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J M Brown

Publications and source records attributed to J M Brown.

At least 55 records · Page 3Linked to original sources
PubMed2001

Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue.

We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs. trans-10, cis-12 CLA on TG content; 3) whether chronic linoleic acid supplementation could rescue the TG content of CLA-treated cultures; and 4) whether trans-10, cis-12-mediated reduction in cellular TG was due to decreased lipogenesis and/or increased lipolysis. In expt. 1, the TG content [micromol/(L x 10(6) cells)] increased as both seeding density and TZD concentration increased. For example, cultures seeded at 4 x 10(4) cells/cm(2) and supplemented with 10 micromol/L BRL 49653 had 10-fold more TG than similarly seeded cultures without BRL 49653. In expt. 2, TG content decreased as the level of trans-10, cis-12 CLA increased from 1 to 10 micromol/L, whereas the TG content increased with increasing concentrations of either linoleic acid or cis-9, trans-11 CLA. In expt. 3, linoleic acid supplementation restored the TG content of cultures treated with trans-10, cis-12 CLA compared with cultures treated with CLA alone, suggesting that attenuation of TG content by CLA is reversible. In expt. 4, glucose incorporation into total lipid decreased with increasing levels of trans-10, cis-12 CLA, whereas neither CLA isomer acutely affected lipolysis. These data suggest that the reported antiobesity actions of a supplement containing a crude mixture of CLA isomers given to humans may be due to inhibition of lipogenesis by the trans-10, cis-12 isomer.

Adipose Tissue↗
PubMed2001

The influence of a baccalaureate program on traditional, RN-BSN, and accelerated students' critical thinking abilities.

Although there are multiple ways of achieving baccalaureate-level nursing education, all graduates must demonstrate critical thinking abilities to practice competently. The purpose of this study was to measure the changes in critical thinking abilities of students pursuing various pathways in the same baccalaureate nursing curriculum. Traditional, registered nurse-bachelor of science (RN-BSN), and accelerated students completed the Watson-Glaser Critical Thinking Appraisal (WGCTA) at the beginning and end of their nursing course sequence. Findings revealed a significant difference between the pre- and post-WGCTA scores of traditional students (t = -2.84, P = .007) and RN-BSN students (t = -2.28, P = .029), but not of accelerated students. Similarities between the curricular pathways that could account for the results were analyzed. Further research is needed to determine the best combination of liberal arts and nursing courses for the development of critical thinking abilities.

Adult↗
PubMed2001

Stationary phantoms and grating induction with oblique inducing gratings: implications for different mechanisms underlying the two phenomena.

The visibility of stationary visual phantoms and the grating induction (GI) effect were concurrently analyzed with both black and gray inspection areas (IA) using the same subjects with counterbalanced orders of measurements. Oblique inducing gratings were employed in order to compare the visibility of obliquely aligned and vertically misaligned appearances between the two phenomena. Aligned and misaligned phantom responses with a black IA were similar, whereas overall phantom visibility was severely suppressed when the IA was gray. In contrast, misaligned GI dominated with a gray IA, whereas aligned and misaligned GI responses were similar with a black IA. Phantoms appear to be related to visual mechanisms' selectively utilizing relative luminance information between the inducing grating and IA in a manner consistent with more global figural characteristics of the display (e.g., modal and amodal completion). On the other hand, GI may be predominantly due to locally operating brightness/contrast mechanisms.

Adult↗
PubMed2001

Regulation of the vesicular monoamine transporter-2: a novel mechanism for cocaine and other psychostimulants.

The plasmalemmal dopamine (DA) transporter (DAT) is a principal site of action for cocaine. This report presents the novel finding that in addition to inhibiting DAT function, cocaine administration rapidly alters vesicular DA transport. Specifically, cocaine treatment abruptly and reversibly increased both the V(max) of DA uptake and the B(max) of vesicular monoamine transporter-2 (VMAT-2) ligand (dihydrotetrabenazine) binding, as assessed ex vivo in purified rat striatal synaptic vesicles. Selective inhibitors of the DAT (amfonelic acid and GBR12935), but not the plasmalemmal serotonin transporter (fluoxetine), also increased vesicular DA uptake. Moreover, DA depletion resulting from administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine had cocaine-like effects. Conversely, administration of the DA-releasing agent methamphetamine rapidly decreased vesicular uptake. Taken together, these data demonstrate for the first time ex vivo that cocaine treatment rapidly alters vesicular monoamine transport, and suggest that alterations in cytoplasmic DA concentrations contribute to stimulant-induced changes in vesicular DA uptake. Hence, the VMAT-2 may be an important target for developing strategies to treat not only cocaine addiction but also other disorders involving alterations in neuronal DA disposition, including Parkinson's disease.

Animals↗
PubMed2001

Cocaine-induced increases in vesicular dopamine uptake: role of dopamine receptors.

The vesicular monoamine transporter-2 is the sole transporter responsible for sequestration of monoamines, including dopamine (DA), into synaptic vesicles. Previous studies demonstrate that agents that inhibit DA transporter function, such as cocaine, increase vesicular [(3)H]DA uptake and binding of the ligand [(3)H]dihydrotetrabenazine ([(3)H]DHTBZ), as assessed in vesicles prepared from treated rats. The present studies examine the role of DA receptors in these cocaine-induced effects. Results demonstrate that administration of the D(2) DA receptor antagonist, eticlopride, but not the D(1) DA receptor antagonist, SCH23390, inhibited these cocaine-induced increases. Similar to the effects of cocaine, treatment with the D(2) agonist, quinpirole, increased both vesicular [(3)H]DA uptake and [(3)H]DHTBZ binding. In contrast, administration of the D(1) agonist, SKF81297, was without effect on vesicular [(3)H]DA uptake or [(3)H]DHTBZ binding. Finally, coadministration of quinpirole and cocaine did not further increase vesicular [(3)H]DA uptake or [(3)H]DHTBZ binding when compared with treatment with either agent alone. These data suggest that cocaine-induced increases in vesicular DA uptake and DHTBZ binding are mediated by a D(2) receptor-mediated pathway. Furthermore, results indicate that D(2) receptor activation, per se, is sufficient to increase vesicular DA uptake.

Animals↗
PubMed2001

Serum osteoprotegerin levels are increased in patients with advanced prostate cancer.

PURPOSE: Osteoprotegerin (OPG) is a soluble osteoclastogenesis inhibitor that regulates bone turnover. We reported recently that OPG protein expression is significantly increased in prostate cancer (CaP) cells present in bone metastases. The aim of this study was to determine serum OPG levels in patients at different stages of CaP and correlate the results with disease status. EXPERIMENTAL DESIGN: OPG levels were examined in patients with benign prostatic hyperplasia, clinically localized CaP, early recurrence of CaP, and advanced CaP and evidence of bone metastases. Serum OPG levels were measured by sandwich ELISA assays. The serum Crosslaps (sCTX) assay was used to quantify bone resorption in the advanced CaP group. RESULTS: Serum OPG levels were increased significantly in the advanced CaP group versus all other groups. There was no significant correlation between serum OPG levels and PSA levels either in the advanced CaP group or within any of three treatment subclasses of this group: no Tx, those not treated; Tx, those treated; and R, those treated with resorption blockers. Levels of OPG were negatively correlated with sCTX levels only in the advanced CaP Tx group. sCTX levels correlated with prostate-specific antigen levels in the advanced CaP Tx and R groups but not in the no-Tx group. CONCLUSIONS: Our data show that serum OPG levels are increased with advanced CaP. We hypothesize that OPG levels are related to CaP progression and suggest that further studies of the biological effects of OPG on CaP metastases are warranted.

Adult↗
PubMed2001

Use of albumin in intensive care units in the United kingdom.

OBJECTIVE: To review the use of intravenous albumin solutions in intensive care units in the United Kingdom. METHODS: A postal questionnaire was sent to the clinical directors of all intensive care units in the United Kingdom (n = 292) asking about their use and indications for intravenous albumin solutions. RESULTS: Responses were received from 261 (89.4%) intensive care units (ICUs). The units were classified as general ICUs (n = 198), paediatric ICUs (n = 22) and combined intensive care/coronary care units (ICU/CCUs) (n = 41). Of the 261 units that replied, 181 (69.3%) reported using intravenous albumin, although the indications varied between units particularly in paediatric intensive care units. The alternatives to albumin also varied between the units. The general ICUs favoured hydroxyethyl starch (n = 129, 65.2%) and/or gelatin solutions (n = 87, 43.9%), as did the combined ICU/CCUs (n = 28, 68.3% and/or n = 23, 56.1% respectively). However, of the paediatric ICUs that used an alternative to albumin solutions (n = 21/22), 12 favoured crystalloid solutions (54.5%) and 9 favoured gelatin solutions (40.9%). We also assessed the impact of the recent review by the Cochrane Injuries Group Reviewers on the use of albumin and found that the respondents of 131 units (50.2%) reported that this study influenced their use of intravenous albumin. Of the 80 units that did not use albumin solutions, 33 units reported that they had ceased using intravenous albumin following the review from the Cochrane Injuries Group Reviewers. CONCLUSIONS: Approximately two-thirds of intensive care units in the United kingdom reported using intravenous albumin, although the indications varied between units. In many of these units the use of intravenous albumin had been influenced by the recent review by the Cochrane Injuries Group Reviewers on the use of albumin.

Journal Article↗
PubMed2000

The Chatt-Dewar-Duncanson model revisited: X-ray, DFT and NMR studies of rhodium-alkene binding--deviations from structural ideality.

An analysis has been made of deviations from ideal centrosymmetric bonding of alkenes to transition metals in square-planar complexes. Three separate approaches have been employed. Firstly, the geometries obtained for a series of X-ray crystal structures of monosubstituted rhodium-alkene complexes have been obtained. Secondly, DFT computations on closely related rhodium-alkene complexes are reported. Thirdly. the data have been augmented by recourse to the crystal structure serach and retrieval file (CSSR) database to retrieve the X-ray data for square-planar ethene and monosubstituted alkene complexes. The results obtained from these analyses provide a consistent picture. Two distortions from ideality are important: twisting of the alkene about the axis between the metal (M) and the alkene centroid and rolling of the alkene around a cylinder enclosing the metal, such that the two C-M bonds remain equal in length. The presence of both of these is verified through both X-ray structure determinations and DFT calculations. For the rolling distortion, there is a relationship between the electronic character of the substituent on the alkene and the direction of roll. The net effect of this is to place the more nucleophilic carbon of the alkene closer to the square plane. The significance of this for the regiochemistry of the Heck reaction is briefly discussed.

Journal Article↗
PubMed2000

Pancreatic tumors show high levels of hypoxia.

PURPOSE: Because of the dismal outcomes of conventional therapies for pancreatic carcinomas, we postulated that hypoxia may exist within these tumors. METHODS AND MATERIALS: Seven sequential patients with adenocarcinomas of the pancreas consented to intraoperative measurements of tumor oxygenation using the Eppendorf (Hamburg, Germany) polargraphic electrode. RESULTS: All 7 tumors demonstrated significant tumor hypoxia. In contrast, adjacent normal pancreas showed normal oxygenation. CONCLUSION: Tumor hypoxia exists within pancreatic cancers.

Aged↗
PubMed2000

An early oxygen-dependent step is required for dexamethasone-induced apoptosis of immature mouse thymocytes.

The roles of oxygen and reactive oxygen intermediates in apoptosis are unclear at present. Although oxygen and reactive oxygen intermediates are not required for the execution of apoptosis, oxygen may be involved in at least some forms of apoptosis. In this study we show that dexamethasone (Dex)-induced apoptosis of immature mouse thymocytes is completely inhibited by hypoxic culture. In contrast, anti-CD95 thymocyte apoptosis is unaffected by hypoxia, indicating the existence of two forms of thymocyte apoptosis: an oxygen-dependent pathway (Dex induced) and an oxygen-independent pathway (anti-CD95 induced). Furthermore, hypoxia inhibited mitochondrial permeability transition (PT) in Dex-treated, but not in anti-CD95-treated, thymocytes, suggesting that the oxygen-sensitive step is upstream of mitochondria. Both Dex- and anti-CD95-induced PT and apoptosis were dependent on activation of IL-converting enzyme-like protease, as PT and apoptosis were inhibited by preincubation with Cbz-Val-Ala-Asp-fluoromethyl ketone, an irreversible inhibitor of IL-converting enzyme-like proteases. In addition, hypoxia inhibited the activation by Dex of caspase-3 (CPP32)-like proteases. Our data show that the private signaling pathways of Dex (oxygen dependent) and anti-CD95 (oxygen independent) both converge upstream of mitochondrial changes. The oxygen-dependent step in Dex-induced apoptosis lies upstream of caspase-3-like protease activation. Our observations support a model of apoptosis signaling in which independent pathways (oxygen dependent and oxygen independent) particular to each stimuli converge at a central point in the apoptotic cascade.

Animals↗
PubMed2000

A region of the vertebrate neural plate in which neighbouring cells can adopt neural or epidermal fates.

Cells in the neurogenic region of the fly, Drosophila melanogaster, become either neural stem cells or epidermis and the selection of the former requires the activity of the proneural genes [1]. In contrast, it is commonly thought that all cells in the vertebrate neural plate contribute to the neural tube and that consequently there is no need for the selection of individual neural precursors (e.g., [2]). Here we present a detailed fate map of the chick caudal neural plate (CNP), a cell population that generates the posterior hindbrain and spinal cord. We show that this is a unique region of the neural plate where neighbouring cells can contribute to neural tube or epidermis. Further, neural tube precursors leave the CNP in an approximate rostro-caudal order and give rise to discrete portions of the neural tube where they or their progeny behave as neural stem cells [3]. Our data suggest that neural and epidermal cell fates are acquired on a cell-by-cell basis within the CNP and thus in a manner strikingly similar to that in the fly. Indeed, the assignment of neural cell fate in this region may prove to be mediated by the functional homologue of the fly proneural genes (chick achaete-scute homologue 4, cash4), which is expressed heterogeneously within this cell population [4].

Animals↗
PubMed2000

Differential effects of methamphetamine on Na(+)/Cl(-)-dependent transporters.

It has been demonstrated that methamphetamine (METH) administration affects Na(+)/Cl(-)-dependent transporters; for example, METH treatment rapidly and reversibly decreases dopamine (DA) and serotonin (5HT) transporter function in rat striatum in vivo, as assessed in synaptosomes prepared from METH-treated rats. Because acute effects of METH on other transporters within this family have been less studied, the responses of norepinephrine (NE) and gamma-aminobutyric acid (GABA) transporters to METH administration(s) were determined. Both single and multiple METH administrations inhibited hippocampal NE uptake 1 h after METH treatment(s). In contrast, striatal GABA uptake was not affected by either treatment paradigm. The effects observed after both single and multiple METH administrations on NE transporters were attributable to increases in K(m,) with no changes in V(max); effects that were eliminated by repeated washing of the synaptosomes. These 'washout' data suggest that residual METH introduced by the in vivo subcutaneous injection(s) directly reduced NE transporter activity in the in vitro assay and that, unlike DA and 5HT transporters, METH did not indirectly alter NE transporter function. Taken together, these data demonstrate differences in the responses of NE, GABA, DA, and 5HT transporters to METH treatment.

Animals↗
PubMed2000

Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent.

Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensitizing agent that combines preferential tumor uptake with detection of drug localization by magnetic resonance imaging (S. W. Young et al., Proc. Natl. Acad. Sci. USA, 93: 6610-6615, 1996). In view of the initial report on this compound, four radiobiology laboratories undertook independent efforts to further study radiosensitization by Gd-tex. In addition to repeating the previously reported studies on Gd-tex in HT-29 cells, we tested five other human tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7). These studies included a Gd-tex treatment period of 24 h before irradiation (as in the original publication), with concentrations of Gd-tex ranging from 20-500 microM. In neither the HT-29 cells nor any of the other five human cell lines did we see radiation sensitization by Gd-tex. Two cell lines (MCF-7 and U-87 MG) were further tested for radiosensitization by Gd-tex under hypoxic conditions. No radiosensitization was observed in either case. Finally, the radiation response of two tumor lines were assessed in vivo. Neither HT-29 xenografts in severe combined immunodeficient (SCID) mice nor RIF-1 tumors growing in C3H mice demonstrated radiosensitization after Gd-tex treatment before single or fractionated doses of radiation. Our results raise questions about the efficacy of Gd-tex as a radiosensitizing agent.

Animals↗
PubMed2000

Diastereoselectivity in scalemic tartrate/titanium epoxidations.

Nonlinearity in the diastereoselectivity of epoxidation of allylic alcohols with mixtures of titanium isopropoxide, tertbutyl hydroperoxide, and diethyl tartrate was observed. Racemic and enantiomerically pure alcohols E-2-methyl-4-hexen-3-ol and E-1-methoxy-5-(O-tertbutyldimethylsilyloxy)-2-penten-4-ol were prepared. Epoxidation reactions were carried out with Ti(OPri)4 and ButOOH accompanied by diethyl tartrate of varying enantiomeric purity. The simplest explanation of these results is that a dimeric epoxidation reagent is involved, with significantly different reactivity for the homochiral and racemic forms.

Journal Article↗
PubMed2000

Transportation or noise is associated with tolerance to myocardial ischemia and reperfusion injury.

Myocardial stress can result in myocellular phenotypic changes including enhanced activity of antioxidant enzyme systems. Accordingly, endogenous tissue antioxidant enzyme activity has been associated with resistance to cardiac ischemia and reperfusion injury. The present study was designed to determine if environmental perturbations could alter myocardial antioxidant enzyme (catalase) activity and function after ischemia. Isolated perfused rat hearts (Langendorff apparatus, 37 degrees C) were subjected to 20 min global ischemia (37 degrees C) and 40 min reperfusion. Rats studied immediately following shipment had increased myocardial catalase activity (1330 +/- 3.5 U/g, P < 0.05 vs quarantined control) and increased resistance to ischemia and reperfusion injury (end reperfusion developed pressure, DP 55 +/- 4.0 mm Hg, P < 0.05 vs quarantined control). However, control rats that were quarantined for 4 weeks exhibited a progressive decrease in catalase activity (760 +/- 10 U/g) for 3 weeks of quarantine. There was a concurrent decrease in resistance to myocardial ischemia and reperfusion injury (DP 40 +/- 3.6 mm Hg). Similarly, quarantined rats subjected to construction-related noise levels in excess of 90 dB (A scale) had increased myocardial catalase activity (1140 +/- 3.3 U/g, P < 0.05) and functional tolerance to ischemia and reperfusion (DP 66 +/- 3.3 mm Hg, P < 0.05). Finally, rats experiencing 90-dB noise levels for 2 days exhibited increased myocardial catalase activity (1125 +/- 30 U/g, P < 0.05) and myocardial ischemia and reperfusion injury tolerance (DP 62 +/- 1.7 mm Hg, P < 0.05). We conclude that variations in environmental conditions can relate to changes in antioxidant defense mechanisms and tolerance to myocardial ischemia and reperfusion injury in the rat.

Adaptation, Physiological↗