Power spectral analysis of heart rate variability (HRV) has been used frequently to assess cardiac autonomic function; however, the relationship of low frequency (LF) power of HRV to cardiac sympathetic tone has been unclear. With or without adjustment for high frequency (HF) power, total power, or respiration, LF power seems to provide an index not of cardiac sympathetic tone but of baroreflex function. Manipulations and drugs that change LF power or LF:HF may do so not by affecting cardiac autonomic outflows directly but by affecting modulation of those outflows by baroreflexes.

The induction of stable mixed allogeneic chimerism as an approach to transplantation tolerance has recently been reviewed in detail (1). Two murine models for the induction of such stable mixed chimerism involve total lymphoid irradiation (TLI)' followed by infusion of allogeneic bone marrow (BM) (2) and lethal whole body irradiation (WBI) followed by reconstitution with a mixture of T cell-depleted (TCD) syngeneic and allogeneic BM (3, 4). Both ofthese regimens have been shown to produce long-term mixed lymphohematopoietic chimerism and specific tolerance to donor skin grafts, and in both cases the resulting mixed chimeras have been shown to be otherwise immunocompetent (4, 5).One major drawback, however, to the clinical use of these approaches to the induction of transplant tolerance has been the excessive toxicity of both irradiation regimens required for the establishment of mixed chimeras . The recent report by Cobbold et al. (6) that treatment of mice with anti-T cell mAbs could promote allogeneic marrow engraftment was therefore ofboth theoretical and practical interest . However, the chimerism achieved by these authors was transient unless relatively high doses of whole body irradiation (600 and 850 rad) were administered in addition to the mAb treatment. Animals prepared in this fashion demonstrated fully allogeneic reconstitution rather than mixed chimerism (6), and the immunocompetence of these chimeras was not examined.In present study we have attempted to reproduce and extend these results. We have found that treatment of mice with antiT cell mAbs leads to profound peripheral T cell depletion but fails to deplete mature T cells from the thymus . We therefore reasoned that the requirement for high dose whole body irradiation to achieve stable chimerism in the studies by Cobbold et al. might have been due to the need for removal ofmature thymic T cells. While thymectomy might overcome this problem, it would also leave an animal without thymic stromal elements capable of educating new T cells from host and donor stem cell populations. We therefore attempted selective thymic irradiation (TI) to deplete thymic T cells. We report here that this procedure

Intra-neuronal metabolism of dopamine (DA) begins with production of 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is toxic. According to the ‘catecholaldehyde hypothesis,’ DOPAL destroys nigrostriatal DA terminals and contributes to the profound putamen DA deficiency that characterizes Parkinson’s disease (PD). We tested the feasibility of using post-mortem patterns of putamen tissue catechols to examine contributions of altered activities of the type 2 vesicular monoamine transporter (VMAT2) and aldehyde dehydrogenase (ALDH) to the increased DOPAL levels found in PD. Theoretically, the DA : DOPA concentration ratio indicates vesicular uptake, and the 3,4-dihydroxyphenylacetic acid : DOPAL ratio indicates ALDH activity. We validated these indices in transgenic mice with very low vesicular uptake (VMAT2-Lo) or with knockouts of the genes encoding ALDH1A1 and ALDH2 (ALDH1A1,2 KO), applied these indices in PD putamen, and estimated the percent decreases in vesicular uptake and ALDH activity in PD. VMAT2-Lo mice had markedly decreased DA:DOPA (50 vs. 1377, p < 0.0001), and ALDH1A1,2 KO mice had decreased 3,4-dihydroxyphenylacetic acid:DOPAL (1.0 vs. 11.2, p < 0.0001). In PD putamen, vesicular uptake was estimated to be decreased by 89% and ALDH activity by 70%. Elevated DOPAL levels in PD putamen reflect a combination of decreased vesicular uptake of cytosolic DA and decreased DOPAL detoxification by ALDH.