The Yale Affiliated Hospital Program in Internal Medicine

In July, 1975, the Departments of Internal Medicine at the Yale University School of Medicine and eight community hospitals in southern and western Connecticut formed the Yale Affiliated Hospital Program (YAHP) in Internal Medicine. The YAHP provides a planned and focused program of continuing education for medical staff and housestaff at the affiliated hospitals. Six formats for the over 1,000 rounds, lectures, and conferences given annually are used. The members of the YAHP also cooperate in housestaff and faculty recruiting, evaluation of quality of care and evaluation of the process of continuing medical education itself. This report summarizes the organization, goals and future plans of the YAHP.     

Analysis of protein main-chain solvation as a function of secondary structure

We have analysed the hydration of main-chain carbonyl and amide groups in 24 high-resolution well-refined protein structures as a function of the secondary structure in which these polar groups occur. We find that main-chain atoms in beta-sheets are as hydrated as those in alpha-helices, with most interactions involving "free" amide and carbonyl groups that do not participate in secondary structure hydrogen bonds. The distributions of water molecules around these non-bonded carbonyl groups reflect specific steric interactions due to the local secondary structure. Approximately 20% and 4%, respectively of bonded carbonyl and amide groups interact with solvent. These include interactions with carbonyl groups on the exposed faces of alpha-helices that have been correlated previously with bending of the helix. Water molecules interacting with alpha-helices occur mainly at the amino and carbonyl termini of the helices, in which case the solvent sites maintain the hydrogen bonding by bridging between residues i and i-3 or i-4 at the amino terminus and between i and i+3 or i+4 at the carbonyl terminus. We also see a number of solvent-mediated Ncap and Ccap interactions. The water molecules interacting with beta-sheets occur mainly at the edges, in which case they extend the sheet structure, or at the ends of strands, in which case they extend the beta-ladder. In summary, the solvent networks appear to extend the hydrogen-bonding structure of the secondary structures. In beta-turns, which usually occur at the surface of a protein, exposed amide and carbonyl groups are often hydrated, especially close to glycine residues. Occasionally water molecules form a bridge between residues i and i+3 in the turn and this may provide extra stabilization.     

Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens.

Hepatitis delta virus (HDV) particles were produced in Huh7 human hepatoma cells by transfection with cloned hepatitis B virus (HBV) DNA and HDV cDNA. The particles were characterized by their buoyant density, the presence of encapsidated viral RNA, and their ability to infect primary cultures of chimpanzee hepatocytes. Successful infection was evidenced by the appearance of increasing amounts of intracellular HDV RNA after exposure to particles. Infection was prevented when particles were incubated with antibodies directed against synthetic peptides specific for epitopes of the pre-S1 or pre-S2 domains of the HBV envelope proteins before exposure to hepatocytes. These data demonstrate that HDV particles produced in vitro are infectious and indicate (i) that infectious particles are coated with HBV envelope proteins that contain the pre-S1 and pre-S2 regions, (ii) that epitopes of the pre-S1 and pre-S2 domains of HBV envelope proteins are exposed at the surface of HDV particles, and (iii) that antibodies directed against those epitopes have neutralizing activity against HDV.     

The role of bactericidal/permeability-increasing protein as a natural inhibitor of bacterial endotoxin.

Systemic release of endotoxin (LPS) after Gram-negative infection initiates a cascade of host cytokines that are thought to be the direct cause of shock, multisystem organ failure, and death. Endogenous LPS-binding proteins may play a role in regulating LPS toxicity in vivo. The human neutrophil granule protein bactericidal/permeability-increasing protein (BPI) shares sequence homology and immunocrossreactivity with an acute phase lipopolysaccharide binding protein (LBP) which has been shown to bind to LPS and accelerate LPS activation of neutrophils and macrophages. Although structurally similar, LBP and BPI are apparently functionally antagonistic. We previously showed that BPI inhibits LPS-mediated neutrophil activation in vitro. Here we demonstrate that BPI binds to LPS near the lipid A domain, and formation of the LPS-BPI complex abrogates detrimental host responses to LPS. For example, BPI blocks LPS-stimulated TNF release in vitro and in vivo, and LPS complexed to BPI is not pyrogenic in rabbits. Results demonstrating that BPI is released by stimulated human neutrophils further support the idea that BPI functions extracellularly in vivo to neutralize endotoxin. Taken together, these data argue that BPI neutralizes the toxic effects of LPS in vivo, and that BPI may represent a new therapeutic approach to the treatment of endotoxic shock.     

Estimating prehistoric American Indian population size for united states area: Implications of the nineteenth century population decline and nadir

Implications of a revised United States American Indian nadir population and the pattern of decline leading to it are examined. Substituting the new nadir for that used by Dobyns (1966) lowers by several million his estimates of Indian population for the United States (and Canada) area. These estimates then become more compatible with ones currently being suggested by other scholars. The nineteenth century decline leading to this nadir is found to be remarkably linear. Assuming linearity in decline from initial European contact through the eighteenth century, an aboriginal population estimate of 1,845,183 for the United States area may be extrapolated, along with estimates for intervening years. The nineteenth century decline is then graphed with the data extrapolated to 1492. The resulting pattern of population decline is quite different from the ones suggested by Mooney (1928) and Dobyns (1966).     

Applicability of phosphorus budget models to southern African man-made lakes

An investigation of the phosphorus loading characteristics of 31 southern African man-made was lakes made. The lakes were characterized by low water retention times, with most of the lakes having retention times of less than one year. Catchment phosphorus export rates showed wide variation (1–162 mg P m^-2 y^-1) with those lakes experiencing excessive municipal wastewater inputs having export rates in excess of 53 mg m^-2 y^-1. The phosphorus data were tested against the Vollenweider (1976) and Dillon & Rigler (1974) phosphorus budget models which predict in-lake steady state concentrations of phosphorus. It was found that both models displayed good potential for the prediction of steady state concentrations of phosphorus, with better results being obtained from the Dillon & Rigler (1974) model. However, because phosphorus concentrations within these lakes may not necessarily be related to trophic status the use of these models as a predictive tool for eutrophication control still requires further development.     

Implications of Catlin's American Indian population estimates for revision of Mooney's estimate

Catlin's population estimates of 37 American Indian tribes for the period 1832 to 1839 are compared with Mooney's estimates for the same tribes that range from the year 1600 to the year 1780. The remarkably close correspondence between the two totals despite the difference in the time periods indicates considerable inaccuracy on the part of either Mooney or Catlin. If Catlin is given credibility, then the necessity of current upward revisions of Mooney's population estimate is supported.     

Bioavailability of arsenic in soil and mine wastes of the Tamar valley,SW England

ABSTRACT

The southern part of the Tamar valley area in SW England is highly mineralised and mines in the region were the world's principal producers of tin, copper and arsenic during the mid nineteenth century. The Devon Great Consols Mine, covering 67.6 ha (167 acres) is situated in this area. Residues from the mining activity resulted in unvegetated spoil tips and local soils highly contaminated with As (range 120–52600 μg/g As). Sequential chemical extraction procedures were conducted on eight surface samples (0–15 cm) taken from a 2.0 km long transect from within the mine site to agricultural grassland. The proportion of water extractable As in agricultural top soils was lower (0.05–0.3%) than the values obtained for mine wastes (0.02–1.2%). Arsenic was found to be concentrated in the Fe-organic and residual fractions, which accounted for up 93 % of the total As in mine spoil and nearby soils.