Acute renal failure and hearing loss due to sodium bromate poisoning: a case report and review of the literature.

Acute renal failure with hearing loss due to sodium bromate intoxication is described. A 48-year-old woman who ingested permanent wave neutralizer in a suicide attempt and developed anuria was admitted to our hospital for hemodialysis. Bromate intoxication was suspected and hemodialysis was carried out; she required maintenance dialysis 3 times a week. Irreversible severe sensorineural hearing loss continued and peripheral polyneuropathy developed in the lower limbs. We measured the concentration of bromine in the serum before and after the first hemodialysis and found its removal rate to be 61.3%. This is the first report that proved the utility of hemodialysis for bromate intoxication in a clinical setting.

Preclinical study of adenoviral p53 gene therapy for esophageal cancer.

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.

Immortalization of human esophageal keratinocytes by E6 and E7 of human papillomavirus type 16.

Transduction of human papillomavirus type 16 (HPV16) E6/E7 into primary culture of human esophageal keratinocytes using a recombinant adenovirus prolonged the life-span, while untreated cells senesced within 14-16 population doublings (PDLs). Up-regulation of telomerase activity and acquisition of serum-resistant growth were observed in the esophageal keratinocytes with extended life-span between 50 and 100 PDLs, and drastically increased after 100 PDLs. A keratinocyte sample with a polymorphism of Pro/Pro at codon 72 of p53 showed resistance to HPV16 E6/E7-induced life-span-extension and immortalization, in contrast to others with p53 polymorphisms of Arg/Arg or Arg/Pro, which did not. The high efficiency of E6/E7-induction by adenovirus vector also revealed the M1 and M2 stages of keratinocyte immortalization first described in this report.

Case report: A case of lymphoepithelioma-like carcinoma of the oesophagus and review of the literature.

A 78-year-old Japanese female was admitted to our hospital with dysphagia and weight loss. An oesophageal tumour was demonstrated radiologically and endoscopically, and was diagnosed as oesophageal cancer by biopsy. Histologically, the resected tumour showed poorly differentiated squamous cell carcinoma with prominent lymphoid stroma and was diagnosed as the so-called lymphoepithelioma-like carcinoma (LELC). Epstein-Barr virus in the tumour was negative by polymerase chain reaction and in situ hybridization. Oesophageal LELC is extremely rare. The cases in the literature, as well as the one reported here, presented with gross features of a submucosal tumour-like appearance. Although the differentiation of the tumour cells is often poor, prognosis seems to be better than for other types of oesophageal cancer. Oesophageal LELC has characteristic clinicopathological features and should be classified by criteria independent of other types of tumour.

Primary Non-Hodgkin's Lymphoma of the Male Breast: A Case Report.

A 69-year-old Japanese man presented with bilateral gynecomastia and a soft, mobile and clearly defined mass beneath the left nipple. A round radiopaque masswas revealed on mammography. The tumor was homogeneous, hypoechoic and measured2.4 x 3.9 cm on ultrasonography. Based on a diagnosis of malignant lymphoma by needle aspiration cytology, a modified radical mastectomy with ipsilateral axillary lymph node dissection was performed. Malignant diffuse large B-cell type lymphoma was diagnosed histologically. Whole body examinations revealed no evidenceof other tumors. Three courses of adjuvant CHOP therapy were subsequently performed. The patient is free of recurrence 12 months after surgery. Primary non-Hodgkin's lymphoma (NHL) of the male breast is extremely rare. The occurrence of lymphoma in this patient could be related to elevated estrogen levels.

P16INK4a expression adenovirus vector to suppress pancreas cancer cell proliferation.

The prognoses of pancreatic cancer patients have been miserable even after radical surgery, and adjuvant therapy is necessary to improve the surgical results. p16(INK4a) (p16) is tight-binding and inhibitory protein for cyclin-dependent kinase 4 to induce G1 arrest of the cell cycle. p16 gene deletion is frequently identified in human pancreas cancer. The impaired gene function of p16 might be a major factor of the uncontrolled proliferation and malignancy of pancreas cancer cells. In this study, we investigated the effect of adenovirus p16 expression vector for pancreas cancer cell proliferation to clarify whether the vector might be a promising mode to assist the surgical therapy for pancreas cancer. We constructed the adenovirus p16 expression vector AdexCACSp16 by inserting p16 cDNA to a cassette cosmid containing a nearly full-length adenovirus type 5 genome with E1 and E3 deletions. Thereafter, we assessed the activity of AdexCACSp16 to induce p16 gene mRNA expression in pancreas cancer cell line MIAPaCa-2 and to control cell proliferation. AdexCACSp16 induced a high level of p16 gene mRNA expression in MIAPaCa-2 cells with 1 h contact to the cells. The cell proliferation was significantly suppressed by AdexCACSp16 compared with the control adenovirus group. These data indicate that AdexCACSp16 has the potential to induce p16 gene expression and control pancreas cancer cell proliferation and that the adenovirus p16 expression vector AdexCACSp16 might be a possible method of gene therapy to improve the surgical therapeutic results for pancreas cancer.

Benign esophageal stricture caused by diffuse severe esophagitis presenting as ascending fibrosis: report of a case.

A 46-year-old Japanese man was referred to our hospital for treatment of an esophageal stricture. Esophageal cancer was suspected after detailed investigations, and a right transthoracic esophagectomy was performed. The resected specimen showed only nonspecific esophagitis with severe fibrous thickening in the submucosa, but no evidence of malignancy. Between 1906 and 1993, only 19 similar cases of benign esophageal strictures with fibrous thickening, excluding congenital and iatrogenic strictures, have been reported in Japan. These lesions occurred in the middle to lower third of the esophagus in 15 of 19 cases (78.9%), and 8 of the 19 patients (42.1%) were aged between 30 and 50 years. The interval between onset and hospital admission was short, being less than 1 year in 8 of the 12 patients for whom this information was available. Our patient demonstrated a disorder resembling the diffuse severe esophagitis described by Roth in 1974.

Intracellular processing and immunogenicity of the envelope proteins of human T-cell leukemia virus type I that are expressed from recombinant vaccinia viruses.

Two types of recombinant vaccinia viruses (VVs) expressing the env gene of the human T-cell leukemia virus type I (HTLV-I) were reported previously. One recombinant VV, WR-proenv1, synthesized the authentic env protein. In the other recombinant VV, WR-env17, the env gene was inserted within the signal sequence of the VV hemagglutinin (HA) gene, so that the reading frame for the env gene was in phase with that for the HA gene. Comparative studies were performed on the mode of expression and processing of the env proteins in relation to their immunogenicity. In WR-env17-infected cells, translation was initiated exclusively from the initiation methionine of the HA to produce nascently the chimeric env protein, including the altered HA signal peptide. Both this altered HA signal peptide and the internalized env signal peptide functioned as insertion signals for the endoplasmic reticulum. Although about half of the nascent chimeric protein was cleaved at the carboxyl terminus of the internalized env signal peptide to produce the authentic env protein, the other half was cleaved at the carboxyl terminus of the altered HA signal peptide alone to synthesize the chimeric protein. These events led to a less efficient transport of the env protein produced by WR-env17 from the rough endoplasmic reticulum to the Golgi apparatus than that of the authentic env protein synthesized by WR-proenv1. The efficiency of the processing and transport of the env protein affected the immunogenicity of these two recombinant VVs.