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Biomedical subjects

C E Bishop

Publications and source records attributed to C E Bishop.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations.

The recent transposition to the Y chromosome of the autosomal DAZL1 gene, potentially involved in germ cell development, created a unique opportunity to study the rate of Y chromosome evolution and assess the selective forces that may act upon such genes, and provided a new estimate of the male-to-female mutation rate (alpham). Two different Y-located DAZ sequences were observed in all Old World monkeys, apes and humans. Different DAZ copies originate from independent amplification events in each primate lineage. A comparison of autosomal DAZL1 and Y-linked DAZ intron sequences gave a new figure for male-to-female mutation rates of alpham = 4. It was found that human DAZ exons and introns are evolving at the same rate, implying neutral genetic drift and the absence of any functional selective pressures. We therefore hypothesize that Y-linked DAZ plays little, or a limited, role in human spermatogenesis. The two copies of DAZ in man appear to be due to a relatively recent duplication event (55 000-200 000 years). A worldwide survey of 67 men from five continents representing 19 distinct populations showed that most males have both DAZ variants. This implies a common origin for the Y chromosome consistent with a recent 'out of Africa' origin of the human race.

Africa↗
PubMed1997

Analysis of mutation rates in the SMCY/SMCX genes shows that mammalian evolution is male driven.

Mammalian evolution is believed to be male driven because the greater number of germ cell divisions per generation in males increases the opportunity for errors in DNA replication. Since the Y Chromosome (Chr) replicates exclusively in males, its genes should also evolve faster than X or autosomal genes. In addition, estimating the overall male-to-female mutation ratio (alpha m) is of great importance as a large alpha m implies that replication-independent mutagenic events play a relatively small role in evolution. A small alpha m suggests that the impact of these factors may, in fact, be significant. In order to address this problem, we have analyzed the rates of evolution in the homologous X-Y common SMCX/SMCY genes from three different species--mouse, human, and horse. The SMC genes were chosen because the X and Y copies are highly homologous, well conserved in evolution, and in all probability functionally interchangeable. Sequence comparisons and analysis of synonymous substitutions in approximately 1kb of the 5' coding region of the SMC genes reveal that the Y-linked copies are evolving approximately 1.8 times faster than their X homologs. The male-to-female mutation ratio alpha m was estimated to be 3. These data support the hypothesis that mammalian evolution is male driven. However, the ratio value is far smaller than suggested in earlier works, implying significance of replication-independent mutagenic events in evolution.

Amino Acid Sequence↗
PubMed1997

The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition.

A peptide recognized by two cytotoxic T cell clones specific for the human minor histocompatibility antigen H-Y and restricted by HLA-A*0201 was identified. This peptide originates from SMCY, as do two other H-Y epitopes, supporting the importance of this protein as a major source of H-Y determinants in mice and humans. In naturally processed peptides, T cells only recognize posttranslationally altered forms of this peptide that have undergone modification of a cysteine residue in the seventh position. One of these modifications involves attachment of a second cysteine residue via a disulfide bond. This modification has profound effects on T cell recognition and also occurs in other class I MHC-associated peptides, supporting its general importance as an immunological determinant.

Animals↗
PubMed1997

Absence of DAZ gene mutations in cases of non-obstructed azoospermia.

Sequenced-tagged site (STS) analysis of the Y chromosome long arm (Yq) of azoospermic males has identified a minimum common deleted region of several hundred kilobases in approximately 13% of cases. A candidate azoospermia gene, DAZ (deleted in azoospermia), has been isolated from this region. DAZ has also been shown to be absent in severely oligozoospermic males albeit at a much lower frequency. These data, although highly suggestive, do not constitute formal proof that DAZ actually plays a role in azoospermia, as no small intragenic deletions, rearrangements or point mutations in the gene have been found. In this study we report the screening of DNA from 168 azoospermic/oligospermic males for the presence of the DAZ gene. Deletions involving DAZ were detected in five out of 43 (11.6%) azoospermic males whereas none were found in the remaining 125 oligospermic patients. We present the genomic structure of the 5' end of the DAZ gene together with its sequence analysis in 30 non-obstructed azoospermic males. No mutations in DAZ were found in any of the patients sequenced. These data provide no formal proof that DAZ is AZF. Thus the possibility is still valid that another gene(s) mapping to the deletion interval may be responsible for, or contribute to, the observed phenotypes. Alternatively, if DAZ is AZF, they suggest that the most frequent cause of gene inactivation is via large deletions possibly mobilized by Y chromosome repetitive sequences.

Base Sequence↗
PubMed1997

On the origin and frequency of Y chromosome deletions responsible for severe male infertility.

The origin of deletions associated with non-obstructive severe oligozoospermia in men are discussed. Deletions could arise during various stages of meiosis, at later stages in spermatids, or post-fertilization. Certain embryonic stages may be highly sensitive. The possibilities of an inherited propensity to these and other deletions, and of mosaicism in embryos are assessed.

Chromosome Deletion↗
PubMed1996

The home health visit: an appropriate unit for Medicare payment?

To contain costs and increase incentives for efficient provision of care, prospective payment methods are being proposed for Medicare home health services. Although a shift to per episode payment is much discussed, the methods rely on the home health visit as a fundamental building block in setting rates and ceilings. Some propose setting fixed per visit prices in the interim until episode payment can be developed. Findings from the evaluation of a Health Care Financing Administration (HCFA) demonstration of per visit payment suggest that this could shorten to the length of visits provided to Medicare beneficiaries. Because of home health agencies' discretion over visit length, we question whether the visit is the appropriate basic unit for developing prospectives payment methods for Medicare home health.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1996

National health expenditure limits: the case for a global budget process.

The health reform cost-containment debate has set up a dichotomy between market and regulatory approaches. Expenditures are excessive in the American health system because there is no effective constraint on aggregate demand, and the rigid limits imposed by sectoral global budgets in other nations do not effectively use supply side forces to achieve efficiency. The case for an intermediate option is presented, a process that can flexibly encompass both what buyers are willing to pay and what suppliers are willing to accept. A negotiated contracting process for multiple payors and multiple providers could constrain aggregate demand and harness provider incentives.

Arizona↗
PubMed1995

The genetic basis of XX-XY differences present before gonadal sex differentiation in the mouse.

There is now a substantial body of data showing that in eutherian mammals (mouse, rat, cow and man) XY conceptuses are developmentally more advanced (and consequently larger) than XX conceptuses of equivalent gestational age. This developmental difference is already discernible in the preimplantation period and it has been suggested that the more advanced development of XY embryos may be a consequence of the preimplantation expression of Y chromosomal genes such as Sry or Zfy. In the present paper sex-chromosomally variant mice were used to analyse the genetic basis of XX-XY differences as manifest at 10.5 days post coitum. The results show that the XX-XY difference is due to a combination of a Y chromosome effect and an effect of the difference in X chromosome constitution (2X v 1X). The Y effect is not dependent on the presence of Sry. In the light of this and other studies, it is concluded that the Y chromosome of most mouse strains carries a factor which accelerates preimplantation development and that the resulting developmental advantage is carried over into the postimplantation period. The retarding effect of two X chromosomes is then superimposed on this Y effect subsequent to the blastocyst stage but prior to 9.5 days post coitum.

Animals↗
PubMed1995

Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein.

H-Y is a transplantation antigen that can lead to rejection of male organ and bone marrow grafts by female recipients, even if the donor and recipient match at the major histocompatibility locus of humans, the HLA (human leukocyte antigen) locus. However, the origin and function of H-Y antigens has eluded researchers for 40 years. One human H-Y antigen presented by HLA-B7 was identified as an 11-residue peptide derived from SMCY, an evolutionarily conserved protein encoded on the Y chromosome. The protein from the homologous gene on the X chromosome, SMCX, differs by two amino acid residues in the same region. The identification of H-Y may aid in transplantation prognosis, prenatal diagnosis, and fertilization strategies.

Amino Acid Sequence↗
PubMed1995

Identification of a mouse male-specific transplantation antigen, H-Y.

The male-specific transplantation antigen, H-Y, causes rejection of male tissue grafts by genotypically identical female mice and contributes to the rejection of human leukocyte antigen-matched male organ grafts by human females. Although first recognized 40 years ago, the identity of H-Y has remained elusive. T cells detect several distinct H-Y epitopes, and these are probably peptides, derived from intracellular proteins, that are presented at the cell surface with major histocompatibility complex (MHC) molecules. In the mouse, the gene(s) controlling H-Y expression (Hya) are located on the short arm of the Y chromosome between the zinc-finger genes Zfy-1 and Zfy-2. We have recently identified Smcy, a ubiquitously expressed gene, in this region and its X-chromosome homologue, Smcx. Here we report that Smcy encodes an H-YKk epitope that is defined by the octamer peptide TENSGKDI: no similar peptide is found in Smcx. These findings provide a genetic basis for the antigenic difference between males and females that contributes towards a tissue transplant rejection response.

Amino Acid Sequence↗
PubMed1995

Understanding the factors behind the decision to purchase varying coverage amounts of long-term care insurance.

OBJECTIVE: This article examines the factors related to an individual's decision to purchase a given amount of long-term care insurance coverage. DATA SOURCE AND STUDY SETTING: Primary data analyses were conducted on an estimation sample of 6,545 individuals who had purchased long-term care (LTC) insurance policies in late 1990 and early 1991, and 1,248 individuals who had been approached by agents but chose not to buy such insurance. Companies contributing the two samples represented 45 percent of total sales during the study year. STUDY DESIGN: A two-stage logit-OLS (ordinary least squares) choice-based sampling model was used to examine the relationship between the expected value of purchased coverage and explanatory variables that included: demographic traits, attitudes, risk premium, nursing home bed supply, and Medicaid program configurations. DATA COLLECTION: Mail surveys were used to collect information about individuals' reasons for purchase, attitudes about long-term care, and demographic characteristics. Through an identification code, information on the policy designs chosen by these individuals was linked to each of the returned mail surveys. The response rate to the survey was about 60 percent. PRINCIPAL FINDINGS: The model explains about 47 percent of the variance in the dependent variable-expected value of policy coverage. Important variables negatively associated with the dependent variable include advancing age, being married, and having less than a college education. Variables positively related include being male, having more income, and having increasing expected LTC costs. Medicaid program configuration also influences the level of benefits purchased: state reimbursement rates and the presence of comprehensive estate recovery programs are both positively related to the expected value of purchased benefits. Finally, as the difference between the premium charged and the actuarially fair premium increases, individuals buy less coverage. CONCLUSIONS: An important finding with implications for policymakers is that changes in Medicaid policy affect the decisions of consumers regarding the acquisition of private LTC policies as well as the level of protection chosen. This is particularly important to states interested in pursuing public-private partnerships in long-term care financing.

Actuarial Analysis↗
PubMed1994

Deletion mapping by immunoselection against the H-Y histocompatibility antigen further resolves the Sxra region of the mouse Y chromosome and reveals complexity of the Hya locus.

A genetic map of the mammalian Y chromosome cannot be produced by standard Mendelian methods because the Y does not participate in meiotic exchange over the majority of its length. However, deletion mapping of the mouse Y chromosome is facilitated by the fact that its short arm carries the histocompatibility-Y (Hya) locus. This locus encodes male-specific (H-Y) antigens that can be selected against in tissue culture by the technique of immunoselection. To produce cells carrying deletions, cytotoxic T lymphocytes (CTLs) specific for H-Y antigens were cocultured with a lymphoblastoid cell line derived from a mouse carrying the portion of the short arm defined by the Sxra translocation on the distal end of its X chromosome. H-Y antigen-loss variant cells that contained Y-specific deletions were identified. Molecular, karyotypic, and immunological analysis of the deletion variants allowed us to define up to 16 ordered intervals and suggested an overall organization of Sxra. The analysis also suggests that at least two and up to five distinct loci encode H-Y antigens.

Animals↗
PubMed1994

A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens.

A new mouse Y chromosome gene, Smcy, has been isolated from the region encoding Spy, a spermatogenesis gene and Hya and Sdma, the genes that, respectively, control the expression of the male specific minor histocompatibility antigen H-Y, as measured by specific T-cell assays and the serologically detected male antigen SDMA. Smcy is well conserved on the Y in mouse, man and even marsupials. It is expressed in all adult male tissues tested and can also be detected during mouse development from as early as two cells. In addition, its human Y homologue, SMCY, is expressed in multiple tissues and maps to the same Yq deletion interval as the human H-Y antigen controlling locus, HY.

Amino Acid Sequence↗
PubMed1994

A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human.

A new gene, designated Smcx, was cloned from the mouse X chromosome by its homology to the Y located gene Smcy. Using direct in situ hybridisation Smcx was mapped to the distal end of the mouse X chromosome (XF2-XF4) and its human homologue, SMCX, was mapped to proximal Xp (Xp11.1-Xp11.2). Further meiotic mapping in the mouse placed Smcx in the Plp-Pdha1 interval. As Smcx/SMCX have widely expressed homologues on the Y chromosome, they appeared good candidates for genes that escape X-inactivation. In the human we show this to be the case as SMCX is expressed in hamster-human hybrids containing either an active or inactive human X chromosome. Two alleles of Smcx were found to be expressed in T(16;X)16H female mice despite the intact X chromosome being inactive in all cells. This indicates that Smcx is also not subject to X-inactivation and provides the first example of a gene that is expressed from inactive and active X chromosomes in the mouse.

Alleles↗
PubMed1994

Recruiting and employing foreign nurse graduates in a large public hospital system.

Recruiting foreign nurse graduates (FNGs) is one way hospitals--particularly those in the nation's inner cities--are responding to the periodic and cyclic shortages that characterize the labor market for registered nurses. Until now, little was known about the overall efficacy of this strategy. This article reports the findings of an 18-month study of the recruitment and employment of FNGs by the New York City Health and Hospitals Corporation. Although considerably more expensive to recruit than domestic nurses, FNGs have higher retention rates than U.S.-educated nurses and possess other characteristics that make them desirable recruits for hospitals experiencing a nursing shortage.

Data Collection↗