Influences of age (3 wk, 2, 7, 19, or 26 mo), long-term dietary restriction (DR) started at 3 wk of age, and acute fasting state on serum thymosin alpha 1 (T alpha 1) levels were measured by radioimmunoassay in female mice from a long-lived strain. The average T alpha 1 level was highest (approximately 60 ng/ml) at 3 wk and fell sharply such that 2 mo old mice fed either normal (N, approximately 80% of ad libitum intake) or restricted (R, approximately 50% of ad libitum intake) diets averaged approximately 20 ng/ml. Any age-related declines after 2 mo of age were mild and statistically significant only for R mice bled 2-4 h (but not 24-48 h) post-feeding. T alpha 1 levels were lower in group R than in group N mice in one experiment at 19 mo of age but not in another at 26 mo. The decline with age in serum T alpha 1 levels is mainly a very early life event for mice of this hybrid strain and appears uninfluenced by DR. T alpha 1 levels are variably reduced by DR later in life.

African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under-represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end-of-treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon-alpha2b (Intron A) thrice weekly. End-of-treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end-of-treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow-up information. The end-of-treatment response was 7% for patients with genotype 1 and 71% for genotype non-1 (P < 0.005 for genotype non-1). The end-of-treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end-of-treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end-of-treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.

An antiserum prepared against thymosin alpha 1, a hormone secreted by the thymus gland, effectively neutralized the AIDS-associated virus [HTLV-III/LAV (clone BH-10)] and blocked its replication in H9 cells. Reverse transcriptase activity and expression of the HTLV-III/LAV antigens p15 and p24 were inhibited by purified immunoglobulin G preparations of antisera to thymosin alpha 1. The antiviral activity of the antiserum was found to be due to a region of homology between thymosin alpha 1 and p17, a product of the gag gene of HTLV-III/LAV. Comparison of the primary sequences of thymosin alpha 1 and the gag protein revealed a 44% to 50% homology in an 18-amino acid region, between positions 11 and 28 on thymosin alpha 1 and 92 and 109 on the gag protein. The effectiveness of the thymosin alpha 1 antiserum and of immunoglobulin G-enriched preparations in blocking replication of HTLV-III(BH-10) in H9 cells suggests a novel approach to the development of an AIDS vaccine. A vaccine directed against the gag protein might overcome the problem of genetic drift in the envelope region of the virus and be useful against all genetic variants of HTLV-III/LAV.

Thymosin a, (Tal), the N-terminal 28-amino acid fragment ofprothymosin a (ProTa), and ProTa, although originally isolated from whole thymus extracts, are also present in nonthymic cells and tissues. We used an ELISA with an antibody raised against Ta1 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 G, 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 Tal.