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Biomedical subjects

K Elliott

Publications and source records attributed to K Elliott.

At least 37 records · Page 2Linked to original sources

Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.

Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Animals↗

The putative tumor suppressor BIN1 is a short-lived nuclear phosphoprotein, the localization of which is altered in malignant cells.

BIN1 is a putative tumor suppressor that was identified in a genetic screen for polypeptides that interact with the MYC oncoprotein. Using a set of six monoclonal antibodies, we identified and examined biochemical features and localization of cellular BIN1. Epitope mapping indicated that a putative nuclear localization motif and the MYC-binding domain were among the regions recognized by five antibodies. In immunoprecipitation and Western analyses, cellular BIN1 was identified in human and rodent cells as a monomeric phosphoprotein of M(r) approximately 70,000. Pulse-chase experiments showed that BIN1 was short-lived, with a half-life of approximately 2 h. Cell immunofluorescence experiments revealed overlapping but unique nuclear localization patterns distinguished by two different antibodies. In normal cells, BIN1 was predominantly nucleoplasmic but was also present in a subnuclear compartment. Conversely, in a panel of tumor cells that expressed BIN1, the predominant localization was the subnuclear compartment. Taken together, the results suggested that the antibodies recognized different isoforms or conformations of BIN1, the localization of which varied between normal and tumor cells. This study will facilitate further analysis of the structure and regulation of BIN1 in normal and malignant cells.

Adaptor Proteins, Signal Transducing↗

Oral ketamine produces a dose-dependent CNS depression in the rat.

The oral to parenteral potency of ketamine to produce central nervous system (CNS) depression was estimated in rats using a behavioral scale. As a function of dose, ketamine produces CNS depression that ranges from ataxia to anesthesia by either route of administration. The oral ED50 value for ketamine was 120 mg/kg (82.2-159.2, 95% CI) while the intravenous ED50 value was 3.7 mg/kg (2.4-5.1, 95% CI). Oral ketamine produces CNS effects comparable to intravenous ketamine, although the drug is approximately 32 fold less potent by the oral route.

Administration, Oral↗

Is there a relationship between proximity to industry and the occurrence of otitis media with effusion in school entrant children?

In a study of the relationship between the prevalence of persistent otitis media with effusion (OME) in school entrant children in Redcar and Cleveland and the distance of the homes of these children from known industrial emission points, 1156 school entrant children were screened for the presence of persistent OME. The social disadvantage scores and map references were determined from the postcode area of each of the study entrants and map references were also obtained of known industrial emission points in the locality. Analyses were conducted on the association between the presence of OME and distance from emission sources and between the presence of OME and disadvantage score. A significantly greater proportion of study entrants with OME lived within 1000 meters of an industrial emission point than further away. However, there was no trend established between the proportion of study entrants with OME and increasing distance from an emissions source, nor was there any significant relationship established between the social disadvantage score of the areas of residence of the study entrants and the presence of OME. Further research is required to establish the effect of confounding variables on this relationship.

Air Pollution↗

Changing infant feeding practices and declining incidence of coeliac disease in West Somerset.

An association was investigated between changing infant feeding practices and a declining incidence of childhood coeliac disease and transient gluten intolerance (TGI) in West Somerset, England during 1971-92. Dietary histories of 18 patients with coeliac disease were compared with 23 controls during 1971-80 and eight patients with coeliac disease and 39 controls during 1981-92. Our findings showed that the declining incidence of coeliac disease and TGI were associated with changing infant feeding practices, characterised by the later introduction of dietary gluten, an increased use of baby rice and gluten free foods for weaning, and an increased incidence of initial breast feeding.

Adolescent↗

The relationships between cardiovascular risk factors and socio-economic status in people with diabetes.

The hypothesis that the prevalence of cardiovascular risk factors in people with diabetes is inversely related to socio-economic status was tested. Demographic and biochemical data were collected on 1246 patients, aged 20-69 years, attending a hospital diabetes clinic. This is estimated to represent between 71% and 78% of all people of this age with a diagnosis of diabetes in the health authority. In total, 296 people were classified as Type 1 (insulin-dependent) diabetic patients (age of onset < 31, now on insulin). Using data from the 1991 census a deprivation score was ascribed to each individual according to their area (enumeration district) of residence. The total study population was ranked by deprivation score and divided into quintiles. The relationships between means and quintiles of deprivation were assessed by ANOVA for linear trend, and between proportions and quintiles of deprivation by the chi-squared test for trend. In Type 1 diabetes increasing quintiles of deprivation were significantly related to mean serum cholesterol (p < 0.01) and proportion smoking (p < 0.01), and in Type 2 (non-insulin-dependent) diabetes to mean body mass index (p < 0.001), proportion smoking (p < 0.001), and proportion with proteinuria (p < 0.05). The need for health measures to prevent cardiovascular disease in people with diabetes is greatest in deprived areas.

Adult↗

Constructing arousal profiles for vegetative state patients--a preliminary report.

Arousal profiles are a method that we have developed for using data derived from time sampling to examine how behaviours such as the frequency with which the eyes are observed open, and the frequency of spontaneous movements, vary in the periods immediately before and immediately after sensory stimulation treatment. We believe changes in such behaviours reflect changes in arousal. The use of this new technique is illustrated with examples from a pilot study using data from 15-day treatment blocks, gathered for 10-minute periods immediately before and after sensory stimulation treatment from three patients using single-case research methods. The patients were diagnosed as being in vegetative state following traumatic brain injury. The possible significance of the differing characteristics of the profiles is discussed.

Adult↗

Interallelic complementation at the suppressor of forked locus of Drosophila reveals complementation between suppressor of forked proteins mutated in different regions.

The Su(f) protein of Drosophila melanogaster shares extensive homologies with proteins from yeast (RNA14) and man (77 kD subunit of cleavage stimulation factor) that are required for 3' end processing of mRNA. These homologies suggest that su(f) is involved in mRNA 3' end formation and that some aspects of this process are conserved throughout eukaryotes. We have investigated the genetic and molecular complexity of the su(f) locus. The su(f) gene is transcribed to produce three RNAs and could encode two proteins. Using constructs that contain different parts of the locus, we show that only the larger predicted gene product of 84 kD is required for the wild-type function of su(f). Some lethal alleles of su(f) complement to produce viable combinations. The structures of complementing and noncomplementing su(f) alleles indicate that 84-kD Su(f) proteins mutated in different domains can act in combination for partial su(f) function. Our results suggest protein-protein interaction between or within wild-type Su(f) molecules.

Alleles↗

Same-sex and cross-sex relationships.

This study examines same-sex and cross-sex close relationships of older adults using a national probability sample survey. Specifically, we focus on three relational characteristics: psychological closeness, geographical proximity, and support exchange. These characteristics are examined with four types of close relationships: spouse, children, siblings, and friends. Results indicate that although older persons tend to have more women in the network and receive more support from those women, they are not necessarily closer, either psychologically or geographically, to the women than to the men in their network. The data also suggest a noticeable shift from same-sex alliance to female salience in the networks when older men, as well as women, become widowed and require more support. The findings are discussed in light of three principles which have guided research on sex differences in close relationships: relation hierarchy, femaleness, and sex commonality.

Aged↗

Quantitation of mu-opioid receptor (MOR-1) mRNA in selected regions of the rat CNS.

The mu opioid receptor (MOR-1) mRNA was quantified in rat CNS by a sensitive solution hybridization (SH) technique, employing a 32P-labeled riboprobe derived from the coding region of MOR-1 cDNA. In a Northern blot analysis this riboprobe hybridized to a 14 kb form of rat MOR-1 mRNA. The linear range of SH assay extends from 1 to 250 pg of MOR-1 sense transcript (equivalent to 9.3-2325 pg of MOR-1 mRNA). A microdissection technique for reproducible sampling of selected CNS regions, followed by the SH assay, allowed for a quantitative study of MOR-1 mRNA distribution. The highest levels of MOR-1 mRNA were present in medial thalamus (17.8 +/- 0.3 pg/micrograms RNA), and the lowest in the cerebellum (0.4 +/- 0.1 pg/microgram RNA). Hypothalamus, dorsal spinal horn, nucleus raphe, periaqueductal gray, and sensorimotor cortex contained intermediate levels. This distribution closely parallels the pattern of mu receptor binding, suggesting that both the mRNA and the receptor protein are colocalized within most of the regions studied.

Amino Acid Sequence↗

CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with morphine or naltrexone.

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/microgram RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the size of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.

Animals↗

N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development.

This laboratory perspective reviews the pharmagologic approaches that have been used in preclinical animal models to demonstrate the ability of competitive (LY274614) and noncompetitive (MK801 and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists to attenuate or reverse the development of morphine tolerance. We provide additional data to support previous observations that these NMDA antagonists modulate morphine (mu) opioid tolerance but do not affect U50488H (kappa 1) opioid tolerance. A strategy, which utilizes efficacy as an NMDA receptor antagonist and clinical safety, provides the basis for a discussion of the clinical potential of dextromethorphan, ketamine, and felbamate as modulators of opioid tolerance in pain patients or opioid addicts. The potential use of NMDA receptor antagonists and nitric oxide synthase (NOS) inhibitors in neuropathic pain is also discussed.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Supraspinal delta opioid receptor mRNA levels are not altered in [D-Ala2]deltorphin II tolerant mice.

Delta opioid receptor (DOR) mRNA levels were studied in mice rendered tolerant to [D-Ala2]deltorphin II by 4 days of repeated intracerebroventricular administration (10 micrograms, [tid]). ED50 determinations on day 5 revealed a 10-fold loss in [D-Ala2]deltorphin II potency with the tail-flick test. Utilization of a microdissection technique followed by quantitative solution hybridization of RNA extracts from mouse brain revealed mean levels of DOR mRNA ranging from 3.9 pg/micrograms RNA in the caudate-putamen to 0.4 pg/micrograms RNA in the cerebellum. DOR mRNA levels were not different when RNA extracts from tolerant and non-tolerant mice were compared. These data suggest that altered DOR mRNA levels are not one of the adaptive changes that occur with delta opioid ([D-Ala2]deltorphin II) tolerance.

Animals↗

Tendon jerks in Parkinson's disease.

Tendon reflexes were examined in 119 patients with idiopathic parkinsonism (IP) and 40 spouse controls to estimate the type and frequency of any alterations in the reflexes. Forty one of 119 patients and 2 of 40 controls had reflex ratings of 3+ at two or more sites (p < 0.001). There was no correlation of reflex score with the severity of disease or with the cardinal signs of IP. In 21 patients with asymmetric tendon jerks the side with the more active reflexes correlated with the side with greater parkinsonian signs. We conclude that an increase in tendon jerks is a feature of IP. The pathophysiology of this change in reflexes should be investigated further to establish if it is a heretofore overlooked manifestation of basal ganglia dysfunction or a link with other neurodegenerative diseases.

Adult↗

Time is running out for entitlement reform.

In 1993, President Clinton created the Bipartisan Commission on Entitlement and Tax Reform as part of the administration's effort to promote economic growth and control the budget deficit. The purpose of the commission, chaired by Senator J. Robert Kerrey (D-NE) and Senator John C. Danforth (R-MO), is to seek bipartisan agreement on long-term entitlement reform and structural changes to the tax system. The final recommendations of the commission, due December 15, will be of great interest to the academic medicine community because of the importance of federal dollars to medical research and education and the crucial role of the Medicare and Medicaid programs in financing the care provided by teaching physicians and teaching hospitals. What follows is a summary of the commission's interim report submitted to the president on August 8; it reflects the commissioners' almost unanimous (30 to 1) agreement on the nature and magnitude of the entitlement problem.

Budgets↗

Case management: a case study.

Prior to institution of case management Mr. G would have remained on the neuroscience acute care unit until nursing home placement could be arranged, a process which often took a year because of the severe shortage of Medicaid beds in South Carolina. Because case managers collaborated to identify and resolve the problem, the outcome for those such as Mr. G has changed. Case management facilitates movement of patients with complex problems from acute care to successful community reentry in a cost-effective manner.

Adult↗

Geographical mapping of diabetic patients from the deprived inner city shows less insulin therapy and more hyperglycaemia.

To determine whether or not economic and social deprivation were associated with different diabetic treatment and metabolic control, data of patients from deprived inner city wards and prosperous wards were compared. A database was obtained for 1528 patients attending our hospital Diabetes Care Centre. Demographic data and postcodes were used to construct geographical maps of disease and deprivation. Blood glucose and glycated haemoglobin were measured. Inner city patients were less likely to be taking insulin, but if they were, they were more likely to have higher blood glucose values (p = 0.02) and higher glycated haemoglobin values (p = 0.02), compared to patients from prosperous wards. Insulin-treated patients from socially and economically deprived wards had worse diabetic control than patients from more prosperous wards. The study emphasizes the needs to target deprived patients for education and motivation to understand diabetes, and to optimize metabolic control.

Adult↗