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H Simmons

Publications and source records attributed to H Simmons.

At least 19 recordsLinked to original sources
PubMed1995

Susceptibility to duck hepatitis B virus infection is associated with the presence of cell surface receptor sites that efficiently bind viral particles.

To test the hypothesis that susceptibility of hepatocytes to duck hepatitis B virus (DHBV) infection requires cell surface receptors that bind the virus in a specific manner, we developed an assay for the binding of DHBV particles to monolayers of intact cells, using radiolabeled immunoglobulin G specific for DHBV envelope protein. Both noninfectious DHBV surface antigen particles and infectious virions bound to a susceptible fraction (approximately 60%) of Pekin duck hepatocytes. In contrast, binding did not occur to cells that were not susceptible to DHBV infection, including Pekin duck fibroblasts and chicken hepatocytes, and binding to Muscovy duck hepatocytes, which are only weakly susceptible (approximately 1% of cells) to DHBV infection, was virtually undetectable. Within a monolayer, individual Pekin duck hepatocytes appeared to differ markedly in the capacity to bind DHBV, which may explain difficulties that have been encountered in infecting 100% of cells in culture. We have also found that the loss of susceptibility to infection with DHBV that occurs when Pekin duck hepatocytes are maintained for more than a few days in culture correlates with a decline in the number of cells that bind virus particles efficiently. All of these results support the interpretation that the binding event detected by our assay is associated with the interaction between DHBV and specific cell surface receptors that are required for initiation of infection. Our assay may facilitate isolation and identification of hepatocyte receptors for this virus.

Animals↗
PubMed1994

Duck hepatitis B virus infection of Muscovy duck hepatocytes and nature of virus resistance in vivo.

To test the hypothesis that in vivo resistance to hepadnavirus infection was due to resistance of host hepatocytes, we isolated hepatocytes from Muscovy ducklings and chickens, birds that have been shown to be resistant to duck hepatitis B virus (DHBV) infection, and attempted to infect them in vitro with virus from congenitally infected Pekin ducks. Chicken hepatocytes were resistant to infection, but we were able to infect approximately 1% of Muscovy duck hepatocytes in culture. Infection requires prolonged incubation with virus at 37 degrees C. Virus spread occurs in the Muscovy cultures, resulting in 5 to 10% DHBV-infected hepatocytes by 3 weeks after infection. The relatively low rate of accumulation of DHBV DNA in infected Muscovy hepatocyte cultures is most likely due to inefficient spread of virus infection; in the absence of virus spread, the rates of DHBV replication in Pekin and Muscovy hepatocyte cultures are similar. 5-Azacytidine treatment can induce susceptibility to DHBV infection in resistant primary Pekin hepatocytes but appears to have no similar effect in Muscovy cultures. The relatively inefficient infection of Muscovy duck hepatocytes that we have described may account for the absence of a detectable viremia in Muscovy ducklings experimentally infected with DHBV.

Animals↗
PubMed1993

Computerised linking of medical records: methodological guidelines.

OBJECTIVES: To report on the development of computer assisted methods for linking medical records and record abstracts. DESIGN: The methods include file blocking, to put records in an order which makes searching efficient; matching, which is the process of comparing records to determine whether they do or do not relate to the same person; linkage, which is the process of assembling correctly matched records into a time sequenced composite record for the individual; and validation checks and corrections, in which any inconsistencies between different records for the same person are identified and corrected. SETTING: The dataset comprising the Oxford record linkage study which includes hospital inpatient records and vital records. RESULTS AND CONCLUSIONS: Probability matching, using an array of identifiers, achieves much higher levels of correct matching than is generally achievable by exact character by character comparisons. The increasing use of information technology to store data about health and health care means that there is increasing scope to link records for research and for patient care. Sophisticated methods to achieve this on a large scale are now available.

England↗
PubMed1992

Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas.

This report concerns the study of Ha-ras gene mutations and ras p21 expression in primary tumors of the urinary bladder. Polymerase chain reaction-based techniques and computerized image analysis were used. The data obtained were related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T) at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was greater in grade III (65%) than in grade II (44%) tumors; no mutations were observed in grade I tumors. The mutation was observed more often in aneuploid (58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen and no codon 61 mutation was detected. The tumors were also tested for the A-->G mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D mutations were identified in seven high-grade aneuploid tumors; six were invasive. The levels of the ras gene product p21 were approximately 10 times higher in tumors with intron D mutation than in those without. These findings confirm on human bladder tumors the observations of the effect of synchronous exon-intron mutations reported on the bladder cancer cell line T24. Our results are the first demonstration of Ha-ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas.

Adult↗
PubMed1992

Recording of deaths in hospital information systems: implications for audit and outcome studies.

STUDY OBJECTIVE: The aim was to report on the extent to which death certificates which specify that death occurred in hospital can be matched and linked with routine hospital inpatient information systems. DESIGN: The study involved linkage of hospital records which specified that death occurred in hospital to corresponding death certificates; and linkage of death certificates which specified that death occurred in hospital to corresponding hospital records. SETTING: Six health districts in southern England covered by medical record linkage. SUBJECTS: Records were examined of patients aged 65 years and over, which specified that death occurred in hospital between 1979 and 1985. MAIN RESULTS: 98.2% of hospital record abstracts which specified that death occurred in hospital were linked by our standard computer-based techniques to death certificates. Conversely, however, only 94.4% of death certificates which specified that death occurred in hospital could be linked to the abstracts of corresponding hospital inpatient records. A major factor contributing to the latter failures may be a difference of definition of what constitutes a death "following hospital admission" in patients who die shortly after arrival at hospital. CONCLUSIONS: Linkage of hospital records to death certificates is both feasible and desirable. Error rates are generally small; but hospital inpatient record abstracts corresponding to death certificates for deaths in hospital may not invariably exist when death occurs shortly after the arrival of the patient at hospital.

Death Certificates↗
PubMed1991

Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts.

Alendronate↗
PubMed1986

A newly identified hepatitis B type virus in tree squirrels.

Virus-associated particles have been isolated from the livers of three common gray tree squirrels (Sciurus carolinensis pennsylvanicus) that have histological evidence of hepatitis. Two of these livers were also positive by orcein staining, suggesting the presence of surface antigen in the cytoplasm of hepatocytes. Fractionation of these particles by CsCl density equilibrium gradient centrifugation and assay of the fractions for surface antigen, core antigen, and DNA polymerase activities demonstrate the presence of all three at an approximate density peak of 1.27. Electron microscopic examination of purified virus preparations showed spherical particles with a mean diameter of 25 nm. Initial characterization of the DNA polymerase product by gel electrophoresis showed a single DNase I sensitive band, migrating slightly faster than the woodchuck hepatitis virus DNA polymerase product. The presence of apparently cross-reacting antibodies was demonstrated by purified hepatitis B surface and/or core antigens binding to some squirrel sera in solid phase assays. Infected tree squirrels appear to lack detectable antigen in their sera. These results suggest that the tree squirrels studied are chronic carriers of a hepatitis B type virus. The host-virus interaction described herein may be useful in understanding the chronic carrier state associated with hepatitis B in man.

Animals↗