Hitoshi Goto

Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.

Analysis of Gene Expression Involved in Brain Metastasis from Breast Cancer Using cDNA Microarray

BackgroundBrain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment.MethodsWe investigated the gene expression profile occurring in brain metastases from a breast cancer cell line. We used cDNA microarrays to compare patterns of gene expression between the mouse breast cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B).ResultsBy Microarray analysis about 350 of 21,000 genes were significantly up-regulated in Jyg MC (B). Many candidate genes that may be associated with the establishment of brain metastasis from breast cancer were included. Interestingly, we found that the expression of astrocyte derived cytokine receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly increased in Jyg MC (B) cells. These results were confirmed by RT-PCR.ConclusionThese results suggest that cytokines produced by glial cellsin vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

Intraductal papillary mucinous neoplasm originating from a jejunal heterotopic pancreas: report of a case

We report a rare case of an intraductal papillary mucinous neoplasm (IPMN) originating from a jejunal heterotopic pancreas, found incidentally during surgery. A 75-year-old woman was referred to our department for surgical treatment of an abdominal aortic aneurysm (AAA) and a concurrent oropharyngeal tumor. During surgery to correct the AAA, we found a jejunal tumor incidentally and performed partial resection of the jejunum. Microscopically, the jejunal tumor showed dilated ducts containing intraluminal papillae lined with mucinous epithelium with low-grade cytological and architectural atypia within the pancreatic tissue. Immunohistochemical staining revealed MUC1 (−), MUC2 (−), MUC5AC (+), and MUC6 (−) proteins. To the best of our knowledge, only six cases of IPMN originating from a heterotopic pancreas have been reported in English, and this is the first report of an IPMN originating from a jejunal heterotopic pancreas.

Surgical Resection and Inferior Vena Cava Reconstruction for Treatment of the Malignant Tumor: Technical Success and Outcomes

OBJECTIVE The purpose of this study was to review patients who underwent inferior vena cava (IVC) resection with concomitant malignant tumor resection and to consider the operative procedures and the outcomes. MATERIALS AND METHODS Between 2000 and 2012, 41 patients underwent resection of malignant tumors concomitant with surgical resection of the IVC at our institute. The records of these patients were retrospectively reviewed. RESULTS Primary tumor resections included nephrectomy, hepatectomy, retroperitoneal tumor extirpation, lymph node dissection, and pancreaticoduodenectomy. The IVC interventions were partial resection in 23 patients and total resection in 18 patients. Four patients underwent IVC replacement. Operation-related complications included pulmonary embolism, acute myocardial infarction, deep vein thrombosis, leg edema and temporary hemodialysis. There were no operative deaths. The mean follow-up period was 24.9 months (range: 2-98 months). The prognosis depended on the type and stage of the tumor. CONCLUSION Resection and reconstruction of the IVC can be performed safely if the preoperative evaluations and surgical procedures are performed properly. The IVC resection without reconstruction was permissive if the IVC was completely obstructed preoperatively, but it may also be considered in cases where the IVC is not completely obstructed.

Absolute configuration of chiral fullerenes and covalent derivatives from their calculated circular dichroism spectra

The theoretical circular dichroism (CD) spectra of optically active C60 and C70 bis-adducts with chiral functionalization patterns and of the enantiomers of inherently chiral D2-C76 and its mono-adducts were calculated by the π-electron SCF-CI-DV MO method. By comparison with the experimental CD spectra, the absolute configurations of these compounds were assigned.

Evaluation of a Poly(l-lactic acid) Stent for Sutureless Vascular Anastomosis

We have developed a sutureless anastomosis device consisting of a biodegradable stent and stainless steel band for end-to-end anastomosis. The aim of this acute phase study was to evaluate the feasibility of a sutureless anastomotic procedure with a bioabsorbable stent during a 4-week period in a swine model. The porcine infrarenal aorta was replaced with an expanded polytetrafluoroethylene graft. A proximal anastomosis was completed using a sutureless anastomotic procedure employing a bioabsorbable stent made of poly(L-lactic acid) (PLLA) and a stainless steel plate. A distal anastomosis completed by manual suturing served as a control. At 4 weeks after surgery, angiography was performed. The animals were then killed, and the specimens were evaluated histologically. The sutureless anastomotic procedure required significantly less time than the suturing technique. Angiograms showed patency of the grafts, and no signs of either stenosis or leakage. Both pressure-proof and tensile tests confirmed the adequate mechanical strength of the anastomoses. Sutureless anastomosis with a PLLA stent appears to be feasible, at least within an observation period of 4 weeks. This simple procedure shortened the time of surgery and would contribute to reducing the risks of operation-related complications.

Sudden cardiac arrest immediately after stent graft deployment during treatment of iliac aneurysm with iliocaval fistula.

An 84-year-old woman with heaviness of the right lower extremity had an iliocaval fistula related to a right internal iliac aneurysm. Immediately after deployment of an endovascular device, cardiac arrest occurred because of severely decreased sympathetic activity. After surgery, the patient recovered well and has been followed up with exclusion of the arteriovenous fistula and resolution of the type II endoleak. Endovascular treatment for large arteriovenous fistulas induces rapid closure of the fistula together with restoration of blood supply to the lower extremity. Markedly deactivated sympathetic nerve traffic could result in a critical hemodynamic status in association with endograft deployment.

Inflammatory Popliteal Aneurysm

A 67-year-old man was referred to our department because of fever, right lower thigh swelling, and redness with pain. Laboratory tests showed slightly elevated leukocytes and markedly elevated C-reactive protein levels. Computed tomography confirmed a popliteal aneurysm with wall thickening, so-called mantle sign. Aneurysmorrhaphy with a reversed autologous saphenous vein reconstruction was performed. Aneurysm sac and perianeurysm tissue cultures were negative for aerobic and anaerobic bacteria. The microscopic appearance of the aneurysm showed thickening of the adventitia and infiltration of inflammatory cells. This report presents, for the first time, findings suggestive of an inflammatory aneurysm of the popliteal artery.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion : Positive Association

BACKGROUND The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). CONCLUSIONS Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.