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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 91 records · Page 5Linked to original sources
PubMed1999

Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system.

"Natural" Igs, mainly IgM, comprise part of the innate immune system present in healthy individuals, including antigen-free mice. These Igs are thought to delay pathogenicity of infecting agents until antigen-induced high affinity Igs of all isotypes are produced. Previous studies suggested that the acquired humoral response arises directly from the innate response, i.e., that B cells expressing natural IgM, upon antigen encounter, differentiate to give rise both to cells that secrete high amounts of IgM and to cells that undergo affinity maturation and isotype switching. However, by using a murine model of influenza virus infection, we demonstrate here that the B cells that produce natural antiviral IgM neither increase their IgM production nor undergo isotype switching to IgG2a in response to the infection. These cells are distinct from the B cells that produce the antiviral response after encounter with the pathogen. Our data therefore demonstrate that the innate and the acquired humoral immunities to influenza virus are separate effector arms of the immune system and that antigen exposure per se is not sufficient to increase natural antibody production.

Animals↗
PubMed1999

Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B).

We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa25-44 MAP compared with mice immunized with the 25-44 monomer. Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25-44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa287-301 determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa287-301 peptide. However, immunization with the multivalent mLa287-301 peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa287-301 peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence.

Amino Acid Sequence↗
PubMed1999

Expression and localisation of stanniocalcin 1 in rat bladder, kidney and ovary.

Bony fish use the glycoprotein hormone stanniocalcin (STC) to counteract hypercalcaemia. This is achieved through dual mechanisms involving gill calcium uptake inhibition and stimulation of renal inorganic phosphate reabsorption. Human STC (hSTC-1) shows considerable homology with both rat and mouse STC (mSTC) and their mRNA is expressed in a wide range of tissues. In fish, STC is produced by endocrine glands known as the corpuscles of Stannius but in mammals the widespread expression is suggestive of a paracrine rather than an endocrine role. In order to determine the distribution and strucutral characteristics of hSTC-1, the recombinant protein was expressed in bacteria, purified by metal-ion affinity chromatography, and a study was made of the likely epitopes for raising an antibody. This novel hSTC-1 antibody was used to test the purification protocol. Since the role of mammalian STC is largely unknown, the specific distribution of STC needed to be addressed. To test the specificity of the antibody, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/Western blotting was undertaken in homogenised rat bladder, ovary and kidney.

Amino Acid Sequence↗
PubMed1999

A longitudinal study of psychological adjustment to familial genetic risk assessment for ovarian cancer.

OBJECTIVES: To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6-12 months later. METHODS: Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc. RESULTS: Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up. CONCLUSION: To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up (R = 0.33, P<0.02, R(2) = 11%).

Adaptation, Psychological↗
PubMed1999

Iontophoretic vincristine in the treatment of postherpetic neuralgia: a double-blind, randomized, controlled trial.

The effect of iontophoretic administration of vincristine in the treatment of postherpetic neuralgia (PHN) was investigated in a prospective, double-blind, placebo-controlled trial. Twenty patients with intercostal or lumbar PHN for more than 6 months that was unresponsive to conventional medical therapy were randomized to receive vincristine 0.01% (n = 11) or saline (n = 9), by iontophoresis over 1 hour daily for 20 days. Demographics and median duration of pain were similar in both groups. Pain scores decreased over the treatment period and were significantly lower on day 20 compared to baseline in both groups. Pain relief was described as moderate or greater in 40% of patients with vincristine and 55% of patients with placebo. There was no statistical difference an actual pain scores on day 20 between the two groups. Moderate or greater pain relief was maintained in 30% of patients with vincristine and 33% of patients with placebo at follow-up on day 90. We conclude that iontophoresed vincristine is no better than iontophoresed saline in the treatment of PHN. The maintained improvement in both groups at 3 months follow-up may reflect the natural history of PHN, or might possibly by related to a beneficial effect of iontophoresis.

Aged↗
PubMed1999

Vascular surgical society of great britain and ireland: non-steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm

BACKGROUND: Prostaglandin E2 (PGE2) and inflammatory cytokine levels are raised in the wall of abdominal aortic aneurysms (AAAs) and inflammatory processes appear to contribute to aneurysm expansion. The effect of PGE2 on aortic smooth muscle cells (SMCs) and the influence of indomethacin on AAA growth and production of inflammatory mediators were investigated. METHODS: Proliferation and apoptosis of aortic SMCs cultured with PGE2 were assessed by 5-bromo-2'-deoxyuridine uptake and oligonucleosome enzyme-linked immunosorbent assay. Full-thickness AAA explant cultures were used to measure the secretion of PGE2, interleukin (IL) 1beta and IL-6 in the presence and absence of indomethacin. In a case-control study, the effect of non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, on AAA growth was examined. RESULTS: PGE2 suppressed proliferation (IC50 6 ng ml-1) and increased apoptosis of aneurysm SMCs. Indomethacin diminished secretion of PGE2, IL-1beta and IL-6 by AAA explants (see Table below). The median AAA growth rate of 19 patients taking NSAIDs was 1.8 (range 0-11.2) mm per year compared with 3.2 (0.4-10.9) mm per year in 59 patients (matched for age, sex, smoking and initial AAA diameter) not taking these drugs (P = 0.004). CONCLUSION: PGE2 is produced in the AAA wall in concentrations that are detrimental to SMCs. Indomethacin reduces PGE2, IL-1beta and IL-6 synthesis in aneurysm tissue and NSAIDs appear to reduce AAA growth. These drugs warrant further consideration for the treatment of AAA.

Journal Article↗
PubMed1999

Dissociation, abuse and the eating disorders: evidence from an Australian population.

OBJECTIVE: A number of European and Northern American studies have investigated a possible association between dissociative phenomena, eating disorders, child sexual abuse and self-mutilation. However, there has been little confirmation from other countries and cultures, and the Australian experience of these interrelationships has not previously been studied. METHOD: Dissociative symptomatology and self-reported history of abusive experiences, physical and sexual, were retrospectively studied in a sample of Australian eating disordered patients using a self-report measure, the Dissociation Questionnaire (DIS-Q). RESULTS: As hypothesised, dissociative symptoms were particularly frequent in those who reported child and adult sexual abuse and in those who self-mutilated. A correlation between multiple forms of abuse and higher dissociation scores was only partially upheld. CONCLUSIONS: Interrelationships between victimisation and dissociation are discussed within the context of current knowledge in the field, and brief suggestions for therapeutic strategies are offered.

Adolescent↗
PubMed1999

Cholesterol-lowering effects of dietary fiber: a meta-analysis.

BACKGROUND: The effects of dietary soluble fibers on blood cholesterol are uncertain. OBJECTIVE: This meta-analysis of 67 controlled trials was performed to quantify the cholesterol-lowering effect of major dietary fibers. DESIGN: Least-squares regression analyses were used to test the effect on blood lipids of pectin, oat bran, guar gum, and psyllium. Independent variables were type and amount of soluble fiber, initial cholesterol concentration, and other important study characteristics. RESULTS: Soluble fiber, 2-10 g/d, was associated with small but significant decreases in total cholesterol [-0.045 mmol L(-1).g soluble fiber(-1) (95% CI: -0.054, -0.035)] and LDL cholesterol [-0.057 mmol.L(-1).g(-1) (95% CI: -0.070, -0.044)]. The effects on plasma lipids of soluble fiber from oat, psyllium, or pectin were not significantly different. We were unable to compare effects of guar because of the limited number of studies using 2-10 g/d. Triacylglycerols and HDL cholesterol were not significantly influenced by soluble fiber. Lipid changes were independent of study design, treatment length, and background dietary fat content. CONCLUSIONS: Various soluble fibers reduce total and LDL cholesterol by similar amounts. The effect is small within the practical range of intake. For example, 3 g soluble fiber from oats (3 servings of oatmeal, 28 g each) can decrease total and LDL cholesterol by approximately 0.13 mmol/L. Increasing soluble fiber can make only a small contribution to dietary therapy to lower cholesterol.

Adult↗
PubMed1999

A prospective study of carotenoid intake and risk of cataract extraction in US men.

BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Adult↗
PubMed1999

Solubility of various forms of strontium titanate in lungs: in vitro and in vivo studies.

At the In-Tank Precipitation Facility of the Savannah River Site, strontium and other radionuclides are removed from high-level radioactive waste and sent to the Defense Waste Processing Facility. Strontium removal is accomplished by adsorption using a slurry that includes monosodium titanate, which forms strontium titanate with unknown lung solubility characteristics. The purpose of this study was to determine the solubility of strontium titanate in the form created at the In-Tank Precipitation facility. An in vitro dissolution study was done with a slurry simulant and with several types of strontium titanate, and the results were compared. An in vivo study was also performed with high-fired SrTiO3 in rats. Strontium and titanium were measured by inductively-coupled plasma/atomic emission spectrometry. The data from both studies were used independently to assign the compounds to an absorption type based on criteria specified in ICRP 71. Results of the in vitro studies showed that the Defense Waste Processing Facility simulant should be assigned to Type M and the strontium titanate should be assigned to Type S. Results of the in vivo study verified that SrTiO3 should be assigned to Type S. Lung clearance data of SrTiO3 from rats showed that 85% cleared within the first 24 h and the remaining 15% cleared with a half-time of 130 d. The initial rapid clearance is attributed to deposition in airways as compared to the alveolar region.

Animals↗
PubMed1999

Intersensory conflict between vision and touch: the response modality dominates when precise, attention-riveting judgments are required.

In four experiments, reducing lenses were used to minify vision and generate intersensory size conflicts between vision and touch. Subjects made size judgments, using either visual matching or haptic matching. In visual matching, the subjects chose from a set of visible squares that progressively increased in size. In haptic matching, the subjects selected matches from an array of tangible wooden squares. In Experiment 1, it was found that neither sense dominated when subjects exposed to an intersensory discrepancy made their size estimates by using either visual matching or haptic matching. Size judgments were nearly indentical for conflict subjects making visual or haptic matches. Thus, matching modality did not matter in Experiment 1. In Experiment 2, it was found that subjects were influenced by the sight of their hands, which led to increases in the magnitude of their size judgments. Sight of the hands produced more accurate judgments, with subjects being better able to compensate for the illusory effects of the reducing lens. In two additional experiments, it was found that when more precise judgments were required and subjects had to generate their own size estimates, the response modality dominated. Thus, vision dominated in Experiment 3, where size judgments derived from viewing a metric ruler, whereas touch dominated in Experiment 4, where subjects made size estimates with a pincers posture of their hands. It is suggested that matching procedures are inadequate for assessing intersensory dominance relations. These results qualify the position (Hershberger & Misceo, 1996) that the modality of size estimates influences the resolution of intersensory conflicts. Only when required to self-generate more precise judgments did subjects rely on one sense, either vision or touch. Thus, task and attentional requirements influence dominance relations, and vision does not invariably prevail over touch.

Adult↗
PubMed1999

Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system.

Fibrosis impairs cardiac function. This project has determined the expression and deposition of collagens and fibronectin and cardiac function in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat after inhibition of the renin-angiotensin system. DOCA-salt hypertension was induced in 8-wk-old male Wistar rats by uninephrectomy and administration of DOCA (25 mg every fourth day, subcutaneously) and 1% NaCl in the drinking water for 4 wk. Starting 2 wk after surgery, rats were given either oral captopril (100 mg/kg), oral candesartan cilexetil (2 mg/kg), or subcutaneous spironolactone (50 mg/kg) daily for 2 wk (reversal protocol). DOCA-salt rats failed to gain weight with markedly increased water intake and decreased food intake; drug treatment did not alter these parameters. Systolic BP increased from 116+/-5 mmHg in uninephrectomized rats to 179+/-7 mmHg in DOCA-salt rats and was not decreased by treatment (captopril 172+/-1 mmHg; candesartan 187+/-2 mmHg; spironolactone 178+/-3 mmHg). Captopril, candesartan, and spironolactone reversed the increased collagen I mRNA in DOCA-salt rats; only candesartan reversed the increased collagen III mRNA. Collagen IV mRNA was unchanged in DOCA-salt rats and following treatment. Total fibronectin mRNA increased without changing the proportion of fibronectin mRNA as the fetal isoforms EIIIA and EIIIB. Captopril, candesartan, and spironolactone reversed the increased deposition of perivascular and interstitial collagen in DOCA-salt rats; the increased cardiac fibronectin deposition was reversed by candesartan and spironolactone. Captopril, candesartan, and spironolactone also attenuated or reversed the increased diastolic stiffness and the increased dP/dt but not the increased rate-pressure products in DOCA-salt rat hearts. Thus, inhibition of the renin-angiotensin system reverses cardiac fibrosis in DOCA-salt rats and returns some indices of myocardial function to normal.

Angiotensin Receptor Antagonists↗
PubMed1998

Direct cloning of polymerase chain reaction products into the pinpoint Xa1-T vector protein expression system.

Expression of recombinant proteins is an important method for the characterisation of the structure and function of proteins. However, many expression methods can be difficult, time-consuming and lead to low protein yields. The Promega Pinpoint Xal-T vector system is a unique, one-step cloning method that allows the direct insertion of polymerase chain reaction (PCR) fragments into the expression vector. We describe our experience of the use of this system to clone and express three proteins (8-12 kDa) directly from their PCR products. The proteins are expressed as fusion proteins with a 13 kDa biotinylated tag that can be used for detection of the expressed protein and affinity purification. In our case, the yield was greater than 20 mg per litre of culture. Expressed proteins were purified by Q-Sepharose anion-exchange chromatography and reverse-phase high-performance liquid chromatography (HPLC) instead of the conventional method of avidin-biotin affinity chromatography. The Pinpoint vector proved to be a relatively simple and fast protein expression technique suitable for wide application for expressing recombinant proteins.

Animals↗