bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein E and ALzheimer's Disease: The Tip of the Susceptibility Iceberg
Authors: ROSES ALLEN D. 
Published: February 2006

ABSTRACT: Apolipoprotein E (APOE) is a true susceptibility polymorphism of the common form of Alzheimer's disease (AD). There are three APOE alleles (ɛ2, ɛ3, ɛ4) that are universally distributed in the population with some variation in allele frequency due to racial and ethnic differences, and are associated with different risks and age of onset distributions. In multiple studies, the positive predictive value for symptomatic possible or probable AD patients who carry at least one ɛ4 allele was consistently >95%. Thus, early in the clinical course of dementia, when diagnoses are only 60‐70% accurate, the presence of an ɛ4 allele raises the diagnostic accuracy of AD to >95%. With the anticipation of a second major late‐onset AD susceptibility locus on chromosome 12, a matrix of relative susceptibility risks in the population raises many ethical and social questions associated with preclinical prediction.The metabolism of apoE (protein) in the brain is a new and exciting area of neurobiology research made relevant by the association with AD. We have constructed transgenic animals using large human genomic fragments containing human APOE on an APOE‐deficit mouse background as well as homologous recombination experiments replacing mouse APOE with human APOE promoter elements. The APOE tissue elements, NOT the human APOE gene coding sequence, is associated with the human pattern of intraneuronal apoE immunoreactivity.
The Effects of Topical Anesthesia on Oral Burning in Burning Mouth Syndromea
Authors: FORMARKER B. K. , MOTT A. E. , FRANK M. E. 
Published: February 2006

ABSTRACT: Burning mouth syndrome (BMS) is an oral pain disorder of uncertain origin. Central or peripheral pain mechanisms may play a role in the oral burning of BMS. We tested the effect of a topical anesthetic (dyclonine HCl) on patients' intensity ratings for oral burning, taste dysgeusia and the taste of two chemical stimuli (1.0 M NaCl and 1.0 M sucrose). A total of 33 patients (9 male and 24 female, average age: 60 yr) are included in this analysis. The anesthetic reduced the perceptual intensity of both chemicals in these patients on four out of five postanesthesia trials (p <0.01).The BMS cohort included 12 patients whose burning increased (p <0.001), 14 patients whose burning did not change, and 7 patients whose burning decreased (p <0.001) after anesthesia. Baseline dysgeusias (n= 13) decreased in intensity (p <0.001) after anesthesia, suggesting BMS dysgeusia is related to the activation of peripheral taste mechanisms. The results also suggest that BMS oral burning may be a disorder of peripheral pain pathways in some patients.
PROP (6‐n‐Propylthiouracil) Supertasters and the Saltiness of NaCla
Authors: BARTOSHUK LINDA M. , DUFFY VALERIE B. , LUCCHINA LAURIE A. , PRUTKIN JORDAN , FAST KATHARINE 
Published: February 2006

ABSTRACT: Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6‐n‐propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In recent years, we have classified tasters into two groups: medium (PROP is moderately bitter) and supertasters (PROP is intensely bitter). With our classification, ∼25% of Americans are nontasters, 50%, medium tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive group. Anatomical studies showed that supertasters have the most fungiform papillae. Psychophysical studies showed that supertasters perceive the most intense bitterness and sweetness from a variety of compounds, the most intense burn from oral irritants, and the most intense tactile sensations from viscous solutions. Oral burn and touch are presumably perceived to be the most intense to supertasters because taste buds in fungiform papillae are innervated by the trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste).The psychophysical scaling method used was magnitude matching with NaCl as the control modality. With this method, subjects rated the intensities of a series of NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with PROP status allowed comparisons of the bitterness of PROP across subjects. Early magnitude matching studies, using sound as the control, had suggested that this assumption was reasonable. However, recent studies challenged that conclusion. Larger samples with more diverse populations, using sound as the control, showed that the taste of NaCl varied with PROP bitterness; supertasters perceived the strongest taste and nontasters, the weakest. Thus our earlier conclusions were conservative because differences between nontasters, medium tasters, and supertasters were concealed by using NaCl as a standard. Using magnitude matching with sound as the standard, or using the Green scale, which employs intensity labels, we found that the differences between PROP groups are larger. Note that the association between PROP status and salt taste is interesting in itself, since variability in salt taste may have important nutritional consequences.
Effect of Gelatin (a Model for Salivary PRP) on the Sensory Astringency of 5‐O‐caffeoylquinic Acid and Tannic Acid
Authors: NAISH M. , CLIFFORD M. N. , BIRCH G. G. 
Published: February 2006

ABSTRACT:The present work investigates differences (triangular tests) between the astringency of 5‐O‐caffeoylquinic acid (5‐CQA) and that of 5‐CQA + gelatin. As an overall reference similar tests are reported using tannic acid (which has been shown to elicit a strong response). Finally, a time‐intensity study on aqueous solutions of tannic acid (TA), TA + gelatin and gelatin, reveals relevant temporal factors.Although, under the experimental conditions, the majority of comparisons revealed statistically significant differences, in the time‐intensity study no significant differences were found between TA + gelatin and gelatin, either for the intensity or the total duration of the response. Moreover, for the fading of the response there was no difference between TA + gelatin and TA.The main temporal contribution to the difference is in the onset of the response and can be related to the spectral differences observed in the earlier studies. It will be argued that these results may represent an important step in our understanding of the mechanisms of astringency.
Studies on Host Resistance to Tick Infestations among Trypanotolerant Bos indicus Cattle Breeds in East Africaa
Authors: MWANGI E. K. , STEVENSON P. , NDUNG'U J. M. , STEAR M. J. , REID S.W. J. , GETTINBY G. , MURRAY M. 
Published: February 2006

ABSTRACT: Recent epidemiological studies carried out in East Africa have indicated that some Bos indicus cattle breeds such as the Orma Boran and Maasai Zebu have a degree of trypanotolerance worth exploitation by their introduction into trypanosomosis endemic areas where other cattle breeds cannot survive. However, in most areas of East Africa, trypanosomosis, ticks, and tick‐borne diseases occur together. It is therefore important to obtain information on the susceptibility of these breeds to tick infestation and tick‐borne diseases. This study was therefore designed to determine the susceptibility of these cattle breeds to tick infestations. They were compared with the Galana Boran (trypanosusceptible) and the Friesian (susceptible to tick infestations, tick‐borne diseases, and trypanosomosis). The four breeds of cattle were exposed to natural tick challenge for a period of seven months and whole body weekly tick counts were done on each animal. Significant differences to tick infestations among the four breeds were observed. For both Rhipicephalus appendiculatus and Boophilus decoloratus, susceptibility to infestation increased in the order, Maasai Zebu, Orma Boran, Galana Boran and Friesian.The results generated by this pilot study so far suggest that variation in susceptibility to tick infestations exists among the four breeds. The Orma Boran and Maasai Zebu showed greater resistance to tick‐infestations than the Galana Boran and Friesian. This suggests that utilization of these trypanotolerant cattle breeds could be feasible even in the face of tick challenge and should therefore be considered when planning integrated trypanosomosis and tick control strategies.
Multiple Actions of a Hybrid PACAP Antagonist: Neuronal Cell Killing and Inhibition of Sperm Motilitya
Authors: GOZES ILLANA , PERL ORLY , ZAMOSTIANO RACHEL , RUBINRAUT SARA , FRIDKIN MATI , SHOCHAT LEAH , LEWIN LAWRENCE M. 
Published: February 2006

Abstract: Pituitary stimulating adenylate cyclase (PACAP) is a major regulatory peptide with two active molecular forms: PACAP‐27 and PACAP‐38. Both molecular forms promote neuronal survival and protect against neurotoxicity. Based on our previous hybrid peptide strategy in designing vasoactive intestinal peptide (VIP) antagonists, novel PACAP analogues were synthesized (neurotensin6‐11 PACAP7‐27 and neurotensin6‐11 PACAP7‐38). In addition to the hybrid modification, the methionine in position 17 was replaced by norleucine (Nle). Treatment of rat cerebral cortical cultures for five days with the putative PACAP antagonists (1 nM) resulted in a 35‐45% reduction in neuronal cell counts as compared to controls. Neuronal cell death was already obtained at picomolar concentrations for the neurotensin6‐11PACAP7‐27 antagonist with 70% death at 10−8 M. Co‐administration of the PACAP hybrid analogue with picomolar amounts of PACAP‐27 or Nle17‐PACAP‐27 attenuated the reduction in neuronal cell counts. While the protective effects of both analogues exhibited a peak at 1 pM concentrations, the Nle‐containing agonist displayed a broader range of active concentrations (10−12 M‐10−9 M)The putative PACAP antagonist also inhibited sperm motility (golden hamster) in a dose‐dependent manner as assessed in vitro. Complete inhibition was observed at 10 μM, suggesting a role for PACAP in sperm motility and sexual function. Thus, previous findings of a large number of PACAP and PACAP receptors in the nervous system and the reproductive system are now correlated with a function in neuronal survival and sperm motility. The structure‐activity studies suggest that the methionine in position 17 and the first six amino acids are important in the determination of PACAP activity, knowledge that may facilitate PACAP‐based drug design.
Counterrotating Galaxies and Accretion Disks
Authors: LOVELACE R.V. E. 
Published: February 2006

ABSTRACT:Theoretical interest in astrophysical disks with counterrotating components of stars and/or gas has been stimulated by recently discovered counterrotating spiral and S0 galaxies. A variety of physical processes can occur in counterrotating disks. We have shown that a strong two‐stream instability can occur for one armed (m= 1) tightly‐wrapped spiral waves between co and counterrotating stellar components and/or between a corotating stellar component and a counterrotating gaseous component. The instability of counterrotating stellar components has been clearly seen in computer simulations. The unstable two‐stream spiral waves can provide an effective viscosity for the gas causing its rapid accretion.Accretion disks consisting of counterrotating gaseous components may exist with an intervening shear layer. Configurations of this type can arise from the accretion of newly supplied counterrotating gas onto an existing corotating gas disk. For example, the gas above the disk midplane can rotate with angular rate +Ω(r) while that well below has the same properties but rotates with rate −V(r). Using the Shakura‐Sunyaev alpha turbulence model, we find self‐similar solutions where a thin (relative to the full disk thickness) equatorial layer accretes very rapidly, essentially at free‐fall speed. This type of accretion flow has now been observed in hydrodynamic simulations.
Modeling the Progression of Flank Wear on Uncoated and Ceramic-Coated Polycrystalline Cubic Boron Nitride Tools in Hard Turning
Authors: Dawson Ty G. , Kurfess Thomas R. 
Published: February 2006

AbstractAccurate wear modeling has always been desired, but has also been difficult and elusive. Most useful wear models have relied on experimental calibration because the physical wear mechanisms are not fully understood. This is particularly true in machining, where contact stresses and temperatures can be extremely high. In machining, the two wear modes most frequently discussed are crater wear and flank wear. Flank wear receives much more attention because it is easier to measure and the mechanism of material loss is thought to be better understood for most machining situations. This work focuses on flank wear for the same reasons. In hard turning, tool life is relatively short and both crater wear and flank wear influence the cutting process substantially. Understanding the progression of flank wear at various cutting conditions is beneficial in itself, but the ability to predict this progression will be extremely valuable. This work addresses both. Experimental flank wear progression is shown for uncoated and ceramic-coated polycrystalline cubic boron nitride (PCBN) tools at a range of cutting conditions. These data are used to calibrate a proposed mechanical wear model that predicts the progression of flank wear and tool failure points based on the cutting speed, feed, and cutting depth. The model was validated by additional experiments, which show good agreement with the predictions.
In-Process Diameter Measurement of Turned Workpiece With Curvatures
by Using Sensor Positioning
Authors: Shiraishi Masatake , Sumiya Hideyasu , Aoshima Shinichi 
Published: February 2006

Abstract
A modified triangular laser displacement sensor having a resolution of 1.0μm was used to measure the diameter of a turned workpiece with curvatures. This sensor was attached to a specially designed stage mounted on a precision slide unit and operated by three drive motors. In the measurement, the laser sensor was controlled by a θ motor depending on workpiece curvatures so that the illuminating laser beam is always normal to the part surface and can measure the workpiece diameter in an on-line fashion. This sensor positioning control was found to be effective for measuring the diameter of a curved workpiece with an accuracy of several micrometers.
Combination Exposure to Zidovudine plus Sulfamethoxazole-Trimethoprim Diminishes B-Lymphocyte Immune Responses toPneumocystis murinaInfection in Healthy Mice
Authors: Feola David J. , Garvy Beth A. 
Published: February 2006

ABSTRACTWe have previously shown that zidovudine plus sulfamethoxazole-trimethoprim exposure decreases immune cell populations in the bone marrow of healthy mice by inducing apoptosis. The hypothesis of the current work was that this toxicity would have an adverse impact on the immune response. To determine this, BALB/c mice were treated with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only (control) via oral gavage for 21 days. On day 4 after dosing completion, the mice were infected intratracheally with 1 × 107Pneumocystis murinaorganisms. Immune cell populations (in lung digest, bronchoalveolar lavage fluid, tracheobronchial lymph node, and bone marrow samples), the lungPneumocystisburden, and serumPneumocystis-specific antibody titers were determined at days 6, 10, and 20 postinfection. While total bone marrow cellularity was recovered by day 6 postinfection in the combination exposure group, B-cell numbers did not recover until 10 days postinfection, primarily due to the persistent depletion of the late pre-B-cell phenotype. The numbers of CD4+and CD8+T cells, as well as the numbers of total B cells and activated B cells in tracheobronchial lymph nodes, were decreased at days 10 and 20 as a result of zidovudine plus sulfamethoxazole-trimethoprim exposure compared to the numbers in the control group. No significant differences in lung lavage or lung digest cell populations were observed. There was a trend of a delay inPneumocystisclearance in the combination treatment group, andPneumocystis-specific serum immunoglobulin G titers were reduced at day 20 postinfection. Together, these data indicate that the combination of zidovudine and sulfamethoxazole-trimethoprim adversely affects the humoral immune response toPneumocystis.
Influence of Exogenous Reproductive Hormones on Specific Antibody Production in Genital Secretions after Vaginal Vaccination with Recombinant Cholera Toxin B Subunit in Humans
Authors: Wassen Lotta , Jertborn Marianne 
Published: February 2006

ABSTRACT

The objective of this study was to investigate the influence of exogenous reproductive hormones on the local and systemic production of specific immunoglobulin A (IgA) and IgG antibodies after vaginal vaccination with recombinant cholera toxin subunit B (CTB). Three groups of women using either progesterone-containing intrauterine devices (
n
= 9), oral contraceptives (
n
= 8), or no hormonal contraceptive methods (
n
= 9) were vaginally immunized twice, 2 weeks apart. Cervical secretions, vaginal fluids, and serum were collected before and after vaccination. Total and CTB-specific IgA and IgG antibodies in genital secretions and serum were analyzed by enzyme-linked immunosorbent assay. A majority of the women presented strong CTB-specific IgA and IgG antibody responses in cervicovaginal secretions after vaccination, whereas the antitoxin responses in serum were weaker. Exogenously administered steroid hormones did not seem to have any impact on the production of specific antibodies. Both the frequencies and the magnitudes of IgA and IgG antitoxin responses in genital secretions were comparable among the three immunization groups. An association, in particular for IgA, was found between the magnitudes of the CTB-specific antibody responses in cervical secretions and vaginal fluids after vaccination. The sensitivities and positive predictive values of vaginal antibody analyses to reflect responses in cervical secretions were also high, suggesting that vaginal fluids alone might be used for evaluation of genital immune responses in large-scale vaccination studies in the future.
Neutralizing Antibodies and Persistence of Immunity following Anthrax Vaccination
Authors: Hanson James F. , Taft Sarah C. , Weiss Alison A. 
Published: February 2006

ABSTRACT
Anthrax toxin consists of protective antigen (PA) and two toxic components, lethal factor (LF) and edema factor (EF). PA binds to mammalian cellular receptors and delivers the toxic components to the cytoplasm. PA is the primary antigenic component of the current anthrax vaccine. Immunity is due to the generation of antibodies that prevent the PA-mediated internalization of LF and EF. In this study, we characterized sera obtained from vaccinated military personnel. Anthrax vaccine is administered in a series of six injections at 0, 2, and 4 weeks and 6, 12, and 18 months, followed by annual boosters. The vaccination histories of the subjects were highly varied; many subjects had not completed the entire series, and several had not received annual boosters. We developed a simple colorimetric assay using alamarBlue dye to assess the antibody-mediated neutralization of LF-mediated toxicity to the J774A.1 murine macrophage cell line. Recently vaccinated individuals had high antibody levels and neutralizing activity. One individual who had not been boosted for 5 years had low immunoglobulin G antibody levels but a detectable neutralization activity, suggesting that this individual produced low levels of very active antibodies.
Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis
Authors: Njoku Dolores B. , Mellerson Jenelle L. , Talor Monica V. , Kerr Douglas R. , Faraday Nauder R. , Outschoorn Ingrid , Rose Noel R. 
Published: February 2006

ABSTRACTIdiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.
The [
PSI
+
] Prion of
Saccharomyces cerevisiae
Can Be Propagated by an Hsp104 Orthologue from
Candida albicans
Authors: Zenthon Joanna F. , Ness Frederique , Cox Brian , Tuite Mick F. 
Published: February 2006

ABSTRACT

The molecular chaperone Hsp104 is not only a key component of the cellular machinery induced to disassemble aggregated proteins in stressed cells of
Saccharomyces cerevisiae
but also plays an essential role in the propagation of the [
PSI
+
], [
URE3
], and [
RNQ/PIN
+
] prions in this organism. Here we demonstrate that the fungal pathogen
Candida albicans
carries an 899-residue stress-inducible orthologue of Hsp104 (CaHsp104) that shows a high degree of amino acid identity to
S. cerevisiae
Hsp104 (ScHsp104). This identity is significantly lower in the N- and C-terminal regions implicated in substrate recognition and cofactor binding, respectively. CaHsp104 is able to provide all known functions of ScHsp104 in an
S. cerevisiae hsp104
null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [
PSI
+
] prion. As also observed for ScHsp104, overexpression of CaHsp104 leads to a loss of the [
PSI
+
] prion. However, unlike that of ScHsp104, CaHsp104 function is resistant to guanidine hydrochloride (GdnHCl), an inhibitor of the ATPase activity of this chaperone. These findings have implications both in terms of the mechanism of inhibition of Hsp104 by GdnHCl and in the evolution of the ability of fungal species to propagate prions.