Search PubMed⌕ Search

Biomedical subjects

K Aozasa

Publications and source records attributed to K Aozasa.

At least 19 recordsLinked to original sources
PubMed1997

Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region: close association with CD56+ immunophenotype and polymorphic-reticulosis morphology.

Association between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has been demonstrated. NTL has 2 types of histologic figures: one is ordinary non-Hodgkin's lymphoma (NHL) with monomorphous proliferation, and the other is polymorphic-reticulosis (PR) morphology. The presence of the EBV genome and its sub-types (A and B) were examined on paraffin-embedded specimens from 36 cases of sino-nasal lymphomas (SNL) collected from Seoul, Republic of Korea, where the frequency of NTL is high. Patients' ages ranged from 2 to 74 years (median 54 years) with a male-to-female ratio of 2.5:1. Immunophenotypically, 8 cases were B-cell type, 11 were T-cell type with CD56-, 14 were CD56+ type, and 3 were null-cell type. Five of 11 cases with ordinary NHL of T-cell type and 9 of 14 cases with PR were CD56+. The EBV genome was found by polymerase chain reaction (PCR) and in the tumor cells by in situ hybridization (ISH) in 1 of 4 B-cell type (25%), 5 of 10 T-cell type (50%), 11 of 13 CD56+ type (85%), and in both of null-cell type (100%). Of 16 cases with PR morphology, 15 (94%) were positive for the EBV genome. All of the 5 NTLs of ordinary NHL with CD56- were negative for EBV. Concerning the sub-type of EBV, 16 cases had type A, while none had type-B EBV. These findings suggest that NTL comprises 2 groups: EBV-positive NTLs are CD56+ and/or histologically PR, and EBV-negative NTLs are CD56- and histologically ordinary NHL. The current results on Korean patients, together with earlier studies on Japanese and Malaysian patients, have shown the predominance of type-A EBV in sino-nasal lymphoma in Asia.

Adolescent↗
PubMed1996

Expression of Epstein-Barr virus latent infection genes and oncogenes in lymphoma cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of the B-cell type and contain Epstein-Barr virus (EBV) DNA. We have established 2 lymphoma cell lines from biopsy specimens of PAL cases, OPL-1 and OPL-2, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. OPL-2 exhibited a more rapid growth and higher saturation density than OPL-1, and only OPL-2 exhibited colony-forming activity in soft agar. OPL-1 and -2 were positive for B-cell differentiation markers and showed clonal surface immunoglobulins. Both line contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. OPL-1 and -2 contained type B and A EBV genome, respectively. Expression of EBV nuclear antigen (EBNA)2 mRNA and protein was detected by Northern and Western blot analysis in OPL-1, but not in OPL-2. On the other hand, the expression of latent membrane protein (LMP)1 mRNA in both OPL-1 and -2 was extremely weak and detectable only by reverse transcription-polymerase chain reaction. Protein expression of LMP1 was not observed by Western blot analysis or immunocytochemistry. Both lines expressed c-myc mRNA. Only OPL-1 expressed mRNA of c-fgr, an oncogene whose expression is upregulated by EBNA2. Both OPLs expressed bcl-2 mRNA without detectable expression of LMP1 protein.

Aged↗
PubMed1996

Histologic changes in small cell lung carcinoma after treatment.

BACKGROUND: Small cell lung carcinoma (SCLC) has been divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. Patients with mixed SC/LC show a worse prognosis than those with pure SCLC. METHODS: Persistence of histologic subtype in SCLC in the primary sites during the course of treatment or in the different organs at autopsy was examined. For this purpose, biopsy or cytologic specimens before chemotherapy, and autopsy specimens from 175 patients with SCLC were reviewed. They included 147 (84%) men and 28 (16%) women with an age range of 29-83 (median, 65) years. RESULTS: The frequency of mixed SC/LC in the primary sites was statistically higher in autopsy (14.3%) than that in biopsy or cytology specimens (8.6%) (P < 0.05). At autopsy, involved organs were categorized into two groups according to frequency of appearance of mixed SC/LC, i.e., a higher frequency group, including the liver (31 of 85; 36.4%), adrenal gland (15 of 56; 26.8%), brain (6 of 9; 66.7%), and extrathoracic lymph nodes (17 of 59; 28.8%) and a lower frequency group, including the lung (metastatic sites) (12 of 102; 11.8%), pleura (8 of 74; 10.8%), and intrathoracic lymph nodes (12 of 94; 12.8%). The difference in frequency between these two groups was statistically significant (P < 0.05). CONCLUSIONS: These findings suggest that primary pure SCLC can progress to mixed SC/LC with an increased potential for distant metastasis.

Adult↗
PubMed1996

Epstein-Barr virus in Hodgkin's disease patients in Japan.

BACKGROUND: The association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiologic, and molecular biologic studies. The high level of EBV association with HD in the developing countries was discussed in relation to the high HD incidence in these areas. Japanese HD shows a distinct peak incidence in older adults. In contrast, Western HD shows a bimodal pattern, the first peak in young adulthood and a second peak in older patients. In the present study, the EBV association with HD in Japan was investigated, and the results were compared with those reported from industrialized and developing countries. METHODS: Fifty-seven patients with HD were studied for the presence or absence of the EBV genome by the polymerase chain reaction and in situ hybridization methods. Seven cases were excluded from the analysis for EBV because of poor preservation of nucleotides in the specimens. RESULTS: EBV genomes were detected in the Reed-Sternberg (R-S) cells of 32 of the 50 patients examined (64%). The EBV association was independently affected by histologic subtype (84% in mixed cellularity and 44% in others), sex (76% in males and 31% in females), and age (76% in patients aged 40 years and older and 38% in patients younger than 40 years of age; P < 0.01). High EBV association is found at the peak in older adults predominantly with mixed cellularity type. Previous studies revealed that the high EBV was associated with the older peak of the bimodal peaks in Western HD, and a unimodal peak in childhood in developing countries. The EBV subtype was predominantly type A, which is identical to the immunocompetent type of HD reported previously. CONCLUSIONS: The results of the current study, together with those reported previously, showed that the presence of the Epstein-Barr virus correlated with mixed cellularity type, age older than 40 years, and male sex.

Adolescent↗
PubMed1996

Prognostic factors in angiosarcoma: a multivariate analysis of 55 cases.

Data for prognostic factors in angiosarcoma (AS) are limited, prompting a large-scale study of AS with multivariate analysis. To analyze prognostic factors in angiosarcoma (AS), clinical and histologic findings in 55 patients collected from hospitals in Japan were reviewed. Prognostic factors were evaluated by univariate and multivariate Cox's proportional hazards models. The study involved 32 males and 23 females, ages 18-93 (median, 69) years. The primary sites of tumors included head and neck (32 cases), trunk (10), extremities (3), spleen (3), breast (3), and other (4). The overall 2-year survival rate was 21%. Univariate analysis of clinical factors including age, sex, size and depth of tumor, tumor-related symptoms, interval between onset of symptoms and admission, surgical procedures, adjuvant chemotherapy, and adjuvant radiotherapy showed that age, tumor size, and mode of treatment were significant for survival. Histologic factors analyzed were mitotic counts, cellularity, cellular pleomorphism, extent of necrosis, vascular differentiation, and nonspecific diagnosis. Only mitotic counts were significant for prognosis. Multivariate analysis on these four factors revealed that tumor size, mode of treatment, and mitotic counts were independent prognostic factors.

Adolescent↗
PubMed1996

Occurrence of monocytoid B lymphocytes in lymph nodes of patients treated by chemotherapy.

Occurrence of monocytoi B lymphocytes (MBL) in the lymph nodes of patients receiving preoperative chemotherapy for cancer was examined and compared to lymph nodes in controls who had not received chemotherapy. Number of patients receiving and not receiving preoperative chemotherapy were 3 and 10 cases in ovarian cancer, 7 and 11 in testicular cancer, and 22 and 8 in lung cancer, respectively. Chemotherapeutic agents for ovarian, testicular, and lung cancer consisted of cisplatin, Adriamycin, and cyclophosphamide; cisplatin, vinblastine, and bleomycin; and cisplatin, vindesin, and mitomycin, respectively. MBL were defined morphologically as having abundant pale cytoplasm with distinct cell borders and small nucleus. Immunohistochemistry revealed a B-cell nature of these cells, i.e., CD20+ and/or MB-1+ together with negative reactivity for antibodies for T lymphocytes (CD43, CD45RO, OPD4) and macrophages (KP-1, PGM-1). Monocytoid cells in two cases showed a positive reactivity for CD43 together with CD20. The occurrence rate of MBL in patients with ovarian, lung, and testicular cancer receiving and not receiving chemotherapy was 67% (2/3) and 10% (1/10), 59% (13/22) and 75% (6/8), and 43% (3/7) and 9% (1/11), respectively. The occurrence rate in the total patients receiving chemotherapy (56%) was significantly higher than for those not receiving chemotherapy (28%) (P < 0.05). These findings suggest that chemotherapy-induced depressed immune function is causative for the occurrence of MBL in the lymph nodes. MBL might be found more frequently in nodes from patients who have received chemotherapy in certain settings.

Adult↗
PubMed1996

Pyothorax-associated lymphoma.

In 1987, we reported three patients with pleural lymphoma developed after a 22-30 year history of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Based on the pathologic and epidemiologic studies, we regarded the chronic pyothorax (CP) to be etiologically important in the development of pleural lymphoma. Through a nation-wide study in Japan, 37 cases of pleural lymphoma were collected. Pleural lymphoma had developed during the 20 year history of CP in all patients. Histologically all were non-Hodgkin's lymphoma with the diffuse large cell type being the most common. Immunologic and immunohistochemical studies revealed that 32 out of 33 cases were of B-cell lymphoma. From these findings, we proposed the term pyothorax-associated lymphoma (PAL). We examined the presence of Epstein-Barr virus (EBV) genome on the paraffin-embedded specimens in 34 PAL cases and 16 cases of CP alone. Combined polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry revealed that the EBV genome was detected in lymphoma cells in all PAL, but only one of the cases with CP alone. These findings suggested the etiological role of EBV for the development of PAL. We also described here the character of cell lines established from PAL, association of PAL with Kaposi's sarcoma-associated herpes virus, results of a case-control study on risk factors for development of PAL, and p53 mutations.

Empyema, Pleural↗
PubMed1996

Hepatoid adenocarcinoma of the endometrium associated with alpha-fetoprotein production.

A 66-year-old woman was hospitalized with a 2-month history of vaginal bleeding. Computed tomography and magnetic resonance imaging on admission showed a uterine tumor. The serum alpha-fetoprotein (AFP) level was 16,170 ng/ml (normal < 20). A total hysterectomy with bilateral salpingo-oophorectomy and regional lymphadenectomy were performed. A grayish-white tumor with focal necrotic areas was located in the posterior wall of the corpus uteri with smaller nodules in the lateral wall of the cervix. The tumor had two histologic patterns: one was a well-differentiated endometrioid adenocarcinoma and the other consisted of nests of cells resembling hepatocytes. In the hepatoid areas, giant cells and mitotic figures were frequent. Tumor cells in both the hepatoid areas and the glandular areas were immunoreactive for AFP. The tumor was diagnosed as a hepatoid adenocarcinoma of the uterus, the first described in this site, although 23 cases of hepatoid adenocarcinoma arising in the stomach, lung, kidney, ovary, duodenum, and urinary bladder have been reported.

Adenocarcinoma↗
PubMed1996

Induction of aldose reductase gene expression in LEC rats during the development of the hereditary hepatitis and hepatoma.

We examined age-related changes in the protein and the mRNA expression of aldose reductase in livers of Long-Evans with a cinnamon-like color (LEC) rats, which develop hereditary hepatitis and hepatoma with aging, using Long-Evans with an agouti color rats as controls. The levels of the protein and mRNA of aldose reductase increased after 20 weeks, at the stage of acute hepatitis, and were maintained at 60 weeks of age, while those of aldehyde reductase seemed to be constant at all ages. The expression of aldose reductase was marked in cancerous lesions in hepatoma-bearing LEC rat liver compared to uninvolved surrounding tissues. These results indicated that elevation of aldose reductase accompanied hepatocarcinogenesis and may be related to the acquisition of immortality of the cancer cells through detoxifying cytotoxic aldehyde compounds.

Aging↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in body cavities.

DNA sequences belonging to the recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV), now provisionally designated human herpesvirus 8, have been previously identified in an uncommonly occurring subset of AIDS-related lymphomas, referred to as body-cavity-based lymphomas (BCBLs), which present as lymphomatous effusions. Pyothorax-associated lymphomas (PALS) are non-Hodgkin's lymphomas that arise in the pleural cavity after long-standing pleural inflammation resulting from therapeutic artificial pneumothorax or from tuberculosis pleuritis. Although PALs present as solid tumor masses, they are otherwise similar to BCBLs in that they also are B cell lymphomas, usually exhibit immunoblastic morphology, and contain Epstein-Barr virus. We investigated whether KSHV sequences are present in 2 BCBLs in patients without AIDS and 12 in Japanese and 2 French PALs. The 2 BCBLs were positive for KSHV sequences, whereaas all 14 PALs were KSHV negative. This finding strongly suggests that BCBLs and PALs are distinct clinicopathological entities and further strengthens the association between the presence of KSHV and an effusion phenotype. Based on these findings, we propose replacing the term body-cavity-based lymphoma with the term primary effusion lymphoma, which describes these non-Hodgkin's lymphomas more accurately and avoids confusion with other lymphomas that may occur in the body cavities, such as the PALs.

Aged↗
PubMed1996

Malignant lymphoma of the adrenal gland: its possible correlation with the Epstein-Barr virus.

Initial manifestation of malignant lymphoma in the adrenal gland is a rare event, and clinical and pathologic features are not fully understood. We conducted a nationwide study in Japan, and 20 patients with malignant lymphoma that showed initial and main manifestation in the adrenal gland were identified. Clinical and pathologic findings were summarized. In addition, the presence of the Epstein-Barr virus (EBV) genome in the tumor cells was examined by using polymerase chain reaction (PCR) and in situ hybridization (ISH), together with the immunohistochemical evaluation of the expression of latent membrane protein-1 (LMP-1). There were 13 men and seven women; their ages at admission ranged from 40 to 87 years (median, 65 yr). Fever, anemia, and elevation of lactic dehydrogenase levels were the common presenting findings. One patient had acquired immunodeficiency syndrome. Adrenal tumors were bilateral in 15 patients and unilateral (all in the left site) in five. Prognosis was very poor; all but two patients died within 1 year after admission. Histologically diffuse large cell type was the commonest type (14 specimens). Immunohistologically, 16 specimens were B-cell type, and one was T-cell type. Another three specimens showing no positive reaction for any antibodies were also judged as B-cell type on purely morphologic grounds. Prominent intravascular proliferation of tumor cells was found in five patients. PCR for EBV genomes gave positive results in five patients; the virus was subtyped as A in three patients and as B in two. The ISH provided positive signals in nine samples, including all five specimens positive for PCR. Four of the nine cases with detectable EBV by PCR and/or ISH expressed LMP-1. The present study shows that adrenal lymphoma is EBV associated and has a B-cell phenotype.

Adrenal Gland Neoplasms↗
PubMed1996

Interleukin-6-mediated growth enhancement of cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PAL are diffuse large cell lymphoma of B cell type that contain Epstein-Barr virus DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Because PAL develop in the sites of chronic inflammation, inflammatory cytokines might be involved in the lymphomagenesis. To address this point, we examined the regulation of the growth of OPL by human IL-6. Human recombinant IL-6 enhanced the growth rate of OPL. OPL-1 responded to recombinant IL-6 by growing faster even at concentrations of less than 0.1 ng/ml, whereas OPL-2 required higher concentrations of recombinant IL-6. OPL expressed IL-6 receptor mRNA detectable by reverse transcriptase PCR analysis and IL-6 receptor on cell surface by flow cytometric analysis, using anti-IL-6 receptor antibodies. On the other hand, only OPL-1 showed expression of IL-6 mRNA, which was detectable only by reverse transcriptase PCR, and secreted IL-6 protein into the culture media. The culture supernatant of OPL-1 exhibited growth-enhancing effects on OPL-1 and OPL-2. The addition of anti-IL-6 antibodies to the cultures inhibited the growth of OPL-1 but not OPL-2. OPL-2 did not secrete IL-6 protein into the media, and the culture supernatant from OPL-2 did not enhance growth of OPL-2. These findings suggest the involvement of IL-6 in the growth regulation of OPL, i.e., an autocrine mechanism of IL-6-related proliferation in OPL-1 and a paracrine mechanism in OPL-2. IL-6 locally produced in chronic pyothorax might also promote the development of PAL.

Base Sequence↗
PubMed1996

[Large granular lymphocyte leukemia].

Large granular lymphocyte leukemia (LGLL) is defined as clonal proliferation of LGLs in peripheral blood. The following studies were conducted to address some issues in chronic LGLL. (1) Chronic LGLL is characterized by the indolent course, and the diagnosis of leukemia is difficult in such patients as those without distinct organomegaly and/or any evidence of monoclonality. We performed immunohistological studies in a patient with persistent NK lymphocytosis. No organomegaly had been seen in the patient during a three-year-observation, who died from cerebrovascular accident. The autopsy findings revealed multi-organ infiltration including spleen, liver, bone marrow, lymph nodes and lung. These findings suggest that the cells of chronic LGLL have infiltrative capacity characteristic of malignant cells. (2) Lymphocytosis in chronic LGLL is usually stable for a long period. We found that both T- and NK-LGLL cells strongly expressed CD95, an apoptosis related protein. Anit-CD95 did not induce apoptosis, but suppressed proliferation induced by IL-2 or anti-CD3. These results suggest that CD95-CD95 ligand system is involved in the slow cell growth characteristic of chronic LGLL. (3) CD4+CD8+ double positive (DP) cases are rarely seen in LGLL, and the physiologic counterpart of the leukemic cells has not been determined yet. We found that the DP-LGLL had alpha alpha type in the CD8 subunit and did not express RAG-1, these findings being characteristic of peripheral T cells. We also found that they expressed IL-4 mRNA and secreted IL-4 on activation. These results strongly suggest that DP-T-LGLL represents an expansion of a rare subset of peripheral DP-T cells, possibly derived from IL-4 activated CD4 single positive T cells.

Aged↗
PubMed1996

[LGL lymphoma].

We reported in this article two patients with large granular lymphocytic lymphoma (abbreviated as LGL lymphoma). One was the patient with LGL leukemia/lymphoma (patient 1) and other was the patient with NK-LGL lymphoma (patient 2). Because the gene of TCR delta was rearranged in the patient 1, the clonality of the LGL leukemia/lymphoma was confirmed. However, it is not determined yet whether the lineage of tumor cells is T cells or NK cells. The cytochemical features of the lymphoma cells of the patient 2 were studied. It was found that NK cell-derived lymphoma cells of the patient were positively stained with these two monoclonal antibodies that are reactive with T cell; one is anti-CD45RO (UCHL-1) and other is anti-CD3. Judging from the result, malignant NK-LGL cells in some patients are cytoplasmic CD3+ and UCHl-1+. It is emphasized that May-Grünwald-Giemsa stain of biopsied specimen of the lymphoma is required for making the diagnosis of LGL lymphoma.

Adult↗
PubMed1995

Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.

E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.

Aging↗
PubMed1995

Use of immunohistochemical procedures in diagnosing angiosarcoma. Evaluation of 98 cases.

BACKGROUND: Differential diagnosis of angiosarcoma, predominantly showing a non- or poorly vasoformative proliferation from other types of sarcomas, poorly differentiated carcinomas, and amelanotic melanoma, is often problematic. METHODS: The use of antibodies directed against Factor VIII-related antigen (FVIIIRA), Ulex europaeus lectin type 1 (UEA-1), CD31, and vascular endothelial growth factor (VEGF) in the diagnosis of angiosarcoma was examined in 98 cases of autopsy-proven angiosarcoma diagnosed during 1974-1990 in a survey of 178 Japanese hospitals. Reactivity of angiosarcoma cells for epithelial membrane antigen, cytokeratin, and melanoma cell antigen (HMB45) also was examined. RESULTS: Histologic specimens were formed exclusively by vasoformative areas in 32 cases and combined vasoformative and varying extents of non- or poorly vasoformative areas in another 66 cases. In vasoformative areas, the proliferating cells showed a diffuse positive reaction in the cytoplasm and/or cell surface for anti-FVII-IRA in 82 (84%) of 98 cases, for anti-CD31 in 78 (80%), and for UEA-1 in 69 (70%). In non- or poorly vasoformative areas, the positivity rate for FVIIIRA, CD31, and UEA-1 was 29%, 62%, and 46%, respectively. A positive reaction was found for either one of three endothelial markers in the non- or poorly vasoformative areas of 57 cases (86%). Epithelial membrane antigen and anticytokeratin antibody were positive in 4 and 11 cases, respectively, in the vasoformative areas and in 3 and 14 cases, respectively, in non- or poorly vasoformative areas with a simultaneous positive reaction for either one of three endothelial cell markers. None of the proliferating cells showed a positive reactivity for HMB45. The positivity rates of the angiosarcoma cells for each marker were different according to the primary tumor sites. The angiosarcoma cells in non- or poorly vasoformative areas showed the lowest positivity rate for anti-FVIIIRA in the heart (9%) and for anti-CD31 in the extremities (17%) and the highest positivity rate for anticytokeratin in the trunk (60%). Ulex europaeus lectin type 1 had almost the same reactivity rate (30-56%) in every organ. Angiosarcoma cells in 13 (36%) of 36 biopsy specimens and 8 (14%) of 56 autopsy specimens were positive for the anti-VEGF antibody. CONCLUSION: These findings suggest that the combined use of endothelial cell markers including FVIIIRA, UEA-1, and CD31 is useful in the diagnosis of angiosarcoma, especially in cases exclusively with a non- or poorly vasoformative pattern.

Adolescent↗