Impact of the new generation coronary care unit.

A 30-bed coronary care unit with facilities for fluoroscopy, haemodynamic monitoring, mechanical heart assistance, and long-term electrocardiographic monitoring operated at a reasonable cost over five years. Much of the work was entrusted to trained nurses, and there was close consultation with cardiac surgeons over those patients who needed catheterisation or surgery. New procedures greatly reduced the numbers of early deaths from cardiac arrest and cardiac failure but had less influence on late mortality. Hospital mortality for all 3353 patients was 6-8%, and for patients under 65 with definite infarction, who were admitted direct it was 5-7%.     

The specificity of a weak gamma delta TCR interaction can be modulated by the glycosylation of the ligand.

The gamma delta T cell clone LBK5 recognizes the MHC molecule IEk. Here, we demonstrate that the affinity of this interaction is weaker than those typically reported for alpha beta TCRs that recognize peptide/MHC complexes. Consistent with our previous finding that peptide bound to the IE molecule does not confer specificity, we show that the entire epitope for LBK5 is contained within the polypeptide chains of the molecule, centered around the polymorphic residues 67 and 70 of the IE beta-chain. However, LBK5 recognition is profoundly influenced by the N-linked glycosylation at residue 82 of the IE alpha-chain. Since infected, stressed, or transformed cells often change the posttranslational modifications of their surface glycoproteins, this finding suggests a new way in which gamma delta T cell Ag recognition can be regulated.     

Epigenetic switches in clag3 genes mediate blasticidin S resistance in malaria parasites

Malaria parasites induce changes in the permeability of the infected erythrocyte membrane to numerous solutes, including toxic compounds. In Plasmodium falciparum, this is mainly mediated by PSAC, a broad‐selectivity channel that requires the product of parasite clag3 genes for its activity. The two paralogous clag3 genes, clag3.1 and clag3.2, can be silenced by epigenetic mechanisms and show mutually exclusive expression. Here we show that resistance to the antibiotic blasticidin S (BSD) is associated with switches in the expression of these genes that result in altered solute uptake. Low concentrations of the drug selected parasites that switched from clag3.2 to clag3.1 expression, implying that expression of one or the other clag3 gene confers different transport efficiency to PSAC for some solutes. Selection with higher BSD concentrations resulted in simultaneous silencing of both clag3 genes, which severely compromises PSAC formation as demonstrated by blocked uptake of other PSAC substrates. Changes in the expression of clag3 genes were not accompanied by large genetic rearrangements or mutations at the clag3 loci or elsewhere in the genome. These resultsdemonstrate that malaria parasites can become resistant to toxic compounds such as drugs by epigenetic switches in the expression of genes necessary for the formation of solute channels.     

The Flora of the Perivaginal Area: The Normal Flora and the Effect of a Deodorant Spray

S ummary . The microbial flora of the thigh adjacent to the vaginal labia and of the mucosal surface of the labia has been examined quantitatively and qualitatively in students from Colleges of Education and a University, and in persons attending a Consultant Gynaecologist for non-suppurative conditions. In the 2 student populations, members of the Micrococcaceae and diphtheroids were the most common organisms but all populations yielded many organisms of gut origin. Differences between the populations may relate to social and hygienic conditions and should make us wary of direct comparisons with other, different populations. The effect of intimate hygiene deodorants containing 0.01% or 0.02% of chlorhexidine was compared with a base spray containing no antibacterial agent. No significant effect of these sprays on the microbial flora could be demonstrated.     

Explaining geographical variation in the isotope composition of mouse lemurs (Microcebus)

Aim We sought to quantify geographical variation in the stable isotope values of mouse lemurs (Microcebus) and to determine whether this variation reflects trophic differences among populations or baseline isotopic differences among habitats. If the latter pattern is demonstrated, then Microcebus can become a proxy for tracking baseline habitat isotopic variability. Establishing such a baseline is crucial for identifying niche partitioning in modern and ancient communities. Location We studied five species of Microcebus from eight distinct habitats across Madagascar. Methods We compared isotopic variation in C₃ plants and Microcebus fur within and among localities. We predicted that carbon and nitrogen isotope values of Microcebus should: (1) vary as a function of abiotic variables such as rainfall and temperature, and (2) covary with isotopic values in plants. We checked for trophic differences among Microcebus populations by comparing the average difference between mouse lemur and plant isotope values for each locality. We then used multiple regression models to explain spatial isotope variation in mouse lemurs, testing a suite of explanatory abiotic variables. Results We found substantial isotopic variation geographically. Ranges for mean isotope values were similar for both Microcebus and plants across localities (carbon 3.5–4.0‰; nitrogen 10.5–11.0‰). Mean mouse lemur and plant isotope values were lowest in cool, moist localities and highest in hot, dry localities. Rainfall explained 58% of the variation in Microcebus carbon isotope values, and mean plant nitrogen isotope values explained 99.7% of the variation in Microcebus nitrogen isotope values. Average differences between mouse lemur and plant isotope values (carbon 5.0‰; nitrogen 5.9‰) were similar across localities. Main conclusions Isotopic data suggest that trophic differences among Microcebus populations were small. Carbon isotope values in mouse lemurs were negatively correlated with rainfall. Nitrogen isotope values in Microcebus and plants covaried. Such findings suggest that nitrogen isotope values for Microcebus are a particularly good proxy for tracking baseline isotopic differences among habitats. Our results will facilitate future comparative research on modern mouse lemur communities, and ecological interpretations of extinct Holocene communities.     

Dorsal Anterior Cingulate Thickness Is Related to Alexithymia in Childhood Trauma-Related PTSD

Alexithymia, or “no words for feelings”, is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex (dACC) has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed the Toronto Alexithymia Scale 20 (TAS–20) and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS–20 scores, controlling for sex and age, in both groups. Average TAS–20 score was significantly higher in the PTSD than the HC group. TAS–20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS–20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology.     

Specific ion effects on macromolecular interactions in Escherichia coli extracts

Protein characterization in situ remains a major challenge for protein science. Here, the interactions of ΔTat‐GB1 in Escherichia coli cell extracts were investigated by NMR spectroscopy and size exclusion chromatography (SEC). ΔTat‐GB1 was found to participate in high molecular weight complexes that remain intact at physiologically‐relevant ionic strength. This observation helps to explain why ΔTat‐GB1 was not detected by in‐cell NMR spectroscopy. Extracts pre‐treated with RNase A had a different SEC elution profile indicating that ΔTat‐GB1 predominantly interacted with RNA. The roles of biological and laboratory ions in mediating macromolecular interactions were studied. Interestingly, the interactions of ΔTat‐GB1 could be disrupted by biologically‐relevant multivalent ions. The most effective shielding of interactions occurred in Mg²⁺‐containing buffers. Moreover, a combination of RNA digestion and Mg²⁺ greatly enhanced the NMR detection of ΔTat‐GB1 in cell extracts.