Letter: Classification of non-Hodgkin's lymphomas.
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Biomedical subjects
Publications and source records attributed to I Katayama.
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The pathognomonic "hairy cell" of leukemic reticuloendotheliosis was studied for ultrastructural localization of tartrate-resistant acid phosphatase activity. The enzyme activity could not be demonstrated by Gomori's method, but it was readily demonstrated in the cytoplasmic vesicles and Golgi saccules of the hairy cell by substitution of naphthol AS-BI phosphoric acid for Na-beta-glycerophosphate of Gomori's medium. This apparent substrate specificity may be used as a marker for electron microscopic identification of the hairy cell, and may facilitate the study of histogenesis of leukemic reticuloendotheliosis.
The pathognomonic neoplastic reticulum cells, or "hairy cells" of leukemic reticuloendotheliosis from 6 patients were studied with the electron microscope. These cells demonstrated characteristic ultrastructural features which were distinctly different from those of lymphocytes, monocytes, or histiocytes. In 3 patients a distinctive ribosome-lamella complex was found. The biologic significance of this unusual cytoplasmic inclusion is still unknown. Its frequent presence in leukemic reticuloendotheliosis and its rarity in other neoplastic diseases suggest a substantial yet unexplained relationship between this complex and leukemic reticuloendotheliosis.
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"Toxic" neutrophils from humans with severe bacterial infections, identified by the presence of Döhle bodies, "toxic" granules, and vacuoles were shown to differ from normal neutrophils both in ultrastructure and in lysosome activity. Döhle bodies were identified as lamellar aggregates of rough endoplasmic reticulum. Toxic granules corresponded to the azurophilic granules usually identified by Romanowsky stains only in neutrophil precursors. By electron microscopy such granules were large, electron-dense, and peroxidase positive; they could usually be distinguished from the smaller, less dense, "specific" granules also present in control neutrophils, but in the latter they became visible by light microscopy only after prolonged staining or following fixation with glutaraldehyde. These observations suggest that toxic granules represent an abnormal staining reaction of the large dense granules in the toxic cells, and not phagocytized material, newly formed abnormal granules or autophagic bodies. Alkaline phosphatase activity was significantly greater in toxic neutrophils than in normal ones; 80% of the activity of both was located in the lysosome fraction. Beta glucuronidase was normal. Total acid phosphatase was normal, but the percentage located in the nonlysosome fraction of toxic neutrophils was increased, suggesting that lysosomes were "labilized." Formation of neutral red vacuoles in supravitally stained preparations, an index of lysosome activity, occurred more rapidly in toxic neutrophils. This reaction paralleled degranulation and the formation of clear vacuoles in unstained wet mounts and could be blocked by colchicine, a lysosome stabilizer, or enhanced by procedures which activate lysosomes. "Autophagic" vacuoles were observed by electron microscopy in some toxic neutrophils. These observations are discussed in relation to the concept that the "toxic" neutrophils in severe bacterial infection reflect cellular immaturity and/or stimulation or degeneration.
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Spiro and coworkers found a 35000 dalton membrane protein (p35) expressed abundantly in hairy cells of a subset of white, American patients with hairy cell leukemia. They subsequently identified p35 to be the human homologue of murine Ii, an electrophoretically invariant protein associated with Ia molecules. Using related analytical techniques, we have studied leukemic cells of two blood and one splenic samples from three Japanese patients with hairy cell leukemia and have demonstrated abundance of p35 in the splenic and one of the blood samples. The second blood sample was negative for p35 by our method of analysis, but the same hairy cells became positive for p35 at 2 months in culture and negative again at 4 months in culture. All 3 samples of this patient (fresh hairy cells and cultured cells at 2 and 4 months) remained consistently positive for Ia and for light chain-restricted immunoglobulin. Control cells from one each of acute lymphoblastic leukemia and Burkitt's lymphoma were negative for abundant p35 expression after culture as well as in the fresh state. One can conclude that the Japanese form of hairy cell leukemia, while varying in several distinct clinical and laboratory features from hairy cell leukemia in caucasians, is characterized also by abundant expression of p35 as seen in a subset of white patients. In addition, this expression of p35 is developed by hairy leukemic cells in culture initially but is lost upon longer term culture, in parallel with the level of tartrate-resistant acid phosphatase reactivity.
The human epidermal keratinocyte cell line K-TL-1, developed from a benign epidermal tumor, was cultured in the presence of the synthetic vitamin D3 analogue tacalcitol [1alpha,24(R)-dihydroxyvitamin D3] to assess the effects on the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured with 10(-8) M of tacalcitol. Supernatants and cell homogenates were collected and NGF concentrations were determined by enzyme-linked immunosorbent assay. The concentration of NGF in the supernatants of cultures treated with tacalcitol peaked within 24 h after the start of tacalcitol treatment and remained stable for 96 h. This NGF induction caused by tacalcitol was dose-dependent, showing an ED50 between 10(-10) and 10(-9) M. Induction of NGF mRNA expression by tacalcitol was also observed by RT-PCR, indicating that tacalcitol induced NGF expression through transcriptional activation. These results suggest that active vitamin D3 could treat peripheral neuropathy by inducing NGF production in the skin.
PURPOSE: Production of the proinflammatory cytokine interleukin (IL) 1alpha, which is stored in keratinocytes (KCs) and is multifunctional, may be enhanced by glucocorticoids. A study was made to confirm whether immunosuppressants such as the macrocyclic lactone FK506 (tacrolimus) possibly serve to modulate glucocorticoid- stimulated IL-1alpha production from chemically treated KCs. METHODS: Using cultured human KCs, the effects of FK506 on the production of IL-1alpha treated with chemicals (trinitrobenzene sulfonic acid sodium salt, TNBS) plus hydrocortisone were analyzed by ELISA and mRNA expression of IL-1alpha using RT-PCR. RESULTS: Intracellular IL-1alpha in TNBS-treated human KCs was increased with a low concentration of 10(-10)M of hydrocortisone. Further FK506 application inhibited significantly this increased production. The mRNA expression of IL-1alpha at various concentrations of chemicals was not remarkably different. CONCLUSIONS: FK506may control the increase in IL-1alpha with glucocorticoid in KCs, suggesting FK506 to suppress harmful effects of glucocorticoids such as steroid rosacea.