Biomedical subjects

James C Smith

Publications and source records attributed to James C Smith.

At least 19 recordsLinked to original sources

PubMed2007

Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA.

B-cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells that are resistant to apoptosis as a result of bcl2 oncogene overexpression. Studies were done to determine the mechanism for the up-regulation of bcl-2 protein observed in CD19+ CLL cells compared with CD19+ B cells from healthy volunteers. The 11-fold higher level of bcl-2 protein in CLL cells was positively correlated with a 26-fold elevation in the cytosolic level of nucleolin, a bcl2 mRNA-stabilizing protein. Measurements of the bcl2 heterogeneous nuclear/bcl2 mRNA (hnRNA)/mRNA ratios and the rates of bcl2 mRNA decay in cell extracts indicated that the 3-fold higher steady-state level of bcl2 mRNA in CLL cells was the result of increased bcl2 mRNA stability. Nucleolin was present throughout the nucleus and cytoplasm of CLL cells, whereas in normal B cells nucleolin was only detected in the nucleus. The addition of recombinant human nucleolin to extracts of normal B cells markedly slowed the rate of bcl2 mRNA decay. SiRNA knockdown of nucleolin in MCF-7 cells resulted in decreased levels of bcl2mRNA and protein but no change in beta-actin. These results indicate that bcl-2 overexpression in CLL cells is related to stabilization of bcl2 mRNA by nucleolin.

B-Lymphocytes↗

PubMed2007

Presystemic influences on thirst, salt appetite, and vasopressin secretion in the hypovolemic rat.

The present studies investigated the influence of presystemic signals on the control of thirst, salt appetite, and vasopressin (VP) secretion in rats during nonhypotensive hypovolemia. Rats were injected with 30% polyethylene glycol (PEG) solution, deprived of food and water overnight, and then allowed to drink water, 0.15 M NaCl, or 0.30 M NaCl. The PEG treatment, which produced 30-40% plasma volume deficits, elicited rapid intakes in an initial bout of drinking, but rats consumed much more 0.15 M NaCl than water or 0.30 M NaCl. In considering why drinking stopped sooner when water or concentrated saline was ingested, it seemed relevant that little or no change in systemic plasma Na(+) concentration was observed during the initial bouts and that the partial repair of hypovolemia was comparable, regardless of which fluid was consumed. In rats that drank 0.15 M NaCl, gastric emptying was fastest and the combined volume of ingested fluid in the stomach and small intestine was largest. These and other observations are consistent with the hypothesis that fluid ingestion by hypovolemic rats is inhibited by distension of the stomach and proximal small intestine and that movement of dilute or concentrated fluid into the small intestine provides another presystemic signal that inhibits thirst or salt appetite, respectively. On the other hand, an early effect of water or saline consumption on VP secretion in PEG-treated rats was not observed, in contrast to recent findings in dehydrated rats. Thus the controls of fluid ingestion and VP secretion are similar but not identical during hypovolemia.

Animals↗

PubMed2006

Suppression of drinking by exposure to a high-strength static magnetic field.

High-strength static magnetic fields of 7 T and above have been shown to have both immediate and delayed effects on rodents, such as the induction of locomotor circling and the acquisition of conditioned taste aversions. In this study, the acute effects of magnet field exposure on drinking were examined. Exposure to a 14.1-T magnetic field for as little as 5 min significantly decreased the amount of a glucose and saccharin solution (G+S) consumed by water-deprived rats over 10 min. The decreased intake could be accounted for largely, but not entirely, by an increase in the latency of magnet-exposed rats to initiate drinking. When intake was measured for 10-60 min after the initiation of drinking, thus controlling for increased latency, magnet-exposed rats still consumed less G+S than sham-exposed rats. The increased latency was not due simply to an inability of magnet-exposed rats to reach the elevated sipper tube of the G+S bottle, providing rats with long tubes that could be reached without raising their heads normalized intake but latency was still increased. The increased latency and decreased intake appeared to be secondary to somatic effects of magnet exposure, however, because during intraoral infusions magnet-exposed rats consumed the same amount of G+S with the same latency to reject as sham-exposed rats. The suppression of drinking by magnetic field exposure is consistent with the acute effects of other aversive stimuli, such as whole-body rotation, on short-term ingestion. These results add to the evidence that high-static strength magnetic fields can have behavioral effects on rodents.

Animals↗

PubMed2006

Neurotrophin receptor homolog (NRH1) proteins regulate mesoderm formation and apoptosis during early Xenopus development.

Recent experiments suggest that Xenopus Neurotrophin Receptor Homolog 1 (NRH1) proteins act through the planar cell polarity pathway to regulate convergent extension movements during gastrulation and neurulation. We show in this paper that NRH1 proteins are also required for the proper expression of mesodermally expressed genes such as Xbra and Chordin, and to a lesser extent, of Xwnt11. Loss of NRH1 function is followed, during gastrula and neurula stages, by a dramatic increase in apoptosis. Apoptosis is delayed by injection of Xbra RNA, suggesting that cell death is a consequence, at least in part, of the down-regulation of this gene, and it is also delayed by expression of activated forms of Rho, Rac and Cdc42. These small GTPases have previously been implicated in the planar cell polarity pathway in Xenopus and, in other systems, in the regulation of apoptosis. We conclude that the effects of NRH1 proteins include the regulation of mesodermal gene expression and that the disruption of gastrulation that is caused by their loss of function is a consequence of the down-regulation of Xbra and other genes, in addition to direct interference with the planar cell polarity pathway. The apoptosis observed in embryos lacking NRH1 function is not an indirect consequence of the disruption of gastrulation, and indeed it may contribute to the observed morphological defects.

Animals↗

PubMed2006

Inhibition of NaCl appetite when DOCA-treated rats drink saline.

Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).

Animals↗

PubMed2006

Zebrafish promoter microarrays identify actively transcribed embryonic genes.

We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation with an antibody directed against tri-methylated lysine 4 of Histone H3, we demonstrate the feasibility of this method in zebrafish. This approach will allow investigators to determine the genomic binding locations of DNA interacting proteins during development and expedite the assembly of the genetic networks that regulate embryogenesis.

Animals↗

PubMed2005

Transcriptional regulation of mesendoderm formation in Xenopus.

Mesoderm and endoderm formation in Xenopus involves the coordinated efforts of maternally and zygotically expressed transcription factors together with growth factor signalling, including members of the TGFbeta and wnt families. In this review we discuss our current state of knowledge of these pathways, and describe in more detail some of the transcription factor-DNA interactions that are involved in mesendoderm formation.

Animals↗

PubMed2005

Inhibition of thirst when dehydrated rats drink water or saline.

The present experiments sought to identify the physiological signals that inhibit thirst when dehydrated rats drink water or NaCl solution. Rats were deprived of drinking fluid but not food overnight. When allowed to drink again, the dehydrated animals consumed water or saline (0.05 M, 0.10 M, 0.15 M, or 0.20 M NaCl solution) almost continuously for 5-8 min before stopping. The volumes consumed were similar regardless of which fluid they ingested, but blood analyses indicated that increased plasma osmolality and decreased plasma volume, or both, still remained when drinking terminated. These results suggest that the composition of the ingested fluid is less significant than its volume in providing an early signal that inhibits thirst and fluid consumption by dehydrated rats. Analyses of the gastrointestinal tracts revealed that the cumulative volume in the stomach and small intestine correlated highly with the amount consumed regardless of which fluid was ingested. These and other results suggest that the volume of fluid ingested by dehydrated rats is sensed by stretch receptors detecting distension of the stomach and small intestine, which provide an early inhibitory stimulus of thirst.

Animals↗

PubMed2005

Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids.

Advances in magnetic resonance imaging are driving the development of higher-resolution machines equipped with high-strength static magnetic fields (MFs). The behavioral effects of high-strength MFs are largely uncharacterized, although in male rats, exposure to 7 T or above induces locomotor circling and leads to a conditioned taste avoidance (CTA) if paired with a novel taste. Here, the effects of MFs on male and female rats were compared to determine whether there are sex differences in behavioral responses and whether these can be explained by ovarian steroid status. Rats were given 10-min access to a novel saccharin solution and then restrained within a 14-T magnet for 30 min. Locomotor activity after exposure was scored for circling and rearing. CTA extinction was measured with two-bottle preference tests. In experiment 1, males were compared with females across the estrous cycle after a single MF exposure. Females circled more and acquired a more persistent CTA than males; circling was highest on the day of estrus. In experiment 2, the effects of three MF exposures were compared among intact rats, ovariectomized females, and ovariectomized females with steroid replacement. Compared with intact rats, ovariectomy increased circling; estrogen replacement blocked the increase. Males acquired a stronger initial CTA but extinguished faster than intact or ovariectomized females. Thus the locomotor circling induced by MF exposure was increased in females and modulated by ovarian steroids across the estrous cycle and by hormone replacement. Furthermore, female rats acquired a more persistent CTA than male rats, which was not dependent on estrous phase or endogenous ovarian steroids.

Animals↗

PubMed2005

Behavioral effects on rats of high strength magnetic fields generated by a resistive electromagnet.

It has been reported previously that exposure to static high magnetic fields of 7 T or above in superconducting magnets has behavioral effects on rats. In particular, magnetic field exposure acutely but transiently suppressed rearing and induced walking in tight circles; the direction of circular locomotion was dependent on the rats' orientation within the magnet. Furthermore, when magnet exposure was paired with consumption of a palatable, novel solution, rats acquired a persistent taste aversion. In order to confirm these results under more controlled conditions, we exposed rats to static magnetic fields of 4 to 19.4 T in a 189 mm bore, 20 T resistive magnet. By using a resistive magnet, field strengths could be arbitrary varied from -19.4 to 19.4 T within the same bore. Rearing was suppressed after exposure to 4 T and above; circling was observed after 7 T and above. Conditioned taste aversion was acquired after 14 T and above. The effects of the magnetic fields were dependent on orientation. Exposure to +14 T induced counter-clockwise circling, while exposure to -14 T induced clockwise circling. Exposure with the rostral-caudal axis of the rat perpendicular to the magnetic field produced an attenuated behavioral response compared to exposure with the rostral-caudal axis parallel to the field. These results in a single resistive magnet confirm and extend our earlier findings using multiple superconducting magnets. They demonstrate that the behavioral effects of exposure within large magnets are dependent on the magnetic field, and not on non-magnetic properties of the machinery. Finally, the effects of exposure to 4 T are clinically relevant, as 4 T magnetic fields are commonly used in functional MRI assays.

Analysis of Variance↗

PubMed2005

Psychobiology and Neuroscience at the Florida State University: a history.

In the 1950s, young faculty in Psychology and Physiology/Biology at the newly established Florida State University recognized common interests in the study of sensory systems. They spontaneously formed one of this country's earliest interdisciplinary research cohorts in the emerging field of "psychobiology". In the 1960s, this group established a formal graduate program in Psychobiology, acquired resources for building a new laboratory and for supporting pre- and post-doctoral students, and began the expansion of faculty and research focuses that continues to this day. In 1991, FSU's Psychobiology Program was re-branded as a Program in Neuroscience that awards a doctoral degree. It now encompasses faculty and students from four academic departments in the Colleges of Arts and Sciences, Human Sciences, and Medicine. This paper traces some main developments in our 50-year history of these research and training efforts.

Behavioral Sciences↗

PubMed2005

Induction and migration of the anterior visceral endoderm is regulated by the extra-embryonic ectoderm.

The anterior visceral endoderm (AVE) is an extra-embryonic tissue required for specifying anterior pattern in the mouse embryo. The AVE is induced at the distal tip of the 5.5 dpc embryo and then migrates to the prospective anterior, where it imparts anterior identity upon the underlying epiblast (the tissue that gives rise to the embryo proper). Little is known about how the AVE is induced and what directs its migration. In this paper, we describe an essential role for another extra-embryonic tissue, the extra-embryonic ectoderm (ExE), in patterning the AVE and epiblast. Removal of the ExE in pre-gastrulation embryos leads to ectopic AVE formation, to a failure of AVE cell migration and to the assumption by the entire epiblast of an anterior identity. Ectopic transplantation of ExE cells inhibits AVE formation and leads to an expansion of the posterior epiblast marker T. These results demonstrate that the ExE restricts the induction of the AVE to the distal tip of the mouse embryo and is required to initiate the migration of these cells to the prospective anterior. Together, these data reveal a novel role for the ExE in the specification of the anteroposterior axis of the mouse embryo.

Animals↗

PubMed2005

The ARID domain protein dril1 is necessary for TGF(beta) signaling in Xenopus embryos.

ARID domain proteins are members of a highly conserved family involved in chromatin remodeling and cell-fate determination. Dril1 is the founding member of the ARID family and is involved in developmental processes in both Drosophila and Caenorhabditis elegans. We describe the first embryological characterization of this gene in chordates. Dril1 mRNA expression is spatiotemporally regulated and is detected in the involuting mesoderm during gastrulation. Inhibition of dril1 by either a morpholino or an engrailed repressor-dril1 DNA binding domain fusion construct inhibits gastrulation and perturbs induction of the zygotic mesodermal marker Xbra and the organizer markers chordin, noggin, and Xlim1. Xenopus tropicalis dril1 morphants also exhibit impaired gastrulation and axial deficiencies, which can be rescued by coinjection of Xenopus laevis dril1 mRNA. Loss of dril1 inhibits the response of animal caps to activin and secondary axis induction by smad2. Dril1 depletion in animal caps prevents both the smad2-mediated induction of dorsal mesodermal and endodermal markers and the induction of ventral mesoderm by smad1. Mesoderm induction by eFGF is uninhibited in dril1 morphant caps, reflecting pathway specificity for dril1. These experiments identify dril1 as a novel regulator of TGF(beta) signaling and a vital component of mesodermal patterning and embryonic morphogenesis.

Animals↗

PubMed2005

XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development.

XPACE4 is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the TGFbeta family of signaling molecules. Studies in mouse suggest it may have important roles in regulating embryonic tissue specification. Here, we examine the role of XPACE4 in Xenopus development and make three novel observations: first, XPACE4 is stored as maternal mRNA localized to the mitochondrial cloud and vegetal hemisphere of the oocyte; second, it is required for the endogenous mesoderm inducing activity of vegetal cells before gastrulation; and third, it has substrate-specific activity, cleaving Xnr1, Xnr2, Xnr3 and Vg1, but not Xnr5, Derriere or ActivinB pro-proteins. We conclude that maternal XPACE4 plays an important role in embryonic patterning by regulating the production of a subset of active mature TGFbeta proteins in specific sites.

Amino Acid Sequence↗

PubMed2005

Functional specificity of the Xenopus T-domain protein Brachyury is conferred by its ability to interact with Smad1.

Members of the T-box gene family play important and diverse roles in development and disease. Here, we study the functional specificities of the Xenopus T-domain proteins Xbra and VegT, which differ in their abilities to induce gene expression in prospective ectodermal tissue. In particular, VegT induces strong expression of goosecoid whereas Xbra cannot. Our results indicate that Xbra is unable to induce goosecoid because it directly activates expression of Xom, a repressor of goosecoid that acts downstream of BMP signaling. We show that the inability of Xbra to induce goosecoid is imposed by an N-terminal domain that interacts with the C-terminal MH2 domain of Smad1, a component of the BMP signal transduction pathway. Interference with this interaction causes ectopic activation of goosecoid and anteriorization of the embryo. These findings suggest a mechanism by which individual T-domain proteins may interact with different partners to elicit a specific response.

Amino Acid Sequence↗

PubMed2005

The novel Smad-interacting protein Smicl regulates Chordin expression in the Xenopus embryo.

In this paper, we investigate the function of Smicl, a zinc-finger Smad-interacting protein that is expressed maternally in the Xenopus embryo. Inhibition of Smicl function by means of antisense morpholino oligonucleotides causes the specific downregulation of Chordin, a dorsally expressed gene encoding a secreted BMP inhibitor that is involved in mesodermal patterning and neural induction. Chordin is activated by Nodal-related signalling in an indirect manner, and we show here that Smicl is involved in a two-step process that is necessary for this activation. In the first, Smad3 (but not Smad2) activates expression of Xlim1 in a direct fashion. In the second, a complex containing Smicl and the newly induced Xlim1 induces expression of Chordin. As well as revealing the function of Smicl in the early embryo, our work yields important new insight in the regulation of Chordin and identifies functional differences between the activities of Smad2 and Smad3 in the Xenopus embryo.

Amino Acid Sequence↗

PubMed2005

Achieving cholesterol target in a managed care organization (ACTION) trial.

STUDY OBJECTIVES: To objectively compare the results of a collaborative approach using pharmacists with the results of usual care for achieving a low-density lipoprotein cholesterol (LDL) goal of 100 mg/dl or less in outpatients with documented coronary heart disease (CHD) who are not at goal, and to document the effect on LDL after removal of such a collaborative model from the study population. DESIGN: Prospective, multiclinic, controlled study. SETTING: Four clinics of a 19-clinic staff model health maintenance organization in Minneapolis and St. Paul, Minnesota. Two clinics treated the intervention patients, two the controls; one clinic for each group was suburban, and one for each was urban. PATIENTS: Four hundred eighty-one patients aged 18 years or older with CHD and whose LDL levels were not at goal. INTERVENTION: Clinical pharmacists implemented the physician-approved care plan for each intervention patient; activities included managing lipid-lowering drug therapy and educating patients on cardiovascular risk reduction. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were changes in LDL level and the proportion of patients achieving goal LDL in the intervention versus the usual care (control) group. Secondary outcomes were the sustainability of the impact observed up to 18 months after discontinuation of the intervention. Mean+/-SD baseline LDL levels were 131+/-28 and 131+/-26 mg/dl (p=NS) for the intervention and control groups, respectively. After a mean of 6.5 months follow-up, 107 (72%) patients in the intervention group and 61 (18%) patients in the control group had attained their LDL goal (p<0.001). Mean LDL levels were reduced by 35.6 mg/dl (27.5%) and 6.7 mg/dl (4.6%) in the intervention and control groups, respectively (p<0.001). When the active program was discontinued, results of the 18-month follow-up indicated that 85 (65%) intervention patients remained at goal compared with 96 (42%) controls (p<0.001). CONCLUSION: This trial provides quantitative evidence to support the effectiveness of the collaborative approach as an intervention to optimize management of patients with CHD whose LDL levels are not at goal; this approach is specifically called for in the executive summary of the National Cholesterol Education Program Adult Treatment Panel III. Furthermore, this study documents both the magnitude and sustainability of the impact collaborative care models can have in managed care environments.

Aged↗

PubMed2005

Haloperidol: an alternative butyrophenone for nausea and vomiting prophylaxis in anesthesia.

Droperidol has been an efficacious, inexpensive butyrophenone used since the early 1970s to prevent or treat postoperative nausea and vomiting. Because of reports of sudden cardiac death in patients receiving droperidol, the US Food and Drug Administration (FDA) recently placed significant restrictions on its administration. These restrictions have essentially removed droperidol from use. Haloperidol is another butyrophenone with antiemetic properties but without the FDA restrictions. This article reviews the literature regarding haloperidol and supports its use as a safe substitute for droperidol in the prevention and treatment of postoperative nausea and vomiting.

Antiemetics↗