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Biomedical subjects

G M Brown

Publications and source records attributed to G M Brown.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of chronic brofaromine administration on biogenic amines including sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa.

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.

Adolescent↗
PubMed1993

The acute effects of starvation on 6-sulphatoxy-melatonin output in subgroups of patients with anorexia nervosa.

Sequential measures of daytime and nighttime sulphatoxy-melatonin (aMT6s) in 10 female patients with anorexia nervosa (AN) and 12 female patients with concurrent AN with bulimic symptoms (AN + BN) were compared with 13 female control subjects. The AN + BN group displayed a significant increase in aMT6s output in the acutely symptomatic state compared with both AN patients and controls. However, there were no subsequent differences after 7 or 14 days between the two patient groups. The AN + BN group also initially demonstrated a significant increase in daytime output of aMT6s compared to nighttime with a trend toward reversing this pattern after 7 and 14 days. Altered melatonin output may influence the course of illness or reflect greater disruption of circadian rhythm in those anorexic patients who also binge and purge compared to restricting anorexics.

Adolescent↗
PubMed1993

Competitive solid-phase enzyme immunoassay for melatonin in human and rat serum and rat pineal gland.

We describe a solid-phase competitive enzyme immunoassay for determination of melatonin in serum. The detection limit of the assay is 1.0 fmol/well. Low cross-reactivity of the antiserum with other indoles, parallel serum extract dilution and melatonin standard curves, good analytical recovery, and within- and between-assay CVs of 6.4-14.4% provide validation of the assay. Linear regression analysis of melatonin concentrations measured with this assay (y) and with a commercial 3H RIA (x) in 88 sera yielded the relation y = 0.62 x - 0.76, Sy/x = 0.03. Values for melatonin in serum samples from healthy subjects are lower during the day than during the night. Melatonin response in rat serum and pineal gland to isoproterenol injection is similar to published RIA data. The analytical procedure is also simple. Thus, the assay should have practical applications in investigation of pineal function in both clinical and basic studies.

Animals↗
PubMed1993

Normal fetal outcome in a pregnancy with central nervous system toxoplasmosis and human immunodeficiency virus infection. A case report.

A pregnant woman was diagnosed with central nervous system toxoplasmosis and human immunodeficiency virus infection. Diagnosis was made by evaluating computed tomography scan results and toxoplasma antibody titers. The patient was treated with pyrimethamine and sulfadiazine, with an excellent fetal outcome. She responded well to this regimen but developed a delayed exanthematous hypersensitivity reaction. Treatment with a substitute regimen resulted in a recurrence of symptoms, leaving undesirable neurologic deficits.

AIDS-Related Opportunistic Infections↗
PubMed1993

Reactive pleural inflammation caused by intratracheal instillation of killed microbes.

To investigate the pleural leucocyte response to severe alveolar inflammation, heat-killed Corynebacterium parvum were instilled intratracheally into the lungs of PVG rats and pleural lavage was performed. Polymorphonuclear neutrophils are not normally resident in the pleural space but were found transiently after intratracheal instillation of C. parvum. Macrophages increased gradually in the pleural space following instillation, reaching a peak at day 5. The activity of plasminogen activator inhibitor in the pleural leucocyte supernatants was increased at day 1, but returned to control levels by day 5. The activities of interleukin-1 and tumour necrosis factor secreted by pleural leucocytes were decreased compared with control pleural leucocytes at day 1 and were further reduced at day 5. The analysis of particle translocation showed that intratracheally instilled C. parvum and fluorescent beads with or without C. parvum did not reach the pleural space. We hypothesize that pleural inflammation resulting from C. parvum-induced inflammation in the lung is the result of transfer of a diffusible factor from the adjacent parenchyma.

Animals↗
PubMed1992

Mutagenic DNA repair in Escherichia coli. XXI. A stable SOS-inducing signal persisting after excision repair of ultraviolet damage.

Mutations to streptomycin resistance induced by ultraviolet light in Escherichia coli can lose their susceptibility to photoreversing light during excision repair and in the absence of chromosomal replication and protein synthesis, i.e., under conditions where SOS induction cannot occur. Using fusions of lac with sulA and umuC we have shown that after excision of UV damage in the presence of chloramphenicol there is a persisting, relatively stable signal capable of inducing SOS genes when protein synthesis is subsequently permitted. The persisting signal is formed roughly in proportion to the square of the UV dose and is about 30% photoreversible. It is suggested that the persisting SOS-inducing signal comprises a UV photoproduct (the target lesion) opposite a gap in the opposing DNA strand, and is formed by excision of one (the ancillary lesion) of a pair of closely opposed photoproducts. Calculations suggest that as few as two or three such configurations in a cell can lead to induction of sulA when protein synthesis is permitted. It is not clear whether these configurations can directly induce the SOS system because of their region of single-stranded DNA or whether the ultimate SOS-inducing signal is a more extensive single-stranded region formed when such configurations encounter a replication fork. Photoproduct/gap configurations have been previously suggested to be potentially mutagenic. UV-induced mutations to streptomycin resistance are mostly at A:T sites and are not photoreversible in fully SOS-induced bacteria in the absence of excision repair, indicating that they are not targeted at cyclobutane-type pyrimidine dimers. In SOS-induced excision-proficient bacteria there is about 39% photoreversibility which is rapidly lost after UV. This photoreversibility is attributed to many ancillary lesions being cyclobutane-type pyrimidine dimers which are excised leading to the exposure of target lesions on the opposing strand which, at these particular sites, are mostly non-photoreversible photoproducts.

Bacterial Proteins↗
PubMed1992

Characterization of 2-[125I]iodomelatonin-binding sites in quail testes at mid-light and mid-dark.

The binding and pharmacological characteristics of 2-[125I]iodomelatonin binding sites in testis membrane preparations of quails were examined. Scatchard analyses yielded an equilibrium dissociation constant (Kd) of 46.6 +/- 8.6 pmol/l and maximum binding capacity (Bmax) of 2.77 +/- 0.20 fmol/mg protein for the gonadal 2-[125I]iodomelatonin binding sites. Except for melatonin, 6-chloromelatonin, 2-iodomelatonin and N-acetylserotonin, all compounds tested elicited no significant inhibition of radioligand binding. Significant diurnal variations were detected in serum melatonin levels of 24-week-old quails while no diurnal difference was detected in the affinities or densities of the gonadal 2-[125I]iodomelatonin binding sites in quails. Results of the present study suggest possible direct gonadal action by pineal melatonin in birds.

Animals↗
PubMed1992

Immobilization of DNA for scanning probe microscopy.

Reproducible scanning tunneling microscope and atomic force microscope images of entire molecules of uncoated plasmid DNA chemically bound to surfaces are presented. The chemically mediated immobilization of DNA to surfaces and subsequent scanning tunneling microscope imaging of DNA molecules demonstrate that the problem of molecular instability to forces exerted by the probe tip, inherent with scanning probe microscopes, can be prevented.

DNA, Bacterial↗
PubMed1992

A sub-population of keratan sulphates derived from bovine articular cartilage is capped with alpha(2-6)-linked N-acetylneuraminic acid residues. Affinity chromatography using immobilized Sambucus nigra lectin and characterization using 1H n.m.r. spectroscopy.

Alkaline borohydride-reduced keratan sulphate (KS) chains derived from bovine femoral head cartilage were fractionated by lectin affinity chromatography with Sambucus nigra agglutinin (SNA) into binding and non-binding populations. Analysis of the SNA-binding and non-binding KS chains using 600 MHz 1H n.m.r. spectroscopy showed that the former population contained alpha(2-6)-N-acetylneuraminic acid residues and the latter contained primarily alpha(2-3)-N-acetylneuraminic acid residues as chain terminators. Both populations contained a similar proportion of alpha(2-3)-N-acetylneuraminic acid residues within their protein-linkage regions, and similar sulphation and fucosylation levels. Analysis of these two fractions by gel-permeation chromatography (g.p.c.) on a TSK-30 XL column showed them to have the same size distributions. It was concluded from the n.m.r. spectra and g.p.c. data that the populations differed primarily in the mode of linkage of the chain-terminating sialic acids.

Animals↗
PubMed1992

Degradation of articular cartilage keratan sulphates using hydrazinolysis and nitrous acid. Environment of fucose residues.

Alkaline borohydride-reduced keratan sulphate (KS) chains from bovine articular cartilage (6-8-year-old animals) were fragmented by an anhydrous hydrazine/nitrous acid procedure, previously used on KS by Hopwood & Elliott to isolate the major disaccharides from the poly-N-acetyl-lactosamine repeat sequence [Hopwood & Elliott (1983) Carbohydr. Res. 117, 263-274]. The resulting oligosaccharides were reduced with NaB3H4 or NaBH4 and subjected to ion-exchange chromatography on a Nucleosil 5SB column. In addition to the major disaccharides, two fucose-containing oligosaccharides were examined by high-field 1H n.m.r. spectroscopy, and shown to have the following structures (where AnManOH is 2,5-anhydro-D-mannitol): [formula: see text] It is evident that the presence of fucose protects the N-acetylglucosamine residue from de-N-acetylation, and therefore fragments are produced which preserve the immediate environment of the fucose residue. It may be of biosynthetic significance that these two oligosaccharides contain an unsulphated galactose on the non-reducing side of the fucose residue. The hydrazine/nitrous acid/NaB3H4 method followed by h.p.l.c. provides a sensitive fingerprinting technique for the assay of KS composition and sub-populations.

Animals↗
PubMed1992

Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization.

Fibre length has been shown to be an important factor in the ability of respirable fibres to cause lung fibrosis and cancer. We have reported that a long sample of amosite asbestos is more carcinogenic and fibrogenic than a short sample of similar diameter. These amosite asbestos samples were studied with regard to their ability to stimulate the release of the pro-inflammatory cytokine tumour necrosis factor (TNF) from rat alveolar macrophages in vitro. The long fibre sample was found to stimulate substantially greater release of the cytokine than the short sample. Furthermore, on treatment of the fibres with rat immunoglobulin G (IgG), there was an increase in the ability of both the long and the short sample to stimulate TNF secretion, although the long sample retained by far the greatest activity. Coating of the fibres with a range of other proteins had no substantial effect on their ability to stimulate TNF secretion. Quartz and titanium dioxide (TiO2) were included as control particles and the TNF-stimulating activity of quartz was notably increased by opsonization with IgG. TiO2 showed a similar low activity to that of the short fibre sample of amosite but this again could be modestly increased by opsonization with IgG. The simulation of TNF release caused by treatment with immunoglobulin-opsonized long fibre amosite could be inhibited by treatment of the macrophages with the protein kinase C-inhibitor staurosporine. The study demonstrates a fibre length-related ability to stimulate cytokine secretion by alveolar macrophages, and its enhancement by opsonization with IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Activated human peripheral blood neutrophils produce epithelial injury and fibronectin breakdown in vitro.

The ability of peripheral blood neutrophils to injure elements of the alveolar septum was assessed. Experiments consisted of activating previously isolated neutrophils (PMNs) with a soluble (phorbol myristate acetate, PMA) and a particulate (zymosan) trigger, and measuring detachment of 51Cr-labeled epithelial cells. In addition, the mechanisms of epithelial injury were investigated by including anti-proteinase and antioxidants in the system. Untriggered PMNs produced only slight detachment injury to epithelial cells at two effector-target cell ratios, this effect being dramatically increased after triggering with PMA; zymosan caused triggering but less than was produced by PMA. Alpha-1-protease inhibitor produced a decrease in detachment when both PMA- and zymosan-triggered cells were the effectors; superoxide dismutase did not significantly reduce detachment. The ability of triggered PMNs to cause proteolysis of fibronectin, as measured in a radiolabeled fibronectin matrix degradation assay, was related to their triggerability in the detachment assay, zymosan being largely ineffective in triggering enhanced proteolysis. These findings suggest that fibronectin is important in maintaining the integrity of the alveolar epithelial surfaces. Furthermore, in inflamed alveoli, activated PMNs can release proteinases, which cause degradation of this matrix component leading to compromise of the alveolar epithelial barrier.

Cell Adhesion↗
PubMed1992

Age-associated changes and sex differences in urinary 6-sulphatoxymelatonin circadian rhythm in the rat.

The circadian rhythm of 6-sulphatoxymelatonin (aMT6s) excretion has been determined in male and female rats at 3 weeks and at 2, 8, 14 and 20 months of age. All animals have a pronounced circadian pattern of aMT6s excretion under a 12 hour dark: 12 hour light cycle. A significant increase in aMT6s excretion is observed from 3 weeks to 14 months followed by a decrease at 20 months. There is a highly significant correlation between aMT6s excretion and body weight (r = 0.73 for female rats and r = 0.74 for male rats; p values are all less than 0.001). Thus, a decrease in aMT6s excretion associated with increasing age occurs when body weight is taken into consideration. aMT6s excretion is higher in males at 3 weeks and at 2 and 8 months of ages. Urinary testosterone in male rats and estradiol in female rats increase from 3 weeks to 8 months and decrease at older ages. These data suggest that increase of body weight from 3 weeks to 14 months is an important factor responsible for the age-related alteration. The sex differences in aMT6s excretion in younger rats may be associated with their sex hormonal milieu.

Age Factors↗
PubMed1992

Effect of chronic antidepressant treatment with adinazolam and desipramine on melatonin output.

Output of melatonin or its main metabolite, 6-sulphatoxy melatonin, provides an index of noradrenergic activity in the pineal gland, which is of interest in major depression and during its treatment with antidepressants. Fifteen female depressed outpatients did not differ in levels of 24-hour urinary 6-sulphatoxy melatonin compared with 13 female control subjects. However, a subgroup of the depressed patients (n = 9) who were treated with desipramine showed a significant elevation of 6-sulphatoxy melatonin levels after 1 week of treatment and a return to baseline levels after 6 weeks. There was also a significant negative correlation between 6-sulphatoxy melatonin levels and symptom severity as measured by the Hamilton Rating Scale for Depression after 3 weeks of treatment with desipramine. The other subgroup of depressed patients (n = 6) were treated with adinazolam, a benzodiazepine with antidepressant properties. Despite comparable antidepressant effects to those achieved with desipramine, adinazolam was not associated with any apparent change in 6-sulphatoxy melatonin output during 6 weeks of treatment. There was also no correlation between 6-sulphatoxy melatonin levels and symptom severity.

Adult↗
PubMed1992

Urinary catecholamines and cortisol in parasuicide.

A relationship of urinary catecholamines and of urinary free cortisol with violent suicide attempts has been reported. We have reexamined this issue in patients within 24 hours of hospital admission. Suicide attempters had significantly higher norepinephrine (NE: mean +/- SD = 58.3 +/- 27.0 micrograms/24 hours; n = 27) than did control patients with suicidal ideation (mean +/- SD = 37.1 +/- 21.3; n = 10). Among suicide attempters, those who used physical means had the highest NE levels (mean +/- SD = 69.7 +/- 21.3) and those who took overdoses of antidepressants (mean +/- SD = 51.9 +/- 17.3; n = 6), benzodiazepines (mean +/- SD = 65.1 +/- 29.7; n = 5), or miscellaneous drugs (mean +/- SD = 59.1 +/- 36.5; n = 11) had lower NE values. In contrast to NE, urinary dopamine (mean +/- SD = 402.6 +/- 392 micrograms/24 hours, epinephrine (EPI: mean +/- SD = 14.3 +/- 4.0 micrograms/24 hours), the NE/EPI ratio (mean +/- SD = 8.3 +/- 0.9), urinary free cortisol (mean +/- SD = 157.9 +/- 11.5 micrograms/24 hours) and serum cortisol (mean +/- SD = 35.0 +/- 13.1 nM/l) did not differ between groups. There were no group differences in age (mean +/- SD = 36.3 +/- 16.5 years), Beck Depression Inventory score (mean +/- SD = 26.3 +/- 12.9), Beck Hopelessness Scale score (mean +/- SD = 10.0 +/- 5.6), Beck Scale for Suicidal Ideation score (mean +/- SD = 13.6 +/- 9.3), or Hamilton Rating Scale for Depression score (mean +/- SD = 19.5 +/- 9.8). In the four parasuicide groups, there was no difference in suicide intent (mean +/- SD = 13.3 +/- 7.9). These findings indicate that there is increased NE output shortly after suicide attempts. Previous reports of a low NE/EPI ratio in suicidal patients may reflect adaptive changes rather than the acute state of the patient at the time of the attempt.

Adult↗
PubMed1992

Scanning tunneling microscopy of DNA: a novel technique using radiolabeled DNA to evaluate chemically mediated attachment of DNA to surfaces.

pBS+ plasmid deoxyribonucleic acid (DNA) was imaged by scanning tunneling microscopy (STM) after mounting microdroplets by aerosol deposition onto heated epitaxial gold surfaces. However, the instability of the adsorbate to forces exerted by the tunneling tip points out the need for more aggressive bonding of molecules to surfaces. We describe a sensitive assay for the qualitative and quantitative evaluation of chemical agents to influence binding of DNA to surfaces using 32P-labeled pBS+ plasmid DNA. We propose that such an assay can make an important contribution to immobilization techniques prior to STM imaging.

DNA↗