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Biomedical subjects

C Dykes

Publications and source records attributed to C Dykes.

5 recordsLinked to original sources

Analysis of env sequence evolution in human immunodeficiency virus-infected patients receiving therapy with nonnucleoside reverse-transcriptase inhibitors.

Nonnucleoside reverse-transcriptase inhibitors (NNRTIs) can rapidly select for drug-resistant human immunodeficiency virus type 1 (HIV-1) variants, although their effect on HIV-1 quasi-species diversity is unknown. To determine if changes in env gene diversification occur with NNRTI therapy, we used the heteroduplex tracking assay (HTA) to study HIV-1 env sequence diversity in 2 groups of patients: those who were on no therapy or were on chronic antiretroviral therapy and those who had just initiated NNRTIs. Forty-nine paired samples from 46 patients were analyzed. Fourteen of 32 paired samples from the NNRTI group and 9 of 17 paired samples from the control group had HTA changes (P>.10). There was no correlation between HTA change and sampling time interval, baseline virus load, change in virus load, or development of NNRTI resistance. Thus, we found no significant correlation of NNRTI therapy with changes in env HTA patterns, suggesting that these treatments had little short-term impact on HIV-1 quasi-species diversity.

Drug Resistance, Microbial↗

Stringent structural and sequence requirements of the human herpesvirus 6B lytic-phase origin of DNA replication.

The lytic-phase origin of DNA replication from human herpesvirus 6B (HHV-6B oriLyt) contains two binding sites for the origin-binding protein (OBPH6B), both of which are required for DNA replication and which are separated by an AT-rich spacer. We have tested the functional significance of the structural, spatial and sequence characteristics of this spacer element by constructing a series of mutated origin sequences and analysing their replication efficiency. Changes in the sequence composition of length of the spacer resulted in dramatic decreases in replication efficiency. Furthermore, in contrast to what has been observed for herpes simplex virus type 1 (HSV-1) oriS, insertion of a complete helical turn of DNA into the spacer also resulted in abrogation of origin function. These data suggest that the arrangement of OBP sites in HHV-6B oriLyt is stringently constrained in terms of spacing and intervening sequence.

Base Sequence↗

Identification and analysis of a lytic-phase origin of DNA replication in human herpesvirus 7.

Human herpesvirus 7 (HHV-7) DNA sequences colinear with the HHV-6 lytic-phase origin of DNA replication (oriLyt) were amplified by PCR. Plasmid constructs containing these sequences were replicated in HHV-7-infected cord blood mononuclear cells but not in HHV-6-infected cells. In contrast, plasmids bearing HHV-6 oriLyt were replicated in both HHV-6- and HHV-7-infected cells. Finally, the minimal HHV-7 DNA element necessary for replicator activity was mapped to a 600-bp region which contains two sites with high homology to the consensus binding site for the HHV-6 origin binding protein. At least one of these binding sites was shown to be essential for replicator function of HHV-7 oriLyt.

Base Sequence↗

Human herpesvirus 6B origin: sequence diversity, requirement for two binding sites for origin-binding protein, and enhanced replication from origin multimers.

A previously identified human herpesvirus 6B (HHV-6B) origin of DNA replication contains two binding sites for the origin-binding protein (OBPH6B). We have investigated the functional significance of these sites by determining the replication efficiencies of mutated origin sequences, using a transient replication assay. The results indicate that both sites are required for DNA replication. In addition, we have tested the functional consequences of linear sequence amplifications in the origin. The data show that tandemized origin elements are more efficiently replicated than single-copy origins. Finally, we have determined the extent of interstrain origin sequence variation that exists among HHV-6 isolates by cloning, sequencing, and analyzing origins from a number of virus isolates, including examples of both HHV-6A and HHV-6B.

Base Sequence↗

Practical computer applications for endoscopy.

A computer can facilitate a nurse's administrative tasks, resulting in increased time to spend with patients. Data can easily be organized and retrieved. Forms can be created when there is no ready-made form at hand. Document revision is easy and cost-effective because the form is not typeset until it has been tried and is ready for permanent adoption. The outcome will be a nursing practice that is more efficient, effective, and professionally rewarding.

Database Management Systems↗