Simultaneous confirmation and differentiation of human T-lymphotropic virus types I and II infection by modified western blot containing recombinant envelope glycoproteins

A modified Western blot (WB) that includes both shared (r21e) and unique recombinant envelope proteins from human T-lymphotropic virus (HTLV) type I (rgp46I) and type II (rgp46II) was compared to conventional HTLV serologic tests in 379 United States blood donors and individuals residing in diverse geographic regions, and the specimens were categorized as positive (n = 158), indeterminate (n = 158), or negative (n = 63) for HTLV infection. Of the 158 HTLV-I/II-positive specimens (66 requiring radioimmunoprecipitation assay [RIPA] for confirmation), 156 reacted concordantly with r21e, gag, and either rgp46I or rgp46II, thus eliminating the need for RIPA in all but two specimens and yielding a test sensitivity of 98.7 percent. Of the 158 indeterminate and 63 negative specimens, none reacted with r21e and rgp46I or rgp46II, yielding a test specificity of 100 percent. Furthermore, analysis of an additional 184 consecutive specimens from a retrovirology reference laboratory demonstrated that the modified WB correctly identified 27 of 28 HTLV-I specimens and all 13 HTLV-II specimens, with a test sensitivity of 97.6 percent. None of specimens that were indeterminate or nonreactive in conventional WB and/or RIPA and none of the screening enzyme immunoassay-negative specimens reacted with r21e and either rgp46I or rgp46II, for a test specificity of 100 percent. Thus, the modified WB appears to be highly sensitive and specific for simultaneous detection and discrimination of HTLV-I from HTLV-II and has the advantage of being a one-step assay that is easily performed in all types of laboratory settings and allows rapid, reliable, and standardized testing for HTLV-I/II infection.     

Adenosine dialdehyde and nitrous oxide induce HL-60 differentiation

Adenosine dialdehyde and nitrous oxide, specific S-adeno- sylhomocysteine hydrolase and methionine synthetase inhibitors, respectively, induced differentiation of the human promyelocytic cell line HL-60. Their effect did not appear to be mediated through changes in transmethylation or decreased S-adenosylmethionine synthesis because (1) there was little correlation between the concentrations of adenosine dialdehyde that induced differentiation and those that changed the ratio of the intracellular concentrations of S- adenosylmethionine to S-adenosylhomocysteine, and (2) inhibition of methionine adenosyltransferase by cycloleucine did not induce differentiation. The differentiation induced by adenosine dialdehyde was prevented by homocysteine and that by nitrous oxide was inversely related to the medium methionine concentration. This suggested that differentiation was secondary to decreased methionine synthesis.     

The neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.