scholarly journals Recombinant interferon alpha can induce rearrangement of T-cell antigen receptor alpha-chain genes and maturation to cytotoxicity in T-lymphocyte clones in vitro.

1986 ◽  
Vol 83 (13) ◽  
pp. 4887-4889 ◽  
Author(s):  
L. K. Chen ◽  
D. Mathieu-Mahul ◽  
F. H. Bach ◽  
J. Dausset ◽  
A. Bensussan ◽  
...  
1991 ◽  
Vol 88 (17) ◽  
pp. 7518-7522 ◽  
Author(s):  
H. Koseki ◽  
H. Asano ◽  
T. Inaba ◽  
N. Miyashita ◽  
K. Moriwaki ◽  
...  

1985 ◽  
Vol 162 (3) ◽  
pp. 1087-1092 ◽  
Author(s):  
M L Hoover ◽  
J Marks ◽  
J Chipman ◽  
E Palmer ◽  
P Stastny ◽  
...  

Two allelic forms of the T cell antigen receptor alpha chain gene were discerned by restriction fragment length polymorphism (RFLP) employing the T cell antigen receptor alpha chain probe pGA5, and the restriction enzyme Bgl II. Analysis revealed that the polymorphic fragments are detected by a probe specific for the constant region exon of the T cell antigen receptor alpha chain gene. Furthermore, the polymorphic fragments were shown to segregate within families. The two allelic forms yield two homozygous states, 3.2/3.2 and 2.9/2.9, at a frequency of 76.5 and 2.9%, respectively, within the normal population. The heterozygous state was observed in 20.6% of the population. The discovery of allelic forms of both the alpha and beta chains of the T cell antigen receptor genes may provide a unique opportunity to study heritable markers of T cell function in several human diseases.


Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 59-64 ◽  
Author(s):  
CR Faltynek

Abstract Interferon-alpha and the adenosine deaminase (ADA) inhibitor deoxycoformycin (dCF) have each been shown to be efficacious in the treatment of some lymphoid malignancies and to have potent antiproliferative activities in vitro. This study examined whether dCF and recombinant interferon-alpha A (rIFN-alpha A) were additive, synergistic, or antagonistic in their effects on the cultured B lymphoblastoid cell line Daudi. Treatment of Daudi cells for three to four days with doses of rIFN-alpha A that were growth inhibitory was unexpectedly found to increase the level of ADA activity per cell two- to threefold and therefore to prevent the inhibition of ADA by limiting concentrations of dCF. However, the opposite effects of dCF and rIFN- alpha A on ADA activity did not lead to antagonistic effects on growth inhibition. The higher concentrations of dCF (with deoxyadenosine) necessary for appreciable growth inhibition could inhibit the increased ADA activity in rIFN-alpha A-treated cells, thus resulting in additive antiproliferative effects.


1986 ◽  
Vol 4 (11) ◽  
pp. 1677-1683 ◽  
Author(s):  
R Kurzrock ◽  
M G Rosenblum ◽  
J R Quesada ◽  
S A Sherwin ◽  
L M Itri ◽  
...  

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.


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