Retroperitoneal foregut cyst

A foregut cyst is formed as a result of abnormal budding and pinching of the tracheobronchial tree when bronchial buds develop to form the primitive respiratory tree. Foregut cysts are clinically classified as bronchogenic, esophageal, enterogastric, or ciliated hepatic. We present a foregut cyst that occurred in the retroperitoneum and was difficult to distinguish from other retroperitoneal cystic mass lesions. Magnetic resonance imaging was useful in revealing the cyst's continuity to adjacent organs. Received: 19 June 1995/Accepted: 23 July 1995     

Microheterogeneity of regional myocardial blood flows in low-perfused rat hearts evaluated by double-tracer digital radiography.

Using (3)H- and (125)I-labeled desmethylimipramine (DMI) for regional flow tracers, we established a two-time measurement method for the spatial pattern of myocardial perfusion in cross-circulated rat hearts. Myocardial extractions and retentions of these tracers were confirmed to be satisfactory; however, the latter were less than 90% after 3 min at a perfusion rate of 2.9 ml/min/g, limiting the present application to a short-time perfusion measurement. Distributions of myocardial depositions were separated by subtraction digital radiography with 400-microm pixel resolution. Its feasibility was examined by regression analysis between local deposition densities of (3)H- and (125)I-DMI injected simultaneously. The slope, y-intercept, and correlation coefficient (r) of the regression line were 0.98+/-0.04, 0.02+/-0.04, and 0.95+/-0.03, respectively, indicating the validity of the present image subtraction technique. The spatial pattern of myocardial perfusion in response to flow reduction was evaluated by the injections of (3)H- and (125)I-DMI, respectively, before and after a nearly 70% flow reduction. A significant correlation between normalized density distributions of these tracers was found in both subepicardium (r=0.77+/-0.12) and subendocardium (r=0.73+/-0.20), indicating the stable pattern of myocardial perfusion. However, the coefficient of variation of tracer densities showed a decrease of subendocardial flow heterogeneity from 35+/-15% to 31+/-16%. Thus, flow differences between originally high- and low-flow regions in subendocardium were reduced on a relative basis during low perfusion.     

Calcitonin inhibits proton extrusion in resorbing rat osteoclasts via protein kinase A

Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H(+) transport. In this study, we examined the effects of calcitonin on H(+) extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2'7'-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H(+) extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H(+)-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A(1)-sensitive and an amiloride-sensitive system [H(+) extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na(+)/H(+) exchanger (NHE), respectively]. Calcitonin inhibited both H(+) extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H(+) extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H(+) transport by calcitonin are important for the regulation of bone resorption.     

HASTE MR cholangiopancreatography in the evaluation of intraductal papillary-mucinous tumors of the pancreas

PURPOSE: The aim of this study was to determine the usefulness of MR cholangiopancreatography (MRCP) of intraductal papillary-mucinous tumors. METHOD: Thirteen patients with intraductal papillary-mucinous tumors were examined by breath-hold MRCP using a half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence with a body phased-array coil. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) and MRCP completely imaged the entire main pancreatic duct in 12 and in all 13 patients, respectively. ERCP demonstrated the whole opacification of the cystic lesion in only one patient. MRCP depicted the whole of the cystic lesion in all 11 patients who had cystic lesions. ERCP and MRCP source images depicted a communicating duct between the main pancreatic duct and the cystic lesion in 8 and in all 11 patients, respectively. ERCP depicted papillary projections in the main pancreatic ducts in two patients. MRCP source images depicted papillary projections in the main pancreatic ducts or cystic lesions in five patients. CONCLUSION: MRCP may be more useful to reveal the main pancreatic duct, cystic lesion, communicating duct between the main pancreatic duct and cystic lesion, and papillary projections than ERCP in patients with intraductal papillary-mucinous tumors of the pancreas.     

Intensification of antitumor effect by T helper 1-dominant adoptive immunogene therapy for advanced orthotopic colon cancer.

PURPOSE: T helper (Th) 1/Th2 balance, controlled by Th1 or Th2 cells producing cytokines, plays important roles in antitumor immunity. Interleukin-18 (IL-18) can act together with IL-12 in promoting the generation of IFN-gamma producing Th1 cells. The goal of this study was to determine whether cytotoxic T lymphocyte (CTL) secreted in a murine IL-18-induced Th1-dominant state inhibited the development of primary tumors and synchronous liver metastases in orthotopic colon cancer model. EXPERIMENTAL DESIGN: Murine IL-18 gene was transduced into activated T lymphocytes by an adenovirus vector encoding IL-18 (AdIL-18) liposome complex method. Efficacy of adoptive immunogene therapy using AdIL-18 with or without IL-12 was tested in advanced orthotopic xenograft of murine colon cancer. To elucidate the mechanism responsible for the adoptive immunogene therapy, serum IL-4, IL-6, IFN-gamma, and tumor necrosis factor alpha production in Th1/Th2 cytokine balance and quantification of tumor vascularity were investigated. RESULTS: By a modified method of adenoviral gene transduction, T lymphocytes achieved efficient IL-18 production without cell toxicity. Against orthotopic colon cancer, when combined with low dose of recombinant (r) IL-12 (AdIL-18-CTL/rIL-12), the therapeutic efficacy showed much smaller tumors with no liver metastases and no disseminated tumors. There was a significant difference in the volume of primary tumors and the number of liver metastases compared with the group treated with AdIL-18-CTL alone or other group (P < 0.01). In addition, the median survival time of the group treated with AdIL-18-CTL was 53.7 +/- 5.8 days and that of AdIL-18-CTL/rIL-12 was 78.4 +/- 6.1 days, which was also a significant difference (P < 0.01). These antitumor mechanisms were involved with Th1-dominant response in serum Th1/Th2 cytokine balance and suppression of neovascularization at primary tumor site. CONCLUSION: These data suggest that a strategy of Th1/Th2 balance-based adoptive immunogene therapy might be useful for advanced cancer patients.     

Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability

We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldosterone via activation of MR. In the present study, we investigated whether MR is expressed in cultured rat mesangial cells (RMCs) and involved in aldosterone-induced RMC injury. MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. Cell proliferation and micromechanical properties were determined by [3H]-thymidine uptake measurements and a nanoindentation technique using an atomic force microscope cantilever, respectively. ERK1/2 activity was measured by Western blotting analysis with an anti-phospho-ERK1/2 antibody. Protein expression and immunostaining revealed that MR was abundant in the cytoplasm of RMCs. Aldosterone (1 to 100 nmol/L) dose-dependently activated ERK1/2 in RMCs with a peak at 10 minutes. Pretreatment with eplerenone (10 micromol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation and decreased the elastic modulus, indicating cellular proliferative and deforming effects of aldosterone, respectively. These aldosterone-induced changes in cellular characteristics were prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor, PD988059 (100 micromol/L). The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.     

Suppressive effect of the Gly389 allele of the beta1-adrenergic receptor gene on the occurrence of ventricular tachycardia in dilated cardiomyopathy.

Beta-1-adrenergic receptor (beta1-AR) blockers reduce both the incidence of sudden death and the ventricular volume in heart failure. In vitro, the Gly389 variant of beta1-AR mediates less adenylyl cyclase activities than the Arg389 variant, so Arg389Gly polymorphism was investigated with regard to the genesis, progression, or arrhythmogenesis of dilated cardiomyopathy (DCM). Allele and genotype frequencies of the Arg389Gly polymorphism were determined in 163 DCM patients and 157 age- and sex-matched controls. There were no differences in genotype and allele frequencies between patients and controls. Echocardiograms, left ventriculograms and 24h-Holter electrocardiograms were evaluated in the DCM patients and none of the clinical indices, other than ventricular tachycardia (VT), differed among the 3 genotypes. The Gly389 allele was more frequent in the VT(-) group than in the VT(+) group (0.46 vs 0.24, p=0.001). In univariate analysis, the odds ratio for VT in patients carrying 1 or 2 copies of the Gly389 allele was 0.29 ([95% confidence interval, 0.13-0.64], p=0.002), when compared with the Arg389 homozygotes. The Gly389 variant supressed the occurrence of VT in DCM, suggesting that this allele confers a decreased risk of sudden death.     

A new prognostic score for the survival of patients with esophageal squamous cell carcinoma

Purpose

Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS.

Methods

One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP.

Results

Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000–9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021–7.112, p = 0.0449).

Conclusions

The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.