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Biomedical subjects

C A Evans

Publications and source records attributed to C A Evans.

At least 19 recordsLinked to original sources

Cellular signalling events stimulated by myeloid haemopoietic growth factors.

In haemopoietic cells, proliferation, commitment to development, lineage restriction and survival via suppression of apoptosis can all be controlled by haemopoietic growth factors. The mechanisms underlying the regulation of these events can now be studied since recombinant forms of most of these haemopoietic growth factors are now available. Recent advances in cell purification techniques and the development of multipotent cell lines (see Spangrude et al, 1988; Whetton, 1990; Heyworth et al, 1988, 1990a; Jones et al, 1990) have provided suitable cell populations on which to study the cellular signalling events associated with differentiation and lineage restriction. This process has started with the elucidation of the structure and expression of many of the myeloid growth factor receptors, which should now facilitate progress in the study of the signal transduction mechanisms these growth factors employ. Another important facet of these studies will be to determine whether a single growth factor with multiple target cell types, ranging from multipotent cells to postmitotic cells (e.g. neutrophils), employs distinct signalling mechanisms depending on the target cell in question. The cellular signalling events elicited by each of these growth factors and the ways in which they can regulate the transcriptional activation of genes associated with specific developmental events are going to be key areas of haemopoietic research in the next few years.

Adult

Induction of apoptosis--new targets for cancer chemotherapy.

Many anticancer agents induce an active cell death process, apoptosis, in sensitive tumour cells. Elucidation of molecular mechanisms underlying apoptosis may shed light on why some tumour cells survive chemotherapy, and may identify new targets for anticancer agents whose effects are not tightly linked to proliferative status. The signal transduction events which initiate apoptosis are unclear. A change in cytosolic calcium is generally assumed to be a key signal for apoptosis although the evidence for this is not conclusive. Other putative signal transducers which may modulate apoptosis are protein kinase C and cAMP. Genes which induce apoptosis in response to such signals are largely unidentified, but certain oncogenes, notably bcl-2, act to delay or suppress apoptosis in several cell types.

Apoptosis

Growth and development in orthodontics.

The recent literature on growth and development of the face and dentition includes important articles about assessment of growth, maturation, growth in the vertical dimension, treatment effects, experimental growth, and craniofacial anomalies. An underlying theme can be detected in these reports--the individuality of the child and his or her response to treatment. Central trends can be determined from growth data, but these generalizations should be applied with caution. When formulating treatment goals and planning mechanics, great variability can exist among growing children.

Adolescent

Gonadotropin, steroid, and inhibin levels in women with incipient ovarian failure during anovulatory and ovulatory rebound cycles.

We have identified a group of women with infertility and regular menses who have persistently raised FSH levels and probable incipient ovarian failure (IOF). Thirteen such women (19 cycles) had serum samples taken for RIA of LH, FSH, estradiol, and progesterone (P) 3 times a week over 1 menstrual cycle. Sixty infertile women with normal ovulatory cycles (as determined by hormones and ultrasound scan) served as controls. Overall, the FSH was higher (P less than 0.01) on all days of the cycle in the IOF group, serum LH was raised on days-14 to-5 before and days 5-11 after the LH surge. There was no difference between estradiol and P levels in the two groups. Ultrasound scanning showed failure of normal ovulation in the IOF group. Inhibin, measured by RIA in 9 cycles in the IOF group was lower (P less than 0.01) during the follicular phase than in 43 normal cycles. The highest inhibin level was seen in the luteal phase, as in normal cycles, but levels were still lower (P less than 0.01) in the IOF group. Inhibin was inversely correlated with FSH (P less than 0.05) during the follicular and luteal phases and was correlated with P during the luteal phase (P less than 0.05) in the IOF group. After 3 weeks of suppression (39 cycles) with an estrogen-progestogen preparation in the IOF group, LH and FSH fell to normal values. Ovulation occurred in 22 cycles on withdrawal of suppression in the presence of high FSH levels and low inhibin levels. No pregnancies occurred. These findings are consistent with the suggestion that diminished ovarian inhibin secretion may contribute to the elevated FSH levels of IOF and indicate that ovulation in the rebound cycle after suppression occurs in the presence of high FSH and low inhibin levels. Such cycles, however, still appear to be subfertile.

Adult

Psychosocial adjustment in children with hemifacial microsomia and other craniofacial deformities.

Psychosocial adjustment was evaluated in different groups of children with craniofacial deformities in order to examine the relationships between symmetry, functional impairments, and social adaptation. Thirty patients, ages 6 through 16 years, were assessed using a battery of standard psychologic measures including Human Figure Drawing, Tasks of Emotional Adjustment, and Children's Depression Inventory. Parents and teachers also provided ratings of the children's functioning using the Child Behavior Checklist (parent and teacher forms). Scores on the outcome measures were summarized with descriptive statistics and then multivariate analyses of variance were conducted to determine the differences in psychosocial development between children with symmetric versus asymmetric craniofacial deformities and between the presence or absence of a functional impairment in children with craniofacial deformities. The results indicate that children with symmetric craniofacial deformities score poorer on measures of psychosocial adjustment than children with asymmetric deformities (F = 3.20, p less than 0.015); however, differences among the groups with or without functional impairments were not significant.

Adolescent

Simultaneous pressure and 19F NMR pH measurements of smooth muscle cells of intact hog carotid arteries at rest and during contractions with norepinephrine.

Using 19F NMR we have measured the intracellular pH of the vascular smooth muscle cells of hog carotid arteries at rest and during contractions induced with norepinephrine. Experiments were performed on single, intact arteries closed at both ends, superfused from the lumen and loaded with the 19F NMR pH indicator alpha-difluoromethylalanine. At rest, luminal pressure was maintained at 100 +/- 2 mm Hg and intracellular pH was 7.12 +/- 0.04. Contractions elicited with 10(-5) M norepinephrine were associated with a pressure increase of 18 +/- 6 mm Hg and a decrease in pH of 0.04 +/- 0.02 units.

Animals

Characterization of rat liver beta-adrenoceptors during perinatal development as determined by [125I]-iodopindolol radioligand binding assays.

1. The subtype specificity of beta-adrenoceptors in foetal (20 days post coitum) rat liver membrane preparations has been determined by use of [125I]-iodopindolol binding assays and the characteristics of radioligand binding have been resolved. 2. The kinetics of radioligand association and dissociation (in the presence of 5 x 10(-4) M isoprenaline) showed an association rate constant of 1.5 x 10(7) M-1 S-1 and dissociation rate constant of 9.1 x 10(-4) S-1, corresponding to a dissociation constant for [125I]-iodopindolol of 60.7 pM. A similar dissociation constant (75 pM) was determined by saturation binding assays. 3. The rank order of potency for displacement of [125I]-iodopindolol binding was consistent with binding to a predominantly beta 2-adrenoceptor population (i.e. ICI 118551 greater than isoprenaline greater than adrenaline greater than noradrenaline greater than atenolol). Computer analysis of displacement curves in the presence of a beta 1-subtype selective agent (atenolol) or a beta 2-subtype selective agent (ICI 118551) revealed the presence of beta 2- and beta 1-adrenoceptor subtypes in a ratio of about 80:20%. 4. Saturation binding assays by use of [125I]-iodopindolol were carried out at different perinatal ages to determine total beta-adrenoceptor concentrations and beta 2-subtype (in the presence of 5 x 10(-7) M atenolol) adrenoceptor concentrations. Competition binding assays with atenolol confirmed that at all ages apparent beta 2-adrenoceptor binding accounted for 84-95% of the total beta-adrenoceptor binding. The total beta- and beta 2-adrenoceptor binding capacity increased by 2.3 fold from 20 days post coitum to birth, and then decreased postnatally at 1 and 2 days post partum. The dissociation constant for [125I]-iodopindolol binding did not show any change with age. 5. The change in beta 2-adrenoceptor concentration with age is discussed in relation to the changing beta-adrenoceptor-mediated responsiveness of glucose production by rat liver during perinatal development.

Animals

Facial skeletal changes following hypertelorbitism correction.

This is a retrospective study of skeletal changes in 19 patients with corrected hypertelorism. A favorable outcome, defined as relapse less than 5 mm, occurred in patients with an average interorbital distance of 32 mm, whereas patients with an average interorbital distance of 40 mm tended to relapse over 5 mm. Neither age, interorbital configuration, nor diagnosis affected the stability of orbital translocation. At last evaluation (mean 6.7 years postoperatively), the mean interorbital distance was 22.4 mm in the favorable outcome group and 28.3 mm in the unfavorable category. This study suggested that the standard hypertelorism operation may interfere with anterior facial growth. Unless psychosocial factors predominate in a child with mild deformity, repair should be postponed until late adolescence. In a young child with gross telorbitism, nasoethmoidal resection and transmaxillary osteotomies or facial bipartition is justified. Another long-term skeletal problem was resorption of the reconstructed nasal complex. Technical and biological explanations for this are given. The correction of hypertelorism is surgery of the nose and of the midface.

Adolescent

RED: a red-cell antibody identification expert module.

We describe a software module in an expert system RED, which interprets data related to red cell antibody identification. There are three portions to this module: the problem-solving component, which incorporates the knowledge required for antibody identification as a hierarchy of programs. The programs in the hierarchy organize within themselves small pieces of knowledge represented in the form of production rules, which are capable of making judgments concerning a specific hypothesis; an intelligent data base for storage of patient data, red cell attributes, and test results; the "overview critic" portion, which combines the atomic hypotheses judged favorably by the antibody programs into a unified judgment concerning the case. Overview makes the decision to terminate processing with a conclusion about which antibodies are actually present and what specific further tests need to be performed to resolve any remaining ambiguities.

Artificial Intelligence

CSF-brain permeability in the immature sheep fetus: a CSF-brain barrier.

The permeability of the neuroependyma between CSF and brain extracellular space has been studied in fetal sheep of 60 and 125 days gestation. Both radioactive ([3H]inulin, [14C]sucrose, [125I]albumin) and visible (horseradish peroxidase) markers have been perfused through the ventricular system for periods of up to 5 h in anaesthetized exteriorized fetal sheep whose physiological condition was monitored continuously. A previously undescribed barrier between CSF and brain extracellular fluid has been discovered in the immature (60-day) fetal sheep. Horseradish peroxidase penetration was confined to a limited depth of the neuroependyma and was mainly into the cells lining the cerebral ventricles; in older fetuses there was extracellular penetration to a distance of several millimetres from the ventricular surface, as previously described in adult animals. The volumes of distribution of sucrose and insulin were less in the immature brain than in the more mature brain, which may be a reflection of restricted diffusion across the neuroependyma in the younger brains. The morphological nature of the barrier in fetuses of 60 days and younger appears to be a membrane specialization between the cells of the neuroependyma. It is of a type not previously described; it seems to have the effect of narrowing rather than obliterating the extracellular pathway between CSF and brain. The possible functional significance of this observation is discussed.

Animals

A computerized multi-use craniofacial patient record.

A computerized craniofacial patient record reinforces the link between clinical research and the treatment process. The availability of microcomputers and appropriate software has made it feasible for most craniofacial groups to organize patient data for easy retrieval and analysis. Selection of the computer system and programs follows careful planning and systematic delineation of the desired functions of the system. An example of a working computerized craniofacial patient record system is described.

Child

Psychosocial aspects of craniofacial disfigurement. A "State of the Art" assessment conducted by the Craniofacial Anomalies Program Branch, The National Institute of Dental Research.

The psychosocial sequelae of craniofacial disfigurement may have as great an impact on the patient as the strictly physical aspects of the problem. Very little systematic work has been focused directly on these effects. The following broad recommendations would constitute initial research steps in this field: Development of satisfactory measures of physical attractiveness and their use in studies to explore the role of craniofacial features in over-all physical attractiveness. The establishment of valid metrics for assessing the severity of craniofacial anomalies through the use of both physiologic and behavioral measures, thus constructing a broader definition of what constitutes a craniofacial handicap. Studies of the relationships among physiologic and behavioral variables using recently developed statistical techniques and computer methods to determine the psychosocial consequences of craniofacial disfigurement. Studies of the process through which persons with various types of malocclusion decide to seek and complete treatment. The studies would include the patients' demographic characteristics, self-perceptions, perceptions of them by others, and the complex patient-clinician interactions during the treatment programs.

Body Image