Seo YK,Zhu B,Jeon TI,Osborne TF
Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900, USA.
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Regulation of steroid 5-alpha reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin.
Exp Cell Res. 2009 Nov 1;315(18):3133-9
In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.
PMID: 19500568
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Bonizzoni M,Afrane Y,Baliraine FN,Amenya DA,Githeko AK,Yan G
Program in Public Health, College of Health Sciences, University of California, Irvine 92697, USA. mbonizzo@uci.edu
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Genetic structure of Plasmodium falciparum populations between lowland and highland sites and antimalarial drug resistance in Western Kenya.
Infect Genet Evol. 2009 Sep;9(5):806-12
Human travel to malaria endemic lowlands from epidemic highlands has been shown to increase the risk of malaria infections in the highlands. In order to gain insight on the impact of human travel, we examined prevalence, genetic variability and population genetic structure of Plasmodium falciparum in asymptomatic children from one highland site and three surrounding malaria endemic lowland sites in Western Kenya, using multilocus microsatellite genotyping. We further analyzed the frequencies of mutations at the genes conferring resistance to chloroquine and sulfadoxine-pyrimethamine. We found a significant decrease in malaria prevalence in the highland site from 2006 to 2007, 1 year after the introduction of the artemisinin-based combination therapy as first-line treatment for uncomplicated malaria and the scale-up of insecticide-treated bed nets. Population genetic diversity, measured by the number of observed and effective microsatellite alleles and Nei's unbiased genetic diversity, was high and comparable for both highland and lowland populations. Analysis of molecular variance did not detect a significant genetic structure across highland and lowland regions. Similarly, mutations at key antimalarial-resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at comparable high frequencies in all four sites. High level of gene flow and lack of significant genetic structure in malaria parasites between highland and lowland areas suggest the importance of human travel in shaping parasite population structure.
PMID: 19398039
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Eshuis H,van Voorhis T
School of Chemistry, University of Bristol, Cantock's Close, Bristol, UKBS8 1TS. Henk.Eshuis@uci.edu.
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The influence of initial conditions on charge transfer dynamics.
Phys Chem Chem Phys. 2009 Nov 28;11(44):10293-8
In this work we address the influence of the initial state on electron transfer dynamics by comparing two different ways of setting up the initial state, namely by taking an electron from the HOMO of a DFT ground state, or by using constrained DFT to self-consistently create the initial state. We solve the TDKS equations for the benzyl-pentafluorobenzene cation. The neutral molecule has a localised HOMO, which gives a natural partitioning in donor and acceptor group. We compare the electronic dynamics for varying angle between donor and acceptor and for varying basis set. We show that the methods lead to essentially equivalent results, but that the use of cDFT gives higher currents and a more consistent initial state with respect to variation of basis set and geometry.
PMID: 19890512
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Brewer AA
Department of Cognitive Sciences, University of California, Irvine, 92617, USA. aabrewer@uci.edu
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Visual maps: To merge or not to merge.
Curr Biol. 2009 Nov 3;19(20):R945-7
A recent study of a child born with one cerebral hemisphere has revealed an extreme developmental reorganization of visual cortex. Self-organizing visual maps demonstrate a surprisingly flexible restructuring in response to cortical loss.
PMID: 19889370
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Steele RE,Dana CE
Department of Biological Chemistry and the Developmental Biology Center, University of California Irvine, Irvine, California, United States of America. resteele@uci.edu
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Evolutionary history of the HAP2/GCS1 gene and sexual reproduction in metazoans.
PLoS One. 2009;4(11):e7680
The HAP2/GCS1 gene first appeared in the common ancestor of plants, animals, and protists, and is required in the male gamete for fusion to the female gamete in the unicellular organisms Chlamydomonas and Plasmodium. We have identified a HAP2/GCS1 gene in the genome sequence of the sponge Amphimedon queenslandica. This finding provides a continuous evolutionary history of HAP2/GCS1 from unicellular organisms into the metazoan lineage. Divergent versions of the HAP2/GCS1 gene are also present in the genomes of some but not all arthropods. By examining the expression of the HAP2/GCS1 gene in the cnidarian Hydra, we have found the first evidence supporting the hypothesis that HAP2/GCS1 was used for male gamete fusion in the ancestor of extant metazoans and that it retains that function in modern cnidarians.
PMID: 19888453
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Szaleniec J,Ole? K,Sk?adzie? J,Strek P
Katedra Klinika Otolaryngologii UJCM w Krakowie. asiat@uci.agh.edu.pl
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[Cat scratch disease--an underestimated diagnosis]
Otolaryngol Pol. 63(3):271-3
INTRODUCTION: Cat scratch disease is a rare and frequently underestimated cause of lymphadenopathy, which may occur also in the head and neck. The infection is most commonly caused by intracellular bacilli Bartonella, transmitted by domestic animals. AIM: We present a case report of a patient treated in the Department of Otolaryngology UJCM in Krakow. The patient presented with a neck tumor. Due to unclear clinical manifestation he underwent surgical treatment. The postoperative histopathological examination suggested cat scratch disease. In detailed anamnesis the patient admitted contact with cats and dogs in his household. No posoperative complications were observed. CONCLUSIONS: In every case of neck tumor it is advisable to consider cat scratch disease, remembering that exclusion of a neoplastic process remains a priority.
PMID: 19886535
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Barleben A,Gandhi D,Nguyen XM,Che F,Nguyen NT,Mills S,Stamos MJ
Department of Surgery, University of California, Irvine, Orange, California 92868, USA. abarlebe@uci.edu
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Is laparoscopic colon surgery appropriate in patients who have had previous abdominal surgery?
Am Surg. 2009 Oct;75(10):1015-9
Laparoscopic techniques in colon surgery reduce postoperative pain, length of hospital stay, and 30-day morbidity when compared with open surgery. The objective of this study was to determine the feasibility of a laparoscopic colectomy in patients who have previously undergone abdominal surgery. We performed a retrospective, single-institution review of laparoscopic colorectal procedures for benign or malignant pathology between October 2002 and September 2008. Our analysis included 55 patients who previously had laparoscopic, open, or a combination of procedures and subsequently underwent laparoscopic colorectal surgery. We observed a 14.5 per cent conversion rate (n = 8). Of the patients who had previous open procedures (n = 48 [87.3%]), the conversion rate was 16.7 per cent. Only one patient (12.5%) who had a history of only laparoscopic surgery required conversion. The highest conversion rate in our study was from patients who underwent a left colectomy (60%, n = 3/5), which was the only statistically significant factor found for conversion. Since the emergence of laparoscopy, use in colon and rectal surgery nationwide has been poor as a result of multiple factors, including a frequent history of abdominal surgery. Our experience shows that laparoscopic colorectal surgery in patients with prior intra-abdominal surgery can be completed with an acceptable conversion rate.
PMID: 19886156
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Reavis KM,Hinojosa MW,Smith BR,Wooldridge JB,Krishnan S,Nguyen NT
Department of Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA. kreavis@uci.edu
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Hospital volume is not a predictor of outcomes after gastrectomy for neoplasm.
Am Surg. 2009 Oct;75(10):932-6
Studies have shown conflicting data with regard to the volume and outcome relationship for gastrectomy. Using the University HealthSystem Consortium national database, we examined the influence of the hospital's volume of gastrectomy on outcomes at academic centers between 2004 and 2008. Outcome measures, including length of stay, 30-day readmission, morbidity, and in-hospital mortality, were compared among high- (13 or greater), medium- (6 to 12), and low-volume (five or less) hospitals. There were 10 high- (n = 593 cases), 36 medium- (n = 1076 cases), and 75 low-volume (n = 500 cases) hospitals. There were no significant differences between high- and low-volume hospitals with regard to length of stay, overall complications, 30-day readmission rate, and in-hospital mortality (2.4 vs 4.4%, respectively, P = 0.06). Despite the small number of gastrectomies performed at the low-volume hospitals, these same hospitals performed a large number of other types of gastric surgery such as gastric bypass for the treatment of morbid obesity (102 cases/year). Within the context of academic medical centers, lower annual volume of gastrectomy for neoplasm is not a predictor of poor outcomes which may be explained by the gastric operative experience derived from other types of gastric surgery.
PMID: 19886138
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Nguyen NT,Slone J,Wooldridge J,Smith BR,Reavis KM,Hoyt D
Department of Surgery, University of California Irvine Medical Center, Orange, California, USA. ninhn@uci.edu
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Minimally invasive esophagectomy without the use of postoperative nasogastric tube decompression.
Am Surg. 2009 Oct;75(10):929-31
A nasogastric tube (NGT) is commonly used in the postoperative period after esophagectomy for decompression of the gastric conduit. The aim of this study was to evaluate the safety of a minimally invasive esophagectomy without the use of NGT decompression. We performed a retrospective review of 124 patients who underwent minimally invasive esophagectomy. Ninety-eight patients had an NGT placed for postoperative decompression and 26 patients did not. The main outcome measure was postoperative complications in regard to the gastric conduit and esophageal anastomosis. There were 96 males with a mean age of 65 +/- 11 years. Three (3%) of 98 patients with operative NGT placement developed postoperative complications directly related to the NGT, which included perforation of the gastric conduit (n = 1) and perforation of the anastomosis (n = 2). In the 26 patients without operative NGT decompression, one patient (3.8%) had distention of the gastric conduit requiring placement of a NGT under fluoroscopic guidance on postoperative Day 1. There was no significant difference in the leak rate between the groups with NGT decompression compared with the group without NGT decompression (9.2 vs 7.7%, respectively). In conclusion, the use of NGT decompression during minimally invasive esophagectomy can be safely omitted. In cases with postoperative gastric conduit distention, an NGT can be safely placed under fluoroscopic guidance.
PMID: 19886137
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Evans WJ,Fang M,Zucchi G,Furche F,Ziller JW,Hoekstra RM,Zink JI
Department of Chemistry, University of California, Irvine, California 92697, USA. wevans@uci.edu
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Isolation of dysprosium and yttrium complexes of a three-electron reduction product in the activation of dinitrogen, the (N2)3- radical.
J Am Chem Soc. 2009 Aug 12;131(31):11195-202
DyI(2) reacts with 2 equiv of KOAr (OAr = OC(6)H(3)(CMe(3))(2)-2,6) under nitrogen to form not only the (N(2))(2-) complex, [(ArO)(2)(THF)(2)Dy](2)(mu-eta(2):eta(2)-N(2)), 1, but also complexes of similar formula with an added potassium ion, [(ArO)(2)(THF)Dy](2)(mu-eta(2):eta(2)-N(2))[K(THF)(6)], 2, and [(ArO)(2)(THF)Dy](2)(mu(3)-eta(2):eta(2):eta(2)-N(2))K(THF), 3. The 1.396(7) and 1.402(7) A N-N bond distances in 2 and 3, respectively, are consistent with an (N(2))(3-) ligand, but the high magnetic moment of 4f(9) Dy(3+) precluded definitive identification. The Y[N(SiMe(3))(2)](3)/K reduction system was used to synthesize yttrium analogues of 2 and 3, {[(Me(3)Si)(2)N](2)(THF)Y}(2)(mu-eta(2):eta(2)-N(2))[K(THF)(6)] and {[(Me(3)Si)(2)N](2)(THF)Y}(2)(mu(3)-eta(2):eta(2):eta(2)-N(2))K, that had similar N-N distances and allowed full characterization. EPR, Raman, and DFT studies are all consistent with the presence of (N(2))(3-) in these complexes. (15)N analogues were also prepared to confirm the spectroscopic assignments. The DFT studies suggest that the unpaired electron is localized primarily in a dinitrogen pi orbital isolated spatially, energetically, and by symmetry from the metal orbitals.
PMID: 19610635
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Saphores JD,Nixon H,Ogunseitan OA,Shapiro AA
Civil and Environmental Engineering, Economics, and Planning, Policy, & Design Departments, University of California, Irvine, CA 92697, USA. saphores@uci.edu
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How much e-waste is there in US basements and attics? Results from a national survey.
J Environ Manage. 2009 Aug;90(11):3322-31
The fate of used electronic products (e-waste) is of increasing concern because of their toxicity and the growing volume of e-waste. Addressing these concerns requires developing the recycling infrastructure, but good estimates of the volume of e-waste stored by US households are still unavailable. In this context, we make two contributions based on a national random survey of 2136 US households. First, we explain how much e-waste is stored by US households using count models. Significant explanatory variables include age, marital and employment status, ethnicity, household size, previous e-waste recycling behavior, and to some extent education, home ownership, and understanding the consequences of recycling, but neither income nor knowledge of e-waste recycling laws. Second, we estimate that on average, each US household has 4.1 small (PMID: 19500898
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Roohk HV,Zaidi AR
Department of Surgery, University of California Irvine , Irvine, California.
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A review of glycated albumin as an intermediate glycation index for controlling diabetes.
J Diabetes Sci Technol. 2008 Nov;2(6):1114-21
INTRODUCTION: This article reviews glycated albumin (GA) as a potential intermediate-term glycation index to fill the gap between self-monitoring of blood glucose (SMBG) and hemoglobin A1c testing in diabetes management. The introduction gives an assessment of available short-, medium-, and long-term glycemic indicators. METHODOLOGIES AND UTILITY: Methods of GA measurement are summarized, and the variance of normal and diabetic GA values are discussed. Greatest uniformity in GA measurement is generally associated with immunoassay and the newer affinity chromatography methodologies utilized by reference laboratories. Utility of GA measurement includes its value as a marker for glycation, its substantial relationship to diabetes complications such as nephropathy and coronary artery disease, and as an unambiguous indicator of glycemic control in diabetes patients undergoing hemodialysis. Studies support the utility of GA in detecting short-term changes in glycemic control, and GA testing has been strongly recommended for gestational diabetes. RESULTS AND DISCUSSION: The results of a survey with mailings to over 3500 diabetes care professionals primarily in the United States are outlined and analyzed (margin of error: +/-6.5%, 95% confidence). Respondents strongly supported the need for a test for intermediate glycemic control as well as the utility of a rapid GA test as a monthly glycemic indicator. CONCLUSIONS: Such a test, as yet unavailable, could increase compliance and enhance empowerment among diabetes patients. It also has the potential to reduce the number of recommended SMBG tests, which may result in significant health care cost savings.
PMID: 19885300
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Chanan G
Department of Physics and Astronomy, University of California, Irvine, California 92697, USA. gchanan@galaxy.ps.uci.edu
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Limitations on the control of hexagonal mirror segment figures by means of edge measurements.
Appl Opt. 2009 Nov 1;48(31):6074-81
Giant segmented telescopes in general require in situ control of the figures of their hexagonal segments. The necessary inputs may be either direct, through surface measurements, or indirect, through measurements of the intersegment edge heights. We investigate the limitations on the indirect (edge height) control that follow from the geometrical properties of hexagonal surfaces and find that these may be substantial. In particular, there are many unmeasurable modes, which we construct and count systematically, and whose potential effect on the segment figure problem we discuss.
PMID: 19881675
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Wodarz D,Levy DN
Department of Ecology and Evolutionary Biology and Department of Mathematics, 321 Steinhaus Hall, University of California, Irvine, California 92697, USA. dwodarz@uci.edu
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Multiple HIV-1 infection of cells and the evolutionary dynamics of cytotoxic T lymphocyte escape mutants.
Evolution. 2009 Sep;63(9):2326-39
Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load.
PMID: 19486149
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King AR,Dotsey EY,Lodola A,Jung KM,Ghomian A,Qiu Y,Fu J,Mor M,Piomelli D
Department of Pharmacology, University of California Irvine, Irvine, CA 92697, USA.
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Discovery of potent and reversible monoacylglycerol lipase inhibitors.
Chem Biol. 2009 Oct 30;16(10):1045-52
Monoacylglycerol lipase (MGL) is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Previous efforts to design MGL inhibitors have focused on chemical scaffolds that irreversibly block the activity of this enzyme. Here, we describe two naturally occurring terpenoids, pristimerin and euphol, which inhibit MGL activity with high potency (median effective concentration, IC(50) = 93 nM and 315 nM, respectively) through a reversible mechanism. Mutational and modeling studies suggest that the two agents occupy a common hydrophobic pocket located within the putative lid domain of MGL, and each reversibly interacts with one of two adjacent cysteine residues (Cys(201) and Cys(208)) flanking such pocket. This previously unrecognized regulatory region might offer a molecular target for potent and reversible inhibitors of MGL.
PMID: 19875078
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Chen C,Xue G,Mei L,Chen C,Dong Q
Department of Psychology and Social Behavior, University of California, Irvine, CA, USA. cschen@uci.edu
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Cultural neurolinguistics.
Prog Brain Res. 2009;178:159-71
As the only species that evolved to possess a language faculty, humans have been surprisingly generative in creating a diverse array of language systems. These systems vary in phonology, morphology, syntax, and written forms. Before the advent of modern brain-imaging techniques, little was known about how differences across languages are reflected in the brain. This chapter aims to provide an overview of an emerging area of research - cultural neurolinguistics - that examines systematic cross-cultural/crosslinguistic variations in the neural networks of languages. We first briefly describe general brain networks for written and spoken languages. We then discuss language-specific brain regions by highlighting differences in neural bases of different scripts (logographic vs. alphabetic scripts), orthographies (transparent vs. nontransparent orthographies), and tonality (tonal vs. atonal languages). We also discuss neural basis of second language and the role of native language experience in second-language acquisition. In the last section, we outline a general model that integrates culture and neural bases of language and discuss future directions of research in this area.
PMID: 19874968
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Vilberg KL,Rugg MD
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697-3800, USA. kvilberg@uci.edu
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Left parietal cortex is modulated by amount of recollected verbal information.
Neuroreport. 2009 Sep 23;20(14):1295-9
In two earlier experiments, we reported that left parietal cortex activity covaried with the amount of pictorial information recollected. The present experiment addressed the question whether our earlier results would generalize to verbal materials. Participants studied a series of word pairs and were then tested on individual old and new words in a modified remember/know task. In this task, participants were required to indicate whether recollection was accompanied by retrieval of study pairmates or not. As before, we operationally defined 'amount recollected' as the contrast between these two types of remember response. We found that the same left parietal region previously identified as sensitive to amount of recollected pictorial information is also sensitive to amount of recollected verbal information.
PMID: 19668014
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Suchard J,Nizkorodov S,Wilkinson S
Department of Emergency Medicine, University of California, Irvine Medical Center, Orange, CA, USA. jsuchard@uci.edu
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1,4-Butanediol content of aqua dots children's craft toy beads.
J Med Toxicol. 2009 Sep;5(3):120-4
INTRODUCTION: The U.S. Consumer Product Safety Commission announced a recall of Aqua Dots (Spin Master Ltd.; Toronto, Canada) on November 7, 2007 due to children becoming ill after swallowing beads from these toy craft kits. Reports suggested that the beads contained 1,4-butanediol (1,4-BD), a precursor to gamma-hydroxybutyrate (GHB), rather than the intended, but more expensive 1,5-pentanediol (1,5-PD). We measured the 1,4-BD and 1,5-PD content of Aqua Dots beads to determine if 1,5-PD had been completely substituted with 1,4-BD by the manufacturer, and if the reported clinical effects from swallowing Aqua Dots beads were consistent with the estimated ingested 1,4-BD dose. METHODS: In vitro bench research using gas chromatography-mass spectroscopy (GC-MS) was performed. Dilute samples of pure 1,4-BD and 1,5-PD in water were used for the calibration of the GC-MS instrument. We then soaked Aqua Dots beads in water for varying durations, and the resultant solutions were analyzed for 1,4-BD and 1,5-PD content. RESULTS: Aqua Dots beads weighed 79.3 mg each (+/- 0.6 mg, SD), and contained 13.7% (+/- 2.4%, SD) 1,4-BD by weight; this corresponds to a 1,4-BD content of 10.8 mg (+/- 1.9 mg, SD) per bead. No 1,5-PD was detected in any beads. CONCLUSIONS: Aqua Dots beads contained a surprisingly high amount (nearly 14%) of extractable 1,4-BD. No 1,5-PD was detected, corroborating reports that this chemical had been completely replaced with a substitute that is metabolized into GHB after ingestion. Reports of ataxia, vomiting, seizure activity, and self-limited coma in children are consistent with the ingestion of several dozen Aqua Dots beads.
PMID: 19655283
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Muftuler LT,Chen G,Hamamura MJ,Ha SH
Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, Irvine, CA 92697-5020, USA. tugan.muftuler@uci.edu
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MREIT with SENSE acceleration using a dedicated RF coil design.
Physiol Meas. 2009 Sep;30(9):913-29
We have adapted a SENSE-accelerated imaging technique to magnetic resonance electrical impedance tomography (MREIT) in order to acquire data faster or improve spatial resolution without increasing the data acquisition time. We also designed and optimized an eight-channel, dedicated phased array coil for this application. The RF coil was designed as two planar arrays so that the open sides could accommodate the MREIT electrodes. A quasi-intrinsic decoupling scheme was used to minimize couplings between coil elements, and a restricted geometry optimization was applied to achieve high and uniform SNR within a given coil geometry and animal size. The impact of variability in the size of animals was also investigated in the optimization. This coil geometry provided approximately three times higher SNR at the center of a phantom when compared to a transmit/receive birdcage coil designed for MREIT of small animals. Therefore, the SNR was superior to the data acquired with volume coils even with three times SENSE acceleration. Both magnitude images and MREIT data were acquired from phantoms with and without SENSE acceleration, and the results were compared. The phantom studies demonstrated that conductivity maps can be reconstructed from MREIT data acquired with three times SENSE acceleration and that no discernible artifacts were observed when accelerated data acquisition was compared to non-accelerated data.
PMID: 19641236
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Chentoufi AA,Nesburn AB,Benmohamed L
Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, USA, aalamich@uci.edu.
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Recent advances in multivalent self adjuvanting glycolipopeptide vaccine strategies against breast cancer.
Arch Immunol Ther Exp (Warsz). 2009 Oct 29;:
Breast cancer (BrCa) is the second leading cause of cancer-related deaths for women worldwide. Evidence from both patients and mouse cancer models suggests that the simultaneous induction of BrCa-specific CD4(+) T cells, CD8(+) cytotoxic T cells, and antibodies is crucial for providing immune resistance. However, almost all current vaccines address only a single arm of the immune system, which may explain their lack of efficacy. We believe that the correct response to monovalent vaccines' "failure" is to increase our knowledge about antitumor protective immunity and to develop a multivalent vaccine molecule that can simultaneously induce multiple arms of the immune system. We highlight here recent advances in anti-BrCa peptide-based vaccine strategies with an emphasis on the self adjuvanting multivalent glycolipopeptide vaccine strategy recently developed in our laboratory and which showed promising results in both immunotherapeutic and immunoprophylactic settings.
PMID: 19866342
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Zoccola PM,Dickerson SS,Lam S
Department of Psychology and Social Behavior, 3340 Social Ecology II, University of California, Irvine, Irvine, CA 92697-7085, USA. p.m.zoccola@uci.edu
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Rumination predicts longer sleep onset latency after an acute psychosocial stressor.
Psychosom Med. 2009 Sep;71(7):771-5
OBJECTIVES: Rumination has been linked to self-reported sleep quality. However, whether rumination is related to an objective sleep parameter has not been tested. This study examined whether rumination predicts sleep onset latency (SOL) on the night after an acute psychosocial stressor. We hypothesized that those who ruminate (assessed with both trait and stressor-specific measures) would have longer SOL (assessed with objective and subjective methods). METHODS: Seventy participants delivered a 5-minute speech in front of an evaluative panel during an afternoon laboratory session. Trait rumination was assessed before the stressor. Stressor-specific rumination was captured with the frequency of task-related thoughts participants experienced during a 10-minute rest period after the stressor. Participants wore actigraphs on their wrists on the night after the laboratory session to measure objective sleep onset latency (SOL-O). Subjective sleep onset latency was estimated by participants on the subsequent morning. RESULTS: Consistent with hypotheses, trait and stressor-specific rumination predicted longer SOL-O and subjective sleep onset latency, respectively. In addition, trait and stressor-specific rumination interacted to predict longer SOL-O. SOL-O was longest among those who engaged in more stressor-specific rumination and had greater trait rumination scores. Neither rumination measure was related to sleep duration or wakefulness after sleep onset. CONCLUSIONS: The findings from this study are consistent with previous research linking rumination to subjective sleep quality. The results also suggest that post-stressor ruminative thought may predict delayed sleep onset for those with a propensity for rumination.
PMID: 19622710
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Hameed AB,Chan K,Ghamsary M,Elkayam U
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of California, Irvine, California, USA. ahameed@uci.edu
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Longitudinal changes in the B-type natriuretic peptide levels in normal pregnancy and postpartum.
Clin Cardiol. 2009 Aug;32(8):E60-2
Normal levels of B-type natriuretic peptide (BNP) are not well established in pregnancy. We obtained longitudinal BNP levels in 29 healthy pregnant women in each trimester and postpartum period, and compared these levels to the 25 nonpregnant controls. There were no significant differences among the cases and controls with respect to weight, diastolic blood pressure, and ethnicity. A total of 116 BNP values were obtained during pregnancy. The median (and range) BNP level during pregnancy was 19 (10-143) pg/ml versus 10 (10-37) pg/ml in the nonpregnant controls (p = 0.003). However, there were no statistically significant differences in the median BNP levels at various stages of pregnancy: first trimester 20 (10-115) pg/ml versus the second trimester 18 (10-112) pg/ml (p = 0.8), second trimester 18 pg/ml versus third trimester 26 (10-143) pg/ml (p = 0.06), and third trimester 26 pg/ml versus postpartum18 (10-62) pg/ml (p = 0.08). There were no significant differences between the BNP levels throughout the trimesters and postpartum period. Pregnant BNP levels were approximately twice as high as the nonpregnant BNP levels. Our study is unique in evaluating longitudinal changes in BNP levels in normal pregnancies and the postpartum period in comparison with healthy, nonpregnant controls. It demonstrates that pregnant BNP levels are approximately 2-fold higher than their nonpregnant counterparts, and do not significantly fluctuate during pregnancy. In conclusion, pregnancy is associated with a significant, but small increase in the BNP levels compared with nonpregnant women.
PMID: 19455566
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Monk BJ,Willmott LJ,Sumner DA
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Building 56, 101 The City Drive, Orange CA 92868, USA.
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Anti-angiogenesis agents in metastatic or recurrent cervical cancer.
Gynecol Oncol. 2009 Oct 25;:
While the incidence of cervical cancer has declined significantly in the United States, it still remains a serious American health threat. When detected early, cervical cancer is generally curable. Early lesions are treated surgically, and locally advanced lesions are managed with concurrent cisplatin chemotherapy and pelvic radiation. Metastatic disease or recurrent lesions not amenable to radical local excision or regional radiation are treated with palliative chemotherapy. Current chemotherapeutic regimens are associated with significant side effects and only limited activity making the identification of active and tolerable novel targeted agents a high priority. Angiogenesis is central to cervical cancer development and progression. The dominant role of angiogenesis in cervical cancer seems to be directly related to HPV inhibition of p53 and stabilization of HIF-1 alpha, both of which increase VEGF. Bevacizumab binding and subsequent inactivation of VEGF seem to shrink cervical tumors and delay progression without appreciable toxicity, and are therefore being studied in a Gynecologic Oncology Group (GOG) phase III trial. Other intracellular tyrosine kinase inhibitors (TKIs) of angiogenesis such as pazopanib are also encouraging, especially in lieu of their oral administration. Further study of angiogenesis and its inhibition are ongoing.
PMID: 19861227
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An WS,Kim HJ,Cho KH,Vaziri ND
Div. of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Bldg. 53, Rm. 125, Rt. 81, Orange, CA 92868, USA.
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Omega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney.
Am J Physiol Renal Physiol. 2009 Oct;297(4):F895-903
Significant reduction of renal mass initiates a series of hemodynamic and nonhemodynamic events which lead to proteinuria, glomerulosclerosis, tubulointerstitial injury, and end-stage renal failure. Lipid mediators derived from fatty acids participate in regulation of renal hemodynamic and nonhemodynamic processes that influence progression of renal disease. Composition of cellular fatty acids and hence related signaling responses are influenced by their dietary contents. Consumption of omega-3 fatty acids (O-3FA) has proven effective in mitigating atherosclerosis. We tested the hypothesis that O-3FA supplementation may retard progression and attenuate upregulation of pathways involved in oxidative stress, inflammation, and fibrosis in rats with renal mass reduction. Sprague-Dawley rats were subjected to 5/6 nephrectomy [chronic renal failure (CRF)] and randomly assigned to the untreated and O-3FA-treated (0.3 g.kg(-1).day(-1) by gastric gavage for 12 wk) groups. Sham-operated rats served as controls. The untreated CRF rats exhibited proteinuria, hypertension, azotemia, upregulations of renal tissue NAD(P)H oxidase, MCP-1, COX-2, PAI-1, TGF-beta, Smad2, alpha-smooth muscle actin, fibronectin, and hepatocyte growth factor, activation of ERK1/2 and NF-kappaB, downregulation of Smad7, intense mononuclear leukocyte infiltration, tubulointerstitial fibrosis, and glomerulosclerosis. O-3FA supplementation significantly lowered COX-2, NAD(P)H oxidase (NOX-4, gp91(phox), p47(phox), p22(phox)), PAI-1, TGF-beta, connective tissue growth factor, alpha-smooth muscle actin, fibronectin, Smad2, and MCP-1, raised Smad7, and attenuated ERK1/2 and NF-kappaB activation, tubulointerstitial fibrosis, and inflammation. Thus, long-term O-3FA supplementation can reduce or reverse upregulation of prooxidant, proinflammatory, and profibrotic pathways and attenuate tubulointerstitial fibrosis in the remnant kidney.
PMID: 19656915
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Winovitch KC,Wing DA,Lagrew DC,Chung JH
Department of Obstetrics and Gynecology, University of California Irvine, Orange, CA, USA. mfm@uci.edu
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The risk of acute neonatal morbidities in the delivery room after primary cesarean at term: influence of labor and stage.
Am J Perinatol. 2009 Sep;26(8):545-51
We evaluated acute neonatal morbidities in the delivery room associated with primary cesarean performed prior to labor and in the first or second stages of labor. A retrospective cohort study was conducted on subjects undergoing term, primary cesareans at the Women's Pavilion, Miller Children's Hospital in Long Beach, California from 2000 to 2007. Acute neonatal morbidities were tabulated as a function of time during labor when cesarean was performed. Composite neonatal morbidity was defined as the presence of at least one of the following: low 5-minute Apgar score, need for intubation, and/or admission to neonatal intensive care unit. One thousand forty-five subjects delivered by cesarean without labor, 3098 in first stage, and 951 in second stage. Five-minute Apgar score < 7 was more common in cesareans performed during second stage than during first stage or without labor [3/1045 (0.3%) versus 28/3098 (0.9%) versus 12/951 (1.3%), P = 0.039]. Composite neonatal morbidity was not significantly different among the stages. Acute neonatal morbidities were not affected by the presence or absence of labor. Potential long-term sequelae require further study.
PMID: 19452426
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