Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible nitinol stent

In order to treat fistulated esophageal cancer using a flexible stent, a covered flexible stent was constructed by wrapping a nitinol stent with a thin sheet of Gore-Tex, preserving the stents original advantages of flexibility and a low-profile introducer system. This stent was used to perform standard radiotherapy in a case of fistulated esophageal cancer.     

Nasal glioma: An immunohistochemical and ultrastructural study

A case of a 14 month old Japanese female infant presenting with nasal glioma Is reported. The tumor had been noticed at the nasal radix since birth and had slowly and progressively enlarged. There was no communication between the tumor and the cranial cavity on radiological examination. The tumor was macroscopically anchored to the nasal septum by a fibrous stalk, and histologically consisted of nests or trabeculae of either polygonal or spindle cells with plump eosinophilic cytoplasm and oval nuclei, separated by vascular-rich connective tissue intermingled with multinu-cleated giant cells. These tumor cells were immunohisto-chemically positive for glial fibrillary acidic protein as well as for S-100 protein and vimentin. An electron microscopic examination revealed collagen fibers and basal lamina between the tumor cells and the fibroblasts. Tumor cells possessed abundant intermediate filaments, which showed occasional Rosenthal fiber-like structures, in their cytoplasm and processes. A few oligodendrocytes and cilia of 9 micro-tubule doublets either with or without 2 central microtubules were also noted. These clinicopathological findings suggested that this tumor was once an encephalo(meningo)cele, which probably degenerated as a result of the loss of intracranial communication and then appeared to be isolated from the intracranial tissue.     

近节指骨段屈肌腱鞘不同范围损伤对肌腱功能的影响

目的 探索手指屈肌腱在近节指骨段不同范围损伤时对屈指肌腱功能的影响。方法 采用12只成人尸体手指。实验分为:第一阶段屈指肌腱完整,以后四个阶段依次沿近节指骨掌侧小线闭开小央1/4、1/2、3/4及全长。在掌指关节被动屈80°和掌指关节屈80°同时近侧指关节屈100°时,测量指浅屈肌腱(FDS)和指深屈肌腱(FDP)的滑动距离。根据肌腱力臂和滑动距离的关系,得出屈指肌腱在掌指关节处和近侧指间关节及肌腱在近节指骨段的弓弦畸形程度。结果 腱鞘中央1/4切开时,指屈肌腱的滑动距离、力臂均无显著变化;1/2切开后,单纯屈曲掌指关节时的FDS腱和掌指、近节指间关节屈曲时的FDS、HDP腱的滑动距离和力臂较腱鞘完整时显苫增大(P<0.05);切开3/4长度后,FDS、FDP腱滑动距离均有统计学意义变化,FDS、FDP腱力臂平均增加8～9％;全切开腱鞘,FDS、FDP腱滑动距离变化正统计学上有高度显著性(P<0.01),两腱力臂分别增加16％和15％。随腱鞘切开范围增大,FDS、FDP在近节指骨段的弓弦畸形程度也越来越大。结论 从肌腱的生物力学变化可见,近节指骨段腱鞘的小范围损伤如中间1/4以内损伤时,对肌腱功能影响小,可以不予修复;若损伤超过1/2长度,尤其对腱鞘全长损伤,应予以修复以恢复肌腱功能。     

Migration of keratinocytes is impaired on glycated collagen I

Advanced glycation end products are the chemical modification of proteins induced by sugars in a hyperglycemic condition. Extracellular matrix proteins are prominent targets of nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of nonenzymatic glycation of type I collagen on the migration of keratinocytes. The migration of keratinocytes was dramatically promoted on native type I collagen-coated dishes compared with that on uncoated dishes. When type I collagen was glycated with glycolaldehyde, large amounts of advanced glycation end products were produced; the glycated collagen I-coated dishes did not promote the migration of keratinocytes. Glycated collagen I did not affect the proliferative capacity of keratinocytes. However, the adhesion of keratinocytes to glycated collagen I was profoundly diminished in a glycation intensity-dependent manner. alpha2beta1 integrin is responsible for the migration and adhesion of keratinocytes to type I collagen. Pretreatment with glycated collagen I did not affect the expression level or functional activity of alpha2beta1 integrin on keratinocytes. These findings suggest that in the presence of glycated collagen I, keratinocytes lose their adhesive and migratory abilities. As the glycation did not modify the alpha2beta1 integrin on keratinocytes, it is suggested that glycation may diminish the binding capacity of type I collagen.     

Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

A new strategy for management of retroperitoneal tumors with supradiaphragmatic vena caval thrombi

A new surgical technique to treat retroperitoneal tumors with supradiaphragmatic vena caval invasion is described. In this technique, hepatic warm ischemia can be avoided with reversed hepatic outflow through the portal vein and neither hypothermic circulatory arrest nor cardiopulmonary bypass is necessary using centrifugal blood pump-driven bypass.     

Jejunal carcinoma with adenoma —Report of a case and review of the Japanese literature—

A rare case of jejunal carcinoma coexisting with adenoma, situated 120 cm distal to the ligament of Treitz in a 53 year old male, is reported herein. We also review cases of adenoma and carcinoma in the jejunum and ileum from the Japanese literature, and discuss the histogenesis of carcinoma of the jejunum and ileum.     

Usefulness of two-dimensional time-of-flight MR angiography combined with surface anatomy scanning for convexity lesions

Thirty-eight patients with convexity lesions were studied prospectively with the two-dimensional time-of-flight (2D-TOF) magnetic resonance angiography (MRA) method. Of these 21 cases had additional surface anatomy scanning (SAS) and 7 cases had three-dimensional phase contrast (3D-PC) MRA. The findings were compared during surgery, and the predictability of 2D-TOF evaluated. 2D-TOF was obtained with 2 mm slice thickness after the administration of contrast media for routine magnetic resonance imaging (MRI). Cortical veins were visualized with a good resolution with a scan time of only 5 minutes. The tumor was also visible in the background, due to enhancement, and thus the tumor-vessels relation was shown. Slow-flow vessels were also adequately seen. SAS was done at the same sitting with fast spin echo (FSE) with a scan time of 3 minutes. Once both images were incorporated, information on gyri and their relation to the lesions and vasculature could be obtained from a single image. We found 2D-TOF alone, or at times in combination with SAS, useful for planning of operation for convexity lesions.