Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong

Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May 1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science 279:393-395, 1998). Gene sequences of this human isolate were compared to those of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in April 1997. Sequence comparisons of all eight RNA segments from the two viruses show greater than 99% sequence identity between them. However, neither isolate's gene sequence was closely (>95% sequence identity) related to any other gene sequences found in the GenBank database. Phylogenetic analysis demonstrated that the nucleotide sequences of at least four of the eight RNA segments clustered with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic analysis also included the sequences from an additional three human and two chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two closely related groups. However, no single amino acid change separated the chicken origin and human origin isolates, but they all contained multiple basic amino acids at the hemagglutinin cleavage site, which is associated with a highly pathogenic phenotype in poultry. In experimental intravenous inoculation studies with chickens, all seven viruses were highly pathogenic, killing most birds within 24 h. All infected chickens had virtually identical pathologic lesions, including moderate to severe diffuse edema and interstitial pneumonitis. Viral nucleoprotein was most frequently demonstrated in vascular endothelium, macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema and generalized cardiovascular collapse were the most likely pathogenic mechanisms responsible for illness and death. In summary, a small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations.     

Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor

When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy.     

The Imbrication Model for the integration of social services in a community

An innovative model for organising social services in a community, the Imbrication Model, is contrasted with two traditional models, the Entrepreneurial and the Umbrella Agency. The structural characteristics and dynamics of the three models are illustrated with actual case histories. Imbrication Model calls for the interlocking of personnel from several agencies, with the purpose of redirecting the dysfunctional interagency rivalry prevalent in the traditional models. Imbrications at all organisational levels--Board of Directors, Administrators and Staff--facilitate adoption of the superordinate goal of providing clients with the best services available, regardless of which particular agency delivers the service. Few observers of the current social service scene would challenge the statement that needs for service are unlimited and resources limited. In the USA the imbalance between needs and resources persists despite a decade of massive governmental programmes intended to alleviate social ills. Recent substantial cutbacks in federal funds, moreover are not likely to improve the situation. The resource shortage involves more than a limitation of funds. Deliverers of service and competent programme administrators are also on critically short supply. These shortages are more often than not exacerbated by a chronic spirit of competition among agencies and programmes at the local level. Three organizational models for the delivery and administration of social services, two conventional and one of more recent date, are examined in this article. The innovative model, which has been named the Imbrication Model, explicitly calls for redirecting interagency rivalry and competition. Its ambitious goal is to integrate the efforts of those attempting to meet a community's social service needs.