Search PubMed⌕ Search

Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 181 records · Page 10Linked to original sources
PubMed1998

Transesophageal echocardiography for ascending aortic dissection: is it enough for surgical intervention?

BACKGROUND: Acute ascending aortic dissection is a surgical emergency that requires expeditious diagnosis and prompt surgical intervention. In many centers, transesophageal echocardiography (TEE) is the test of choice on which surgical decisions are based. Echocardiographic false-positive diagnoses are rare but can occur with potentially severe consequences. CASE REPORT: Two clinical cases where ascending aortic dissections were falsely diagnosed by TEE are presented. DISCUSSION: Recent literature comparing the diagnostic accuracy of TEE and other imaging techniques are reviewed. Anatomical limitations of TEE and potential causes of false-positive results are discussed. Multiplane probe reduces, but does not eliminate, the occurrence of false-positive findings. To improve diagnostic specificity without undue delays in the course of clinical decision making, we recommend dividing positive TEE findings into "definite" and "probable" categories. Such subclassification is helpful in identifying cases where additional confirmatory tests are desirable in situations of uncertain diagnosis.

Adult↗
PubMed1998

Salbutamol treatment in a patient with hyperkalaemic periodic paralysis due to a mutation in the skeletal muscle sodium channel gene (SCN4A).

A 35 year old woman with clinical features of hyperkalaemic periodic paralysis confirmed on provocative exercise testing was investigated. DNA sequence analysis of the gene for the alpha-subunit of the skeletal muscle voltage gated sodium channel (SCN4A) on chromosome 17q23 identified a point mutation at nucleotide position 2188. This results in a threonine to methionine substitution at amino acid position 704. The patient was intolerant of diuretic medication but showed a striking clinical and electrophysiological improvement with salbutamol therapy. Treatment with beta-adrenergic agents should be considered in patients with hyperkalaemic periodic paralysis who are intolerant of, or resistant to, diuretic medications.

Adrenergic beta-Agonists↗
PubMed1998

Dusting off that old proposal: how to survive in the land of research.

Pediatric oncology nursing would benefit from more research directed toward questions that relate to the care of children with cancer. There are many ideas and proposals that are begun but never carried to fruition. This article will detail how to assess and rework a research proposal to provide the basis for a research project that will add to the scientific knowledge of nursing care of children with cancer.

Child↗
PubMed1998

Conditioning in the circadian system.

Light is the dominant environmental cue for entrainment of circadian rhythms. In mammals, light entrains rhythms by resetting the phase of a circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Until recently, the mechanism responsible for pacemaker resetting by light was thought to be exclusively sensitive to photic cues. New experiments indicate, however, that this mechanism is more plastic than once thought; is amenable to conditioned stimulus control; and is capable of acquiring, through conditioning, new response capabilities. These experiments showed that, in rats, a neutral stimulus paired with light in Pavlovian conditioning trials is capable of eliciting cellular and behavioral effects characteristic of circadian clock phase resetting by light, expression of Fos protein in the ventrolateral region of the SCN, and phase shifts of free-running rhythms. These novel results open up a previously unappreciated perspective on photic phase resetting and entrainment of circadian rhythms. Specifically, they suggest that the process normally initiated by light to reset the clock can be modified by learning and events in the environment that reliably precede the onset of light can assume the resetting function of light.

Animals↗
PubMed1998

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.

Adrenergic Antagonists↗
PubMed1997

Alanine mutagenesis of surfactant protein A reveals that lipid binding and pH-dependent liposome aggregation are mediated by the carbohydrate recognition domain.

The carbohydrate recognition domain (CRD) of surfactant protein A (SP-A) is critical for the modulation of surfactant secretion from isolated type II cells and for the Ca(2+)-dependent aggregation of surfactant liposomes, but the domains of SP-A that mediate lipid binding have not been precisely mapped. To determine the role of the CRD in lipid interactions and other functions, the conserved amino acids of the putative Ca2+ and carbohydrate binding site (Glu195, Glu202, Asn214, Asp215) were substituted with alanine. The wild-type recombinant protein, SP-Ahyp, and mutant SP-As SP-Ahyp,E195A, SP-Ahyp,E202A, SP-Ahyp,N214A, and SP-Ahyp,D215A, were expressed in insect cells using baculovirus vectors and compared functionally. The Ca(2+)-dependent binding and aggregation of liposomes at pH 7.0 by SP-Ahyp,N214A were comparable to SP-Ahyp, but these activities were blocked in SP-Ahyp,E195A, SP-Ahyp,E202A, and SP-Ahyp,D215A. In contrast, the SP-Ahyp,D215A but not the other mutant proteins induced the Ca(2+)-independent aggregation of phospholipid liposomes at pH 4.0. The mutant recombinant proteins did not compete with 125I-labeled rat SP-A for high-affinity receptor occupancy on isolated type II cells and were much less potent than SP-Ahyp as regulators of surfactant secretion and uptake from type II cells. We conclude that (1) lipid binding and pH-dependent liposome aggregation are mediated by the CRD of SP-A, (2) distinct but overlapping domains within the CRD are required for pH- and Ca(2+)-dependent liposome aggregation, and (3) conserved acidic and polar residues of the carbohydrate binding site of SP-A are essential for interactions with type II cells.

Alanine↗
PubMed1997

The Cys6 intermolecular disulfide bond and the collagen-like region of rat SP-A play critical roles in interactions with alveolar type II cells and surfactant lipids.

Rat pulmonary surfactant protein A is an oligomer of 18 polypeptide chains which are associated by triple helix formation in the collagen-like domain and interchain disulfide bridges at the NH2 terminus. The roles of the intermolecular bond at Cys6 and the collagen-like domain (Gly8-Pro80) in the interactions of SP-A with phospholipids and alveolar type II cells were investigated using mutant forms of the protein. Wild type SP-A (SP-Ahyp), SP-A with the substitution Cys6 --> Ser to prevent disulfide formation (SP-Ahyp, C6S), and SP-A with the collagen-domain deleted (SP-ADeltaG8-P80) were synthesized in insect cells using recombinant baculoviruses. The SP-As were glycosylated and secreted from the invertebrate cells and the binding affinities of the wild type and mutant proteins for the mannose-Sepharose matrix used for purification were nearly identical. The SP-Ahyp and SP-ADeltaG8-P80 were at least nonameric in solution based on gel exclusion chromatography, and demonstrated extensive sulfhydryl-dependent oligomerization under nonreducing conditions. The SP-Ahyp,C6S was also oligomeric in solution and formed disulfide-dependent dimers, indicating the presence of at least one additional interchain disulfide bond. The SPADeltaG8-P80 but not the SP-Ahyp,C6S aggregated lipid vesicles at 20 degrees C and augmented the surface tension lowering effect of extracts of natural surfactant. The SP-ADeltaG8-P80 competed poorly with native SP-A for receptor occupancy on isolated alveolar type II cells and was a potent but nonspecific (concanavalin A-like) inhibitor of surfactant secretion. In contrast, the SP-Ahyp,C6S partially competed for receptor occupancy and weakly inhibited surfactant secretion in a specific manner. Neither the SP-ADeltaG8-P80 nor the SP-Ahyp,C6S supported the association of phospholipid liposomes with type II cells. We conclude that: 1) the Cys6 interchain disulfide bond of SP-A is required for aggregation of liposomes and for potent inhibition of surfactant secretion. 2) The collagen-like region is required for competition with 125I-SP-A for receptor occupancy and specific inhibition of surfactant secretion in the presence of competing sugars. 3) Both the NH2-terminal disulfide and the collagen-like region are required to enhance the association of phospholipid vesicles with type II cells.

Animals↗
PubMed1997

Functional analysis of the promoter for the human CYP1B1 gene.

Our laboratory has cloned the cDNA (Sutter, T. R., Tang, Y. M., Hayes, C. L., Wo, Y.-Y. P., Jabs, E. W., Li, X., Yin, H., Cody, C. W. , and Greenlee, W. F. (1994) J. Biol. Chem. 269, 13092-13099) and gene (Tang, Y. M., Wo, Y.-Y. P., Jabs, E. W., Stewart, J. C., Sutter, T. R., and Greenlee, W. F. (1996) J. Biol. Chem. 271, 28324-28330) for human CYP1B1, a new member of the cytochrome P450 superfamily. Here, we report on the mapping and function of the CYP1B1 promoter. The CYP1B1 promoter is fully functional, when it is uncoupled from upstream enhancer elements. Deletion analysis and site-directed mutagenesis identified four regulatory elements required for maximum promoter activity: two antisense Sp1 sites (-84 to -89 and -68 to -73), a TATA-like box (-34 to -29), and an initiator motif (-5 to +3). The initiator and the TATA-like elements are both required for basal promoter activity, with enhanced activity mediated by the two antisense Sp1 elements. The CYP1B1 initiator was demonstrated by in vitro transcription analysis to be a positioning element that maintained fidelity of transcription from a single site. Specific binding to a CYP1B1 initiator probe by human nuclear extract proteins was competed either by the highly homologous murine terminal deoxynucleotidyl transferase initiator or, to a lesser extent, by the adenovirus major late initiator. Taken together, these results indicate that the structure and function of the CYP1B1 promoter confers constitutive expression of the gene and assures fidelity of transcription initiation from a single site. The CYP1B1 promoter is distinct from the promoters of the closely related cytochrome P450s CYP1A1 and CYP1A2 and is structurally and functionally similar to the promoters of constitutively expressed genes and at least two viruses.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

Excitotoxic lesions of the prefrontal cortex reduce dopamine D1-like receptors in the ventral tegmental area.

Ventral mesencephalic dopamine D1-like receptors were quantified in brains of male rats ten days after unilateral microinjections of ibotenic acid (2 or 10 microg/microl) or its vehicle into the medial prefrontal cortex. The density of dopamine D1-like receptors was reduced by more than 40% in the ipsilateral ventral tegmental area (both doses) and by 15% (low dose) and 44% (high dose) in the contralateral side; no significant reduction was observed in the substantia nigra. These results suggest that a significant number of ventral tegmental D1-like receptors are localized on afferent terminals from the medial prefrontal cortex.

Animals↗
PubMed1997

Molecular interactions between dynamin and G-protein betagamma-subunits in neuroendocrine cells.

Dynamin and G-proteins both are guanosine triphosphate (GTP) binding proteins, with dynamin active in cellular membrane trafficking and G-proteins in intracellular signal transduction. Here we demonstrate that dynamin physically and functionally interacts with G-protein betagamma-subunits in neuroendocrine GH4C1 cells, on stimulation with thyrotropin-releasing hormone and somatostatin. The interaction appears to be of high affinity and inhibitory on dynamin GTPase activity, mediated by the pleckstrin homology domain and regulated both by the G-protein alpha-subunit and by guanosine nucleotides. Thus, dynamin may target particular sites for receptor-mediated endocytosis by sharing betagamma-subunits with the alpha subunit of G-proteins in neuroendocrine cells.

Animals↗
PubMed1997

Neuropeptide FF in the VTA blocks the analgesic effects of both intra-VTA morphine and exposure to stress.

It has been shown previously that i.c.v. administration of neuropeptide FF (NPFF) attenuates the analgesic effects of exogeneous and endogeneous opioids. Here, we report that intra-ventral tegmental area (VTA) NPFF pre-treatment blocks the analgesia induced by either intra-VTA morphine or exposure to footshock stress in the formalin test for tonic pain. These findings suggest that NPFF in the VTA may play an adaptive role in regulating the response to stress.

Analgesics, Opioid↗
PubMed1997

Behavioral and neurochemical recovery from partial 6-hydroxydopamine lesions of the substantia nigra is blocked by daily treatment with D1/D5, but not D2, dopamine receptor antagonists.

To determine whether D1/D5 dopamine (DA) receptors play a role in normalization of DA extracellular levels of striatal DA and behavioral recovery after partial 6-OHDA lesions of the substantia nigra, animals were treated on days 1-8 after lesioning with the D1/D5 DA receptor antagonists SCH 23390 (0.1 mg/kg, s.c.) and SCH 39166 (1.0 mg/kg, s.c.), the inactive enantiomer SCH 23388 (0.1 mg/kg, s.c.), the D2 antagonist eticlopride (0.1 mg/kg, i.p.), or saline. Spontaneous turning behavior was assessed on days 3 and 15. Basal extracellular DA and metabolites were measured in both striata using microdialysis on days 16 and 17, 8-9 d after termination of drug treatments. On day 3, all animals turned ipsilateral to the lesion. On day 15, animals previously treated with either saline, eticlopride, or SCH 23388 showed no behavioral asymmetries, whereas animals treated with SCH 23390 or SCH 39166 turned ipsilaterally. On days 16 and 17, extracellular DA did not differ on the two sides in animals treated with saline or eticlopride and were higher on the lesioned side after SCH 23388. In animals treated with the D1/D5 receptor antagonists, however, basal levels of DA were lower on the lesioned side, showing no evidence of normalization. These results suggest a role for the D1/D5 DA receptor in the development of compensatory changes in the DA neurons that accompany behavioral recovery from partial lesions of nigrostriatal DA system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Pulmonary surfactant protein SP-B interacts similarly with dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine in phosphatidylcholine/phosphatidylglycerol mixtures.

Porcine pulmonary surfactant-associated protein SP-B was incorporated into bilayers of chain-perdeuterated dipalmitoylphosphatidylglycerol (DPPG-d62) and into bilayers containing 70 mol % dipalmitoylphosphatidylcholine (DPPC) and 30 mol % DPPG-d62 or 70 mol % chain-perdeuterated DPPC (DPPC-d62) and 30 mol % DPPG. The effect of SP-B on the phase behavior, lipid chain order, and dynamics in these bilayers was examined using deuterium nuclear magnetic resonance (2H-NMR). In both DPPG-d62 and the mixed lipid system, SP-B is found to have little effect on chain order in the liquid crystalline phase. With 11% (w/w) SP-B present, both bilayer systems display a continuous change from liquid crystal to gel with no evidence of two-phase coexistence near the transition. Despite its limited effect on chain order in these bilayers, SP-B is found to strongly perturb chain deuteron transverse relaxation in the liquid crystal and gel phases of DPPG-d62 and the DPPC/DPPG (7:3) mixtures. The observation that SP-B associates with the bilayer in a way which substantially alters the slow motions responsible for transverse relaxation without significantly affecting chain order in either the liquid crystal or gel phases may place some constraints on possible models for that association.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats.

We showed previously that brief footshock stress and priming injections of heroin reinstate heroin-seeking after prolonged drug-free periods. Here, we examined whether the adrenal hormone, corticosterone, and brain corticotropin-releasing factor (CRF) were involved in such reinstatement. We tested the effects of adrenalectomy, chronic exposure to the corticosterone synthesis inhibitor metyrapone (100 mg/kg, s.c., twice daily), acute exposure to metyrapone, acute intracerebroventricular injections of CRF (0.3 and 1.0 microgram), and intracerebroventricular injections of the CRF antagonist alpha-helical CRF (3 and 10 micrograms). Rats were trained to self-administer heroin (100 micrograms/kg/infusion, i.v.) for 12-14 d. Extinction sessions were given for 4-8 d (saline substituted for heroin). Tests for reinstatement were given after priming injections of saline and of heroin (0.25 mg/kg, s.c.), and after intermittent footshock (15 or 30 min, 0.5 mA). Adrenalectomy (performed after training) did not affect reinstatement by heroin but appeared to potentiate the reinstatement by footshock. Chronic exposure to metyrapone (from the beginning of extinction) or an acute injection of metyrapone (3 hr before testing) did not alter the reinstatement of heroin-seeking induced by footshock or heroin. Acute exposure to metyrapone alone potently reinstated heroin-seeking. In addition, acute exposure to CRF reinstated heroin-seeking, and the CRF antagonist alpha-helical CRF attenuated stress-induced relapse. The effect of the CRF antagonist on reinstatement by heroin was less consistent. These results suggest that CRF, a major brain peptide involved in stress, contributes to relapse to heroin-seeking induced by stressors.

Adrenalectomy↗
PubMed1997

High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy.

From the somewhat conflicting published data on apolipoprotein E (apoE) genotype in hemorrhage due to cerebral amyloid angiopathy (CAA), it is unclear whether apoE genotype influences the risk of CAA-related hemorrhage independently of its association with concomitant Alzheimer's disease (AD). We determined the apoE genotypes of 36 patients presenting with cerebral hemorrhage associated with histologically confirmed CAA. The frequency of apoE epsilon 2 was 0.25 and the frequency of apoE epsilon 4 was 0.18. Patients with CAA-related hemorrhage and concomitant AD pathology (CERAD criteria, n = 17) had a high apoE epsilon 4 frequency, close to that in AD cases without hemorrhage. Patients in whom CAA-related hemorrhage occurred in the absence of significant AD pathology (n = 13) had an apoE epsilon 4 frequency somewhat lower than non-AD controls without hemorrhage. However, in CAA-related hemorrhage, the apoE epsilon 2 frequency was high regardless of whether significant AD pathology was present. We conclude that whereas possession of apoE epsilon 2 may be a risk factor for cerebral hemorrhage due to CAA, apoE epsilon 4 is a risk factor for concomitant AD but not an independent risk factor for CAA-related hemorrhage.

Aged↗
PubMed1997

Phenotypic variability of CADASIL and novel morphologic findings.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a non-arterio-atherosclerotic, non-amyloidotic arteriopathy affecting preferentially the small arteries and arterioles of the brain. The morphologic hallmark is the presence of a characteristic granular alteration of the arterial media that ultrastructurally corresponds to the accumulation of electron-dense material surrounding the smooth muscle cells. Although the presence of this granular osmiophilic material (GOM) was originally described as limited to brain vessels, identical electron microscopic findings have been demonstrated in the media of peripheral tissue arteries, allowing for a pathologic diagnosis of the disease by a simple skin, muscle or nerve biopsy. We report some atypical features identified in our CADASIL patients that broaden the phenotypic expression of this disease. Firstly, we identified a cortical infarct in an otherwise typical CADASIL patient. Secondly, we observed GOM in skin arteries of a 30-year-old man with hemiplegic migraine, the son of a woman who had died with CADASIL. This confirms that it may be possible to diagnose the disease at a preclinical stage by the ultrastructural evaluation of peripheral tissue biopsy material, particularly for individuals for whom there is a supporting family history. Thirdly, ultrastructural examination of the skin, and subcutaneous and striated muscle of an unrelated and apparently sporadic patient with neuropathologic and neuroradiologic evidence of CADASIL in meningeal and cerebral vessels failed to reveal diagnostic lesions in peripheral arteries. Thus, the possibility of a false-negative pathologic diagnosis in patients with a clinicoradiologic diagnosis of CADASIL, if one relies solely on a peripheral tissue biopsy, does exist. Additionally, we have identified heat shock proteins (Hsp70 and alphaB crystallin) and ubiquitin in the vascular myocytes of affected arteries. B crystallin also seemed to be deposited extracellularly, which suggests that GOM also might be immunoreactive for alphaB crystallin.

Adult↗