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Author (up) Culmsee, C.; Mattson, M.P. file  url
  Title p53 in neuronal apoptosis Type Journal Article
  Year 2005 Publication Biochemical and Biophysical Research Communications Abbreviated Journal Biochem Biophys Res Commun  
  Volume 331 Issue 3 Pages 761-777  
  Keywords Animals; Apoptosis/*physiology; Apoptosis Regulatory Proteins; DNA Damage; Gene Expression Regulation; Humans; Neurodegenerative Diseases/*physiopathology; Neurons/*cytology/*physiology; Nuclear Proteins/physiology; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-2/physiology; Proto-Oncogene Proteins c-mdm2; Synapses/physiology; Transcriptional Activation; Tumor Suppressor Protein p53/*physiology; bcl-2-Associated X Protein  
  Abstract The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 can trigger apoptosis in many cell types including neurons. Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be responsible for neuronal deaths that occur in neurological disorders such as stroke, and Alzheimer's and Parkinson's diseases. p53 production is rapidly increased in neurons in response to a range of insults including DNA damage, oxidative stress, metabolic compromise, and cellular calcium overload. Target genes induced by p53 in neurons include those encoding the pro-apoptotic proteins Bax and the BH3-only proteins PUMA and Noxa. In addition to such transcriptional control of the cell death machinery, p53 may more directly trigger apoptosis by acting at the level of mitochondria, a process that can occur in synapses (synaptic apoptosis). Preclinical data suggest that agents that inhibit p53 may be effective therapeutics for several neurodegenerative conditions.  
  Call Number Serial 2167  
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Author (up) Cummings, D.E. file  url
  Title Ghrelin and the short- and long-term regulation of appetite and body weight Type Journal Article
  Year 2006 Publication Physiology & Behavior Abbreviated Journal Physiol Behav  
  Volume 89 Issue 1 Pages 71-84  
  Keywords Animals; Appetite/*physiology; Body Weight/*physiology; Energy Metabolism; Ghrelin; Humans; Obesity; Peptide Hormones/*metabolism; Receptors, G-Protein-Coupled/physiology; Receptors, Ghrelin; Time Factors  
  Abstract Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues. Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from insulin surges. Consequently, ingested lipids suppress ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation, ghrelin also fulfills established criteria for an adiposity-related hormone involved in long-term body-weight regulation. Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to body-weight alterations. Ghrelin crosses the blood-brain barrier and stimulates food intake by acting on several classical body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic ghrelin administration increases body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the ghrelin or ghrelin-receptor gene causes resistance to diet-induced obesity, and pharmacologic ghrelin blockade reduces food intake and body weight. Ghrelin levels are high in Prader-Willi syndrome and low after gastric bypass surgery, possibly contributing to body-weight alterations in these settings. Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders.  
  Call Number Serial 1442  
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Author (up) Cummings, J.; Spanswick, V.J.; Smyth, J.F. file  url
  Title Re-evaluation of the molecular pharmacology of mitomycin C Type Journal Article
  Year 1995 Publication European Journal of Cancer (Oxford, England : 1990) Abbreviated Journal Eur J Cancer  
  Volume 31a Issue 12 Pages 1928-1933  
  Keywords Antibiotics, Antineoplastic/pharmacokinetics/*pharmacology; Biotransformation; DNA Adducts; Humans; Mitomycin/pharmacokinetics/*pharmacology  
  Abstract Mitomycin C (MMC) is a naturally occurring antibiotic that was

isolated in 1958 from the fermentation broth of Strepturyces

caespitosus. It was shown to exhibit a broad spectrum of antitumour

activity in preclinical animal screens and less toxicity

compared to other mitomycins, and was introduced into clinical

trials in Japan where anticancer activity was conlirmed in

humans [ 11. MMC, which remains an important component in

combination chemotherapy of breast, lung and prostate cancer,

is among the few drugs to possess even marginal activity

against colorectal cancer, and is probably the drug of choice for

intravesical administration in superficial bladder cancer [ 21.

A number of recently published studies have extended and

challenged many of our longstanding views on the molecular

pharmacology of MMC, particularly in the areas of mechanism

of action, DNA adduct profiles, enzymology of metabolic activation

and drug metabolism. Therefore, it was considered timely

to re-evaluate these areas and attempt to present a picture which

is both cohesive and consistent.
  Call Number Serial 201  
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Author (up) Cunnington, R.; Windischberger, C.; Robinson, S.; Moser, E. file  url
  Title The selection of intended actions and the observation of others' actions: a time-resolved fMRI study Type Journal Article
  Year 2006 Publication NeuroImage Abbreviated Journal Neuroimage  
  Volume 29 Issue 4 Pages 1294-1302  
  Keywords Adult; Arousal--physiology; Attention--physiology; Brain Mapping; Contingent Negative Variation--physiology; Female; Gestures; Gyrus Cinguli--physiology; Humans; Image Interpretation, Computer-Assisted; Imagination--physiology; Imitative Behavior--physiology; Intention; Magnetic Resonance Imaging; Male; Motor Cortex--physiology; Nerve Net--physiology; Parietal Lobe--physiology; Prefrontal Cortex--physiology; Psychomotor Performance--physiology; Set (Psychology); Visual Cortex--physiology; Visual Pathways--physiology  
  Abstract Whenever we plan, imagine, or observe an action, the motor systems that would be involved in preparing and executing that action are similarly engaged. The way in which such common motor activation is formed, however, is likely to differ depending on whether it arises from our own intentional selection of action or from the observation of another's action. In this study, we use time-resolved event-related functional MRI to tease apart neural processes specifically related to the processing of observed actions, the selection of our own intended actions, the preparation for movement, and motor response execution. Participants observed a finger gesture movement or a cue indicating they should select their own finger gesture to perform, followed by a 5-s delay period; participants then performed the observed or self-selected action. During the preparation and readiness for action, prior to initiation, we found activation in a common network of higher motor areas, including dorsal and ventral premotor areas and the pre-supplementary motor area (pre-SMA); the more caudal SMA showed greater activation during movement execution. Importantly, the route to this common motor activation differed depending on whether participants freely selected the actions to perform or whether they observed the actions performed by another person. Observation of action specifically involved activation of inferior and superior parietal regions, reflecting involvement of the dorsal visual pathway in visuomotor processing required for planning the action. In contrast, the selection of action specifically involved the dorsal lateral prefrontal and anterior cingulate cortex, reflecting the role of these prefrontal areas in attentional selection and guiding the selection of responses.  
  Call Number Serial 69  
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Author (up) Curtis, A.; Lyons, V.; Fink, G. file  url
  Title The human hypothalamic LHRH precursor is the same size as that in rat and mouse hypothalamus Type Journal Article
  Year 1983 Publication Biochemical and Biophysical Research Communications Abbreviated Journal Biochem Biophys Res Commun  
  Volume 117 Issue 3 Pages 872-877  
  Keywords Aged; Animals; Female; Gonadotropin-Releasing Hormone/*biosynthesis; Humans; Hypothalamus/*metabolism; Male; Mice; Molecular Weight; Protein Biosynthesis; Protein Precursors/*isolation & purification; Rats; Species Specificity  
  Abstract The synthesis of the decapeptide luteinizing hormone releasing hormone (LHRH) in human, rat and mouse brain has been investigated by studying the in vitro translation products of Poly A+ mRNA extracts from the hypothalamus. The translation products of all three species contained a single 28000 MW polypeptide which immunoprecipitated with a specific anti-LHRH serum. This polypeptide was not present in the translation products of Poly A+ mRNA extracts from the hypothalamus of the hypogonadal mouse, a mutant strain totally deficient in LHRH. These results show that in the human, rat and normal mouse, LHRH is synthesized as a component of a precursor peptide with a molecular weight of 28000.  
  Call Number Serial 325  
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Author (up) Czerlinski, G.; Ypma, T. file  url
doi  openurl
  Title Mechanisms of telomerase-dimer catalysis Type Journal Article
  Year 2008 Publication Journal of Theoretical Biology Abbreviated Journal J Theor Biol  
  Volume 250 Issue 3 Pages 512-523  
  Keywords Allosteric Regulation/physiology; Catalysis; HIV/genetics; Humans; *Models, Genetic; RNA/metabolism/*physiology; Telomerase/metabolism/*physiology; Telomere/metabolism; Templates, Genetic  
  Abstract There is evidence that human telomerase acts as a dimer [Wenz, C., Enenkel, B., Amacker, M., Kelleher, C., Damm, K., Lingner, J., 2001. Human telomerase contains two cooperating telomerase RNA molecules. EMBO J. 20, 3526-3534]. Three possible mechanisms have been proposed. We translate those proposals into three detailed mechanistic models for telomerase action, also introducing optional isomerizations with equilibrium constants inversely related to the number of bound nucleotides. To distinguish between these models by in situ experiments we propose a microscopic system which uses two-photon excitation of fluorescence in a volume of about 0.5 microm(3). A variety of detection strategies and experimental designs are considered; we focus on those best suited to observation of a small volume under limitations imposed by diffusion to and from the reacting micro-volume, and consequently restrict ourselves to constant flow. Numerical simulation is used to help identify an optimal experimental design. The detection of mechanistic changes hinges on linking fluorescence reporters to selected reaction components, either directly (chemically) or indirectly (via an indicator reaction). We show that rapid mixing experiments are better than chemical relaxation experiments, as the statistics of single molecule kinetics affects the latter more than the former. However, some fast reaction steps can only be revealed by chemical relaxation coupled with mixing experiments. We explore connections between our methods and studies of HIV and other systems with RNA to DNA transcription.  
  Call Number Serial 129  
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Author (up) Dales, L.; Hammer, S.J.; Smith, N.J. file  url
  Title Time trends in autism and in MMR immunization coverage in California Type Journal Article
  Year 2001 Publication Jama Abbreviated Journal Jama  
  Volume 285 Issue 9 Pages 1183-1185  
  Keywords Autistic Disorder/*epidemiology/*etiology; California/epidemiology; Child; Child, Preschool; Humans; Infant; Measles-Mumps-Rubella Vaccine/*adverse effects; Retrospective Studies; Vaccination/*statistics & numerical data  
  Abstract CONTEXT: Considerable concern has been generated in the lay and medical communities by a theory that increased measles-mumps-rubella (MMR) immunization among young children may be the cause of an apparent marked increase in autism occurrence. OBJECTIVE: To determine if a correlation exists in secular trends of MMR immunization coverage among young children and autism occurrence. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analyses of MMR immunization coverage rates among children born in 1980-1994 who were enrolled in California kindergartens (survey samples of 600-1900 children each year) and whose school immunization records were reviewed to retrospectively determine the age at which they first received MMR immunization; and of autism caseloads among children born in these years who were diagnosed with autism and were enrolled in the California Department of Developmental Services regional service center system. MAIN OUTCOME MEASURES: Measles-mumps-rubella immunization coverage rates as of ages 17 months and 24 months and numbers of Department of Developmental Services system enrollees diagnosed with autism, grouped by year of birth. RESULTS: Essentially no correlation was observed between the secular trend of early childhood MMR immunization rates in California and the secular trend in numbers of children with autism enrolled in California's regional service center system. For the 1980-1994 birth cohorts, a marked, sustained increase in autism case numbers was noted, from 44 cases per 100 000 live births in the 1980 cohort to 208 cases per 100 000 live births in the 1994 cohort (a 373% relative increase), but changes in early childhood MMR immunization coverage over the same time period were much smaller and of shorter duration. Immunization coverage by the age of 24 months increased from 72% to 82%, a relative increase of only 14%, over the same time period. CONCLUSIONS: These data do not suggest an association between MMR immunization among young children and an increase in autism occurrence.  
  Call Number Serial 1120  
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Author (up) Danielsson, K.G.; Marions, L.; Bygdeman, M. file  url
  Title Effects of mifepristone on endometrial receptivity Type Journal Article
  Year 2003 Publication Steroids Abbreviated Journal Steroids  
  Volume 68 Issue 10-13 Pages 1069-1075  
  Keywords Contraception; Contraceptives, Oral, Synthetic/pharmacology; Endometrium/*drug effects; Fallopian Tubes/drug effects; Female; Hormone Antagonists/pharmacology; Humans; Immunohistochemistry; Microscopy, Electron; Mifepristone/*pharmacology; Ovulation/drug effects; Progesterone/metabolism; Receptors, Progesterone/metabolism; Reverse Transcriptase Polymerase Chain Reaction  
  Abstract At the development of receptivity the endometrium undergoes specific changes. Several factors have been suggested as markers of endometrial receptivity. A common feature for most of these factors is that they are directly, or indirectly, regulated by progesterone. The effect of various doses and regimens of mifepristone on endometrial development and markers of receptivity has been studied. Timed endometrial biopsies were assessed by immunhistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and electron microscopy. In addition the contraceptive efficacy of these regimens was investigated. Administration of 200 mg of mifepristone immediately post ovulation has a pronounced effect on endometrial development and on suggested markers of receptivity. This regimen has been shown to be an effective contraceptive method. When 10 mg is given pre or post ovulation, only minor effects on the endometrium are observed. Our studies show that mifepristone, when administered in low doses that do not affect ovulation, significantly affects some of the studied markers of endometrial receptivity and reduces pregnancy rates; however, these activities are more pronounced with the higher dose, which is more effective. Our findings provide insight into the regulation of progesterone receptors of various suggested markers of endometrial receptivity and the possibility of using mifepristone for endometrial contraception.  
  Call Number Serial 1601  
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Author (up) Davis, J. file  url
  Title The effect of qualifying language on perceptions of drug appeal, drug experience, and estimates of side-effect incidence in DTC advertising Type Journal Article
  Year 2007 Publication Journal of Health Communication Abbreviated Journal J Health Commun  
  Volume 12 Issue 7 Pages 607-622  
  Keywords Adult; Advertising as Topic/*standards; Analysis of Variance; Drug Industry/*standards; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Likelihood Functions; Male; Patient Satisfaction/*statistics & numerical data; *Persuasive Communication; *Pharmaceutical Preparations; Risk Assessment/*standards; Surveys and Questionnaires; *Terminology as Topic; United States; United States Food and Drug Administration  
  Abstract This study examined how the use of qualifying language in direct-to-consumer (DTC) pharmaceutical advertising affects consumers' perceptions of drug appeal, anticipated pleasantness of drug usage, and the expected incidence of side-effect occurrence. A sample of 669 individuals participated in a 2 x 8 complete factorial design. The design manipulated the number of side effects associated with drug use and the type of qualifying language used to describe the side effects. The eight experimental qualifying language cells represented one control condition (no qualifying language), three cells where each of three types of qualifying language were presented individually, and four cells where qualifying language was combined. The results indicate that qualifying language has a profound effect on drug perceptions, especially when used in combination. Drug appeal and the anticipated drug-using experience almost always were more positive in the presence of qualifying language. Qualifying language appears to exert its influence by causing individuals to reduce their estimate of the likelihood of experiencing individual side effects. Policy implications of the research, particularly for evaluation of “fair balance” and the reporting of side effects, are presented.  
  Call Number Serial 1390  
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Author (up) Dawson, G.; Webb, S.; Schellenberg, G.D.; Dager, S.; Friedman, S.; Aylward, E.; Richards, T. file  url
  Title Defining the broader phenotype of autism: genetic, brain, and behavioral perspectives Type Journal Article
  Year 2002 Publication Development and Psychopathology Abbreviated Journal Dev Psychopathol  
  Volume 14 Issue 3 Pages 581-611  
  Keywords Autistic Disorder/*complications/*genetics; Brain/*abnormalities; Child; Child Behavior Disorders/*etiology; Evoked Potentials/physiology; Humans; Language Disorders/etiology; Magnetic Resonance Imaging; Perceptual Disorders/etiology; Phenotype; Phonetics; Speech Perception; Temporal Lobe/abnormalities; Twin Studies as Topic  
  Abstract Achieving progress in understanding the cause, nature, and treatment of autism requires an integration of concepts, approaches, and empirical findings from genetic, cognitive neuroscience, animal, and clinical studies. The need for such integration has been a fundamental tenet of the discipline of developmental psychopathology from its inception. It is likely that the discovery of autism susceptibility genes will depend on the development of dimensional measures of broader phenotype autism traits. It is argued that knowledge of the cognitive neuroscience of social and language behavior will provide a useful framework for defining such measures. In this article, the current state of knowledge of the cognitive neuroscience of social and language impairments in autism is reviewed. Following from this, six candidate broader phenotype autism traits are proposed: (a) face processing, including structural encoding of facial features and face movements, such as eye gaze; (b) social affiliation or sensitivity to social reward, pertaining to the social motivational impairments found in autism; (c) motor imitation ability, particularly imitation of body actions; (d) memory, specifically those aspects of memory mediated by the medial temporal lobe-prefrontal circuits; (e) executive function, especially planning and flexibility; and (f) Language ability, particularly those aspects of language that overlap with specific language impairment, namely, phonological processing.  
  Call Number Serial 1118  
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