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Biomedical subjects

R Askew

Publications and source records attributed to R Askew.

11 recordsLinked to original sources

The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK.

MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels.

Animals↗

Physical therapists' perception of patients' pain and its effect on management.

BACKGROUND AND PURPOSE: The purpose of this qualitative study was twofold: (1) to determine the factors that affected physical therapists' (PTs) perception of patients' pain and (2) to determine how this perception affected the management of patients. METHODS: Forty-six PTs with at least two years' experience practicing in pain management clinics, outpatient clinics or sports medicine clinics were interviewed. The data collected were transcribed, coded and analyzed for main themes. RESULTS: The most predominant factors found to affect PTs' perception of patients' pain were the therapist's personal and professional experience, area of practice and evaluative findings. CONCLUSIONS: In this sample there exists a common link between experience and evaluative findings: the longer PTs have been practicing the more proficient they become in performing and interpreting a thorough subjective and objective evaluation. PTs practicing in pain clinics were found to have a more holistic and multidisciplinary approach to patient care, whereas therapists practicing in outpatient and sports medicine facilities were more apt to focus on patients' physical symptoms and complaints. Four main themes of perceived patient pain and their corresponding management were developed: (1) patients presenting with legitimate/acute pain profiles render a slow, conservative approach by the PT; (2) patients presenting with debilitating/chronic pain were most often treated with an approach that stressed functional gains and patient independence; (3) the preferred treatment of patients characterized with a non-legitimate pain profile was an aggressive and multidisciplinary approach; (4) 'special cases' and their management were dependent upon the patient's functional level and pain tolerance.

Adult↗

The distribution of estrogen receptor-beta mRNA in forebrain regions of the estrogen receptor-alpha knockout mouse.

Neurons in the hypothalamus of estrogen receptor alpha-knockout (ER alphaKO) mice have been shown to concentrate radiolabeled estrogen and estrogen treatment regulates the expression of progesterone receptor mRNA. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of ER beta mRNA in ER alphaKO mouse forebrain. The results of these studies revealed an extensive distribution of ER beta mRNA in the hypothalamic regions including medial preoptic area, suprachiasmatic nucleus, paraventricular nucleus, dorsomedial nucleus, medial tuberal nucleus, and the premammillary nuclei. Additional labeled perikarya were also detected in the glomerular layer of the olfactory bulb; tenia tecta; anterior septum; bed nucleus of the stria terminalis; medial, basolateral and cortical nuclei of the amygdala; cerebral and entorhinal cortex; the septohippocampal nucleus; Ammon's horn of the hippocampus and the dorsal raphe. The results of these in situ hybridization histochemical studies have provided novel information about the distribution of ER beta mRNA in the ER alphaKO mouse forebrain. In addition, these morphological data provides evidence that estrogen may exert its actions in the ER alphaKO mouse brain via ER beta and thereby maintain organizational and activational effects.

Animals↗

Structure-function studies of the Na,K-ATPase.

Na,K-ATPase catalyzes the movement of sodium and potassium ions across the cell membrane utilizing ATP as an energy source. This enzyme is present in almost all tissues of higher organisms but is most abundant in the kidney where it is responsible for reabsorbing sodium ions from the glomerular filtrate. The enzyme is composed of two subunits and serves as the receptor for cardiac glycosides. Utilizing an expression/selection system it has been possible to identify several amino acid residues that affect sensitivity to the cardiac glycoside, ouabain. Those identified to date are located in the first transmembrane region and first extracellular region. The fact that amino acid residues within a transmembrane region affect ouabain sensitivity suggests that the drug is partially internalized in the lipid bilayer. In an effort to determine whether any of the amino acid residues which affect ouabain sensitivity interact with the sugar part of cardiac glycosides, ouabain and ouabagenin were tested in terms of their ability to inhibit enzyme containing substitutions at these positions. The two compounds differ in that ouabagenin lacks a sugar moiety. Interestingly, the ratio of I50's for the substituted enzymes remains the same as the wild type, which suggests that the amino acids identified as determinants of ouabain sensitivity to date are not likely to interact with the sugar. Another set of studies focused on cation binding. It has been proposed that cation transport involves negatively charged residues in one or more transmembrane regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Enamel opacities in children whose mothers took part in a dental health education scheme.

One well recognised cause of enamel opacities is excessive fluoride ingestion during the period of tooth development. In the past, "fluorosis", or opacities arising from this cause, has been reported to occur in children given fluoride supplements. In a large experiment in dental health education, fluoride supplements were given regularly to many of the children in two out of three experimental groups. 126 children were dentally examined 10 yr after the scheme began, of whom 79 had regularly received fluoride drops and/or tablets for at least part of the period between birth and 5 yr of age. Labial surfaces of each child's erupted incisor teeth were examined for enamel opacities. 75% of the 126 children had at least one affected tooth. There was a statistically insignificant, but consistent, trend for the prevalence of opacities to increase with increasing duration of use of fluoride supplements.

Child, Preschool↗

Second assessment of London children involved in a scheme of dental health education in infancy.

In the mid-1970's, a scheme was set up providing dental health education at home visits to mothers with young children. A free supply of fluoride supplements for their children was offered to mothers in two of the three groups taking part. In the 10th year, 126 of the children were examined for caries and gingivitis. Few statistically significant results were seen in this small sample remaining from the scheme, but trends for better dental health amongst children whose mothers had been visited at home had been seen in a previous assessment and were seen again here.

Child↗

Effects of dental health education for mothers with young children in London.

Dental health education for mothers with young children is thought to be capable of achieving a high standard of dental health for these children. This study considers the dental health of a sample of 5-yr-old children whose mothers were given dental health education at an early stage in their child's life. The dental health education was given to one group during home visits and to a second through leaflets sent by post. Comparisons were made with a third group of children whose mothers had been randomly selected to form a control group. Sixty-nine percent of children whose mothers were given advice at home were caries free, compared to 58% of children in the control group. Scores for gingivitis were also significantly lower in the first group. No significant differences in disease levels were seen between children whose mothers had been sent leaflets through the post and those in the control group. In relation to the use of fluoride supplements, 25% of the children whose mothers had been given personal advice received fluoride supplements regularly throughout the period of the study. Children of these highly motivated mothers showed less caries (83% were caries free) and lower levels of gingivitis than children who had never received supplements.

Attitude to Health↗

Dental health education through home visits to mothers with young children.

In the course of a recent experiment a group of 314 mothers with very young children were visited at home by a dental health educator on three occasions. Mothers were given advice about dental health for their children and were offered a free supply of fluoride drops. Results drawn from questionnaires completed at each home visit suggested that dental health education given in this way was able to influence maternal attitudes and behaviour. Virtually all mothers accepted the offer of fluoride drops for their children and after 14-16 months, 65% of the group were still using the supplements.

Adult↗