bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separate Basic Region Motifs within the Adeno-Associated Virus Capsid Proteins Are Essential for Infectivity and Assembly
Authors: Grieger Joshua C. , Snowdy Stephen , Samulski Richard J. 
Published: May 2006

ABSTRACT

Adeno-associated virus (AAV) is gaining momentum as a gene therapy vector for human applications. However, there remain impediments to the development of this virus as a vector. One of these is the incomplete understanding of the biology of the virus, including nuclear targeting of the incoming virion during initial infection, as well as assembly of progeny virions from structural components in the nucleus. Toward this end, we have identified four basic regions (BR) on the AAV2 capsid that represent possible nuclear localization sequence (NLS) motifs. Mutagenesis of BR1 (
120
QAKKRVL
126
) and BR2 (
140
PGKKRPV
146
) had minor effects on viral infectivity (∼4- and ∼10-fold, respectively), whereas BR3 (
166
PARKRLN
172
) and BR4 (
307
RPKRLN
312
) were found to be essential for infectivity and virion assembly, respectively. Mutagenesis of BR3, which is located in Vp1 and Vp2 capsid proteins, does not interfere with viral production or trafficking of intact AAV capsids to the nuclear periphery but does inhibit transfer of encapsidated DNA into the nucleus. Substitution of the canine parvovirus NLS rescued the BR3 mutant to wild-type (wt) levels, supporting the role of an AAV NLS motif. In addition, rAAV2 containing a mutant form of BR3 in Vp1 and a wt BR3 in Vp2 was found to be infectious, suggesting that the function of BR3 is redundant between Vp1 and Vp2 and that Vp2 may play a role in infectivity. Mutagenesis of BR4 was found to inhibit virion assembly in the nucleus of transfected cells. This affect was not completely due to the inefficient nuclear import of capsid subunits based on Western blot analysis. In fact, aberrant capsid foci were observed in the cytoplasm of transfected cells, compared to the wild type, suggesting a defect in early viral assembly or trafficking. Using three-dimensional structural analysis, the lysine- and arginine-to-asparagine change disrupts hydrogen bonding between these basic residues and adjacent beta strand glutamine residues that may prevent assembly of intact virions. Taken together, these data support that the BR4 domain is essential for virion assembly. Each BR was also found to be conserved in serotypes 1 to 11, suggesting that these regions are significant and function similarly in each serotype. This study establishes the importance of two BR motifs on the AAV2 capsid that are essential for infectivity and virion assembly.
A Novel Assay for Viral MicroRNA Function Identifies a Single Nucleotide Polymorphism That Affects Drosha Processing
Authors: Gottwein Eva , Cai Xuezhong , Cullen Bryan R. 
Published: May 2006

ABSTRACT

MicroRNAs (miRNAs) are a class of ∼22-nucleotide noncoding RNAs that inhibit the expression of specific target genes at the posttranscriptional level. Recently, 11 miRNAs encoded by the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) were cloned from latently infected cells. While the expression of these miRNAs has been confirmed by Northern analysis, their ability to inhibit target gene expression has not been demonstrated. We have devised a novel assay for miRNA function that uses lentiviral indicator vectors carrying two perfectly complementary target sites for each given miRNA in the 3′ untranslated region of the
Renilla
luciferase gene. This assay allowed us to demonstrate the activity of each viral miRNA upon cotransduction of cells with the
Renilla
luciferase indicator vector together with a firefly luciferase control vector. In KSHV-infected BC-1 and BCBL-1 cells, but not uninfected control cells,
Renilla
luciferase expression was selectively reduced up to 10-fold. Interestingly, one of the viral miRNAs (miR-K5) exhibited much higher activity in BC-1 cells than in BCBL-1 cells. Sequence analysis of both viral genomes revealed a single nucleotide polymorphism in the miR-K5 precursor stem-loop, which inhibits the expression of mature miR-K5 in BCBL-1 cells. We show that the primary miR-K5 sequence present in BCBL-1 results in diminished processing by Drosha both in vivo and in vitro. This is the first report of a naturally occurring sequence polymorphism in an miRNA precursor that results in reduced processing and therefore lower levels of mature miRNA expression and function.
A phase II study of hydrocodone for cough in advanced cancer
Authors: Homsi Jade , Walsh Declan , Nelson Kristine A. , Sarhill Nabeel , Rybicki Lisa , LeGrand Susan B. , Davis Mellar P. 
Published: May 2006

Purpose: Cough is a common symptom in advanced cancer. The use of hydrocodone as an antitussive has not been studied previously in this setting. This study evaluates hydrocodone for cough in advanced cancer. Methods: The results presented are from a phase II study with dose titration. Setting: Palliative medicine program in a tertiary referral center. Patients: 25 consecutive patients with cough from irreversible causes, on a stable opioid regimen for the prior 24 hours, and no previous or current use of hydrocodone for cough. Intervention: 5 mg hydrocodone was administered twice daily. The dose was then titrated daily (maximum: 60 mg/24 h), if needed, until a 3 50 percent improvement of the frequency of cough was achieved and then maintained for three consecutive days. Measurements: Cough severity, frequency, complications, and hydrocodone side effects. Results: 20 persons (10 women and 10 men) completed study evaluation. Median age was 63 years (range: 42-82). Nine patients had lung cancer and seven had lung or pleura metastases; 19 patients had at least 50 percent improvement of their cough frequency. The median best response was 70 percent improvement in the cough frequency (range: 50-90 percent). Median hydrocodone dose associated with the best response was 10 mg/day (range: 5-30 mg/day). Cough severity, frequency, associated symptoms and complications, and activities of daily living improved significantly. Side effects of hydrocodone (dry mouth, nausea, and drowsiness) were tolerable and rated as mild. Conclusions: Hydrocodone is effective and safe to treat cough in advanced cancer. A starting dose of 10 mg per day in divided doses seems effective. Dose escalation may be required. Most improved within one day.
Management of hiccups in the palliative care population
Authors: Smith Howard S. , Busracamwongs Atichat 
Published: May 2006

There are close to a hundred causes for hiccups, or singultus, the most common of which are gastrointestinal. Causes may be natural or drug induced, and the same agents that are used to treat hiccups may also induce them. Hiccups can be classified by their duration, as follows: up to 48 hours, acute; longer than 48 hours, persistent; and more than two months, intractable. Treatment options for hiccups can include both pharmacologic and nonpharmacologic agents. If the cause of hiccups can be identified, it is, of course, preferable to direct the treatment at that cause. However, many times a cause cannot be identified; in this case, general measures or treatments should be instituted. Intractable hiccups can occur in the palliative care population. When they do, it can be extremely distressing and have a significant impact on quality of life. Pharmacologic approaches are often the most rational therapies for these patients. Baclofen seems to be a promising drug for use with both palliative care and perioperative patients, and using garabentin as an add-on to baclofen may also be a reasonable option to consider.
End-of-life care: Perspectives of family members of deceased patients
Authors: Marco Catherine A. , Buderer Nancy , Thum Dorothy 
Published: May 2006

This study was undertaken to determine the opinions of family members of deceased patients regarding end-of-life care. This multisite cross-sectional survey was administered to 969 volunteer participants during 1997 to 2000. Eligible participants included immediate family members of deceased patients at five local institutions in a regional health system. Among 969 respondents, most (84.4 percent) indicated that the care for their family member was excellent. Reasons cited for satisfaction included overall care (40.2 percent), staff effort (23.2 percent), and communication (16.4 percent). Reasons cited for dissatisfaction included perceived incompetence (9.7 percent), perceived uncaring attitude (8.4 percent), and perceived understaffing (3.7 percent). Respondents were more satisfied with communication from nursing staff (88 percent) than physicians’ communication (78 percent, p < 0.001, Bowker’s test). Respondents indicated higher overall satisfaction with nursing (90 percent) and pastoral care (87 percent), than with physician care (81 percent, p < 0.001 and p = 0.006, Bowker’s test). A unique survey instrument can be used to measure family perceptions and opinions regarding end-of-life care.
Non-invasive pain control in the terminally ill patient
Authors: Kinzbrunner Barry M. , Policzer Joel , Miller Barbara , Neiber Linda 
Published: May 2006

Although terminal patients with chronic pain are best managed with oral analgesia, patients who cannot take oral medication of ten receive treatment liy parenteral routes. Seventy consecutive terminal patients admitted to our hospice inpatient facility were evaluatedfor pain control over a three day period. Level ofpain was evaluated on a scale of zero to three (0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain). Patients were also evaluated for level of consciousness on a scale of one to four (1=alert, 2=confused, 3=semi-comatose, 4=comatose). Patients were medicated with morphine sulfate, either orally or by suppository, on a regular, four-hour schedule. Level of pain and level ofconsciousness evaluations were performed at the time each dose of morphine sulfate was administered. Data were compared for the level of pain and level of consciousness for the three day study period using Chisquared analysis. The results showed a significant decrease in levelofpain over the study period (p<.005). During this time, no significant alteration in level of consciousness was noted. Thirtynine out of 65 patients were treated via the suppository route and a significant decrease in the level of pain was seen in this sub-group as well (p<.005). Median morphine sulfate dose in all patients on day three was 15 mg. every four hours, with no significant difference between oral and suppository sub-groups. Parenteral analgesia was not required by any patient to achieve adequate pain control. This study demonstrates that effective pain control in terminal patients can be achieved withoutparenteral administration of analgesia and without alteration in level of consciousness. In patients unable to receive oral analgesia, the use of suppository analgesia is an effective alternative, avoiding the increased discomfort associated with parenteral analgesia administration.
Relationship between right-to-die and satisfaction with life
Authors: Huber Ruth 
Published: May 2006

To examine the relationship between right-to-die attitudes and satisfaction with life, 108 institutionalized elderly residents in a random sample were interviewed inthe summer of 1990.’ Overall, 55 percent responded Yes or Probably Yes to a question pertaining to the legalization of some form of control of death circumstances. Those who were moderately or most satisfied with their lives more often responded Yes or Probably Yes to the legalization question.The purpose of this article is to discuss findings from a random sample of 108 institutionalized elderly concerning the relationship between their responses to right-to-die questions and their self-reported satisfaction with life.
Student-led exercise sessions yield significant fitness gains for Alzheimer's patients
Authors: Arkin Sharon M. 
Published: May 2006

At a time when they are losing skills in virtually all arenas of life, persons with Alzheimer's disease can experience significant, esteem-building achievements in physical fitness and mood through supervised participation in an exercise program. The effects of physical exercise plus cognitive and social stimulation on persons with early stage Alzheimer's disease were assessed in a longitudinal study. Twenty-four such individuals, aged 54 to 88 at program entry, participated in 16 to 20 exercise sessions and 10 community activity sessions per semester for two to eight semesters. Half of the weekly exercise sessions included memory and language stimulation activities. Students, supplemented by family caregivers, supervised the sessions. Exercise sessions consisted of flexibility, balance, aerobic, and weight resistance activities. Preparticipation and semiannual post-testing of aerobic fitness and duration and upper and lower body strength was done. Highly significant fitness gains (p < .001) were achieved in the six-minute walk test, upper and lower body strength, and duration of aerobic exercise. Five participants, aged 86 to 91, completed six to eight semesters and were doing 27 to 45 minutes of aerobics per session at program's end. Five participants scored within the normal range for age-matched healthy active adults on the sixminute walk test at baseline. Nine others achieved and three exceeded the normal range during treatment. Cognitive decline was slowed and mood improved. Firstyear cognitive outcomes have been published elsewhere. 1-4 An article reporting final cognitive outcomes is in preparation; Outcome data is summarized on the project website: www.u.arizona.edu/~sarkin/elderrehab.html. The benefits of physical exercise can be made available at nominal cost to Alzheimer's patients and other elderly persons by using students to provide transportation, supervision, and the motivational support that is key to exercise adherence. Further research is needed to determine the relative contributions of each program component to the positive outcomes.
Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation
Authors: Lee Gloria , Lo Annie , Short Sarah A. , Mankelow Tosti J. , Spring Frances , Parsons Stephen F. , Yazdanbakhsh Karina , Mohandas Narla , Anstee David J. , Chasis Joel Anne 
Published: May 2006

AbstractErythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule 4 (ICAM-4), an immunoglobulin superfamily member, participates in island formation. Earlier, we identified αV integrins as ICAM-4 counterreceptors. Because macrophages express αV, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knock-out mice and developed quantitative, live cell techniques for harvesting intact islands and for re-forming islands in vitro. We observed a 47% decrease in islands reconstituted from ICAM-4 null marrow compared to wild-type marrow. We also found a striking decrease in islands formed in vivo in knock-out mice. Further, peptides that block ICAM-4/αV adhesion produced a 53% to 57% decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage αV functions in island integrity. Importantly, we documented that αV integrin is expressed in macrophages isolated from erythroblastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/αV adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.
Failure of non-invasive ventilation in patients with acute lung injury: observational cohort study
Authors: Rana Sameer , Jenad Hussam , Gay Peter C , Buck Curtis F , Hubmayr Rolf D , Gajic Ognjen 
Published: May 2006

Abstract
Introduction
The role of non-invasive positive pressure ventilation (NIPPV) in the treatment of acute lung injury (ALI) is controversial. We sought to assess the outcome of ALI that was initially treated with NIPPV and to identify specific risk factors for NIPPV failure.

Methods
In this observational cohort study at the two intensive care units of a tertiary center, we identified consecutive patients with ALI who were initially treated with NIPPV. Data on demographics, APACHE III scores, degree of hypoxemia, ALI risk factors and NIPPV respiratory parameters were recorded. Univariate and multivariate regression analyses were performed to identify risk factors for NIPPV failure.

Results
Of 79 consecutive patients who met the inclusion criteria, 23 were excluded because of a do not resuscitate order and two did not give research authorization. Of the remaining 54 patients, 38 (70.3%) failed NIPPV, among them all 19 patients with shock. In a stepwise logistic regression restricted to patients without shock, metabolic acidosis (odds ratio 1.27, 95% confidence interval (CI) 1.03 to 0.07 per unit of base deficit) and severe hypoxemia (odds ratio 1.03, 95%CI 1.01 to 1.05 per unit decrease in ratio of arterial partial pressure of O2 and inspired O2 concentration – PaO2/FiO2) predicted NIPPV failure. In patients who failed NIPPV, the observed mortality was higher than APACHE predicted mortality (68% versus 39%, p < 0.01).

Conclusion
NIPPV should be tried very cautiously or not at all in patients with ALI who have shock, metabolic acidosis or profound hypoxemia.
A New Photoisomerization Process of the 4-Cyanobutyl Group in a Cobaloxime Complex Crystal Observed by Neutron Diffraction
Authors: Hosoya Takaaki , Uekusa Hidehiro , Ohashi Yuji , Ohhara Takashi , Kuroki Ryota 
Published: May 2006

Abstract
The 4-cyanobutyl group of (4-cyanobutyl)[3,4-lutidine](dimethylglyoximato)[O-(diphenylboryl)dimethylglyoximato]cobalt(III) was isomerized to the 1-cyanobutyl group with retention of the single-crystal form, although the corresponding cobaloxime complex without diphenylboryl in the equatorial ligands did not show such a photoisomerization. The trans–cis–cis conformation of the 4-cyanobutyl group caused by the steric repulsion from the diphenylboryl group is favorable to the crystalline-state reaction. In order to elucidate the detailed isomerization mechanism, two hydrogen atoms of the 4-cyanobutyl group were replaced with the deuterium atoms such as –CH2CH2CH2CD2CN. After the photoisomerization, the crystal structure with deuterated 4-cyanobutyl group was analyzed by neutron diffraction. Only one of the two deuterium atoms of the 4-cyanobutyl group was transferred to the C1 atom such as –CD(CN)CH2CH2CDH2. This result made clear that the photo-produced cyanobutyl radical turned upside down after homolytic cleavage of the Co–C bond, and then the Co(II) atom and the radical made a bond to form the 1-cyanobutyl group.
Component Analysis of Particulate Products in Electron Beam-Irradiated Xylene/Air Mixtures Using an Atmospheric Pressure Ionization Mass Spectrometer
Authors: Hakoda Teruyuki , Sako Toshihiro , Shimada Akihiko , Ishida Tsuneo , Kojima Takuji 
Published: May 2006

Abstract
Particulate and gaseous organics are formed, as transient products, from dilute concentrations of xylene in air under electron beam irradiation; however, the components of the particulate organic products and the particle formation process are unknown. In the present study, the component analysis of particulate products were performed employing an atmospheric pressure ionization mass spectrometer (APIMS) based on a temperature-programmed desorption method to identify the components of the particles from o-xylene as a function of their gasification temperatures. Ions of 139–203 u with a peak interval of the m/z of 16 u, the same as the value of O+, were observed as vaporized particle components at correspondent temperatures. The ions of 43, 47, 61, 97, 111, 135, and 139 u were detected as the vaporized components at 333 K. The ions of 155, 171, and 187 u were observed at 363 K, besides that of 203 u at 393 K. The ions of 392–421 u were also appreciable with peak heights of 10−2 order lower than those for the ions of 139–203 u at temperatures higher than 393 K. The gaseous products in irradiated o-xylene/air mixtures were also analyzed with the APIMS. The ions with m/z lower than 139 u were detected as gaseous products.
On the Stereoselectivity of Asymmetric Strecker Synthesis in a Cyclohexane System: Synthesis of Optically Active cis- and trans-1-Amino-2-hydroxycyclohexane-1-carboxylic Acids
Authors: Shinada Tetsuro , Kawakami Tadashi , Sakai Hiroshi , Matsuda Hiromi , Umezawa Taiki , Kawasaki Masaki , Namba Kosuke , Ohfune Yasufumi 
Published: May 2006

Abstract
Stereoselective synthesis of both optically active cis- and trans-1-amino-2-hydroxycyclohexane-1-carboxylic acids (Ahhs) 1a and 1b was accomplished by an asymmetric version of the Strecker synthesis. Stereochemical aspects of their chiral induction processes are investigated.
Isolation and Physical Properties of an Electron-Rich 3,4-Diacetoxy-8,8-dimethylheptafulvene
Authors: Yin Bing Zhu , Mori Akira , Takeshita Hitoshi , Inoue Hironao 
Published: May 2006

Abstract
An electron-rich 3,4-diacetoxy-8,8-dimethylheptafulvene was isolated. The crystal structure shows that the seven-membered ring exists in an “envelope” conformation and the exocyclic C=C bond length is 1.343 Å.
Conjugate Addition of Allylic Groups to α,β-Enones via Photoinduced Electron Transfer Reaction of Allylic Stannanes
Authors: Takuwa Akio , Nishigaichi Yutaka , Iwamoto Hidetoshi 
Published: May 2006

Abstract
Conjugate addition of allylic groups, including allyl and cinnamyl systems, to a variety of α,β-unsaturated ketones could be achieved by photoirradiation with allylic stannanes.
Living Ring-opening Oligomerization of Cyclosiloxanes with an Aluminum-Tetraphenylporphyrin Complex Initiator
Authors: Yoshinaga Kohji , Iida Yoshikazu 
Published: May 2006

Abstract
An aluminum-tetraphenylporphyrin (Al(TPP)) catalyzed the ring-opening oligomerization of cyclosiloxanes with narrow molecular weight distribution, involving selection as for ring-size.
Catalytic Behavior of Iron(III)-8-quinolinol Complex in the Chemiluminescence Reaction of Luminol with Hydrogen Peroxide in Reverse Micelles
Authors: Fujiwara Terufumi , Tanimoto Noriyuki , Nakahara Kazue , Kumamaru Takahiro 
Published: May 2006

Abstract
Upon mixing of tris(8-quinolinolato)iron(III), an enhancement in the chemiluminescence emission resulting from the luminol-hydrogen peroxide reaction in reversed micellar solution was observed. Uptake of the complex by reverse micelles and its subsequent decomposition in the micelles appear to occur easily in the process.
Novel [4+2]-Type Reaction of 2-(Dimethylamino)cyclobutanecarboxylic Esters with Carbonyl Compounds
Authors: Shimada Shigeru , Saigo Kazuhiko , Nakamura Hideyuki , Hasegawa Masaki 
Published: May 2006

Abstract
In the presence of titanium(IV) chloride, 2-(dimethylamino)cyclobutanecarboxylic esters, equivalents of 1,4-zwitterions, reacted with carbonyl compounds to give δ-lactols or dihydropyrans.
Unusual Rotamer Equilibria in Solution and Atropisomerism in 9-(1,3-Dioxolan-2-y1)-1,2,3,4-tetraf1uorotriptycene
Authors: Yamamoto Gaku 
Published: May 2006

Abstract
The title compound exists as a 1:1 mixture of ap and ±sc rotamers at equilibrium in CDCl3. The origin of the unusually high population of the ap rotamer was explored by molecular mechanics calculations. The two rotamers were separately isolated as crystals by selective crystallization.