297 research outputs found
Direct activation of RNA polymerase III transcription by c-Myc
The proto-oncogene product c-Myc has a direct role in both metazoan cell growth and division. RNA polymerase III (pol III) is involved in the generation of transfer RNA and 5S ribosomal RNA, and these molecules must be produced in bulk to meet the need for protein synthesis in growing cells. We demonstrate here that c-Myc binds to TFIIIB, a pol III-specific general transcription factor, and directly activates pol III transcription. Chromatin immunoprecipitation reveals that endogenous c-Myc is present at tRNA and 5S rRNA genes in cultured mammalian cells. These results suggest that activation of pol III may have a role in the ability of c-Myc to stimulate cell growt
Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat
The present study examined whether an abnormality in the myogenic response
of renal arterioles that impairs autoregulation of renal blood flow (RBF)
and glomerular capillary pressure (PGC) contributes to the development of
renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of
whole kidney, cortical, and medullary blood flow and PGC were compared in
young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in
volume-replete and volume-expanded conditions. Baseline RBF, cortical and
medullary blood flow, and PGC were significantly greater in FHH than in
FHL rats. Autoregulation of renal and cortical blood flow was
significantly impaired in FHH rats compared with results obtained in FHL
rats. Myogenically mediated autoregulation of PGC was significantly
greater in FHL than in FHH rats. PGC rose from 46 +/- 1 to 71 +/- 2 mmHg
in response to an increase in renal perfusion pressure from 100 to 150
mmHg in FHH rats, whereas it only increased from 39 +/- 2 to 53 +/- 1 mmHg
in FHL rats. Isolated perfused renal interlobular arteries from FHL rats
constricted by 10% in response to elevations in transmural pressure from
70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats
increased by 15%. These results indicate that the myogenic response of
small renal arteries is altered in FHH rats, and this contributes to an
impaired autoregulation of renal blood flow and elevations in PGC in this
strain
Impaired autoregulation of renal blood flow in the fawn-hooded rat
The responses to changes in renal perfusion pressure (RPP) were compared
in 12-wk-old fawn-hooded hypertensive (FHH), fawn-hooded low blood
pressure (FHL), and August Copenhagen Irish (ACI) rats to determine
whether autoregulation of renal blood flow (RBF) is altered in the FHH
rat. Mean arterial pressure was significantly higher in conscious,
chronically instrumented FHH rats than in FHL rats (121 +/- 4 vs. 109 +/-
6 mmHg). Baseline arterial pressures measured in
ketamine-Inactin-anesthetized rats averaged 147 +/- 2 mmHg (n = 9) in FHH,
132 +/- 2 mmHg (n = 10) in FHL, and 123 +/- 4 mmHg (n = 9) in ACI rats.
Baseline RBF was significantly higher in FHH than in FHL and ACI rats and
averaged 9.6 +/- 0.7, 7.4 +/- 0.5, and 7.8 +/- 0.9 ml. min-1. g kidney
wt-1, respectively. RBF was autoregulated in ACI and FHL but not in FHH
rats. Autoregulatory indexes in the range of RPPs from 100 to 150 mmHg
averaged 0.96 +/- 0.12 in FHH vs. 0.42 +/- 0.04 in FHL and 0.30 +/- 0.02
in ACI rats. Glomerular filtration rate was 20-30% higher in FHH than in
FHL and ACI rats. Elevations in RPP from 100 to 150 mmHg increased urinary
protein excretion in FHH rats from 27 +/- 2 to 87 +/- 3 microg/min,
whereas it was not significantly altered in FHL or ACI rats. The
percentage of glomeruli exhibiting histological evidence of injury was not
significantly different in the three strains of rats. These results
indicate that autoregulation of RBF is impaired in FHH rats before the
development of glomerulosclerosis and suggest that an abnormality in the
control of renal vascular resistance may contribute to the development of
proteinuria and renal failure in this strain of rats
22: Ex-vivo expansion (EvE) of previously cryopreserved cord blood (CB) into natural killer (NK) cells with enhanced AML and neuroblastoma cytotoxicity Potential role of CB NK cells in adoptive cellular immunotherapy (ACI)
Newsletter providing "a lighter, human interest side of the news" from the Boston University Medical Campus
Proton Stripping to Stretched States in 26-Al, 52-Cr, and 60-Si
This research was sponsored by the National Science Foundation Grant NSF PHy 87-1440
The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia
Energetics and Possible Formation and Decay Mechanisms of Vortices in Helium Nanodroplets
The energy and angular momentum of both straight and curved vortex states of
a helium nanodroplet are examined as a function of droplet size. For droplets
in the size range of many experiments, it is found that during the pickup of
heavy solutes, a significant fraction of events deposit sufficient energy and
angular momentum to form a straight vortex line. Curved vortex lines exist down
to nearly zero angular momentum and energy, and thus could in principle form in
almost any collision. Further, the coalescence of smaller droplets during the
cooling by expansion could also deposit sufficient angular momentum to form
vortex lines. Despite their high energy, most vortices are predicted to be
stable at the final temperature (0.38 K) of helium nanodroplets due to lack of
decay channels that conserve both energy and angular momentum.Comment: 10 pages, 8 figures, RevTex 4, submitted to Phys. Rev.
Self-consistent solution of the Schwinger-Dyson equations for the nucleon and meson propagators
The Schwinger-Dyson equations for the nucleon and meson propagators are
solved self-consistently in an approximation that goes beyond the Hartree-Fock
approximation. The traditional approach consists in solving the nucleon
Schwinger-Dyson equation with bare meson propagators and bare meson-nucleon
vertices; the corrections to the meson propagators are calculated using the
bare nucleon propagator and bare nucleon-meson vertices. It is known that such
an approximation scheme produces the appearance of ghost poles in the
propagators. In this paper the coupled system of Schwinger-Dyson equations for
the nucleon and the meson propagators are solved self-consistently including
vertex corrections. The interplay of self-consistency and vertex corrections on
the ghosts problem is investigated. It is found that the self-consistency does
not affect significantly the spectral properties of the propagators. In
particular, it does not affect the appearance of the ghost poles in the
propagators.Comment: REVTEX, 7 figures (available upon request), IFT-P.037/93,
DOE/ER/40427-12-N9
Sibling Rivalry among Paralogs Promotes Evolution of the Human Brain
Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution
An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ
Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow
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