Use of epicardial electrocardiograms for detecting cardiac allograft rejection.

Since the advent of cyclosporin A surface electrocardiograms have been unreliable for diagnosing cardiac allograft rejection. Although several noninvasive methods have been proposed, none have been sufficiently accurate to be considered for clinical use. We have studied the use of the QRS complex amplitude, the unipolar peak-to-peak amplitude, recorded from intramyocardial electrodes for detecting rejection. Ten adult mongrel dogs underwent placement of intramyocardial electrodes on each ventricle. After stabilization of signals the hearts were transplanted heterotopically into unmatched recipients receiving cyclosporin A, azathioprine and methylprednisolone. Endomyocardial biopsies were performed after stabilization of unipolar peak-to-peak amplitude, twice weekly thereafter, and when unipolar peak-to-peak amplitude fell significantly. This detected 13 of 14 episodes of rejection. There was one false-positive and one false-negative result. The false-negative study became positive the following day. Thus, analysis of unipolar peak-to-peak amplitude detected all episodes of rejection in a clinically relevant time frame and was able to detect mild forms of rejection and multiple episodes of rejection in the same heart even in the presence of therapeutic levels of cyclosporin A.     

Heterodimerization of type II phytochromes in Arabidopsis

Coimmunoprecipitation of members of the phytochrome red/farred photoreceptor family from plant extracts has been used to analyze their heteromeric binding interactions. Phytochrome (phy)B or phyD apoproteins with six myc epitopes fused to their N termini are biologically active when expressed in Arabidopsis. Immunoprecipitation of either of these tagged proteins from seedling extracts coprecipitates additional type II phytochromes: six myc (myc6)-phyB coprecipitates phyC-phyE; and myc6-phyD coprecipitates phyB and phyE. No interaction of the epitope-tagged proteins with type I phyA was detected. Gel filtration chromatography shows that all five of the Arabidopsis phytochromes are present in seedlings as dimers, and that the heteromeric type II phytochrome complexes migrate at molecular masses characteristic of heterodimers. Similar levels of heterodimer formation are observed in extracts of dark-grown seedlings, where the phytochromes are cytosolic, and light-grown seedlings, where they are predominantly nuclear. These findings indicate that Arabidopsis, which until now has been thought to contain five homodimeric forms of phytochrome, in fact contains multiple species of both homodimeric and heterodimeric phytochromes. The conservation of the phytochrome family throughout angiosperms suggests that heterodimeric red/far-red receptors may be present in many flowering plants.     

Opsin exhibits cGMP-activated single-channel activity.

Low concentrations of cGMP evoked reversible single-channel currents in patches excised from liposomes that contained purified bovine opsin. Two elementary conductances, of 32 and 17 pS, were observed in the presence of 10-200 microM cGMP. Both individual channel openings (mean open times, approximately 1.6 ms for the 32-pS conductance and approximately 1.0 ms for the 17-pS conductance) and bursts of openings (mean burst duration, approximately 2-3 ms for the large events) were observed. The cGMP-activated channel activity could be observed in the presence or absence of Ca2+. These results raise the possibility that opsin or rhodopsin, an opsin/rhodopsin isoform, or an opsin/isoform multimer serves as a cGMP-modulated pore in the rod outer segment.     

Linked morphological changes during palate evolution in early tetrapods

We examined the shapes and sizes of dermal bones of the palate of selected Palaeozoic tetrapods in order to identify the ancestral states of palatal bone morphologies in the earliest tetrapods, to learn how the composition of the palate varies within and among early tetrapod radiations, and to recognize evolutionary correlations among the size and shapes of skeletal elements in this important group of animals. We find that whereas the palatal bones themselves and their arrangements are usually conserved, considerable correlated evolutionary change occurs in the shapes and sizes of the bones. Some of the changes in the bones are allometrically linked to overall palate size, which varies more than 100‐fold among the taxa in our sample. Often, these allometries were only hinted at in traditional independent contrasts‐based regressions of log transformed data, particularly because many allometries are subtle, their slopes may vary among subclades, and the scatter around some trendlines is high. Rather, the allometries showed up in analyses of size‐standardized palatal bone dimensions investigated using independent contrasts, bivariate phylomorphospace plots, and mirrored character reconstructions on the phylogenetic tree. We find negative allometry for parasphenoid lengths and widths essentially across the entire tree of Palaeozoic tetrapods, but with different trajectories characterizing the two largest clades, the temnospondyls and the lepospondyls. The lengths of several other elements may show positive allometries, either across the entire tree or in just a subclade. One possible positive allometry exists for the ectopterygoid, which appears to shorten allometrically in temnospondyls that evolve small body and palate size, and, as in Doleserpeton can be lost altogether. Both shortening and loss could be by the same developmental change, paedomorphosis, a form of heterochrony. Paedomorphosis might also account for evolution of relatively large parasphenoids in both lepospondyls and diminutive temnospondyls, but does not seem to explain evolution of ectopterygoid loss in lepospondyls. A regularity observed across nearly all taxa in our study set is an inverse correlation between the lengths of the vomer and pterygoid, bones that lie adjacent to one another along the long palatal axis. Further work is needed to learn whether such correlated evolution might be due to adaptation and/or to developmental bias, and particularly to learn how correlations and allometries themselves evolve.     

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: first results of the endometrial sub-protocol following 2 years of treatment

BACKGROUND: Tamoxifen treatment results in a doubling of the risk of endometrial cancer after 1-2 years of treatment and a quadrupling after 5 years. Anastrozole, a third-generation aromatase inhibitor, with superior efficacy to tamoxifen, may also offer tolerability benefits in terms of effects on the endometrium. METHODS AND RESULTS: A sub-protocol of the ATAC trial compared the incidence/type of intrauterine changes following treatment with these agents in a subgroup of patients (n = 285) from the main trial. After 2 years anastrozole treatment, endometrial thickness remained 相似文献   

Do reminder signs promote use of safety belts?

STUDY OBJECTIVE: To determine whether reminder signs placed at the exits to parking decks increase the rate of safety belt use. METHODS: The subjects in this study were drivers of automobiles with permits to park in campus decks at a major university. Volunteer observers were positioned near the exits of 5 parking decks around the campus. Rates of safety belt use were noted before and at 2 intervals after reminder signs were installed. RESULTS: A total of 6, 780 observations were collected. The baseline rate of safety belt use was 83%. Female drivers were significantly more likely to wear a safety belt than male drivers (85.3% versus 79.6%, P <.001). Safety belt use did not increase after the signs were installed (83.3% before versus 83.5% after, P =.86). CONCLUSION: Placing reminder signs at the exits to parking decks did not boost the rate of safety belt use at our institution. Other strategies are needed to achieve the National Highway Traffic Safety Administration's goal of increasing the overall rate of safety belt usage to 90% by the year 2005.