome. CONCLUSIONS: Hepatic lymphatic vessels were demonstrated in 3.1% of tumors treated by ultraselective TACE. Iodized oil in the lymphatic vessels may be retained for a relatively long time without specific symptoms.