Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Growth hormone as an early embryonic growth and differentiation factor

In this review we consider the evidence that growth hormone (GH) acts in the embryo as a local growth, differentiation, and cell survival factor. Because both GH and its receptors are present in the early embryo before the functional differentiation of pituitary somatotrophs and before the establishment of a functioning circulatory system, the conditions are such that GH may be a member of the large battery of autocrine/paracrine growth factors that control embryonic development. It has been clearly established that GH is able to exert direct effects, independent of insulin-like growth factor-I (IGF-I), on the differentiation, proliferation, and survival of cells in a wide variety of tissues in the embryo, fetus, and adult. The signaling pathways behind these effects of GH are now beginning to be determined, establishing early extrapituitary GH as a bona fide developmental growth factor.     

Efficiency of cross presentation of vaccinia virus-derived antigens by human dendritic cells.

Dendritic cells (DC) utilize at least two pathways to process viral antigens onto MHC class I molecules. The conventional endogenous route is used to acquire antigens from both infectious and non-replicating virions. Exogenous pathways are used by DC to acquire and "cross-present" antigens derived from virus-infected donor cells that by themselves lack the ability to activate T cells directly. We analyzed the role of this pathway for antigens derived from vaccinia, a virus which inhibits DC maturation and causes extensive apoptosis of infected cells, yet is highly immunogenic. Using recombinant vaccinia virus encoding the influenza matrix protein as model vector, DC were shown to cross-present vaccinia-derived antigens from both apoptotic and necrotic infected cells to antigen-specific CD8(+) T cells. Efficient cross presentation required uptake of dead cells by immature DC and exposure to maturation stimuli, especially CD40 ligand. The responding CD8(+) T cells secreted IL-2 and IFN-gamma, proliferated and developed into cytotoxic effectors. Quantification of the cross presentation of vaccinia-derived antigens showed this pathway to be highly efficient, corresponding to a peptide pulse of 10-100 nM. While monocytes also phagocytosed apoptotic and necrotic cells, they were far less efficient at cross-presenting vaccinia-derived antigens to CD8(+) T cells. The ability of DC to cross-present vaccinia-derived antigens from infected apoptotic cells or necrotic cell lysates, bypasses the deleterious effects of direct infection of DC and provides one explanation for this pathogen's immunogenicity.     

Reporting basal cell carcinoma: a survey of the attitudes of histopathologists

AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer.     

Advancement to independent living: a model behavioral program for the intermediate care of adults with behavioral and emotional problems

This article describes and evaluates the treatment effectiveness of a behaviorally oriented intermediate day-care clinic for adults with psychiatric disturbances. The goals of the program included reducing the number of psychiatric hospital admissions and readmissions, providing a community-based controlled environment to assist patients in the modification of specific problem behavior, improving interpersonal relations with "significant others" in the natural environment, teaching patients how to use community resources, and preparing them for employment and/or continued outpatient treatment. The program was structured so that patients advance through a series of four achievement levels for a variety of extrinsic and intrinsic reinforcers. While in the program, patients were introduced to available community resources, and were gradually phased into follow-up services. Results showed that 79% of all patients thus far treated partially, if not completely, advanced through the levels. There was also a high probability that a patient would advance from any given level. Outside-clinic behavior showed sustained improvement, with the authors concluding that the day-care clinic offered promise for the future.     

EA rosette-forming lymphoid cells in chickens: specificity of the Fc receptor and its relationship to other surface antigens.

The receptor for erythrocyte-antibody (EA) complexes on the surface of chicken lymphoid cells was investigated using a rosette assay. The chicken EA receptor binds chicken immunoglobulin of the IgG class but not the IgM class. Binding to the EA receptor is dependent upon the Fc region of the immunoglobulin. No receptor for complement analogous to the mammalian C3b receptor was demonstrated on chicken lymphoid cells using the rosette assay. Inhibition studies utilizing immunoglobulins from several species demonstrated that chicken spleen cells do not bind mammalian immunoglobulin but may bind immunoglobulin of other avian species (turkey and duck) and a reptilian species (turtle). The chicken EA receptor is distinct from cell membrane bound immunoglobulin light chains, bursa-specific antigens and thymus-specific antigens. The receptor for EA complexes on chicken lymphoid cells is compared with the Fc receptor on mammalian lymphoid cells in the light of these observations.     

Cost effectiveness of vaccination against pneumococcal pneumonia

We used cost-effectiveness analysis to examine the medical-care costs of vaccination against pneumococcal pneumonia in relation to its effects on health. Vaccination could add a year of healthy life among all age groups for about $4,800 in net medical-care costs. Cost-effectiveness ratios vary according to the age of the person vaccinated--from $1,000 per year of healthy life for an adult 65 years old or older to $77,000 per year of healthy life for a child between the ages of two and four. These ratios may change substantially with variations in such factors as the cost of vaccination, the duration of immunity, the efficacy and composition of the vaccine, and the percentage of pneumonia that is pneumococcal. This analysis has particular relevance for the Medicare program, since present legislation excludes coverage of most immunizations and other preventive services. Provision of pneumococcal vaccine to the elderly and inclusion of the vaccine as a Medicare benefit merit serious consideration.     

Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation

Human herpesvirus type 6 (HHV6) is known to reactivate after hematopoetic stem cell transplantation (HSCT) and has been suggested to be associated with increased mortality and severe clinical manifestations, including graft versus host disease (GvHD). The exact etiological role of HHV6 reactivation in increased morbidity and mortality after HSCT remains unclear. This review will focus on the current available evidence of HHV6 reactivation after HSCT and its immuno-modulatory capacities, with particular emphasis on the severe complication GvHD. At present, no effective specific antiviral treatment for HHV6 reactivation has been identified. The currently available antiviral agents are outlined, as well as possible future strategies for the treatment of HHV6 reactivation. Non-toxic, specific treatment or prevention of HHV6 reactivation might improve the safety and efficacy of the HSCT procedure.