Successful neoadjuvant treatment with radiochemotherapy and systemic chemotherapy for the locally advanced pancreatic head cancer: report of a case

A 49-year-old man was admitted to the hospital for the upper abdominal pain and was diagnosed as unresectable pancreatic head cancer because of the invasion around the superior mesenteric artery. He was treated with radiochemotherapy, followed by systemic gemcitabine alone for 3 courses. He was further treated with systemic gemcitabine plus S?1 combination therapy for 5 courses. CT examination after these treatments showed a dramatic reduction of the tumor at the head of the pancreas and a pancreatoduodenectomy was performed. Pathologically, there was no residual malignant tumor. He has had no recurrent tumor up until now. Several studies of gemcitabine plus S-1 combination therapy show higher response rates for unresectable tumors. The current case indicates the effectiveness of the radiochemotherapy and gemcitabine plus S?1 combination therapy for locally advanced pancreatic head cancer as a neoadjuvant setting. We consider that multidisciplinary treatment including gemcitabine plus S?1 therapy may prolong the survival time by curative operation.     

Formation of unconventional standing waves at graphene edges by valley mixing and pseudospin rotation

We investigate the roles of the pseudospin and the valley degeneracy in electron scattering at graphene edges. It is found that they are strongly correlated with charge density modulations of short-wavelength oscillations and slowly decaying beat patterns in the electronic density profile. Theoretical analyses using nearest-neighbor tight-binding methods and first-principles density-functional theory calculations agree well with our experimental data from scanning tunneling microscopy. The armchair edge shows almost perfect intervalley scattering with pseudospin invariance regardless of the presence of the hydrogen atom at the edge, whereas the zigzag edge only allows for intravalley scattering with the change in the pseudospin orientation. The effect of structural defects at the graphene edges is also discussed.     

Structural and functional analysis of an essential nucleoporin heterotrimer on the cytoplasmic face of the nuclear pore complex

So far, only a few of the interactions between the ≈30 nucleoporins comprising the modular structure of the nuclear pore complex have been defined at atomic resolution. Here we report the crystal structure, at 2.6 Å resolution, of a heterotrimeric complex, composed of fragments of three cytoplasmically oriented nucleoporins of yeast: Nup82, Nup116, and Nup159. Our data show that the Nup82 fragment, representing more than the N-terminal half of the molecule, folds into an extensively decorated, seven-bladed β-propeller that forms the centerpiece of this heterotrimeric complex and anchors both a C-terminal fragment of Nup116 and the C-terminal tail of Nup159. Binding between Nup116 and Nup82 is mutually reinforced via two loops, one emanating from the Nup82 β-propeller and the other one from the β-sandwich fold of Nup116, each contacting binding pockets in their counterparts. The Nup82-Nup159 interaction occurs through an amphipathic α-helix of Nup159, which is cradled in a large hydrophobic groove that is generated from several large surface decorations of the Nup82 β-propeller. Although Nup159 and Nup116 fragments bind to the Nup82 β-propeller in close vicinity, there are no direct contacts between them, consistent with the noncooperative binding that was detected biochemically. Extensive mutagenesis delineated hot-spot residues for these interactions. We also showed that the Nup82 β-propeller binds to other yeast Nup116 family members, Nup145N, Nup100 and to the mammalian homolog, Nup98. Notably, each of the three nucleoporins contains additional nuclear pore complex binding sites, distinct from those that were defined here in the heterotrimeric Nup82•Nup159•Nup116 complex.     

Is Intercellular Space Different Among Layers in Normal Esophageal Mucosa? An Electron Microscopic Study

Background/Introduction

Dilatation of intercellular space (IS) of esophageal epithelial cells is described as a sensitive early marker for epithelial damage by refluxate. Esophageal epithelia are morphologically subdivided into three layers according to the shape of the cells and nuclei. Meanwhile, ten transmission electron microscopy (TEM) photographs and ten randomly selected measurements per photo from gastroesophageal reflux disease (GERD) patients have been widely accepted without any theoretical criticism. We assumed that the IS differs among each layer and thus studied IS according to subdivided layers of normal esophageal epithelium. We also evaluated an optimal number of IS measurements per photograph.

Materials and Methods

Esophagogastroduodenoscopy was performed in 15 healthy adults without any symptom of GERD, taking biopsies from mucosa above 5 cm from the squamo-columnar junction. Tissues were handled and prepared for TEM, verifying three layers of esophageal mucosa, i.e., squamous cell layer, prickle cell layer, and basal layer. Ten digital photomicrographs were taken from each three layers by TEM, and ISs were measured with a computerized image analysis program. For the method of measuring IS, 5, 10, 20, 30, and 40 measurements per photomicrograph were respectively performed by four different examiners. Mean value and intraclass correlation coefficient (ICC) was also yielded.

Results

Mean IS of lower esophagus irrelevant to three epithelial layers were 0.39 ± 0.30 ??m. When subdivided into three layers, however, mean IS of squamous cell layer was 0.62 ± 0.23 ??m, prickle cell layer 0.23 ± 0.19 ??m, and basal layer 0.55 ± 0.36 ??m, with their difference statistically significant (p < 0.05). On the other hand, ICC of 5, 10, 20, 30, and 40 measurements were 0.688, 0.917, 0.837, 0.790, and 0.765, respectively.

Conclusions

Mean IS values of each three layers of esophageal epithelium in normal subjects were significantly different, and reconsideration of the standard measurement method is needed. Ten measurements per photo had an adequate inter-observer agreement.     

The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis

There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures--a challenging process for these complex, multiorgan system diseases. The international OMERACT Vasculitis Working Group has developed and implemented an iterative research agenda that has utilized accumulated experience and datasets from several multicenter clinical trials and large cohort studies. This work has led to the development, evaluation, validation, and endorsement, through the OMERACT consensus and validation processes, of a "core set" of outcome measurements for use in clinical trials of AAV. The core set includes domains of disease activity, damage assessment, patient-reported outcomes, and mortality; there is at least one validated outcome measurement instrument available for each domain. This report reviews the domains of illness in AAV included in the OMERACT core set, describes the instruments validated to measure these domains, and presents the approved core set.     

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.     

The novel role of mast cells in the microenvironment of acute myocardial infarction

Mast cells are multifunctional cells containing various mediators, such as cytokines, tryptase, and histamine, and they have been identified in infarct myocardium. Here, we elucidated the roles of mast cells in a myocardial infarction (MI) rat model. We studied the physiological and functional roles of mast cell granules (MCGs), isolated from rat peritoneal fluid, on endothelial cells, neonatal cardiomyocytes, and infarct heart (1-hour occlusion of left coronary artery followed by reperfusion). The number of mast cells had two peak time points of appearance in the infarct region at 1 day and 21 days after MI induction in rats (p < 0.05 in each compared with sham-operated heart). Simultaneous injection of an optimal dose of MCGs modulated the microenvironment and resulted in the increased infiltration of macrophages and decreased apoptosis of cardiomyocytes without change in the mast cell number in infarct myocardium. Moreover, MCG injection attenuated the progression of MI through angiogenesis and preserved left ventricular function after MI. MCG-treated cardiomyocytes were more resistant to hypoxic injury through phosphorylation of Akt, and MCG-treated endothelial cells showed enhanced migration and tube formation. We have shown that MCGs have novel cardioprotective roles in MI via the prolonged survival of cardiomyocytes and the induction of angiogenesis.     

The prevalence and clinical predictors of atherosclerotic renal artery stenosis in patients undergoing coronary angiography

Renal artery stenosis is an important cause of secondary hypertension as well as ischemic nephropathy. The purpose of this study was to determine the clinical predictors in patients with renal artery stenosis in a population referred for coronary angiography. From March 1998 to July 1999, 1459 patients undergoing coronary angiography for various indications were routinely screened for renal artery stenosis by undergoing abdominal aortography. Coronary angiography, carotid angiography, and abdominal aortography was performed via either the radial or the femoral approach. The data were analyzed retrospectively. Out of 1459 patients undergoing abdominal aortography, 158 (10.8%) were found to have significant renal artery stenosis with 24 of the patients having bilateral stenosis. Significant coronary artery diseases were found in 994 of the 1459 study population (68.1%), with 134 (13.5%) of these patients having concomitant renal artery stenosis. Multivariate logistic regression showed that extracranial carotid artery stenosis odds ratio [(OR) 4.89 (95% confidence interval 2.57–9.33), P < 0.001], peripheral artery disease [OR 4.64 (2.65–9.33), P < 0.001], renal insufficiency [OR 2.68 (1.43–5.02), P = 0.002], significant coronary artery disease [OR 2.01 (1.12–3.59), P = 0.019], hypercholesterolemia [OR 1.92 (1.07–3.43), P = 0.028], hypertension [OR 1.85 (1.16–2.95), P = 0.010], and old age (>60 years) [OR 1.64 (1.01–2.64), P = 0.044] were significant clinical predictors of renovascular disease. The prevalence of indolent atherosclerotic renal artery stenosis is relatively high in selected groups of patients with high clincial risk factors for this underdiagnosed disease. Renal artery stenosis should be highly suspected in patients who have these risk factors because early detection of this disease may reverse the progression to chronic renal failure and end-stage renal disease.     

Genomic organization of mouse ZAKI-4 gene that encodes ZAKI-4 alpha and beta isoforms, endogenous calcineurin inhibitors, and changes in the expression of these isoforms by thyroid hormone in adult mouse brain and heart

OBJECTIVE: ZAKI-4 was identified as a thyroid hormone-responsive gene in cultured human fibroblasts. A single ZAKI-4 gene encodes two isoforms, ZAKI-4 alpha and beta, both inhibiting calcineurin activity. ZAKI-4 alpha and beta differ at their N termini, and show distinct distribution profiles in human tissues. The aim of this study was to elucidate the organization of the mouse ZAKI-4 gene and to determine the effect of thyroid hormone on the expression of ZAKI-4 isoforms in vivo. DESIGN: We cloned mouse homologues of human ZAKI-4 alpha and beta cDNA. Fluorescence in situ hybridization and bioinformatics analysis were employed to determine the gene organization. The effect of thyroid hormone on the expression of ZAKI-4 isoforms in mouse brain and heart was also studied. METHODS: Total RNA extracted from mouse cerebellum was used to clone ZAKI-4 alpha and beta cDNAs by RT-PCR followed by rapid amplification of cDNA ends. Mice were rendered hypothyroid by feeding a low iodine diet supplemented with propylthiouracil for 2 weeks. In one group (hyperthyroid) L-T(3) was injected i.p. for the last 4 days whereas another group (hypothyroid) received vehicle only. Non-treated mice were controls. RESULTS AND CONCLUSION: Mouse ZAKI-4 alpha and beta cDNAs were highly homologous to the human isoforms. The gene was mapped on chromosome 17qC, syntenic to human chromosome 6 where the human ZAKI-4 gene is located. As observed in human, ZAKI-4 alpha mRNA was expressed only in brain whereas beta mRNA was distributed in other tissues as well, such as heart and skeletal muscle. ZAKI-4 alpha mRNA was lower in the cerebral cortex of hypothyroid mice. Injection of L-T(3) caused an increase in ZAKI-4 beta mRNA in heart; however, expression of neither ZAKI-4 alpha nor beta mRNA was influenced by thyroid status in other tissues. These results indicate that expression of ZAKI-4 alpha and beta isoforms is regulated by thyroid hormone in vivo, and the regulation is isoform- and tissue-specific.     

A case of polymyositis with concomitant diffuse alveolar damage following interstitial pneumonia]

A 68-year-old woman had been given a diagnosis of interstitial pneumonia (NSIP pattern) and followed up at our hospital for 3 years. She was admitted to our hospital because of dyspnea, lower limb edema and myalgia. On admission, serum CPK and CRP levels were elevated and an electromyogram suggested inflammatory myopathy. We diagnosed polymyositis (PM) with progressive interstitial pneumonia (IP). Although methylprednisolone pulse therapy and immunosuppressive agents were administered, pulmonary lesions became aggravated. The patient died due to respiratory failure as a result of the progress of IP. The autopsy lung revealed diffuse alveolar damage (DAD) at the both acute and fibrotic phases, suggesting that DAD could coincide with PM. We report here a rare case of polymyositis with diffuse alveolar damage (DAD).