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Biomedical subjects

C Jackson

Publications and source records attributed to C Jackson.

At least 37 records · Page 2Linked to original sources

Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection.

The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-gamma)-mediated resolution of replicative Legionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-gamma mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior to L. pneumophila infection inhibited induction of intrapulmonary IFN-gamma production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-gamma and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.

Animals↗

Characterization of a novel outer membrane hemin-binding protein of Porphyromonas gingivalis.

Porphyromonas gingivalis is a gram-negative, anaerobic coccobacillus that has been implicated as a major etiological agent in the development of chronic periodontitis. In this paper, we report the characterization of a protein, IhtB (iron heme transport; formerly designated Pga30), that is an outer membrane hemin-binding protein potentially involved in iron assimilation by P. gingivalis. IhtB was localized to the cell surface of P. gingivalis by Western blot analysis of a Sarkosyl-insoluble outer membrane preparation and by immunocytochemical staining of whole cells using IhtB peptide-specific antisera. The protein, released from the cell surface, was shown to bind to hemin using hemin-agarose. The growth of heme-limited, but not heme-replete, P. gingivalis cells was inhibited by preincubation with IhtB peptide-specific antisera. The ihtB gene was located between an open reading frame encoding a putative TonB-linked outer membrane receptor and three open reading frames that have sequence similarity to ATP binding cassette transport system operons in other bacteria. Analysis of the deduced amino acid sequence of IhtB showed significant similarity to the Salmonella typhimurium protein CbiK, a cobalt chelatase that is structurally related to the ATP-independent family of ferrochelatases. Molecular modeling indicated that the IhtB amino acid sequence could be threaded onto the CbiK fold with the IhtB structural model containing the active-site residues critical for chelatase activity. These results suggest that IhtB is a peripheral outer membrane chelatase that may remove iron from heme prior to uptake by P. gingivalis.

Amino Acid Sequence↗

Opioid peptide receptor studies. 10. Nor-BNI differentially inhibits kappa receptor agonist-induced G-protein activation in the guinea pig caudate: further evidence of kappa receptor heterogeneity.

There is strong evidence supporting the existence of multiple kappa receptors. Previous studies proposed that U69,593 and (+)-tifluadom act on different kappa receptor subtypes, kappa(1) (kappa(1)) and kappa(2) (kappa(2)), respectively. In this study, we investigated the effects of the kappa selective antagonist nor-binaltorphimine (Nor-BNI) on U69,593- and (+)-tifluadom-induced receptor-mediated stimulation of [(35)S]-GTP-gamma-S binding in the guinea pig caudate. The IC(50) value of Nor-BNI in the presence of a stimulating concentration of U69,593 (1 microM) was 0.19+/-0.02; while the IC(50) for Nor-BNI in the presence of (+)-tifluadom (1 microM) was 13.9+/- 1.62 nM. The mu-opioid receptor antagonist CTAP (10,000 nM) significantly reduced (+)-tifluadom-stimulated [(35)S]-GTP-gamma-S binding in rat brain sections and guinea pig brain membranes, indicating that (+)-tifluadom has mu agonist activity. Under conditions in which the mu agonist activity of (+)-tifluadom was blocked by 1000 nM CTAP the Ki value for Nor-BNI for inhibition of U69,593-stimulated [(35)S]-GTP-gamma-S binding was 0.036+/-.004 nM, whereas, its Ki value for the (+)-tifluadom-stimulated [(35)S]-GTP-gamma-S binding was 0.27+/-.015 nM. These results suggest that (+)-tifluadom and U69,593 activate pharmacologically different receptors. This study provides functional evidence in support of kappa receptor heterogeneity.

Animals↗

Pulmonary evaluation and prevalence of non-invasive ventilation in patients with amyotrophic lateral sclerosis: a multicenter survey and proposal of a pulmonary protocol.

In order to evaluate the current standard of care for the management of respiratory failure in patients with amyotrophic lateral sclerosis (ALS), a questionaire was mailed to the Medical Directors of 48 multidisciplinary ALS centers in the United States. Twenty centers reported information on 2357 patients, mean of 124 patients per center. Pulmonary function tests were performed at each visit in 17/20 institutions. Arterial blood gases, maximal expiratory pressures and maximal inspiratory pressures were followed in three centers and serum chloride was monitored in only four centers. The use of non-invasive ventilation (NIV) was extremely variable (range 0-50%) and included 360 patients (15%). The majority of centers used symptoms/signs of hypoventilation and worsening forced vital capacity (FVC) to initiate NIV with no established protocol. A FVC between 20 and 40% was used by most centers to initiate NIV. Due to great variability in the approach to monitoring pulmonary function among ALS centers and the modest effects of current medications to slow disease progression, we propose the use of a structured protocol which can prospectively study the role of NIV in prolonging survival and improving quality of life.

Amyotrophic Lateral Sclerosis↗

Changes in serum chondroitin sulphate epitopes 3-B-3 and 7-D-4 in early rheumatoid arthritis.

OBJECTIVES: The aims of the present rheumatoid arthritis (RA) study were (1) to examine the levels of serum 3-B-3 and 7-D-4 to find out whether they are different from controls, (2) to find out whether the concentrations of these epitopes change with disease duration in early RA and (3) whether the serum concentrations of 3-B-3 and 7-D-4 in early RA are prognostic for subsequent disease progression. METHODS: The concentrations of 3-B-3 and 7-D-4 in sera were quantitated by immunoassays. RESULTS: The levels of 3-B-3 and 7-D-4 were significantly lower in RA than in controls (3- to 30-fold, P < 0.001). Changes in 3-B-3 and 7-D-4 were apparent with disease duration. At first presentation, the 3-B-3 concentration was lowest and increased at 12 months (3-fold, P < 0.001). This increase was transient since by 24 and 36 months the concentrations were not different to those at first presentation. The level of 7-D-4 was also lowest when the patients first presented at clinic and increased with time at 6 months (2-fold, P < 0.001). The increase was more prolonged for 7-D-4, remaining elevated at 12, 24 and 36 months. The lack of correlations of serum 3-B-3 and 7-D-4 with clinical measurements showed that these markers were not prognostic for disease severity. CONCLUSIONS: The levels of 3-B-3 and 7-D-4 differed between RA and control sera, and changed with disease duration. These markers were not prognostic in predicting disease outcome.

Adult↗

Short day length alone does not inhibit spermatogenesis in the seasonally breeding four-striped field mouse (Rhabdomys pumilio).

This study was an examination of the effect of photoperiod on spermatogenesis and the accessory glands of the four-striped field mouse (Rhabdomys pumilio), a seasonally breeding rodent that occurs through Southern Africa. Adult scrotal males were exposed to either short day length (10L:14D), long day length (14L:10D), or natural photoperiod in constant-environment rooms (25 degrees C, 41% humidity; food and water ad libitum) for 8 wk in late summer, when males in the wild were spermatogenically active, and in mid-winter, when they were inactive. In neither experiment did prolonged exposure to short day length or naturally decreasing day length inhibit spermatogenic activity, and we conclude that the normal cessation of spermatogenesis that occurs in most male four-striped field mice in winter is not stimulated by day length alone.

Animals↗

Ocular manifestations of equine motor neuron disease.

The characteristics of the ocular manifestations of equine motor neuron disease (EMND) are described. Forty-two horses with histories, clinical signs and necropsies compatible with EMND were the subjects of this study. Ophthalmoscopic lesions that varied in severity were found in 40 of 42 horses and appeared as a distinct pigmented reticulated pattern at the tapetal-nontapetal junction or throughout the fundus, depending upon severity. The pattern colours ranged from yellow brown to black. Areas of hyperreflectivity formed mosaic patterns in the tapetal fundus. ERG B-wave amplitudes were usually at least 50% reduced and many animals showed extinguished amplitudes. None of the horses had apparent visual impairment. Histopathologically, all 42 horses had retinal pigment epithelial (RPE) congestion with ceroid-lipofuscin. Retinal degeneration was variable even within the eyes. Thin layer chromatography (TLC) analysis of the RPE and neural retina identified both green and orange emitting fluorescent compounds not found in normal horses. All unsupplemented horses had plasma vitamin E levels <1.0 microg/ml. The potential significance of this report is the pathognomonic role the ocular manifestations exhibit in helping to diagnose equine motor neuron disease.

Animals↗

Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators.

BACKGROUND AND PURPOSE: No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS. METHODS: We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome. RESULTS: The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity. CONCLUSIONS: This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome.

Brain↗

Alcohol-specific socialization, parenting behaviors and alcohol use by children.

OBJECTIVE: This panel study examined the relations between alcohol-specific socialization by parents (monitoring of alcohol use by children, allowing alcohol use by children at home, communicating against alcohol use and setting rules against alcohol use), general dimensions of parenting behavior (responsiveness and demandingness) and alcohol use by children. METHOD: A sample of 488 fifth-grade children reported their perceptions of alcohol-specific socialization by parents, parental responsiveness and parental demandingness. These variables were used to predict alcohol use when children in the panel were in seventh grade. RESULTS: Nineteen percent of seventh-grade children reported alcohol use in the past 30 days. Logistic regression analyses indicated that, after accounting for children's age, sex, single parent status, prior use of alcohol and exposure to parental modeling of alcohol use, the odds of alcohol use were significantly greater among children who perceived no parental monitoring of alcohol use, who had been allowed by parents to have a drink with alcohol at home and who perceived relatively low levels of parental demandingness. Rules against alcohol use, parental communication against alcohol use and parental responsiveness were unrelated to the study outcome. CONCLUSIONS: Parental monitoring of alcohol use by children, family norms regarding alcohol use by children at home and parental ability to set and enforce behavioral rules merit consideration as factors that should be modified by prevention programs. There is a need, however, for additional research that further examines the relations between exposure to such parenting behaviors during childhood and alcohol use during adolescence.

Alcohol Drinking↗

Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice.

Systemic administration of brain-derived neurotrophic factor (BDNF) decreases nonfasted blood glucose in obese, non-insulin-dependent diabetic C57BLKS-Lepr(db)/lepr(db) (db/db) mice, with a concomitant decrease in body weight. By measuring percent HbA1c in BDNF-treated and pair-fed animals, we show that the effects of BDNF on nonfasted blood glucose levels are not caused by decreased food intake but reflect a significant improvement in blood glucose control. Furthermore, once established, this effect can persist for weeks after cessation of BDNF treatment. Oral glucose tolerance tests were performed to examine the effects of BDNF on blood glucose control in the fasted state and after an oral glucose challenge. BDNF treatment normalized fasting blood glucose from initially hyperglycemic levels and also showed evidence for beneficial, although less marked, effects on the ability to remove exogenous glucose from blood. One means to lower fasting blood glucose is to reduce the glucose output of peripheral tissues that normally play a part in the maintenance of fasting hyperglycemia. Because the liver is the major endogenous source of glucose in blood during fasting, and because hepatic weight and glucose output are increased in type 2 diabetes, we evaluated the effects of BDNF on liver tissue. BDNF reduced the hepatomegaly present in db/db mice, in association with reduced liver glycogen and reduced liver enzyme activity in serum, supporting the possible involvement of liver tissue in the mechanism of action for BDNF.

Animals↗

A GP prescribing educational intervention involving a medication panel.

AIM: To trial an educational intervention for general practitioners promoting Quality Use of Medicines. METHOD: Twenty-three general practitioners (GPs) from the Brisbane Inner South Division participated in 12 prescribing upskilling sessions over 13 months. The educational intervention utilised an interactive small group, case based approach with panel input from a GP, pharmacist, clinical specialist, consumer with a related diagnosis, and clinical pharmacologist, focusing on areas of nominated interest. Participants also had access to a therapeutic drug management phone service. RESULTS: Twenty-one (91%) participants completed nine or more sessions and a total of 319 of a possible 324 (98.5%) format evaluations were completed on educational sessions three to eleven. Pre and post session multiple choice questions (MCQs) were used to evaluate change in prescribing knowledge for eight of the sessions. All sessions showed a statistically significant improvement post intervention in both individual participant and overall group knowledge scores (p < 0.001). Participant feedback highlighted that: 100% agreed or strongly agreed that the educational content, panel discussion and summaries were relevant to their practice; 80% agreed or strongly agreed that the sessions were helpful in the management of their patients; 85% agreed or strongly agreed that they had gained new knowledge/skills they would apply in their practice. The therapeutic drug management phone service was utilised at least once by 72% of participants. DISCUSSION: The use of an interactive, case based prescribing intervention with medication team input, positively influences GP prescribing knowledge and management intent.

Australia↗

The effect of perceived control over eating on the life satisfaction of women and men: results from a community sample.

OBJECTIVE: To test whether overweight, or perception of lack of control over eating, or both, contributed to the level of life satisfaction for women and men in a random sample of community-dwelling adults. METHOD: This study examined the effects of body mass index (BMI) and perceived control over eating on life satisfaction for women and men in a community-based sample of 1,069 women and 963 men. RESULTS: For women, both lack of perceived eating control and higher BMI were associated with less life satisfaction, and lack of control over eating was the more important predictor. For men, only lack of perceived eating control was associated with less life satisfaction. Furthermore, for both women and men, the contribution of eating control to life satisfaction was unaffected by BMI, that is, the life satisfaction of heavier people was not more affected by perceived control over eating than was the life satisfaction of lighter people. DISCUSSION: These findings suggest that psychological issues related to eating and weight can affect global aspects of well-being.

Adolescent↗

Molecular characterization of Warthin tumor.

OBJECTIVE: Warthin tumor of the salivary gland is composed of oncocytic epithelium with a prominent follicular lymphoid infiltrate. The purpose of this study was to characterize the clonality of this lymphoid component by means of polymerase chain reaction technology. STUDY DESIGN: DNA was isolated from paraffin-embedded tissue from 20 cases of typical Warthin tumor of the salivary gland and amplified by polymerase chain reaction to assess B- and T-cell clonality. RESULTS: No dominant clonal populations were identified in any tumor. However, minor clonal expansions of both B and T cells were detected in up to 50% of tumors (immunoglobulin H, 50%; T-cell antigen receptor beta, 10%; T-cell antigen receptor gamma, 5%). No tumors showed evidence of bcl-2 proto-oncogene translocation, whereas 95% contained detectable Epstein-Barr virus DNA. CONCLUSION: The B- and T-cell components of Warthin tumor are polyclonal with oligoclonal expansion of both T and B cells in some lesions.

Adenolymphoma↗