VEGF function for upregulation of endogenous PlGF expression during FGF-2-mediated therapeutic angiogenesis

Vascular endothelial growth factor (VEGF) is a major positive angiogenic factor. Using a murine hindlimb ischemia model, we previously showed that fibroblast growth factor-2 (FGF-2) enhances the expression of endogenous VEGF which highly contribute to the therapeutic effect of FGF-2 gene transfer. Recently, placental growth factor (PlGF) has been shown to play an important role in angiogenesis. However, the molecular mechanism of endogenous PlGF during FGF-2-mediated angiogenesis has not been elucidated. Severe hindlimb ischemia stimulated PlGF expression that was more strongly enhanced by FGF-2 gene transfer, and a blockade of PlGF activity diminished the recovery of blood flow by FGF-2-mediated angiogenesis. The PlGF expression in cultured endothelial cells was significantly enhanced by VEGF stimulation, but not by FGF-2. The upregulation of endogenous PlGF expression was significantly decreased by the inhibition of endogenous VEGF activity in vivo. Subsequent signal inhibition experiments revealed that the PKC, MEK, and possibly NF-κB-related pathways were essential in stimulating PlGF expression with VEGF, while p70S6K is the regulator for VEGF expression. These results indicate that the FGF-2-mediated enhancement of PlGF expression was dependent on VEGF function, and the FGF-2/VEGF axis participates in FGF-2-mediated angiogenesis indirectly via PlGF as well as directly.     

Pericardio-peritoneal drainage using a subcostal approach

A 56-year-old man admitted to our hospital for cardiac tamponade due to dilated cardiomyopathy did not respond to treatment by usual medical means or surgery. Pericardio-peritoneal drainage was conducted using a subcostal approach. Seven months later, the patient remains well and free of signs of pericardial tamponade. This method has proved to be safe and effective in patients with persistent massive pericardial effusion.     

Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons

Neurocalcin (NC) is a recently described calcium-binding protein isolated and characterized from bovine brain. NC belongs to the neural calcium-sensor proteins defined by the photoreceptor cell-specific protein recoverin that have been proposed to be involved in the regulation of calcium-dependent phosphorylation in signal transduction pathways. We analyzed the distribution and morphology of the NC-immunoreactive (IR) neurons in the rat dorsal hippocampus and the coexistence of NC with GABA and different neurochemical markers which label perisomatic inhibitory cells [parvalbumin (PV) and cholecystokinin (CCK)], mid-proximal dendritic inhibitory cells [calbindin D28k (CB)], distal dendritic inhibitory cells [somatostatin (SOM) and neuropeptide Y (NPY)], and interneurons specialized to innervate other interneurons [calretinin (CR) and vasoactive intestinal polypeptide (VIP)]. NC-IR cells were present in all layers of the dentate gyrus and hippocampal fields. In the dentate gyrus, NC-IR cells were concentrated in the granule cell layer, especially in the hilar border, whereas in the CA fields they were most frequently found in the stratum radiatum. NC-IR cells were morphologically heterogeneous and exhibited distinctive features of non-principal cells. In the dentate gyrus, pyramidal-like, multipolar and fusiform (horizontal and vertical) cells were found. In the CA3 region most NC-IR cells were multipolar, but vertical and horizontal fusiform cells also appeared. In the CA1 region, where NC-IR cells showed most frequently vertically arranged dendrites, multipolar, bitufted and fusiform (vertical and horizontal) cells could be distinguished. All the NC-IR cells were found to be GABA-IR in all hippocampal layers and regions, and they represented about 19% of the GABA-positive cells. NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively. NC and CCK did not coexist in the dentate gyrus; however, 9% of the NC-IR cells in the CA fields also contained CCK. No coexistence of NC with PV, SOM or NPY was found in any hippocampal region. We conclude that NC is exclusively expressed by interneurons in the rat hippocampus. NC-IR cells are a morphologically and neurochemically heterogeneous subset of GABAergic non-principal cells, which, on the basis of the known termination pattern of the colocalizing markers, are also functionally heterogeneous and are mainly involved in feed-forward dendritic inhibition in the commissural-associational and Schaffer collateral termination zones (CB containing cells), in innervation of other interneurons (CR- and VIP-containing cells), and in perisomatic inhibition (CCK-containing cells). NC is never present in perisomatic inhibitory PV-containing cells, or in feed-back distal dendritic inhibitory SOM/NPY-containing cells. Hippocampus 1998;8:2–23. © 1998 Wiley-Liss, Inc.     

Diagnostic Performance of Whole-Body Diffusion-Weighted Imaging Compared to PET-CT Plus Brain MRI in Staging Clinically Resectable Lung Cancer

Background: Precise staging of lung cancer is usually evaluated by PET-CT and brain MRI. Recently, however, whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) has be applied. The aim of this study is to determine whether the diagnostic performance of lung cancer staging by WB-DWI is superior to that of PET-CT+brain MRI. Materials and Methods: PET-CT + brain MRI and WB-DWI were used for lung cancer staging before surgery with 59 adenocarcinomas, 16 squamous cell carcinomas and 6 other carcinomas. Results: PET-CT + brain MRI correctly identified the pathologic N staging in 67 patients (82.7%), with overstaging in 5 (6.2%) and understaging in 9 (11.1%), giving a staging accuracy of 0.827. WB-DWI correctly identified the pathologic N staging in 72 patients (88.9%), with overstaging in 1 (1.2%) and understaging in 8 patients (9.9%), giving a staging accuracy of 0.889. There were no significant differences in accuracies. PET-CT + brain MRI correctly identified the pathologic stages in 56 patients (69.1%), with overstaging in 7 (8.6%) and understaging in 18 (22.2%), giving a staging accuracy of 0.691. WB-DWI correctly identified the pathologic stages in 61 patients (75.3%), with overstaging in 4 (4.9%) and understagings in16(19.7%), giving a staging accuracy of 0.753. There were no significant difference in accuracies. Conclusions: Diagnostic efficacy of WB-DWI for lung cancer staging is equivalent to that of PET-CT + brain MRI.     

Clinical Investigation of Patients Who Develop Neuropathic Tooth Pain After Endodontic Procedures

IntroductionThis study aimed to determine the characteristics of patients with neuropathic tooth pain (NTP) who were selected from a group of patients who developed persistent pain after undergoing endodontic procedures.MethodsOf 271 patients who had chronic persistent pain that did not respond to previous endodontic procedures and were referred to the Endodontic Team of the Nippon Dental University Hospital, 16 patients (5.9%; mean age, 46.8 years; 13 women) who fulfilled the diagnostic criteria for NTP were recruited. The inclusion criteria for the patients were the presence of chronic persistent pain and other pain-related symptoms, despite the absence of major pathology.ResultsPain predominantly occurred in the maxilla (14 patients). In 10 patients (62.5%), NTP developed after retreatment. Daily application of tricyclic antidepressants produced pain relief in 11 patients (68.8%).ConclusionsThese results indicated that NTP is a rare type of chronic intractable endodontic pain and that careful diagnosis of NTP is important.     

Sudden fetal death associated with both duodenal atresia and umbilical cord ulcer: a case report and review

We encountered one case of duodenal atresia complicated by massive intrauterine hemorrhage due to the perforation of an umbilical cord ulceration (UCU). UCU is an extremely rare complication in the perinatal period. Although the prenatal diagnosis of upper intestinal atresia has been established, little is known about the association between UCU and upper intestinal atresia. In this article, we report our case, review past articles, and discuss the underlying pathophysiological mechanisms of the cause of an UCU. Given the characteristic sites of upper intestinal atresia, we speculate that regurgitation of gastric or intestinal juice into the amniotic fluid could be responsible for the development of UCU. We also believe that close observation is required for patients who have upper intestinal atresia.     

Successful Surgical Treatment of a Ruptured Abdominal Aortic Aneurysm Without Homologous Blood Transfusion in a Jehovah's Witness: Report of a Case

We report herein the case of a 47-year-old woman of the Jehovah's Witness faith in whom Y-grafting for a ruptured abdominal aortic aneurysm was successfully performed without a homologous blood transfusion. We used a Cell Saver (Haemonetics, Braintree, MA, USA) red cell salvaging device and an aortic occlusion balloon catheter, and performed gentle and minimal dissection during the operation. Postoperatively, the patient was kept heavily sedated and required hypothermic therapy for only 14 h. We treated her severe anemia using conventional drugs, including iron and folic acid, and her hemoglobin increased smoothly. Although her hemoglobin level decreased to 2.8 g/dl during the operation, her postoperative course was uneventful. Received: November 24, 2000 / Accepted: May 15, 2001     

A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia

Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557 Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.     

Frequency-Dependent Electrophysiological Effect of Ibutilide on Human Atrium and Ventricle

Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.