Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34<Superscript>+</Superscript> cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.     

Delayed Gastric Emptying by Helicobacter pylori Lipopolysaccharide in Conscious Rats

The present study was carried out to investigatethe possibility that lipopolysaccharide deprived fromHelicobacter pylori may alter gastric motility. Toaddress the question, we examined the effect of H. pylori lipopolysaccharide on gastricemptying in conscious rats. Gastric emptying wasevaluated by the phenol red method. Time-course anddose-related effects of intraperitoneal administrationof H. pylori lipopolysaccharide were investigated.Intraperitoneal injection of H. pylorilipopolysaccharide significantly suppressed gastricemptying of a liquid meal in a dose-dependent manner.The inhibitory action of H. pylori lipopolysaccharide wasobserved 2, 4, 8, or 12 hr after the injection. Theseresults suggest for the first time that H. pylorilipopolysaccharide may suppress gastric emptying in along-lasting fashion. It is also suggested that H. pylorimay influence gastric function through its cell wallstructure named lipopolysaccharide.     

Trends in Asthma Mortality in Japan

Asthma mortality has been increasing in many developed countries in recent years, so we have described the epidemiological features of asthma in Japan. Data on all certified asthma deaths from 1950 to 1997 were obtained from The National Vital Statistics, published annually by the Ministry of Health and Welfare. Trends in crude and age-adjusted asthma mortality rates, as well as age-specific mortality rates, were analyzed. Age and birth cohort effects on mortality rates were also examined using multiplicative models. Between 1950 and 1980, crude asthma mortality rates steadily decreased in both sexes and began to level off thereafter. Age-adjusted mortality rates have also decreased since 1950, and showed a persistent downward trend in both sexes even in recent years. Asthma mortality rates were higher in males than in females during the entire study period. When analysis was restricted to those aged 5 to 34 years, an upward trend since 1980 was observed. The multiplicative model showed a rapidly decreasing cohort effect on mortality among those born after 1860. However, the slope increased in the cohorts born after 1950 in both sexes. The age effect increased linearly with advancing age after 50 years in both sexes. Overall asthma mortality rates have been decreasing during the past five decades in Japan, but the mortality rate has increased among the 5-34-year-old age group since 1980. The high fatality rate stemming from the overuse of beta 2-agonists may account for the mortality increase.     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

Fas ligand expressing mononuclear cells around intrahepatic bile ducts co‐express CD68 in primary biliary cirrhosis

Abstract: Aims/Background: Apoptosis, including the Fas system, has been implicated in progressive bile duct loss in primary biliary cirrhosis (PBC). In this study, we attempted to analyze Fas ligand (FasL) expressing mononuclear cells infiltrating in the portal tracts of PBC. Methods: We immunohistochemically assessed co‐expression of leukocyte markers and FasL on infiltrating mononuclear cells in 18 patients with PBC. Twenty‐five patients with chronic hepatitis C (CH‐C) were used as controls. Results: In PBC, FasL expressing cells were scattered in the portal tracts, and some were accentuated around the damaged bile ducts. In addition, these cells co‐expressed CD68 (71%), a marker of monocytes, but not UCHL‐1, CD3 and CD57, markers of activated T cells and natural killer cells. By contrast, in CH‐C, the biliocentric pattern of FasL expression was not evident, and about half of FasL expressing cells (42–56%) co‐expressed UCHL‐1, CD3 or CD57. CD14, a receptor for bacterial products such as lipopolysaccharides, was also detected on a proportion of FasL expressing mononuclear cells around the damaged bile ducts in PBC. Conclusion: The results suggest that in PBC, FasL expressing CD68+ monocytes are at least partly involved in apoptotic bile duct loss mediated by the Fas system, and a surface molecule, CD14, participates in this process.     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).     

Successful catheter ablation of left ventricular epicardial tachycardia originating from the great cardiac vein: a case report and review of the literature.

A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site.     

Vascular access site complications with the use of closure devices in patients treated with platelet glycoprotein IIb/IIIa inhibitors during rescue angioplasty.

The objective of this study was to evaluate the effectiveness of two different closure devices in patients undergoing rescue percutaneous coronary intervention (PCI) using IIb/IIIa inhibitors and to compare it with patients undergoing elective PCI. One hundred sixty-two patients undergoing rescue PCI treated with IIb/IIIa inhibitors underwent vascular access site closure (6 Fr Perclose, n = 92, or 6 Fr Angioseal, n = 70). Vascular complications were compared with a sex- and age-matched group (n = 100) of patients undergoing manual compression after sheath removal and a similar group of patients undergoing elective PCI (n = 196). The incidence of access site complications was not significantly different between the three groups undergoing rescue PCI and was not higher than in patient receiving GP IIb/IIIa inhibitors without fibrinolysis (RR = 0.95; 95% CI = 0.88-1.01). In patients undergoing rescue PCI and receiving IIb/IIIa inhibitors, closure devices allow early sheath removal and are associated with similar outcomes compared with manual compression and elective PCI regardless of the type of closure device used.