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Biomedical subjects

F E Weller

Publications and source records attributed to F E Weller.

10 recordsLinked to original sources

Serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in large cohorts of healthy adults.

Enzyme linked immunosorbent assays were used to measure serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in 681 healthy adults (range 18 yr-101 yr). Immunoreactive thymosin alpha 1 was found to occur at a geometric mean of 540 pg/ml with a range from 252 to 1158 pg/ml. There were no differences in the levels when analyzed according to race, sex or age. Immunoreactive thymosin beta 4 was measured at a geometric mean of 12.6 ng/ml with a range from 6.9 to 23.0 ng/ml. There were no differences in the levels when analyzed according to race or sex, however, there was a slight upward trend with increasing age. This data may be useful as a reference when monitoring clinical studies, determining the kinetics of drug metabolism and distinguishing patient groups with elevated levels of either of these peptides.

Adolescent↗

Cellular levels of thymosin immunoreactive peptides are linked to proliferative events: evidence for a nuclear site of action.

Thymosin alpha 1 (T alpha 1), the N-terminal 28-amino acid fragment of prothymosin alpha (ProT alpha), and ProT alpha, although originally isolated from whole thymus extracts, are also present in nonthymic cells and tissues. We used an ELISA with an antibody raised against T alpha 1 to investigate the relationship between intracellular levels of thymosin immunoreactive peptide(s) (TIP) and cell proliferation in a rat small intestinal IEC-6 cell line. Increasing TIP levels were observed during cell proliferation, which decreased when proliferation was halted by cellular contact inhibition. Serum feeding of cells previously rendered quiescent by serum starvation resulted in a significant increase in TIP within 1 hr. Conversely, serum starvation decreased TIP levels within 1 hr. Peak TIP levels appeared after 3 hr of serum incubation, while maximum [3H]thymidine incorporation was noted after 9 hr, suggesting maximum TIP concentrations in the G1 phase of the proliferative cycle. Immunoelectron microscopy demonstrated an association of TIP with condensed nuclear chromatin. These results support a relation of intracellular TIP levels to IEC-6 cell proliferation and also a nuclear site of action. HPLC analysis of cellular homogenates from proliferating IEC-6 cells revealed a peak of immune reactivity that elutes in the position of T alpha 1.

Animals↗

Enzyme immunoassay measurement of thymosin beta 4 in human serum.

An enzyme immunoassay (EIA) for measurement of human serum thymosin beta 4 is described. Antiserum to synthetic thymosin beta 4, raised in rabbits, is incubated with a standard or serum. The unbound antibody in liquid-phase then binds with solid-phase thymosin beta 4. The EIA is both sensitive and accurate and is capable of detecting as little as 2.5 ng/ml thymosin beta 4 in serum. No cross-reactivity was observed with common serum proteins or other putative thymic hormones. High-performance liquid chromatography of serum samples reveals a single thymosin beta 4 peak that corresponds to the authentic thymosin beta 4 peak in the standard. Human serum levels range from 3 to 82 ng/ml in 142 healthy adult human volunteers. Newborn cord serum levels of thymosin beta 4 are lower than in adults.

Alkaline Phosphatase↗

Enzyme immunoassay measurement of thymosin beta 4.

An enzyme immunoassay for the measurement of thymosin beta 4, a chemically characterized thymic polypeptide, is described. A limited amount of reagent antiserum to synthetic thymosin beta 4 is incubated with liquid-phase thymosin beta 4. Unbound antibody is then incubated with solid-phase thymosin beta 4. The method is specific, sensitive, highly reproducible and capable of detecting as little as 2.5 ng/ml of thymosin beta 4.

Animals↗

Maternal and fetal circulating levels of thymosin alpha 1 during parturition.

The thymus directs T-lymphocyte development and contributes to the maintenance of immune homeostasis, in part, through its production of peptides known as thymosins. In pregnancy, maternal serum levels of thymosin alpha 1 have been reported to be low at midgestation and to increase by term, suggesting that maternal levels represent fetal levels. To evaluate this further, we obtained maternal venous and newborn mixed cord blood from 90 pregnancies between 20 and 42 weeks of gestation at delivery. An ELISA was used for thymosin alpha 1 assay, and analysis was by paired t test and regression. Maternal and newborn levels were independent of gestational age, but an apparent association (r = 0.51) between the two was inconclusive. Maternal levels (1,207 +/- 947 pg/ml) tended to be higher than those of healthy adults (1,043 +/- 576 pg/ml). Mixed umbilical cord serum levels (1,466 +/- 940 pg/ml) were higher than maternal levels (P less than or equal to 0.005). Although maternal thymosin alpha 1 levels may reflect fetal levels, immunological perturbations related to parturition appear to influence both.

Adolescent↗

MicroELISA method for measurement of human serum thymosin alpha 1.

A microELISA for the estimation of human serum thymosin alpha 1 is described. In this assay, antibody to thymosin alpha 1 is pre-incubated with the standard or serum at 4 degrees C. Unbound antibody in the liquid-phase then binds with solid-phase thymosin alpha 1. The method is sufficiently sensitive for measuring serum levels of thymosin alpha 1 and highly reproducible. The serum levels measured with the microELISA are comparable to serum levels of thymosin alpha 1 determined by the previously described radioimmunoassay for thymosin alpha 1.

Antibody Specificity↗

Measurement of thymosin alpha 1 by disassociation microELISA.

A disassociation microELISA was devised for the estimation of thymosin alpha 1, a chemically characterized thymic polypeptide isolated from bovine thymosin fraction 5. Antiserum to synthetic thymosin alpha 1 was raised in rabbits. Thymosin alpha 1 in liquid phase competed with a solid-phase-bound thymosin alpha 1 for this highly specific antibody. The method is specific, sensitive, reproducible and capable of detecting as little as 100 pg/ml of thymosin alpha 1.

Animals↗

Increased thymic hormone responsive suppressor T lymphocyte function in chronic active hepatitis.

Mitogen-induced suppressor T lymphocyte function was evaluated in patients with chronic active hepatitis (CAH). The in vitro effect of the biological response modifier, thymosin fraction 5, on the suppressive activity of peripheral blood mononuclear cells (PBM) was also assessed. Suppressor cell activity was significantly decreased in patients with CAH when compared to controls (P less than 0.001). In the absence of the inducing mitogen, thymosin-treated PBM from both patients and controls promoted enhancement of tritiated thymidine uptake by cocultured allogeneic lymphocytes. When thymosin-treated mononuclear cells were mitogen-activated; patients, but not the controls, showed a marked increase in suppressor activity (P less than 0.001). These results indicate that the polypeptides contained in thymosin fraction 5 can promote a helper effect in patients and controls. Furthermore, PBM from patients with CAH contain a subset of lymphocytes that can express a suppressive function following thymosin treatment. We conclude that thymosin fraction 5 can promote an in vitro restoration of suppressor T cell function in patients with CAH.

Adolescent↗