bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidd Blood‐Group Antigens of Leukocytes and Platelets
Authors: Marsh W. L. , ØYen R. , Nichols M. E.
Published: October 2009

Neutrophil leukocytes have a strong absorptive capacity for anti‐JkaJkb, made by Jk (a‐b‐) persons, but do not absorb anti‐Jka or anti‐Jka. The Jka Jkb antigen does not appear to be present on lymphocytes or platelets. The results indicate that JkaJkb activity is not a crossreaction between Jka and Jkb, but is a distinct and separable specificity.
Intensive Multiunit Plateletpheresis of Normal Donors
Authors: Schiffer C. A. , Buchholz D. H. , Wiernik P. H.
Published: October 2009

Intensive plateletpheresis was performed on 39 donors on 104 occasions in order to provide compatible platelets for patients refractory to transfusions from random donors. From three to eight units of platelet concentrate were obtained at each donation and repeated donations could be performed efficiently and safely. As many as 29 units of platelets were removed on four consecutive days. Donor platelet counts decreased an average of 20 per cent during donation. With consecutive donations, there was a 13 per cent day‐to‐day mean decline in count. Platelet yield correlated with the initial count although considerable variation prevented accurate prediction of yield in individual cases. Yields fell between the first and second units removed, but remained stable thereafter and the yield per bag was often greater with five to eight unit plateletphereses than with four unit donations. Donors tolerated the procedure extremely well. It is concluded that repeated multiunit plateletpheresis is a safe and practical means of obtaining large numbers of platelets for transfusion.
Microcapillary Agglutination for the Detection of Leukocyte Antibodies: Evaluation of the Method and Clinical Significance in Transfusion Reactions
Authors: McCullough J. , Burke M. E. , Wood N. , Carter S. J. , Weiblen B. J. , Yunis E. J.
Published: October 2009

The method for detection of anti‐leukocyte antibodies by microcapillary agglutination (MCA) is described in detail, as are the procedures used to establish positive and negative results and reproducibility. MCA was found to be more sensitive than lymphocytotoxicity (LC) and antisera which appeared to be monospecific by LC were multispecific when tested by MCA. In addition, MCA was found to have more clinical significance than LC. Eighty‐four per cent of 25 patients with nonhemolytic transfusion reactions and a temperature elevation of > 1 F had anti‐leukocyte antibodies detected by MCA, while only 36 per cent of these patients had anti‐leukocyte antibodies detected by LC. MCA defined a group of transfusion reactions in patients who had more previous transfusions, more pregnancies, and a higher average temperature elevation than did patients without detectable anti‐leukocyte antibodies. Although LC methods are currently in widespread use for organ matching in transplantation, other methods such as MCA for the detection of anti‐leukocyte antibodies may have more relevance to the problems of blood transfusion.
Red Cell D Antigen Sites and Titration Scores in a Family with Weak and Normal Du Phenotypes Inherited from a Homozygous Du Mother
Authors: Bush M. , Sabo B. , Stroup M. , Masouredis S. P.
Published: October 2009

The family of an obstetrical patient with an unusually weak Du phenotype has been studied. Strong positive reactions in the Du test were observed with the cells of four siblings who are of the DucE phenotype whereas very weak reactions were obtained with the proposita and one sib who are DuCe. The father is Rh negative thus proving the mother to be homozygous Du (DuCe/DucE). The two Du phenotypes and the homozygous Du mother were compared by titration scores and by the uptake of labeled anti‐D. The correlation was good between the titration score and the number of D antigen sites. However, red blood cells with normal D antigen content and one of the two weakly reactive DuCe/dce cells had titration scores that were too low in comparison to the number of D sites.
Altered Filterability of CPD‐Stored Sickle Trait Donor Blood
Authors: Hipp M. J. , Scott R. B.
Published: October 2009

Previous studies have shown that in sickle trait (AS) donor blood very little sickling is visible. AS donor blood was evaluated by a method of blood filtration, which would be sensitive to intracellular gellation of S hemoglobin which might not be evident morphologically. Blood was collected from normal and sickle trait subjects into CPD solution and stored at 4 C. Blood was removed over a 21‐day period and filtered through paper filters at unit gravity and also examined microscopically. Sickling was not evident in saline wet preparations, but was seen in each AS sample in 10 per cent formalin‐saline. At 4, 25, and 37 C, AS blood filtered less rapidly than did normal (P < 0.01). AS blood filterability became progressively prolonged as temperature rose; conversely normal blood filterability shortened with increasing temperature. Over 21 days, AS blood remained less filterable than normals. AS samples with high hemoglobin S percentages filtered significantly more slowly than did those with less S hemoglobin.

Recognizing that these studies refer only to blood in vitro, no conclusions are drawn with respect to reversibility of the altered filterability or any possible clinical implications.
Studies of MNSsU Antigen Activity on Leukocytes and Platelets
Authors: Marsh W. L. , ØYen R. , Nichols M. E. , Charles H.
Published: October 2009

Leukocytes or platelets from donors of appropriate blood type do not absorb anti‐M, anti‐N, anti‐S, or anti‐s. Leukocytes from U‐positive donors absorb anti‐U, but white blood cells collected from U‐negative donors do not absorb the antibody. Tests with separated platelets, lymphocytes, and neutrophils indicate that U‐antigen is probably restricted to the neutrophils.
Experiences with Frozen Erythrocytes in a Private Hospital
Authors: Bryant L. R. , Wallace M. E.
Published: October 2009

Frozen erythrocytes can provide a valuable addition to many blood banks for better patient care. Exaggerated fears concerning cost and complexity have frightened many blood bankers from consideration of a frozen erythrocyte program for their hospital blood bank. This type of program promotes improved blood banking as it emphasizes the need for increased utilization of specific blood components in hemotherapy. Since better inventory control is achieved, the patient is more likely to receive the desired component when needed. Erythrocytes containing optimal levels of DPG and ATP always are available. As compared to ordinary whole blood, frozen erythrocytes markedly reduce the incidence of febrile and hypersensitivity reactions, and the incidence of hepatitis may be reduced. A frozen erythrocyte program is also advantageous in that an autotransfusion program can be developed successfully and blood from selected donors lacking certain antigens can be stored for future transfusions to patients presenting problems.
Interaction Effects Analysis of Platelet Transfusion Data
Authors: Parker R. D. , Yamamoto L. A. , Miller W. R.
Published: October 2009

A statistical method is described for determining which recipient factors influence the efficacy of platelet transfusions in the treatment of thrombocytopenia caused by bone marrow depression. The method, known as interaction effects detection, is useful because it will relate a dependent variable 12‐hour posttransfusion in vivo platelet increment which is numerical to independent variables (recipient factors), which are not necessarily numerical or even rank ordered, in such a manner as to reveal the interactions among the independent variables. The results of the analysis suggest that seven of the 23 independent variables could be key ones in determining the efficacy of a transfusion, as measured by the dependent variable.
A New Rapid Method for Thawing Fresh Frozen Plasma
Authors: Sherman L. A. , Dorner I. M.
Published: October 2009

The use of fresh frozen plasma (FFP) often results in unused thawed units because of the time required to thaw FFP prior to use. A rapid thawing technique was studied, utilizing a microwave oven. Resultant levels of coagulation factors were compared with conventional slow thawing in a 37 C water bath. Mean prefreezing, rapid thaw and conventional thaw values were fibrinogen 246, 223, 238 mg/100 ml; prothrombin 101, 103, 105 per cent; factor V; 102, 79, 86 per cent; factor VIII 94, 77, 75 per cent; factor IX 103, 92, 90 per cent; factors VII/X 101, 107, 103 per cent; and factor × 84, 79, 82 per cent. No significant differences existed between rapid thawing and conventional thawing for any coagulation factor studied. Average thawing times were five minutes for rapid thawing (RT) and 25 minutes for conventional thawing. Although careful establishment of thawing time is required for each oven, microwave thawing permits better utilization of FFP for surgery and speeds delivery in emergencies, without destroying coagulation proteins.
The Use of Autologous Blood in Open‐Heart Surgery
Authors: Lubin J. , Greenberg J. J. , Yahr W. Z. , Haynes J. L. , Paul E.
Published: October 2009

A fairly simple method for obtaining from two to four units of fresh autologous whole blood and as many as six units of autologous fresh, frozen plasma is described. The only special equipment necessary is a refrigerated centrifuge. The procedure is well tolerated by the patients. The need for heterologous units of blood is diminished or entirely eliminated.
A Second Example of Anti‐Fy3 in the Duffy Blood Group System
Authors: Oberdorfer C. E. , Kahn B. , Moore V. , Zelenski K. , ØYen R. , Marsh W. L.
Published: October 2009

An example of anti‐Fy3 has been found in an Fy(a — b—) Negro patient whose serum also contains separable anti‐Fya. The serological reactions of the anti‐Fy3 component duplicate those of the original serum, except that in this case Fy(a +) or Fy(b +) red blood cells from newborn infants are not agglutinated. Both of the antibodies appear to be an immune response to a single blood transfusion.
Blood Donor Eligibility, Recruitment, and Retention
Authors: Miller T. R. , Weikel M. K.
Published: October 2009

To study the motivation and actions of potential and active blood donors, a literature search, a limited survey, and associated analytic efforts were undertaken. It is estimated that 61 million of the 114 million age‐eligible donors meet Red Cross criteria of health‐eligibility. The 1971 donor participation rate, calculated as the percentage ratio of active donors to eligible donors, was estimated to be between 8 and 9 per cent. Total collections appear to be increasing at a stable rate of 1 per cent per year and 15 per cent of each year's collections apparently come from first‐time donors. Thus, 14 per cent of those who donate blood in any given year must replace other donors who have stopped donating. Roughly 25 per cent of those who are health‐eligible to donate blood have done so in the last ten years. Literature and survey analyses indicate that donor reaction rates are considerably underestimated by most collectors. A limited survey showed that the main reason for nonparticipation is fear, while common reasons for discontinuing participation are adverse reaction and medical disqualification.
Book Review
Authors: Schmidt P. J.
Published: October 2009

Military Blood Banking 1941–1973. Lessons Learned Applicable to Civil Disasters and Other Considerations. F. R. Camp, Jr., N. F. Conte, and J.R. Brewer. U. S. Army Medical Research Laboratory, Ft. Knox, Kentucky, 1973.
Identification of Hemodynamically Unstable Arrhythmias Using Subcutaneous Photoplethysmography
Authors: TURCOTT ROBERT G. , PAVEK TODD J.
Published: October 2009

Hemodynamic Assessment Using Photoplethysmography. Introduction: Determination of hemodynamic status is central to arrhythmia management in the inpatient setting. In contrast, therapy decisions in implantable cardioverter defibrillators (ICDs) are based exclusively on the arrhythmia's electrical signature. Hemodynamic sensing in ICDs would allow tailoring of therapy according to perfusion status. Subcutaneous photoplethysmography (PPG) is an attractive technology for this application because it responds to changes in arterial pressure and can be readily incorporated into the housing of implanted devices. This study evaluated the accuracy of PPG in identifying hemodynamically unstable simulated arrhythmias in an animal model.

Methods and Results:
Rapid atrial and ventricular pacing was used to simulate arrhythmias in an acute preparation of 7 healthy dogs. Aortic pressure and subcutaneous PPG were simultaneously recorded. Simulated arrhythmias were defined as hemodynamically unstable if aortic pressure decreased by ≥15 mmHg, marginally unstable if pressure decreased by 5–15 mmHg, and hemodynamically stable if pressure either increased or decreased by no more than 5 mmHg. An average of 56 arrhythmias were simulated in each animal. Changes in pressure and PPG output were highly correlated, with correlation coefficient of 0.7–0.9. Subcutaneous PPG identified hemodynamically unstable episodes with a sensitivity of 100% for 6 subjects and 80% for 1 subject. Specificity was more than 90% for 6 subjects and was 50% for 1 subject.

Conclusions:
Subcutaneous PPG detects hemodynamically unstable simulated arrhythmias in an acute canine preparation. If successfully validated in humans, this technology may allow ICD therapy to be specifically tailored according to the hemodynamic status of the arrhythmia. (J Cardiovasc Electrophysiol, Vol. 21, pp. 448–454, April 2010)
Income Transfers Alone Won't Eradicate Poverty
Authors: Besharov Douglas J. , Call Douglas M.
Published: October 2009

Even in the current economic situation, in developed countries, rhetoric about cutting “poverty” is misleadingly outmoded—because it implicitly suggests that government income transfers can be the vehicle for achieving substantial reductions in poverty. Almost all Americans already live far above subsistence poverty: most because of their earnings, and the rest because of government transfer programs. This decline in material poverty is obscured by weaknesses in how the official U.S. poverty measure counts income. What is now called poverty is really “income inequality.” Reducing income inequality is also a vitally important social goal, but it cannot be accomplished through income transfers alone. The authors argue that, although income transfers have a role to play in lessening the impact of material deprivation, real progress in raising incomes will require building the human capital of the economically disadvantaged. This means both increasing the earnings capacity of lower‐income workers and reducing the number of female‐headed families.
Policy Entrepreneurship and Policy Change
Authors: Mintrom Michael , Norman Phillipa
Published: October 2009

This article reviews the concept of policy entrepreneurship and its use in explaining policy change. Although the activities of policy entrepreneurs have received close attention in several studies, the concept of policy entrepreneurship is yet to be broadly integrated within analyses of policy change. To facilitate more integration of the concept, we here show how policy entrepreneurship can be understood within more encompassing theorizations of policy change: incrementalism, policy streams, institutionalism, punctuated equilibrium, and advocacy coalitions. Recent applications of policy entrepreneurship as a key explanation of policy change are presented as models for future work. Room exists for further conceptual development and empirical testing concerning policy entrepreneurship. Such work could be undertaken in studies of contemporary and historical policy change.
Effects of U.S. States' Social Welfare Systems on Population Health
Authors: Kim Ae‐Sook , Jennings Edward T.
Published: October 2009

Social scientists have studied the welfare state extensively. Many studies seek to understand the determinants of the welfare state; however, a few have explored the social consequences of social welfare systems, especially on health outcomes of the population. Even though cross‐national comparative studies support the thesis that the welfare state regime type, which represents different levels of commitment on social welfare, is closely linked to population health, there is little research to support this argument at a sub‐national level. To fill the gap, this study explores the effects of the U.S. states' social welfare systems on health using age‐adjusted mortality rates as a proxy for population health. By operationalizing social welfare systems as three dimensions—public expenditures, tax structures, and welfare program rules—we find that more generous education spending, progressive tax systems, and more lenient welfare program rules help to improve population health. The model corrects for first‐order serial correlation using Prais‐Winsten regression methods and is estimated with state and year‐fixed effects.
The Multistep Nature of the Kaolinite Dehydroxylation: Kinetics and Mechanism
Authors: Ortega Andres , Macías Manuel , Gotor Francisco J.
Published: October 2009

The thermal dehydroxylation of kaolinite has been reexamined using small sample weights, a homogeneous particle size distribution and high‐vacuum conditions in order to reduce the influences of heat and mass‐transfer phenomena. The controlled rate thermal analysis (CRTA) technique, which was specially developed to minimize the pressure and temperature gradients through the sample, was employed to carry out meaningful kinetic experiments. Two advanced isoconversional methods, the Vyazovkin and the Galwey methods, were used complementarily to determine the dependence of the activation energy on the degree of conversion. For this purpose, the Vyazovkin method has been adapted to CRTA experiments. It was demonstrated that there are at least two different stages, revealing the multistep nature of this reaction. The activation energy for the first step, which is assigned to nucleation and the growth of nuclei, decreases from 100 to 75 kJ/mol. The second stage corresponds to a diffusion process and the activation energy rises to 120 kJ/mol because of the metakaolinite formation, which closes the interlamellar channels and leaves isolated patches of kaolinite from which the water escapes with difficulty.
Use of Heat‐Treated Water Treatment Residuals in Fly Ash‐Based Geopolymers
Authors: Guo Xiaolu , Shi Huisheng , Dick Warren
Published: October 2009

Geopolymerization is a developing field that can beneficially use heat‐treated water treatment residuals (WTRs) to create fly ash‐based geopolymers. In this study, geopolymers made only from fly ash (FA) and from FA plus calcined WTRs (FA–WTRs) were evaluated. The proper calcining condition for WTRs is 900°C for 1 h and the optimum amount of WTRs to mix with FA is 10 wt%. Compressive strength of samples cured at 75°C for 24 h can reach 68.1 MPa, and when cured at 23°C for 28 days the values were >50 MPa. Further studies were conducted on FA and FA–WTRs geopolymer samples cured at 75°C for 8 h followed by 23°C for 28 d. X‐ray diffraction patterns of geopolymers made from FA indicate the presence of amorphous geopolymeric and calcium silicate hydrate (C–S–H) gels, and a type of zoelite similar to gismondine. When WTRs replaced some of the FA, amorphous geopolymeric gels are mainly formed. Scanning electron micrographs indicate spherical unreactivated FA and other particles are combined and surround the geopolymeric and C–S–H gels. Utilization of WTRs in creation of FA‐based geopolymers can lead to a new type of cementitious binder.
A Rapidly Responding Sensor for Methanol Based on Electrospun In2O3–SnO2 Nanofibers
Authors: Zheng Wei , Lu Xiaofeng , Wang Wei , Dong Bo , Zhang Hongnan , Wang Zhaojie , Xu Xiuru , Wang Ce
Published: October 2009

In this paper, we presented a simple and effective electrospinning technique for the preparation of In2O3–SnO2 composite nanofibers. The morphology and chemical structure of the as‐prepared samples were analyzed by scanning electron microscopy, transmission electron microscopy, and X‐ray diffraction. The results showed that large quantities of In2O3–SnO2 composite nanofibers with diameters from 60 to 100 nm were obtained. The In2O3–SnO2 composite nanofibers exhibited excellent gas sensing properties to methanol, such as fast response/recovery properties, high sensitivity, and good selectivity.
Adolescent Suicide Risk Screening in the Emergency Department
Authors: King Cheryl A. , O’Mara Roisin M. , Hayward Charles N. , Cunningham Rebecca M.
Published: October 2009

Objectives:  Many adolescents who die by suicide have never obtained mental health services. In response to this, the National Strategy for Suicide Prevention recommends screening for elevated suicide risk in emergency departments (EDs). This cross‐sectional study was designed to examine 1) the concurrent validity and utility of an adolescent suicide risk screen for use in general medical EDs and 2) the prevalence of positive screens for adolescent males and females using two different sets of screening criteria.

Methods:  Participants were 298 adolescents seeking pediatric or psychiatric emergency services (50% male; 83% white, 16% black or African American, 5.4% Hispanic). The inclusion criterion was age 13 to 17 years. Exclusion criteria were severe cognitive impairment, no parent or legal guardian present to provide consent, or abnormal vital signs. Parent or guardian consent and adolescent assent were obtained for 61% of consecutively eligible adolescents. Elevated risk was defined as 1) Suicidal Ideation Questionnaire‐Junior [SIQ‐JR] score of ≥31 or suicide attempt in the past 3 months or 2) alcohol abuse plus depression (Alcohol Use Disorders Identification Test‐3 [AUDIT‐3] score of ≥3, Reynolds Adolescent Depression Scale‐2 [RADS‐2] score of ≥76). The Beck Hopelessness Scale (BHS) and Problem Oriented Screening Instrument for Teenagers (POSIT) were used to ascertain concurrent validity.

Results:  Sixteen percent (n = 48) of adolescents screened positive for elevated suicide risk. Within this group, 98% reported severe suicide ideation or a recent suicide attempt (46% attempt and ideation, 10% attempt only, 42% ideation only) and 27% reported alcohol abuse and depression. Nineteen percent of adolescents who screened positive presented for nonpsychiatric reasons. One‐third of adolescents with positive screens were not receiving any mental health or substance use treatment. Demonstrating concurrent validity, the BHS scores of adolescents with positive screens and the POSIT scores of those with positive screens due to alcohol abuse and depression indicated substantial impairment. The addition of alcohol abuse with co‐occurring depression as a positive screen criterion did not result in improved case identification. Among the subgroup screening positive due to depression plus alcohol abuse, all but one (>90%) also reported severe suicide ideation and/or a recent suicide attempt. This subgroup (approximately 17% of adolescents who screened positive) also reported significantly more impulsivity than other adolescents who screened positive.

Conclusions:  The suicide risk screen showed evidence of concurrent validity. It also demonstrated utility in identifying 1) adolescents at elevated risk for suicide who presented to the ED with unrelated medical concerns and 2) a subgroup of adolescents who may be at highly elevated risk for suicide due to the combination of depression, alcohol abuse, suicidality, and impulsivity.
Asymptomatic Hypertension in the Emergency Department: A Matter of Critical Public Health Importance
Authors: Levy Phillip D. , Cline David
Published: October 2009

Asymptomatic hypertension (HTN) is commonly encountered in the emergency department (ED), but in most circumstances little is done about it. While many factors may contribute to this, the failure to recognize asymptomatic HTN as a public health problem is particularly important. Given the established long‐term consequences of elevated blood pressure (BP), a reconsideration of methods that could enhance surveillance and intervention in the ED is needed. In this article, we discuss the relevant epidemiology of asymptomatic HTN and present a novel approach using a modified version of the Haddon’s matrix to systematically address the challenges that contribute to ineffective screening and suboptimal outcomes.
Metabolic profiling reveals key metabolic features of renal cell carcinoma
Authors: Catchpole Gareth , Platzer Alexander , Weikert Cornelia , Kempkensteffen Carsten , Johannsen Manfred , Krause Hans , Jung Klaus , Miller Kurt , Willmitzer Lothar , Selbig Joachim , Weikert Steffen
Published: October 2009

Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α‐tocopherol, hippuric acid, myoinositol, fructose‐1‐phosphate and glucose‐1‐phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.
Identifying environmental signals from population abundance data using multivariate time‐series analysis
Authors: Fujiwara Masami , Mohr Michael S.
Published: October 2009

Individual organisms are affected by various natural and anthropogenic environmental factors throughout their life history. This is reflected in the way population abundance fluctuates. Consequently, observed population dynamics are often produced by the superimposition of multiple environmental signals. This complicates the analysis of population time‐series. Here, a multivariate time‐series method called maximum autocorrelation factor analysis (MAFA) was used to extract underlying signals from multiple population time series data. The extracted signals were compared with environmental variables that were suspected to affect the populations. Finally, a simple multiple regression analysis was applied to the same data set, and the results from the regression analysis were compared with those from MAFA. The extracted signals with MAFA were strongly associated with the environmental variables, suggesting that they represent environmental factors. On the other hand, with the multiple regression analysis, one of the important signals was not identifiable, revealing the shortcoming of the conventional approach. MAFA summarizes data based on their lag‐one autocorrelation. This allows the identification of underlying signals with a small effect size on population abundance during the observation. It also uses multiple time series collected in parallel; this enables us to effectively analyze short time series. In this study, annual spawning adult counts of Chinook salmon at various locations within the Klamath Basin, California, were analyzed.
Biochemical alterations in the palatal processes in fetuses of biotin‐deficient mice
Authors: Watanabe Toshiaki , Suzuki Ai , Ebara Shuhei , Negoro Munetaka , Fukui Toru
Published: October 2009

To clarify the role of biotin in palatal formation, we investigated the effects of biotin deficiency on the development of palatal processes in mouse fetuses at midgestation. We also investigated protein expressions in the palatal processes. Pregnant mice were given either a biotin‐deficient diet or a biotin‐supplemented (control) diet from day 0 of gestation (dg 0). Some dams in the biotin‐deficient group were changed to a biotin‐supplemented diet on dg 12, 13 or 14. On dg 15, the palatal processes were dissected from these fetuses and their peptides were characterized using two‐dimensional electrophoresis and liquid chromatography/tandem mass spectrometry (LC‐MS/MS) system. Regarding Trasler's stage for the growth of the palatal processes in mouse fetuses on dg 15, the average stage of palatal development was 5.83 ± 0.39 in the biotin‐supplemented group, 5.39 ± 0.66 in the dg 13‐supplemented group, and 4.64 ± 0.90 in the biotin‐deficient group. The development of the palatal processes significantly increased in relation to the earlier day of biotin supplementation. In a protein analysis of palatal processes by isoelectro focusing (IEF) and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), a 19‐kDa spot was confirmed around position at pI 6–7 in the biotin‐supplemented group, but this protein was not present in either the biotin‐deficient group or the dg 13‐supplemented group. From the MS/MS database of peptides, adenosine diphosphate (ADP)‐ribosylation factor 2 (arf2) and α‐crystallin were detected in the mesenchyme of the palatal processes. It is suggested that the expression of these proteins may be downregulated by biotin deficiency, inducing the inhibited development of palatal processes.
Congenital polymicrogyria including the perisylvian region in early childhood
Authors: Takano Tomoyuki , Matsuwake Kumiko , Yoshioka Seiichirou , Takeuchi Yoshihiro
Published: October 2009

Six pediatric cases including four infants with congenital polymicrogyria including the perisylvian region are presented herein. Their clinical features were analyzed and compared with patients suffering from congenital bilateral perisylvian syndrome (CBPS). Two specific abnormalities were diagnosed as accompanying disorders in two cases, namely Kabuki syndrome and Peters' anomaly. In the other four cases, the pathogenetic etiology was not elucidated. Subtle symptoms, such as choking and drooling became detectable in one case each, and expressive language development was delayed in two patients. A developmental delay became apparent in five cases during the follow‐up period, and epilepsy was observed in one patient with onset at 12 years of age. Our results indicate that the presence of perisylvian polymicrogyria may not always result in the development of oropharyngoglossal dysfunction or dysarthria, although most patients tend to gradually show the onset of developmental disorders. To support cognitive and psychosocial development, an early integrated approach, including not only conventional speech and language therapy, but also various communication methods is essential for patients with congenital polymicrogyria including the perisylvian region.
Inhalation Device Allows Novel Administration of Apomorphine in Men with Erectile Dysfunction—Efficacy and Safety Findings
Authors: Riley Alan , Main Mark , Morgan Frazer
Published: October 2009

Introduction

Erectile dysfunction (ED) treatment is greatly influenced by patient preference, and currently available oral therapies do not meet all patients’ needs. New therapies and formulations are therefore being investigated.

Aim

The aim of this article is to assess the clinical efficacy and safety of inhaled apomorphine, VR004, in men with mild to severe ED.

Main Outcome Measures

Efficacy outcomes were the change in the proportion of positive responses to sexual encounter profile questions, International Index of Erectile Function (IIEF) scores and onset of therapeutic effect. Safety outcomes included a change in vital signs at an orthostatic challenge and adverse events (AEs).

Methods

Two consecutive, multicenter trials each comprised a 4-week no-treatment period and a 12-week “at home” treatment period with regular clinic visits. Patients (N=211 and N=389) were randomized to receive one of three set doses of VR004 (100–300 µg) or matching placebo in each trial. VR004 was administered by a dry-powder inhaler at least once a week.

Results

Efficacy was generally dose dependent. The proportion of per-protocol patients maintaining an erection long enough for successful intercourse increased in all VR004 groups vs. placebo. IIEF scores were higher in the VR004 groups compared with placebo, and the majority of responders achieved an erection within 10 minutes of dosing. The safety profile of VR004 was generally similar to that of placebo, and AEs were mild or moderate in severity. The incidence of treatment-related AEs was dose dependent. Few patients (4%) withdrew because of treatment-related AEs, and the majority of these withdrawals occurred on the day of the stringent orthostatic challenge.

Conclusions

The VR004 system administers low apomorphine doses that are well tolerated without compromising efficacy. This route of administration ensures a rapid onset of action and reproducible efficacy and safety profiles. Inhaled apomorphine is therefore a potential first-line treatment for ED.
Adenosine Deaminase Enzyme Therapy Prevents and Reverses the Heightened Cavernosal Relaxation in Priapism
Authors: Wen Jiaming , Jiang Xianzhen , Dai Yingbo , Zhang Yujin , Tang Yuxin , Sun Hong , Mi Tiejuan , Kellems Rodney E. , Blackburn Michael R. , Xia Yang
Published: October 2009

Introduction

Priapism featured with painful prolonged penile erection is dangerous and commonly seen in sickle cell disease (SCD). The preventive approaches or effective treatment options for the disorder are limited because of poor understanding of its pathogenesis. Recent studies have revealed a novel role of excess adenosine in priapism caused by heightened cavernosal relaxation, and therefore present an intriguing mechanism-based therapeutic possibility.

Aim

The aim of this study was to determine the therapeutic effects of adenosine deaminase (ADA) enzyme therapy to lower adenosine in priapism.

Methods

Both ADA-deficient mice and SCD transgenic (Tg) mice display priapism caused by excessive adenosine. Thus, we used these two distinct lines of mouse models of priapism as our investigative tools. Specifically, we treated both of these mice with different dosages of polyethylene glycol–modified ADA (PEG–ADA) to reduce adenosine levels in vivo. At the end points of the experiments, we evaluated the therapeutic effects of PEG–ADA treatment by measuring adenosine levels and monitoring the cavernosal relaxation.

Main Outcome Measures

Adenosine levels in penile tissues were measured by high-performance liquid chromatography, and cavernosal relaxation was quantified by electrical field stimulation (EFS)-induced corporal cavernosal strip (CCS) assays.

Results

We found that lowering adenosine levels in penile tissues by PEG–ADA treatment from birth in ADA-deficient mice prevented the increased EFS-induced CCS relaxation associated with priapism. Intriguingly, in both ADA-deficient mice and SCD Tg mice with established priapism, we found that normalization of adenosine levels in penile tissues by PEG–ADA treatment relieved the heightened EFS-induced cavernosal relaxation in priapism.

Conclusions

Our studies have identified that PEG–ADA is a novel, safe, and mechanism-based drug to prevent and correct excess adenosine-mediated increased cavernosal relaxation seen in two independent priapic animal models, and suggested its therapeutic possibility in men suffering from priapism.
Combined 3D‐QSAR Modeling and Molecular Docking Study on Quinoline Derivatives as Inhibitors of P‐selectin
Authors: Zeng Huahui , Cao Ran , Zhang Huabei
Published: October 2009

P‐selectin is a promising target for developing novel atherosclerosis drugs. To understand the structure–activity correlation of quinolines‐based P‐selectin inhibitors, we have carried out a combined molecular docking and three‐dimensional quantitative structure–activity relationship (3D‐QSAR) modeling study. The study has resulted in two types of satisfactory 3D‐QSAR models, including the CoMFA model (r2, 0.863; q2, 0.589) and CoMSIA model (r2, 0.866; q2, 0.636), to predict the biological activity of new compounds. The detailed microscopic structures of P‐selectin binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D‐QSAR models (CoMFA with r2, 0.934; q2, 0.591; CoMSIA with r2, 0.896; q2, 0.573). The contour maps obtained from the 3D‐QSAR models in combination with the docked binding structures help to better interpret the structure–activity relationship. All of the structural insights obtained from both the 3D‐QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D‐QSAR models and the obtained P‐selectin‐inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design.
QM/MM Study of Epitope Peptides Binding to HLA‐A*0201: The Roles of Anchor Residues and Water
Authors: Li Yuanchao , Yang Yadong , He Ping , Yang Qingwu
Published: October 2009

A hybrid quantum mechanics/molecular mechanics scheme is described to explore the structural basis and energetic behavior of short peptide segments binding to HLA‐A*0201. This method was used to analyze 50 structurally diverse non‐americ peptides and results showed that the quantum mechanics/molecular mechanics‐derived interaction energy, in conjugation with empirical desolvation free energy, linearly correlate well with the experimentally determined affinity. Further systematic investigations of several HLA‐A*0201–peptide complexes confirmed the importance of anchor residues and water molecules in peptide binding, and quantitatively showed that: (i) the primary and second anchor residues provide a larger binding energy contribution (>3 kcal/mol) than the non‐anchor residues (<2 kcal/mol), (ii) native hydrophobic anchor residues replaced by polar amino acids will lead to a significant destabilization for bound complexes (>4 kcal/mol), and (iii) water molecules contribute significantly to stabilization of the complexes (>8 kcal/mol). We believe that this work is helpful for elucidating the roles of anchor residues and water molecules in peptides recognized and bound by HLA‐A*0201.
Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity
Authors: Beher Dirk , Wu John , Cumine Suzanne , Kim Ki Won , Lu Shu‐Chen , Atangan Larissa , Wang Minghan
Published: October 2009

Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD+‐dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys‐SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys‐SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53‐derived peptide substrate or acetylated PGC‐1α isolated from cells, and (iii) although SIRT1 deacetylates PGC‐1α in both in vitro and cell‐based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.
Stereotypical Relations and Utterance Understanding: An Introduction to Xu Sheng‐Huan’s Stereotypical Relation‐Based Approach to Pragmatics
Authors: Bing‐zhang Wu
Published: October 2009

An utterance hardly provides adequate information for its understanding, but the stereotypical relations (SRs) suggested by its linguistic components and mode of expression help to complement the explicitly expressed content, thus making the utterance serve its communicative function. Stereotypical relations are a speaker/hearer’s perception and memory of the relations between things in the experiential world. Such relations, once entrenched, are the cognitive device by which humans understand, represent, and express the world. Things in SRs are interdependent; the presence of one entails that of another. Therefore, an utterance implicates the necessary information by SRs to ‘fill up’ the information gap in the context of communication. Stereotypical relations can be characterized in terms of similarity and proximity, both of which are categories of degree.
Quantified Conditionals and Compositionality
Authors: Huitink Janneke
Published: October 2009

The interpretation of conditionals in the scope of a quantifier (as in ‘No student will succeed if he goofs off’) presents a troubling puzzle. Either we are forced to abandon the thesis that natural language obeys the compositionality principle, or we must commit to a semantics for conditionals that involves an uncomfortably high degree of stipulation. This article surveys the recent literature on quantified conditionals and aims to pinpoint the issues that stand in the way of a compositional analysis.
Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age‐related macular degeneration in Hungarian patients
Authors: Losonczy Gergely , Fekete Ágnes , Vokó Zoltán , Takács Lili , Káldi Ildikó , Ajzner Éva , Kasza Márta , Vajas Attila , Berta András , Balogh István
Published: October 2009

Purpose:  Recent studies strongly support the role of genetic factors in the aetiology of age‐related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors.

Methods:  In a case‐control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls. Detailed patient histories were recorded with the use of a questionnaire focusing on known risk factors for AMD.

Results:  In the early AMD subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9‐fold (95% confidence interval [CI] 1.7–14.2), 7.4‐fold (95% CI 2.1–26.2) or 10.1‐fold (95% CI 2.5–40.8) risk of disease, respectively. In the late AMD subgroup, carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7‐fold (95% CI 3.7–31.0), 11.3‐fold (95% CI 3.2–40.4) or 13.5‐fold (95% CI 3.3–55.4) greater disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination conferred a 15.0‐fold (95% CI 3.2–71.0) increase in risk, whereas two LOC387715 risk alleles combined with one CFH risk allele was associated with a 14.0‐fold (95% CI 2.1–95.1) increased risk for late AMD. ApoE alleles neither increased disease risk nor proved to be protective.

Conclusions:  The CFH, LOC387715 and HTRA1 polymorphisms are strongly associated with the development of AMD in the Hungarian population. The association is particularly pronounced when homozygous risk alleles are present and in the late stages of the disease.
The Challenge of Pluralism and Peace: The Changing Relationships Among the Churches in Colombia1
Authors: Gros Jeffrey
Published: October 2009

When one church predominates in any society, ecumenism is notoriously difficult. Colombia is no exception. The 1991 Constitution disestablished the Catholic Church and subsequent decisions create a new legal situation for the churches together. These changes, along with the particular Protestant bodies in Colombia, the climate of civil conflict, the unique history of the country and the diversity of its peoples create a new context in which the challenge of ecumenism develops. This essay is an outsider's perspective on the contextual development of ecumenism, its hopes and challenges, in the current situation. The time has come for common witness to replace competition.
Redox modulation of global phosphatase activity and protein phosphorylation in intact skeletal muscle
Authors: Wright Valerie P. , Reiser Peter J. , Clanton Thomas L.
Published: October 2009

Skeletal muscles produce transient reactive oxygen species (ROS) in response to intense stimulation, disuse atrophy, heat stress, hypoxia, osmotic stress, stretch and cell receptor activation. The physiological significance is not well understood. Protein phosphatases (PPases) are known to be highly sensitive to oxidants and could contribute to many different signalling responses in muscle. We tested whether broad categories of PPases are inhibited by levels of acute oxidant exposure that do not result in loss of contractile function or gross oxidative stress. We also tested if this exposure results in elevated levels of global protein phosphorylation. Rat diaphragm muscles were treated with either 2,3‐dimethoxy‐1‐naphthoquinone (DMNQ; 1, 10, 100 μm; a mitochondrial O2•−/H2O2 generator) or exogenous H2O2 (5, 50, 500 μm) for 30 min. Supernatants were assayed for serine/threonine PPase (Ser/Thr‐PPase) or protein tyrosine PPase (PTP) activities. With the exception of 500 μm H2O2, no other oxidant exposures significantly elevated protein carbonyl formation, nor did they alter the magnitude of twitch force. DMNQ significantly decreased all categories of PPase activity at 10 and 100 μm and reduced PTP at 1 μm. Similar reductions in Ser/Thr‐PPase activity were seen in response to 50 and 500 μm H2O2 and PTP at 500 μm H2O2. ROS treatments resulted a dose‐dependent increase in the phosphorylation states of many proteins. The data are consistent with the concept that PPases, within intact skeletal muscles, are highly sensitive to acute changes in ROS activity and that localized ROS play a critical role in lowering the barriers for effective phosphorylation events to occur in muscle cells, thus increasing the probability for cell signalling responses to proceed.