[A case of T-cell malignancy with clinical manifestations of chronic leukemic reticuloendotheliosis].
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Biomedical subjects
Publications and source records attributed to M Shamoto.
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The effect of ascorbate in reducing Adriamycin toxicity has been examined in mice and guinea pigs. Ascorbate had no effect on the antitumor activity of Adriamycin in mice inoculated with leukemia L1210, but it significantly prolonged the life of mice and guinea pigs treated with Adriamycin. Adriamycin elevated lipid peroxide levels in serum and liver, and ascorbate prevented the elevation. The significant prevention of Adriamycin-induced cardiomyopathy by ascorbate was proved by means of electron microscopy. The earliest alterations of dilation of the sarcoplasmic reticulum and transverse tubular system and the appearance of a large number of cytoplasmic fat droplets, which were seen in cardiac tissue from guinea pigs receiving Adriamycin, were apparently reduced in animals that were treated with ascorbate.
An electron microscopic study of adult T-cell leukemia, which might be a new distinct disease entity of T-cell malignancies, is presented. The most characteristic feature of adult T-cell leukemia was an extremely irregular nucleus with condensed heterochromatin in the nuclear periphery, the greater part of which was very similar to the small-cell variant form of Sézary syndrome, although some nuclei were similar to normal-appearing lymphocytes or atypical lymphoid cells with slightly indented nuclei or Sézary cells. Nuclear pockets containing tubuloreticular structures and filamentous structures etc., were also characteristic. Regarding the cytoplasmic features, the appearance of clustered dense bodies seemed to be a distinguishing feature of adult T-cell leukemia. Tubuloreticular structures were also observed in some cases. The nature of the test tube-shaped or ring-shaped forms in rough endoplasmic reticulum, which appeared in one case, is not clear.
In case of blast crisis of chronic myelocytic leukemia, the blast cells contained several kinds of normal hematopoietic cells. The peroxidase reaction was strongly positive in the neutrophilic granules of the engulfed neutrophils. These engulfed cells appeared to be normal and the limiting membranes of the engulfing cells seemed to be intact. We speculated therefore that this phenomenon might be emperipolesis. In a case of chronic myelocytic leukemia and a case of acute myelocytic leukemia, some megakaryoblasts showed the same phenomenon. These megakaryoblasts did not phagocytize latex particles. The limiting membranes of the engulfing megakaryoblasts were stained with ruthenium red but those of the engulfed hematopoietic cells were not stained. By phase microscopy, the engulfed cells were actively moving inside the megakaryoblasts and it was observed that the engulfed cells were actually living within the engulfing cells. These results demonstrated that this phenomenon was emperipolesis. Observations with an electron microscope and the phase microscope are indispensable for distinguishing emperipolesis from phagocytosis.
In a 62 year-old male with chronic myelogenous leukaemia, an acute phase developed with appearance of large immature cells in the bone marrow. A significant proportion of these cells was found to have engulfed autologous immature and polymorphonuclear neutrophils, erythroblasts, red cells and platelets. These abnormal cells were Philadelphia chromosome positive, and considered to be derived from the leukaemic cell line. Electron microscopic examinations revealed, in the cytoplasm of engulfed cells, no lysosomes or phagosomes which are typically seen in phagocytic cells, nor any evidence of degenerative changes in either engulfing or engulfed cells. These findings suggest that this phenomenon be considered as emperipolesis rather than phagocytosis. The pathophysiological mechanism of this phenomenon is uncertain.
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The effect of 5-S-cysteinyl-L-3,4-dihydroxyphenylalanine (cys-dopa), an intermediate in the pathway from L-3,4-dihydroxyphenylalanine (L-dopa) to pheomelanin, on the growth of eight human tumor cell lines in culture was compared to that of L-dopa. The tumor cell lines tested comprise two neuroblastomas (NB-1 and YT-nu), two amelanotic melanomas (HMV and SEKI), a gastric carcinoma (MKN-28), and three squamous cell carcinomas (HeLa-S3, KB, and a salivary gland carcinoma). Cys-dopa at a concentration of 1 mM inhibited growth of NB-1 (66%), YT-nu (67%), HMV (44%), SEKI (60%), MKN-28 (47%), HeLa-S3 (24%), KB (64%), and salivary gland carcinoma (33%), while L-dopa exhibited similar or even lower degree of inhibition at a concentration of 6 mM. On the other hand, both catechols had little effect on the growth of two fibroblasts derived originally from normal tissues (mouse fibroblast L929 and Chinese hamster fibroblast Don-6). Cys-dopa and L-dopa inhibited DNA and protein synthesis in YT-nu cells, but RNA synthesis was less affected. Treatment with cys-dopa at a dose of 1000 mg/kg i.p. for 7 days prolonged by 50% the life span of mice inoculated with L1210 leukemia. Normal mice given cys-dopa at a dose of 1000 mg/kg for 12 days showed no signs of toxicity. These results suggest the potential of cys-dopa as an antitumor agent.
Virus-like particles which seemed to be oncogenic have not been observed clinically in human neoplasms. However, we found some virus-like particles in the cytoplasm of a few proliferating cells in the lymph nodes of one patient with angioimmunoblastic lymphadenopathy. These were very similar to intracytoplasmic type A particles seen in the Mazon-Pfizer monkey virus and a mammary tumor virus in a mouse.
A new classification for non-Hodgkin's malignant lymphoma is proposed as the one suited for the Lymphomas in Japan, which is to provide a new subtype "pleomorphic" for those more or less rapid-growing lymphomas of peripheral T-cell nature, along with another subtype lymphoblastic, after Nathwani et al. for those of central T-cell nature. The proposal is based on the result of the investigation by the Study Group for Histopathological Diagnosis on Malignant Lymphoma that (1) the presence of a significant number of T-cell lymphomas with peculiar "pleomorphism" is responsible for the very low reproducibility rate of histopathological diagnosis on the diffuse, mixed L&H type of Rappaport classification, and (2) the relative incidence of lymphoms as peripheral T-cell nature including the so-called adult T-cell leukemia is much higher in Japan than in the Western countries.
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Mitochondria, rough endoplasmic reticulum, Golgi apparatus and other cytoplasmic organelles were found within the nuclei, not in 'nuclear pseudo-inclusions', of some cells in several hematopoietic disorders. Mitoses were fairly often observed in the atypical cells of these cases. We suggest that these intranuclear cytoplasmic organelles may be trapped in the nucleus during an abnormal mitosis.
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Four cases of malignant histiocytosis with leukemic manifestations and chronic course were reported. Light microscopic, ultrastructural and ultrastructural cytochemical details of these atypical cells were demonstrated. Ultrastructurally these cells resembled hairy cells most closely among the known varieties of leukemic cells. However, ribosome-lamella complexes were not found and some atypical cells had a few short cytoplasmic projections. In addition, tartrate-resistant acid phosphatase was absent from these cells. We speculate that this leukemic reticuloendotheliosis with a chronic course seen in Japan seems to be analogous to malignant histiocytosis with massive splenomegaly reported by Vardiman et al.
Several mitotic histiocytes containing Langerhans cell granules were found in the lymph nodes of Letterer-Siwe disease. Some histiocytes of Hand-Schüller-Christian disease contained Langerhans cell granules within the nuclei. These Langerhans cell granules were not in 'nuclear pseudo-inclusions,' but were freely scattered inside the nuclei. We suggest that the Langerhans cell granules may get trapped in the nucleus during mitosis, since several investigators have suggested that mitosis causes other intranuclear organelles to get trapped. We also speculate that cells containing Langerhans cell granules may divide and increase by mitosis.
Hepatitis B surface antigen (HBsAg) in epoxy-embedded liver tissues can be stained by aldehyde-fuchsin stain. Sections are oxidized in KMnO4 acidified with H2SO4, then bleached in NaHSO3, both at 70 C. Heating for oxidation and bleaching are absolutely necessary. Diluted aldehyde-fuchsin stain adjusted to pH 1.5 to 1.8 with NaOH is used for staining. HBsAg is specifically stained purple. Other components such as mitochondria and bile pigments are also strained, but are easily distinguished from HBsAg. This staining method is advantageous for the identification of HBsAg-positive cells for electron microscopic observation.
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