A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom

OBJECTIVE: To demonstrate the value of a national register for surveillance of services for an inherited disorder. METHODS: Data from the United Kingdom Thalassaemia Register and the United Kingdom Register of Prenatal Diagnosis for Haemoglobin Disorders were combined in a database; these registers include all fetuses known to have been diagnosed with beta thalassaemia major, beta thalassaemia intermedia, or haemoglobin E/beta thalassaemia in the United Kingdom. Data were extracted to show outcomes (selective abortion or live birth) of all fetuses and the status of those born with a disorder (alive, dead, successful bone marrow transplant, or lost to follow-up) by parents' region of residence and ethnicity. FINDINGS: At the end of 1999 the register included 1074 patients, 807 of whom were alive and residing in the United Kingdom. A successful bone marrow transplant has been performed for 117 out of 581 (20%) patients born since 1975. Residents of Pakistani origin are now the main group at risk in the United Kingdom, replacing residents of Cypriot origin. This has led to a marked shift in the need for services from the south-east of England to the Midlands and the north of England. Despite the acceptability of prenatal diagnosis, the proportion of affected births remains 50% higher than would be expected, reflecting a widespread failure to deliver timely screening and counselling to carriers. Even though effective treatment is available the annual number of deaths is rising, indicating that better tolerated treatments are needed. CONCLUSION: A national diagnosis register is a powerful instrument for monitoring the treatment and prevention of inherited disorders and for highlighting correctable shortcomings. In view of the increasing possibilities for genetic screening there is a strong case for central funding for such databases within modern health services

Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype.

Extracellular matrix (ECM)' plays an important regulatory role in cellular growth, migration, and differentiation (1-4). Pathologic processes such as tumor cell invasion and metastasis are also determined by cellular interactions with ECM (5, 6). Biochemical studies have identified collagens, fibronectin, laminin, proteoglycans, and several other proteins as major ECM components (1-3), and have shown that ECM composition varies between different normal and tumor tissues. The complexity and heterogeneity of ECM composition have hampered the molecular analysis of ECM-cell interactions . However, a range of phenotypic changes has been described for cultured cells after transfer from plastic surfaces to substrates coated with native ECM (7, 8) or with purified ECM components; ECM-induced phenotypic changes include enhanced substrate adhesiveness, cell spreading and migration, changes in cell morphology and proliferative activity, and expression of differentiated cellular functions (I-4). Some of these effects, e.g., increased substrate adhesion, may result directly from the binding of specialized cell surface structures to ECM molecules. Others are likely mediated by an active cellular response triggered by the interaction of ECM with cell surface receptors. Thus, ECM-derived signals (9) may activate a cascade of molecular changes within the cell and on the cell surface that account for the pleiotropic effects observed with ECM

LEUKEMIA-ASSOCIATED TRANSPLANTATION ANTIGENS RELATED TO MURINE LEUKEMIA VIRUS : THE X.1 SYSTEM: IMMUNE RESPONSE CONTROLLED BY A LOCUS LINKED TOH-2

Two BALB radiation leukemias are strongly rejected by hybrids of BALB with certain other mouse strains, although BALB mice themselves exhibit no detectable resistance whatever. Hybrids immunized with progressively increased inocula are resistant to 200 x 106 or more leukemia cells; their serum is cytotoxic for the leukemia cells in vitro and protects BALB mice against challenge with these BALB leukemias. The antigenic system thus identified has been named X.1. In (BALB x B6) hybrids the major determinant of resistance was shown to be a B6 gene in the K region of H-2. This is likely to be the Rgv-1 (Resistance to gross virus) locus of Lilly, which may thus be identified in this case as an Ir (Immune response) allele conferring ability to respond to X.1 antigen on MuLV and leukemia cells, and so responsible for production of X.1 antibody and the rejection of X.1+ leukemia cells by hybrid mice. Immunoelectron microscopy with X.1 antiserum (from immunized hybrids) shows labeling both on the cell surface and on virions produced by the leukemia cells. It is not known whether X.1 comprises only one or more than one antigen. Three radiation-induced BALB leukemias, one A strain radiation-induced leukemia, and 15/15 AKR primary spontaneous leukemias were typed X.1+ by the cytotoxicity test. Several other leukemias, including one induced by passage A Gross virus and one long-transplanted AKR ascites leukemia carried in (B6 x AKR)F1 hybrids, were X.1-. Normal mice of strains with a high incidence of leukemia and one other strain (129) express X.1 antigen, but evidently in amounts too small for certain detection in vitro; by the method of absorption in vivo, however, these strains could be typed X.1+ and other strains X.1-. We ascribe the X.1 antigen system tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub-type in strains with a high incidence of leukemia. After repeated passage in hybrids, one of the BALB leukemias became relatively resistant to rejection by the hybrid, partially lost its sensitivity to X.1 antiserum in vitro, and in electron micrographs was seen to produce fewer virions. The serum of untreated (BALB x B6) hybrids often contains cytotoxic antibody against leukemia cells, some of it probably anti-X.1. But another commonly occurring antibody, which is cytotoxic for C57BL leukemia EL4, appears to belong to another (undefined) system

Circulation, Vol. 14, No. 3

Fall 2007 issue of CCPO Circulation featuring article Analysis of Time Series Data from the Chesapeake Bay Mouth Cruises by S. Sackett and J. L. Blancohttps://digitalcommons.odu.edu/ccpo_circulation/1013/thumbnail.jp

RELATION OF CHROMOSOME 4 (LINKAGE GROUP VIII) TO MURINE LEUKEMIA VIRUS-ASSOCIATED ANTIGENS OF AKR MICE

Genes specifying or controlling the expression of GIX (cell surface), GCSA (cell surface), and gs (internal viral) antigens are located in chromosome 4 (linkage group [LG] VIII) of the AKR mouse. All three antigens may exhibit mendelian inheritance, mice being antigen positive or antigen negative, but each may also appear in leukemic cells of mice whose inherited genotype was antigen negative. The GIX-determining gene in LG VIII of AKR mice apparently is equivalent to Gv-1, which determines expression of the same antigen in 129 strain mice, but which in the latter strain is located in LG IX. As the estimated distance of Gv-1 from H-2 in 129 mice is considerable (37 units) further tests are now indicated to assess the possibility of pseudolinkage in this case. The Fv-1 locus, also located in LG VIII, influences the mouse's titer of MuLV, and might thereby be thought to regulate the GIX and gs phenotypes of AKR backcross segregants. But the data indicate a discrete LG VIII locus for GIX, since expression of this antigen is mendelian and independent of infectious virus titer. Since the GIX and GCSA phenotypes of AKR backcross segregants were invariably concordant, these two antigens must be specified or controlled by closely linked genes, and the latter also is presumably independent of virus titer. The question as to what extent expression of gs antigen in the segregants is secondary to virus production is undecided

Indian health conditions.

This volume is a compendium of scholarly analyses of the health conditions that together constitute most of the illness borne by American Indians and Alaska Natives. Topics include; health intervention; cancer; cardiovascular diseases; diabetes; digestive system diseases; infant mortality; infectious diseases; maternal health; mental health and mental illness; musculosketetal system disease; oral disease; end-stage renal disease; respiratory diseases; violence; substance abuse; and accidental injuries. This publication was developed in 1986 and although, the data are several years old, much of the analyses and recommendations are still relevant today. It also serves as an important historical or reference document for the Indian Health Service. Each analysis provides an overview of a particular health condition as it affects the IHS service population nationwide and suggests, recommendations regarding the steps that IHS can take to reduce and eventually eliminate the described health problems

CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens

The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen articles