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Biomedical subjects

R Cook

Publications and source records attributed to R Cook.

At least 55 records · Page 3Linked to original sources
PubMed1998

A preliminary study of parental stress and child behaviour in families with twins conceived by in-vitro fertilization.

This paper reports on a preliminary study of parenting quality, parental stress and child behaviour in families with twins conceived by in-vitro fertilization (IVF) in comparison with families with naturally conceived twins. No differences were found between the types of family in parenting quality or child behaviour. However, parents whose children were conceived by IVF reported greater stress associated with parenting than parents with naturally conceived twins.

Child Behavior↗
PubMed1998

Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon.

In order to investigate if immune responses to the fusion (F) protein of respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant vaccinia viruses (rVV) carrying both the F gene of RSV and the gene for murine interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-gamma) were constructed. In vitro characterization of rVV revealed that insertion of the cytokine gene into the VP37 locus of the vaccinia virus genome resulted in 100- to 1,000-fold higher expression than insertion of the same gene into the thymidine kinase (TK) locus. In comparison, only a two- to fivefold difference in the level of expression of the F protein was observed when the gene was inserted into either of these two loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-gamma cleared rVV more rapidly than mice inoculated with a control rVV and developed only low levels of RSV-specific serum antibody. In addition, these recombinants were much less effective at priming RSV-specific memory cytotoxic T lymphocytes (CTL) and IFN-gamma production by spleen cells than rVV expressing the F protein alone. In contrast, mice vaccinated with rVV expressing high levels of IL-4 showed signs of delayed rVV clearance. RSV-specific serum antibody responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as there was a significant reduction in IgG2a antibody responses compared with serum antibody responses in mice vaccinated with rVV expressing the F protein alone. However, vaccination with rVV expressing the F protein together with high levels of IL-4 did not alter the development of RSV-specific memory CTL or IFN-gamma production by RSV-restimulated splenocytes.

Animals↗
PubMed1998

A 1-year community-based health economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.

OBJECTIVE: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period. DESIGN: Randomized, multicenter, parallel-group, open-label study. SETTING: Outpatient general practice. PATIENTS: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence). MAIN OUTCOME MEASURES: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group. RESULTS: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario). CONCLUSIONS: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

Adolescent↗
PubMed1998

Running a seminar.

A seminar may be less complicated to arrange than a study day but there are still things that can go wrong. Rosemary Cook outlines what is essential to a successful presentation.

Audiovisual Aids↗
PubMed1997

Influenza vaccination.

The availability of influenza vaccines brings relief to high-risk categories. For trained and competent nurses this means carrying out an audit of high-risk people and ordering sufficient doses in the spring and summer, and then administering vaccines to this group in the autumn.

Humans↗
PubMed1997

Monomeric isomers of human interleukin 5 show that 1:1 receptor recruitment is sufficient for function.

The normally dimeric human interleukin 5 (IL-5) was re-engineered into two monomeric isomer forms to investigate mechanistic features of receptor recognition. One form, denoted GM1-IL-5, is a CD-loop expanded form, in which an 8-residue linker designed for flexibility was inserted between residues 85 and 86. The second, denoted DABC-IL-5, is a circularly permuted form of human IL-5 in which a chain discontinuity was introduced in the CD loop and the two consequent chain fragments were joined at the normal N and C termini by a di-glycyl linker. Both IL-5 isomers folded into stable monomers in solution as shown by sedimentation equilibrium and CD and formed an intrachain disulfide bond predicted from the structure of wild type IL-5. From titration microcalorimetry and optical biosensor analyses, both monomers were shown to interact with the IL-5 receptor alpha chain with 1:1 stoichiometry and affinities 30- to 40-fold weaker than for the dimeric wild type protein. And both monomers stimulated cell proliferation of human IL-5 receptor positive cells with a concentration dependence close to that of wild type. The data show that both monomeric and dimeric forms of IL-5 function through similar 1:1 receptor alpha chain recruitment processes and that it is the helical packing of the monomeric four-helix bundle unit in IL-5, rather than the helical connectivity itself, that appears to play the major role in presenting structural epitopes to trigger functional receptor activation.

Binding Sites↗
PubMed1997

Broadcast.

Explore the source record for details and available documents.

Humans↗
PubMed1997

The significance of fibres found in head hair.

The incidence of four common fibres in the head hair of 100 individuals has been established. A total of 37 matching fibres were found in the hair of 22 people with a maximum of five fibres on any one head. Two subjects had fibres matching two sources in their hair.

Animals↗
PubMed1997

Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2.

NGG1p/ADA3p and ADA2p are dual function regulators that stimulate or inhibit a set of yeast transcriptional activator proteins. In vitro, NGG1p and ADA2p associate in a complex that also contains GCN5p (Horiuchi, J., Silverman, N., Marcus, G. A., and Guarente, L. (1995) Mol. Cell. Biol. 15, 1203-1209). We have found that NGG1p and ADA2p are coimmunoprecipitated from yeast whole cell extracts. In fact, <2% of cellular ADA2p was not associated with NGG1p. Also in agreement with their association in vivo, the stability of ADA2p and NGG1p depended on the presence of each other. In addition, three NGG1p- and ADA2p-containing peak fractions were resolved by Q-Sepharose Fast Flow ion-exchange chromatography of whole cell extract. The presence of another high molecular mass complex was supported by the separation of one of the NGG1p- and ADA2p-containing peak fractions by gel-filtration chromatography. Together, the combination of ion-exchange and gel-filtration chromatography suggests a total of four complexes, two with sizes of >2 MDa and single complexes of approximately 900 and 200 kDa. At least one of these complexes was found to associate with the TATA-binding protein (TBP) since TBP was present in immunoprecipitates with NGG1p. The association of TBP with the ADA proteins required amino acids 274-307 of NGG1p, a region of NGG1p required for activity. This supports a role for NGG1p in the interaction with TBP and suggests that the interaction with TBP is functionally relevant.

Blotting, Western↗
PubMed1997

Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics.

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.

Anaerobiosis↗
PubMed1997

The European study of assisted reproduction families: a comparison of family functioning and child development between Eastern and Western Europe.

Developments in reproductive technology over the past 20 years have given infertile couples new opportunities to have children. Although assisted reproduction does not appear to lead to negative consequences with respect to parent-child relationships or the socioemotional development of the child, the outcome for children and their parents may well differ according to the social and cultural environment. The aim of the present study was to compare family functioning and the social and emotional development of children in families created as a result of assisted reproductive techniques in Western Europe with assisted reproduction families in an Eastern European country (Bulgaria) where there is a history of specific pronatalist interventions. The findings indicate greater difficulties in parental adjustment and child behavior in assisted conception families in Eastern Europe. In addition, Eastern European parents were more uncertain than Western European parents about whether they would tell the child, and Eastern European parents were much more secretive with respect to telling others. Thus the outcomes of assisted reproduction for family functioning and child development appear to be independent, to some extent at least, on the social context in which these techniques are carried out.

Adaptation, Psychological↗
PubMed1996

Mutants of single chain interleukin 5 show asymmetric recruitment of receptor alpha and betac subunits.

Dual asymmetric mutagenesis of single-chain interleukin 5 (scIL5) was used to obtain evidence that the normally homodimeric IL5 molecule, which contains two 4-helix bundle domains arranged symmetrically about a 2-fold axis, can recruit receptor alpha and betac subunits asymmetrically. Functionally active scIL5 was constructed using recombinant DNA methods by linking two IL5 monomers with a Gly-Gly linker. Mutants were constructed at residues Arg91, Glu110, and Trp111, previously shown to be involved in IL5 receptor alpha chain binding, and at residue Glu13, known to be involved in signal transduction presumably through interaction with the receptor betac chain. Mutants were examined for receptor alpha chain binding by an optical biosensor assay and for bioactivity using a cell proliferation assay. Substitution of the two binding site residues R91 and W111 in the same 4-helix bundle domain caused a 5-fold greater reduction in receptor binding affinity than when the two substitutions were distributed one in each domain. Substitution of E13 and R91 either in the same or in opposite domains gave comparable IL5Ralpha chain binding kinetics, essentially unchanged from those of scIL5. However, in contrast to the binding affinity pattern observed with R91A/W111A dual mutants, distributing the E13A/R91A mutations between the two 4-helix bundle domains caused a 5-6-fold greater loss of bioactivity than when the two changes were in the same domain, leaving the other domain unaltered. Taken with previous mutagenesis data, these results are consistent with a single shared-site model of IL5-IL5Ralpha chain recognition in which a single alpha chain can orientate in either of two modes, each one of which is stabilized preferentially by one of the two 4-helix bundles of IL5. Furthermore, the results suggest that a single betac molecule is activated for each IL5, through the Glu13 residue on the same helix bundle domain that dominates the IL5Ralpha interaction.

Animals↗