Characteristics of cutaneous lymphomas in Osaka, Japan (1988-1999) based on the European Organization for Research and Treatment of Cancer classification.

Based on accumulating information, European investigators proposed a new classification for primary cutaneous lymphomas known as the European Organization for Research and Treatment of Cancer (EORTC) classification. The clinical utility of this classification in Japanese cases has not been evaluated. Material from 65 patients with cutaneous lymphomas (48 with primary disease and 17 with secondary disease) who were admitted to Osaka University Hospital during the period 1988 through 1999 was reviewed.

Cytologic finding of chyloascites in lymphangioleiomyomatosis. A case report.

Background: Lymphangioleiomyomatosis is a rare disease, histologically characterized by an abnormal proliferation of smooth muscle around the lymphatics. Lung is the most common site of involvement, and patients usually present with dyspnea, chest pain, and cough. Chylous pleural effusion and ascites occasionally appear during the course of the disease.

Role of hypermethylation of DAP-kinase CpG island in the development of thyroid lymphoma.

Death-associated protein-kinase (DAP-Kinase) is a serine/threonine kinase with a death domain that is involved in apoptosis induced by interferon-gamma, TNF-alpha, and Fas ligand. Epigenetic down-regulation of DAP-Kinase gene expression by hypermethylation of its promoter region was reported in B-cell malignancies. Previous pathoepidemiologic studies indicated that thyroid lymphoma (TL) evolves among active lymphoid cells in chronic lymphocytic thyroiditis (CLTH).

Epstein-Barr virus associated B-cell lymphoma of brain developing in myelodysplastic syndrome with c-kit mutation (Try-557 -->stop).

The first case of B-cell lymphoma of brain in a patient with myelodysplastic syndrome (MDS) was reported. A 68-year-old man was admitted because of anemia, fever, and thrombocytopenia and was diagnosed as having MDS (refractory anemia with excess of blasts) on the basis of the findings of bone marrow aspiration and chromosomal analysis. The patient was followed up without chemotherapy, but a brain tumor appeared after 3 years.

Sequences of cytotoxic T-lymphocyte epitopes in the Epstein-Barr virus (EBV) nuclear antigen-3B gene in a Japanese population with or without EBV-positive lymphoid malignancies.

Latent infection antigens of EBV, including EBV nuclear antigens (EBNAs) and latent membrane proteins, are expressed in latently infected and immortalized B cells but work as target antigens for host cytotoxic T-lymphocyte (CTL) responses in an HLA class I-restricted manner. Among these latent antigens, the immunodominant CTL epitopes in EBNA3B (EBNA3B 399-408 and EBNA3B 416-424) are well characterized. Mutations and strain differences in these sequences, compared to the prototype A sequence, reduce CTL responses to latently infected B cells.

Expression of interleukin-7 and its receptor in thyroid lymphoma.

Patho-epidemiological studies have shown that thyroid lymphomas (TL) develop in thyroids affected by chronic lymphocytic thyroiditis (CLTH). Cytokines produced in CLTH might play a pivotal role for lymphomagenesis, because previous reports indicate an important role of cytokines in lymphomagenesis. We examined the expression of interleukin-7 (IL-7), a pleiotropic cytokine that acts mainly on cells of the hematolymphoid system, and IL-7 receptor (IL-7R) in both TL and CLTH by RT-PCR.

p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of laser capture microdissected specimens from non-transition and transition zones.

Prostatic intraepithelial neoplasia (PIN) is characterized by intraluminal proliferation of epithelial cells and is divided into high-grade (HGPIN) and low-grade (LGPIN) lesions. HGPIN is regarded as the most likely precursor of prostatic cancer (PCA). Microdissected DNA selectively extracted from paraffin-embedded sections of 27 cases with PCA were analyzed for p53 mutation in exons 5 - 8 by single-strand conformation polymorphism of polymerase chain reaction-amplified DNA fragments (PCR-SSCP) followed by direct sequencing.

Interleukin-10 gene transfer improves the survival rate of mice inoculated with Escherichia coli.

Objective: To determine whether administration of recombinant adenovirus vectors encoding the interleukin (IL)-10 protein (AxCAmIL-10) decreases the mortality of septic mice.

Design: Prospective, randomized, controlled study.

Setting: University research laboratory.

Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination.

We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner.

[Genomic instability analysis in hereditary cancer syndrome].

The discovery of microsatellite instability (MSI) and its association to hereditary nonpolyposis colorectal cancer (HNPCC) in 1993 gave rise to a new criterion in tumor biology. By using five microsatellite markers, colorectal carcinomas (CRC) may be classified either as high frequency-MSI (MSI-H) if two or more of the five markers show instability, or as low frequency-MSI (MSI-L)/microsatellite stable (MSS) if one or less shows instability. MSI-H tumors which comprise about 15% of total CRC show distinctive clinicopathologic features: proximal colon location, mucinous and undifferentiated histology, presence of tumor-infiltrating lymphocytes, and a less aggressive clinical course.

Low frequency of HLA-A*0201 allele in patients with Epstein-Barr virus-positive nasal lymphomas with polymorphic reticulosis morphology.

Lymphoproliferative diseases of the nasal cavity and paranasal sinuses occur frequently in Asian countries and are histologically categorized as monomorphic ordinary lymphoma and polymorphic reticulosis (PR) with apparent inflammatory cell infiltration. The large atypical cells in PR show natural-killer cell nature and frequently contain Epstein-Barr virus (EBV) DNA. Among the EBV genes involved in latent infection, those encoding EBV latent membrane proteins are frequently expressed in PR.

Catheterized urine cytology of mucinous carcinoma arising in the renal pelvis. A case report.

Background: Primary mucinous carcinoma of the renal pelvis is a rare tumor; therefore, criteria for cytologic diagnosis of this tumor have not been established.

Case: An 81-year-old woman suffered from macrohematuria for six months and was found to have a tumor in the right kidney by radiographic examination. Catheterized urine obtained from the right renal ureter was viscous and contained spherical clusters of cells with occasionally vacuolated, lacy and basophilic cytoplasm.

Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6.

Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear.

Transition zone biopsy in the detection of prostate cancer.

Objective: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer.

Methods: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies).

Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated cell death.

Reactive oxygen species (ROS) released from polymorphonuclear leukocytes and macrophages could cause DNA damage, but also induce cell death. Therefore inhibition of cell death must be an important issue for accumulation of genetic changes in lymphoid cells in inflammatory foci. Scavengers in the post culture medium of four lymphoid cell lines, lymphoblastoid cell lines (LCL), Raji, BJAB and Jurkat cells, were examined.

Analysis of T-cell antigen receptor gamma chain gene rearrangement by polymerase chain reaction in combination with denaturing gradient gel electrophoresis in the differential diagnosis of cutaneous T-lymphoproliferative diseases.

A polymerase chain reaction (PCR)-based strategy has been developed for analysis of clonal rearrangement of the T-cell receptor gamma gene (TCR gamma) and was shown to be useful for detection of clonal T-cell populations. In this study, we performed PCR combined with denaturing gradient gel electrophoresis (DGGE) on fresh frozen biopsy samples from 16 patients with cutaneous T-lymphoproliferative diseases in whom a definite diagnosis was difficult to make on morphological and immunohistochemical grounds alone. Ages of the patients at biopsy ranged from 28 to 81 (median 62) years, and the subjects consisted of 8 men and 8 women.

Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan.

Sinonasal lymphoma is one of the constituents of lethal midline granuloma, which is a clinical term for progressive, destructive lesions affecting the midline of the face. The majority of sinonasal lymphomas, especially those showing polymorphous patterns of proliferation and thus termed polymorphic reticulosis, recently were categorized as sinonasal natural killer/T-cell lymphomas. They are more prevalent in Asia than Europe or North America and are associated with EBV infection.

Mutations of the p53 gene in nasal NK/T-cell lymphoma.

Mutations of the p53 tumor suppressor gene are reported in various kinds of malignancies including lymphomas. However, p53 gene mutations in nasal NK/T-cell lymphoma have not been reported because most parts of tumors are necrotic and a small amount of living tumor tissues is available for the molecular study. Expression and mutations of the p53 gene were examined in the paraffin-embedded specimens of the nasal lesions from 42 Chinese (Beijing and Chengdu) and Japanese (Okinawa and Osaka) patients with nasal NK/T-cell lymphoma by the immunohistochemistry and single strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) amplified products followed by direct sequencing.

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms.

Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.

Microsatellite instability and k-ras, p53 mutations in thyroid lymphoma.

Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type.

[Epstein-Barr virus and malignant lymphoma].

Association between Epstein-Barr virus and malignant lymphomas such as Burkitt's lymphoma, Hodgkin's disease(HD), nasal T/NK cell lymphoma(NTL), immunodefficiency-associated lymphoma, and pyothorax associated lymphoma (PAL) has been suggested. Among these, HD, SNL, PAL are relatively common in Japan. For HD, EBV association was found in the disease peak incidences; those are peak in older adults in Japan, older peak of the bimodal peaks in Western countries, and unimodal peak in the childhood in the developing countries.

Cancer immunotherapy targeting Wilms' tumor gene WT1 product.

The Wilms' tumor gene WT1 is expressed at high levels not only in acute myelocytic and lymphocytic leukemia and in chronic myelocytic leukemia but also in various types of solid tumors including lung cancers. To determine whether the WT1 protein can serve as a target Ag for tumor-specific immunity, three 9-mer WT1 peptides (Db126, Db221, and Db235), which contain H-2Db-binding anchor motifs and have a comparatively higher binding affinity for H-2Db molecules, were tested in mice (C57BL/6, H-2Db) for in vivo induction of CTLs directed against these WT1 peptides. Only one peptide, Db126, with the highest binding affinity for H-2Db molecules induced vigorous CTL responses.

Extent and zonal distribution of prostatic intraepithelial neoplasia in patients with prostatic carcinoma in Japan: analysis of whole-mounted prostatectomy specimens.

Background: Prostatic intraepithelial neoplasia (PIN), an intraluminar proliferation of epithelial cells in ducts and acini, is divided into high-grade (HGPIN) and low-grade (LGPIN), based on morphologies. HGPIN is considered to be a putative precursor of prostatic adenocarcinoma (PCA). Information on PIN has been limited in Japan, because PIN had not been regarded as a precursor lesion for PCA.

[Differential diagnosis of Hashimoto's thyroiditis from thyroidal neoplastic diseases].

Thyroid lymphoma is a relatively rare disease, but has attracted the attention of many investigators because of its putative relationship with Hashimoto's thyroiditis. The definite diagnosis of thyroid lymphoma, especially the histologic distinction from small cell carcinoma or Hashimoto's thyroiditis, has been problematical and even regarded as impossible during the past decades. Recent progress in immunological methods including molecular biology has resolved many of the diagnostic problems in this field, thereby providing a scientific basis for approaching these diseases.