Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor dissection

BACKGROUND: Laparoscopic wedge resections are increasingly applied for gastric submucosal tumors such as gastrointestinal stromal tumor (GIST). Despite this, no defined strategy exists to guide the surgeon in choosing the appropriate laparoscopic technique for an individual case on the basis of tumor characteristics such as location or size. This study aimed to introduce a laparoscopic and endoscopic cooperative surgery (LECS) for gastric wedge resection that is applicable for submucosal tumor resection independent of tumor location and size. METHODS: Seven patients underwent LECS for the resection of gastric submucosal tumors. Both mucosal and submucosal layers around the tumor were circumferentially dissected using endoscopic submucosal dissection via intraluminal endoscopy. Subsequently, the seromusclar layer was laparoscopically dissected on the exact three-fourths cut line around the tumor. The submucosal tumor then was exteriorized to the abdominal cavity and dissected with a standard endoscopic stapling device. RESULTS: In all cases, the LECS procedure was successful for dissecting out the gastric submucosal tumor. In four of seven cases, the tumor was located in the upper gastric portion near the esophagogastric junction. The remaining three tumors were in the posterior gastric wall. In two cases, the tumors were more than 5 cm in diameter, and one was a GIST of the remnant stomach. The mean operation time was 169 +/- 17 min, and the estimated blood loss was 7 +/- 2 ml. The postoperative course was uneventful in all cases. CONCLUSIONS: The LECS procedure for dissection of gastric submucosal tumors such as GIST may be performed safely with reasonable operation times, less bleeding, and adequate cut lines. In addition, the success of the procedure does not depend on the tumor location such as the vicinity of the esophagogastric junction or pyloric ring.     

RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv(16) subtype

Correlative and functional studies support the involvement of the RUNX gene family in haematological malignancies. To elucidate the role of epigenetics in RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23 leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1 and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly variable among patient samples, with clear association to cytogenetic status. High frequency of RUNX3 hypermethylation (85% of the 20 studied cases) was found in AML patients with inv(16)(p13.1q22) compared to other AML subtypes (31% of the other 49 cases). RUNX3 hypermethylation was also frequent in ALL (100% of the six cases) but low in MDS (21%). In support of a functional role, hypermethylation of RUNX3 was correlated with low levels of protein, and treatment of cell lines with the DNA demethylating agent, decitabine, resulted in mRNA re‐expression. Furthermore, relapse‐free survival of non‐inv(16)(p13.1q22) AML patients without RUNX3 methylation was significantly better (P = 0·016) than that of methylated cases. These results suggest that RUNX3 silencing is an important event in inv(16)(p13.1q22) leukaemias.     

Intravenous administration of class I antiarrhythmic drug induced T wave alternans in an asymptomatic Brugada syndrome patient

A 53-year-old man with an abnormal ECG was referred to the Nihon University School of Medicine. The 12-lead ECG showed right bundle branch block and saddleback-type ST elevation in leads V1-V3 (Brugada-type ECG). Signal-averaged ECG showed positive late potentials. Double ventricular extrastimuli (S1: 500 ms, S2: 250 ms, S3: 210 ms) induced VF. Amiodarone (200 mg/day) was administered for 6 months and programmed ventricular stimulation was repeated. VF was induced again by double ventricular stimuli (S1: 600 ms, S2: 240 ms, S3: 170 ms). Intravenous administration of class Ic antiarrhythmic drug, pilsicainide (1 mg/kg), augmented ST-T elevation in leads V1-V3, and visible ST-T alternans that was enhanced by atrial pacing was observed in leads V2 and V3. Visible ST-T wave alternans disappeared in 15 minutes. However, microvolt T wave alternans was present during atrial pacing at a rate of 70/min without visible ST-T alternans.     

Fos plays no role in apoptosis of epithelia in the mouse male accessory sex organs and uterus

Roles of Fos in apoptosis of epithelia in the mouse male accessory sex organs and uterus were investigated using Fos-deficient mice. Normal 30- and 50-day-old and Fos-deficient 50-day-old male and female mice were castrated, and testosterone propionate and estradiol-17 beta were daily injected into male and female mice, respectively, for 5 days. An apoptotic index (a percentage of apoptotic cells) in the epithelium was examined from the day following the last injection (day 1) to day 8. The body weights and the weights of the ventral prostate (VP), coagulating gland (C), seminal vesicle (SV) and epididymis (Ep) and uterus of 50-day-castrated Fos-deficient mice on day 1 suggested that the development of these mice corresponded to that of 30-day-castrated normal mice at the most. The extents of apoptosis estimated by an apoptotic index in the VP, C, SV, Ep and uterus in 50-day-castrated Fos-deficient mice were comparable to those in 30-day-castrated normal mice. The extents of apoptosis in the SV, Ep and uterus in 30-day-castrated normal and 50-day-castrated Fos-deficient mice were similar to those in 50-day-castrated normal mice, while the extents of apoptosis in the VP and C in the former two groups of mice were less than those in the latter mice. The present results show that Fos-deficiency does not affect apoptosis in the SV, EP and uterus. However, the extents of apoptosis in the VP and C were less in 50-day-castrated Fos-deficient mice than in 50-day-castrated normal mice. This seems to be due to the retarded development of 50-day-castrated Fos-deficient mice, but not to a role of Fos in apoptosis.     

Pulmonary Artery Diameter (PAD) and the Pulmonary Artery to Aorta Ratio (PAD/AAD) as Assessed by Non-contrast Cardiac CT: The Association with Left Ventricular (LV) Remodeling and the LV Function

Objective Dilatation of the pulmonary artery itself (PAD: pulmonary artery diameter) or in relation to the ascending aorta (PAD/AAD: pulmonary artery diameter to ascending aortic diameter ratio) has been reported to be associated with pulmonary hypertension and with a prognostic outcome of either heart failure or cardiovascular events. We herein aimed to assess the correlations between pulmonary hypertension-related parameters PAD (or PAD/AAD) and left ventricular (LV) remodeling and LV function. Methods This retrospective study included 193 patients (ages: 67±12 years) who underwent both coronary CT angiography (CCTA) and echocardiography. The PAD and the AAD were measured on a transaxial non-contrast CCTA image at the level of the pulmonary artery bifurcation. Left ventricular mass (LVM), relative wall thickness ratio (RWT), left ventricular ejection fraction (LVEF), left atrial volume (LAV), and early mitral inflow velocity to mitral annular early diastolic velocity ratio (E/e'') were evaluated by echocardiography. The relationships between PAD (or PAD/AAD) and echocardiography parameters were assessed, and adjusted for the demographic data and cardiovascular disease (CVD) risk factors by a multivariable linear regression analysis. Results PAD (mean±SD: 2.6±0.4 cm) was positively correlated with LVM (r=0.34, p＜0.001), LAV (r=0.41, p＜0.001), and E/e'' (r=0.29, p＜0.001). PAD/AAD (mean±SD: 0.76±0.12 cm) was positively correlated with LVM (r=0.12, p=0.09), LAV (r=0.24, p＜0.001), and E/e'' (r=0.15, p=0.04). These correlations remained significant after adjusting for demographic data and CVD risk factors. PAD (or PAD/AAD) did not correlate with LVEF or RWT (p＞0.05). Conclusion Greater PAD or PAD/AAD is significantly associated with LV remodeling and an impaired LV function.     

中药白芷的基原植物研究Ⅳ.白芷的基原植物、栽培历史以及其近缘野生植物演化的讨论

目的 :确认中药白芷的基原植物 ,探讨其栽培历史变化以及有关近缘野生植物的演化。方法 :对已取得的各项研究结果作综合分析 ,并结合历史文献、分布现状等进行讨论。结果 :各项研究结果与历史文献、分布现状等均较为一致。结论 :①中药白芷的基原植物应是台湾白芷。②建议将雾灵当归处理为兴安白芷的变种 ,定名为A .dahuricavar.porphyrocaulis。③对川 (杭 )白芷和祁 (禹 )白芷不应作分类学上的区分。同时 ,还对中药白芷的使用栽培历史和白芷的野生近缘植物兴安白芷、台湾白芷和雾灵当归的演化关系作出了推断。     

5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a synthetic orally active hallucinogenic tryptamine derivative, known also as Foxy or Foxy methoxy. However, few studies have examined its effects in vitro. In the present study, we investigated the actions of 5-MeO-DIPT against monoamine neurotransmitter transporters, including the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using COS-7 cells heterologously expressing these transporters and rat brain synaptosomes. 5-MeO-DIPT specifically inhibited the uptake of [³H]serotonin (5-HT) by the SERT-expressing COS-7 cells and rat striatal synaptosomes in a high affinity manner at concentrations similar to those for cocaine. The effect was reversible and competitive. 5-MeO-DIPT failed to stimulate reverse transport of [³H]5-HT through SERT, while it prevented the releasing action of methamphetamine. 5-MeO-DIPT induced cell toxicity at high concentrations in COS-7 cells, and it was not influenced by the expression of SERT. These results demonstrated that 5-MeO-DIPT acts as a competitive SERT inhibitor and has an inability to cause reverse transport, underlying its serotonergic actions.     

Human endothelial cell growth factors derived from thyroid anaplastic cell carcinoma

Human endothelial cell growth factors were partially isolated from transplanted thyroid anaplastic cell carcinoma propagated in nude mice. Purification was monitored in human umbilical cord vein endothelial cell cultures by (3H)-thymidine incorporation into DNA. Crude tumor extracts with 0.1 M Tris-HCl, pH 7.2 were fractionated by ammonium sulfate precipitation. The active materials precipitated by 35% to 50% ammonium sulfate were further purified by Bio-Rex 70 (Bio-Rad, Richmond, Calif.) cation exchange chromatography. Active fractions eluted by 0.5 M to 0.7 M NaCl were further analyzed via heparin-sepharose affinity chromatography. This resulted in separation of one major peak eluted by 0.9 M to 1.2 M NaCl and confirmed to promote human umbilical cord vein endothelial cell proliferations, and three other peaks. The molecular weight determination of the most active fraction performed by high-pressure liquid chromatography utilizing TSK 2000 gel column indicates 41,000 and 19,000 daltons for the active materials, respectively. Our results demonstrate that the angiogenesis properties of a solid tumor (thyroid anaplastic cell carcinoma), are not composed of a simple mechanism in vivo.