Myeloblastoma of the brain.
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Brain Neoplasms↗
Biomedical subjects
J C Barton
Publications and source records attributed to J C Barton.
Immunoreactive lactoferrin in resting, activated, and neoplastic lymphocytes.
Lactoferrin (Lf) in lymphocytes was assessed with immunofluorescence/flow cytometric technique. Surface Lf was detected primarily among B-cell-enriched preparations. Tonsillar B-cells of different densities expressed surface Lf similarly. Very small percentages of CALLA+ ALL, HCL, or EBV-transformed B-cells expressed surface Lf, whereas B-CLL lymphocytes had the highest percentages of surface Lf positivity. Few resting, cultured, or neoplastic T-lymphocytes expressed Lf. The pattern of immunofluorescence and analyses of surface and total cellular immunoreactive Lf indicated that Lf is associated primarily with the lymphocyte surface. The percentage and/or intensity of surface Lf-specific fluorescence were not significantly altered in B- or T-cells by incubation with physiologic concentrations of differric Lf, and the percentages of Lf-positive cells detected in respective subjects remained stable over time. Surface Lf positivity was unrelated to the expression of other surface antigens (except those marking B- or T-cell lineage) or cell cycle. Expression and/or binding of Lf in B-lymphocytes may become increased during certain stages of cell maturation.
B-Lymphocytes↗
Tumor lysis syndrome in nonhematopoietic neoplasms.
A 57-year-old woman developed severe tumor lysis syndrome characterized by acute hyperuricemic nephropathy, hyperphosphatemia, hyperkalemia, and hypocalcemia after therapy with cyclophosphamide, methotrexate, and 5-fluorouracil for metastatic infiltrating ductal carcinoma of the breast involving the chest wall, lungs, pleurae, and liver. Similar metabolic derangements developed in a 58-year-old man after therapy with vinblastine and bleomycin for classical seminoma with widespread, bulky lymph node metastases. Both patients died of infection associated with granulocytopenia within 2 weeks after the initiation of chemotherapy despite significant improvement in the manifestations of tumor lysis syndrome. At autopsy, there was anatomic evidence of extensive tumor necrosis in each case. The pathogenesis of this problem in the present cases is discussed, and this unusual complication of the treatment of nonhematopoietic malignancies is reviewed.
Antineoplastic Combined Chemotherapy Protocols↗
Retention of radiolead by human erythrocytes in vitro.
An in vitro method was developed to assess human erythrocyte lead uptake and release directly, rapidly, and reproducibly; the technique requires small aliquots of blood and uses silicone fluid to separate erythrocytes from their suspending media. Uptake occurred rapidly and was directly related to temperature. Increasing quantities of available elemental lead were associated with increasing absolute quantities but decreasing percentages of uptake. Low values of pH diminished the uptake and enhanced the release of radiolead by erythrocytes, and could be correlated with diminished lead-hemoglobin binding para-Chloromecuribenzoate increased and dithiothreitol inhibited radiolead uptake but neither compound affected lead release, suggesting that sulfhydryl groups are important for lead binding to the erythrocyte. Cyanamide and N-ethylmaleimide did not significantly affect the net uptake or release of radiolead. Calcium disodium EDTA, penicillamine, and dimercaprol significantly reduced lead uptake, although only incubation with dimercaprol resulted in a net removal of lead from erythrocytes. Iron and ceruloplasmin significantly decreased radiolead uptake, but inorganic metal cations other than iron, hyperosmolarity, human serum albumin, cholesterol, and transferrin had no significant effect on uptake or release.
Chelating Agents↗
Myeloblastoma of the brain.
Two patients developed intraparenchymal myeloblastomas (granulocytic sarcomas) of the brain. One patient with acute myelogenous leukemia in hematological remission had multiple myeloblastomas in the cerebrum and thalamus. The second patient, who had Philadelphia-chromosome-positive chronic myelogenous leukemia, developed a solitary lesion of the cerebrum without systemic evidence of blastic transformation of leukemia. By light microscopy, each biopsy specimen revealed a tendency for the malignant cells to appear in perivascular locations, and the presence of cytoplasmic naphthol AS-D chloroacetate esterase activity in some cells. Ultrastructural analysis demonstrated the presence of primary granule-like lysosomal structures in these cells, confirming their granulocytic origin. The lack of continuity of the myeloblastomas with the dura mater and the perivascular clusters of blast cells suggest that the pathogenesis of these lesions in the present cases could best be accounted for by the direct, hematogenous spread of mitotically competent leukemic cells to brain parenchyma.
Adult↗
Prevalence of granular lymphocyte proliferation in patients with rheumatoid arthritis and neutropenia.
PURPOSE: Granular lymphocyte proliferation and neutropenia with or without splenomegaly occurs with unknown frequency in rheumatoid arthritis. We decided to evaluate the prevalence of Felty's syndrome and granular lymphocyte proliferation among patients with rheumatoid arthritis and to determine the fraction of patients with granular lymphocyte proliferation who also had rheumatoid arthritis. PATIENTS, METHODS, AND RESULTS: We retrospectively analyzed 1,053 cases of rheumatoid arthritis and 13,505 marrow examination reports for the decade 1978 to 1987. Among patients with Felty's syndrome rheumatoid arthritis with neutropenia/leukopenia, and rheumatoid arthritis with splenomegaly, we identified 18 patients with neutropenia as a manifestation of rheumatoid arthritis. We also identified marrow examinations in 150 patients with rheumatoid arthritis. Using blood counts, microscopy of marrow, and surface antigen analysis of mononuclear cells, we determined that 12 patients had typical Felty's syndrome and six had granular lymphocyte proliferation, representing prevalences of 1.1 percent and 0.6 percent, respectively. No patient had granular lymphocyte proliferation without neutropenia. CONCLUSION: Granular lymphocyte proliferation and neutropenia with or without splenomegaly in rheumatoid arthritis commonly resembles typical Felty's syndrome. Further, the six patients with granular lymphocyte proliferation represent 20 percent of our institution's patients with granular lymphocyte proliferation, supporting the previously described common association of this disorder with rheumatoid arthritis. The relatively large fraction of deaths (due to malignancy and infection) among the patients with typical Felty's syndrome suggests that their mean survival may be comparatively less than in those with granular lymphocyte proliferation.
Adult↗
Thrombotic thrombocytopenic purpura in systemic sclerosis.
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Adult↗
Assessment of total immunoreactive lactoferrin in hematopoietic cells using flow cytometry.
Cell-associated lactoferrin (Lf) was analyzed using a new method involving cell permeabilization, indirect immunofluorescence staining, and flow cytometry. Statistical techniques to evaluate the results for percentage of positive cells, relative fluorescence and homogeneity of Lf distribution were also devised. Most normal adult neutrophils (97.1 +/- 0.3% (SEM), range 92.7-99.6%, n = 41) had brilliant fluorescence homogeneously distributed among the cells. There was significantly greater homogeneity of neutrophil Lf distribution in post-menopausal than pre-menopausal females. In chronic myelogenous leukemia (n = 13) and cord blood (n = 7), fractions of Lf-positive neutrophils were decreased (77.3 +/- 7.5%, range 13.3-96.3%; 71.4 +/- 9.3, range 32.0-95.6%, respectively). Normal monocyte-rich isolates had moderate fluorescence (28.7 +/- 3.6%, range 9.3-76.8%, n = 22). Among blood lymphocyte-rich preparations, 13.1 +/- 1.3% of cells had weak positivity (range 4.9-26.6%, n = 19); monoclonal B and T lymphocytes had similar parameters. No other cells had detectable Lf. Our results were significantly correlated with those obtained manually (r = 0.98, P less than 0.001), and are consistent with Lf quantity and distribution determined using other methods.
Adult↗
Modulation of the development of bleomycin-induced fibrosis by deferoxamine.
Bleomycin is an antineoplastic compound which produces a time- and dose-dependent pulmonary fibrosis. The mechanisms which cause this fibrosis are not known. The ability of bleomycin to produce oxygen radicals in the presence of iron and molecular oxygen appears to be related to the fibrosis. Previous studies, which have examined single time points utilizing the ferric ion chelator deferoxamine and iron-deficient diets, suggest that iron plays a central role in bleomycin-induced pulmonary fibrosis. Therefore, the present study was designed to determine the effects of deferoxamine on the development of bleomycin-induced pulmonary fibrosis. Deferoxamine pretreatment and daily injections resulted in a significant reduction in lung collagen content and lung lipid peroxidation 21 days after intratracheal bleomycin compared with bleomycin treatment alone. In addition deferoxamine treatment significantly inhibited lung DNA increases at 4, 7, and 14 days after bleomycin treatment compared with bleomycin treatment alone. These data indicate that deferoxamine treatment reduces the development of bleomycin-induced pulmonary fibrosis in the later phase. The mechanism might be by the prevention of iron-catalyzed, free-radical formation and modulation of some cellular functions.
Animals↗
Neutrophil lactoferrin content: variation among mammals.
Lactoferrin (Lf) in blood and/or marrow neutrophils was semiquantified using indirect immunofluorescence technique in nine mammalian species. Neutrophil iron-binding reactivity (NFeBR), which corresponds primarily to Lf, was also visualized and semiquantified using functional cytochemical (FeNTA-AF) technique at the light microscopic level in these nine and in an additional fifteen mammalian species, and in selected species at the ultrastructural level. Neutrophil immunoreactive Lf was positively correlated with total cellular and granule content of NFeBR among these nine species, and with previously reported concentrations of neutrophil Lf quantified by radioimmunoassay. Relative levels of Lf in neutrophil extracts from rat, hamster, and human were confirmed using SDS-polyacrylamide gel electrophoresis and immunoblotting. Relatively high levels of immunoreactive neutrophil Lf and/or NFeBR were observed in carnivores (ten species) and primates (six species). Among rodents (five species), the levels were variable, and the artiodactyls (four species) studied had low levels. These results demonstrate that neutrophil Lf levels vary widely among mammalian species. In addition, FeNTA-AF technique provides a rapid means of evaluating animals for relative quantities of neutrophil Lf.
Animals↗
Differential staining of neutrophils and monocytes: surface and cytoplasmic iron-binding proteins.
Lactoferrin, transferrin, and ferritin were systematically visualized and semiquantified in neutrophils and monocytes/macrophages using indirect immunofluorescence and functional cytochemical techniques. They localized on cell surfaces and within the cytoplasm at the light and electron microscopical levels. In normal subjects, subpopulations of blood neutrophils and monocytes had surface lactoferrin, but little surface transferrin or ferritin was observed on these cells. Most neutrophils had brilliant granular cytoplasmic positivity for lactoferrin; variable fractions of monocytes had weak to moderate diffuse cytoplasmic lactoferrin staining localized most prominently to the cytoplasmic matrix. Most neutrophils had cytoplasmic ferritin, but few had cytoplasmic transferrin, whereas larger subpopulations of monocytes had cytoplasmic staining reactions for both proteins. To analyse maturing cells, the iron nitrilotriacetate-acid ferrocyanide method was adapted for the light microscopical analysis of neutrophils and monocytes/macrophages in soft agar culture. Further, a combined stain that visualizes iron nitrilotriacetate-acid ferrocyanide reactivity and alpha-naphthyl butyrate esterase activity in cells in blood and marrow smears was developed. The relative quantities and subcellular distribution of iron-binding proteins in neutrophils and monocytes/macrophages defined by the present methods can be correlated with biochemical, maturational, and functional properties of these cells.
Bone Marrow↗
Neoplastic meningitis with eosinophilic pleocytosis in Hodgkin's disease: a case with cerebellar dysfunction and a review of the literature.
A 31-year-old man had Hodgkin's disease (stage IIA, nodular sclerosis) in apparent remission after radiotherapy. Nine months after the diagnosis of Hodgkin's disease, he developed neoplastic meningitis with eosinophilic pleocytosis and neurologic findings suggestive of peri-fourth ventricle infiltration. Morphologic and surface marker analysis of cerebrospinal fluid cells showed large numbers of T-lymphocytes and Reed-Sternberg variant cells positive for CD15, the Lex hapten expressed on myeloid cells and on a variety of malignant cells. Therapy with intrathecal methotrexate, oral dexamethasone, and cranial irradiation resulted in prompt resolution of his cerebrospinal fluid abnormalities and neurologic deficits. Ten months after the diagnosis of eosinophilic meningitis, systemic relapse of Hodgkin's disease occurred in right iliac and inguinal lymph nodes. The diagnosis, pathogenesis, and therapy of this unusual complication of Hodgkin's disease are reviewed.
Adult↗
Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster.
Bleomycin produces a dose- and time-dependent interstitial pulmonary fibrosis in humans, and is widely used to produce an animal model for the study of interstitial pulmonary fibrosis. The mechanism(s) for bleomycin-induced pulmonary fibrosis is (are) unknown, but the production of oxygen radicals by a ferrous ion-molecular oxygen pathway might be related to the fibrosis. Therefore, we studied the effect of iron deficiency on the biochemical, inflammatory, and morphologic parameters of bleomycin-induced pulmonary fibrosis in the hamster. Mild iron deficiency was induced in hamsters by bleeding via the retro-orbital sinus and maintenance on an iron-deplete diet. After intratracheal administration of bleomycin (1 U), there was no accumulation of lung collagen in the iron-deficient bleomycin-treated animals. In comparison, iron-replete animals treated with bleomycin exhibited a significant (p less than 0.01) increase in lung collagen. In addition, bleomycin-treated iron-replete animals had increased lung lipid peroxidation (p less than 0.05), whereas bleomycin-treated iron-deficient animals did not (p greater than 0.05). Lung DNA and morphometric estimates of the lesion severity were significantly increased in both iron-replete and iron-deficient bleomycin-treated animals. These data indicate that iron deficiency is associated with a reduction in the severity of bleomycin-induced pulmonary fibrosis, possibly by the prevention of iron-catalyzed oxygen-radical formation and lipid peroxidation.
Animals↗
Ultrastructural silver enhancement of Prussian blue-reactive iron in hematopoietic and intestinal cells.
Prussian blue has been widely used to localize iron in a variety of tissues at the light and electron microscopic level. In the present study, thin sections of human marrow and blood cells and rat duodenal cells were exposed to silver proteinate (SP) after staining en bloc with acid ferrocyanide (AF), with and without prior iron saturation using iron nitrilotriacetate (FeNTA). Silver deposition was observed over Prussian blue-reactive sites and significantly enhanced sites of minimal AF and FeNTA-AF staining. AF-SP stain deposits were present in the cytoplasmic matrix, granules, and occasionally on the surfaces of macrophages, monocytes, and erythroblasts. FeNTA-AF-SP stained additional cytoplasmic and surface sites in erythroblasts and stained neutrophil granules intensely. Duodenal epithelium from iron-loaded rats demonstrated strong AF-SP staining of ferric iron in microvilli, apical cytoplasmic matrix, and lateral membranes. Similar preparations from iron-replete rats stained sparsely; however, intense AF-SP staining was observed after iron saturation with FeNTA. SP similarly enhanced luminal ferrous iron deposits stained with acid ferricyanide in rats given intraluminal ferrous iron. AF-SP stain deposits were removed by exposure of thin sections to NH4OH, KCN, or HNO3 but were not affected by prior exposure to HIO4 or NaBH4, consistent with a silver cyanide or complex stain precipitate rather than reduced silver or silver ferriferrocyanide. SP enhancement of Prussian blue allows identification of reactive sites not readily visualized with AF or FeNTA-AF alone, and offers the potential for differentiating AF staining from other deposits or organelles of comparable density.
Animals↗
Iron-binding reactivity in mature neutrophils: relative cell content quantification by cytochemical scoring.
We have developed a technique that permits evaluation and semi-quantification of iron-binding function in mature neutrophils. Neutrophil iron-binding reactivity (NFeBR) visualized using the iron nitrilotriacetate-acid ferrocyanide technique was rated 0 to 5+ in 100 segmented cells; the ratings were totaled to yield a score (NFeBRS). Males and post-menopausal females had significantly higher NFeBRS than pre-menopausal females. Neonates had low values, and a homogeneous distribution of NFeBR among neutrophils. In pregnancy and acute infection, NFeBRS were significantly increased. In a patient with congenital lactoferrin (Lf) deficiency, the NFeBRS was very low. In Ph1-positive chronic myelogenous leukemia, 13 of 17 patients had low NFeBRS due to decreased NFeBR, which was heterogeneously distributed among mature neutrophils. By ultrastructural analysis of mature neutrophils in two such patients, the stain deposits in FeBR-positive granules were of normal intensity, but the numbers of positive granules were decreased in many cells. NFeBRS were also low in 12 of 23 patients with other myeloproliferative disorders, and in seven of 15 patients with acute non-lymphoblastic leukemia, but in only seven of 63 patients with other neoplasms. NFeBRS were significantly correlated (p less than 0.008) with values of neutrophil Lf content quantified by immunologic assays in a wide variety of conditions and over a broad range of values. These results augment observations of neutrophil Lf made using immunological methods.
Adult↗
Cytochemistry and ultrastructural morphometry of cultured HL60 myeloid leukemia cells.
Cultured human myeloid leukemia (HL60) cells were characterized using ultrastructural cytochemical methods and differences identified when cells were compared for low (17 to 47), middle (69 to 100), and high (214 to 244) passages or to normal promyelocytes aspirated from bone marrow. Endoplasmic reticulum and transition structures (pre-Golgi compartment) of HL60 cells stained positively for peroxidase using diaminobenzidine but stained sparsely for reducing groups with osmium-zinc iodide. Staining of Golgi elements was relatively indistinct with diaminobenzidine and strong with osmium-zinc iodide, in comparison to freshly harvested promyelocytes which have intense diaminobenzidine and osmium-zinc iodide staining of the pre-Golgi and Golgi compartments. Cytoplasmic polyribosomes were more numerous in middle and high passage cells, whereas dilatation of endoplasmic reticulum was less prominent in these cells. The mean granule size was significantly increased in low passage cells, and staining of peroxidase was more prominent by light and electron microscopy when compared to high passage cells. Cytoplasmic granules demonstrated strong complex carbohydrate staining, indicating a lack of granule maturation in HL60 cells. Terminally differentiated myeloid cells were more frequent in low passage samples, and some neutrophil granule maturation appeared to occur within these cells, whereas all eosinophil granules consistently remained immature with intense complex carbohydrate staining and lack of crystalloid formation. These studies demonstrate significant differences between HL60 cells and normal promyelocytes, and also passage-dependent maturational differences in HL60 cells. These differences should be considered in evaluating parameters of cell growth and maturation and in the biochemical and enzymatic characterization of these cells.
3,3'-Diaminobenzidine↗
Acute cryoglobulinemic renal failure after intravenous infusion of gamma globulin.
A 39-year-old woman had mixed IgM/IgG cryoglobulinemia, but was later found to have a lymphoma that produced an IgM kappa paraprotein with rheumatoid factor activity. With intermittent chlorambucil and prednisone therapy, the lymphoma was controlled for five years and she had no evidence of cryoglobulinemia. Because of the presence of intractable pulmonary infection and hypogammaglobulinemia G, she was given an intravenous infusion of gamma globulin. Within 72 hours, renal failure and a sustained decrease in serum concentrations of IgM and IgG began concurrently. A kidney biopsy specimen obtained five days after the infusion showed hyaline "thrombi" in numerous glomerular capillaries and glomerular necrosis, consistent with acute, severe mixed cryoglobulinemic nephropathy. Immunostaining showed strong positivity for IgM, IgG, and light chains in glomerular capillary lumina and subendothelial sites; immunostaining with a monoclonal antiidiotypic antibody specific for the patient's paraprotein established the presence of the rheumatoid factor paraprotein in the deposits. These observations strongly suggest that complexes consisting of IgM kappa rheumatoid factor, IgG, and complement initiated the renal damage. Therefore, demonstrable serum rheumatoid factor activity in patients with B cell neoplasms should be considered a contraindication to the administration of intravenous gamma globulin.
Acute Kidney Injury↗
Analysis of paraprotein transport into the saliva by using anti-idiotype antibodies.
To determine the extent of clonal involvement of the secretory immune system and the origin of salivary immunoglobulins (Ig) in monoclonal gammopathy patients, saliva and serum samples were collected from five affected individuals (two IgA myelomas, one IgG myeloma, one IgG benign monoclonal gammopathy, and one IgM lymphoma) and were assayed for the presence of monoclonal Ig. Purified polyclonal or monoclonal anti-idiotype (Id) antibodies were prepared against each of the isolated serum paraproteins. In all five individuals, the patient saliva samples inhibited the binding of 125I-labeled homologous Ig to the corresponding anti-Id antibodies, but normal saliva did not. The concentration of Id in patients' saliva varied from 1 to 400 micrograms/ml; i.e., 0.004 to 1.0% of the corresponding serum values. Saliva of a lymphoma patient whose IgM kappa protein exhibited rheumatoid factor (RF) activity also contained RF. The salivary Id-bearing molecules were found to have the same Ig isotype as the serum paraproteins. The myeloma IgA represented a minor component (0.4 and 3.9%) of the total salivary IgA. The salivary IgA myeloma proteins were associated at least in part with secretory component, but the salivary IgG paraproteins were not. In an IgA myeloma patient, a minority (17%) of the IgA+ plasma cells found in the lacrymal gland biopsy specimen were Id+, whereas the great majority (98%) of bone marrow IgA plasma cells were Id+. The results suggest active transport rather than passive transudation of myeloma IgA into the patients' saliva, and the integrity of the secretory immune system was not compromised by the neoplastic process.
Biological Transport↗