Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.     

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

IHPBA in Tokyo, 2002: surgical treatment of IPMT vs MCT: a Japanese experience

The differences and similarities between intraductal papillary mucinous tumor (IPMT) and mucinous cystadenoma or carcinoma (mucinous cystic tumor; MCT) of the pancreas have been noted. The similarities include: (1) both tumors originate from pancreatic duct cells, (2) massive mucin production is found in both tumors, and (3) papillary projection is a common histological characteristic. However, there are also many differences. IPMT is most frequently found in men in their sixties, and originates in the head of the pancreas, with 62% (123/199) of tumors reported to be found in the head of the pancreas. This tumor sometimes spreads throughout the entire pancreas. The tumor itself basically is of the dilated pancreatic duct type, and the prognosis is generally good. In contrast, MCT frequently develops in women in their forties. This tumor is usually large, round, and almost totally encapsulated by fibrous tissue, with no communication with the pancreatic duct. The tumor histologically has an ovarian-like stroma. It most often develops in the body or tail of the pancreas. Invasion is often present and the operative prognosis is not good. IPMT resembles the shape of a bunch of grapes and MCT resembles that of an orange. From the differences between these two types of tumors, they are classified into different categories. With regard to therapeutic strategies for MCT, the tumor should be resected with lymph node dissection immediately when it is detected. In contrast, some patients with branch-type IPMT can be followed without surgical procedures. Because IPMT shows good prognosis and little tendency for infiltration, some kinds of organ-preserving procedures would be possible for some patients with this tumor. Such organ-preserving procedures are: duodenum-preserving pancreas head resection, spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, and so on.     

Expression of RHOC is associated with metastasis of gastric carcinomas.

OBJECTIVES: RHOC, a member of the RAS-related small GTPase protein family, regulates cytoskeletal structures and has the potential to transform cultured cells. It has recently been reported that RHOC contributes to the metastatic phenotype of melanoma cells. The purpose of this study was to clarify its biological relevance to gastric carcinogenesis and metastasis. METHODS: We examined the expression of RHOC by quantitative RT-PCR in 51 cases of gastric carcinoma tissues from prior surgical cases (intestinal type: 24 cases, diffuse type: 27 cases) and in 8 gastric carcinoma cell lines. RESULTS: RHOC expression levels in primary tumors were significantly higher in cases with metastasis than in those without metastasis (p = 0.0202; Mann-Whitney U test). RHOC expression levels in primary tumor and their metastatic tumors were significantly higher than their corresponding nonneoplastic mucosa (p = 0.0357, and 0.0173, respectively; Wilcoxon signed rank test). RHOC mRNA expression was confirmed in the gastric carcinoma cell lines. CONCLUSION: Our findings suggest that elevated expression of the RHOC gene may be involved in the metastasis of gastric carcinomas and may be a good genetic marker for the prediction of a metastatic potential.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

3D kinematic analysis of the acromioclavicular joint during arm abduction using vertically open MRI.

Many researchers have evaluated the motions of the shoulder girdle, especially scapular and humeral motion. However, few reports exist that describe motions of the acromioclavicular joint. The purpose of the present study was to analyze the 3D kinematics of the acromioclavicular joint during arm abduction using 3D MR images obtained by a vertically open MRI. Fourteen shoulders of seven volunteers were examined in seven static positions from 0 degrees to the maximum abduction in a seated position. 3D surface models of the clavicle and scapula were created, and the movements of the acromioclavicular joint from 0 degrees to each position were calculated using the volume-based registration technique. From these calculations, the translations were evaluated and the rotational motions were analyzed using the concept of the screw axis. In the anteroposterior direction, the clavicle translated most posteriorly (-1.9 +/- 1.3 mm) at 90 degrees of abduction and most anteriorly (1.6 +/- 2.7 mm) at maximum abduction. In the superoinferior direction, the clavicle translated slightly superiorly (0.9 +/- 1.9 mm). When analyzing relative motion of the scapula with respect to the clavicle, the scapula generally rotated about a specific screw axis passing through the insertions of both the acromioclavicular and the coracoclavicular ligaments on the coracoid process. The average rotation was 34.9 +/- 8.4 degrees.