Antiviral effect of sulfated sialyl lipid against a clinical strain of adenovirus

PURPOSE: Currently, there is no antiviral drug for adenovirus(AdV). We have reported that sulfated sialyl lipid(NMSO) 3, a NMSO, has an antiviral effect against AdV prototype strains. We evaluated the antiviral inhibitory effect and the mechanism of NMSO 3 against AdV strains from patients with conjunctivitis in vitro. METHODS: Viruses used for the experiment were clinically isolated AdV type 3(AdV 3), AdV type 4(AdV 4), type 8(ADV 8), AdV type 19(AdV 19), and type 37(AdV 37). We examined three antiviral agents, i.e., NMSO 3, cidofovir(HPMPC), and zalcitabine(ddC). 50% effective concentration(EC50), 50% cytotoxic concentration(CC50), and selectivity index(SI) of compounds were determined for AdV infection in HEp-2 cells using 3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods. We also evaluated the anti-AdV activity of NMSO 3 when it was added during the stage of virus adsorption. RESULTS: NMSO 3, HPMPC, and ddC showed an inhibitory effect against all five AdV clinical strains. The EC50 values of NMSO3 were lower than those of HPMPC and ddC. NMSO 3 exhibited minimal cytotoxicity. NMSO 3 inhibited AdV infection only when it was added during the stage of virus adsorption. CONCLUSIONS: NMSO 3 inhibited the replication of all clinical AdV serotypes tested. NMSO 3 was the most potent and selective anti-AdV compound. The mechanism of anti-AdV activity by NMSO 3 was inhibition of viral adsorption to cells.     

Effect of human cationic antimicrobial protein 18 Peptide on endotoxin-induced uveitis in rats

PURPOSE. Human cationic antimicrobial protein 18 (hCAP18, 18 kDa) was originally identified in leukocytes on the basis of its antimicrobial activity. The peptide composed of the 27 C-terminal amino acids of hCAP18 (hCAP18(109-135)) binds lipopolysaccharide (LPS). The purpose of the present study was to investigate the effects of hCAP18 peptide on endotoxin-induced uveitis (EIU) in rats. METHODS. EIU was induced by footpad injection of LPS. Each rat was injected intravenously with 1, 10, or 100 micro g hCAP18 peptide in 0.1 mL of PBS immediately after LPS injection in male Lewis rats. At 24 hours after LPS injection, enzyme-linked immunosorbent assay was performed to evaluate concentrations of protein, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, prostaglandin (PG)-E2, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 in aqueous humor. Also, EIU was evaluated by counting inflammatory cells in aqueous humor. RESULTS. hCAP18 peptide at 10 and 100 micro g significantly suppressed an LPS-induced increase in the number of inflammatory cells and the levels of protein, NO, TNF-alpha, PGE2, MCP-1, and MIP-2. The anti-inflammatory effect of 10 micro g hCAP18 peptide was as strong as that of 100 micro g hCAP18 peptide. Treatment with 1 micro g hCAP18 peptide did not suppress EIU, compared with the LPS group. CONCLUSIONS. The present results indicate that hCAP18 peptide suppresses development of EIU. A possible mechanism for the ocular anti-inflammatory effect of hCAP18 peptide is that it suppresses onset of LPS-triggered inflammatory reactions by binding directly to LPS.     

The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?

The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation. IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.     

Detection of pannus by multidetector-row computed tomography

Prosthetic valve dysfunction (PVD) due to pannus formation is an infrequent but serious complication. A 72-year-old man who underwent aortic valve replacement was diagnosed with PVD and aneurysm of the Sinus of Valsalva. Multidetector-row computed tomography (MDCT) was used to examine the cause of PVD before reoperation. MDCT demonstrated that tissue regarded as pannus extended from the left ventricular septum into the pivot guard. These findings were confirmed by observations during reoperation. MDCT can be a useful diagnostic technique for the anatomical and functional evaluation of PVD.     

Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers

Chemoresistance is a major problem in the chemotherapy of non-small cell lung cancers (NSCLCs). Several mechanisms are thought to be involved in drug resistance, including those associated with apoptosis, drug transport and detoxification. Here, we investigated the predictive value of P53, Bcl-2 and lung resistance-related protein (LRP) expression for response to platinum-based chemotherapy, using transbronchial biopsy (TBB) specimens from patients with NSCLC. We evaluated TBB specimens from 57 patients with NSCLC who had not previously been treated with either chemotherapy or radiotherapy before TBB, and who were treated with systemic platinum-based chemotherapy. The specimens included 33 adenocarcinomas, 22 squamous cell carcinomas and two large cell carcinomas. One to 6 courses of chemotherapy were administered. Expression of P53, Bcl-2 and LRP was analyzed by immunohistochemistry using TBB specimens. Positive expression of P53, Bcl-2 and LRP was observed in 28 (49%), 41 (71%) and 42 (73%) of the 57 NSCLCs, respectively. P53 expression correlated significantly with response to chemotherapy in nonsquamous cell carcinomas, including adenocarcinomas and large cell carcinomas (response rates, 38% and 6% for patients with P53-positive and P53-negative tumors, respectively, P =0.03). LRP expression significantly correlated inversely with response to chemotherapy in squamous cell carcinomas (response rates, 33% and 100% for patients with LRP-positive and LRP-negative tumors, respectively, P=0.02). Bcl-2 expression did not correlate with response to chemotherapy. These findings indicate that im-munostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups. (Cancer Sci 2003; 94: 394–399)     

Ethnic difference in serology of Helicobacter pylori CagA between Japanese and non-Japanese Brazilians for non-cardia gastric cancer

The usefulness of serology against CagA of Helicobacter pylori as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear among several ethnic populations with a high prevalence of cagA-positive strains. We investigated ethnic differences of CagA serology in two sets of case-control subjects, Japanese-Brazilians (JB) and non-Japanese Brazilians (NJB). We performed a cross-sectional comparison of IgG antibody titers to CagA (CagA-Ab) and the combination of CagA-Ab with conventional surface antigen (Hp-Ab) in 80 JB and 178 NJB ncGC patients and their controls (160 JB and 178 NJB). The level of CagA-Ab titer in cancer cases was significantly higher in NJB than in JB. The strength of the association between CagA-Ab seropositivity (+) (>10 U/ml) and ncGC was almost 2-fold higher in NJB than in JB [odds ratio (OR) (95% confidence interval), 4.5 (2.6–7.8) and 2.1 (1.2–3.6), respectively]. However, in both JB and NJB, the OR was highest in CagA-Ab(+) subjects with low titer (10–29 U/ml), and decreased inversely with elevating CagA-Ab titer. In addition, the serological status of CagA-Ab(+) and Hp-Ab(-) showed a similar close association with ncGC between JB and NJB [5.4 (1.9–15.3) and 5.4 (2.0–15.0), respectively]. These results suggest that although the roles of CagA in the carcinogenic process of ncGC might be different between JB and NJB, the CagA-Ab could be a useful marker for ncGC, independently of ethnicity, particularly in high-risk individuals with the serological status of CagA-Ab(+) with low IgG titer or combined with Hp-Ab(-). (Cancer Sci 2003; 94: 64–69)     

Initial predictors of development of pure red cell aplasia in myasthenia gravis after thymectomy

Pure red cell aplasia (PRCA) is well known to be concomitant with myasthenia gravis (MG), but it is difficult to predict the development of PRCA in patients with MG. Of 135 patients with MG, four (2.9%) had PRCA. All patients developed PRCA after thymectomy during a period when MG was in remission. The frequencies of thymoma, bulbar involvement and high anti-acetylcholine receptor (AChR) antibody levels were significantly higher in four patients with PRCA. Japanese MG patients with these characteristics at presentation were at significant risk for the development of PRCA after thymectomy.     

Wiskott-aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia with small platelets, eczema, recurrent infections, autoimmune disorders, IgA nephropathy, and an increased incidence of hematopoietic malignancies. The identification of the responsible gene, WASP (Wiskott-Aldrich Syndrome Protein), revealed clinical heterogeneity of the syndrome, and showed that X-linked thrombocytopenia without, or with only mild immunodeficiency and eczema, is also caused by mutations of WASP. The study of WASP and its mutations demonstrates how a single gene defect can cause multiple and complex clinical symptoms.     

A Collision Tumor Composed of Adenocarcinoma and Malignant Lymphoma in the Remnant Stomach After Pancreatoduodenectomy: Report of a Case

The occurrence of a collision tumor in the stomach, consisting of adenocarcinoma and malignant lymphoma, is extremely rare. We report herein the case of a patient who had undergone a pancreatoduodenectomy for bile duct cancer 5 year earlier, in whom an ulcerating tumor of the remnant stomach developed and grew rapidly within 5 months. Surgical exploration revealed a tumor in the remnant stomach, multiple liver metastases, and multiple lymph node metastases. Total resection of the remnant stomach was performed, and pathological examination revealed a collision tumor consisting of adenocarcinoma and malignant lymphoma. The patient died of liver metastases and lymph node metastases 7 months after his second operation. The coexistence of both adenocarcinoma and malignant lymphoma of the remnant stomach and the etiology of this unusual combination, never previously reported, is discussed. Received: December 20, 1999 / Accepted: November 20, 2000     

Surgical Management of a Graftenteric Fistula: A Modified Method of In Situ Reconstruction

Between December 1989 and May 1998, we performed a modified method of in situ reconstruction on three of seven patients with graftenteric fistulas (GEFs) at the Kurume University Hospital. The modification involved performing an anastomosis of the infrarenal abdominal aorta and running a new prosthesis through the left side of the descending colon in the retroperitoneal cavity, and wrapping the proximal anastomosis and the proximal site of the prosthesis in the greater omentum. Good results were achieved in all three patients. We describe herein this modified method of in situ reconstruction for a GEF and summarize the case reports of these three patients. Received: February 2, 2000 / Accepted: July 25, 2000