Paraganglioma of the posterior mediastinum diagnosed by immunohistochemical staining

Paraganglioma of the mediastinum are rare neoplasms. To date, no definitive morphologic criteria exist that correlate with the clinical outcome of these tumors. We have encountered a case of paraganglioma in which biological behavior was assessed by immunohistochemical staining to determine whether supplementary postoperative treatment was needed. A 28-year-old man came to our hospital because of an abnormal shadow on a radiogram of the chest. He had no symptoms. Hematological findings were unremarkable. Diagnostic imaging suggested a neurogenic tumor. Surgical resection was performed in September, 2002. A typical nesting pattern (Zellballen) and positivity for chromogranin on immunohistochemical staining were evident, indicating neuroendocrine characteristics, and paraganglioma was diagnosed. Tissue specimens indicated an MIB-1-labeling index of 1.3% on MIB-1 staining, and a relatively well maintained distribution of S-100 protein-positive sustentacular cells, which were suggestive of a benign tumor. The patient did not receive any supplementary therapy postoperatively but was given careful follow-ups.     

The Batista Operation in Patients with Dilated Cardiomyopathy

Abstract Between December 1996 and October 1998,34 patients with nonischemic dilated cardiomyopathy (DCM) received cardiac volume reduction surgery. The patients' ages ranged from 14 to 67 years (mean = 48 years) and included 28 males and 6 females. Associated mitral regurgitation was present in 31 patients, tricuspid regurgitation in 19 patients, and aortic regurgitation in 4 patients. We performed a partial left ventriculectomy (PLV) using antegrade intermittent warm blood cardioplegia in 15 patients (group A), and in 19 patients (group B) PLV was performed using the on-pump beating heart technique. In group A, the mean aortic clamping time was 79 ± 33 minutes and the total cardiopulmonary bypass time was 155 ± 58 minutes. In group B the mean cardiopulmonary bypass time was 121 ± 43 minutes. There were eight hospital deaths (five in group A and three in group B). Five of 10 survivors of group A required inotropic support for 13.8 ± 25.3 days after the operation, while 5 of 12 survivors in group B required inotropes for 4.2 ± 3.1 days. Hospital mortality was 86% in 7 emergent cases and 7% in 27 elective cases. Echocar-diographic study showed that the left ventricular ejection fraction improved from a mean of 18.7% to 30.3% and the left ventricular diameter decreased from a mean of 80.2 mm to 62.3 mm after the operation. All 26 hospital survivors were followed for 1 to 20 months. Three patients died at early follow-up because of congestive heart failure, thrombosed valve, and hepatic failure, respectively. Nineteen patients were in New York Heart Association (NYHA) Class I or II and four were in NYHA Class III. In conclusion, cardiac volume reduction surgery is effective when the operative technique and proper judgment of patient selection are established, and emergent operation is avoided.     

A point mutation at Asn-534 that disrupts a conserved N-glycosylation motif of the E2 glycoprotein of hepatitis C virus markedly enhances the sensitivity to antibody neutralization

The molecular basis of antibody neutralization against hepatitis C virus (HCV) is poorly understood. The E2 glycoprotein of HCV is critically involved in viral infectivity through specific binding to the principal virus receptor component CD81, and is targeted by anti‐HCV neutralizing antibodies. A previous study showed that a mutation at position 534 (N534H) within the sixth N‐glycosylation motif of E2 of the J6/JFH1 strain of HCV genotype 2a (HCV‐2a) was responsible for more efficient access of E2 to CD81 so that the mutant virus could infect the target cells more efficiently. The purpose of this study was to analyze the sensitivity of the parental J6/JFH1, its cell culture‐adapted variant P‐47 possessing 10 amino acid mutations and recombinant viruses with the adaptive mutations to neutralization by anti‐HCV antibodies in sera of HCV‐infected patients. The J6/JFH1 virus was neutralized by antibodies in sera of patients infected with HCV‐2a and ‐1b, with mean 50% neutralization titers being 1:670 and 1:200, respectively (P < 0.00001). On the other hand, the P‐47 variant showed 50‐ to 200‐times higher sensitivity to antibody neutralization than the parental J6/JFH1 without genotype specificity. The N534H mutation, and another one at position 416 (T416A) near the first N‐glycosylation motif to a lesser extent, were shown to be responsible for the enhanced sensitivity to antibody neutralization. The present results suggest that the residues 534, and 416 to a lesser extent, of the E2 glycoprotein are critically involved in the HCV infectivity and antibody neutralization. J. Med. Virol. 84:229–234, 2012. © 2011 Wiley Periodicals, Inc.     

Left heart bypass support with the Rotaflow Centrifugal Pump? as a bridge to decision and recovery in an adult

Since left heart bypass or biventricular circulatory assist with an extracorporeal centrifugal pump as a bridge to decision or recovery sometimes requires long-time support, the long-term durability of extracorporeal centrifugal pumps is crucial. The Rotaflow Centrifugal Pump(?) (MAQUET Cardiopulmonary AG, Hirrlingen, Germany) is one of the centrifugal pumps available for long-term use in Japan. However, there have been few reports of left heart bypass or biventricular circulatory support over the mid-term. This is a case report of left heart bypass support with the Rotaflow Centrifugal Pump(?) as a bridge to decision and recovery for an adult patient who could not be weaned from cardiopulmonary bypass and percutaneous cardiopulmonary support after cardiac surgery. We could confirm that the patient's consciousness level was normal; however, the patient could not be weaned from the left heart bypass support lasting 1 month. Therefore, the circulatory assist device was switched to the extracorporeal Nipro ventricular assist device (VAD). This time, left heart bypass support could be maintained for 30 days using a single Rotaflow Centrifugal Pump(?). There were no signs of hemolysis during left heart bypass support. The Rotaflow Centrifugal Pump(?) itself may be used as a device for a bridge to decision or recovery before using a VAD in cardiogenic shock patients.     

Luminal trypsin induces enteric nerve-mediated anion secretion in the mouse cecum

Proteases play a diverse role in health and disease. An excessive concentration of proteases has been found in the feces of patients with inflammatory bowel disease or irritable bowel syndrome and been implicated in the pathogenesis of such disorders. This study examined the effect of the serine protease, trypsin, on intestinal epithelial anion secretion when added to the luminal side. A mucosal-submucosal sheet of the mouse cecum was mounted in Ussing chambers, and the short-circuit current (I _sc) was measured. Trypsin added to the mucosal (luminal) side increased I _sc with an ED₅₀ value of approximately 10 μM. This I _sc increase was suppressed by removing Cl^? from the bathing solution. The I _sc increase induced by 10–100 μM trypsin was substantially suppressed by tetrodotoxin, and partially inhibited by a neurokinin-1 receptor antagonist, but not by a muscarinic or nicotinic ACh-receptor antagonist. The trypsin-induced I _sc increase was also significantly inhibited by a 5-hydroxytryptamine-3 receptor (5-HT₃) antagonist and substantially suppressed by the simultaneous addition of both 5-HT₃ and 5-HT₄ receptor antagonists. We conclude that luminal trypsin activates the enteric reflex to induce anion secretion, 5-HT and substance P playing important mediating roles in this secreto-motor reflex. Luminal proteases may contribute to the cause of diarrhea occurring with some intestinal disorders.     

Blockade of platelet-derived growth factor receptor-beta pathway induces apoptosis of vascular endothelial cells and disrupts glomerular capillary formation in neonatal mice

Platelet-derived growth factor (PDGF), a potent chemotactic and proliferation factor for mesenchymal-derived cells, has been demonstrated to play critical roles in kidney development. Two receptors for PDGF, PDGFR-alpha and PDGFR-beta, have been identified and we previously analyzed the effects of blockade of PDGFR-alpha signal in neonatal mice. In the current study, we examined the role of PDGFR-beta in glomerular development by blocking PDGFR-beta signal in neonatal mice by administration of antagonistic anti-PDGFR-beta monoclonal antibody. Unlike the mice injected with anti-PDGFR-alpha antibody, the mice injected daily with anti-PDGFR-beta antibody could be kept alive at least for 2 weeks after birth but showed severe disruption of the glomerular structure, whereas no apparent deformation was observed in the collecting ducts. In the disrupted glomeruli, the number of the mesangial cells was reduced markedly. Electron microscopic analysis and immunohistochemical studies with terminal deoxynucleotidyl transferase nick-end labeling staining revealed that the capillary endothelial cells of the glomeruli in the outer cortex region underwent apoptosis. However, the glomeruli located near the medulla were less affected. Because PDGFR-beta is not expressed in the endothelial cells, the effects of the blockade of PDGFR-beta might have caused glomerular endothelial cell apoptosis by inducing the loss of mesangial cells and/or pericytes.