Search PubMed⌕ Search

Biomedical subjects

D Ambrose

Publications and source records attributed to D Ambrose.

69 records · Page 4Linked to original sources
PubMed2003

Search for a W' boson decaying to a top and bottom quark pair in 1.8 TeV pp collisions.

We report the results of a search for a W' boson produced in pp; collisions at a center-of-mass energy of 1.8 TeV using a 106 pb(-1) data sample recorded by the Collider Detector at Fermilab. We observe no significant excess of events above background for a W' boson decaying to a top and bottom quark pair. In a model where this boson would mediate interactions involving a massive right-handed neutrino (nu(R)) and have standard model strength couplings, we use these data to exclude a W' boson with mass between 225 and 536 GeV/c(2) at 95% confidence level for M(W')>>M(nu(R)) and between 225 and 566 GeV/c(2) at 95% confidence level for M(W')<M(nu(R)).

Journal Article↗
PubMed2003

Clinical course and short-term outcome of hospitalized adolescents with eating disorders: the success of combining adolescents and adults on an eating disorders unit.

Although significant controversy exists regarding the appropriate setting for treating adolescents with eating disorders, empirical studies have been lacking. This study aimed to evaluate, and compare with adults, the clinical course and short-term outcome of adolescents with eating disorders hospitalized on an adult eating disorders unit. One hundred forty-four consecutive inpatient admissions on a weight gain protocol (28% minors and 72% adults) completed psychometric measures and were assessed on clinical indices. No differences between minors and adults were demonstrated for weight gain per week on either inpatient or partial hospitalization admissions. Whereas inpatient length of stay was equivalent, adolescents stayed significantly longer in partial hospitalization than adults. Minors did not differ from adults on the presence of problematic eating disordered behaviors or most psychometric measures, although they had less functional interference due to their eating disorders. Results suggest that an adult eating disorders specialty program can be an appropriate and efficacious setting for adolescents.

Adolescent↗
PubMed2002

Limits on extra dimensions and new particle production in the exclusive photon and missing energy signature in pp collisions at square root [s]=1.8 TeV.

The exclusive gammaE(T) signal has a small standard model cross section and is thus a channel sensitive to new physics. This signature is predicted by models with a superlight gravitino or with large extra spatial dimensions. We search for such signals at the Collider Detector at Fermilab, using 87 pb(-1) of data at square root [s]=1.8 TeV, and extract 95% C.L. limits on these processes. A limit of 221 GeV is set on the scale |F|(1/2) in supersymmetric models. For 4, 6, and 8 extra dimensions, model-dependent limits on the fundamental mass scale M(D) of 0.55, 0.58, and 0.60 TeV, respectively, are found. We also specify a "pseudo-model-independent" method of comparing the results to theoretical predictions.

Journal Article↗
PubMed2002

Search for new physics in photon-lepton events in pp collisions at sqrt[s] = 1.8 TeV.

We present the results of a search in pp collisions at sqrt[s] = 1.8 TeV for anomalous production of events containing a photon and a lepton (e or mu), both with large transverse energy, using 86 pb(-1) of data collected with the Collider Detector at Fermilab during the 1994-1995 collider run at the Fermilab Tevatron. The presence of large missing transverse energy (E(T)), additional photons, or additional leptons in these events is also analyzed. The results are consistent with standard model expectations, with the possible exception of photon-lepton events with large E(T), for which the observed total is 16 events and the expected mean total is 7.6+/-0.7 events.

Journal Article↗
PubMed2002

Upsilon production and polarization in p p macro collisions at square root of s = 1.8 TeV.

We report on measurements of the Upsilon(1S), Upsilon(2S), and Upsilon(3S) differential cross sections (d(2)sigma/dp(T)dy)(/y/<0.4), as well as on the Upsilon(1S) polarization in p p macro collisions at square root of s = 1.8 TeV using a sample of 77+/-3 pb(-1) collected by the collider detector at Fermilab. The three resonances were reconstructed through the decay Upsilon-->mu(+)mu(-). The measured angular distribution of the muons in the Upsilon(1S) rest frame is consistent with unpolarized meson production.

Journal Article↗
PubMed2002

Diffractive dijet production at sqrt[s] = 630 and 1800 GeV at the Fermilab Tevatron.

We report a measurement of the diffractive structure function F(D)(jj) of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in pp collisions at sqrt[s] = 630 GeV at the Fermilab Tevatron. The ratio of F(D)(jj) at sqrt[s] = 630 GeV to F(D)(jj) obtained from a similar measurement at sqrt[s] = 1800 GeV is compared with expectations from QCD factorization and other theoretical predictions. We also report a measurement of the xi ( x-Pomeron) and beta ( x of parton in Pomeron) dependence of F(D)(jj) at sqrt[s] = 1800 GeV. In the region 0.035<xi<0.095, /t/<1 GeV2, and beta<0.5, F(D)(jj)(beta,xi) is found to be of the form beta(-1.0+/-0.1)xi(-0.9+/-0.1), which obeys beta-xi factorization.

Journal Article↗
PubMed2000

Improved branching ratio measurement for the decay K(0)(L) --> &mgr;(+)&mgr;(-)

We report results from Experiment 871, performed at the BNL AGS, of a measurement of the branching ratio K(0)(L)-->&mgr;(+)&mgr;(-) with respect to the CP-violating mode K(0)(L)-->pi(+)pi(-). This experiment detected over 6200 candidate &mgr;(+)&mgr;(-) events, a factor of 6 more than that seen in all previous measurements combined. The resulting branching ratio gamma(K(0)(L)-->&mgr;(+)&mgr;(-))/gamma(K(0)(L)-->pi(+)pi(-)) = (3. 474+/-0.057)x10(-6) leads to a branching fraction B(K(0)(L)-->&mgr;(+)&mgr;(-)) = (7.18+/-0.17)x10(-9), which is consistent with the current world average, and reduces the uncertainty in this decay mode by a factor of 3.

Journal Article↗
PubMed1998

Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.

Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinase-dead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts.

Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling.

Animals↗
PubMed1994

Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors.

Insulin-like growth factor-1 (IGF-1) and IGF-2 are critical regulators of cell proliferation. The growth-promoting action of both ligands is mediated by the type 1 IGF receptor (IGF-1R). We have investigated the role of the IGF-1R in the growth and tumorigenicity of rat C6 glioblastoma cells. For this purpose, antisense RNA to IGF-1R RNA was introduced into cells by either the addition of oligodeoxynucleotides or by transfection with plasmids that express antisense RNA to IGF-1R RNA. At low cell density, C6 cells grew slowly in serum-free medium and proliferated with the sole addition of IGF-1 or IGF-2. Both antisense IGF-1R oligodeoxynucleotides and stable transfection with a plasmid expressing an antisense IGF-1R RNA inhibited IGF-1-mediated growth in monolayers and clonogenicity in soft agar. Sense oligodeoxynucleotides and sense-expressing plasmid had no effect on either parameter. In stable antisense transfectants, tyrosine-phosphorylated IGF-1 receptors were not detectable, although they were easily detected in wild-type cells. When wild-type C6 cells were injected s.c. into syngeneic immunocompetent rats, tumors developed within 1 week. In contrast, stably transfected C6 cells overexpressing antisense IGF-1R RNA were nontumorigenic. Moreover, when C6 IGF-1R antisense cells were injected, subsequent tumor formation by wild-type C6 cells was completely prevented. Finally, injection of C6 IGF-1R antisense cells into rats carrying an established wild-type C6 tumor caused complete regression of the tumors. The results demonstrate the critical importance of the IGF-1R in glioblastoma cell growth, clonogenicity, and tumorigenicity. Although the mechanism is presently unknown, the fact that the injection of C6 cells expressing an antisense RNA to IGF-1R RNA leads to regression of already established wild-type C6 tumors suggests the possibility of practical applications.

Animals↗
PubMed1994

Growth regulation of human glioblastoma T98G cells by insulin-like growth factor-1 and its receptor.

The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is an important step in the control of cell proliferation and development. In particular, IGF-1 and IGF-2 are key regulators of central nervous system development, and may modulate the growth of glial tumors. We have investigated the growth factor regulation of the human glioblastoma cell line T98G. These cells growth arrested in serum-free medium at 34 degrees C, despite their secretion of substantial amounts of bioactive IGF-1. To be stimulated to divide, growth-arrested cells required the addition of platelet-derived growth factor (PDGF) or its equivalent, 1% serum. Cell proliferation in serum-free medium could also be obtained by shifting the cells to a temperature of 39.6 degrees C. Treatment of growth-arrested cells with PDGF or temperature shift was accompanied by a transient increase in the expression of the mRNA for the IGF-1 receptor. Transfection with a plasmid constitutively expressing the full cDNA for the human IGF-1 receptor allowed autonomous growth in serum-free medium at 34 degrees C. By contrast, growth induction by growth factors or temperature shift was abrogated by transfection of the cells with a plasmid expressing a 300 bp segment of mRNA antisense to the IGF-1 receptor mRNA. Cloning in soft agar was also inhibited by expression of antisense IGF-1 receptor mRNA. These results demonstrate that the IGF-1 receptor is strictly required for the growth of T98G glioblastoma cells. Moreover, the autocrine interaction of IGF-1 with its receptor regulates both autonomous and anchorage-independent growth of these cells.

Base Sequence↗
PubMed1993

Ethanol inhibits the autophosphorylation of the insulin-like growth factor 1 (IGF-1) receptor and IGF-1-mediated proliferation of 3T3 cells.

The effect of ethanol on cell proliferation was studied in Balb/c 3T3 cells and in stably transfected 3T3 cells constitutively overexpressing the human insulin-like growth factor 1 (IGF-1) receptor (p6 cells). Ethanol inhibited growth of both cell lines when they were cultured in serum-free medium supplemented with individual growth factors, i.e. platelet-derived growth factor and IGF-1 for 3T3 cells, and IGF-1 only for p6 cells. Increases in cell number were prevented in both cell lines even when ethanol was present exclusively during the period of IGF-1 stimulation. The inhibitory effect of ethanol was concentration-dependent, with a 30% inhibition observed at 10 mM ethanol. IGF-1 receptor tyrosine autophosphorylation was completely prevented by ethanol both in intact cells and in immunopurified IGF-1 receptor preparations. The binding of IGF-1 to its receptor on intact cells was unaffected by ethanol. Ethanol also inhibited the stimulation of IGF-1 receptor autophosphorylation and the corresponding growth of p6 cells induced by IGF-2. Transcription of c-myc, c-fos, and c-jun in response to IGF-1 was inhibited by ethanol. These findings demonstrate that ethanol at low concentrations markedly inhibits IGF-1 receptor autophosphorylation and IGF-1-mediated cell growth.

3T3 Cells↗
PubMed1993

Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.

BACKGROUND: IGF-1 regulates the growth of diverse mammalian cell types including several human carcinoma cell lines. The IGF-1 receptor is a glycosylated heterodimer which, upon binding with IGF-1, undergoes tyrosine autophosphorylation. The autophosphorylation of the beta-receptor subunit is a strict requirement for its mitogenic properties. EXPERIMENTAL DESIGN: In this study, we have assessed the role of the IGF-1 receptor in the proliferation of ovarian carcinoma cell lines in culture. Effects of anti-sense and sense oligodeoxynucleotides to IGF-1 receptor RNA were tested. RESULTS: The human ovarian carcinoma cell lines OVCAR-3 and CaOV-3 both grew autonomously in serum-free medium, and their growth was further stimulated by the addition of IGF-1. Incubation of cells with anti-sense oligodeoxynucleotides corresponding to the IGF-1 receptor RNA markedly inhibited cell proliferation both in serum-free medium and in the presence of IGF-1. The inhibition of cell growth by the oligodeoxynucleotides corresponded to a reduction in the amount of detectable phosphorylated IGF-1 receptor. CONCLUSIONS: The findings indicate that IGF-1 and its specific receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.

Animals↗
PubMed1990

31P nuclear magnetic resonance (NMR) identification of sugar phosphates in isolated rat ovarian follicular granulosa cells and the effects of follicle-stimulating hormone.

Immature female rats (23-30 days old) were implanted subcutaneously with diethylstilbestrol (DES) in silastic capsules. After 48 h their ovaries were removed and the granulosa cells isolated (Foreman et al. (1984) Life Sci. 35, 1273-1279). The cells were incubated in Hepes balanced saline buffer with substrates with or without follicle-stimulating hormone (FSH). At the end of incubation perchloric acid extracts were made for 31P NMR spectroscopy. The resonances of fructose 1-phosphate, fructose 6-phosphate, glucose 1-phosphate, and ribose 5-phosphate were identified in the granulosa cell extracts. The relative intensities of fructose 6-phosphate to ribose 5-phosphate decreased after incubation with FSH in vitro. This suggests that FSH increases the activity of the pentose pathway within 1 h. Thus, FSH can acutely activate those metabolic pathways which provide nicotinamide-adenine dinucleotide phosphate (NADPH) to be used in steroid synthesis and cholesterol mobilization.

Animals↗