Cholesterol Primer for Health Professionals

As research continues in the field of coronary artery disease, more information is revealed about various etiological factors. Emerging lipoprotein risk factors have been identified and are now starting to surface as instrumental in the cause and prevention of coronary artery disease. In order to conduct comprehensive cholesterol screening programs and counseling sessions a health professional must have a thorough understanding of lipid metabolism. Recent changes in cholesterol guidelines make it necessary to have a review that addresses the specifics of lipid management. A health professional needs an appropriate knowledge base to be able to understand a major coronary artery disease risk factor and thereby more effectively educate the public about lipid management and coronary artery disease risk reduction. Therefore, the purpose of this article is to review the role of cholesterol in both normal physiological functioning and disease causation and to examine the research concerning new emerging cholesterol risk factors

Experimental Limit on the Cosmic Diffuse Ultra-high Energy Neutrino Flux

We report results from 120 hours of livetime with the Goldstone Lunar Ultra-high energy neutrino Experiment (GLUE). The experiment searches for <10 ns microwave pulses from the lunar regolith, appearing in coincidence at two large radio telescopes separated by 22 km and linked by optical fiber. Such pulses would arise from subsurface electromagnetic cascades induced by interactions of >= 100 EeV neutrinos in the lunar regolith. No candidates are yet seen, and the implied limits constrain several current models for ultra-high energy neutrino fluxes.Comment: 4 pages, 4 figures, revtex4 style. New intro section, Fig. 2, Fig 4; in final PRL revie

Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules

Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules. Loin painhematuria (LPH) syndrome is a poorly understood disorder in which the patients, mainly young women, experience unexplained severe chronic unilateral or bilateral flank pain associated with gross and/or microscopic hematuria. By contrast, thin glomerular basement membrane (GBM) disease is generally thought to be a benign disorder, affecting males and females equally, in which the major manifestation is asymptomatic microscopic hematuria. Herein we describe seven patients (6 females, 1 male) in whom thin GBM appeared to be the cause of the LPH syndrome. The gross hematuria in these patients could be attributed to thin GBM disease because the renal biopsy demonstrated red cells in renal tubules (indicating glomerular hematuria) and the only glomerular abnormality present was thin GBM. In addition, the other causes of gross hematuria were excluded by appropriate testing. The flank pain in these patients might also have been the result of their thin GBM disease. This is suggested by renal biopsy findings of multiple renal tubules filled with red cells, apparently occluding the tubules. We suggest that occlusion of a relatively small fraction of renal tubules could cause renal pain if back-leak of glomerular filtrate occurred that was of sufficient magnitude to expand renal parenchymal volume and stretch the renal capsule. Preliminary observations suggest that treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril importantly reduces the frequency and severity of the episodes of gross hematuria and flank pain in most patients. ACE inhibition might decrease glomerular hemorrhage in patients with thin GBM by decreasing glomerular hydrostatic pressure. We conclude that (1) Thin GBM disease can be the cause of gross hematuria, apparently as a result of rupture of thin GBM. (2) Rupture of thin GBM resulting in hemorrhage into renal tubules may be the cause of the flank pain and gross hematuria in some patients with the LPH syndrome

Hypoxia-inducible factor-1α polymorphisms and TSC1/2 mutations are complementary in head and neck cancers

BACKGROUND: Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF-1alpha) that increases its activity and stability under normoxia have recently been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1α. Here, we investigate the novel polymorphisms in exon 12, that approximate the oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28 patients with oral squamous carcinomas. Moreover, we assess for the presence of polymorphisms and mutations in TSC1 and TSC2, to ascertain if dysregulation of such might complement HIF-1alpha expression. RESULTS: Denaturing high pressure liquid chromatography (DHPLC) analysis on PCR fragments in exon 12 of HIF-1alpha from 28 patients with OSCC revealed that 6 of 28 patients had mismatched heteroduplex patterns. Genomic DNA was extracted from peripheral blood leukocytes and direct sequencing showed that in 5 of the six cases these changes represented polymorphisms while, one case was a somatic mutation. Analyses of TSC1 and TSC2 revealed heteroduplexes in exons: TSC1 exon 17; TSC2 exons 36,40, and 41. The relative levels of HIF-1alpha were significantly greater for tumors possessing a HIF-1alpha polymorphism or mutation within exon 12, whereas tumors possessing a deletion or polymorphism in TSC1/TSC2 displayed a trend for higher levels of HIF-1alpha. Western blot analyses for HIF-1alpha, TSC1 and TSC2 in five SCC cell lines revealed high levels of HIF-1alpha in SCC cells possessing TSC1 and/or TSC2 mutations. Wild-type TSC2 cells targeted with siRNA to TSC2 exhibited increased levels of HIF-1alpha. Transfection of a HIF-1alpha mutant produced higher levels of HIF-1alpha in TSC1/TSC2 mutant cell lines than in wild type cells. TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild type TSC1/TSC2. CONCLUSION: Dysregulation of the TSC1/TSC2 complex by mutation compliments HIF-1α polymorphisms in the expression of HIF-1alpha in SCC of the head and neck, and may provide biomarkers to predict responses to specific therapies and overall disease prognosis

Phase behaviour of charged colloidal sphere dispersions with added polymer chains

We study the stability of mixtures of highly screened repulsive charged spheres and non-adsorbing ideal polymer chains in a common solvent using free volume theory. The effective interaction between charged colloids in an aqueous salt solution is described by a screened-Coulomb pair potential, which supplements the pure hard-sphere interaction. The ideal polymer chains are treated as spheres that are excluded from the colloids by a hard-core interaction, whereas the interaction between two ideal chains is set to zero. In addition, we investigate the phase behaviour of charged colloid-polymer mixtures in computer simulations, using the two-body (Asakura-Oosawa pair potential) approximation to the effective one-component Hamiltonian of the charged colloids. Both our results obtained from simulations and from free volume theory show similar trends. We find that the screened-Coulomb repulsion counteracts the effect of the effective polymer-mediated attraction. For mixtures of small polymers and relatively large charged colloidal spheres, the fluid-crystal transition shifts to significantly larger polymer concentrations with increasing range of the screened-Coulomb repulsion. For relatively large polymers, the effect of the screened-Coulomb repulsion is weaker. The resulting fluid-fluid binodal is only slightly shifted towards larger polymer concentrations upon increasing the range of the screened-Coulomb repulsion. In conclusion, our results show that the miscibility of dispersions containing charged colloids and neutral non-adsorbing polymers increases, upon increasing the range of the screened-Coulomb repulsion, or upon lowering the salt concentration, especially when the polymers are small compared to the colloids.Comment: 25 pages,13 figures, accepted for publication on J.Phys.:Condens. Matte

HDAC I Inhibition in the Dorsal and Ventral Hippocampus Differentially Modulates Predator-Odor Fear Learning and Generalization

Although predator odors are ethologically relevant stimuli for rodents, the molecular pathways and contribution of some brain regions involved in predator odor conditioning remain elusive. Inhibition of histone deacetylases (HDACs) in the dorsal hippocampus has been shown to enhance shock-induced contextual fear learning, but it is unknown if HDACs have differential effects along the dorso-ventral hippocampal axis during predator odor fear learning. We injected MS-275, a class I HDAC inhibitor, bilaterally in the dorsal or ventral hippocampus of mice and found that it had no effects on innate anxiety in either region. We then assessed the effects of MS-275 at different stages of fear learning along the longitudinal hippocampal axis. Animals were injected with MS-275 or vehicle after context pre-exposure (pre-conditioning injections), when a representation of the context is first formed, or after exposure to coyote urine (post-conditioning injections), when the context becomes associated with predator odor. When MS-275 was administered after context pre-exposure, dorsally injected animals showed enhanced fear in the training context but were able to discriminate it from a neutral environment. Conversely, ventrally injected animals did not display enhanced learning in the training context but generalized the fear response to a neutral context. However, when MS-275 was administered after conditioning, there were no differences between the MS-275 and vehicle control groups in either the dorsal or ventral hippocampus. Surprisingly, all groups displayed generalization to a neutral context, suggesting that predator odor exposure followed by a mild stressor such as restraint leads to fear generalization. These results may elucidate distinct functions of the dorsal and ventral hippocampus in predator odor-induced fear conditioning as well as some of the molecular mechanisms underlying fear generalization

Neutrinos Have Mass - So What?

In this brief review, I discuss the new physics unveiled by neutrino oscillation experiments over the past several years, and discuss several attempts at understanding the mechanism behind neutrino masses and lepton mixing. It is fair to say that, while significant theoretical progress has been made, we are yet to construct a coherent picture that naturally explains non-zero, yet tiny, neutrino masses and the newly revealed, puzzling patterns of lepton mixing. I discuss what the challenges are, and point to the fact that more experimental input (from both neutrino and non-neutrino experiments) is dearly required - and that new data is expected to reveal, in the next several years, new information. Finally, I draw attention to the fact that neutrinos may have only just begun to reshape fundamental physics, given the fact that we are still to explain the LSND anomaly and because the neutrino oscillation phenomenon is ultimately sensitive to very small new-physics effects.Comment: invited brief review, 15 pages, 1 eps figure, typo corrected, reference adde

Observations of Microwave Continuum Emission from Air Shower Plasmas

We investigate a possible new technique for microwave measurements of ultra-high energy cosmic ray (UHECR) extensive air showers which relies on detection of expected continuum radiation in the microwave range, caused by free-electron collisions with neutrals in the tenuous plasma left after the passage of the shower. We performed an initial experiment at the AWA (Argonne Wakefield Accelerator) laboratory in 2003 and measured broadband microwave emission from air ionized via high energy electrons and photons. A follow-up experiment at SLAC (Stanford Linear Accelerator Center) in summer of 2004 confirmed the major features of the previous AWA observations with better precision and made additional measurements relevant to the calorimetric capabilities of the method. Prompted by these results we built a prototype detector using satellite television technology, and have made measurements indicating possible detection of cosmic ray extensive air showers. The method, if confirmed by experiments now in progress, could provide a high-duty cycle complement to current nitrogen fluorescence observations of UHECR, which are limited to dark, clear nights. By contrast, decimeter microwave observations can be made both night and day, in clear or cloudy weather, or even in the presence of moderate precipitation.Comment: 15 pages, 13 figure

Two-Dimensional Quantum XY Model with Ring Exchange and External Field

We present the zero-temperature phase diagram of a square lattice quantum spin 1/2 XY model with four-site ring exchange in a uniform external magnetic field. Using quantum Monte Carlo techniques, we identify various quantum phase transitions between the XY-order, striped or valence bond solid, staggered Neel antiferromagnet and fully polarized ground states of the model. We find no evidence for a quantum spin liquid phase.Comment: 4 pages, 4 figure

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers

Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 μg intraperitoneally or 5 μg subcutaneously (s.c.) resulted in a significant 43–45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 μg s.c. produced a 43–58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells. © 2000 Cancer Research Campaig