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Biomedical subjects

K Nasu

Publications and source records attributed to K Nasu.

At least 181 records · Page 10Linked to original sources

Distinctive phorbol ester-induced morphological and surface antigen changes in mycosis fungoides, the Sézary syndrome, and adult T-cell leukemia.

Clinical and pathological studies of cutaneous T-cell lymphomas (CTCL) reveal variations in tumor cell morphology and surface membrane phenotype that are of diagnostic and prognostic importance. Our study investigates blastic transformation and surface antigen change on CTCL cells in vitro under the influence of tumor-promoting phorbol ester (TPA) and phytohemagglutinin. Both agents transformed tumor cells with cerebriform nuclei into blast cells within 5 days; however, Sézary cells were somewhat resistant to transformation with phytohemagglutinin. Multinucleated cells with prominent nucleoli resembled Reed-Sternberg cells of Hodgkin's disease. These morphological changes simulated the appearance of the aggressive tumor stage of mycosis fungoides. During blastic transformation, the erythrocyte rosette receptor was induced by TPA on sheep erythrocyte-rosette-negative Sézary cells from one patient. During the first 24 hr in vitro, Sézary and MF cells stimulated by TPA lost Leu 3a (T4) antigen while maintaining original high levels of Leu 1 antigen. In contrast, leukemia cells from patients with adult T-cell leukemia (ATL) were resistant to modulation of Leu 3a antigen by TPA; 3A1 antigen on CTCL and ATL cells was unaffected by TPA. Blastic transformation of CTCL cells was observed with both TPA and phytohemagglutinin, but helper T-cell antigen Leu 3a (T4) and erythrocyte rosette receptor changes occurred only with TPA. Thus, blastic transformation and surface differentiation were not directly related. These results provide a possible model for the study of blastic transformation and surface antigen/receptor variation in CTCL. They also may provide an independent test for the distinction of CTCL and ATL in vitro. Finally, they illustrate the relative resistance of ATL to surface antigen modulation as previously shown for Tac antigen modulation by anti-Tac antibody.

Adult↗

Karyotype evolution in B-cell lymphoid malignancy with an 8;14 translocation.

To evaluate the significance of karyotypic evolution of tumor cells with an 8;14 translocation [t(8;14)(q24;q32)], we examined the clinicopathologic features and immunologic phenotypes of nine Japanese patients with various types of B-cell malignancy with the translocation. All these patients had structural rearrangements of the long arm of chromosome No. I (Iq) in a stem line or the subline of tumor cells with a t(8;14). The rearrangements were composed of a translocation involving Iq with other chromosomes and a tandem duplication of Iq, and they were exclusively associated with a partial trisomy for Iq. Two patients with diffuse large-cell lymphoma, whose tumor cells did not express surface immunoglobulins (s-Ig), had the Iq translocation in their highly complex karyotypes. Tumor cells from the other seven patients expressed s-Ig and the karyotypes were relatively simple. Among these patients, the Iq translocation was found in two patients with Burkitt's lymphoma, and the Iq duplication were observed in a stem line or the sublines from four patients with Burkitt's lymphoma-leukemia and one each with small non-cleaved-cell or diffuse large-cell lymphoma. Except for one patient in the stage of IE, these patients had a poor prognosis because of the clinical conversion of extranodal metastases in the earlier disease phase. These findings are compatible with those of Western patients with a t(8;14). Therefore, tumor cells marked primarily with a t(8;14) could have "major routes" in the karyotypic evolution, for which potentials should be recognized as clinical risk factors, and the morphologic presentation and the expression of surface immunoglobulins may be associated with the process of karyotypic evolution.

Adult↗

Co-existence of malignant squamous cells and herpes simplex virus type 2-infected cells.

A case is presented in which malignant squamous cells and herpes virus infected cells were recognized concomitantly at routine cytologic examination for detection of cervical cancer. Further examinations on admission revealed Stage Ib carcinoma of the cervix and characteristic pathologic changes of herpetic infection in the tumor cell nests. Virus was isolated from the cancerous tissues in the ectocervix following radical hysterectomy, and was identified as herpes simplex virus type 2 (HSV-2). The typical HSV-2 particles were detected by electron microscopic observation on the infected FL monolayer cells with isolation. Neutralizing antibody levels against HSV-2 declined and remained low after hysterectomy. The HSV-2, isolated and identified, might be considered as "passenger" virus. The role of this isolated virus as an etiologic agent of the cervical cancer was not clear.

Carcinoma, Squamous Cell↗

Cytogenetic approaches to the clarification of pathogenesis in lymphoid malignancies: clinicopathologic characterization of 14q+ marker-positive non-T-cell malignancies.

The clinicopathologic features of 53 patients with various types of non-T-cell malignancies were compared with the karyotypic findings. Although all chromosomes underwent numerical and structural rearrangements, a 14q+ marker chromosome (14q32 translocation), which was found in 31 patients, was the single most common abnormality. In terms of survival, no significant difference was noted between the 14q+ positive and negative patients. Donor chromosomes of a 14q32 translocation, which were identified in 27 patients, were quite variable. However, certain chromosomes were predisposed to act as donor chromosomes in the 14q32 translocation. An 8;14 translocation [t(8;14) (q24;q32)] was found in six patients with diffuse non-Burkitt's lymphoma and in four patients with Burkitt's lymphoma-leukemia; in all these patients a stem line or the subline with a t(8;14) had partial trisomy for 1q. An 11;14 translocation [t(11;14) (q13;q32)] was observed in one patient each with diffuse or follicular lymphoma and in two with myeloma; three of the four patients had also structural rearrangements of chromosome 1 in the same cells. A 14;18 translocation [t(14;18) (q32;q21)] was found in six patients with follicular lymphoma and in one with diffuse lymphoma; however, no common involvement of other chromosomes was detected among clones of these abnormal cells with a t(14;18). The median survival was 8 months for patients with a t(8;14) and 39 months for patients with a t(11;14). The difference between the two survival curves was of borderline significance [p = 0.06]. In contrast, patients with a t(14;18) survived significantly longer than those with a t(8;14) [p less than 0.001] or those with a t(11;14) [p = 0.03]. These findings revealed that in non-T-cell malignancies, the clinicopathologic features of the patients with a 14q+ marker depend upon the precise 14q32 translocation and the subsequent karyotypic evolution, although the translocation was not always correlated with a particular type of lymphoid malignancy.

Adult↗

Incidence of antibody to adult T-cell leukemia-virus-associated antigen among T-cell malignancies in the Kyoto District, with a report of two unusual cases.

Titration of antibody to adult T-cell leukemia (ATL)-virus-associated antigen (ATLA) is of much help for diagnosing ATL, because almost all patients with ATL are seropositive even in an ATL-nonendemic area such as Kyoto. In T-cell lymphoma, anti-ATLA antibody was thought to be related to the birthplace of the patients and the epidermotropism of their skin lesions, but it was not confirmative because the number of cases was so small. We present here two curious cases of anti-ATLA-negative T-cell leukemia/lymphoma. A 53-yr-old man, born in a nonendemic area, had manifestations similar to those of ATL except for the lack of skin involvement, but the morphology of his leukemic cells was less like that of ATL cells than that of prolymphocytic leukemia cells. Therefore, his leukemia was not diagnosed as ATL. A 52-yr-old woman, whose parents' hometown was in an endemic area, showed typical manifestations of nonleukemic T-cell lymphoma, and her biopsied lymph node was compatible with diffuse, pleomorphic lymphoma histologically. In the latter patient, the negative anti-ATLA finding might be due to titration sensitivity. Therefore, the clinical and hematologic features are still informative for distinguishing ATL from other T-cell malignancies.

Antibodies, Viral↗

Establishment and cytological characteristics of two in vitro T-cell lines derived from a child with acute lymphatic leukemia and a man with adult T-cell leukemia in Japan.

Two permanent T-cell leukemia lines designated KH-1 and KH-2 were established from the peripheral blood of a 9-year-old boy with acute lymphoblastic leukemia and a 47-year-old man with adult T-cell leukemia (ATL). No T-cell growth factor was used. KH-1 cells grew as single cells and KH-2 cells formed clusters in suspension culture. Erosette formation, the absence of immunoglobulin determinants and Epstein-Barr-virus-associated nuclear antigen, and the presence of T-cell antigens revealed by monoclonal antibodies were characteristics of these cell lines as in other established T-cell leukemia lines. Chromosome analysis at the beginning revealed mosaic presence of cells with 46, XY, t(8q+; 15q-) and 46, XY which was later completely replaced by the latter karyotype in KH-1, and abnormal karyotype, 47, XY, +3, t (8q-; 10p+) was maintained throughout the period of in vitro passage in KH-2. The donor patient of KH-2 formerly lived in the south-western part of Japan where ATL is considered endemic and numerous type-C virus particles were detected electron microscopically, in KH-2 cell pellets.

Cell Line↗

Several marker analyses of T-lymphoma cells in eight Japanese adults.

Lymphoma cells in eight adult Japanese patients with no evidence of overt leukemia throughout their clinical course were demonstrated to be of T-cell nature by combining studies of various immunologic cell surface markers and cytochemistry. The histologic diagnosis of these patients was diffuse histiocytic lymphoma in four patients, poorly differentiated lymphocytic lymphoma in two patients and mixed histiocytic and lymphocytic lymphoma in two patients, according to Rappaport's classification. In seven of the eight patients, the malignant appearance and the large number of E-rosetting cells readily led to the diagnosis of T-cell lymphoma. Human Ia-like antigens were unexpectedly detected on the malignant T cells in seven of the eight patients. TdT activity was elevated in two of the four patients tested. Acid phosphatase activity was always observed in the neoplastic T-cells, and this activity was tartrate resistant. Focal activity of acid alpha-naphthyl acetate esterase was detected in the malignant cells with somewhat mature appearances, but large immature cells had no or weak dispersed activity. Except for E-rosetting ability, malignant T-cells showed such variable properties that multiple marker analyses seem to be necessary in the diagnosis and the prediction of prognosis of these disorders. Frequent occurrence of T-cell malignancy in Japan was also discussed.

Adult↗