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Biomedical subjects

K Bailey

Publications and source records attributed to K Bailey.

At least 73 records · Page 4Linked to original sources

Purification and characterisation of a brain-derived neurotrophic factor/neurotrophin-3 (BDNF/NT-3) heterodimer.

The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are known to exist in solution as non-covalently linked homodimeric proteins. The recent elucidation of the crystal structure of the NGF homodimer, as well as the conservation of structural motifs in the neurotrophins, raised the possibility that neurotrophin heterodimers might also occur. The formation of BDNF/NT-3 heterodimers was explored using a vaccinia virus expression system. Upon co-infection of cells with viruses expressing BDNF and NT-3, we could identify a BDNF/NT-3 heterodimer as a biosynthetic product and separate it from the BDNF and NT-3 homodimers. We could also show that the BDNF/NT-3 heterodimers can be formed irrespective of wild-type or exchanged prosequences, indicating that prosequence specificity does not influence dimer formation. In all neuronal survival assays that were used, the BDNF/NT-3 heterodimer was shown to be 10-fold less active compared with a mixture of BDNF and NT-3 homodimers. This lower specific activity was also measured in a neuronal population co-expressing receptors for BDNF and NT-3. The low biological activity of the heterodimer observed with neurons was not paralleled by a reduced ability of the heterodimer to interact with trkB or trkC receptors, as assessed by the induction of tyrosine phosphorylation of these receptors expressed by fibroblast cell lines.

Amino Acid Sequence↗

Phylogeny of Drosophila and related genera inferred from the nucleotide sequence of the Cu,Zn Sod gene.

The phylogeny and taxonomy of the drosophilids have been the subject of extensive investigations. Recently, Grimaldi (1990) has challenged some common conceptions, and several sets of molecular data have provided information not always compatible with other taxonomic knowledge or consistent with each other. We present the coding nucleotide sequence of the Cu,Zn superoxide dismutase gene (Sod) for 15 species, which include the medfly Ceratitis capitata (family Tephritidae), the genera Chymomyza and Zaprionus, and representatives of the subgenera Dorsilopha, Drosophila, Hirtodrosophila, Scaptodrosophila, and Sophophora. Phylogenetic analysis of the Sod sequences indicates that Scaptodrosophila and Chymomyza branched off the main lineage before the major Drosophila radiations. The presence of a second intron in Chymomyza and Scaptodrosophila (as well as in the medfly) confirms the early divergence of these two taxa. This second intron became deleted from the main lineage before the major Drosophila radiations. According to the Sod sequences, Sophophora (including the melanogaster, obscura, saltans, and willistoni species groups) is older than the subgenus Drosophila; a deep branch splits the willistoni and saltans groups from the melanogaster and obscura groups. The genus Zaprionus and the subgenera Dorsilopha and Hirtodrosophila appear as branches of a prolific "bush" that also embraces the numerous species of the subgenus Drosophila. The Sod results corroborate in many, but not all, respects Throckmorton's (King, R.C. (ed) Handbook of Genetics. Plenum Press, New York, pp. 421-469, 1975) phylogeny; are inconsistent in some important ways with Grimaldi's (Bull. Am. Museum Nat. Hist. 197: 1-139, 1990) cladistic analysis; and also are inconsistent with some inferences based on mitochondrial DNA data. The Sod results manifest how, in addition to the information derived from nucleotide sequences, structural features (i.e., the deletion of an intron) can help resolve phylogenetic issues.

Animals↗

Evidence for positive selection in the superoxide dismutase (Sod) region of Drosophila melanogaster.

DNA sequence variation in a 1410-bp region including the Cu,Zn Sod locus was examined in 41 homozygous lines of Drosophila melanogaster. Fourteen lines were from Barcelona, Spain, 25 were from California populations and the other two were from laboratory stocks. Two common electromorphs, SODS and SODF, are segregating in the populations. Our sample of 41 lines included 19 SodS and 22 SodF alleles (henceforward referred to as Slow and Fast alleles). All 19 Slow alleles were identical in sequence. Of the 22 Fast alleles sequenced, nine were identical in sequence and are referred to as the Fast A haplotypes. The Slow allele sequence differed from the Fast A haplotype at a single nucleotide site, the site that accounts for the amino acid difference between SODS and SODF. There were nine other haplotypes among the remaining 13 Fast alleles sequenced. The overall level of nucleotide diversity (pi) in this sample is not greatly different than that found at other loci in D. melanogaster. It is concluded that the Slow/Fast polymorphism is a recently arisen polymorphism, not an old balanced polymorphism. The large group of nearly identical haplotypes suggests that a recent mutation, at the Sod locus or tightly linked to it, has increased rapidly in frequency to around 50%, both in California and Spain. The application of a new statistical test demonstrates that the occurrence of such large numbers of haplotypes with so little variation among them is very unlikely under the usual equilibrium neutral model. We suggest that the high frequency of some haplotypes is due to natural selection at the Sod locus or at a tightly linked locus.

Animals↗

Expression of the BDNF gene in the developing visual system of the chick.

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.

Animals↗

Less lice in Bolton.

Public concern when routine head inspections by school nurses were discontinued in Bolton's schools prompted the launch of a 'Less lice' campaign. Janet Dare and Kathleen Bailey describe how the campaign aims to reduce incidence of infection by making the public and professionals aware that head lice can affect anyone and are not primarily a schools problem.

Child↗

Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death.

OBJECTIVE: To determine the effects of female gender on long-term survival and subsequent coronary heart disease events in a population developing first clinical manifestations of coronary artery disease. DESIGN: Follow-up of all Rochester, Minn, residents first diagnosed with either angina pectoris or myocardial infarction/sudden unexpected death between January 1, 1960, and December 31, 1979. MAIN OUTCOME MEASURES: Patients with angina pectoris were followed up through 1982 for survival and time to initial myocardial infarction/cardiac death. Patients with myocardial infarction were followed up through 1982 for survival and time to recurrent myocardial infarction/cardiac death. RESULTS: Angina pectoris was the initial diagnosis for 529 women and 504 men. Myocardial infarction or sudden unexpected death was the initial diagnosis for 611 women and 997 men. The average age of patients diagnosed with angina pectoris was 67.0 years (SE, 0.5 years) for women and 60.0 years (SE, 0.5 years) for men. The average age of patients diagnosed with myocardial infarction/sudden unexpected death was 71.9 years (SE, 0.5 years) for women and 62.0 years (SE, 0.4 years) for men. Women presenting with angina pectoris survived significantly longer and had a lower incidence of subsequent myocardial infarction/cardiac death compared with men of similar age (P < .01). When rates of myocardial infarction and sudden unexpected death were combined to assess all cardiac endpoints with objective criteria ("hard" endpoints), women presenting with myocardial infarction/sudden unexpected death had survival rates and risk of subsequent myocardial infarction/coronary death that were similar to men of the same age. When survival following myocardial infarction was analyzed separately, survival also did not vary by gender. CONCLUSION: In this population, women with angina pectoris as an initial diagnosis, but not those with myocardial infarction or sudden unexpected death, have longer survival and lower risk of subsequent myocardial infarction/cardiac death than do men with the same presentation and of a similar age.

Adult↗

Are patients with neoplasia at an increased risk for cardiac myxomas?

A case-control study was undertaken to assess whether a significant association exists between the presence of a neoplasm or malignancy and the presence of a cardiac myxoma. We identified 13 patients seen at our institution between 1935 and 1990 whose autopsies revealed a cardiac myxoma that was undetected during the patient's lifetime. For each patient four control subjects were selected among the autopsied patients who had never had a cardiac myxoma; these were matched for age at death, gender, and year of autopsy. The institutional medical records and autopsy reports revealed that 46% of the patients and 65% of their controls had a neoplasm diagnosed prior to or at autopsy. The estimated odds ratio was 0.34 (95% confidence interval, 0.05 to 1.84). There was insufficient evidence to conclude that an association exists between the presence of a neoplasm and the presence of a cardiac myxoma (P = .2722).

Adult↗

Transport regulation of recombinant gene expression in E. coli and B. subtilis.

Expression kinetics of the lactose (lac) operon in Escherichia coli are reviewed for both wild-type and recombinant cell cultures under chemostatic conditions. A unified model which involves regulation of active inducer (lactose) transport, promoter-operator regulated expression of the lac operon, glucose-mediated inducer exclusion, and catabolite repression is summarized and supporting data is shown to verify its accuracy. The synthesis of alpha-amylase with a recombinant form of Bacillus subtilis is also reviewed to point out generic features in transport regulation, the lac operon model providing a point of departure. While there are many similarities in the influence of transport on both regulating models, there are also important differences. In a chemostat system, the synthesis of alpha-amylase is nongrowth associated, while beta-galactosidase is a growth-associated enzyme. Nevertheless, transport regulation is an important feature in both instances.

Journal Article↗

Fetal haemoglobin and early manifestations of homozygous sickle cell disease.

The relevance of fetal haemoglobin (HbF) concentration to the development of early clinical manifestations of homozygous sickle (SS) disease has been investigated by examining the time to first occurrence and the proportional hazard of these complications in three groups of the HbF distribution at age 5 years. HbF was significantly related to dactylitis, painful crises, acute chest syndrome, and acute splenic sequestration. The relationship suggested that a critically low HbF concentration increased the risk, little difference in risk occurring between the medium and high HbF groups. The abdominal painful crisis and hypersplenism were not related to HbF concentration suggesting that the degree of sickling may not be important in their genesis. Parental education on acute splenic sequestration should be focused on children with HbF concentrations in the lowest part of the HbF distribution for age.

Adolescent↗

Emboli in infective endocarditis: the prognostic value of echocardiography.

OBJECTIVE: To determine whether vegetations visualized on two-dimensional echocardiography are an independent risk factor for the development of subsequent emboli in patients with infective endocarditis and to assess the timing of emboli relative to the initiation of antimicrobial therapy. DESIGN: Investigator-blinded, retrospective incidence cohort study. SETTING: Tertiary referral center. PATIENTS: Patients with left-sided native valve infective endocarditis who had two-dimensional echocardiography within 72 hours of beginning antimicrobial therapy. MEASUREMENTS AND MAIN RESULTS: The crude incidence rate of first embolic events in patients receiving antimicrobial therapy was 6.2 per 1000 patient-days (95% CI, 4.2 to 9.2). The rates in patients with and without vegetations were 7.1 and 4.9 per 1000 patient-days, respectively (incidence rate ratio, 1.4; 95% CI, 0.6 to 3.3). The relation between vegetations and risk for emboli was microorganism-dependent: Stratified incidence rate ratios were 6.9 (95% CI, 1.1 to 42.5; P less than 0.05) and 1.0 (95% CI, 0.2 to 3.9) for viridans streptococcal and Staphylococcus aureus endocarditis, respectively. The rate of first embolic events diminished over time (P less than 0.001), falling from 13 per 1000 patient-days during the first week of therapy to less than 1.2 per 1000 patient-days after completion of the second week of therapy. CONCLUSIONS: Overall, the presence of vegetations on echocardiography was not associated with a significantly higher risk for embolus in patients with left-sided native valve infective endocarditis. The relative risk for embolic events associated with echocardiographically visualized vegetations may be microorganism-dependent, with a significantly increased risk seen only in patients with viridans streptococcal infection. The rate of embolic events declines with time after initiation of antimicrobial treatment.

Adolescent↗

The structure of expert diagnostic knowledge in occupational medicine.

Development of an artificial intelligence expert system for diagnosing occupational lung disease requires explicit specification of the structure of knowledge necessary in clinical occupational medicine independent of the process by which the knowledge is utilized. Furthermore, explicit recognition of sources of uncertainty is necessary. Seven categories of knowledge define the diagnostic knowledge base in occupational pulmonary medicine. These include four objects (jobs, industries, exposures, and diseases) and three relationships between pairs of objects. This analysis demonstrates some of the unique aspects of occupational medicine expertise.

Algorithms↗

Trauma internship: a success story.

Internships, valuable mechanisms that bridge the gap between academic preparation and initial clinical experience, are attractive to new graduates who have had limited exposure to different aspects of nursing and want a chance to learn more about a particular specialty. Upon completion of an internship, nurses have a broader knowledge base than those who have had an indepth orientation to just one nursing unit. This article describes the development and implementation of a trauma internship in a 570-bed tertiary care, level I trauma center. Program components and evaluation are presented.

Curriculum↗

Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family.

The survival and functional maintenance of vertebrate neurons critically depends on the availability of specific neurotrophic factors. So far, only two such factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been characterized and shown to have the typical features of secretory proteins. This characterization has been possible because of the extraordinarily large quantities of NGF in some adult tissues, and the virtually unlimited availability of brain tissue from which BDNF was isolated. Both NGF and BDNF promote the survival of distinct neuronal populations in vivo and are related in their primary structure, suggesting that they are members of a gene family. Although there is little doubt about the existence of other such proteins, their low abundance has rendered their identification and characterization difficult. Taking advantage of sequence identities between NGF and BDNF, we have now identified a third member of this family, which we name neurotrophin-3. Both the tissue distribution of the messenger RNA and the neuronal specificity of this secretory protein differ from those of NGF and BDNF. Alignment of the sequences of the three proteins reveals a remarkable number of amino acid identities, including all cysteine residues. This alignment also delineates four variable domains, each of 7-11 amino acids, indicating structural elements presumably involved in the neuronal specificity of these proteins.

Amino Acid Sequence↗