Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation

Air pollutants including diesel exhaust particles (DEPs) have been shown to enhance allergic responses. DEPs stimulate airway epithelial cells to produce various cytokines; however, the intracellular signal transduction pathway and the involvement of reduction and oxidation (redox) control in DEP-activated signaling have not been determined. In the present study, we therefore examined the role of p38 mitogen-activated protein (MAP) kinase in DEP-induced interleukin 8 (IL-8) and RANTES production by human bronchial epithelial cells (BECs) in order to clarify the intracellular signal transduction pathway that regulates IL-8 and RANTES production. In addition, we also examined the effect of a thiol-reducing agent, N-acetylcysteine (NAC), on DEP-induced p38 MAP kinase activation and cytokine production in order to clarify the redox control mechanism in DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. The results showed that DEP induced IL-8 and RANTES production and the threonine and tyrosine phosphorylation of p38 MAP kinase, reflecting the activation of p38 MAP kinase in BECs. SB 203580, as the specific inhibitor of p38 MAP kinase activity, inhibited DEP-induced IL-8 and RANTES production. NAC inhibited DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. These results indicate that p38 MAP kinase plays an important role in the DEP-activated signaling pathway that regulates IL-8 and RANTES production by BECs and that the cellular redox state is critical for DEP-induced p38 MAP kinase activation leading to IL-8 and RANTES production.     

Basement membrane-like matrix sponge for the three-dimensional proliferation culture of differentiated retinal horizontal interneurons

As the neurons in the central nervous system (CNS) form a neuronal network in a three-dimensional (3D) manner, a 3D proliferation culture system for differentiated neurons has been desired. Although differentiated neurons were previously thought to never proliferate, differentiated horizontal interneurons of Rb-/-; p107+/-; p130-/- (p107-single) retina clonally proliferated without dedifferentiation in vivo. In the present study, we developed a basement membrane-like matrix sponge (BM-sponge) for the 3D proliferation culture of differentiated horizontal interneurons. p107-single horizontal interneurons, but not other types of retinal neurons, proliferated in the BM-sponge in a 3D manner. These interneurons expressed presynaptic marker and developed synaptic vesicles. These data demonstrated that p107-single horizontal interneurons cultured in the BM-sponge proliferate while maintaining their differentiated features. We described here the 3D proliferation culture system for differentiated neurons.     

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

Given the poor prognosis for cholangiocarcinoma, new and effective treatments are urgently needed. HMG-CoA reductase inhibitors (statins) reportedly exert anticancer effects in a variety of diseases, but there have been no reports of these effects in cholangiocarcinoma. In this study, we investigated the utility of statins for cholangiocarcinoma treatment. Proliferation suppression by pitavastatin and atorvastatin was investigated in the human cholangiocarcinoma cell lines HuCCT1 and YSCCC while changes in the cell cycle and intracellular signals were examined by FACS and Western blotting, respectively. Additive proliferation suppression by statins and pre-existing anticancer drugs was also investigated. HuCCT1 and YSCCC cell proliferation was dramatically suppressed by incubation with statins for 72 h or longer. Cell cycle analysis revealed a reduction in the G2M fraction and an increase in the sub-G1 fraction in statin-treated cells, while Western blotting showed increased levels of cleaved caspase-3 and a reduction in p-ERK. Furthermore, statins in combination with gemcitabine, cisplatin and 5-FU showed additive proliferation suppression. In this study, treatment of human cholangiocarcinoma cells with statins induced apoptosis via suppression of the classical MAPK pathway. Together, these results suggest that statins may be a new cholangiocarcinoma treatment option that could potentially enhance the anticancer effect of pre-existing anticancer drugs.     

Cuffed anastomosis for above-knee femoropopliteal bypass with a stretch expanded polytetrafluoroethylene graft

PURPOSE: To evaluate the patency and limb-salvage rates associated with cuffed anastomosis in above-knee femoropopliteal (FP) bypasses using prosthetic grafts. METHODS: Between January 1997 and December 2005, 96 patients (99 limbs) underwent above-knee FP bypass grafting for peripheral vascular disease, with disabling claudication in 81%. All grafts were 6-mm, thin-walled, ringed, expanded polytetrafluoroethylene (ePTFE) stretch grafts anastomosed to the above-knee segment of the popliteal artery in an end-to-side fashion, with a protruding area created around the anastomotic toe and an angle of less than 30 degrees between the graft and the artery. Postoperatively, graft patency was monitored by several objective methods. Patency and limb-salvage rates were calculated by actuarial methods and Kaplan-Meier analysis. RESULTS: The mean follow-up period was 40.4 months; 15 patients were lost to follow-up. The 1-, 3-, and 5-year primary graft patency rates were 94.5%, 88.2%, and 85.7%, respectively. The 1-, 3-, and 5-year secondary patency rates were 95.6%, 94.1%, and 90.8%. The 1-, 3-, and 5-year limb-salvage rates were 98.9%, 97.3%, and 97.3%. There were three graft infections. CONCLUSION: The use of a cuffed anastomosis in FP bypass with an ePTFE stretch prosthesis appears to increase graft patency rates.     

Surgical Treatment and Subsequent Outcome of Patients with Carcinoma of the Splenic Flexure

Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who under-went curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites. Received: February 17, 2000 / Accepted: September 26, 2000     

The proximal form of mural thrombus in aortoiliac occlusive disease using computed tomography.

BACKGROUND: It is important to know the nature of proximal thrombus in patients with aortoiliac occlusive disease (AIOD) when juxtarenal aortic clamping is scheduled. This study was aimed to evaluate the shape and nature of thrombi at several sites of the abdominal aorta in patients with AIOD using enhanced computed tomography (CT). Final judgment was made according to the operative findings. METHODS: Between the years 1999 and 2001, 22 patients, who underwent aortobifemoral bypass, were enrolled. The shape and nature of their thrombi were examined at 4 points (superior mesenteric, suprarenal, juxtarenal and infrarenal arteries at the level of the 2 cm before the renal artery) and 88 slices of CT were examined retrospectively. RESULTS: There was mural thrombus in 31 slices, which could be classified into 4 shapes (crescent-shaped: 10 cases; magatama: 2; wavy: 12; circular: 6). The wavy and circular shaped thrombi were found to be atheromatous. Nine cases (40.9%) on operative findings were atheroma (wavy: 4; circular shaped: 5). The crescent shape might correspond to fibrin thrombus. Atheromatous thrombus clamping near the renal artery was thought to cause microthromboembolism to surrounding organs. CONCLUSIONS: It is recommended that the more proximal aorta or splanchnic arteries should be temporarily clamped during proximal procedures in patients with wavy or circular shaped thrombi at the juxtarenal aorta to prevent kidney or bowel infarction.     

Alopecia Areata Associated with Haloperidol

Abstract: A patient with a 7-year history of depression relapsed after self-discontinuation of antidepressant drugs. He was admitted to our hospital and re-administered amoxapine 150 mg. p. o. per day, and further given haloperidol 5 mg i. m. or p. o. per day because he was suicidal and excited. One month later, an area of alopecia was found on the back of his head. Immediately, he received dermatological treatment. The psychotropic drugs were continued, but the hair loss was unchanged after one month. So, haloperidol alone was discontinued. One week later, the hair loss had stopped and a month later alopecia had virtually disappeared. We suggest that alopecia areata is associated with haloperidol.