Search PubMed⌕ Search

Biomedical subjects

C Rooney

Publications and source records attributed to C Rooney.

At least 37 records · Page 2Linked to original sources
PubMed1997

The time taken to register a death.

This article analyses delays in the registration of death and discusses their effect on mortality statistics. It is shown that the longest delays arise when deaths are the subject of a coroner's inquest, in particular deaths in road traffic accidents. These delays mean that it may be many months before an acceptable proportion of deaths occurring in a year have been registered, so affecting how early a reliable extract of annual data can be taken. It also shows that the difference in the number of deaths occurring and the number registered in a year is strongly influenced by the weekdays on which holidays fall at the New Year.

Cause of Death↗
PubMed1996

Osteolysis circumscripta evanescans.

A circumscribed radiolucent skull abnormality was detected on plain radiographs obtained to evaluate minor cranial trauma in a young boy. The lesion disappeared on follow-up X-rays performed later in the day. Analysis of the case revealed that the lesion was an artifact resulting from a superimposed hole in a wooden backboard on which the patient was X-rayed initially. Radiographs shot through a protective backboard may be misleading, and not all abnormalities identified belong to the patient.

Artifacts↗
PubMed1996

Increasing mortality from Creutzfeldt-Jakob disease in England and Wales since 1979: ascertainment bias from increase in post-mortems?

Creutzfeldt-Jakob disease (CJD) is a rare and fatal dementing illness. A direct link has been proposed between cattle infected with bovine spongiform encephalopathy (BSE) and a newly-identified variant of CJD. One possible explanation for the emergence of this new variant, together with a general increase in death due to classical CJD, would be ascertainment bias, due to an increase in the frequency of post-mortems in death attributed to dementia. This article uses national mortality records to look at trends in the proportion of deaths due to dementing illnesses for which a post-mortems was carried out. The results show an increase in deaths due to both CJD and other dementing illnesses, but a slight decrease in the proportion of post-mortems. We conclude that an increase in post-mortems is unlikely to explain the increase in deaths certified as due to CJD. Similarly, the appearance of the new variant of CJD since 1994 cannot easily be attributed to this form of ascertainment bias, in line with the conclusion reached by the Spongiform Encephalopathy Advisory Committee in March 1996.

Adult↗
PubMed1996

Mortality trends by cause of death in England and Wales 1980-94: the impact of introducing automated cause coding and related changes in 1993.

This article describes the implementation of a computerised system for coding the cause of death from death registrations in England and Wales since the beginning of 1993, and the impact this has had on national cause of death statistics. Overall the automated system has been effective and reliable at deriving ICD-9 codes for the underlying cause of death and other conditions mentioned on the certificate. Automation increases the consistency and international comparability of cause of death coding. However, it has led to discontinuities in time trends between 1992 and 1993, which are explored here. The largest effect was related to expected changes in the application of ICD-9 selection rule 3. However there were other effects which were not expected. The automated system does not deal adequately with external causes of death, which are certified after coroner's inquest, and ONS has reverted to coding these clerically. Lessons for the implementation of ICD-10 for mortality have been learnt.

Adolescent↗
PubMed1996

Transfer of marker genes into hemopoietic progenitor cells.

Ex vivo gene marking of normal and malignant hemopoietic cells allows the cells to be subsequently tracked in vivo. Marking has shown that even when marrow is in remission, it may contain malignant cells that contribute to relapse. These studies have also shown that it is possible to obtain long-term gene expression in human long-lived hemopoietic progenitor cells and T lymphocytes in vivo. Current marker studies use two distinguishable vectors to track two distinctively treated cell populations in a single individual. This modification greatly increases the power of the technique. It is now possible to study the effects of purging on residual malignant cells in marrow, to determine the action of growth-promoting agents (such as cytokines and stroma) on short- and long-term repopulation by transduced marrow, and to discover which phenotypic subsets of hemopoietic progenitor cells have long-term repopulating potential. The information gained will be invaluable for improving therapeutic gene transfer protocols in which marrow-derived cells are the targets.

Bone Marrow Cells↗
PubMed1993

Case-control study of prostatic cancer in employees of the United Kingdom Atomic Energy Authority.

OBJECTIVE: To investigate the relation between risk of prostatic cancer and occupational exposures, especially to radionuclides, in employees of the United Kingdom Atomic Energy Authority. DESIGN: Case-control study of men with prostatic cancer and matched controls. Information about sociodemographic factors and exposures to radionuclides and other substances was abstracted and classified for each subject from United Kingdom Atomic Energy Authority records without knowledge of who had cancer. SUBJECTS: 136 men with prostatic cancer diagnosed between 1946 and 1986 and 404 matched controls, all employees of United Kingdom Atomic Energy Authority. MAIN OUTCOME MEASURES: Documented or possible contamination with specific radionuclides. RESULTS: Risk of prostatic cancer was significantly increased in men who were internally contaminated with or who worked in environments potentially contaminated by tritium, chromium-51, iron-59, cobalt-60, or zinc-65. Internal contamination with at least one of the five radionuclides was detected in 14 men with prostatic cancer (10%) and 12 controls (3%) (relative risk 5.32 (95% confidence interval 1.87 to 17.24). Altogether 28 men with prostatic cancer (21%) and 46 controls (11%) worked in environments potentially contaminated by at least one of the five radionuclides (relative risk 2.36 (1.26 to 4.43)); about two thirds worked at heavy water reactors (19 men with prostatic cancer and 32 controls (relative risk 2.13 (1.00 to 4.52)). Relative risk of prostatic cancer increased with increasing duration of work in places potentially contaminated by these radionuclides and with increasing level of probable contamination. Prostatic cancer was not associated with exposure to plutonium, uranium, cadmium, boron, beryllium, or organic or inorganic chemicals. CONCLUSIONS: Risk of prostatic cancer risk was increased in United Kingdom Atomic Energy Authority workers who were occupationally exposed to tritium, 51Cr, 59Fe, 60Co, or 65Zn. Exposure to these radionuclides was infrequent, and their separate effects could not be evaluated.

Adult↗
PubMed1993

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability.

The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B-cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.

B-Lymphocytes↗
PubMed1992

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. I. Suppression of T-cell activation.

Considerable attention has been directed at defining the health deficits associated with exposure to mercurial compounds. While numerous studies have been conducted, the findings have been somewhat contradictory and have led to a confused understanding of the immunotoxicology of mercury. It is becoming clear, however, that the immunotoxic effects of heavy metals in general, and mercury in particular, are dependent upon the assays and source of cells. The major goal of our study was to assess whether low level mercury exposure modulates human T-cell function. Following treatment of T-cells with HgCl2 (0-1000 ng) and MeHgCl (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in T cell proliferation, however, the effect was dependent upon the presence of monocytes. Moreover, in the absence of monocytes, HgCl2 enhance PMA induced T-cell proliferation. MeHgCl was approximately 5-10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize and secrete IL-1. Analysis of the expression of activation markers on the cell surface indicated that one of the earliest markers of lymphocyte activation, CD69, was not effected by mercury. In comparison, T-cell expression of IL-2R and the transferrin receptor was impaired. Of particular interest, cells activated by mitogen for 24 hr became refractory to the immunotoxic effects of mercury. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in T-cell function following exposure to mercury indicates that this metal is immunotoxic at very low exposure levels.

Antigens, CD↗
PubMed1992

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. II. Alterations in cell viability.

The major goal of this investigation was to examine the cytotoxic properties of both HgCl2 and MeHgCl, in terms of their ability to alter human T-cell and monocyte viability. Following treatment with HgCl2 (0-20 micrograms/ml) or MeHgCl (0-2 micrograms/ml), there was minimal reduction in lymphocyte viability at 1-4 hr. However, after exposure to mercury for 24 hr, cell death was apparent. In comparison, monocytes exhibited significant loss of viability during the early exposure periods. MeHgCl was approximately 5-10 times more potent than HgCl2. Other indicators of cell death were also determined. Measurement of the energy charge ratio indicated profound changes in cellular energy conservation. Electron microscopic analysis of cells treated with mercury revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. In concert with these nuclear changes, there was destruction of cytoplasmic organelles with loss of membrane integrity. Studies of phospholipid synthesis by mercury treated cells confirmed that there were alterations in membrane structure. Thus, there was a decrease in total phosphatide synthesis by treated cells. Moreover, monocyte phospholipid synthesis appeared to be more sensitive to the presence of mercury then lymphocytes. Finally, both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. These morphological and biochemical changes are consistent with the notion that mercury initiates cytotoxic changes associated with programmed cell death.

Animals↗
PubMed1989

Influence of Burkitt's lymphoma and primary B cells on latent gene expression by the nonimmortalizing P3J-HR-1 strain of Epstein-Barr virus.

The Epstein-Barr virus (EBV) genes expressed in B lymphocytes immortalized in vitro or in Burkitt's lymphoma (BL) cells infected in vivo have been characterized previously; however, the viral products which are essential for immortalization or for establishment of EBV latency are still not known. To approach this question, we compared the kinetics of expression of EBV nuclear antigens and the two EBV-encoded small RNAs, EBER1 and EBER2, after infection of primary B cells or EBV genome-negative BL cells with either an immortalizing EBV strain (B95-8) or the nonimmortalizing deletion mutant (HR-1). Following infection of primary cells with B95-8 virus, EBV nuclear antigen (EBNA)-2 was expressed first, followed by EBNA-1, -3, and -4 (also called leader protein [LP]) and the two small RNAs. Infection of EBV genome-negative BL cells with the same strain of virus resulted in a similar pattern of gene expression, except that the EBNAs appeared together and more rapidly. EBERs were not apparent in one BL cell line converted by B95-8. The only products detected after infection of primary B lymphocytes with the HR-1 deletion mutant were the EBNA-4 (LP) family and trace amounts of EBER1. Although HR-1 could express neither EBNA-1, EBNA-3, nor EBER2 in primary cells, all these products were expressed rapidly after HR-1 infection of EBV genome-negative BL cell lines. The results indicate that the mutation in HR-1 virus affects immortalization not only through failure to express EBNA-2, a gene which is deleted, but also indirectly by curtailing expression of several other EBV genes whose coding regions are intact in the HR-1 virus and normally expressed during latency. The pattern of latent EBV gene expression after HR-1 infection is dependent on the host cell, perhaps through products specific for the cell cycle or the state of B-cell differentiation.

Antigens, Viral↗
PubMed1989

Expression of the BZLF1 latency-disrupting gene differs in standard and defective Epstein-Barr viruses.

Previous experiments using gene transfer of plasmids with heterologous promoters identified an Epstein-Barr virus (EBV) gene (BZLF1) whose product (ZEBRA) switches the virus from a latent to a replicative state. We have now studied expression of ZEBRA in lymphoid cells harboring either standard virus or a mixture of standard and defective (heterogeneous [het]) viruses. A high-titer rabbit antiserum to a TrpE-BZLF1 fusion protein was used to identify ZEBRA expressed from standard and het EBV DNA. These ZEBRA proteins could be distinguished from each other on the basis of their electrophoretic mobilities. ZEBRA could not be detected in cells latently infected with standard EBV. However, within 6 h after induction of replication by sodium butyrate, ZEBRA appeared and persisted long thereafter. Synthesis of ZEBRA was insensitive to phosphonoacetic acid or acycloguanosine, behavior characteristic of an early replicative protein. ZEBRA was constitutively expressed in cells containing both defective and standard EBV genomes. ZEBRA was made predominantly from the het genome but also from the standard genome. Control of BZLF1 expression appears to occur at the transcriptional level. No BZLF1-specific transcript was detected in cells containing only standard latent EBV. BZLF1 transcripts could be detected in these cells if virus replication was induced by treatment with butyrate. Cells bearing both standard and het genomes did not require addition of an exogenous inducing agent to transcribe the BZLF1 gene. The experiments suggest that regulation of transcription of the BZLF1 gene is a pivotal event in the control of EBV replication.

Burkitt Lymphoma↗
PubMed1988

Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency.

A defective Epstein-Barr virus (EBV) containing a deleted and rearranged genome (het DNA) causes latent EBV to replicate. This activity maps to the 2.7-kilobase-pair WZhet fragment. The BZLF1 open reading frame, present within WZhet as well as in the standard viral BamHI Z fragment, encodes the protein ZEBRA, which induces viral replication. Using gene transfers into Burkitt lymphoma cells, we now demonstrate that rearranged sequences juxtaposed to BZLF1 in het DNA facilitate expression of ZEBRA protein. Two stretches of EBV sequences within a palindromic region of het DNA contain positive regulatory elements. One set, derived from the viral large internal repeat, is newly positioned upstream of BZLF1; the second set is downstream of BZLF1 in het DNA. The capacity of defective HR-1 viruses to disrupt latency of the standard EBV genome is due to abnormal regulation of the BZLF1 gene as a result of genomic rearrangements.

Base Sequence↗
PubMed1987

Selective lack of antibody to a component of EB nuclear antigen in patients with chronic active Epstein-Barr virus infection.

The sera of 12 patients with presumed chronic active Epstein-Barr virus (EBV) infection lacked antibody to a component of the Epstein-Barr nuclear antigen (EBNA) complex encoded by the BamHI K fragment of viral DNA. This anomaly, detected in approximately 18% of sera obtained from patients with a diagnosis of "chronic mononucleosis," was more often found in patients with severe disease (approximately 32%) who had objective clinical findings and markedly elevated antibody titers to EBV replicative antigens than in those patients with the "fatigue syndrome" (10%). The lack of antibody to the K nuclear antigen is specific because most of those who did not have antibody to the K antigen made antibody to other latent nuclear (EBNA 2) antigens or nuclear early antigens. Such patients are thus able to lyse immortalized cells, release nuclear products, and present them to the immune system. Three hypotheses are suggested to explain the lack of antibody to the K antigen: a viral mutation, a failure of immune recognition, or lack of in vivo expression of the antigen due to extensive viral replication. Lack of antibody to one component of EBNA may serve as an objective serological marker for certain patients with chronic EBV infection.

Adolescent↗
PubMedDate not supplied

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content.

The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗