Thymopoietin and bursopoietin: induction signals regulating early lymphocyte differentiation.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
G Goldstein
Publications and source records attributed to G Goldstein.
Do surgeons contribute adequately to stoma aftercare?
Explore the source record for details and available documents.
Abdominal Muscles↗
Induction of human granulocyte differentiation in vitro by ubiquitin and thymopoietin.
Human bone marrow cells were separated according to density by centrifugation on Ficoll-Hypaque gradients and then according to size by velocity sedimentation. This procedure resulted in fractions enriched for immature granulocytes, mature granulocytes, and lymphocytes. Cells in these fractions were analyzed for their expression of certain surface and functional differentiation markers and for their ability to respond to thymopoietin and ubiquitin with the expression of additional differentiation markers. A higher percentage of band form and segmented granulocytes than of more immature granulocytes expressed complement receptors on their surfaces. Thymopoietin and ubiquitin induced a significant percentage of the cells in the immature granulocyte fraction to express this marker. These data suggested that the complement receptor may be viewed as a differentiation marker on human granulocytes, the expression of which can be induced in vitro by thymopoietin and ubiquitin. Furthermore, fractions containing predominantly band form granulocytes were induced by ubiquitin (but not thymopoietin) to develop the capacity to respond to chemotactic agents, and cell fractions containing predominantly myelocytes and metamyelocytes were induced by thymopoietin and ubiquitin to develop the capacity to phagocytose latex particles. These findings indicated that thymopoietin and ubiquitin, two agents known to induce a number of stages of human and mouse lymphocyte differentiation, are also capable of inducing some stages of human granulocyte differentiation in vitro.
Binding Sites, Antibody↗
Separation of polycyclic aromatic hydrocarbons by liquid chromatography on cross-linked polyvinylpyrrolidone.
Polycyclic aromatic hydrocarbons (PAHs) can be separated by liquid chromatography on cross-linked polyvinylpyrrolidone (PVP) stationary phase using a polar solvent as eluent. The order of elution is determined primarily by the number of condensed aromatic rings Efficient separations were obtained with a column packed with 63-90 mum particles of PVP and isopropanol as eluent. Capacity factors (k') ranged from 0.3-10 for PAHS having from one to five aromatic rings, and theoretical plate heights were between 0.3 and 0.5 mm. This technique is being used to assist in the characterization of products from coal liquifaction processes.
Chromatography, Liquid↗
Terminal deoxynucleotidyl transferase is found in prothymocytes.
Terminal deoxynucleotidyl transferase is an enzyme which has the unique property of polymerizing polydeoxynucleotides onto a primer in the absence of a template (1,2). This enzyme is found both in the thymus and the bone marrow of birds, rodents, and humans (3-7). Whether the marrow cells that contain terminal transferase are related to thymocytes, or are on a separate pathway of differentiation, is not yet known (7,8). To determine the lineage of the murine bone marrow cells that have terminal transferase, we have investigated whether these cells have the antigen Thy-1 induced on the cells by treatment with thymopoietin (9). Thymopoietin is known to induce a set of characteristic T-cell markers including the Thy-1 alloantigen on the surface of a subpopulation of bone marrow cells committed to T-cell differentiation (prothymocytes) (10). Destruction of Thy- 1-positive cells after exposure to thymopoietin allows elimination of a substantial fraction of those bone marrow cells that can repopulate an irradiated thymus (11). We find that such an elimination after induction with the thymic polypeptide removes a substantial amount of terminal transferase from the bone marrow cell population, suggesting that at least one-half of the marrow cells bearing this enzyme are related to those found in the thymus.
Animals↗
Lymphocyte-differentiating hormone of bursa of fabricius.
Induction of early lymphocyte differentiation was studied in vitro in fractionated bone marrow cells of newly hatched chickens, with alloantiserums to identify newly differentiated B cells (Bu-1+) and T cells (Th-1+). Thymus extract induced selective T cell differentiation; the activity of the extract corresponds to that of thymopoietin. Bursal extract induced both B cell and T cell differentiation, but at lower concentrations B cell differentiation was always greater. This activity is ascribed to a lymphocyte-differentiating hormone of the bursa of Fabricius, for which the name bursopoietin is suggested.
Animals↗
Ameloblastic sarcoma: pathogenesis and treatment with chemotherapy.
A recurrent tumor in a young male demonstrates the progression of an ameloblastic fibroma to an ameloblastic sarcoma. Chemotherapy with Actinomycin D, Vincristine, and Cytoxan produced a complete response without evidence of recurrence 4 years after initiation of chemotherapy. The patient developed an aggressive malignant melanoma 1 year after all chemotherapy was discontinued.
Adult↗
Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis.
Bone marrow from a patient with aplastic anemia was shown by multiple criteria to have a block in early myeloid differentiation. This block was overcome in vitro by elimination of marrow lymphocytes. Furthermore, this differentiation block was transferred in vitro to normal marrow by coculturing with the patient's marrow. We suggest that some cases of aplastic anemia may be due to an immunologically based suppression of marrow cell differentiation rather than to a defect in stem cells or their necessary inductive environment.
Adult↗
Sensitivity reactions to intradiscal injection of chymopapain during general anesthesia.
Explore the source record for details and available documents.
Adult↗
Differentiation of thymocytes: evidence that induction of the surface phenotype requires transcription and translation.
Induction of thymocyte differentiation requires transcription of DNA and translation of RNA but not replication of DNA. This was determined in vitro by studying the effects of cytosine arabinoside, hydroxyurea, actinomycin D, camptothecin, cordycepin, cycloheximide, and puromycin on the induction by thymopoietin of thymocyte differentiation, measured by the acquisition of the differentiation allo-antigens TL and Thy-1 by and inducible fraction of mouse spleen cells. This requirement for transcription does not establish whether the new mRNA represents transcripts of structural genes for the thymocyte allo-antigen markers; an answer to this question awaits the results of further experiments.
Animals↗
Heterogeneity of stem cells in severe combined immunodeficiency.
Two patients with severe combined immunodeficiency disease (SCID) having variable B-cell development have been shown to have marrow precursors of lymphoid cells which can be induced in vitro by thymic factors to express certain T-cell surface characteristics (HTLA+ phenotypes). Their marrow cells could not, however, be induced by these same factors to develop the E-rosette marker or functional activities of T lymphocytes. The marrow of these children also showed, when compared to that of normal adults, a different distribution of cellular elements on density gradient fractionation. The findings support the view that the disorder under study has a different pathogenesis from other forms of SCID previously analysed.
Age Factors↗
The abnormal hepatic scan of chronic liver disease: its relationship to hepatic hemodynamics and colloid extraction.
To help explain the characteristic hepatic scan pattern of chronic liver disease, the degree of scan abnormality (scan score, SS) after administration of technetium-99m sulfur colloid (Tc) was compared with data obtained at hepatic vein catheterization in 28 patients. Although SS showed a correlation with wedged hepatic vein pressure (r = +0.491), the scan abnormality was not directly due to portal hypertension because it remained unchanged when the latter was relieved by portacaval shunt. Also, the scan abnormality was found to be unrelated to a low hepatic blood flow. Scan abnormality was not attributable primarily to hyperactivity of the reticuloendothelial (RE) cells of the spleen and bone marrow since fractional clearance (K) of Tc from the blood was decreased rather than increased in patients with abnormal scans. SS was inversely correlated with K or Tc (r = -0.575) and with hepatic extraction efficiency for Tc (r = -0.673), showing that the basic abnormality was poor extraction of the colloid by the RE cells of the liver with a resultant increase in the amount available for extrahepatic localization. Indirect evidence suggests that this poor extraction of colloid is due to intrahepatic shunts bypassing hepatic RE cells.
Blood Pressure↗
Radioimmunoassay for thymopoietin.
A radioimmunoassay for thymopoietin was developed that detects thymopoietin concentrations greater than 5 ng/ml. A critical point in development of the radioimmunossay was preparation of 125I-labeled thymopoietin by the Bolton-Hunter method, since direct iodination of tyrosyl residues impaired the immunoreactivity of thymopoietin.
Hormones↗
Differentiation of T cells in nude mice.
Cells bearing the T-cell differentiation alloantigens TL and Thy-1 were enumerated in preparations of spleen and lymph node cells of nu/nu mice. Healthy nu/nu mice had few or no demonstrable TL+ or Thy-1+ cells whereas mice with viral hepatitis, including some born of nu/nu X nu/nu matings, had many. Healthy nu/nu mice were treated daily with the thymic hormone thymopoietin or with ubiquitin, polypeptides that induce the differentiation of TL+Thy-1" cells from TL-Thy-1- precursors in vitro. After 14 days, 20 to 40 percent of their spleen cells were of the TL+Thy-1+ phenotype typical of thymocytes and 10 to 25 percent of their lymph node cells were TL-Thy-1+, typical of later T-cell differentiation. Similar frequencies of such cells were found in untreated nu/nu mice suffering from severe viral hepatitis. These data conform to the current view that prothymocytes are preprogrammed cells whose maturation to thymocytes, normally induced in the thymus by thymopoietin, can be triggered by other agents under abnormal circumstances. Tests of T-cell function were not included in this study.
Animals↗
Thymopoietin and myasthenia gravis: neostigmine-responsive neuromuscular block produced in mice by a synthetic peptide fragment of thymopoietin.
Thymopoietin is the thymic hormone responsible for inducing the differentiation of thymocytes. A synthetic peptide corresponding to positions 29-41 of bovine thymopoietin II, which can reproduce this function of the parent molecule in vitro, also caused neostigmine-responsive neuromuscular block in mice similar to that which thymopoietin itself produces, and which resembles the neuromuscular block of myasthenia gravis. This 13 aminoacid sequence must therefore contain the key residues in the thymopoietin molecule responsible for both T-cell differentiation and neuromuscular effects. These data provide further support for the view that myasthenia gravis is a consequence of thymic disease associated with systemic release of thymopoietin, with ensuing neuromuscular block. This evidence supports the empirically proven treatment of myasthenia gravis by early total thymectomy.
Action Potentials↗
Molecular conservation of 74 amino acid sequence of ubiquitin between cattle and man.
Explore the source record for details and available documents.
Amino Acid Sequence↗
The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells.
The complete amino acid sequence was determined for bovine ubiquitin, and adenylate cyclase stimulating polypeptide, which is probably represented universally in living cells. Ubiquitin has a molecular weight of 8451 and consists of a single polypeptide chain containing 74 amino acid residues. It contains four arginine residues but no cysteine or trytophan residues. The first 61 amino acid residues were obtained by automated Edman degradations. Tryptic digestion of maleated ubiquitin yielded four peptide fragments that were resolved by molecular sieve chromatography and coded in order of decreasing chain length (MT-1, MT-2, MT-3, and MT-4). The automated sequenator determinations on native ubiquintin provided overlapping sequence data for three of these fragments that gave an order of MT-1, MT-3, and then MT-2; Peptide MT-4, a dipeptide, was therefore assigned to the C terminus, and the placement of peptide MT-2 was corroborated by analysis of data from carboxypeptidase digestions of maleated ubiquitin. Peptide MT-2 was domaleated and sequenced by manual Edman degradations through a single lysine residue. It was cleaved at this residue with trypsin, and the two resultant peptides were separated by ion-exchange chromatography. Manual sequencing of the C-terminal demaleated tryptic peptide of MT-2 completed the sequence of MT-2 and that of native ubiquitin. The sequence of ubiquitin was further confirmed and supported by amino acid and parital sequence anlysis of fragments obtained by digestion of maleated ubiquitin with chymotrypsin or staphylococcal protease.
Adenylyl Cyclases↗
The isolation of thymopoietin (thymin).
The isolation from bovine thymus of two closely related polypeptides, thymopoietin I and II, is described. These are considered to be thymic hormones, which physiologically induce the differentation of prothymocytes to thymocytes within the thymus. Ths isolation of the thymopoietins was monitored not by their differentiative effects, but by a presumably secondary effect on neuromuscular transmission. This was discerned in experimental studies related to the human disease myasthenia gravis in which it was suggested that autoimmune thymitis was regularly present. In an animal model, experimental autoimmune thymitis, the thymic disease was shown to result in the release of a substance that depressed neuromuscular transmission and this substance was shown to be also secreted in small amounts by the normal thymus. A bioassay was developed, this being the delayed appearance of neuromuscular impairment after in vivo injection of the active material, and this bioassay was used to monitor the fractionation of thymus extracts and isolate thymopoietin. Pure thymopoietin was active at subnanogram concentrations, both in producing its effect on neuromuscualr transmission and in inducing the differentiation of prothymocytes to thymocytes. This potency of activity of the purified polypeptide, as well as its specificity in inducing the differentiation of T-cells and not B-cells, support the consideration that thympoietin is a physiological inducing hormone produced by the thymus. This is further supported by the evidence that thymopoietin is only produced in the thymus: neuromuscular blocking effects are not present in extracts of other tissues and immunofluorescent localization of thymopoietin shows it to be present only in thymic epithelial cells.
Animals↗