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Biomedical subjects

G M Brown

Publications and source records attributed to G M Brown.

At least 19 recordsLinked to original sources
PubMed2005

Photochemical hydrosilylation of 11-undecenyltriethylammonium bromide with hydrogen-terminated Si surfaces for the development of robust microcantilever sensors for Cr(VI).

We report a novel approach to the design and development of microcantilever sensors in which photochemical hydrosilylation is used to modify the microcantilever surface. This process enables individual microcantilevers in multicantilever array chips to be modified separately by focusing the activating UV light sequentially on each particular cantilever. Photochemical hydrosilylation of 11-undecenyltriethylammonium bromide with hydrogen-terminated silicon microcantilever surfaces was carried out to yield a robust quaternary ammonium terminated organic monolayer suitable for chromate detection. The surface functionalities retain their affinity toward Cr(VI), and the organic monolayer is dense enough to generate significant surface stress upon subsequent adsorption of chromate ions from aqueous solutions.

Letter↗
PubMed2004

Observation of the surface stress induced in microcantilevers by electrochemical redox processes.

The potential-induced surface stress of a solid electrode was investigated in an electrochemical cell. Gold-coated atomic force microscopy microcantilevers were used as working electrodes to measure the current-potential response (by cyclic voltammetry) and simultaneous bending characteristics in solutions of NaNO3 and K3Fe(CN)6/NaNO3. The observed changes of differential surface stress at a microcantilever electrode were attributed to electrochemical-potential-induced changes in surface charge density, ion adsorption/desorption, and electron transfer across the electrode surface. The potential dependent change in stress shows promise for the study of microscopic properties at the solid-electrolyte interface.

Journal Article↗
PubMed2003

Gene regulation of melatonin and dopamine receptors during eye development.

To gain insight into the role of melatonin and dopamine in retinal development, gene expression of two melatonin receptors, MT1 and MT2, as well as five dopamine receptors, D1, D2, D3, D4 and D5, in the rat eye was analyzed by reverse transcription-polymerase chain reaction across various developmental stages. MT1 transcript levels reached maximum levels at embryonic day (E) 16 and then decreased gradually until reaching adult levels by postnatal day (P) 14. MT2 transcript levels similarly peaked at E16, but then decreased dramatically until birth to its lowest levels, which were maintained throughout the postnatal period. Thus, gene expression of both the MT1 and MT2 receptors showed a striking inverse correlation with maturation of the eye. In contrast to melatonin receptors, gene expression of all dopamine receptor subtypes, except for D3, showed only an increase as development proceeds with highest levels in adulthood. The D3 message was not detected throughout the developmental period examined. Gene expression of D1-like receptors, D1 and D5, showed a substantial increase to adult levels during the fetal period at E16 and E20, respectively. Transcript levels of D2-like receptors, D2 and D4, on the other hand, were not detected before birth but increased significantly to adult levels by P7 and P14, respectively. The present findings suggest the presence of unique developmental mechanisms by which transcription of various G protein-coupled receptors are regulated in the eye.

Aging↗
PubMed2003

Attitudes to the treatment of chronic anal fissure in ano after failed medical treatment.

OBJECTIVE: The treatment of chronic fissure may be medical or surgical. Indications for assessment, which is the better treatment and under what circumstances, are vital for the appropriate management. The aim of the study was to assess the management of this condition by an expert group of surgeons. METHODS: Consultant members of the Association of Coloproctology of Great Britain and Ireland (n=452) were approached and requested to answer a preset multiple-choice questionnaire. The questionnaire was designed to assess their management strategy and their approach to investigation and treatment under different clinical situations. RESULTS: The overall response was 78% (n = 356). Medical treatment was the first line treatment in 95% of the responders. Lateral anal sphincterotomy without pre-operative endoanal ultrasound and/or anorectal physiology was performed by 57%. Anal dilatation was performed selectively by 36% but only 35% of these would perform a pre-operative endoanal ultrasound or anorectal physiology. CONCLUSION: In the selected group of clinicians lateral anal sphincterotomy remains the procedure of choice in both sexes. Pre-operative assessment using endoanal ultrasound and anorectal physiology is used selectively especially in postpartum women. Anal dilatation remains a subjective procedure and though used selectively, is performed without pre-operative endoanal ultrasound and/or anorectal physiology in majority of cases.

Adult↗
PubMed2001

Age-related changes in the sulphation of the chondroitin sulphate linkage region from human articular cartilage aggrecan.

The chondroitin sulphate (CS) linkage regions have been isolated from human articular cartilage aggrecan (from 10- to 72-year-olds) by chondroitin ABC endolyase digestion and size-exclusion chromatography. Linkage region hexasaccharides have been characterized and their abundance estimated by high-pH anion-exchange chromatography. The basic structure for the CS linkage region oligosaccharides identified from human aggrecan is as follows: DeltaUA(beta1-3)GalNAc[0S/4S/6S](beta1-4)GlcA(beta1-3)Gal[0S/6S](beta1-3)Gal(beta1-4)Xyl, where DeltaUA represents 4,5-unsaturated hexuronic acid, 4S and 6S represent an O-ester sulphate group on C-4 and C-6 respectively, and 0S represents zero sulphation. There are significant age-related changes in the abundance of the various N-acetylgalactosamine (GalNAc) sulphation forms identified, occurring up to approx. 20 years old. During the period from 10 to 20 years old the level of GalNAc 6-sulphation at the linkage region increases from approx. 43% to approx. 75%, while there is a corresponding reduction in unsulphated (approx. 30% to approx. 20%) and 4-sulphated (approx. 25% to approx. 6%) GalNAc residues. There is also an increase in the incidence of linkage region galactose 6-sulphation (approx. 2% to approx. 10%) which was only observed in linkage regions with GalNAc 6-sulphation. Beyond 20 years old there are few changes in the relative abundance of these GalNAc sulphation variants; however, there is a slight increase in the abundance of 6-sulphation between approx. 20 years old and approx. 40 years old and a slight decrease in its abundance beyond approx. 40 years old. Our data show that in the majority of chains from tissues of all ages the GalNAc residue closest to the linkage region is 6-sulphated, but the level of GalNAc 6-sulphation within the linkage region is lower than the average level observed within the repeat region.

Adolescent↗
PubMed2001

Regeneration of perchlorate (ClO4-)-loaded anion exchange resins by a novel tetrachloroferrate (FeCl4-) displacement technique.

Selective ion exchange is one of the preferred treatment technologies for removing low levels of perchlorate (ClO4-) from contaminated water because of its high efficiency and minimal impact on water quality through the addition or removal of chemicals and nutrients. However, the exceptionally high affinity of ClO4- for type I anion-exchange resins makes regeneration with conventional NaCl brine extremely difficult and costly for practical applications. The present study entails the development of a novel regeneration methodology applicable to highly selective anion-exchange resins. Tetrachloroferrate (FeCl4-) anions, formed in a solution of ferric chloride and hydrochloric acid (e.g., 1 M FeCl3 and 4 M HCl), were found to effectively displace Cl04- anions that were sorbed on the resin. A mass-balance analysis indicated that a nearly 100% recovery of ion-exchange sites was achieved by washing with as little as approximately 5 bed volumes of the regenerant solution in a column flow-through experiment There was no significant deterioration of the resin's performance with respect to ClO4- removal after repeated loading and regeneration cycles. Thus, the new methodology may offer a cost-effective means to regenerate ClO4- -loaded resins with improved regeneration efficiency, recovery, and waste minimization in comparison with conventional brine regeneration techniques.

Anion Exchange Resins↗
PubMed2001

Ultrasensitive detection of CrO4(2-) using a microcantilever sensor.

Microcantilevers modified with a self-assembled monolayer respond sensitively to specific ion concentrations. Here, we report the detection of trace amounts of CrO4(2-) using microcantilevers modified with a self-assembled monolayer of triethyl-12-mercaptododecylammonium bromide. The self-assembled monolayer was prepared on a silicon microcantilever coated with a thin layer of gold on one side. The microcantilever undergoes bending due to sorption of CrO4(2-) ions on the monolayer-modified side. It was found that a concentration of 10(-9) M CrO4(2-) can be detected using this technology in a flow cell. Other anions, such as Cl-, Br-, CO3(2-) (or HCO3-), and SO4(2-), have minimal effect on the deflection of this cantilever. The mechanics of the bending and the chemistry of cantilever modification are discussed.

Journal Article↗
PubMed2001

Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O PET study of the neuromodulatory effects of clonidine.

BACKGROUND: Noradrenergic dysfunction has been consistently implicated in depression. Much of the evidence, though, has been indirect, such as an attenuated growth hormone response to the alpha2-adrenoceptor agonist clonidine. To more directly examine central functioning of the noradrenergic system in depression, we have used [15O] H2O positron emission tomography (PET) to measure cerebral blood flow (rCBF) in combination with clonidine as a neuromodulatory probe. METHODS: Subjects were six depressed and six healthy women, medication free and matched for age and phase of menstrual cycle. Two PET scans were acquired at baseline and two scans at 20 and 35 min following an intravenous clonidine infusion of 1.4 microg/kg while subjects performed a sustained attention task. RESULTS: The growth hormone response did not show a significant difference between groups. However, PET results revealed a difference in the right superior prefrontal cortex that was resolved as an interaction from decreased rCBF in healthy control subjects but increased rCBF in the depressed group, which was not accounted for by differences in task performance. CONCLUSIONS: This differential effect of clonidine in the right prefrontal cortex provides in vivo evidence of noradrenergic dysfunction in depression, which we postulate arises from functionally impaired presynaptic alpha2-adrenoceptors as well as regionally "supersensitive" postsynaptic cortical alpha2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed2001

Characterization of oligosaccharides from the chondroitin sulfates. (1)H-NMR and (13)C-NMR studies of reduced disaccharides and tetrasaccharides.

Chondroitin sulfates were fragmented using the enzymes chondroitin sulfate ABC endolyase and chondroitin ACII lyase; both disaccharide and tetrasaccharide fragments were isolated after reduction to the corresponding 2-deoxy-2-N-acetylamino-D-galactitol (GalNAc-ol) form. These have the structures: Delta UA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)L-IdoA(alpha 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol and Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, where Delta UA represents a 4,5-unsaturated hexuronic acid (4-deoxy-alpha-Lthreo-hex-4-enepyranosyluronic acid) and 6S/4S/2S represent O-ester sulfate groups at C6/C4/C2 sites. Complete (1)H-NMR and (13)C-NMR data are derived for these species, which may help to alleviate some of the significant difficulties resulting from signal complexity that are currently hindering the characterization and assignment of major and minor structural components within chondroitin sulfate and dermatan sulfate polymers.

Animals↗
PubMed2001

The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study.

OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.

Adolescent↗
PubMed2001

Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin.

The pineal hormone melatonin plays an important role in the neuroendocrine control of reproductive physiology, but its effects on hypothalamic GnRH neurons are not yet known. We have found that GT1-7 GnRH-secreting neurons express membrane-bound G protein-coupled melatonin receptors, mt1 (Mel-1a) and MT2 (Mel-1b) as well as the orphan nuclear receptors ROR alpha and RZR beta. Melatonin (1 nM) significantly downregulates GnRH mRNA levels in a 24-h cyclical manner, an effect that is specifically inhibited by the melatonin receptor antagonist luzindole (10 microM). Repression of GnRH gene expression by melatonin appears to occur at the transcriptional level and can be mapped to the GnRH neuron-specific enhancer located within the 5' regulatory region of the GnRH gene. Using transient transfection of GT1-7 cells, downregulation of GnRH gene expression by melatonin was further localized to five specific regions within the GnRH enhancer including -1827/-1819, -1780/-1772, -1746/-1738, -1736/-1728, and -1697/-1689. Interestingly, the region located at -1736/-1728 includes sequences that correspond to two direct repeats of hexameric consensus binding sites for members of the ROR/RZR orphan nuclear receptor family. To begin to dissect the mechanisms involved in the 24-h cyclical regulation of GnRH transcription, we have found that melatonin (10 nM) induces rapid internalization of membrane-bound mt1 receptors through a beta-arrestin 1-mediated mechanism. These results provide the first evidence that melatonin may mediate its neuroendocrine control on reproductive physiology through direct actions on the GnRH neurons of the hypothalamus, both at the level of GnRH gene expression and through the regulation of G protein-coupled melatonin receptors.

Animals↗
PubMed2001

Maternal mortality: clinical implications of international perspectives.

Although the root causes of maternal mortality (MM) in nonindustrialized nations differ from those in the United States, some approaches to improving MM may be universal. Access to care is an issue in the United States aswell as internationally. There are many steps providers can take to improve access, from reducing language an cultural barriers, to taking adequate histories, to addressing such chronic conditions as obesity, diabetes, an hypertension before conception. When providers obtain adequate information before or during pregnancy, they can assess patient risk, plan educational and medical interventions, and introduce preventive measures that can reduce MM-in both the United States and the developing world.

Developed Countries↗
PubMed2000

Increased left posterior parietal-temporal cortex activation after D-fenfluramine in women with panic disorder.

It is unclear whether the functional changes found in panic disorder reflect disturbed physiology of particular neurotransmitters. One method of investigating altered neurotransmission is to assess regional brain activations in response to agonist challenges. D-Fenfluramine is a medication that induces neuronal release of serotonin. Using ¿15OH(2)O and positron emission tomography (PET), measurements of regional cerebral blood flow (rCBF) were done at t=-20, -5, +20 and +35 relative to the IV D-fenfluramine injection (t=0) in nine panic-disordered and 18 healthy subjects. Subjects were otherwise healthy, right-handed, non-smoking and not taking psychotropic medication. ¿15OH(2)O PET scans were assessed with Statistical Parametric Mapping using individual global cerebral blood flow as a covariate. Comparisons of the (baseline) first two scans between healthy and panic-disordered subjects showed a decreased rCBF in the left posterior parietal-superior temporal cortex in the patient group. Fenfluramine-induced increases as defined by the last two scans minus the first two scans were compared between groups and a significantly greater increase in the same left posterior parietal-superior temporal region was found in panic-disordered subjects. Consistent with this finding, differences between the last two scans (post-fenfluramine) of the healthy and panic-disordered subjects showed an increased rCBF in the left superior temporal cortex in panic-disordered subjects. Functional pathology in the left parietal-superior temporal cortex in panic disorder may be related to abnormal modulation by serotonin.

Adolescent↗
PubMed2000

Potential involvement of mt1 receptor and attenuated sex steroid-induced calcium influx in the direct anti-proliferative action of melatonin on androgen-responsive LNCaP human prostate cancer cells.

Melatonin, a pineal secretory product, has been shown to exert a direct anti-proliferative action on the androgen-sensitive LNCaP prostate cancer cell line through hitherto undefined mechanisms. In this communication, expression of mt1 melatonin receptor protein in human prostate cancer tissues and LNCaP cells was demonstrated by immunohisto(cyto)chemistry and western blotting, hence supporting the use of LNCaP cell line as a model for the study of melatonin signaling in prostate cancer cell growth. Using 3H-thymidine incorporation assay, LNCaP cell proliferation was inhibited by 2-iodomelatonin, a high-affinity melatonin receptor agonist. Furthermore, melatonin inhibited 3H-thymidine incorporation into LNCaP cells and attenuated 5alpha-dihydrotestosterone (DHT) or 17beta-estradiol (E2)-induced stimulation of LNCaP cell proliferation at physiological and pharmacological concentrations. Similar concentration-dependent inhibition of sex steroid-induced stimulation of thymidine incorporation into LNCaP cells by 2-iodomelatonin was also observed. Interestingly, attenuation of sex steroid-stimulated calcium influx into LNCaP cells by pharmacological concentrations of melatonin was recorded, whereas 2-iodomelatonin had no effect on cytosolic calcium changes induced by sex steroids. In addition, proliferative and cytosolic calcium changes were associated with inhibition of total prostate-specific antigen (PSA) production by LNCaP cells at high physiological and pharmacological concentrations of melatonin. Our data suggest that activated mt1 receptor and attenuated sex steroid-induced calcium influx are two important mechanisms mediating the direct anti-proliferative action of melatonin on androgen-responsive human prostate cancer cells.

Adenocarcinoma↗
PubMed2000

Influence of sensitivity on response bias in taste and audition.

A detection theoretic analysis was employed to examine sensitivity and response bias in two modalities. In Experiment 1, 6 tasters made same-different judgments about the concentration of either sucrose or quinine in pairs of tonic water samples. The beverages were colored, but color was not predictive of the concentration of the sweet or bitter ingredient. When same-different ratings were collapsed to approximate the outcome of a categorical decision, tasters with poorer sensitivity appear to have adopted more extreme response criteria than did tasters with greater sensitivity, irrespective of taste quality, color, or whether pairs of solutions comprised the same or different colors. In Experiment 2, 3 individuals discriminated pairs of 1000-Hz sinusoids differing in amplitude. Six amplitude differences were tested. Rating-scale versions of two paradigms: The single-interval yes-no task and the two-interval same-different task were used to measure sensitivity and bias. There was a preponderance of "same" responses in the same-different task. Estimates of bias obtained from collapsed ratings in both tasks were unaffected by sensitivity, but a consideration of the range over which sets of criteria were spread suggested a general tendency toward more conservative response biases as sensitivity declined.

Adult↗
PubMed2000

Use of slow-release melatonin in treatment-resistant depression.

OBJECTIVE: To examine antidepressant augmentation with and hypnotic effects of slow-release melatonin (SR-melatonin) in patients with treatment-resistant depression. DESIGN: Open-label trial. SETTING: Tertiary care outpatient depression clinic. PATIENTS: Nine outpatients who had failed to respond to 2 or more 8-week trials of antidepressant medication. INTERVENTIONS: Patients received SR-melatonin 5 mg per day for the first 2 weeks and 10 mg per day for the final 2 weeks, in addition to their antidepressant medication. OUTCOME MEASURES: Structured Clinical Interview for DSM-IV, Axis 1 Disorders, Hamilton Rating Scale for Depression (HRSD), Beck Depression Inventory, Response Style Questionnaire, sleep and fatigue measures. RESULTS: One patient was excluded after 1 week because of the development of a mixed affective state. In the remaining 8 patients there was a 20% mean decrease in HRSD scores after 4 weeks of treatment, with no individual achieving an improvement of 50% or more. There was a 36% decrease on the 3-item HRSD related to insomnia, with 4 of 8 patients showing at least a 50% improvement on this measure. The greatest decrease in insomnia occurred during the last 2 weeks of the study, following the increase in dosage to 10 mg per day of SR-melatonin. Patients also reported significantly lower levels of fatigue post-treatment. CONCLUSIONS: SR-melatonin may be a useful adjunct for sleep, but does not substantially augment existing antidepressant therapies in some patients with treatment-resistant depression.

Adult↗
PubMed1999

Expression of mt1 melatonin receptor in rat retina: evidence for multiple cell targets for melatonin.

Melatonin is synthesized in the retina at night and acts as a local modulator within this tissue by mediating the effects of darkness. We investigated the expression and localization of the mt1 (Mel1a) melatonin receptor in rat retina in order to disclose the cellular and molecular bases of melatonin's action in the mammalian retina. Western blotting of the mt1 receptor in rat retina exhibited a single immunoreactive band of approximately 37,000 mol. wt, which corresponds to the predicted molecular size of the receptor. The mt1 receptor was immunocytochemically localized to both the inner and outer plexiform layers. During postnatal development, retina from two-week-old rats showed the highest mt1 immunoreactivity; the outer plexiform layer and horizontal cell bodies were strongly immunolabeled, with weaker labeling in the inner plexiform layer. Expression of mt1 receptor messenger RNA in the rat retina was demonstrated by reverse transcription-polymerase chain reaction and in situ hybridization. mt1 receptor transcripts were localized to ganglion cells, amacrine cells and horizontal cells. These results suggest that melatonin influences retinal physiology by acting on multiple retinal cell types, including ganglion, amacrine and horizontal cells, via the mt1 receptor expressed in their processes.

Animals↗