Biomedical subjects

M Shiota

Publications and source records attributed to M Shiota.

At least 109 records · Page 6Linked to original sources

PubMed1994

Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3.

Ki-1 lymphoma is a subtype of human malignant lymphoma characterized by the expression of CD30 (Ki-1) and a peculiar morphology. It is occasionally accompanied by a unique reciprocal chromosomal translocation t(2;5)(p23;q35). A Ki-1 lymphoma cell line, AMS3, was established by maintaining biopsied tumor cells in SCID (severe combined immunodeficiency) mice. To investigate abnormalities of the signal transduction in Ki-1 lymphomas, AMS3 lysate was immunoprecipitated with anti-phosphotyrosine monoclonal antibody, 25.2G4, and the immunoprecipitates were subjected to kinase assay and immuno-blotting with 25.2G4. A unique phosphotyrosine-containing protein of MW 80,000, designated p80, was found only in AMS3 cells and not in other cell lines or mononuclear cells from healthy donors. Subsequent amino acid sequence analysis of its tryptic digests showed that p80 was a hitherto undescribed tyrosine phosphoprotein similar to Ltk (leukocyte tyrosine kinase). Furthermore, physical interaction of p80 with CD30 was suggested from immunoprecipitation experiments with AMS3 lysates.

Animals↗

PubMed1993

Engraftment of human non-Hodgkin lymphomas in mice with severe combined immunodeficiency.

BACKGROUND: Malignant non-Hodgkin lymphoma (NHL) is one of the most difficult neoplasms to transplant into nude mice. Mice with severe combined immunodeficiency (SCID) accept various human cancers much more efficiently than do nude mice. The authors investigated whether SCID mice could be used as convenient hosts in which to grow human NHL in vivo. METHODS: Fifty NHL specimens were engrafted into SCID mice. The original specimens and the tumors that developed in SCID mice were studied immunohistologically and by Southern blot analysis to clarify their clonal identity and to determine if they were Epstein-Barr virus (EBV)-transformed B cell proliferations. RESULTS: SCID tumors developed from 23 of 50 NHL specimens. Ten tumors were identical immunophenotypically and, partly, genotypically to the original NHL, showing that the original NHL grew in the SCID mice. B-cell NHL rather than T-cell NHL and high-grade rather than low-grade malignancy groups were much more easily heterotransplanted. Most of the heterotransplanted NHL were maintained by successive transplantation. In two other SCID tumors, the original NHL clones and a newly developed B-cell clone coexisted. The remaining 11 SCID tumors were composed of newly developed clones. The latter 13 tumors were shown to be human cells of B-cell lineage bearing EBV latent proteins--latent membrane protein 1 and EB nuclear antigen 2--suggesting that they originated from EBV-infected B-cells that were present in the original tumor tissues. CONCLUSION: SCID mice accept human NHL far more efficiently than do nude mice. However, frequent occurrence of spontaneous EBV-associated B-cell proliferation must be kept in mind.

Animals↗

PubMed1993

Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin.

Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.

Acetylglucosamine↗

PubMed1993

Expression of cytochrome b558 on B cell- and CD 30 positive-lymphomas.

Expression of cytochrome b558, an essential constituent of the superoxide generating system in phagocytes, was demonstrated in B-lymphocytes. To determine its expression in malignant lymphoma (ML), 103 non-Hodgkin's MLs and 18 Hodgkin's (HD) MLs, together with non-tumorous lymphoid tissues were immunohistochemically analyzed, using two antibodies specific for the cytochrome. In non-tumorous tonsils and lymph nodes, B-lymphocytes, especially in the mantle zones, and histiocytes stained heavily, while T-lymphocytes failed to stain. Among the 55 B-MLs, all follicular lymphomas (9/9) and 18/46 of the diffuse lymphomas were found to express cytochrome b558. Among 48 T-MLs, 46 were unstained by antibodies against the cytochrome. The two cytochrome b558-positive cases were CD 30-positive anaplastic large cell lymphomas. Sixteen of 18 HD patients had CD 30-positive Reed-Sternberg cells which also stained with antibody alpha LC (an anticytochrome b558 antibody). Thus, cytochrome b558, represents a new lymphocyte differentiation antigen.

B-Lymphocytes↗

PubMed1993

Adaptive changes in zonation for gluconeogenic capacity in liver lobules of cold-exposed rats.

The rate of gluconeogenesis from lactate increased in perfused livers after exposure of rats to cold for 5 days, and it returned to the control rate after 20 days [M. Shiota, T. Tanaka, and T. Sugano. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E281-E286, 1985.]. The relationship between the increased gluconeogenic activity and its zonal distribution in liver lobules was studied in cold-exposed rats that had been starved for 24 h by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H), which had been isolated by the digitonin-collagenase perfusion technique. In the control group, the rate of gluconeogenesis from lactate or alanine was three times higher in PP-H than in PV-H. The rate of gluconeogenesis from these substrates in PP-H was not changed by exposure of rats to cold. The rates of PV-H increased to the level in PP-H after 5 days of exposure of rats to cold and then returned to the control rates after 20 days. The rate of gluconeogenesis from fructose was not altered in either preparation of cells by cold treatment of rats. The change in gluconeogenic capacity in PV-H caused by exposure of rats to cold was unrelated to changes in the activity of the malate-aspartate shuttle and of pyruvate kinase. The increased capacity in mitochondrial respiration was observed in both preparations of cells by cold treatment of rats for 5 days. The activity of phosphoenolpyruvate carboxykinase was higher in PP-H than in PV-H in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1993

Responses to catecholamines in perfused livers of hypothalamic-lesioned rats.

The responses of hepatic glycogenolysis to catecholamines in ventromedial hypothalamus (VMH)-lesioned male rats were examined in perfused livers. Seven days after bilateral electrical lesioning of the VMH, the livers were perfused. Isoproterenol, a beta-agonist, stimulated greater glucose production in VMH-lesioned rats than in controls (32.8 vs. 5.6 mumol glucose.h-1.g liver-1), while responses to phenylephrine, an alpha-agonist, decreased significantly compared with controls (44.4 vs. 69.8 mumol glucose.h-1.g liver-1). There were no significant differences in responses of livers to glucagon and vasopressin between control and VMH-lesioned rats. Adrenodemedullation showed the same effect on beta-responses as lesions in the VMH, but no effect on alpha-responses. Plasma epinephrine levels were not detectable with the high-performance liquid chromatography analysis in VMH-lesioned rats. The periodicity of plasma corticosterone levels was observed in both VMH-lesioned and control rats, although daytime increases in plasma corticosterone were blocked by VMH lesions. These results suggest that the lesions in the VMH cause changes in the levels of adrenergic receptor and that the increase in beta-responses is caused mostly by the reduction of plasma epinephrine.

Adrenalectomy↗

PubMed1993

Antibodies to human cytomegalovirus 65-kilodalton Fc binding protein in rheumatoid arthritis: idiotypic mimicry hypothesis of rheumatoid factor production.

We previously reported that rheumatoid factors (RFs) might bear the internal image of Fc gamma-binding proteins (FcBPs) of herpes family viruses, suggesting the possibility that some RFs may be produced as antiidiotypic antibodies to anti-viral FcBP antibodies. Since human cytomegalovirus (HCMV) has been implicated in the pathogenesis of RA, we made an attempt to detect antibodies to 65 KD major HCMV FcBP in sera and synovial fluid from patients with RA. Western blotting was performed using HCMV-infected MRC-5 cell lysate as the antigen. Eleven of 23 patients with RA possessed strong serum antibodies to HCMV-65 KD protein, whereas such antibodies were found in only 2 of 23 normal controls. In the synovial fluid, 10 of 19 RA patients showed anti-HCMV 65 KD reactivity. Pepsin-digested IgG retained anti-65 KD reactivity, indicating that false-positive reaction due to the presence of IgG Fc portion and/or RF was unlikely. 65 KD protein was shown to be different from human heat shock proteins (hsps) using monoclonal antibodies against human hsps. Patients' IgG F(ab')2 also reacted with the 65 KD protein of purified HCMV virion itself. These results support the possibility that some RFs could be produced as antiidiotypic antibodies to anti-viral FcBP antibodies.

Adolescent↗

PubMed1993

Expression of Lyn protein on human malignant lymphomas.

BACKGROUND: lyn is one of the src family genes encoding protein-tyrosine kinases, expressed preferentially in B lymphocytes and monocytes/macrophages. Its gene product, Lyn protein, is thought to participate in cell membrane-associated signal transduction on B lymphocytes by associating physically and functionally with membrane-bound IgM. EXPERIMENTAL DESIGN: To investigate the expression of Lyn on human malignant lymphomas (MLs), 50 ML biopsies, 12 ML samples maintained in mice with severe combined immunodeficiency, and 4 African Burkitt type cell lines were studied with the use of immunohistology, immunochemistry, and Southern blot analysis. RESULTS: Among biopsy specimens, 27 of 27 B-MLs, 5 of 21 T-MLs, and 2 of 2 null-MLs were stained. In severe combined immunodeficiency mouse-maintained B-MLs, unlike biopsied B-MLs, 4 of 11 were found to be unstained. Further analysis disclosed that all 4 of these unstained B-MLs were the Epstein Barr virus transformed B cells proliferating in severe combined immunodeficiency mice and not the original ML cells, suggesting the presence of a specific mechanism down-regulating the Lyn protein in this group. One IgA+ IgM- B-ML and one IgG+ IgM- B-ML were stained by the antibody, indicating the possible existence of molecular mechanisms other than membrane-bound IgM that facilitate Lyn protein expression. Decrease of Lyn expression was also noted in 3 of 4 Epstein-Barr virus-positive African Burkitt's ML lines. Complementary Western blot analysis of 8 immunostained and 4 unstained MLs confirmed the immunohistologic findings. However Southern blot analysis showed that the lyn gene in Lyn-positive and -negative cases were apparently unchanged. CONCLUSIONS: The level of Lyn expression in MLs reflects mainly their normal counterpart, whereas it can be expressed somewhat differently in some cases, especially in Epstein Barr virus-transformed MLs that occur in immunocompromised hosts, on which it is often down-regulated. This is the first report of Lyn expression on human MLs.

Animals↗

PubMed1992

Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells.

Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.

Animals↗

PubMed1992

Different preparations of zymosan induce glycogenolysis independently in the perfused rat liver. Involvement of mannose receptors, peptide-leukotrienes and prostaglandins.

Zymosan (non-boiled) induced glycogenolysis biphasically, with no lag time, in the perfused rat liver. After the zymosan was boiled, it could be separated into two fractions, both of which stimulated glycogenolysis independently. The soluble fraction of boiled zymosan (zymosan sup) showed homologous desensitization, indicating that zymosan sup-induced glycogenolysis is a receptor-mediated event. Mannan (polymannose), which is known to be a biologically active component of zymosan, induced a glycogenolytic response similar to that produced by zymosan sup, and desensitized the response to the latter. Preinfusion of platelet-activating factor (PAF, 20 nM) or isoprenaline (10 microM) did not extinguish the glycogenolytic response to zymosan sup, while the response to a secondary infusion of PAF was blocked. The glycogenolytic response to zymosan sup was completely inhibited by nordihydroguaiaretic acid (NDGA, 10 microM), a lipoxygenase inhibitor, and by ONO-1078 (100 ng/ml), a leukotriene (LT) D4 receptor antagonist. On the other hand, the glycogenolytic effect of zymosan pellet (the particulate fraction of boiled zymosan) was not affected by preinfusion of zymosan sup, and was inhibited by ibuprofen (20 microM), a cyclo-oxygenase inhibitor. Prostaglandins (PGs) detected in the perfusate were augmented with infusion of zymosan pellet. Opsonization of the zymosan pellet by serum (complement) enhanced the glycogenolytic response without a lag period, and with a concomitant enhancement of PG output. Correlations between glucose production and PGs were r = 0.832 (PGD2), r = 0.872 (PGF2 alpha), r = 0.752 (PGE2) and r = 0.349 (6-oxo-PGF1 alpha). The glycogenolytic response to non-boiled zymosan was delayed and the biphasic glycogenolytic response was not observed when mannan was infused first. NDGA mimicked the effects of the preinfusion of mannan, while ibuprofen had no effect on the non-boiled-zymosan-induced glycogenolysis. These results suggest: (1) that non-boiled zymosan stimulates glycogenolysis through a mannose receptor-dependent, but unidentified, pathway, (2) that zymosan sup induces glycogenolysis via mannose receptor activation through the production of peptide-LTs but not PAF, and (3) that zymosan pellet causes glycogenolysis through the production of prostanoids, which is enhanced in the presence of complement.

Animals↗

PubMed1992

Immunoglobulin idiotype expression in reactive lymphoid tissues and B-cell lymphomas.

In an investigation of the immunoglobulin idiotypic expression of non-tumour and neoplastic B lymphocytes in situ, fresh-frozen specimens of reactive tonsils, lymph nodes and B-cell malignant lymphomas (B-MLs) from Japanese patients were studied immunohistochemically with 39 different anti-idiotype antibodies. In reactive lymphoid tissues, while idiotype-bearing cells were largely distributed sparsely in follicles and perifollicular areas, some were heavily crowded in particular germinal centres (GCs), suggesting the presence of oligoclonal proliferations of B-cells in GCs. Forty-eight out of 100 B-MLs reacted with anti-idiotype antibodies. This proportion was significantly higher than those reported in Western cases (27-36%), indicating that Japanese B-MLs share public idiotypes much frequently than western cases. The idiotypes demonstrated in these lymphomas, in contrast to those not expressed in any B-ML, were found much commonly in non-tumour lymphocytes, suggesting that such public idiotypes as were common in B-MLs were frequently shared by normal B-lymphocytes.

Antibodies↗

PubMed1992

Treatment of vasospasm by balloon angioplasty: experimental studies and clinical experiences.

The vasodilation mode and degree of the invasion caused by balloon angioplasty were experimentally examined. Assessment by light microscopy and scanning electron microscopy demonstrated that the invasion to the implanted arterial wall, taken from a patient who died from vasospasm, was minimized by the use of the balloon under the condition at 1 atm, 10 times for 10 seconds. Furthermore, we applied angioplasty to eight patients who developed severe vasospasm after subarachnoid haemorrhage, and five showed improvement in neurophysiological (transcranial Doppler sonography), neuroradiological, and clinical examinations. In addition, blood vessels obtained from one patient who died 10 days after angioplasty, demonstrated similar findings to those of the experimental studies. It can be said that angioplasty will be one of the effective therapeutic methods to manage vasospasm when it is applied under the conditions mentioned above.

Adult↗

PubMed1992

Effects of nerve stimulation and zymosan on glycogenolysis in perfused livers from cold-exposed rats.

The effects of sympathetic nerve stimulation and zymosan (cell wall particles from yeast) on glycogenolysis were studied in perfused livers from rats kept for 5 and 20 days at 4 degrees C. The rate of glycogenolysis induced by nerve stimulation decreased significantly without any decrease in norepinephrine outflow during cold exposure, and the rate induced by norepinephrine did not change. By contrast, the rate of zymosan-induced glycogenolysis increased markedly during cold exposure. The rats with denervated hepatic nerves did not show the increased response to zymosan. In cold-exposed rats, both mepacrine and ibuprofen inhibited the effects of zymosan and of nerve stimulation without any inhibition of the outflow of norepinephrine. Neither inhibitor had any effect on the effects of norepinephrine. The metabolic effects of nerve stimulation and zymosan were not additive in cold-exposed rats. These results suggest that cold exposure may modulate the metabolism of arachidonic acid in Kupffer cells via hepatic nerve and decrease the eicosanoid-dependent glycogenolysis by nerve stimulation.

Animals↗

PubMed1992

Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients.

Follicular lymphoma shows a wide geographic variation in incidence, occurring more frequently in the U.S. than in Japan. A translocation involving the bcl-2 gene on chromosome 18 and the immunoglobulin heavy chain gene on chromosome 14 is frequently found in follicular lymphomas and is believed to play a critical role in the pathogenesis of these tumors. Recently, bcl-2/IgH rearrangements have been detected in reactive lymphoid tissue obtained from European patients, indicating that such rearrangements occur at some low but measurable background rate. In non-malignant tissues, the polymerase chain reaction was used to study the frequency of bcl-2/IgH rearrangements in reactive lymphoid tissue obtained from American and Japanese patients to find out whether geographic variation in the incidence of follicular lymphoma was caused by differences in sporadic occurrence of the t(14;18). We found such rearrangements in 5 of 15 American hyperplastic tonsils and lymph nodes and 5 of 10 Japanese tonsils, an incidence close to that previously seen in European patients. These data suggest that the background incidence of such rearrangements is similar in all populations, regardless of the incidence of follicular lymphoma.

Adult↗

PubMed1991

Effects of calmodulin antagonists on hydrogen-translocating shuttles in perfused rat liver.

The effects of calmodulin antagonists on the capacity of hydrogen-translocating shuttles were studied in the perfused rat liver. The capacity was estimated by measuring the changes in the rate of production of glucose from sorbitol during the oxidation of ethanol [T. Sugano, T. Ohta, A. Tarui, and Y. Miyamae. Am. J. Physiol. 251 (Endocrinol. Metab. 14): E385-E392, 1986]. Thyroxine given to intact rats increased the activity of alpha-glycerophosphate dehydrogenase (alpha-GPD). Glucocorticoid replacement in adrenalectomized rats decreased the activity of the alpha-GPD to values obtained after treatment with PTU. In either thyroxine-treated or steroid-replaced rats, the capacity of hydrogen-translocating shuttles increased markedly. However, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), trifluoperazine, and chlorpromazine inhibited the increased capacity in steroid-replaced rats and had no effect on the increased capacity in thyroxine-treated rats. W-7 inhibited the stimulatory effects of norepinephrine on the capacity of the malate-aspartate shuttle without inhibition of efflux of intracellular Ca2+. The stimulatory effects of vasopressin on the malate-aspartate shuttle were also inhibited by W-7, trifluoperazine, and chlorpromazine. The results suggest that the malate-aspartate shuttle may be regulated by Ca(2+)-calmodulin.

Adrenalectomy↗

PubMed1991

[Clinical significance of serum sialyl Tn antigen in patients with gynecological cancer. STN Study Group].

Serum sialyl Tn antigen was assayed in gynecological cancer and benign patients by means of "STN OTSUKA" kits. Fifty-eight of 140 (41.1%) ovarian cancer patients showed a significant elevation of sialyl Tn antigen in serum above the cut-off level of 45 unit/ml (mean +2SD) determined from normal controls. There was no feature of positive frequency in tissue type, including serious carcinoma (47.6%), mucinous carcinoma (45.5%), clear cell carcinoma (30.4%) and endometrioid carcinoma (55.6%), but the positive frequency of mucinous carcinoma (36.8%) was higher than that of serous carcinoma (11.1%) in stage I. Compared with other markers, sialyl Tn antigen showed a very much lower false-positive rate (3.6%) in benign gynecological diseases. In the diagnosis of ovarian cancers, the combination assay of sialyl Tn antigen and CA 125 increased diagnostic efficiency compared with any other combination assays. Therefore, sialyl Tn antigen will be a useful tumor marker for ovarian cancers.

Antigens, Neoplasm↗

PubMed1990

Follicle lysis in HIV-free lymphoid tissues.

Follicle lysis (FL), the 'moth-eaten' degeneration of follicular dendritic cells (FDCs), previously regarded as specific for HIV-infected lymph follicles, was later claimed to exist in HIV-free patients. This study was performed to clarify the differences between HIV-free and HIV-induced FL. HIV-free and HIV-infected lymphoid tissues were analyzed immunohistologically. Most of HIV-free FLs were shown to lack the dark zones, the areas in germinal center composed mostly of much larger and clumped noncleaved cells, whereas HIV-induced FL in persistent generalized lymphadenopathy (PGL) lymph nodes included highly proliferative dark zones. Thus, FL in HIV-free lymphoid organs was suggested to be a physiological degenerative process with poor proliferative activity, while FL in PGL nodes includes two processes, FDC degeneration and B lymphocyte proliferation.

Dendritic Cells↗

PubMed1990

[Mechanism of hyperferritinemia in a case of malignant histiocytosis].

We report a case of malignant histiocytosis diagnosed by liver-spleen biopsy under laparoscopy. A 49-year-old woman was admitted to our hospital with thrombocytopenia, moderate anemia and hypoproteinemia. Her bone marrow findings revealed erythroid and megakaryocyte hyperplasia, and the serum ferritin concentration was 2,250 ng/ml though she had not received any blood transfusions. Ferrokinetics analysis showed the pattern of ineffective erythropoiesis, and the half-lives of erythrocytes and platelets were both shortened. Her hepatosplenomegaly gradually increased accompanied by increasing serum ferritin level to 10,000 ng/ml. Liver-spleen biopsy was carried out under laparoscopy and revealed infiltration of atypical histiocytes with erythrophagocytosis, which were positive for S-100 and ferritin but negative for lysozyme. The rate of glycosylation in whole serum ferritin, analyzed by using concanavalin-A binding method, showed that her glycosylated ferritin content was only 8.3%, whereas in sera after iron overloading, it was about 70%. Serum isoferritin profiles by isoelectric focussing were studied, and isoferritin pattern from malignant histiocytosis was the same as that in iron overloading after neuraminidase treatment. These findings suggest that serum ferritin is synthesized in proliferating histiocytes and released in the plasma as a nonsecretory type (nonglycosylated ferritin) in this case.

Female↗