bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular receptive range variation among mouse odorant receptors for aliphatic carboxylic acids
Authors: Repicky Sarah E. , Luetje Charles W. 
Published: January 2009

AbstractThe ability of mammals to identify and distinguish among many thousands of different odorants suggests a combinatorial use of odorant receptors, with each receptor detecting multiple odorants and each odorant interacting with multiple receptors. Numerous receptors may be devoted to the sampling of particularly important regions of odor space. In this study, we explore the similarities and differences in the molecular receptive ranges of four mouse odorant receptors (MOR23‐1, MOR31‐4, MOR32‐11 and MOR40‐4), which have previously been identified as receptors for aliphatic carboxylic acids. Each receptor was expressed in Xenopus oocytes, along with Gαolf and the cystic fibrosis transmembrane regulator to allow electrophysiological assay of receptor responses. We find that even though these receptors are relatively unrelated, there is extensive overlap among their receptive ranges. That is, these receptors sample a similar region of odor space. However, the receptive range of each receptor is unique. Thus, these receptors contribute to the depth of coverage of this small region of odor space. Such a group of receptors with overlapping, but distinct receptive ranges, may participate in making fine distinctions among complex mixtures of closely related odorant compounds.
Contactin‐associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS
Authors: Oiso Shigeru , Takeda Yasuo , Futagawa Toshitaka , Miura Takehiko , Kuchiiwa Satoshi , Nishida Kentaro , Ikeda Ryuji , Kariyazono Hiroko , Watanabe Kazutada , Yamada Katsushi 
Published: January 2009

AbstractTo identify proteins interacting with the intracellular domain of the neural cell adhesion molecule contactin‐associated protein 2 (Caspr2), yeast two‐hybrid screening was performed. We identified carboxypeptidase E (CPE) as a Caspr2‐interacting candidate protein. Glutathione S‐transferase pull‐down and immunoprecipitation analyses indicated that Caspr2 was associated with CPE in vitro and in vivo. Both Caspr2 and CPE were expressed predominantly in the CNS. Immunohistochemical analyses revealed that both Caspr2‐ and CPE‐like immunoreactivities were found to co‐localize in the apical dendrites and cell bodies of rat cortical neurons. In subcellular localization analysis, Caspr2‐ and CPE‐like immunoreactivities were co‐migrated in the fractions of Golgi/ER. Additionally, in COS‐7 cells co‐transfected with CPE and Caspr2 cDNAs, Caspr2‐ and CPE‐immunoreactivities were co‐localized in both Golgi and membrane, whereas it was only observed in Golgi of either COS‐7 cell transfected with CPE or Caspr2 cDNA alone. It is known that the membrane‐bound form of CPE functions as a sorting receptor of prohormones in the trans‐Golgi network. Taken together, our data suggest that CPE may be a key molecule to regulate Caspr2 trafficking to the cell membrane.
Nuclear respiratory factor 1 co‐regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons
Authors: Dhar Shilpa S. , Liang Huan Ling , Wong‐Riley Margaret T. T. 
Published: January 2009

AbstractNeuronal activity, especially of the excitatory glutamatergic type, is highly dependent on energy from the oxidative pathway. We hypothesized that the coupling existed at the transcriptional level by having the same transcription factor to regulate a marker of energy metabolism, cytochrome c oxidase (COX) and an important subunit of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid glutamate receptors, GluR2 (Gria2). Nuclear respiratory factor 1 (NRF‐1) was a viable candidate because it regulates all COX subunits and potentially activates Gria2. By means of in silico analysis, electrophoretic mobility shift and supershift, chromatin immunoprecipitation, and promoter mutational assays, we found that NRF‐1 functionally bound to Gria2 promoter. Silencing of NRF‐1 with small interference RNA prevented the depolarization‐stimulated up‐regulation of Gria2 and COX, and over‐expression of NRF‐1 rescued neurons from tetrodotoxin‐induced down‐regulation of Gria2 and COX transcripts. Thus, neuronal activity and energy metabolism are tightly coupled at the molecular level, and NRF‐1 is a critical agent in this process.
Changes in left ventricular ejection time and pulse transit time derived from finger photoplethysmogram and electrocardiogram during moderate haemorrhage
Authors: Middleton Paul M. , Chan Gregory S.H. , O’Lone Emma , Steel Elizabeth , Carroll Rebecca , Celler Branko G. , Lovell Nigel H. 
Published: January 2009

SummaryObjectives:  Early identification of haemorrhage is difficult when a bleeding site is not apparent. This study explored the potential use of the finger photoplethysmographic (PPG) waveform derived left ventricular ejection time (LVETp) and pulse transit time (PTT) for detecting blood loss, by using blood donation as a model of controlled mild to moderate haemorrhage.Methods:  This was a prospective, observational study carried out in a convenience sample of blood donors. LVETp, PTT and R‐R interval (RRi) were computed from simultaneous measurement of the electrocardiogram (ECG) and the finger infrared photoplethysmogram obtained from 43 healthy volunteers during blood donation. The blood donation process was divided into four stages: (i) Pre‐donation (PRE), (ii) first half of donation (FIRST), (iii) second half of donation (SECOND), (iv) post‐donation (POST).Results and conclusions:  Shortening of LVETp from 303+/−2 to 293+/−3 ms (mean+/−SEM; P<0·01) and prolongation of PTT from 177+/−3 to 186+/−4 ms (P<0·01) were observed in 81% and 91% of subjects respectively when comparing PRE and POST. During blood donation, progressive blood loss produced falling trends in LVETp (P<0·01) and rising trends in PTT (P<0·01) in FIRST and SECOND, but a falling trend in RRi (P<0·01) was only observed in SECOND. Monitoring trends in timing variables derived from non‐invasive ECG and finger PPG signals may facilitate detection of blood loss in the early phase.
Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2‐deficient mice
Authors: Jackman KA , Miller AA , De Silva TM , Crack PJ , Drummond GR , Sobey CG 
Published: January 2009

Background and purpose:  Reactive oxygen species (ROS) derived from Nox2‐containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2‐selective inhibitors have yet been identified, and thus it is unclear whether isoform non‐selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2‐containing NADPH oxidase in the effects of apocynin was assessed using Nox2−/− mice.Experimental approach:  Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg·kg−1, i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia‐reperfusion was measured in brain sections of wild‐type mice at 24 h using dihydroethidium fluorescence.Key results:  Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild‐type but not Nox2−/− mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels.Conclusions and implications:  Apocynin improves outcome following stroke when administered before ischaemia in wild‐type but not Nox2−/− mice.Mandarin translation of abstract
Hemospan: Design Principles for a New Class of Oxygen Therapeutic
Authors: Vandegriff Kim D. , Winslow Robert M. 
Published: January 2009

AbstractHemoglobin‐based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross‐linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell‐free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site‐specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early‐generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well‐tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe.
Review of Hemoglobin‐Vesicles as Artificial Oxygen Carriers
Authors: Sakai Hiromi , Sou Keitaro , Horinouchi Hirohisa , Kobayashi Koichi , Tsuchida Eishun 
Published: January 2009

AbstractBlood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: infection, blood type mismatching, immunological response, short shelf life, and screening test costs. Blood substitutes have been under development for decades to overcome such problems. Plasma component substitutes have already been established: plasma expanders, electrolytes, and recombinant coagulant factors. Herein, we focus on the development of red blood cell (RBC) substitutes. Side effects hindered early development of cell‐free hemoglobin (Hb)‐based oxygen carriers (HBOCs) and underscored the physiological importance of the cellular structure of RBCs. Well‐designed artificial oxygen carriers that meet requisite criteria are expected to be realized eventually. Encapsulation of Hb is one idea to shield the toxicities of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved: difficulties related to regulating the molecular assembly, and management of its physicochemical and biochemical properties. Hb‐vesicles (HbV) are a cellular type of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have been studied extensively. The results illustrate the potential of HbV as a transfusion alternative and promise its use for other clinical applications that remain unattainable using RBC transfusion.
Liposome‐Encapsulated Hemoglobin, TRM‐645: Current Status of the Development and Important Issues for Clinical Application
Authors: Kaneda Shinichi , Ishizuka Takanobu , Goto Hiroshi , Kimura Tetsuhiro , Inaba Katsutoshi , Kasukawa Hiroaki 
Published: January 2009

AbstractClinical application of artificial oxygen carriers as a substitute for blood transfusion has long been expected to solve some of the problems associated with blood transfusion. Use for oxygen delivery treatment for ischemic disease by oxygen delivery has also been examined. These prospective applications of artificial oxygen carriers are, however, still in development. We have developed liposome‐encapsulated hemoglobin (LEH), developmental code TRM‐645, using technologies for encapsulation of concentrated hemoglobin (Hb) with high encapsulation efficiency as well as surface modification to achieve stability in circulating blood and a long shelf life. We have confirmed the basic efficacy and safety of TRM‐645 as a red blood cell substitute in studies on the efficacy of oxygen delivery in vivo, and the safety of TRM‐645 has been studied in some animal species. We are now examining various issues related to clinical studies, including further preclinical studies, management of manufacturing and the quality assurance for the Hb solution and liposome preparations manufactured by the GMP facility.
Liposome‐Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen Affinity
Authors: Fukumoto Dai , Kawaguchi Akira T. , Haida Munetaka , Yamano Mariko , Ogata Yoshitaka , Tsukada Hideo 
Published: January 2009

AbstractLiposome‐encapsulated hemoglobin (LEH) with a low oxygen affinity (l‐LEH, P50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O2 affinity (h‐LEH, P50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h‐LEH as well as l‐LEH. Both h‐LEH and l‐LEH significantly reduced the extent of cortical infarction. h‐LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l‐LEH (MED: 2 mL/kg) in the cortex. h‐LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l‐LEH provided no significant protection. h‐LEH provided better protection than l‐LEH. The protective effect of both high‐ and low‐affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h‐LEH over l‐LEH supports an optimal O2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.
In Vivo Distribution of Liposome‐Encapsulated Hemoglobin Determined by Positron Emission Tomography
Authors: Urakami Takeo , Kawaguchi Akira T. , Akai Shuji , Hatanaka Kentaro , Koide Hiroyuki , Shimizu Kosuke , Asai Tomohiro , Fukumoto Dai , Harada Norihiro , Tsukada Hideo , Oku Naoto 
Published: January 2009

AbstractPositron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter‐labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome‐encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [15O]H2O imaging, distribution of 18F‐labeled LEH in the region was gradually increased during 60‐min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real‐time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution.
S‐Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in Rats
Authors: Kawaguchi Akira T. , Nakai Kunihiko , Fukumoto Dai , Yamano Mariko , Haida Munetaka , Tsukada Hideo 
Published: January 2009

AbstractCell‐free hemoglobin‐based oxygen carriers have well‐documented safety and efficacy problems such as nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S‐nitrosylated pegylated hemoglobin (SNO‐PEG‐Hb, P50 = 12 mm Hg) and tested it in a brain ischemia and reperfusion model. Neurological function and extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery in the rat. Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by triphenyltetrazolium chloride staining in rats receiving various doses of SNO‐PEG‐Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated hemoglobin without S‐nitrosylation (PEG‐Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO‐PEG‐Hb but not PEG‐Hb to be effective in reducing the size of cortical infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO‐PEG‐Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical infarction, however, without functional improvement.
Responsiveness and Clinical Utility of the Geriatric Self‐Efficacy Index for Urinary Incontinence
Authors: Tannenbaum Cara , Brouillette Judith , Michaud Julie , Korner‐Bitensky Nicol , Dumoulin Chantale , Corcos Jacques , Tu Le Mai , Lemieux Marie‐Claude , Ouellet Stephane , Valiquette Luc 
Published: January 2009

OBJECTIVES: To report on the responsiveness testing and clinical utility of the 12‐item Geriatric Self‐Efficacy Index for Urinary Incontinence (GSE‐UI).DESIGN: Prospective cohort study.SETTING: Six urinary incontinence (UI) outpatient clinics in Quebec, Canada.PARTICIPANTS: Community‐dwelling incontinent adults aged 65 and older.MEASUREMENTS: The abridged 12‐item GSE‐UI, measuring older adults' level of confidence for preventing urine loss, was administered to all new consecutive incontinent patients 1 week before their initial clinic visit, at baseline, and 3 months posttreatment. At follow‐up, a positive rating of improvement in UI was ascertained from patients and their physicians using the Patient's and Clinician's Global Impression of Improvement scales, respectively. Responsiveness of the GSE‐UI was calculated using Guyatt's change index. Its clinical utility was determined using receiver operating curves.RESULTS: Eighty‐nine of 228 eligible patients (39.0%) participated (mean age 72.6+5.8, range 65–90). At 3‐month follow‐up, 22.5% of patients were very much better, and 41.6% were a little or much better. Guyatt's change index was 2.6 for patients who changed by a clinically meaningful amount and 1.5 for patients having experienced any level of improvement. An improvement of 14 points on the 12‐item GSE‐UI had a sensitivity of 75.1% and a specificity of 78.2% for detecting clinically meaningful changes in UI status. Mean GSE‐UI scores varied according to improvement status (P<.001) and correlated with changes in quality‐of‐life scores (r=0.7, P<.001) and reductions in UI episodes (r=0.4, P=.004).CONCLUSION: The GSE‐UI is responsive and clinically useful.
The Co‐Occurrence of Chronic Diseases and Geriatric Syndromes: The Health and Retirement Study
Authors: Lee Pearl G. , Cigolle Christine , Blaum Caroline 
Published: January 2009

OBJECTIVES: To analyze the co‐occurrence, in adults aged 65 and older, of five conditions that are highly prevalent, lead to substantial morbidity, and have evidence‐based guidelines for management and well‐developed measures of medical care quality.DESIGN: Secondary data analysis of the 2004 wave of the Health and Retirement Study (HRS).SETTING: Nationally representative health interview survey.PARTICIPANTS: Respondents in the 2004 wave of the HRS aged 65 and older.MEASUREMENTS: Self‐reported presence of five index conditions (three chronic diseases (coronary artery disease, congestive heart failure, and diabetes mellitus) and two geriatric syndromes (urinary incontinence and injurious falls)) and demographic information (age, sex, race, living situation, net worth, and education).RESULTS: Eleven thousand one hundred thirteen adults, representing 37.1 million Americans aged 65 and older, were interviewed. Forty‐five percent were aged 76 and older, 58% were female, 8% were African American, and 4% resided in a nursing home. Respondents with more conditions were older and more likely to be female, single, and residing in a nursing home (all P<.001). Fifty‐six percent had at least one of the five index conditions, and 23% had two or more. Of respondents with one condition, 20% to 55% (depending on the index condition) had two or more additional conditions.CONCLUSION: Five common conditions (3 chronic diseases, 2 geriatric syndromes) often co‐occur in older adults, suggesting that coordinated management of comorbid conditions, both diseases and geriatric syndromes, is important. Care guidelines and quality indicators, rather than considering one condition at a time, should be developed to address comprehensive and coordinated management of co‐occurring diseases and geriatric syndromes.
Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources
Authors: Åberg Anna‐Maja , Sojka Birgitta Nilsson , Winsö Ola , Abrahamsson Pernilla , Johansson Göran , Larsson Jan Erik 
Published: January 2009

BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umeå, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette.STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography.RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 µmol/L). In 6 percent of the samples, the concentrations were higher than 130 µmol per L. The highest CO concentration was 561 µmol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half‐lives from 4.7 to 8.4 hours.CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.