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Biomedical subjects

S Jordan

Publications and source records attributed to S Jordan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Peptide inhibitors of src SH3-SH2-phosphoprotein interactions.

Activated pp60c-src has been implicated in a number of human malignancies including colon carcinoma and breast adenocarcinoma. Association of the src SH2 domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus, of great interest in defining the role(s) of src in signal transduction pathways. To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay measures inhibition of binding of a fusion construct (glutathione S-transferase src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain. Activities of phosphopeptide segments derived from potential src SH2 cognate phosphoprotein partners were determined, with the focal adhesion kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity. Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac-Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2 A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and provided a useful framework for understanding the structure-activity relationships. Additionally, Ac-Y*EEIE was able to block interactions between src and its cellular phosphoprotein partners in vanadate-treated cell lysates from MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate proliferation of MDA-MB-468 cells in culture, presumably because of poor cell penetration and/or lability of the phosphate group on tyrosine.

Amino Acid Sequence↗
PubMed1994

Learned helplessness sensitizes hippocampal norepinephrine to mild restress.

A proportion of rats exposed to inescapable tailshock stress displayed a performance deficit, termed learned helplessness, in a subsequent shuttlebox avoidance task. The technique of in vivo microdialysis was used to determine hippocampal norepinephrine levels in learned helpless, nonhelpless and nonprestressed control rats. Similar basal norepinephrine levels were detected in samples between rat groups. Following an exposure to a milder form of inescapable shock, an increase in norepinephrine output was detected in learned helpless rats, which was significantly greater than nonhelpless, nonprestressed, or control animals. Thus, inescapable stress appears to sensitize the hippocampus to increase norepinephrine release in response to a subsequent smaller stressor. This hypersensitivity might underlie the avoidance impairment of learned helplessness. Therefore, the possibility exists that similar neurochemical changes may also be responsible for some of the symptoms of human posttraumatic stress disorder (PTSD), such as the poor coping associated with seemingly mild stress.

Animals↗
PubMed1994

Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues.

The merits of microwave-based antigen retrieval methods for diagnostic immunohistochemistry have recently been emphasized. As such technology has drawbacks for busy routine laboratories, we have investigated an alternative method of heat-mediated antigen retrieval (HMAR), using a domestic pressure cooker as a source of superheating. A simple protocol, with superheating in 0.01 M citrate buffer (pH 6.0) for 2 min, gave results comparable to those obtainable in a microwave oven. The range of antigens retrieved and the antigens for which heating was ineffective matched the published microwave experience. The advantages included the speed of treatment, the reproducibility of results with large batches of slides, the ability to use metal slide racks, and economy of time and equipment costs.

Antigens↗
PubMed1994

In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine.

In vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5-HT to a lesser extent. Similar dose-dependent increases in DA and 5-HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5-HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5-HT by the same amount in a dose-dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo.

Animals↗
PubMed1994

Previous stress increases in vivo biogenic amine response to swim stress.

In vivo microdialysis was used to determine biogenic amines in medial prefrontal cortex of rats exposed to eight minutes of swim stress on two consecutive days. On the first day of stress, norepinephrine (NE) efflux increased by 183% over baseline after stress, while dopamine (DA) and serotonin (5-HT) remained stable throughout. On the second day of stress, a robust increase was observed in all 3 neurotransmitters measured, with (NE), (DA), and (5-HT) increasing by 310%, 441% and 496% respectively, and remaining elevated for an hour or more after stress. This suggests that the first exposure to swim stress, while not causing dramatic changes in biogenic amine release, may sensitize biogenic amines in medial prefrontal cortex to subsequent swim stress. Our results also serve as preliminary data concerning the neurochemical changes which might underlie the forced swimming model of "behavioral despair".

Animals↗
PubMed1994

Daily variability in exercise ventilation.

The purpose of this study was to quantify daily variability in ventilation (VE) during submaximal exercise and establish the number of testing sessions required to produce stable exercise ventilation measures. Following 60 min of treadmill accommodation, four male (M) and four female (F) distance runners completed 5 weeks of daily treadmill testing at the same time of day while engaged in a normal routine of training and racing. During each test session, subjects completed three 6-min level treadmill runs at either 3.13, 3.57, and 4.02 m.sec-1 for F or 3.57, 4.02, and 4.47 m.sec-1 for M. Measures of VE were obtained during the last 2 min of each 6-min run. Results indicated that the mean coefficient of variation (CV) for VE across speeds was 4.33%. Reliability analyses examining all possible combinations of testing days over the 5-week period revealed that 97% of the variation in mean VE was accounted for in either 2 consecutive or non-consecutive days, while 98% of the variation in mean VE was accounted for in 5 consecutive days. These data suggest that when treadmill exposure and circadian variation are controlled, intraindividual differences in exercise VE are relatively small in male and female subjects following an unrestricted program of training and competitive racing. Additionally, acceptably stable VE values in this cohort can be derived by averaging duplicate measures obtained from consecutive or non-consecutive testing sessions.

Adult↗
PubMed1994

Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma.

Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

Administration, Inhalation↗
PubMed1994

In vivo serotonin release and learned helplessness.

Learned helplessness, a behavioral depression caused by exposure to inescapable stress, is considered to be an animal model of human depressive disorder. Like human depression, learned helplessness has been associated with a defect in serotonergic function, but the nature of this relationship is not entirely clear. We have used in vivo microdialysis brain perfusion to measure serotonin (5-hydroxytryptamine, 5HT) in extracellular space of medial frontal cortex in conscious, freely moving rats. Basal 5HT levels in rats perfused before exposure to tail-shock stress did not themselves correlate with subsequent learned helplessness behavior. However, 5HT release after stress showed a significant increase with helpless behavior. These data support the hypothesis that a cortical serotonergic excess is causally related to the development of learned helplessness.

Animals↗
PubMed1994

Should nurses be studying bioscience? A discussion paper.

The growth of bioscience knowledge over the last two decades has increased the potential benefits of scientifically based patient care by contributing to the theory of clinical care. However, there is little evidence that knowledge, derived from the human biosciences is being fully incorporated into nursing theory and practice. Nursing has developed its own unique professional body of knowledge, heavily influenced by behavioural science. If nursing theory leans towards behavioural science, but practice is devoted to problems of biological disturbance, nursing may be facing a widening theory-practice gap, greater than other professions. The theory-practice gap in nursing may be widened by the exclusion of bioscience from nursing theory. Nurses' relative disinterest in the natural sciences can be attributed both to sociological reasons and to problems stemming from the symbol-object dichotomy that recur in the teaching of natural sciences. Reflection on practice and examination of education method are suggested as strategies for re-introducing bioscience into nursing theory and practice. A challenge facing nurse educators is the integration of biological science into the nurses' conceptual ecologies. For, if nursing fails to make bioscience its own, much of the clinical welfare of patients will become a medical monopoly.

Behavioral Sciences↗
PubMed1994

Lymphocyte infiltration and thickness of the nasal mucous membrane in perennial and seasonal allergic rhinitis.

We have used immunocytochemical techniques to study infiltration by lymphocytes in biopsy specimens of the nasal mucosal membrane in 24 atopic patients and 10 normal volunteers. Twelve patients had perennial rhinitis and 12 had seasonal allergic rhinitis (SR) to grass pollen. Biopsy specimens were taken both in and out of the pollen season in patients with SR. Biopsy specimens were strained with the indirect immunoperoxidase technique and monoclonal antibodies to CD3, CD4, CD8, CD22, and CD25. T helper cells (CD4+) and CD24+ cells were significantly more numerous in patients exposed to allergen (those with perennial rhinitis and SR in season) compared with normal volunteers, whereas values for SR out of season were intermediate. The thickness of the nasal epithelium was significantly (p < 0.05) greater in biopsy specimens from patients with perennial rhinitis (mean, 51.43 microns) than in those from patients with SR in season (median, 32.44 microns). These results suggest that in allergic rhinitis, natural exposure to allergen is accompanied by increased infiltration of the nasal mucous membrane by T-helper and CD25+ cells.

Adolescent↗
PubMed1994

Diastematomyelia: diagnosis by prenatal sonography.

OBJECTIVE: Diastematomyelia is a form of spinal dysraphia involving a sagittal cleft in the spinal cord with splaying of the posterior spinal elements. This may be an isolated abnormality or in association with more serious dysraphic conditions. In isolated diastematomyelia, the skin is intact and the prognosis excellent. This study aimed to determine the usefulness of prenatal sonography in diagnosing diastematomyelia and in predicting the isolated form. SUBJECTS AND METHODS: The usefulness of the sonographic findings of an extra posterior echogenic focus between the fetal spinal laminae and splaying of the posterior elements for the prenatal sonographic diagnosis of diastematomyelia was assessed in five cases prospectively and in one case retrospectively. The posterior echogenic focus was first seen on prenatal sonograms at a mean age of 19 weeks' gestation (range, 18-20 weeks). The final diagnosis of diastematomyelia was made at autopsy in two cases (one with an associated meningocele), at postmortem radiography in one, at surgery in one, and at CT myelography in two. Postnatal spinal sonograms were obtained in each case. The ability to detect fetal spinal widening on prenatal sonograms was compared with the postnatal radiologic appearance on spinal plain film radiographs. RESULTS: Diastematomyelia was confirmed in all five cases where the extra posterior echogenic focus was seen at prenatal sonography. The double spinal cord was within a single dural sheath in three cases, with no bony bar present. A double dural sheath with a bony bar was noted in a fourth case. In the fifth case, a bony bar was seen on a postmortem spinal X-ray, but a double dural sheath could not be confirmed because an autopsy was not performed. In the case where diastematomyelia was not suspected on prenatal sonograms, the dural sheath was single and no bony bar was present. Splaying of the posterior elements was seen on postnatal radiographs in all cases but was suspected in only four on prenatal sonograms. Prenatal sonography accurately predicted isolated diastematomyelia in four cases and complicated diastematomyelia in one case. The one case missed prenatally was of isolated diastematomyelia. CONCLUSION: A diagnosis of diastematomyelia can be made if an extra posterior echogenic focus is seen on prenatal sonography. Splaying of the posterior elements of the fetal spine is frequently present. The pregnancy should be managed differently depending on whether the diastematomyelia is isolated, with the skin intact, or is in association with more serious neural tube defects. This distinction is possible prenatally.

Female↗
PubMed1993

Isolated follicular lymphoma cells are resistant to apoptosis and can be grown in vitro in the CD40/stromal cell system.

Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germinal centers. B lymphocytes from normal germinal centers and lymph nodes infiltrated by follicular lymphoma were isolated by immunomagnetic depletion of cells bearing CD4, CD8, or slgD for study in vitro. Follicular lymphoma cells expressing Bcl-2 protein were shown to resist apoptosis after isolation, and could be induced to proliferate in a culture system previously described for the growth of normal B lymphocytes. By the use of a mouse fibroblast monolayer transfected with the CDw32 Fc receptor to present CD40 monoclonal antibody in the presence of interleukin-4, prolonged culture was possible. Karyotypic analysis of cultured lymphoma cells showed the t(14;18) translocation, with clonal identity confirmed by polymerase chain reaction amplification of the breakpoints and direct sequence analysis. These findings support the hypothesis that resistance to apoptosis is an influence on the initiation of follicular lymphoma, and provide a novel means of studying in vitro the intercellular reactions that may be important in progression of the disease.

Animals↗
PubMed1993

Central alpha-2 adrenoceptors are responsible for a clonidine-induced cue in a rat drug discrimination paradigm.

Clonidine produces an interoceptive discriminative stimulus or "cue" in rat drug discrimination studies. This cue may be mediated by its alpha-2 adrenoceptor agonist properties and/or its affinity for the non-adrenoceptor imidazoline preferring receptor. Six rats were trained to respond differentially after receiving clonidine (0.02 mg kg-1, IP) or a saline vehicle. The alpha-2 adrenoceptor agonists clonidine, UK14, 304 and rilmenidine, which bind to the imidazoline preferring receptor, and guanabenz which does not, dose-dependently substituted for (i.e. > 80% total responding was clonidine associated) the clonidine-induced cue in doses up to 0.02, 0.16, 1.25 and 0.32 mg kg-1, respectively. Furthermore, the cue was blocked when clonidine was given in combination with 30-min pretreatments of the highly selective alpha-2 adrenoceptor antagonists RX811059 (2.5 mg kg-1) and fluparoxan (3 mg kg-1). Since the clonidine-induced cue was substituted for by guanabenz, which does not act at the imidazoline-preferring receptor, and antagonised by RX811059 and fluparoxan it appears to be mediated by alpha-2 adrenoceptors. Moreover, abolition of the clonidine-induced cue did not occur with the peripherally acting alpha-2 adrenoceptor antagonist L659, 066 suggesting it involves central as opposed to peripheral sites.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1993

Segment-specific modulation of the electrophysiological activity of leech Retzius neurons by acetylcholine.

1. The acetylcholine responses of Retzius neurons were electrophysiologically and pharmacologically characterized in situ and in culture. Single-electrode voltage-clamp was used to record currents from leech Retzius neurons from standard segments [Rz(X)] and from reproductive segments [Rz(5,6)]. 2. A 1 s pressure pulse of acetylcholine (ACh) produced a fast inward current followed by a slower outward current in Rz(X) neurons, whereas it produced only an outward current in Rz(5,6) neurons. These segment-specific responses were maintained when the two types of Retzius neurons were isolated in culture for up to 12 days. 3. The inward current of Rz(X) reversed at around -25 mV and was partially carried by Na+. This cationic current desensitized rapidly. The outward current of Rz(X) and Rz(5,6) neurons reversed at around -65 mV and was carried by Cl-. This anionic current desensitized very slowly upon prolonged applications of ACh. 4. The expression of the ACh-induced outward current in Rz(X) was season-dependent and was recorded in a larger proportion of Rz(X) neurons during the summer than during the winter. The expression of the ACh-induced outward current in Rz(5,6) did not show any seasonal pattern. 5. The fast inward current of Rz(X) was also elicited by nicotine; it was blocked by d-tubocurarine, hexamethonium and mecamylamine, but was not affected by alpha-bungarotoxin. The outward current of Rz(X) and Rz(5,6) was also elicited by nicotine and by 4-[N-(3-chlorophenyl)carbamoxyloxy]2-butynyltrimethylammonium chloride (a muscarinic agonist); it was blocked by d-tubocurarine and by alpha-bungarotoxin, but it was not affected by hexamethonium or mecamylamine. 6. The results show that the serotonergic Retzius neurons of the leech could be tonically inhibited by ACh. In addition, the Retzius neurons from standard segments could also be phasically excited by ACh. The receptors responsible for the excitation fit into the classification of neuronal nicotinic receptors, whereas the receptors mediating the inhibition are closer in type to the muscular nicotinic receptor.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗