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Biomedical subjects

C Jackson

Publications and source records attributed to C Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Lipid peroxidation contributes to age-related membrane rigidity.

The aim of this work was to assess the relative contributions of lipid peroxidation and cholesterol content to the increase in membrane rigidity observed during senescence. Membrane fluidity was manipulated through exposure to peroxidized or cholesterol-loaded liposomes. Small unilamella liposomes were prepared and either peroxidized by Fe(++)-ADP-ascorbic acid or loaded with cholesterol. After incorporation of the liposomes into rat liver microsomal membranes, membrane fluidity was quantitated by measuring changes in polarization. Membranes exhibited a greater sensitivity to peroxidation than cholesterol in that incorporation of peroxidized liposomes induced microsomal membrane rigidity substantially more than did cholesterol-loaded liposomes. Thus it is proposed, based on data from the present and earlier studies, that membrane fluidity can be modulated readily by lipid peroxidation of membrane phospholipids, irrespective of the influences of cholesterol. These results support the proposal that alterations of lipid structure are more potent and effective than compositional changes in cholesterol in inducing age-related increases in membrane rigidity.

Aging↗
PubMed1995

Protection of the germinal epithelium in the rat from the cytotoxic effects of chemotherapy by a luteinizing hormone-releasing hormone agonist and antiandrogen therapy.

OBJECTIVES: The protection of spermatogenesis during chemotherapy using an antiandrogen and a luteinizing hormone-releasing hormone (LHRH) agonist was examined in the rat. Previous studies using LHRH agonists alone have been inconclusive, as both protective and deleterious effects on the germinal epithelium have been reported. Flutamide has not previously been used in this manner but theoretically should protect the germinal epithelium, since flutamide rapidly blocks testosterone at the cellular level and also minimizes the testosterone "flare" when LHRH agonist therapy is initiated. METHODS: Mature Sprague-Dawley rats were pretreated with flutamide, sustained-release goserelin acetate (Zoladex), or a combination of flutamide and sustained-release goserelin acetate for 14 days before 4 weekly doses of procarbazine were initiated. The seminiferous tubules were evaluated histologically after a 90-day regeneration period using the stem cell assay test. RESULTS: After treatment with procarbazine alone, only 43% of the seminiferous tubules were active; however, 80% were active if protected with flutamide, 91% if protected with sustained-release goserelin acetate, and 95% if protected with both flutamide and goserelin acetate. CONCLUSION: Flutamide, sustained-release goserelin acetate, and a combination of these agents were effective in protecting the germinal epithelium of the rat during chemotherapy. A combination of flutamide and goserelin acetate provided the best protection. This study demonstrates for the first time the protective effect of flutamide and flutamide with goserelin acetate on the germinal epithelium during chemotherapy.

Animals↗
PubMed1995

Screening for glaucoma in a Brisbane general practice--the role of tonometry.

OBJECTIVES: (1) To pilot, and evaluate, a tonometry training intervention for general practitioners; (2) to evaluate the efficacy of three types of tonometer (Perkins, Schiotz and Tonopen) in the hands of these general practitioners; (3) to evaluate the predictive value of tonometry in screening for glaucoma in a general practice population; and (4) to evaluate the acceptability of tonometry to general practice patients. DESIGN: After being trained, three general practitioners recruited 73 of their patients over 50 years of age to attend for measurement of intraocular pressure by tonometry. Intraocular pressure was initially measured by an ophthalmologist using the Goldmann applanation tonometer, and then recorded in random order by GPs using three types of tonometer--the Perkins, Schiotz and Tonopen. SETTING: A group general practice in a middle-class suburb in southern Brisbane. OUTCOME MEASURES: (1) Comparison of measurements on the Perkins, Schiotz and Tonopen tonometers with that of the 'gold standard', the Goldmann Applanation tonometer; (2) prevalence of disc and perimetric abnormality suggestive of glaucoma among those patients with increased intraocular pressure; and (3) the acceptability of contact tonometry to general practice patients. RESULTS: There was considerable variability between intraocular values obtained across doctors and across instruments (6% to 95% of values within 4 mm of the 'gold standard'). The Schiotz tonometer provided the most uniform assessment of intraocular pressure across the groups. Nineteen of the 73 patients (26%) had intraocular pressures > or = 21 mmHg using the 'gold standard'. Of these, 18 were followed up with funduscopy, gonioscopy, repeat measurement of intraocular pressure and visual field assessment. Five had persistent elevations of intraocular pressure > or = 21 mmHg on subsequent assessment, and two had mild abnormalities of cup-disc ratio with normal fields on testing with Humphrey computerised perimetry. CONCLUSION: No one hand-held tonometer proved highly accurate in the hands of all three doctors. Even measured optimally, increased intraocular pressure alone was a poor predictor of glaucoma. Of the population screened, two patients (3%) showed evidence of mild cup-disc abnormality requiring follow-up.

Australia↗
PubMed1995

Brisbane GPs' perceptions of screening for primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG) is one of the three leading causes of blindness in Australia, often causing considerable visual field loss before the patient becomes symptomatic. Recent years have seen a quickening of public health interest in primary open-angle glaucoma. Our study evaluates the attitudes and skills of Brisbane GPs with regard to screening for POAG. OBJECTIVES: To evaluate general practitioners' current use of possible screening modalities for POAG. To evaluate general practitioners' attitudes to screening for POAG. To evaluate general practitioner's levels of satisfaction with their knowledge and skills in the diagnosis of common ophthalmological conditions. METHOD: A questionnaire was distributed to 130 randomly selected GPs in the Brisbane metropolitan area. Response rate was 94%. RESULTS: Tonometry and funduscopy were infrequently used in Brisbane general practice. Only 15% of the sample were satisfied with their current knowledge and skills concerning the detection of POAG. 88% felt that patients > 50 years should be screened for POAG and nominated a variety of sources -75% advocating ophthalmology screeners, 65% GP screeners, and 41% optometrist screeners. Ninety-nine per cent believed ophthalmologists should be treating glaucoma patients, and 57% believed GPs should have a role in management. Only 1% supported a therapeutic role for optometrists. Major perceived barriers to glaucoma screening in the elderly were the inaccuracy of current general practice screening tools (65%) and paucity of information concerning the desirability of screening (32%). CONCLUSION: Brisbane general practitioners believe patients > 50 years old should be screened for POAG. They advocated a role for screening by ophthalmologists, GPs and optometrists. Major perceived barriers to current screening in general practice are the inaccuracy of current general practice tools (65%) and paucity of information on the subject (32%). The majority (85%) requested further information and provision of skills in this area.

Attitude of Health Personnel↗
PubMed1995

Model for the neuromuscular complications of systemic lupus erythematosus.

The purpose of this study is to evaluate nerve and muscle physiology and histopathology in a murine lupus model. Muscle strength, compound muscle action potentials (distal latency and amplitude), proximal limb muscle, sciatic nerve and joint specimens were studied in MRL/lpr (lupus model) and MRL/++ (control) mice. MRL/lpr mice showed decreased muscle strength (P < 10(-6, Wilcoxon rank sum), lower compound muscle action potential mean amplitude and prolonged distal latency (P = 0.005 and 0.042. Mann-Whitney U-test), and muscle and nerve inflammation (P = 0.002 and P = 0.037, Fisher's exact test) compared with MRL/++ mice. The MRL/lpr strain evaluated in this study demonstrated muscle weakness, abnormal motor nerve conduction studies and inflammation of both muscle and nerve. These features make it an excellent model for studying the neuromuscular complications of lupus.

Action Potentials↗
PubMed1995

Epidemiologic evidence for clustering of equine motor neuron disease in the United States.

OBJECTIVE: To examine the regional variations in the distribution of equine motor neuron disease (EMND) in the United States and the factors that might explain those variations. DESIGN: Cluster investigation and case-control study. SAMPLE POPULATION: The study population consisted of 97 horses with histopathologically confirmed EMND and 698 controls with diagnosis of other spinal cord disorders at 21 US veterinary teaching hospitals participating in the Veterinary Medical Data Base. PROCEDURE: The total horse population of the United States was divided into 21 regions, and the regional incidence rates of EMND from January 1985 through January 1995 were estimated. Moran's index of spatial autocorrelation was calculated to test for spatial clustering of the disease. The 21 regions were then joined in broader areas according to the similarity of their EMND rates by means of the cluster analysis statistical technique. Finally, the role of potential confounding factors (age at diagnosis, month of diagnosis, breed, and sex) in the present distribution of EMND was assessed, using logistic regression analysis. RESULTS: Differences in estimated rates across the 21 regions resulted in a strong pattern of spatial clustering of EMND in the United States. The geographic units were grouped into 5 risk regions, with the gradient of EMND incidence rates increasing from the western states (almost 0 cases/1,000,000 horse-years) toward New England (20.78 cases/1,000,000 horse-years). Reported risk factors of EMND (age, breed) and other extraneous factors (sex, month of diagnosis) could not explain the observed geographic variations of disease rates. Nevertheless, there is evidence of some confounding attributable to age and breed. CONCLUSIONS: Although the mechanism responsible for the clustering of EMND in northeastern states is still unexplained, it is not an epiphenomenon caused by regional differences in the distribution of the factors investigated.

Animals↗
PubMed1995

Optimizing inhaled drug delivery in patients with asthma.

Successful management of asthmatic patients depends on achieving adequate delivery of inhaled drugs to the lung. This assumes particular importance for inhaled corticosteroids where the therapeutic goal should be to achieve a high ratio of airway anti-inflammatory efficacy to local and systemic side effects. The availability of user-friendly inhaler devices requires a critical appraisal of their effectiveness and an evaluation of whether improved lung deposition of anti-asthma drugs translates into improved clinical efficacy. There is evidence to suggest that the routine use of large-volume spacers for inhaled corticosteroids may not be the best first-line option, in that reduced drug delivery is associated with multiple actuations, inhalation delay and the presence of static electricity. Breath-actuated pressurized aerosol devices or dry powder inhaler devices may be a better option for many asthmatic patients, although the efficiency of drug delivery varies considerably between these devices. There is good evidence with a reservoir dry powder inhaler device to show that improved lung deposition translates into better therapeutic response, both in terms of beta 2-agonist and corticosteroid delivery. For inhaled corticosteroids, such as fluticasone propionate and budesonide, there is evidence to show that systemic bioactivity is mainly determined by lung bioavailability rather than gastrointestinal bioavailability, because of the absence of first-pass metabolism of these drugs in the lung. There is also evidence to show that the greater glucocorticoid potency of fluticasone propionate translates directly into greater systemic bioactivity, but not into enhanced efficacy, at doses above 1 mg daily. The use of efficient delivery systems, such as the reservoir dry powder inhaler device, may not only improve control of asthma and compliance with therapy, but may also allow dose reduction ('step-down' therapy) and hence may possibly reduce overall prescribing costs in the long term.

Anti-Asthmatic Agents↗
PubMed1994

CD8 cells play a critical role in delayed type hypersensitivity to intact Cryptococcus neoformans.

Although cell-mediated immunity is critical for optimal host defense to C. neoformans, the role of T lymphocyte subsets is complex and poorly understood. CD8 cells are important both for optimal host defense against C. neoformans, and for expression of delayed type hypersensitivity (DTH). Because host defense correlates with the ability to mount a DTH response to C. neoformans, the current studies were performed to determine the mechanism by which CD8 cells participate in DTH. Mice were immunized by the intratracheal route with live C. neoformans, or by the subcutaneous route with heat-killed C. neoformans. Mice were depleted of CD8 cells in vivo by administration of mAb. After challenge with soluble cryptococcal Ag, the DTH response was quantified as footpad swelling. We found that mice depleted of CD8 cells before immunization were unable to express DTH. Mice depleted of CD8 cells after immunization but before challenge also were unable to express DTH. Splenocytes of mice depleted of CD8 cells in vivo, before immunization, failed to transfer DTH to naive, undepleted mice. Immune splenocytes depleted of CD8 cells in vitro also failed to transfer DTH to naive, undepleted mice. These data indicate that CD8 cells were necessary during the challenge and immunizing phases of DTH, and were necessary for expression of DTH. However, CD8 cell depletion did not abrogate DTH in mice immunized with either soluble cryptococcal Ag in complete Freund's adjuvant, or sheep red blood cells, which are mediated by CD4 cells. These data suggest that CD8 cells play a critical role in the cell-mediated immune response to C. neoformans. Based on this information, it may be possible to protect hosts with deficiencies of CD4 cells, such as in AIDS, by designing immunizing strategies for stimulating CD8 cells.

Animals↗
PubMed1994

Women in management. Why women in the NHS don't get a share of the action.

The survey was designed to give a representative picture of staff attitudes across the South East Thames region. A key intention of the survey was to collect information from all staff groups and locations. Questionnaires were sent out during September and October 1992 to a random sample of women and men. By the close of the survey, 1,886 usable questionnaires had been returned from members of the survey sample, representing a response rate of 43 per cent. In addition, 512 questionnaires had been received from volunteers. The analysis presented in the report is based on 2,398 survey respondents, 18 per cent of whom were men.

Administrative Personnel↗
PubMed1994

The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic systems during behaviorally effective infusions to the substantia nigra.

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) have both been identified as ligands for the TrkB receptor, yet differences have emerged in terms of their in vitro potencies for neuronal survival and differentiation. This has prompted the in vivo study of their effects on behavior and neuro-chemical parameters associated with dopamine, serotonin, and GABAergic neurons in the basal ganglia. Two-week supranigral infusions of NT-4/5 and BDNF were similar in their ability to augment levels of the dopamine metabolite homovanilic acid (HVA) (63 and 78%, respectively) and the ratios of dihydroxphenylacetic acid/dopamine (DOPAC/DA) (39, 48%) and HVA/DA (85, 77%) in the caudate-putamen of the hemisphere ipsilateral to the nigral infusion. Striatal concentrations of DOPAC were elevated 45% by BDNF but not by NT-4/5. The 3-MT/dopamine ratio, an indicator of dopamine release, was elevated by 38 and 32% in the striata of BDNF- and NT-4/5-infused rats, respectively. Striatal indoleamine metabolism, determined by the ratio of 5-hydroxyindoleacetic acid (5HIAA)/serotonin was also elevated by NT-4/5 and BDNF in the caudate-putamen (29, 32%), and the 5HIAA content of the substantia nigra was elevated by both factors (43, 40%). The activity of GAD within the superior colliculus was elevated 21 and 41% by BDNF and NT-4/5, respectively. A contraversive rotational bias was induced in BDNF and NT-4/5-treated rats challenged with d-amphetamine, and these responses were blocked by pretreatment with selective D1 or D2 receptor antagonists but not by opiate receptor antagonism. Thus, NT-4/5 and BDNF can elevate the turnover of dopamine through both metabolic and release pools and augment the behavioral response to d-amphetamine. The role for dopamine in this behavioral response is indicated by the requirement of unoccupied D1 and D2 receptors, but may also involve changes in serotonergic, GABAergic, or other pathways. The TrkB receptor-specific actions of BDNF and NT-4/5 may have implications for understanding the etiology or treatment of basal ganglia disorders.

Animals↗
PubMed1994

In vivo depletion of murine CD8 positive T cells impairs survival during infection with a highly virulent strain of Cryptococcus neoformans.

Cell-mediated immunity plays an important but incompletely understood role in host defense against Cryptococcus neoformans. Because of their multiple capacities as cytokine-secreting cells, cytotoxic cells, and antigen-specific suppressor cells, CD8 positive T lymphocytes could potentially either enhance or impair host defense against C. neoformans. To determine whether CD8 T cells enhance or inhibit host defence during an infection with a highly virulent strain of C. neoformans, we examined the effect of in vivo CD8 cell depletion on survival and on the number of organisms in mice infected by either the intratracheal or intravenous routes. Adequacy of depletion was confirmed both phenotypically and functionally. Regardless of the route of infection, we found that survival of mice depleted of CD8 T cells was significantly reduced compared to undepleted mice. Surprisingly, however, CD8 depletion did not alter organism burden measured by quantitative CFU assay in mice infected by either route. These data demonstrate that CD8 positive T cells participate in the immune response to a highly virulent strain of C. neoformans. By contrast to minimally virulent isolates that do not cause a life threatening infection, the immune response to a highly virulent isolate does not alter the burden of organisms, but does enhance host defense as it is necessary for the optimal survival of infected mice.

Animals↗
PubMed1994

Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions.

Brain-derived neurotrophic factor (BDNF) promotes the survival of dopamine (DA) neurons, enhances expression of DA neuron characteristics, and protects these cells from 6-hydroxydopamine (6-OHDA) toxicity in vitro. We tested the ability of BDNF or neurotrophin-3 (NT-3) to exert similar protective effects in vivo during chronic delivery of 6-OHDA to the rat neostriatum. Chronic infusions of BDNF or NT-3 (12 micrograms/day) above the substantia nigra were started 6 days before and continued during an 8-day chronic intrastrial infusion of 6-OHDA. In control and neurotrophin-treated animals, 6-OHDA treatment selectively depleted 50-60% of nigrostriatal DA nerve terminals but produced little if any loss of pars compacta DA cell bodies. This partial DA lesion resulted in three rotations per minute toward the lesioned hemisphere after treatment with the DA release-inducing drug d-amphetamine. Compared with supranigral infusions of vehicle, BDNF and NT-3 decreased the number of these ipsiversive rotations by 70 and 48% and increased by 20- and 10-fold, respectively, the number of contraversive rotations observed after amphetamine injection. When challenged with the DA receptor agonist apomorphine, BDNF- and NT-3-treated animals also exhibited a seven- and 3.5-fold increase in the number of contraversive rotations relative to the vehicle group, respectively. Compared with vehicle, BDNF increased striatal levels of homovanillic acid (HVA; 86%), 3,4-dihydroxyphenylacetic acid (DOPAC; 42%), and 5-hydroxyindoleacetic acid (5-HIAA; 32%) and the HVA/DA (43%) and 5-HIAA/serotonin (34%) ratios in the DA-denervated striatum. NT-3 augmented only striatal 5-HIAA levels (24%). Neither factor altered the 6-OHDA-induced decrease in striatal DA levels or high-affinity DA uptake and thus did not protect against the destruction of DA terminals and did not alter striatal D1 or D2 ligand binding. Choline, GABA, and glutamate uptake in the striatum were not altered by the lesion or neurotrophin treatment. Thus, BDNF and to a lesser extent NT-3 reverse rotational behavioral deficits and augment striatal DA and 5-HT metabolism in a partial DA lesion model.

3,4-Dihydroxyphenylacetic Acid↗