Enantioselective One-Pot Synthesis of Cyclopropane-Fused Tetrahydroquinolines via a Ru-Catalyzed Intramolecular Cyclopropanation.

A highly enantioselective one-pot synthesis of cyclopropane-fused tetrahydroquinolines bearing carbonyl functionalities, which are difficult to synthesize using conventional methods, is reported. Employing readily accessible alkene-tethered anthranilaldehydes, hydrazone formation and subsequent Ru-catalyzed intramolecular cyclopropanation furnish the desired products in ≤87% yield and ≤95% ee under mild conditions. Various anthranilaldehydes, functionalized alkenes, and -aryl sulfonyl groups are tolerated, and a series of synthetic transformations were conducted to demonstrate the practical utility.

Intestinal Failure-Associated Liver Disease and Eicosapentaenoic Acid/Arachidonic Acid Ratio.

Intestinal failure-associated liver disease (IFALD) is a fatal complication of short bowel syndrome managed with parenteral nutrition. A clinical cohort study reported the usefulness of parenteral administration of fish-derived omega-3 fatty acids in improving IFALD; however, no biomarker has been developed as yet. The authors report the case of a preterm infant with IFALD complicated by extensive short bowel syndrome.

Cross-Cultural Interprofessional Faculty Development in Japan: Results of an Integrated Workshop for Clinical Teachers.

Background: Faculty development programs, studied both home and abroad, have been shown to be helpful for enhancing the scholarly and academic work of nonacademic clinicians. Interprofessional education and faculty development efforts have been less well studied. This project investigated the effect of a well-studied faculty development program applied in an interprofessional fashion across health profession educators in medicine and nursing.

Nickel-Catalyzed Directed C6-Selective C-H Alkylation of 2-Pyridones with Dienes and Activated Alkenes.

A pyridine-directed, C6-selective nickel-catalyzed ring-contracting C-H alkylation of 2-pyridones with 1,5-cyclooctadiene (cod) has been developed. The reaction proceeds smoothly under external-ligand-free conditions and is accelerated uniquely by a KPO base. Preliminary mechanistic investigations with deuterium-labeled substrates and related reactions with some alkenes are also disclosed.

Rhodium-Catalyzed C6-Selective C-H Borylation of 2-Pyridones.

A pyridine-directed, rhodium-catalyzed C6-selective C-H borylation of 2-pyridones with bis(pinacolato)diboron (pinB-Bpin) has been developed. The reaction proceeds smoothly under relatively mild conditions, and the corresponding C6-borylated 2-pyridones are obtained with perfect site selectivity. Subsequent palladium-catalyzed Suzuki-Miyaura cross-coupling is followed by the removal of the pyridine directing group to form the C6-arylated NH-pyridone in an acceptable overall yield.

Copper-Mediated Oxidative Coupling of Benzamides with Maleimides via Directed C-H Cleavage.

A Cu(OAc)2/Cy2NMe-mediated oxidative direct coupling of benzamides with maleimides has been developed. The aromatic C-H alkenylation with the aid of an 8-aminoquinoline-based bidentate directing group is followed by an intramolecular aza-Michael-type addition to form the isoindolone-incorporated spirosuccinimides, which are of potent interest in medicinal chemistry.

Rumor diffusion and convergence during the 3.11 earthquake: a twitter case study.

We focus on Internet rumors and present an empirical analysis and simulation results of their diffusion and convergence during emergencies. In particular, we study one rumor that appeared in the immediate aftermath of the Great East Japan Earthquake on March 11, 2011, which later turned out to be misinformation. By investigating whole Japanese tweets that were sent one week after the quake, we show that one correction tweet, which originated from a city hall account, diffused enormously.

Effect of coagulation of nodes in an evolving complex network.

We propose a new type of stochastic network evolution model based on annihilation, creation, and coagulation of nodes, together with the preferential attachment rule. The system reaches a unique quasistatistically steady state in which the distribution of links follows a power law, lifetime of nodes follows an exponential distribution, and the mean number of links grows exponentially with time. The master equation of the model is solved analytically by applying Smoluchowski's coagulation equation for aerosols.

Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines.

Stanniocalcin (STC) is a calcium (Ca)-regulating hormone that was originally discovered in the fish Stannius body, which is a unique endocrine organ. Hypercalcemia increases STC secretion, which inhibits Ca uptake by the gills and normalizes serum Ca level. In this study we investigated the STC expression in human normal and abnormal adrenal cells.

Changes in clinical features and long-term prognosis in patients with pheochromocytoma.

To investigate changes in preoperative clinical features and the long-term outcome of tumor recurrence, mortality, and morbidity in patients with pheochromocytoma, we retrospectively examined changes in the clinical features by comparing 49 patients from 1957 to 1985 (group I) with 46 patients from 1986 to December 1995 (group II). In addition in these 95 patients (excluding 2 who had died before operation), we evaluated long-term postoperative outcome from the initial operation to August 1996 (909 patient-years). The mean age in group II was older than that of group I.

Multiple endocrine neoplasia type 2A with the identical somatic mutation in medullary thyroid carcinoma and pheochromocytoma without germline mutation at the corresponding site in the RET proto-oncogene.

A germline mutation either in exon 10 or 11 of the RET proto-oncogene is found in the majority of patients with multiple endocrine neoplasia type 2A (MEN 2A). A 41-year-old female patient was referred for further evaluation of incidentally discovered right adrenal tumor. She had bilateral adrenal pheochromocytomas and medullary thyroid carcinomas detected by endocrinological and radiological examination, and diagnosed as MEN 2A.

Preferential changes in hepatosplanchnic hemodynamics in patients with borderline hypertension.

To investigate changes in systemic and regional hemodynamics during the development of human hypertension, we simultaneously measured cardiac index (CI) by the indocyanine green (ICG) dye dilution method, hepatosplanchnic blood flow (HBF) by the ICG clearance method using a two-compartment model, and renal blood flow (RBF) by the p-aminohippurate clearance method in patients with borderline and essential hypertension. In patients with borderline hypertension (BH, n = 27), HBF (435 +/- 15 ml/min/m2) and HBF/CI (16 +/- 1%) were significantly (p < 0.05) lower than in age-matched normotensive controls (528 +/- 21 and 19 +/- 1, respectively, n = 21), while CI, RBF and RBF/CI were similar.

Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones.

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e.

Two cases of malignant pheochromocytoma treated with cyclophosphamide, vincristine and dacarbazine in a combined chemotherapy.

Two patients with malignant pheochromocytoma were treated with a combination chemotherapy regimen consisting of cyclophosphamide vincristine, and dacarbazine (CVD). With the first few cycles of the treatment, one patient, a 29-year-old man had a marked improvement of clinical symptoms and decreases in tumor size and catecholamine levels in plasma and urine. He had been in a clinically stable condition for 18 months but died 34 months after starting of this treatment because the CVD regimen became ineffective and rapid growth of the metastatic tumors occurred.

Two cases of pheochromocytoma diagnosed histopathologically as mixed neuroendocrine-neural tumor.

We treated two rare cases of pheochromocytoma which were histopathologically diagnosed as mixed neuroendocrine-neural tumor (MNNT): a 35-year-old male patient associated with ganglioneuroblastoma and cutaneous neurofibromatosis and a 42-year-old male patient with ganglioneuroma. Both patients showed typical clinical manifestations of pheochromocytoma without any familial traits. Although each of the diseases has its own entity and clinical features, these tumors are all derived from the neural crest tissues.

Plasma free dopamine: physiological variability and pathophysiological significance.

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma.

Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in hypertensive patients.

To investigate the peripheral dopaminergic modulation in the pathogenesis of human hypertension, we examined the responses of plasma free dopamine (DA) to dexamethasone (Dx) administration, which is suggested to activate dopaminergic activity. We administered Dx 2 mg intravenously to patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT). Plasma free DA was increased significantly in all groups and the responses were more remarkable in PA than in EH and NT.

Renal dopamine spillover rate using 3H-dopamine radiotracer technique as an index of renal dopaminergic nerve activity.

Renal and total dopamine (DA) spillover rates at rest were measured in 25 conscious rabbits with chronically implanted renal vein catheters. Renal DA spillover rate was calculated from veno-arterial difference in plasma free DA concentrations across the kidney corrected by the fractional extraction of infused 3H-DA. Plasma free DA concentrations were 11.

Immunohistochemical Localization of Chromostatin and Pancreastatin, Chromogranin A-Derived Bioactive Peptides, in Normal and Neoplastic Neuroendocrine Tissues.

Despite the widespread distribution of chromogranin A (CgA) in neuroendocrine tissues, the biological function of CgA has not yet been elucidated. The primary amino acid sequence of CgA, elucidated by cDNA analysis, has been revealed to include several pairs of basic amino acid residues that are homologous to the bioactive peptides, such as pancreastatin (PST) and chromostatin (CST). Using antibodies for human PST and CST, the immunohistochemical localization of these peptides was investigated in neuroendocrine tissues, including human pituitary glands, pancreas, adrenal medulla, various types of neuroendocrine neoplasms (13 pheochromocytomas, 10 medullary thyroid carcinomas, 11 pancreatic endocrine tumors, and 19 carcinoid tumors), and the cell line QGP-1N derived from human somatostatin-producing pancreatic endocrine tumor.

Ki-67 is an indicator of progression of neuroendocrine tumors.

No current histological or cytological indices can distinguish reliably malignant from benign tumors in neuroendocrine tumors, including pheochromocytomas, pancreatic endocrine tumors, and carcinoid tumors. We investigated immunohistochemically the expression of Ki-67 in 52 neuroendocrine tumors, including 17 pheochromocytomas, 9 pancreatic endocrine tumors, 23 carcinoid tumors, 2 neuroendocrine carcinomas (NEC), and 1 neuroblastoma with liver metastasis. Of the 52 tumors, distant metastasis was observed in 4 pheochromocytomas, 2 pancreatic endocrine tumors, 4 carcinoids, 2 NEC, and 1 neuroblastoma.

Dna ploidy of pheochromocytoma on cytology specimen by image analysis.

Pheochromocytoma usually shows prominent nuclear atypia, but the presence of such atypical cells is known to be an unreliable predictor of malignancy. DNA ploidy of pheochromocytomas has been analyzed by flow cytometry or photospectrometry on paraffinem-bedded tissue, but the results were controversial. We performed DNA analysis on cytology specimens of 11 pheochromocytomas using an image analysis system.