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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 379 records · Page 21Linked to original sources

Startle reflex modulation during exposure to pleasant and unpleasant odors.

The eyeblink component of the startle response to acoustic probes was measured while subjects smelled pleasant odors, unpleasant odors, or no odor. Peak electromyogram (EMG) 20-90 ms after probe onset was greater during unpleasant than during no odor conditions; EMGs for pleasant odors did not differ from those for no odor. Base tension in orbicularis oculi muscles was also higher during unpleasant odors. The results for unpleasant odors parallel those found in previous studies that have used a variety of methods for producing negatively valenced experiences. The results for pleasant odors diverge from those of most previous studies, which have found startle attenuation during positively valenced experiences. However, the results may be compatible with the suggestion (Lang, Bradley, & Cuthbert, 1992) that the motivational state that modulates startle involves both valence and arousal. Pleasant odors may require appropriate contexts to produce the positive motivational state required for startle attenuation.

Acoustic Stimulation↗

The drug-of-choice phenomenon psychological differences among drug users who preferred different drugs.

The Eysenck Personality Questionnaire, the Sensation Seeking Scale, and the Brief Symptom Inventory were administered to 125 recovering drug users with three or more months abstinent from drugs. Subjects were divided according to drug preference: opiates, stimulants, marijuana, alcohol, and a polydrug preference. Opiate users were significantly higher in Susceptibility to Boredom. Alcohol misusers compared to a combined stimulant, opiate, and polydrug group were significantly lower in Extroversion and Susceptibility to Boredom. Subjects raised in drug/alcohol-using families scored significantly higher on Neuroticism and on the Positive Symptom Total of the BSI, and had a higher rate of suicidality.

Adolescent↗

Digital image databasing.

A previous two-part article by Simon Brown described the acquisition, editing, compression and initial storage of digital images taken in the clinical studio. Due to the higher-than-expected demand for this clinical service, additional factors had to be considered when dealing with large numbers of images. These included storage on writable compact disc (CD) drives and a system for retrieving images from these devices which was flexible enough to handle the requirements of different specialities and be usable by all medical illustration staff.

CD-ROM↗

Improving quality and resource utilization through the clinical technologist.

This paper reports on the significant benefits realized during the implementation of a Clinical Technologist position in two wards of a major teaching hospital. In addition to efficient and effective handling of specimens and test results, the program results in significant savings and in enhanced patient care.

Cost Savings↗

The 13q- syndrome: the molecular definition of a critical deletion region in band 13q32.

Patients with interstitial deletions of the long arm of chromosome 13 may have widely varying phenotypes. From cytogenetic analysis, we have postulated that there is a discrete region in 13q32 where deletion leads to a syndrome of severe malformations, including digital and brain anomalies. To test this hypothesis at the molecular level, we have studied the deletions in 17 patients; 5 had severe malformations, while the remaining 12 had only minor malformations. Our results indicate that the deletions in the severely affected patients all involve an overlapping region in q32, while the deletions in the mildly affected patients include some, but not all, of this overlapping region. Our findings are consistent with the hypothesis that the severely malformed 13q- phenotype results from the deletion of a critical region in 13q32. This region is presently defined as lying between D13S136 and D13S147 and is on the order of 1 Mb in size.

Abnormalities, Multiple↗

Distinct apoptotic responses in maturation sensitive and resistant t(15;17) acute promyelocytic leukemia NB4 cells. 9-cis retinoic acid induces apoptosis independent of maturation and Bcl-2 expression.

Apoptosis has been investigated in NB4, a t(15;17) human promyelocytic leukemia cell line susceptible to maturation by all-trans or 9-cis retinoic acid, and in NB4-R1, a subclone resistant to differentiation. Maturation resistant NB4-R1 cells exhibited an onset of cell death after RA-treatment (72 h), whereas maturation responsive NB4 cells showed no such apoptosis, cell death being considerably delayed after cell maturation. Only a few NB4-R1 cells underwent apoptosis in response to low doses of RA (below 0.1 microM), the surviving cells became refractory to higher doses of RA. While these cells became 'resistant' to apoptosis they became competent for maturation. Typically, these RA-'primed' cells responded to cAMP by maturation, then apoptosis followed rapidly. This model furnishes situations where cells are either resistant or susceptible to apoptosis, depending on whether they can or cannot undergo maturation. The potential role of the Bcl-2 protein in the regulation of apoptosis was analyzed. In NB4 and NB4-R1 cell lines, a high expression of the Bcl-2 protein was detected by immunocytology and Western blotting. NB4 cells treated with either all-trans or 9-cis retinoic acid (1 microM) were induced to differentiate and the level of Bcl-2 protein decreased to undetectable levels during terminal maturation when only a few apoptotic cells were detected. In NB4-R1 cells, while treatment with retinoids does not induce maturation, as much as 64% of cells became apoptotic, and immunocytological labelling of NB4-R1 showed a strong cytoplasmic labelling of Bcl-2. Although the expression of Bcl-2 remained high, cells were not protected from apoptosis. To assess whether Bcl-2 expression could be modulated as a consequence of differentiation, NB4-R1 cells previously 'primed' for maturation were triggered with cAMP. Downregulation of Bcl-2 protein occurred concomitant with maturation, followed by apoptosis. Clearly, NB4 and NB4-R1 cells show reciprocal behavior with regards to proliferation, maturation, Bcl-2 regulation and apoptosis in response to RA. Our results suggest, first, that the Bcl-2 downregulation in NB4 cells belongs to the maturation program rather than to apoptosis, and second, that neither a high Bcl-2 expression in NB4 cells is sufficient to protect cells from 9-cis RA induced apoptosis, nor is its full downregulation sufficient to produce apoptosis. Finally, this work suggests that apoptosis and maturation programs include events which cannot occur simultaneously.

Apoptosis↗

Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis.

From the cohort taking part in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter investigation of atherosclerosis and its sequelae in women and men ages 45-64 years, a sample of 145 subjects with significant carotid artery atherosclerosis but without clinically recognized coronary heart disease was identified along with 224 group-matched control subjects. The aim of this paper is to measure the association of the apolipoprotein (apo) E polymorphism with the prevalence of significant carotid artery atherosclerotic disease (CAAD) after considering the contribution of established risk factor variables. The first model used a stepwise selection procedure to define a group of significant physical and lifestyle characteristics and a group of significant plasma lipid, lipoprotein, and apolipoprotein variables that were predictive of CAAD status in this sample. Those variables selected included age (years), body mass index (BMI; kg/m2), consumption of cigarettes (CigYears; number of cigarettes/d x the number of smoking years), hypertension status, high-density lipoprotein (HDL)-cholesterol (mg/dl), total cholesterol (mg/dl), and Lp[a] (micrograms/ml). The second model was built by forcing into the equation an a priori set of demographic, anthropometric, and lipoprotein variables, which were age, BMI, CigYears, hypertensive status, LDL-cholesterol, and HDL-cholesterol. In both models, the apo E genotype epsilon 2/3 was related to CAAD status. For both models, the estimated odds ratio of being a CAAD case associated with the apo E genotype epsilon 2/3 was > 2:1. The mechanism of the observed association between the epsilon 2/3 genotype and carotid atherosclerosis is unknown, but it is likely due to the known effects of the E2 isoform in causing delayed clearance of triglyceride-rich lipoproteins.

Adult↗

The Waterloo Vision and Mobility Study: postural control strategies in subjects with ARM.

Binocular vision function and standing balance control was assessed in 16 subjects with age-related maculopathy (ARM) (mean age 73.9 +/- 7.4 years) and 19 controls (mean age 69.1 +/- 5.5 years). Balance control was assessed using the center of pressure signal from force plate data. It was quantified using the root mean square (RMS) error of the amplitude, sampled over a 1 min period. This was evaluated during normal standing, and while the input from the kinesthetic and/or visual systems were disrupted. The two subject groups showed significantly different RMS values across conditions (P < 0.005). The differences in RMS between ARM and control groups were only significant when the input to the kinesthetic sensory system was disrupted. Our results suggest that in the normal standing condition, the kinesthetic and vestibular systems compensated for the lack of useful information from the visual system in ARM subjects. When kinesthetic system input was disrupted, balance control of the ARM group was significantly poorer than the control. There was a weak correlation between postural control and contrast sensitivity. Various strategies for preventing falls in elderly patients with low vision are suggested.

Aged↗

Depression after childbirth. Does social context matter?

OBJECTIVE: To explore the relationships between women's emotional well-being after childbirth and several measures of the social context of motherhood. DESIGN AND PARTICIPANTS: Case-control study of 45 women who were identified as depressed in a population-based postal survey 8-9 months after giving birth and 45 randomly selected women who were not depressed. At follow-up about two years after the birth, the women were interviewed at home about their experiences of motherhood and their emotional well-being since the birth. They also completed five standard questionnaires: Life Experiences Questionnaire; Toddler Temperament Scale; Social Support Questionnaire; Experience of Motherhood Questionnaire; and the Edinburgh Postnatal Depression Scale. RESULTS: Women in the case group were more likely to be depressed at follow-up than women in the control group. They reported less practical and emotional support from their partners and saw themselves as having less social support overall. They had also experienced more negative life events since the birth, had poorer health and were somewhat more likely to have a "difficult" toddler. CONCLUSIONS: It is important to take social context into account in understanding depression after childbirth and in helping mothers who are depressed.

Case-Control Studies↗

Loss of the ORF in the SSUrDNA group I intron of one Naegleria lineage.

We have found a Naegleria lineage in which the SSUrDNA contains a group I intron with a length of 375 nucleotides. This is a unique finding because all group I introns detected until now in Naegleria are 1.3 kilobases long and contain an open reading frame coding for 245 amino acids. Sequence data show that the 375 nucleotide-long intron is at the same place in the SSUrDNA as, and is descendant from, the 1.3 kilobase group I intron present in other species of Naegleria. Our data indicate that in one lineage of Naegleria the group I intron lost part of its DNA that is not contributing to the secondary structure but that carries the open reading frame. The amoeboflagellate genus Naegleria contains strains without the intron and strains with the intron, with or without an open reading frame. Therefore, this genus provides a unique opportunity to study the function and evolution of both the group I intron and the open reading frame.

Animals↗

Inhibition of human platelet aggregation by GR91669, a prototype fibrinogen receptor antagonist.

In order to produce more potent and specific fibrinogen receptor (GpIIb/IIIa) antagonists, the Arg-Gly of a chemical series based upon Arg-Gly-Asp was replaced by alkyl chains of varying lengths. The most potent in this series, GR91669, inhibited aggregation of human gel-filtered platelets (GFP) in vitro induced by ADP or the thromboxane A2 mimetic, U46619, with IC50 values of 200nM and 500nM respectively and was selected for further studies. Its inhibitory effects on GFP were reversed by addition of excess fibrinogen. The compound also inhibited ADP- or U46619-induced platelet aggregation in human whole blood (IC50 values of 700nM in both cases). 125I-Fibrinogen binding to ADP-stimulated platelets was inhibited by GR91669 with an IC50 (65nM) similar to that against platelet aggregation. GR91669 (1mM) did not inhibit U46619-induced platelet shape change or 14C-5HT secretion from platelets stimulated by collagen, U46619 or thrombin. Therefore GR91669 inhibits aggregation but has no significant effect on stimulus-response events, a profile consistent with fibrinogen receptor blockade. In addition, GR91669 (1mM), unlike echistatin or Gly-Arg-Gly-Asp-Ser, did not disrupt vitronectin recptor-dependent attachment of cultured HUVECS in vitro and similarly did not inhibit Mac-1 dependent adhesion of human granulocytes. Thus, of the integrins tested, GR91669 appears to be specific for GpIIb/IIIa. Following intravenous administration to marmosets of 1 or 10 mg/kg GR91669, ADP (10 microM)-induced platelet aggregation ex vivo was abolished for 15 and 60 minutes respectively. Greater than 50% inhibition was maintained for 30 minutes and 2 hours respectively. GR91669, therefore appears to be a potent, specific fibrinogen receptor antagonist in vitro and which is also active in vivo.

Amino Acid Sequence↗

Activation of the cell cycle machinery and the isoflavonoid biosynthesis pathway by active Rhizobium meliloti Nod signal molecules in Medicago microcallus suspensions.

We have shown that treatment of Medicago microcallus suspensions with the cognate Rhizobium meliloti Nod signal molecule NodRm-IV(C16:2,S) can modify gene expression both qualitatively and quantitatively. At concentrations of 10(-6) - 10(-9) M, this host specific plant morphogen but not the inactive non-sulfated molecule stimulated cell cycle progression as indicated by the significantly enhanced thymidine incorporation, elevated number of S phase cells, increase in kinase activity of the p34cdc2-related complexes and enhancement of the level of expression of several cell cycle marker genes, the histone H3-1, the cdc2Ms and the cyclin cycMs2. The presented data suggest that at least part of the physiological role of the Nod factor may be linked to molecular events involved in the control of the plant cell division cycle. In situ hybridization experiments with antisense H3-1 RNA probe indicated that only certain cells of the calli were able to respond to the Nod factor. High (10(-6) M) but not low (10(-9) M) concentrations of the active Nod factors induced the expression of the isoflavone reductase gene (IFR), a marker gene of the isoflavonoid biosynthesis pathway in most callus cells. Our results indicate that Medicago cell responses to the Nod signal molecules can be investigated in suspension cultures.

CDC2 Protein Kinase↗

Post-transcriptional regulation of interleukin 1 alpha in various strains of young and senescent human umbilical vein endothelial cells.

Human umbilical vein endothelial cell (HUVEC) senescence in vitro is characterized by the loss of proliferative potential and an increase in cell size. Because HUVEC senescence in one strain (H101) has been characterized by the increase in the steady-state mRNA level for the signal-peptideless cytokine, interleukin (IL) 1 alpha, we have examined young and senescent populations of five additional HUVEC strains (H3605, H103, H928, H929, and H930) to determine whether the elevated levels of IL-1 alpha mRNA could be observed in all HUVEC strains. Consistent with the data from strain H101, strains H3605 and H930 also exhibited a low steady-state level of the IL-1 alpha mRNA in young populations compared to elevated levels of IL-1 alpha mRNA in the senescent populations. However, three strains (H103, H928, and H929) did not exhibit reduced levels of IL-1 alpha mRNA in the young populations, and interestingly, strain H928, at times, expressed relatively high IL-1 alpha mRNA levels in the young populations. In addition, expression of the steady-state level of plasminogen activator inhibitor 1 and cyclooxygenase 2 was elevated in senescent populations of all HUVEC strains examined, whereas young populations exhibited a low level of expression for these genes regardless of the IL-1 alpha mRNA level. Further, the level of the IL-1 alpha polypeptide was elevated in senescent HUVEC populations relative to young populations that expressed either a high or low level of the IL-1 alpha mRNA. We have also demonstrated that the elevated level of IL-1 alpha mRNA in the senescent population of strain H3605 may be regulated by mRNA stability; however, this mechanism does not apply to all the HUVEC strains examined in this study. Thus, we suggest that while mRNA levels of the IL-1-response genes for plasminogen activator inhibitor 1 and cyclooxygenase 2 are appropriate markers for HUVEC senescence, HUVEC strain-specific post-transcriptional mechanisms may exist to regulate the function of IL-1 alpha as a modifier of HUVEC senescence in vitro.

Base Sequence↗