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Biomedical subjects

H Wakasa

Publications and source records attributed to H Wakasa.

At least 19 recordsLinked to original sources

Histogenesis of diffuse small cleaved cell lymphoma. An immunohistochemical and molecular genetic (bcl-2 gene) study with comparison to follicular small cleaved cell lymphoma and mantle zone lymphoma.

Immunohistochemical and molecular genetic (bcl-2 gene) studies were performed on specimens from 24 patients with follicular small cleaved cell lymphoma (FSCCL), 24 patients with diffuse small cleaved cell lymphoma (DSCCL) and 4 patients with mantle zone lymphoma (MZL) to determine the cellular origin of the disease and whether or not DSCCL represents the diffuse counterpart of FSCCL. Two patients with FSCCL, 22 patients with DSCCL, and all of the patients with MZL had a phenotype of mantle zone (MZ) B-lymphocytes (SIgD+, Leu-1+, Leu-8+, positive alkaline phosphatase [ALPase+], and negative common acute lymphoblastic leukemia antigen [CALLA-]), and all the tested patients (2 patients with FSCCL, 13 patients with DSCCL, and 4 patients with MZL) had germlines of bcl-2 gene. Fourteen patients with FSCCL and 1 patient with DSCCL had a phenotype of follicular center cells (FCC) (CALLA+, SIgD-, Leu-1-, Leu-8- and negative ALPase), and 11 patients with FSCCL had bcl-2 gene rearrangements. These results indicate that FSCCL are almost always derived from FCC, whereas some FSCCL, most DSCCL, and all MZL are derived from MZ B-lymphocytes, and these lymphomas should be included in the same category as MZ B-lymphocyte-derived lymphomas. Histologically diagnosed DSCCL often may represent a diffuse counterpart of MZ B-lymphocyte-derived lymphoma. MZ B-lymphocyte-derived lymphomas histologically show a follicular (nodular), a follicular MZ, or a diffuse growth pattern and clinically show a high incidence of peripheral blood (PB) involvement or bone marrow (BM) involvement.

Adult

Establishment and characterization of a human T-cell lymphoblastic lymphoma cell line (HT-1) carrying an inversion of chromosome 14.

A new human lymphoblastic lymphoma cell line was established (designated HT-1) from the pleural fluid lymphoma cells of a patient with lymphoblastic lymphoma of T-cell type. The HT-1 cells expressed CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD57, and terminal deoxynucleotidyl transferase (TdT) but lacked B-cell-associated antigens and myeloid-associated antigens. In addition, HT-1 cells had rearranged T-cell receptor (TCR) beta-chain gene and gamma-chain gene but retained germlines of immunoglobulin (Ig) heavy chain gene. These findings indicate that HT-1 cell line represents a common thymocyte in the T-cell lineage. Cytogenetic studies revealed that HT-1 cells carry an inversion (inv) of the long arm of chromosome 14. This cell line is the second T-cell line carrying inv(14) chromosome and may be useful for the molecular investigation of the cytogenetic break points of inv(14).

Adult

Characterization and comparison of two newly established Epstein-Barr virus (EBV)-negative and EBV-positive Burkitt's lymphoma cell lines. EBV-negative cell line with a low level of expression of ICAM-1 molecule and EBV-positive cell line with a high level of expression of ICAM-1 molecule.

Two human Burkitt's lymphoma cell lines (HBL-4 and HBL-5) were established individually from two patients with small noncleaved cell lymphoma (Burkitt's type). The HBL-4 cell line is Epstein-Barr virus (EBV)-negative, and the HBL-5 cell line is EBV-positive. Cytogenetically, both cell lines had the same chromosomal translocation, t(8;14)(q24;q32) as those observed in the primary malignant cells from individual patients. Morphologic, immunophenotypic, cytogenetic, and molecular studies confirmed that both cell lines were derived from the primary lymphoma cells in vivo. HBL-4 cells lacked CD23(H107), CD11a(LFA-1), and latent membrane protein (LMP) but expressed CD54(ICAM-1) at low levels, whereas HBL-5 cells showed the high level of expression of CD54 and faint expression of LMP but lacked CD11a. In addition, the EBV-positive lymphoblastoid cell line (LCL) expressed CD11a, CD23, CD54, and LMP at high levels. Therefore, an HBL-5 phenotype with expression of CD54 and LMP tends toward an LCL phenotype, and the augmentation of CD54 on the HBL-5 cells in comparison with primary lymphoma cells is likely to be upregulated by LMP, probably resulting from the EBV infection. There was little difference in the BrdUrd uptake in vivo and in vitro, doubling time, tumorigenicity, and dynamics of tumor growth in athymic nude mice between both cell lines. These findings indicate that the potentiality of cell growth and tumorigenicity of these two cell lines are unlikely to be related with EBV.

Adult

Four cases of metastatic lymphoma into the temporal bone.

A histopathological study on 17 temporal bones obtained from 9 patients who died of malignant lymphoma revealed metastasis of malignant lymphoma in 7 temporal bones from 4 of them. There were no differences in stages at the initial diagnosis between the cases with metastasis and those without metastasis. However, the higher was the frequency of metastasis, the longer became the period from the first medical examination to death. In addition, malignant lymphoma was considered to metastasize into the temporal bone by the following two routes, 1) direct infiltration or invasion from the cerebrospinal fluid and 2) hematogenous metastasis or invasion.

Adult

Immunohistochemical evaluation with Ki-67: an application to salivary gland tumours.

Using Ki-67, a monoclonal antibody, the proliferating capacity of 15 salivary gland tumours, including nine pleomorphic adenomas, four adenoid cystic carcinomas, one mucoepidermoid carcinoma and one acinic cell carcinoma was determined immunohistochemically, using normal salivary gland tissue as a control. The frequency of Ki-67 positive cells was 4.7 percent in the normal salivary gland and one percent in pleomorphic adenomas, whereas the average frequency in malignant tumours was 18.3 percent. Among adenoid cystic carcinomas, the frequency was related to the morphological type; the solid sub-type had the highest frequency of Ki-67-positive cells. As this sub-type is recognized as the most aggressive of these tumours, this technique has the potential of providing an early indication of the clinical behaviour of a tumour.

Carcinoma, Adenoid Cystic

[CD3-negative natural killer cell leukemia with aggressive clinical course].

The authors report an autopsy case of CD3- large granular cell leukemia with an aggressive clinical course. A 15-year-old male was admitted to our hospital with complaint of high fever. Clinical examination revealed cervical lymphadenopathy and hepatosplenomegaly. His white blood cell count was 7,000/microliters with 45% large granular lymphocytes. A biopsy specimen of the cervical lymph node showed diffuse lymphoma, mixed small and large cells (DM). Surface marker analysis by immunohistochemical technique revealed that neoplastic cells expressed CD2, CD38, CD56 and HLA-DR but lacked CD3, CD4 and CD8. Southern blot analysis of immunoglobulin (Ig) and T cell receptor (TCR) genes showed germ line of Ig and TCR. These findings indicate that this case was a large granular cell leukemia with the natural killer cell phenotype. Despite anti-leukemic therapy, he died of hyperkalemia and acidosis. Autopsy showed a marked swelling of the liver (3,122 g) and spleen (2,434 g) with leukemic cell infiltration.

Adolescent

Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin's B-cell lymphomas.

Using three separate bcl-2 probes, we examined involvement of the bcl-2 gene in Japanese patients with non-Hodgkin's B-cell lymphomas. Of 52 patients with follicular lymphoma (FL), 24 had rearrangements. In a group of 50 patients with diffuse lymphoma, three of 32 patients with diffuse large cell lymphoma had rearrangements. The frequency of rearrangements in each of these groups, as detected by both major and minor breakpoint cluster region probes, was compatible with that found in other Far Eastern studies. However, the difference in frequency between the groups studied in the Far East and the West was significant, and these two geographically distinct populations also displayed a difference in the breakpoint distribution. In the immunophenotype study of 33 patients with FL, the expression of CD10 antigen correlated with bcl-2 involvement, whereas none of the other B markers emerged as parameters to distinguish between the two lymphoma groups; those with, and without, the rearrangements.

Humans

Necrotizing lymphadenitis: a clinicopathological and immunohistochemical study of four familial cases and five recurrent cases.

We report the clinicopathological and immunohistological findings of nine cases of necrotizing lymphadenitis, consisting of four cases of familial infection and five cases of recurrence. Fever, cervical lymphadenopathy, leucopenia and swelling of the tonsils are characteristic clinical findings. Morphological features of the lymph nodes include the presence of immunoblasts, plasmacytoid T cells, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Ultrastructurally, tubuloreticular structures are observed not only in lymphoid cells, but in vascular endothelial cells. Immunological studies of peripheral blood using monoclonal antibodies disclose that CD 8+ (Leu 2a+; suppressor/cytotoxic) cells predominate at the onset, but they gradually decrease with the clinical course and the ratio of CD 4+: CD 8+ (helper:suppressor) increases as the disease progresses. However, in the affected lymph nodes, CD4+ (Leu 2a+: helper/inducer) cells often increase with the clinical progression, but the ratio of CD 4+:CD 8+ in the lymph nodes does not correlate with clinical progression. In addition, Ki-67+CD 8+ cells are more often seen than Ki-67+CD 4+ cells. It is suggested that necrotizing lymphadenitis is an infectious disease in which CD 4+ cells are disrupted and CD 8+ cells undergo transformation to blastoid cells. This results in a change in the ratio of T subsets.

Adolescent

Monocytoid B lymphocytes and epithelioid cell clusters in abscess-forming granulomatous lymphadenitis. With special reference to cat scratch disease.

In order to clarify the appearance of monocytoid B lymphocytes (MBLs) in abscess-forming granulomatous lymphadenitis (AGL) and the relation between AGL and cat-scratch disease (CSD), 48 cases of AGL were studied histologically. MBLs were present in about 50% of AGL cases. Warthin-Starry (WS) silver stain-positive bacteria, which are the causative agent of CSD, were present in 52.4% of AGL cases with MBLs and 59.2% of AGL cases without MBLs. The appearance of MBLs in AGL was not related to various clinical features, including disease interval from initial lymphadenopathy to lymph node biopsy. Histologically, epithelioid cell clusters appeared in about 70% of MBL-positive AGL cases, but were not observed in MBL-negative AGL. Therefore, a close interaction between MBLs and epithelioid cells in AGL is suggested, and we emphasize that the histological features of some AGL cases resemble those of toxoplasmic lymphadenitis.

Abscess

A novel monoclonal antibody specific for human pre-B cell leukemia/lymphoma.

A novel monoclonal antibody, designated WH14-antibody (WH14-Ab), was produced by using a non-T ALL cell line (HBL-3) as an immunogen. 35S-labelled immunoprecipitate revealed that the antigen reacting with WH14-Ab was estimated to be 30 Kd. Immunoglobulin isotype of WH14-Ab was IgG1. In the normal hematopoietic tissue, WH14-Ab reacted with a small number of monocytes (less than 30%) in the peripheral blood, but neither with the lymphocytes nor granulocytes. WH14-Ab reacted with HBL-3 and REH, but not with other B-cell leukemia/lymphoma and EBV-transformed cell lines. In addition, WH14-Ab reacted with most non-T ALL and pre-B lymphoblastic lymphoma. WH14-Ab did not react with all T-cell lymphomas. These findings indicate that the WH14-Ab may recognize the cell surface determinant shared by immature B cells, especially pre-B cells, in the B-cell lineage. WH14-Ab may be useful not only for the detection of pre-B cell leukemia/lymphomas but also for the investigation of maturation and differentiation of B-cell lineage.

Animals

High incidence of 17p13 chromosomal abnormalities in malignant histiocytosis.

Cytogenetic analyses of three patients during autopsy who had a pathologic diagnosis of malignant histiocytosis and of one patient who was strongly suspected to have malignant histiocytosis because of her clinical and hematologic findings were done. All three patients studied with bone marrow specimens showed polyploidy (3.4-20%). Two of three patients with chromosomal abnormalities showed 17p+ markers with a breakpoint at 17p13. Seven of 22 previously reported malignant histiocytosis patients (32%) with descriptions of detailed whole karyotypes have the 17p+ markers, including two of the authors' patients. Five of seven patients with 17p+ involved 17p13. Although breakpoints at the 17p+ in the remaining two were not described, their karyotypes were shown to possibly involve 17p13. The high incidence of this abnormality is not considered accidental, and this breakpoint is not usual in many other neoplastic disorders. These facts may indicate that 17p13 chromosome abnormality is a specific change of malignant histiocytosis.

Adolescent

A newly established human acute lymphoblastic leukemia cell line with characteristics of the earliest B-cell maturation.

A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was established from the bone marrow of a patient with non-T-ALL. The HBL-3 cell line expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface immunoglobulin (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked the common acute lymphoblastic leukemia antigen (CALLA) and antigenic markers characteristic of T-cell and myeloid cell lineages. The HBL-3 cells had structural rearrangements of both the homologous chromosome 9s, including a translocation with chromosome 1 which has been reported in a patient with common ALL. The cell line had rearranged immunoglobulin heavy chain genes but retained germ-line kappa light chain genes and germ-line T-cell receptor beta- and gamma-chain genes. The HBL-3 cell line was strongly positive for terminal deoxynucleotidyl transferase (TdT). These findings indicate that the HBL-3 cell line is derived from the earliest B-cell committed to B-cell lineage.

B-Lymphocytes

A case of pancreatic oncocytic tumor.

An uncommon case of potentially malignant oncocytoma arising in the pancreatic tail of 54-year-old woman is reported. The tumor was encapsulated and measured 11 x 7 x 6 cm. The tumor cells were uniform in appearance, plump and polyhedral, with distinct finely granular eosinophilic cytoplasm, and were arranged in solid acinar groups. Electron microscopy revealed that the tumor cells contained numerous mitochondria in the cytoplasm. In the present case, the tumor cells showed perineural and small venous invasion in the pancreas and potentially malignant characteristics. However, neither recurrence nor metastasis has been detected 3 years after resection. These findings indicate that the present tumor had apparent low-grade malignancy.

Adenoma

A case of fibrous hamartoma of infancy: an immunohistochemical study.

To clarify the histogenesis and immunohistochemical nature of fibrous hamartoma of infancy, we have studied a typical case of this disease using an immunohistochemical technique with a large panel of antibodies. It was found that immature-appearing stellate and spindle-shaped cells were mesenchymal in nature, but it was not ascertained whether those cells were differentiated into various specialized connective tissues corresponding with embryonic stages of connective tissue differentiation. These results reveal the immunohistochemical nature of tissue components of fibrous hamartoma but poorly support the previously described concept that fibrous hamartoma of infancy is a hamartomatous disease.

Arm

[Two cases of allergic granulomatosis and angiitis (AGA); Churg-Strauss syndrome].

AGA is an angiitis syndrome that has some characteristic features, for example preceding asthma and polyneuritis. And histological findings are granulomatous angiitis or extravascular granuloma. We report two typical cases of AGA. Case 1; 51-year-old woman had been suffering from asthmatic dyspnea for one year and developed in 1987 multiple neuritis in her extremities. Eosinophilia and high level of IgE were noted. Pathologic diagnosis of the biopsied right calf muscle specimen was granulomatous angiitis. Case 2; 40-year-old woman had been suffering from asthmatic dyspnea for two years. She complained of severe cough and myalgia in 1986 and her chest X-ray showed homogeneous shadows in right upper and left lower fields. And her blood showed eosinophilia and high level of IgE. The histology of the biopsied subcutaneous nodules of hands showed extravascular granuloma. These two cases had specific features of AGA. About symptoms of angiitis, case 1 showed multiple neuritis and case 2 had subcutaneous nodules of hands. About laboratory data, case 1 showed WBC count of 9400/mm3 with 85% eosinophils and high level of IgE at 1400 IU/ml, case 2 had WBC count of 13200/mm3 with 22% eosinophils and IgE at 846 IU/ml. The vary of eosinophil count and IgE level were related to the degree and course of illness. These symptoms and laboratory data, except neuritis, improved by an administration of prednisolone. In early stage of AGA, prednisolone is effective, so the criteria of AGA and usage of corticosteroids must be considered.

Adult

[A primary malignant lymphoma of the appendix].

A malignant lymphoma (ML) of the gastrointestinal tract occurs most frequently in the stomach, and ML of the appendix is very rare, with only 16 cases reported in the Japanese literature. Reported is a case of a primary ML the appendix in a 48 year old male, in whom an ileocecal resection was carried out. This case was pathohistologically diagnosed as a diffuse large lymphoma of the B cell type, according to the LSG classification. Therapeutic problems were encountered because of the difficulty in making an early diagnosis.

Antineoplastic Combined Chemotherapy Protocols

Common acute lymphoblastic leukemia-associated antigen (CALLA)-positive B cell lymphoma.

We analyzed the expression of common acute lymphoblastic leukemia-associated antigen (CALLA) in 134 cases of non-Hodgkin's lymphoma of the B cell type using an immunohistochemical method. The incidence of CALLA expression in B cell lymphomas was higher in follicular lymphomas (29%) than in diffuse lymphomas (15%). Malignant lymphoma (ML), follicular small cleaved cell (FSC) according to the histologic type, showed a considerably high incidence of CALLA (43%), whereas ML, diffuse small cleaved cell (DSC) displayed a very low incidence (5%). These findings suggest the possibility that these two morphologically similar lymphomas may be derived from distinct populations of B cells [CALLA+-germinal center (GC) cells, CALLA- -germinal center (GC) cells or mantle zone (MZ) cells]. In addition, one case of DSC expressed surface immunoglobulin D (SIgD) and alkaline phosphatase (ALPase) as well as CALLA. This indicates that CALLA-positive small cleaved cell lymphoma expressing SIgD or ALPase may represent neoplastic proliferation of CALLA-positive MZ cells of secondary follicles in lymph nodes.

Antigens, Differentiation