Requirement of N-glycan on GPI-anchored proteins for efficient binding of aerolysin but not Clostridium septicum alpha-toxin.

Aerolysin of the Gram-negative bacterium Aeromonas hydrophila consists of small (SL) and large (LL) lobes. The alpha-toxin of Gram-positive Clostridium septicum has a single lobe homologous to LL. These toxins bind to glycosylphosphatidylinositol (GPI)-anchored proteins and generate pores in the cell's plasma membrane.

Significance and diagnostic accuracy of renal calculi found by ultrasonography in patients with asymptomatic microscopic hematuria.

Background: The purpose of the present study was to evaluate the clinical significance and the accuracy of the diagnosis of renal calculi incidentally found by ultrasonography (US).

Methods: A total of 906 subjects (639 men and 267 women) aged 18-78 years were referred for asymptomatic microscopic hematuria. Of these, 743 patients who underwent US were studied.

A case of cutaneous ganglioneuroma developing within a lesion of seborrheic keratosis.

A 67-year-old man noticed on the abdominal skin a coin-sized verrucous plaque, in which a small granulation-like lesion developed several weeks before the first consultation at our clinic. The histology of the biopsied granulation-like lesion showed a well demarcated, but not associated with the collagenous capsule, mass of proliferating eosinophilic cells, consisting of intervening spindle-shaped Schwann cells and mature ganglion cells scattered in the tumor nest. We diagnosed this tumor nest as a ganglioneuroma, which rarely develops in the skin tissue.

Identification of a receptor-binding domain of Bordetella dermonecrotic toxin.

Bordetella dermonecrotic toxin (DNT) stimulates the assembly of actin stress fibers and focal adhesions by deamidating or polyaminating Gln63 of the small GTPase Rho. DNT is an A-B toxin which is composed of an N-terminal receptor-binding (B) domain and a C-terminal enzymatically active (A) domain. In this study, to analyze the functional and structural organization of DNT, we prepared 10 clones of hybridoma producing anti-DNT monoclonal antibodies.

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors.

A convenient synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines via Pictet-Spengler reaction using titanium(IV) isopropoxide and acetic-formic anhydride.

A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.

In vivo modifications of small GTPase Rac and Cdc42 by Bordetella dermonecrotic toxin.

Bordetella dermonecrotic toxin (DNT) is known to activate the small GTPase Rho through deamidation or polyamination. In this study, we examined whether Rac and Cdc42, the two other members of the Rho family, serve as intracellular targets for the toxin. Immunoprecipitation and immunoblot assays revealed that DNT deamidated or polyaminated intracellular Rac and Cdc42.

Dominant-negative Rho, Rac, and Cdc42 facilitate the invasion process of Vibrio parahaemolyticus into Caco-2 cells.

To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.

Congestion of superior mesenteric veins and small bowel mucosal injury after endoscopic treatment of esophageal varices in patients with portal hypertension.

We investigated treatment-induced changes in venous return from the small bowel and small bowel intestinal mucosal injury induced by the treatment of esophageal varices in patients with portal hypertension. A total of 14 patients (age 59.8+/-9.

Escherichia coli cytotoxic necrotizing factors and Bordetella dermonecrotic toxin: the dermonecrosis-inducing toxins activating Rho small GTPases.

Escherichia coli cytotoxic necrotizing factors (CNFs) and Bordetella dermonecrotic toxin (DNT) have been recently found to comprise a novel family of dermonecrosis-inducing toxins which activate the small GTPases of the Rho family. They are single chain polypeptides consisting of an N-terminal domain responsible for binding to target cells and a C-terminal catalytic domain. CNFs (CNF1 and 2) and DNT share in the catalytic domain about 30% identical residues and a consensus sequence where the catalytically active center Cys resides.

Intramolecular capture of pummerer reaction intermediates by an aromatic nucleophile: selective construction of 1,4-benzothiazine and indole ring systems.

The simple alkyl sulfoxide 6 carrying two aromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction conditions), underwent an intramolecular aromatic sulfenylation of the 6-exo-tet process in an exclusive manner to yield two regioisomeric 1,4-benzothiazine derivatives, 8 and 9. On the other hand, a similar reaction of the alpha-acyl sulfoxide 7, possessing identical aromatic nucleophiles, caused an intramolecular aromatic alkylation of the 5-exo-trig process to produce the 3-oxo-indole derivative 14 in a quantitative yield. These results demonstrate that the construction of 1,4-benzothiazine and indole ring systems can be achieved in a selective manner by proper choice of the sulfoxide side chain.

A synthesis of 3-phenyl-1,2,3,4-tetrahydroisoquinoline and 2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine via Pummerer-type cyclization: enhancing effect of boron trifluoride diethyl etherate on the cyclization.

A synthesis of 6,7-dimethoxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline (14a) and 7,8-dimethoxy-2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine (14b) was achieved via the cyclization of N-(3,4-dimethoxyphenyl)methyl-1-phenyl-2-(phenylsulfinyl)ethylformamide (6a) and N-2-(3,4-dimethoxyphenyl)ethyl-1-phenyl-2-(phenylsulfinyl)-ethylformamide (6b) using the Pummerer reaction as a key step, respectively. The Pummerer reaction of 6a,b under usual conditions using trifluoroacetic anhydride yielded the vinyl sulfides (8a, b), non-cyclized products, as a major product. The cyclization proceeded when boron trifluoride diethyl etherate was used as an additive reagent, thus giving rise to the corresponding cyclized products (7a) and (7b) in moderate yields.

A dual signaling cascade that regulates the ectodomain shedding of heparin-binding epidermal growth factor-like growth factor.

Ectodomain shedding is an important mechanism to regulate the biological activities of membrane proteins. We focus here on the signaling mechanism of the ectodomain shedding of heparin-binding epidermal growth factor (EGF)-like growth factor (pro HB-EGF). Lysophosphatidic acid (LPA), a ligand for seven-transmembrane G protein-coupled receptors, stimulates the shedding of pro HB-EGF, which constitutes a G protein-coupled receptor-mediated transactivation of the EGF receptor.

Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide.

Recent investigations have demonstrated the efficacy of autologous dendritic cells (DCs) pulsed with tumor antigens to generate tumor-specific CTLs against cancer cells. Melanoma antigens (MAGE) are a family of tumor-specific antigens shown to be expressed in various tumors, including bladder cancers and melanoma, but not in normal tissues except for the testis. Because invasive bladder cancers are frequently reported to express MAGE, we explored the possibility of establishing a new immunotherapeutic modality against advanced bladder cancer using autologous DCs pulsed with one of the MAGE-3 epitope peptides (IMPKAGLLI), which is synthesized to bind specifically to HLA-A24.

Useful applications of DNA repair tests for differential diagnosis of atypical dyschromatosis symmetrica hereditaria from xeroderma pigmentosum.

Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease characterized by the presence of pigmented and hypopigmented macules on the extremities and freckles on the face. However, if clinical features are not fully developed in infantile patients, it is difficult to differentiate DSH from xeroderma pigmentosum by clinical features alone. A 2-year-old boy (patient 1), revealed atypical features of DSH with slight susceptibility to sunburn.

Synthesis of methoxy-2-quinolones via pummerer-type cyclization of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides.

The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the synthesis of methoxy-2-quinolones.

Long-term follow-up of sustained responders to interferon therapy, in patients with chronic hepatitis C.

Interferon (IFN) therapy has been proven to induce the normalization of serum alanine aminotransferase (ALT) levels and to eradicate the hepatitis C virus (HCV) in some patients with chronic hepatitis C, and these patients are usually defined as 'sustained responders'. However, there have been some reports of hepatocellular carcinoma (HCC) in these patients, and the development of HCC remains life-threatening in patients who clear HCV. We analysed the long-term prognoses of patients with chronic hepatitis C in whom HCV was eradicated with IFN.

Eradication of hepatitis C virus 1b by interferon in a health care worker with acute hepatitis following needlestick transmission from a patient with chronic hepatitis C unresponsive to interferon.

Hepatitis C virus (HCV) was successfully eradicated by a short course of interferon (IFN) therapy in a nurse with acute HCV infection from a needlestick accident. The source patient had chronic hepatitis C and was a nonresponder to IFN therapy. The HCV genotype was 1b in patients, and a single point mutation (H-->R in amino acid 2218) was observed in the IFN sensitivity-determining region of the nonstructural 5A gene, in comparison with sequences of HCV-J, in HCV RNA from both the source patient (before and after IFN therapy) and the recipient (before IFN therapy).

Long-term follow-up of periodontitis in a patient with Chédiak-Higashi syndrome. A case report.

Chediak-Higashi syndrome (CHS) is an extremely rare hereditary disease characterized by leukocyte dysfunction. We report on a 21-year-old woman who presented at the age 9 years with CHS and serious periodontal tissue destruction around erupted teeth. The patient had received systemic, radiographic, immunological, microbial, and clinical periodontal examinations since childhood.

Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: a liposome-mediated gene therapy treatment for bladder cancer.

We have developed a novel liposome-mediated immunogene therapy using interleukin 2 (IL-2) and B7.1 in a murine bladder cancer model. A carcinogen-induced murine bladder cancer cell line, MBT-2, was transfected with cationic liposome 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleolylphosphatidylethanolamine and IL-2 plasmid.

Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients.

Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein.

Claudins (claudin-1 to -18) with four transmembrane domains and two extracellular loops constitute tight junction strands. The peptide toxin Clostridium perfringens enterotoxin (CPE) has been shown to bind to claudin-3 and -4, but not to claudin-1 or -2. We constructed claudin-1/claudin-3 chimeric molecules and found that the second extracellular loop of claudin-3 conferred CPE sensitivity on L fibroblasts.