Search PubMed⌕ Search

Biomedical subjects

J C Barton

Publications and source records attributed to J C Barton.

At least 91 records · Page 5Linked to original sources

Suppression of in vitro monoclonal human rheumatoid factor synthesis by antiidiotypic antibody. Target cells and molecular requirements.

Previous studies have indicated that antiidiotypic antibody can modulate expression of idiotype both in vivo and in vitro. Although the precise mechanisms underlying modulation of idiotype expression by antiidiotype remains unclear, a requirement for intact IgG antiidiotypic antibody has been suggested and T cells appear to play a role in some systems. We have studied peripheral blood mononuclear leukocytes (MNL) from a patient with a B cell lymphoma and a circulating IgMK rheumatoid factor (RF) paraprotein in an effort to delineate mechanisms involved in regulation of idiotype expression by antiidiotypic antibody. 1-10% of MNL from this patient could be cytoplasmically stained with specific F(ab')2 antiidiotypic antibody. MNL from the patient spontaneously synthesized IgM RF in culture that possessed the same idiotype as the circulating IgM RF paraprotein. Production of RF by MNL was suppressed by pretreatment with either intact IgG or the F(ab')2 fragments of antiidiotypic antibody (50% inhibitory concentration was 0.2 and 1.1 micrograms/culture, respectively). In contrast, the Fab' fragment of antiidiotypic antibody was not inhibitory (up to 57 micrograms/culture) despite retaining demonstrable antiidiotype activity. Suppression of RF production was not observed over the same concentration range with the IgG or F(ab')2 fractions of a non-cross-reactive antiidiotypic antibody prepared against another monoclonal IgMK RF paraprotein or with IgG or F(ab')2 fractions prepared from normal rabbit serum. Inhibition of RF production by antiidiotypic antibody did not require T cells. Antiidiotypic antibody decreased intracellular and extracellular levels of idiotype indicating diminished synthesis of idiotype by the patient's B cells. Synthesis of IgM RF by MNL obtained from unrelated donors was not suppressed by the antiidiotypic antibody specific for the patient's paraprotein. The results indicate that (a) antiidiotypic antibody is capable of directly suppressing human B cell release of idiotype, (b) the bivalent antigen-binding fragment (F[ab']2) of antiidiotypic antibody is sufficient for mediating such suppression, (c) an intact Fc portion of antiidiotypic antibody enhances suppression of idiotype, and (d) antiidiotypic antibody inhibits idiotype expression by suppressing synthesis of idiotype.

Animals↗

Calcium inhibition of inorganic iron absorption in rats.

Calcium significantly diminishes the absorption of ferrous and ferric iron in a dose-related manner, whether the test doses of calcium and radioiron are administered orally or introduced into isolated intestinal segments; the effect is maximal in the duodenum and jejunum. Electron microscopic observations and quantitative studies of the mucosal uptake and transfer of iron show that calcium decreases the entry of iron into the microvilli of intestinal epithelial cells. Animals fed a high-calcium, iron-replete diet developed iron depletion; animals consuming high-calcium food of marginal iron content developed mild iron deficiency anemia. Further, more radioiron was absorbed from human milk than either bovine milk or human milk supplemented with calcium. These data suggest that individuals consuming a high-calcium diet contain marginal amounts of iron could develop iron deficiency anemia and may explain why infants who are fed cow's milk have a greater incidence of iron deficiency anemia than those fed human milk.

Anemia, Hypochromic↗

Ultrastructural localization of lactoferrin and iron-binding protein in human neutrophils and rabbit heterophils.

Lactoferrin in marrow and blood granulocytes from rabbits and humans was stained with an immunoferritin method. Iron-binding protein(s) was localized by the staining of granulocytes with acid ferrocyanide after saturation of the iron-binding protein with iron. The latter was most readily accomplished by treatment of the glutaraldehyde-fixed cell suspension with 1% saponin, followed by treatment with an iron-nitrilotriacetate (Fe-NTA 3mM:4mM) solution, adjusted to pH 7.0 with NaHCO3. The affinity of purified lactoferrin and transferrin for radioiron after such treatment was minimally diminished. Both immunoferritin and iron-binding methods heavily stained osmiophiliuc (phospholipid-containing) mature primary granules in late promyelocytes, myelocytes, and polymorphonuclear cells. Early promyelocytes containing abundant immature primary granules lacked immunoferritin or iron staining. Trypsin digestion of rabbit marrow cells considerably diminished the cytochemically demonstrable iron-binding capability of the mature primary granules. Specimens sequentially stained for peroxidase and immunostained for lactoferrin or cytochemically stained for iron-binding protein confirmed that lactoferrin and iron-binding protein were in peroxidase-positive primary granules. Some peroxidase positive granules appeared to lack staining for lactoferrin and iron-binding proteining protein, and all secondary granules uniformly lacked staining. Treatment of human neutrophils with phorbol myristate acetate demonstrated early release of granules containing iron-binding protein with subsequent agglutination of neutrophils and attachment of iron-binding protein to the cell surface. In summary, this study distinguishes at least two subpopulations of primary granules and identifies lactoferrin and an iron-binding protein(s) in a subpopulation of peroxidase-positive primary granules in rabbit heterophils and human neutrophils.

Animals↗

Factors affecting iron balance.

The availability of radioisotopes of iron led to the performance of physiologic studies of the absorption, excretion, and kinetics of iron. The effects of dietary constituents and intestinal secretions upon iron absorption have been thoroughly explored and have permitted the development of tools for nutritional studies in various geographic areas of the world. The basic mechanisms for regulation of iron absorption are not fully understood. However, the isolation and characterization of newer iron-binding proteins, the existence of mucosal receptors in which there is competition for iron-binding sites with other metals, and the identification of a number of animal models with genetic abnormalities of iron absorption provide promise for development in the foreseeable future. The means by which the body informs the intestine to increase or decrease iron absorption is poorly understood, and the abnormality in hemochromatosis and iron overloading disorders remains unexplained. Much has been learned in recent years regarding the structure of iron-containing proteins and the variations that exist in different species. Similar problems remain to be solved with regard to the intermediary metabolism of iron in red blood cell precursors and other cells in the body. It is postulated that the combined usage of physiologic, biochemical, and immunologic investigations will provide the basic information required.

Absorption↗

15-Hydroxyprostaglandin dehydrogenase and delta 13 reductase content of gastrointestinal organs of rabbits and rats.

15-Hydroxyprostaglandin dehydrogenase was measured in various gastrointestinal and non-gastrointestinal tissues from rabbits and rats. In addition, delta 13 reductase activity was measured in fundic and antral mucosae and gastric muscle from rabbits. In rabbits, antral mucosa contained the greatest activity of 15-hydroxyprostaglandin dehydrogenase and was 6 times more active than rabbit lung and fundic mucosa. In rat, duodenal mucosa was more active than antral mucosa or pancreas, suggesting that interspecies variations may exist. delta 13 reductase in rabbit gastric tissues was also more active in antral mucosa than in fundic mucosa or gastric muscle. The high activities of these enzymes in antral mucosa in conjunction with the known large prostaglandin content, particularly PGE2 and PGI2, suggest a large biological turnover of prostaglandin in these tissues.

15-Oxoprostaglandin 13-Reductase↗

Effect of phosphate on the absorption and retention of lead in the rat.

An inverse relationship between lead retention and dietary phosphate content has been known to exist for many years but the reasons for this association remained unknown. In rats, the manipulation of dietary phosphate content had no significant effect upon the absorption of lead from isolated gastrointestinal segments, but animals fed low phosphate content food had increased whole-body retention and bone deposition of intravenously administered tracer doses of radiolead. Intraluminal phosphate decreased the absorption of test doses of radiolead from the small intestine, possibly due to precipitation of lead in the gut lumen. Further, rats fed low phosphate diets absorbed increased quantities of an oral lead dose. Dietary phosphate deficiency may significantly increase body lead burdens by decreasing intraluminal lead precipitation and increasing lead retention, primarily in bone. Increased dietary phosphate, however, acts primarily to limit lead absorption.

Animals↗

Nonhemolytic, noninfectious transfusion reactions.

The delivery of optimal transfusion therapy requires that the physician first have a thorough understanding of his patient's disease and prior transfusion history. Sometimes the need for blood product administration is more apparent than real. In the selection of necessary therapy, particular blood components, their volumes, and the timing of their administration should be carefully planned. The transfusion of whole blood, particularly as single-unit transfusions, is rarely indicated. Often forgotten, autotransfusion represents a means whereby many subjects who have repeated, unusual, or severe reactions may receive safe treatment. An appreciation of the frequency and manifestations of transfusion-related problems permits effective treatment of ongoing reactions. The prophylactic measures which should be taken against future reactions in most patients are specific, and are the responsibility of the clinician, based upon his bedside observations and laboratory studies. Problems should be discussed with either a hematologist, pathologist, or blood banking expert without hesitation. These guidelines help conserve a precious resource and assure that safe, effective, and economical transfusion therapy is available for all patients in need.

Animals↗

Ultrastructural, cytochemical, and radioautographic localization of placental iron.

Maternal-fetal iron transfer across the guinea pig hemomonochorial placenta during the first, second, and third trimesters was examined using ultrastructural, cytochemical, radioautographic, and ferrokinetic methods. Acid ferrocyanide stained inorganic ferric iron on and in sinusoidal microvilli, cytoplasmic matrix or ground substance, and the outer basal plasmalemma of epithelial cells. Some stain deposits were observed within and on either side of the basement membrane. The extraluminal outer plasmalemma, intercellular junctions, and cytoplasm of endothelial cells frequently contained numerous stain deposits. Staining of trophoblast sinusoidal microvilli was similar during early and late gestation, whereas the staining of the basement membrane and endothelial cells was most prominent during the second and third trimesters. Staining of ferric iron was encountered in rare cytoplasmic granules of epithelial cells during late gestation, but not during early gestation. Placental macrophages contained acid-ferrocyanide-reactive ferric iron in large heterophagosomes and hyaloplasm. Acid ferricyanide failed to localize ferrous iron in either epithelial cells or macrophages. Light-microscopic radioautographic studies localized radioiron in placental epithelial cells and Prussian-blue-positive macrophages in specimens obtained 30 minutes after injection of radioiron ((55)Fe, (59)Fe) into the maternal saphenous vein. At the ultrastructural level labeling was observed (in order of decreasing grain density) in or on the epithelial basal plasmalemma and basement membrane, endothelial cytoplasm, epithelial sinusoidal microvilli, and epithelial cytoplasm. Significant staining or radiolabeling was not observed in mitochondria, trophoblast granules, or nuclei. These results indicate that placental non-heme iron is trivalent and moves from the maternal to the fetal circulation by passing through trophoblast microvilli, cytoplasmic matrix, basal plasmalemma, basement membrane, endothelial cell junctions, and cytoplasm.

Animals↗

Isolated marrow lymphoma: an entity of possible T-cell derivation.

Seven adults had a distinct clinicopathologic type of lymphoproliferative disorder of the bone marrow. All patients presented with weakness and pancytopenia; no evidence of gross extramedullary involvement was found. In 5 cases severe and prolonged bone marrow hypoplasia was associated with combination chemotherapy; 1 patient died of infection during initial therapy. In 6 of the 7 cases, clinical improvement occurred following therapy. As a terminal event, 2 patients developed a leukemic phase. Tumor cell from 4 patients were studied immunologically, and in 2 patients surface marker characteristics suggestive of T-cell tumor origin were found. In 2 cases, ultrastructural studies of lymphoid cells were compatible with a T-cell neoplasm. The above data suggest that these cases represent a distinct type of chemotherapy-sensitive lymphoma in which conservative initial treatment may induce a response without prolonged bone marrow hypoplasia.

Adult↗

Acute lymphoblastic leukemia in idiopathic refractory sideroblastic anemia: evidence for a common lymphoid and myeloid progenitor cell.

Acute leukemia of myeloblastic or erythroblastic morphology occasionally occurs as a complication of idiopathic refractory sideroblastic anemia, but the development of acute lymphoblastic leukemia has not been previously reported in these cases. A patient with idiopathic refractory sideroblastic anemia is described in whom acute lymphoblastic leukemia occurred. The leukemic cells were characterized by typical lymphoblastic morphology on Wright's stain, periodic acid-Schiff-positive cytoplasmic clumps, elevated levels of deoxynucleotidyl transferase (143 units/10(8) cells), high numbers of specific glucocorticoid binding sites (16,845 sites/cell, Kd = 5.40 x 10(-9) M), non-B, non-T cell immunologic characteristics and clinical responsiveness to therapy with vincristine, prednisone, and methotrexate. Ultrastructural studies of the lymphoblasts identified ferruginous material in lysosomes and occasional mitochondria similar to but less abundant than that seen in abnormal sideroblasts. The concurrence of these two disorders supports the theory that in humans both lymphoid and myeloid cell lines arise from a common pluripotent stem cell.

Anemia, Sideroblastic↗

Provoked priapism in sickle cell anemia.

Two patients with sickle cell anemia are reported who developed relative impotence after repeated episodes of priapism. They learned that excessive ethanol ingestion produced an erection and utilized this mechanism to satisfy sexual partners. Hospitalization and transfusion therapy were required for repeated episodes of priapism. Extensive interviews were required in order to learn the sequence of events. This synergistic relationship between ethanol and priapism should be sought in patients with repeated hospitalizations for this complication of sickle cell anemia because it is preventable with appropriate counseling.

Adult↗

Isolated chylopericardium associated with lymphoma.

We have described the occurrence of isolated chylopericardium associated with lymphocytic lymphoma in remission. The effusion may have been related to previous mediastinal lymphoma. Further, pericardial and mediastinal exploration for pericardial effusion represents appropriate treatment of patients with malignancies in whom preliminary studies fail to demonstrate conclusive evidence of residual neoplasm.

Chyle↗

Effects of vitamin D on the absorption and retention of lead.

A relationship between lead retention and vitamin D has been recognized for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary vitamin D content had no significant effect on the absorption of lead from isolated gut loops and parenteral vitamin D stimulation did not affect lead absorption in rachitic animals. In contrast, dietary vitamin D deficiency and repletion resulted in increased absorption in intact animals due to prolonged gastrointestinal transit time. Both dietary vitamin D deficiency and repletion were associated with decreased body retention of radiolead given intravenously. Further, single doses of parenteral vitamin D administered to animals previously given tracer radiolead resulted in a dose-related enhancement of lead excretion and changes in tissue lead content.

Animals↗