Immune deficiency and expanded population of granular lymphocytes after bone marrow transplantation.
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Adult↗
Biomedical subjects
J C Barton
Publications and source records attributed to J C Barton.
Malignant hemangiopericytoma: computed tomography and magnetic resonance imaging.
Computed tomography and magnetic resonance imaging of a malignant hemangiopericytoma in a 58-year-old woman are described. The tumor was initially found in the abdomen and resected 34 years ago, but recurred 18 years later, followed by repeated recurrence and eventually metastasis to the lung and then to the liver. The lung nodules were round or oval, homogeneous, and well circumscribed while the massive tumor in the right lobe of the liver was poorly delineated with irregular areas of cystic necrosis. With proper setting of the repetition time and echo delay, the metastatic tumor became distinct from the uninvolved hepatic tissue on magnetic resonance imaging. In this case computed tomography and magnetic resonance imaging were complementary in evaluation of such a tumor.
Abdominal Neoplasms↗
Immune thrombocytopenia: effects of maternal gamma globulin infusion on maternal and fetal serum, platelet, and monocyte IgG.
A 24-year-old woman with lupus-like serologic abnormalities had immune thrombocytopenia that resolved after splenectomy, but increased quantities of platelet surface IgG persisted. Three years later, during the 36th week of her first pregnancy, gamma globulin (400 mg/kg daily for 5 days) was administered intravenously to decrease the risk and/or severity of immune thrombocytopenia in her infant. The infusion produced marked but transient elevations of maternal concentrations of serum IgG and quantities of monocyte surface IgG, but no significant changes in Fc receptor-mediated rosetting of peripheral blood monocytes with antibody-sensitized platelets occurred. Modest increases in quantities of platelets and plasma platelet-specific IgG were demonstrated. The infant, delivered by cesarean section 2 days after the end of the infusion, had a normal platelet count; cord blood had a normal concentration of serum IgG, but an elevated quantity of platelet surface IgG (by comparison with values for normal adults). Infant values of plasma platelet-specific IgG, monocyte surface IgG, and monocyte/platelet rosettes also were within the range of normal for adults. Anticytomegalovirus antibody was present in large amounts in the gamma globulin infused, first appeared in maternal serum after therapy, and was detected in cord serum. The significance of these observations to the management of immune neonatal thrombocytopenia is discussed.
Adult↗
Seasonal changes in lead absorption in laboratory rats.
A retrospective study of the relationship of season to the absorption of radiolead in laboratory rats was performed using data representing 305 animals from 36 experiments over 6 calendar years. Male Wistar rats weighing 200 to 250 g were given 1 microgram of radiolabeled lead in an aqueous solution, pH 4.0, in isolated small intestine, and absorption of the radiolead was quantified after a 4-hour interval using whole-body counting. Similar values of absorption occurred in the summer (June-August) and fall (September-November), 20.51 +/- 1.11% (1 SEM) and 23.0 +/- 1.23% of the test dose, respectively, but significantly lower values occurred in the winter (December-February) and spring (March-May): 16.51 +/- 0.77%, p less than 0.01, and 11.87 +/- 0.99%, p less than 0.01, respectively. Harmonic analysis yielded an excellent approximation of the mean quarterly absorption data. The resulting cosine function had a period of 4.08 +/- 0.05 quarter-years with an amplitude of 7.32 +/- 1.06%; predicted peak absorption values fell precisely between summer and fall. The relationships of these observations to possible mechanisms of lead absorption and to summertime epidemics of lead poisoning in children are discussed.
Animals↗
Ultrastructural morphology of granular lymphocytes (GL) from patients with immunophenotypically homogeneous expansions of GL populations (GLE).
We studied the morphology of large granular lymphocytes (GL) from 19 patients with expanded populations of GL (GLE) of homogeneous surface immunophenotype. By definition, all patients had increased numbers of medium-sized lymphocytes with azurophilic granules, and neutropenia, thrombocytopenia, and/or anemia. In all cases, the GL had an extended Golgi apparatus and prominent centrioles. Among cells from individual patients, the GL were homogeneous with respect to their granule morphology. GL containing parallel tubular arrays (PTA), commonly associated with GLE, were observed in 9 of 19 cases; granules containing scarce matrix with or without associated vesicles (SMG) were present in the remaining 10 cases. In all cases in which the cells had PTA, there was co-expression of CD3 and CD8, the T suppressor cell-associated phenotype, whereas only 4 of 10 cases with SMG expressed CD3 and CD8 (p less than 0.01, chi-square test). We conclude that the morphologic homogeneity of GL in individual patients with GLE differs significantly from the heteromorphism usually seen in reactive GL, and is consistent with, but not diagnostic of, a clonal proliferation of GL in persistent GLE.
Antibodies, Monoclonal↗
Preleukemia in Fanconi's anemia: hematopoietic cell multinuclearity, membrane duplication, and dysgranulogenesis.
A 25-year-old male had Fanconi's anemia characterized by small stature, the onset of pancytopenia in the first decade of life, a high spontaneous breakage rate of the chromosomes, and the development of acute myeloblastic leukemia. In the preleukemic phase, marrow erythroblasts were multinucleated, and had duplicated nuclear and cytoplasmic membranes with frequent nuclear pockets and cytoplasmic vacuoles, respectively. All neutrophilic and eosinophilic granulocytes had severe quantitative and qualitative defects of granulogenesis; autophagy and nuclear pockets were also observed in the majority of granulocytic cells. Platelets had decreased granulation and extremely dilated canaliculi. Decreased titration scores with anti-I and anti-i were observed with the patient's erythrocytes and those of his clinically normal mother. The unusual morphologic and serologic findings in this patient appear to have resulted from a membrane abnormality affecting the cells of several hematopoietic lines and their organelles.
Adult↗
Peroxidase-containing microgranules in human neutrophils: physical, morphological, cytochemical, and secretory properties.
A microgranule fraction, isolated from human neutrophils by using a novel high-resolution Percoll density gradient system contained granules with the lowest density and diameter when compared with 12 other isopycnic granule fractions. Ultrastructurally, from 34% to 50% of the microgranules showed homogeneous diaminobenzidine (DAB) staining under conditions for localizing peroxidase reactivity. The presence of myeloperoxidase (MPO) was further confirmed by biochemical and spectral analysis and immunodiffusion methods. Periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) intensely stained vicinal glycols in the matrix of greater than 97% microgranules in contrast to the weak or absent staining seen in larger primary granules. Directly sampled segmented neutrophils contained small DAB- and PA-TCH-SP-positive granules, which often appeared in clusters. These DAB-positive microgranules selectively remained within the cells after stimulation of exocytosis with the calcium ionophore A23187. The enriched DAB-positive microgranule fraction recovered from A23187-treated cells also contained lysozyme and beta-glucuronidase but lacked vitamin B12 binding protein activity. A similar small, DAB- and PA-TCH-SP-positive granule type was also identified in normal promyelocytes and was the predominant or only granule type observed in leukemic or preleukemic myeloid cells from four patients. This study demonstrates a unique subpopulation of MPO-containing microgranules in normal and leukemic human myeloid cells that are distinguished from (other) primary granules by their extremely low density, small size, content of complex carbohydrates, and resistance to secretion.
Adult↗
Ultrastructural morphology and cytochemistry of iron-deficient polymorphonuclear leukocytes.
Previous studies have documented decreased activities of certain enzymes and altered function in polymorphonuclear leukocytes (PMN) during iron deficiency. The present study was undertaken to determine if the enzymatic abnormalities could be correlated with morphologic or quantitative change in PMN granules. Ultrastructural examination of primary and secondary granules and assessment of the secondary granule components alkaline phosphatase and vicinal glycol-containing glycoconjugates was performed in rabbit bone marrow, peripheral blood, and peritoneal heterophils. In addition, biochemical quantifications of the secondary granule component alkaline phosphatase and the primary granule marker beta-glucuronidase were performed. The results confirmed that a marked, significant decrease in alkaline phosphatase occurs in iron-deficient animals; however, no biochemical decrease in beta-glucuronidase activity was observed. Ultrastructurally, PMN secondary granules of iron-deficient rabbits tended to be more numerous than in controls when examined with morphometric and glycoconjugate staining methods, but lacked staining in alkaline phosphatase preparations. These results demonstrate that iron-deficient rabbits produce normal to increased quantities of primary and secondary granules, despite a uniform deficiency of alkaline phosphatase, a secondary granule marker.
Alkaline Phosphatase↗
Bone metastases in malignant gastrinoma.
Six patients (4 women, 2 men) with malignant gastrinoma developed multiple bone metastases; osteolytic as well as osteoblastic lesions occurred. All lesions involved the central skeleton, most caused symptoms, and, in 2 cases, there was associated hypercalcemia with normal serum parathormone levels. Poor responses were observed after treatment with cytotoxic drugs, but good symptomatic responses occurred after radiotherapy in 2 of the 4 patients in whom it was used. The peptic ulcer component of the disease was well controlled in all patients by cimetidine with or without anticholinergic supplements or by ranitidine alone in doses of 300-600 mg daily. Five of the 6 patients died with a mean survival after diagnosis of Zollinger-Ellison syndrome of 3.3 yr (range 1.0-7.0 yr), suggesting that bone metastases are associated with a poor prognosis in metastatic gastrinoma.
Adult↗
Light microscopic, non-immunologic demonstration of iron-binding proteins in hematopoietic cells.
Iron-binding proteins were localized by their saturation with iron using iron nitrilotriacetate (FeNTA), maintenance of protein-iron-binding at specific values of pH, and visualization of the iron with acid ferrocyanide (AF). Human neutrophilic cells showed strong blue granular and diffuse cytoplasmic staining. Human mid- and late-stage erythroblasts showed moderate diffuse cytoplasmic staining. Monocytes and macrophages showed reactions similar to those seen with AF technique alone. Other hematopoietic cells showed minimal or no stain positivity. Nuclear positivity was not observed in any cells. Concanavalin A (ConA) treatment of purified neutrophils reduced their FeNTA-AF positivity; supernatants from these cells showed precipitin lines of identity with anti-lactoferrin (Lf) stainable with FeNTA and AF. Cellulose acetate electrophoresis of crude neutrophil extracts treated with [59Fe]NTA showed multiple protein bands; one band co-migrated with purified Lf and showed autoradiographic positivity. Rabbit heterophils and rat neutrophils showed less FeNTA-AF positivity, consistent with less Lf in these cells than in human neutrophils. Washing smears with 0.1 M citrate, pH 6.0, between FeNTA and AF treatments eliminated only erythroblast positivity; 0.1 M citrate, pH 4.0, ablated neutrophil staining as well. Ferritin-hemosiderin staining was preserved at both values of pH. These results indicate that FeNTA-AF technique specifically visualizes neutrophil Lf, and suggest that the observed erythroblast positivity is due to transferrin (Tf).
Animals↗
Rheumatoid arthritis associated with expanded populations of granular lymphocytes.
Two patients with classic rheumatoid arthritis developed severe neutropenia and increased numbers of large granular lymphocytes in the blood and bone marrow. These lymphocytes exhibited homogeneous surface membrane immunophenotypes of Leu5+, Leu11-, Leu4+, Leu3-, Leu2-, Leu7+ and Leu5+, Leu11+, Leu4+, Leu3-, Leu2+, Leu7-, respectively. In both patients, neutropenia was initially corrected with corticosteroid therapy; long-term improvement followed low-dose oral cyclophosphamide and methotrexate therapies. In these 2 patients and 12 previous patients with rheumatoid arthritis associated with expanded populations of immunophenotypically homogeneous large granular lymphocytes, neutropenia occurred in all 14, thrombocytopenia in 6, anemia in 7, and mild or moderate splenomegaly in 12. In contrast to Felty's syndrome, granular lymphocyte expansions in rheumatoid arthritis usually occur in older patients, may appear simultaneously with arthritis, and are usually associated with normal or elevated blood leukocyte counts. Mild hemocytopenias in these patients can often be managed with observation. Therapy with corticosteroids or immunosuppressive-cytotoxic drugs may be beneficial in more severe cases, but splenectomy is not recommended.
Aged↗
Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation.
The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma-interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.
Antibodies, Monoclonal↗
Coagulation testing of Hickman catheter blood in patients with acute leukemia.
We quantified coagulation parameters in vitro using standard automated methods in 12 adult patients with acute leukemia who also had Hickman catheters (HC). Test results from simultaneously obtained HC blood and control peripheral venous blood (PB) samples were compared in the respective patients. Heparin solutions (100 U/mL, US Pharmacopoela) used to prevent the formation of clots within the HC appeared to cause, to a significant degree, spuriously elevated levels of fibrin degradation products (FDP), decreased levels of fibrinogen (FBG), and prolongations of the prothrombin time (PT) and activated partial thromboplastin time (PTT) in the first 10 mL of HC blood. The second 10 mL sample from the HC showed that FBG levels were comparable with those demonstrable in PB samples, as were levels of FDP in eight of 12 cases. Both PT and PTT times, however, remained significantly prolonged. An alternative maneuver for obtaining HC blood studied in four patients showed significant prolongation of PTT values in the second 10-mL sample despite levels of FDP, FBG, and PT similar to those in the PB. Because heparin contamination of HC blood can mimic the laboratory findings of disseminated intravascular coagulation or other coagulopathies in patients with acute leukemia, we suggest that only values obtained from PB be used for interpretation of coagulopathy in these patients.
Acute Disease↗
Isolated thrombocytopenia in a 56-year-old man with mitral stenosis.
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Coronary Vessels↗
Ultrastructural localization of transferrin, transferrin receptor, and iron-binding sites on human placental and duodenal microvilli.
Ultrastructural methods were used to determine the subcellular location of the transferrin receptor, transferrin and iron-binding sites on human term placenta and human duodenum microvillus surfaces. The transferrin receptor and transferrin were localized by immunocytochemical methods employing either OKT9, a human transferrin receptor monoclonal antibody, or mouse anti-human transferrin (ATfn), both followed by a horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG (GAM-HRP) and diaminobenzidine (DAB) sequence. Iron-binding sites were localized by acid ferrocyanide (AF) staining after saturation of tissue specimens with iron, accomplished with iron nitrilotriacetate (FeNTA), a known transferrin iron donor. Placental microvillus surfaces demonstrated staining for the OKT9-GAM-HRP-DAB-reactive transferrin receptor, ATfn-GAM-HRP-DAB-reactive transferrin, and FeNTA-AF-reactive iron acceptor, whereas enterocyte microvillus surfaces lacked significant staining with each of these methods. FeNTA-AF stained iron-binding substance in placental and enterocyte microvilli and cytoplasmic matrix. Thus using the same ultrastructural immunostaining and cytochemical methods transferrin receptor, transferrin, and nitrilotriacetate iron acceptor sites can be demonstrated on the microvillus surface of human placenta but not on the microvillus surface of human duodena.
Binding Sites↗
Active transport of lead-210 by everted segments of rat duodenum.
Everted gut sacs prepared from rat duodenum can transfer 210Pb from mucosal to serosal surfaces against concentration gradients in vitro. The mechanism requires oxygen and is significantly inhibited by sodium azide, sodium iodoacetate, 2,4-dinitrophenol, sodium cyanide, and sodium fluoride. Lack of oxygen or the presence of metabolic inhibitors produced greater relative inhibition of net serosal transfer but greater absolute decrements of net mucosal uptake. Treatment of rats prior to sac preparation with either intravenous FeCl2 or endotoxin, or the addition of FeCl2 to the mucosal medium, selectively inhibited net serosal transfer. Net mucosal uptake and net serosal transfer were significantly negatively correlated with animal weight. Jejunal or ileal sacs did not actively transport 210Pb.
2,4-Dinitrophenol↗
Ultrastructural cytochemical identification of the siderophilic enterocyte.
Specific iron-binding sites in the gut were visualized by the sequential incubation of glutaraldehyde-fixed specimens in iron nitrilotriacetate (FeNTA) and acid ferro-cyanide (AF). In rat duodenum, jejunum, and ileum, approximately half of the enterocytes from the crypt to the distal villus contained FeNTA-AF-reactive material. The staining intensity of individual enterocytes appeared to decrease progressively in more distal locations in the gut. Maximal FeNTA-AF staining was observed in cells in the upper half of the villus, and was localized primarily in microvilli, apical cytoplasm, and lateral membranes. In duodenal crypt cells, stain deposits were present primarily in the microvilli. FeNTA-AF stained sites in the cytoplasmic and microvillus matrix were approximately 100-fold greater in number than were sites of intrinsic iron stained with AF alone. FeNTA-AF and AF staining in human duodenal enterocytes was similar to that observed in rat duodena, demonstrating the applicability of this methodology to human samples. In rat duodena, the distribution of AF staining alone in specimens taken 10 min after the in vivo intraduodenal administration of FeCl2 was similar to that of FeNTA-AF staining in tissue from fasted animals not given iron. The distribution and frequency of iron-binding sites stainable with the FeNTA-AF method which occur in a subpopulation of enterocytes can be correlated closely with physiologic, histologic, and ultrastructural parameters of inorganic iron absorption previously reported.
Animals↗
Blastic transformation of essential thrombocythemia: dual expression of myelomonoblastic/megakaryoblastic phenotypes.
Three patients developed blastic transformation of essential thrombocythemia (tET). Morphological studies in all patients showed that the majority of blasts had either myeloblastic or myelomonoblastic differentiation. Immunologic assays of hematopoietic cells were performed in two patients. In patient 1, 86% of peripheral blood mononuclear cells (predominantly blasts) reacted with a monoclonal antibody specific for granulocytes and monocytes (MMA), and 15% of mononuclear cells reacted with Tab, a monoclonal antibody specific for megakaryocyte-platelet glycoproteins (PGP) IIb and IIIa. In patient 2, 41.5% of peripheral blood mononuclear cells (predominantly blasts) were MMA-positive, 22.5% were Tab-positive, and 40% reacted with rabbit anti-human PGP. These results suggest either that two subpopulations of blast cells exist in tET, or that blast cells simultaneously express surface markers of myeloblastic/monoblastic and megakaryoblastic differentiation. In these three and in nine previously reported cases of tET, neither age, sex, nor previous therapy were obvious etiologic factors. tET occurred 24.2 +/- 14.4 mo after diagnosis of essential thrombocythemia, and a majority of patients had hepatomegaly and/or splenomegaly, anemia, leukocytosis, and thrombocytopenia. Leukemic cell morphology was myeloblastic and/or monoblastic in 12/12 patients, 5/12 had marrow fibrosis. Despite various treatments, death occurred in 3.6 +/- 2.7 mo; one patient had a brief complete remission.
Aged↗