Endogenous CD8+ T cell expansion during regression of monoclonal EBV-associated posttransplant lymphoproliferative disorder.

There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vbeta repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vbeta pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vbeta-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells.     

Chemical synthesis of a tetradecamer in the deoxyribonucleic acid series

The chemical synthesis of a tetradecadeoxyribonucleotide, d-EtSp(A-T-G-G-A-A-A-C-T-G-C-G-G-C), is described. This oligomer, designated Fragment 4δ, constitutes the 5′-terminus of the plus strand of a projected duplex coding for S-Peptide_2–14 derived from Ribonuclease A. The Fragment was constructed by block condensation via a phosphorothioate anchor. Complications due to inadvertent phosphotriester condensations are discussed. Arguments justifying the sequence selection are presented.     

Internal Rhythmic Pattern of ECG Signal and the Efficiency of Adaptation to Cyclic Muscular Work

Spectral, coherent, and phase analysis within the low-frequency range of ECG records of athletic runners revealed that oscillations of ECG intervals (PQ-, RT-, P–T-, TP, and PP-intervals) were observed during orthostasis. These data were compared with the results of athletic exercise tests performed after the ECG examination. It was shown that the most effective type of adaptive reaction in these tests corresponds to a phase advance of the PQ-interval oscillations relative to the RT-interval oscillations. In the low-frequency range, the phases of the PQ-, RT-, and (P–T)-interval oscillations were ahead of the TP-interval oscillations, whereas the spectral density of the TP interval oscillations was significantly higher than the spectral density of the oscillations of the PC-, RT-, and (P–T)-intervals measured at the same frequency. The least effective type of adaptive reaction was shown to correlate with the phase advance of the TP-interval oscillations relative to the PQ-, RT-, and (P–T)-interval oscillations within the low-frequency range as well as with the lack of low-frequency modulation of the autospectra of the cardiac intervals of interest.     

Role of Ca2+-activated K+ channel in regulation of NaCl reabsorption in thick ascending limb of Henle's loop

1. Reabsorption of NaCl in the thick ascending limb of Henle's loop involves the integrated function of the Na+,K+,Cl- -cotransport system and a Ca2+-activated K+ channel in the luminal membrane with the Na+,K+-pump and a net Cl- conductance in the basolateral membrane. 2. Assay of K+ channel activity after reconstitution into phospholipid vesicles shows that the K+ channel is stimulated by Ca2+ in physiological concentrations and that its activity is regulated by calmodulin and phosphorylation from cAMP dependent protein kinase. 3. For purification luminal plasma membrane vesicles are isolated and solubilized in CHAPS. K+ channel protein is isolated by affinity chromatography on calmodulin columns. The purified protein has high Ca2+-activated K+ channel activity after reconstitution into vesicles. 4. The purified K+ channel consists of two proteins of 51 and 36 kDa. Phosphorylation from cAMP dependent protein kinase stimulates K+ channel activity and labels the 51 kDa band. The 36 kDa band is rapidly cleaved by trypsin and may be involved in Ca2+ stimulation. 5. Opening of the K+ channel by Ca2+ in physiological concentrations and regulation by calmodulin and phosphorylation by protein kinase may mediate kinetic and hormonal regulation of NaCl transport across the tubule cells in TAL.