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T L Low

Publications and source records attributed to T L Low.

At least 37 records · Page 2Linked to original sources
PubMed1981

Thymosin stimulates secretion of luteinizing hormone-releasing factor.

Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.

Animals↗
PubMed1981

Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations.

The amino acid sequence of thymosin beta 4, a polypeptide isolated from calf thymus, was determined. Thymosin beta 4 is composed of 43 amino acid residues and has a molecular weight of 4982 and an isoelectric point of 5.1. The NH2 terminus of the peptide is blocked by an acetyl group. This molecule induces expression of terminal deoxynucleotidyl transferase (DNA nucleotidylexotransferase, EC 2.7.7.31) in transferase-negative murine thymocytes in vivo and in citro. Thus, it appears that thymosin beta 4 acts on lymphoid stem cells and may control the early stages of the maturation process of thymus-dependent lymphocytes. This peptide is one of several present in thymosin fraction 5 that participates in the regulation, differentiation, and function of thymus-dependent thymocytes.

Amino Acid Sequence↗
PubMed1980

Production of biologically active N alpha-desacetylthymosin alpha 1 in Escherichia coli through expression of a chemically synthesized gene.

Thymosin alpha 1, an immune restorative polypeptide hormone, was synthesized in Escherichia coli by using recombinant DNA cloning techniques. Based on the known amino acid sequence, a gene coding for the thymosin alpha 1 polypeptide chain was designed and enzymatically assembled from chemically synthesized oligodeoxyribonucleotide fragments. The gene was ligated into plasmid pBR322 and placed under lac operon control, and N alpha-desacetylthymosin alpha 1 was expressed as part of a beta-galactosidase chimeric protein. Cyanogen bromide cleavage of this protein gave a mixture of polypeptides, among which thymosin alpha 1 activity was detected by radioimmunoassay (RIA). The E. coli product is identical with native thymosin alpha 1 isolated from calf thymus in the amino acid sequence but lacks the N-terminal acetyl group. Results of a guinea pig migration inhibition factor (MIF) assay, a terminal deoxyribonucleotidyl transferase (TdT) assay, and radioimmunoassay indicate that the N alpha-desacetylthymosin alpha 1 produced by deoxyribonucleic acid (DNA) cloning techniques has biological activity equivalent to that of the native hormone.

Amino Acid Sequence↗
PubMed1980

Thymosin: basic properties and clinical application in the treatment of immunodeficiency diseases and cancer.

Thymosin fraction 5 contains a family of polypeptides with varying biological activities. Current efforts in the thymosin research program are involved in further chemical characterization of thymosin peptides and evaluation of clinical immunotherapeutic protocols. Recent clinical studies with thymosin fraction 5 have shown therapeutic potentials for treatment of patients with primary immunodeficiency diseases and cancer.

Cyclic GMP↗
PubMed1979

Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain.

In order to establish the complete amino acid sequence of the human IgA alpha1 chain Bur, IgA1 protease from Streptococcus sanguis was employed to generate Fabalpha and Fcalpha fragments in the final stage of this investigation. Cyanogen bromide cleavage of the Fabalpha fragment followed by reduction and aminoethylation produced the Fd' fragment (residues 84 to 227); this contains part of the variable region (VR), the whole first constant domain (Calpha1), and part of the hinge region of this heavy chain. The tryptic peptides of the Fd' fragment were isolated, characterized, and sequenced. The results together with the data in the preceding papers on chymotryptic, tryptic, and thermolysin peptides permitted the complete amino acid sequence of the human IgA alpha1 chain to be established.

Amino Acid Sequence↗
PubMed1979

Primary structure of a human IgA1 immunoglobulin. II. Isolation, composition, and amino acid sequence of the tryptic peptides of the whole alpha1 chain and its cyanogen bromide fragments.

As part of the strategy for determining the covalent structure of a human IgA1 molecule (Bur), a tryptic digest was prepared of the reduced and carboxymethylated alpha1 heavy chain. In addition to the main experiment, tryptic peptides were prepared from the succinylated aminoethylated alpha1 chain and from fragments obtained by CNBr scission of the alpha1 chain. Complete recovery of the peptides was impeded by the large size of some of the tryptic peptides and of the principal CNBr fragment, and difficulty in separating other glycopeptides. Twenty-eight tryptic peptides of the reduced and carboxymethylated alpha1 chain were purified and sequenced, accounting for more than 300 residues. Additional information was obtained by sequence analysis of trypudies described in this series of papers contributed to the complete sequence analysis of the alpha1 chain.

Amino Acid Sequence↗
PubMed1979

Primary structure of a human IgA1 immunoglobulin. III. Isolation, composition, and amino acid sequence of the thermolysin peptides.

As part of the strategy for determination of the complete covalent structure of a human IgA immunoglobulin, 66 peptides were isolated from a thermolysin digest of reduced and carboxymethylated IgA alpha1 chain Bur and were purified. They range in length from 2 to 24 residues. Some of the peptides have been characterized and sequenced in order to supply needed information that was not obtained from the chymotryptic and tryptic peptides. These thermolysin peptides provide much necessary data to produce a rigorous proof for the primary structure of the human alpha1 chain. The remaining peptides from the thermolysin digest whose amino acid composition and NH2-terminal residues were sufficient to identify them unequivocally have also been assigned in the structure. They supply additional information that helps remove ambiguity in the structure, and they provide useful data about the profile of the peptide bonds that are susceptible to thermolysin digestion.

Amino Acid Sequence↗
PubMed1979

The chemistry and biology of thymosin. I. Isolation, characterization, and biological activities of thymosin alpha1 and polypeptide beta1 from calf thymus.

A partially purified extract from thymus tissue termed thymosin Fraction 5 has been shown to reconstitute immunological deficiencies resulting from the lack of thymic function in several animal models, as well as humans with primary and secondary immunodeficiency diseases. Thymosin Fraction 5 consists of a family of polypeptides with molecular weights ranging from 1,000 to 15,000. Several of these polypeptides contribute individually to the biological activity of the parent compound. Two polypeptide components of thymosin Fraction 5, termed thymosin alpha1 and polypeptide beta1, have been characterized chemically and biologically. Thymosin alpha1 is a highly acidic molecule composed of 28 amino acid residues. This polypeptide has potent biological activity and has been found to be 10 to 1,000 times as active as thymosin Fraction 5 in one in vivo and several in vitro bioassay systems designed to measure differentiation and function of thymus-dependent lymphocytes (T cells). Polypeptide beta1, in contrast, is inactive in our bioassay systems, suggesting that it is not involved in thymic hormone action. Sequence analysis and homology studies have indicated that polypeptide beta1, although present in Fraction 5, does not contribute to the biological activity of thymosin Fraction 5.

Animals↗
PubMed1979

The chemistry and biology of thymosin. II. Amino acid sequence analysis of thymosin alpha1 and polypeptide beta1.

The amino acid sequences of two polypeptide components of thymosin Fraction 5 termed thymosin alpha1 and polypeptide beta1 have been established. The sequences were determined by automatic Edman degradation of the intact molecules as well as by manual sequence analysis of the enzymatic cleavage products. Thymosin alpha1, an immunologically active polypeptide, is highly acidic with an isoelectric point of 4.2. This molecule is composed of 28 amino acid residues with acetylserine as the NH2 terminus. A chemically synthesized molecule of thymosin alpha1 has been found to be as active as the natural molecule in our bioassay systems. Polypeptide beta1 is a molecule consisting of 74 amino acid residues and has an isoelectric point of 6.7. This peptide is not biologically active in our assay systems, suggesting that it is not involved in thymic hormone action. The sequence of beta1 was found to be identical with ubiquitin and a portion of protein A24, a nuclear chromosomal protein. The relationships among these proteins are discussed.

Amino Acid Sequence↗
PubMed1979

Current status of thymosin research: evidence for the existence of a family of thymic factors that control T-cell maturation.

Thymosin fraction 5 contains several distinct hormonal-like factors which are effective in partially or fully inducing and maintaining immune function. Several of the peptide components of fraction 5 have been purified, sequenced and studied in assay systems designed to measure T-cell differentiation and function. These studied indicate that a number of the purified peptides act on different subpopulations of T-cells (see Figure 1). Thymosin beta 3 and beta 4 peptides act on terminal deoxynucleotidyl transferase (TdT) negative precursor T-cells to induce TdT positive cells. Thymosin alpha 1 induces the formation of functional helper cells and conversion of Lyt- cells to Lyt 1+, 2+, 3+ cells. Thymosin alpha 7 induces the formation of functional suppressor T-cells and also converts Lyt- cells to Lyt 1+, 2+, 3+ cells. These studies have provided further evidence that the thymus secretes a family of distinct peptides which act at various sites of the maturation sequence of T-cells to induce and maintain immune function. Phase I and Phase II clinical studied with thymosin in the treatment of primary immunodeficiency diseases, autoimmune diseases, and cancer point to a major role of the endocrine thymus in the maintenance of immune balance and in the treatment of diseases characterized by thymic malfunction. It is becoming increasingly clear that immunological maturation is a process involving a complex number of steps and that a single factor initiating a single cellular event might not be reflected in any meaningful immune reconstitution unless it is the only peptide lacking. Given the complexity of the maturation sequence of T-cells and the increasing numbers of T-cell subpopulations that are being identified, it would be surprising if a single thymic factor could control all of the steps and populations involved. Rather, it would appear that the control of T-cell maturation and function involves a complex number of thymic-specific factors and other molecules that rigidly control the intermediary steps in the differentiation process.

Amino Acid Sequence↗
PubMed1978

Overview of thymosin activity.

Our current research program centers around the biologic and chemical characterization of the family of polypeptides present in thymosin fraction 5. A system of nomenclature has been developed and the peptides are being systematically isolated and chemically characterized. Thymosin fraction 5 and its component parts influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, and expression of certain surface markers. Thymosin is being used in clinical trials to investigate its effects on immunodeficiency diseases, malignant diseases, and autoimmune diseases.

Animals↗
PubMed1977

Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide.

The amino acid sequence of a biologically active polypeptide isolated from calf thymus, termed thymosin alpha1, has been determined. Thymosin alpha1 is a heat stable, highly acidic molecule composed of 28 amino acid residues. This peptide is one of several present in thymosin fraction 5 that may participate in the regulation, differentiation and function of thymus-dependent lymphocytes (T cells). A nomenclature for the family of polypeptides present in thymosin fraction 5 is suggested.

Amino Acid Sequence↗