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Biomedical subjects

J S Chapman

Publications and source records attributed to J S Chapman.

At least 19 recordsLinked to original sources

An unhydrolyzable analogue of N-(4-hydroxyphenyl)retinamide. synthesis and preliminary biological studies.

The synthesis of a nonhydrolyzable, carbon-linked analogue (4-HBR) of the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) using Umpolung methods is described. Preliminary studies of biological activity show 4-HBR is similar to 4-HPR in its actions although a potentially relevant and desirable difference is its reduced suppression of plasma vitamin A levels. These results show that 4-HPR does not have to be hydrolyzed to retinoic acid to produce its chemotherapeutic effects.

Animals↗

Nurses' experience with implementing developmental care in NICUs.

The aim of this study was to gain insight into nurses' (N = 8) experience of working in a neonatal intensive-care unit (NICU) that incorporated the developmental-care approach. Although Als's model is family centered, the basic social process identified by nurses was putting the baby first. The process of putting the baby first was uncovered using grounded-theory methodology. The process included three phases: learning, reacting, and advocating/nonadvocating. In each of the phases, four main concepts--encountering, appraising, supporting, and gaining sensitivity--emerged from the data. Nurses appraised the advantages and disadvantages of this therapeutic approach not only to the infant but also to themselves.

Child Development↗

Holding on: parents' perceptions of premature infants' transfers.

OBJECTIVE: To describe parents' perceptions of their infants' transfers within a regional system of perinatal care. DESIGN: Qualitative; grounded theory methodology. SETTING: Interviews were conducted in an office adjacent to a neonatal intensive care unit (NICU), in an intermediate care unit (IMCU), and in the homes of parents. PARTICIPANTS: Fifteen parents of premature infants were recruited and interviewed during the 3 days before their infants were transferred from a NICU to an IMCU or home. The 15 parents were interviewed again during the 5 days after the initial interview to learn their feelings about the transfer. DATA COLLECTION: After consent was obtained, unstructured interviews were recorded and transcribed. Analyses of the data were ongoing, and the second interviews with parents were more focused. RESULTS: Parents identified four phases that described their transfer experience. Within the four phases, four categories were identified to depict parents experiences further. The core category of holding on reflected the belief that transfer home would become a reality and normal family life eventually would ensue. CONCLUSIONS: Nurses in NICUs and IMCUs have a responsibility to educate the parents of infants at high risk. Nurses sensitive to parental perceptions of neonatal transfer can better facilitate a positive transfer experience.

Adaptation, Psychological↗

Methylchloroisothiazolone-induced growth inhibition and lethality in Escherichia coli.

Exposure of log phase Escherichia coli cells to inhibitory levels of 5-chloro-2-methyl-isothiazolin-3-one (MCI) results in rapid bacteriostasis and a delayed onset of bactericidal activity. Inhibition of respiration occurs within the same time frame as bacteriostasis, and is followed by a decline in intracellular ATP levels. In vitro and in vivo experiments suggest that growth inhibition is the result of selective inhibition of particular targets, with succinate dehydrogenase being identified as a possible target. Such selectivity was not anticipated from this highly reactive molecule. MCI-induced lethality is positively correlated with a loss of reduced protein sulphydryls (r2 = 0.79). A greater than equimolar loss of reduced protein sulphydryls, compared with the number of MCI molecules added, and a reduction in killing by MCI after induction of the OxyR regulon suggest that free radical generation may have a role in the antibacterial activity of MCI. We present an examination of the in vivo effects of MCI exposure on bacterial cells, and evidence that the isothiazolones exhibit selectivity in their cellular targets and antimicrobial effects.

Adenosine Triphosphate↗

Low-level resistance to the cephalosporin 3'-quinolone ester Ro 23-9424 in Escherichia coli.

Four spontaneous, single-step mutants of Escherichia coli K-12 resistant to low levels of the cephalosporin 3'-quinolone ester Ro 23-9424 were isolated at a frequency of 10(-10) to 10(-11) mutants per CFU plated. The mutants were cross-resistant to both cephalosporin (cefotaxime) and quinolone (fleroxacin) components. Accordingly, they had altered porins and replicative DNA biosynthesis resistant to fleroxacin. There was no increase in beta-lactamase activity when tested with nitrocephin, and the penicillin-binding protein profiles were normal.

Anti-Infective Agents↗

Supporting: men's experiences with the event of their partners' miscarriage.

The purpose of this study was to investigate men's experiences with the event of their partner's miscarriage. Grounded theory methodology was employed to gather data from eight men whose partners had experienced a total of 10 miscarriages. Data were collected through informal, unstructured interviews. Four sequential phases emerged from the data: (a) recognizing sign(s), (b)confirming the news, (c) working through it, and (d) getting on with life. Supporting was the basic social process that emerged, and four major concepts arose: (a) living the feelings, (b) waiting, (c) seeking help, and (d) accepting. The implications for practice are examined and recommendations for future research are presented.

Abortion, Spontaneous↗

Hemodynamic responses and activity tolerance to stair climbing during the second week post-myocardial infarction.

The purpose of this study was to evaluate the hemodynamic responses and activity tolerance to stair climbing of second week post-myocardial infarction (MI) patients. Forty MI patients were stratified into beta-blocker medication users and non-users and randomly assigned to the experimental or control conditions. The 21 experimental subjects performed a walk/stair climb, and the 19 control subjects, a walk/stand activity protocol. Changes in heart rate and blood pressure from before, to immediately after both the walk/stair and walk/stand activity protocols were clinically small. No significant differences existed in the distribution of hemodynamic signs among the experimental and control subjects. However, proportionately more experimental than control subjects had symptoms of activity intolerance (7/21 vs 1/19; p less than 0.05). No correlation existed between activity (in) tolerance and either days post-MI or time required for stair climbing. Based upon these preliminary findings, assessment of tolerance to stair climbing activities is warranted during the second week post-MI.

Activities of Daily Living↗

Holding death at bay: the experience of the spouses of patients undergoing cardiovascular surgery.

This study utilized a grounded theory design to investigate the experiences related to being the spouse of a cardiovascular surgical patient during five subject-identified phases: a) finding out the surgery was necessary, b) waiting for surgery, c) waiting during surgery, d) the intensive care unit (ICU) experience, and e) the recovery period before hospital discharge. Data were collected from each of eight subjects via three unstructured, tape-recorded interviews conducted a) on the day of the patients' hospital admission, b) during the first 48 hours of the patients' ICU stay and c) just before the patients' hospital discharge. Holding Death at Bay was identified as the core category. Three main categories: uncertainty, helping commitment and reorganization emerged from the data and were apparent in each of the five subject-identified phases of the spouses' experience. Main categories and subcategories of the core category emerging from the data are described. Implications of this research for nursing practice and further nursing research are discussed.

Adaptation, Psychological↗

Fluorometric assay for fleroxacin uptake by bacterial cells.

A sensitive and convenient method for quinolone determination has been developed, based on the natural fluorescence of the quinolone nucleus. Fleroxacin (Ro 23-6240; AM 833), used as a prototype quinolone in these studies, had an excitation maximum at 282 nm and an admission maximum at 442 nm (pH 3.0). Fluorescence intensity was pH dependent, being maximal at pH 3.0 and linear at quinolone concentrations between 1 and 200 ng/ml. A protocol for the fluorometric monitoring of fleroxacin uptake in Escherichia coli was developed. Intracellular quinolone concentrations measured by the fluorometric assay correlated well with values obtained by the bioassay. The results indicate that the fluorometric assay is an attractive alternative to the more laborious bioassay.

Ciprofloxacin↗

Fleroxacin resistance in Escherichia coli.

Spontaneous fleroxacin-resistant mutants of Escherichia coli K-12 were isolated at a frequency of 10(-10) to 10(-11) mutants per CFU plated. All mutants exhibited quinolone-resistant replicative DNA biosynthesis, and 4 of 11 mutants also had decreased amounts of OmpF or OmpC porin. None of the mutants had changes solely in porin proteins.

Anti-Bacterial Agents↗

Mode of action of the dual-action cephalosporin Ro 23-9424.

Ro 23-9424 is a broad-spectrum antibacterial agent composed of a cephalosporin and a quinolone moiety. Its biological properties were compared with those of its two components and structurally related cephalosporins and quinolones. Like ceftriaxone and cefotaxime but unlike its decomposition product, desacetyl cefotaxime, Ro 23-9424 bound at less than or equal to 2 micrograms/ml to the essential penicillin-binding proteins 1b and 3 of Escherichia coli and 1, 2, and 3 of Staphylococcus aureus. In E. coli, Ro 23-9424 produced filaments exclusively and decreased cell growth; cefotaxime produced both filaments and lysis. Like its decomposition product fleroxacin but unlike quinolone esters, Ro 23-9424 also inhibited replicative DNA biosynthesis in E. coli. In an E. coli strain lacking OmpF, growth continued after addition of Ro 23-9424, decreased after addition of cefotaxime, and stopped immediately after addition of fleroxacin. The results, together with the chemical stability of Ro 23-9424 (half-life, approximately 3 h at pH 7.4 and 37 degrees C), suggest that in E. coli the compound acts initially as a cephalosporin with intrinsic activity comparable to that of cefotaxime but with poorer penetration. Subsequent to the decomposition of Ro 23-9424 to fleroxacin and desacetyl cefotaxime, quinolone activity appears. The in vitro antibacterial activity reflects both mechanisms of action.

Anti-Infective Agents↗

Routes of quinolone permeation in Escherichia coli.

The uptake of quinolone antibiotics by Escherichia coli was investigated by using fleroxacin (RO 23-6240, AM 833) as a prototype compound. The uptake of fleroxacin was reduced and its MIC was increased in the presence of magnesium. Quinolones induced lipopolysaccharide release, increased cell-surface hydrophobicity and outer membrane permeability to B-lactams, and sensitized cells to lysis by detergents. These effects were also antagonized by magnesium and were very similar to those seen with EDTA and gentamicin. MICs of quinolones in portin-deficient strains were increased relative to those of the parent strain, consistent with a porin pathway of entry. However, MICs were further increased in the presence of magnesium; the size of the additional increase showed a positive correlation with quinolone hydrophobicity in an OmpF- OmpC- OmpA- strain. When quinolones were mixed with divalent cations in solution, changes in quinolone fluorescence suggestive of metal chelation were observed. The addition of fleroxacin to a cell suspension resulted in a rapid initial association of fluorescence with cells, followed by a brief decrease and a final time-dependent linear increase in cell-associated fluorescence. We interpret these results as representing chelation of outer membrane-bound magnesium by fleroxacin and other quinolones, dissociation of the quinolone-magnesium complex from the outer membrane, and diffusion of the quinolone through both porins and exposed lipid domains on the outer membrane. For a given quinolone, the contribution of the porin and nonporin pathways to total uptake is influenced by the hydrophobicity of the quinolone.

Aminoglycosides↗

Outer membrane penetration by (2,3)-methylenepenams.

The penetration of the Escherichia coli outer membrane by two sterically restricted analogs of penicillin G was determined. The analog corresponding to the "open" conformation of penicillin G penetrated faster than the "closed"-form analog did, and both analogs penetrated faster than penicillin G did. The results suggest that the conformation of the beta-lactam nucleus may affect penetrability via the porin-mediated pathway.

Anti-Bacterial Agents↗

Preliminary indication of unusual codon usage in the DNA coding sequence of the attachment protein of Mycoplasma pneumoniae.

From a Mycoplasma pneumoniae genomic library, three recombinant clones encoding approximately one-third of the attachment (P1) gene were identified. P1 fusion proteins expressed by these clones in Escherichia coli were found to be much smaller than expected from the sizes of the cloned DNA fragments. Nucleotide sequence analysis revealed the presence of UGA codons in the open reading frames of two of the clones, explaining the incomplete translation of the inserts. Sequencing data further revealed that two of the recombinant clones did have similar but not identical carboxyl-end sequences. This finding suggests the existence of more than one genomic DNA sequence coding for the 3'-end of the P1 gene. Potential transcriptional regulatory sequences, a possible termination signal at the 3'-end of the P1 gene and possible promoter-like structures, have been recognized.

Amino Acid Sequence↗

Dust exposure, dust recovered from the lung, and associated pathology in a group of British coalminers.

The relation between dust exposure, retained lung dust, and pneumoconiosis have been examined in 430 dead coalminers who had participated in a large scale epidemiological survey of respiratory health. The men were divided into three groups depending on the presence of particular lesions in their lungs. Lungs containing no fibrotic lesions in excess of 1 mm were included in the "M" group, those with fibrotic lesions of between 1 mm and 9 mm in diameter were included in the "F" group, and those with any lesion 10 mm or more were categorised as having progressive massive fibrosis (PMF). The men were further divided into four groups according to the rank of coal mined at the colliery of employment. The mean weight of lung dust increased over the pathological range (M----F----PMF) regardless of the rank of coal mined. The men with PMF had not received unusually high exposures to dust in life but were found to have accumulated more dust in their lungs per unit of dust exposure than men without PMF, providing further evidence for differences in the patterns of deposition or clearance, or both, of dust in these men compared with those who do not develop PMF. For men who had mined the higher rank coals there was no difference in the composition of the lung dust between the pathological groups. Lungs from men mining low rank coal, however, showed a striking increase in the proportion of ash over the pathological groups (M, F, and PMF). In men who had mined low rank coal the proportion of ash in the airborne dust to which they had been exposed and in the dust retained in their lungs was, as expected, greater than in men who had worked with higher rank coals. For the same men, and particularly associated with the presence of some dust related fibrosis, the proportion of ash in retained dust was higher than that in the dust to which the men were exposed suggesting the occurrence of selective deposition or retention of the mineral components of dust in this group.

Aged↗