bluuebunny/crossref_metadata_2025 huggingface dataset:
Galantamine Activates Muscle-Type Nicotinic Acetylcholine Receptors without Binding to the Acetylcholine-Binding Site
Authors: Akk Gustav , Steinbach Joe Henry
Published: February 2005

Galantamine (Reminyl; Janssen Pharmaceutica, Titusville, NJ) belongs to a class of acetylcholinesterase inhibitors approved for symptomatic treatment of Alzheimer's disease. The drug presumably acts by raising and prolonging the profile of acetylcholine (ACh) via an inhibitory effect on the esterase. However, there is also evidence demonstrating that galantamine can activate the nicotinic ACh receptor or modulate its activation by ACh.

In this study, we have examined the ability of galantamine to directly activate the muscle-type nicotinic ACh receptor or to modulate receptor activation by selected nicotinic agonists.

Studies of direct activation by galantamine demonstrated that this ligand is a low-efficacy agonist of the muscle-type ACh receptor. Point mutations in the M2-M3 linker (αS269I) and the M2 transmembrane domain (ϵT264P) had similar effects on receptor activation by galantamine and nicotinic agonists, suggesting that the general features of receptor activation by galantamine are similar to that in the presence of ACh.

Experiments performed in the simultaneous presence of galantamine and various nicotinic ligands showed that channel activation by the nicotinic ligands studied (ACh, carbachol, and choline) was not affected by the presence of galantamine at concentrations up to 100 μm. In addition, galantamine did not reduce the initial rate of binding for125I-α-bungarotoxin. These results demonstrate that galantamine does not interfere with the occupation of the nicotinic agonist binding site by ACh, carbachol, or choline. We conclude that galantamine activates the muscle-type ACh receptor by interacting with a binding site that is distinct from the site for nicotinic agonists.
Calcium-Independent, cGMP-Mediated Light Adaptation in Invertebrate Ciliary Photoreceptors
Authors: del Pilar Gomez Maria , Nasi Enrico
Published: February 2005

Calcium is thought to be essential for adaptation of sensory receptor cells. However, the transduction cascade of hyperpolarizing, ciliary photoreceptors of the scallop does not use IP3-mediated Ca release, and the light-sensitive conductance is not measurably permeable to Ca2+. Therefore, two typical mechanisms that couple the light response to [Ca]ichanges seem to be lacking in these photoreceptors. Using fluorescent indicators, we determined that, unlike in their microvillar counterparts, photostimulation of ciliary cells under voltage clamp indeed evokes no detectable change in cytosolic Ca. Notwithstanding, these cells exhibit all of the hallmarks of light adaptation, including response range compression, sensitivity shift, and photoresponse acceleration. A possible mediator of Ca-independent sensory adaptation is cGMP, the second messenger that regulates the light-sensitive conductance; cGMP and 8-bromo cGMP not only activate light-dependent K channels but also reduce the amplitude of the light response to an extent greatly in excess of that expected from simple occlusion between light and chemical stimulation. In addition, these substances accelerate the time course of the photocurrent. Tests with pharmacological antagonists suggest that protein kinase G may be a downstream effector that controls, in part, the cGMP-triggered changes in photoresponse properties during light adaptation. However, additional messengers are likely to be implicated, especially in the regulation of response kinetics. These observations suggest a novel feedback inhibition pathway for signaling sensory adaptation.
Bangladesh in 2004: The Politics of Vengeance and the Erosion of Democracy
Authors: Riaz Ali
Published: February 2005

The year 2004 was not typical for Bangladesh; unfortunately, it was worse than usual. The country's fragile democracy suffered serious reversals. Rising political violence and religious militancy, coupled with the government's vindictive attitude and the main opposition party's intransigence, have created an unstable environment that is likely to inflict still further damage on Bangladesh's democracy.
Malaysia in 2004: Out of Mahathir's Shadow?
Authors: Welsh Bridget
Published: February 2005

During 2004, Prime Minister Abdullah Ahmad Badawi faced the difficult challenge of carving out his own brand of leadership, maintaining economic competitiveness, and redefining Malaysia abroad. This article assesses his success and argues that Abdullah has created a new identity but ironically made himself more politically vulnerable.
Brunei in 2004: Window-Dressing an Islamizing Sultanate
Authors: Horton A. V. M.
Published: February 2005

Negara Brunei Darussalam continued to enjoy tranquillity in 2004. The principal events in the country during the year were the wedding of the Crown Prince al-Muhtadee Billah and Dayangku (Lady) Sarah and the resurrection of the Legislative Council. Twenty years of independence have witnessed significant progress in many fields, but political and religious freedom remains wanting.
Russia and the CIS in 2004: Putin's Offensive and Defensive Actions
Authors: Kimura Hiroshi
Published: February 2005

President Putin started his second term in Russia with overwhelming popularity and power. Ironically, however, since that time he has been confronted with mounting domestic and international problems. The most serious issue is how to deal with increasing terrorist attacks. Putin's political initiatives of centralizing state power in the Kremlin has been criticized domestically and in the West as an attempt to strengthen his grip on power, thereby endangering democracy in Russia.
Navigating Sonata Space in Mendelssohn's Meeresstille und glückliche Fahrt
Authors: Haney Joel
Published: February 2005

Felix Mendelssohn's establishment of the concert overture as a domain of lively compositional innovation represents one of the most important achievements of orchestral music from the period immediately following Beethoven's death. In their remarkable ability to evoke lofty extramusical subjects through a purely instrumental medium, Mendelssohn's overtures were christened as vessels of musical progress in a manner that anticipated significantly the claims of the midcentury Lisztian symphonic poem. To grasp more fully the overtures' progressivism, though, we must attend closely to the relationship within them between formal particularity and programmatic implication. This endeavor is especially appropriate to Mendelssohn's Meeresstille und gluckliche Fahrt, whose idiosyncratic formal dimension raises pressing hermeneutical questions. Mendelssohn based this work on two poems by Goethe that trace a liberating progression from the deathly immobility of a becalmed sea to the redemptive vitality of a rising wind and the promise of homecoming. While commentators have often noted the overtly pictorial moments of Mendelssohn's overture, only recently has programmatic inquiry turned toward the unfolding of the considerably broad musical voyage itself. But here the analytical privileging of the work's thematic process has supported the image of a journey with little risk. By contrast, a more thoroughly genre-based look at the overture's Gluckliche Fahrt portion reveals a voyage laden with perils as well as possibilities.
Silence, Echo: A Response to "What the Sorcerer Said"
Authors: Caballero Carlo
Published: February 2005

In "What the Sorcerer Said," Carolyn Abbate proposed a reading of Dukas's Sorcerer's Apprentice (1897) focused on the possibility of musical narration. The present essay shifts that focus to the question of the work's uncanniness and excess. In particular, where Abbate finds that the slow part of the epilogue resonates with her understanding of the work as an instance of narration, I begin with the final two measures of the work, which suddenly revert to the fast tempo of the central scherzo. These final measures, which Abbate does not mention, produce a disturbing regression that suggests another reanimation of the broom. This "third beginning" (thus heard in relation to the two preceding moments of animation) marks the broom as an agent of the uncanny (heimlich and unheimlich) in the sense identified by Freud in his essay "Das Unheimliche" (1919). Indeed, Dukas's work as a whole is haunted by motives Freud later identified as uncanny: magic, the omnipotence of thought, animism, and involuntary repetition. The essay works backward from the final noise of the piece into a re-reading founded on musical details such as the representation of the brooms through minor- and major-third dyads, the role of the pitch-class Ab, the structure of the central "reanimation scene," and the dismal interplay of motives associated with the broom and the Apprentice. Close attention is given to Dukas's immediate literary source, Goethe's ballad "Der Zauberlehrling," whose use of assonance and repeating rhymes provides subtle structural cues echoed in Dukas's music; I argue that the relationship between the ballad and Dukas's score is more homologous than Abbate was willing to allow. A number of revisions to Abbate's account also emerge through reference to a descriptive note on The Sorcerer's Apprentice left by Dukas in manuscript (Paris B.N.F. Musique MS 1037). Finally, I suggest that this "symphonic scherzo after Goethe" conflates literary and musical logics into a peculiar kind of fiction that points to the uncanny nature of narrative itself. Dukas's work ultimately engages the issue of mastery by focusing the listener's attention on the failure of authority and the contingency of animation or de-animation. In this Lacanian "overflow" into the unknown, the musical work goes beyond its literary sources, for the broom, not the human figure of the Apprentice, becomes the true protagonist of Dukas's work.
Levels of Cytokine Receptor Activator of Nuclear Factor κB Ligand in Gingival Crevicular Fluid in Untreated Chronic Periodontitis Patients
Authors: Vernal Rolando , Chaparro Alejandra , Graumann Rebecca , Puente Javier , Valenzuela Maria Antonieta , Gamonal Jorge
Published: February 2005

Background: Receptor activator of nuclear factor κB ligand (RANK‐L) is a cytokine involved in the regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis. One of the major causes of tooth loss in humans is bone destruction. The aim of our study was to determine the presence of RANK‐L in gingival crevicular fluid (GCF) samples from adult patients with untreated chronic periodontitis and in healthy controls. We also identified the RANK‐L present in lesions undergoing episodic attachment loss from GCF.

Methods: GCF samples were collected from two periodontally affected sites (probing depth ≥5 mm, attachment loss ≥3 mm) in 20 patients (N = 40). After monitoring for 4 months, seven patients showed active periodontal disease, and GCF samples were collected from one active and one inactive site (N = 14 samples). The comparison with healthy controls was carried out by collecting GCF samples from 12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip, and enzymelinked immunosorbent assay (ELISA) was performed to determine the total amount of RANK‐L.

Results: RANK‐L was found in a higher proportion (85%) of samples from patients than from controls (46%). The total amount of RANK‐L was significantly higher in patients (115.53 ± 78.18 picograms [pg]) than in healthy subjects (63.08 ± 55.08 pg) (P = 0.003). Active sites, presumably associated with tissue destruction, had significantly higher levels of RANK‐L than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007).

Conclusion: GCF total amount of RANK‐L is significantly increased in periodontal disease, supporting its role in the alveolar bone loss developed in this disease. J Periodontol 2004;75: 1586‐1591.
Augmented Transforming Growth Factor‐β1 in Gingival Crevicular Fluid of Smokers With Chronic Periodontitis
Authors: Stein Sidney H. , Green Bryan E. , Scarbecz Mark
Published: February 2005

Background: Patients who smoke are at increased risk for chronic periodontitis (CP). Also, CP patients who smoke exhibit significantly less reduction of probing depths and gains in clinical attachment compared to non‐smokers following periodontal therapy. Several studies suggest that the effects of smoking on the host response may be paramount in regulating the basal systemic inflammatory status and therapeutic outcomes in this cohort. Growth factors, specifically transforming growth factor β1 (TGF‐β1), are critical in regulating the wound healing response by controlling cell division, differentiation, and motility. The hypothesis to be tested was that gingival crevicular fluid (GCF) TGF‐β1 production was altered in smokers compared to nonsmokers with CP.

Methods: GCF was collected from smokers and non‐smokers with CP, both at baseline and 1 to 2 weeks after initial therapy. GCF volume was determined using an electronic device and TGF‐β1 concentration was measured by enzyme‐linked immunosorbent assay (ELISA).

Results: Smokers exhibited a higher mean concentration of GCF TGF‐β1 at baseline compared to non‐smokers (P = 0.03). After initial therapy, smokers exhibited significantly less reduction in mean GCF volume compared to non‐smokers (P = 0.04).

Conclusions: Augmented constitutive production of GCF TGF‐β1 in smokers may explain the clinical appearance of fibrotic gingival tissue exhibited by this patient cohort. A diminished reduction in GCF volume in smokers following root instrumentation suggests a chronic inflammatory status in conjunction with an ineffective host response. These findings support the concept that smokers with CP display an altered local inflammatory response after initial therapy, perhaps symptomatic of colonization by residual periodontal pathogens.J Periodontol 2004;75:1619‐1626.
Association Analysis Between Interleukin‐1 Family Polymorphisms and Generalized Aggressive Periodontitis in a Chinese Population
Authors: Li Qi Yan , Zhao Hong Shan , Meng Huan Xin , Zhang Li , Xu Li , Chen Zhi Bin , Shi Dong , Feng Xiang Hui , Zhu Xiao Ling
Published: February 2005

Background: It has been suggested that aggressive periodontitis (AgP) has a genetic basis, but this theory has not been confirmed. The intent of this investigation was to study whether specific interleukin (IL)‐1 genotypes and/or alleles could be used to predict susceptibility to generalized AgP (GAgP) in Chinese.

Methods: The GAgP group consisted of 122 patients, and the control group included 95 healthy subjects. Single nucleotide polymorphisms at IL‐1A (+4845) and IL‐1B (–511, +3954) were analyzed by standard polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay. The polymorphism of a variable number tandem repeat (VNTR) in intron 2 of IL‐1RN was detected by PCR amplification and fragment size analysis.

Results: There was no significant association of IL‐1 polymorphisms with GAgP in the unstratified subjects. However, when cases were stratified by gender, the frequencies of A2+ genotype and allele 2 at IL‐1A +4845 were significantly increased in male patients compared to male controls (genotype: odds ratio [OR] 5.58, 95% confidence interval [CI]: 1.09 to 28.68, P = 0.039; allele: OR 4.97, 95% CI: 1.01 to 24.50, P = 0.049; adjusted for age and smoking status). The frequency of IL‐1B –511 A1/A2 heterozygote was significantly increased in male GAgP group compared to male controls (adjusted OR 3.16, 95% CI: 1.01 to 9.89, P = 0.048). In females, no significant differences were found between patients and controls in corresponding analyses at all polymorphic loci. A possible combined effect of IL‐1B –511 polymorphism and smoking on the elevated risk to GAgP was observed. The OR of GAgP for combined A2+ genotype and smoking was 12.45 (95% CI: 1.43 to 108.06, P = 0.022), and for combined allele 2 and smoking was 18.25 (95% CI: 2.32 to 143.86, P = 0.006).

Conclusions: The polymorphisms of IL‐1A +4845 and IL‐1B –511 may play an important role in determining GAgP susceptibility in Chinese males. Furthermore, a possible combined effect of the polymorphism of IL‐1B –511 and smoking on GAgP susceptibility was suggested. J Periodontol 2004;75:1627‐1635.
Distribution of Systemic Ciprofloxacin and Doxycycline to Gingiva and Gingival Crevicular Fluid
Authors: Lavda Maria , Clausnitzer C. Esther , Walters John D.
Published: February 2005

Background: Systemic fluoroquinolones and tetracyclines reach steady‐state levels in gingival crevicular fluid (GCF) that are several‐fold higher than their levels in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts are known to accumulate these agents. Uptake by fibroblasts could enhance their distribution to gingiva. To test this hypothesis, steady‐state levels of these agents were assayed in serum, gingival connective tissue (GCT), and GCF.

Methods: Healthy subjects who needed resective periodontal surgery participated in the study. Approximately 78 hours prior to the surgical appointment, each subject began a 3‐day regimen of ciprofloxacin or doxycycline. At the surgical appointment (scheduled approximately 6 hours after the last dose), samples of blood and GCT were collected. GCF samples were collected on paper strips and measured with an electronic device. Samples were extracted and analyzed by high performance liquid chromatography.

Results: Mean ciprofloxacin levels in serum, GCT, and GCF were 0.40 µg/ml, 1.38 µg/g, and 1.66 µg/ml, respectively (P <0.001, N = 9). For doxycycline, these levels were 1.11 µg/ml, 2.03 µg/g, and 2.41 µg/ml, respectively (P = 0.002, N = 8). For both agents, the GCT and GCF levels were significantly higher than serum levels (P <0.05), but not significantly different from each other.

Conclusions: Our findings suggest that fibroblasts could play an important role in the distribution of fluoroquinolones and tetracyclines to the gingiva. By accumulating these agents in GCT, fibroblasts could contribute to the relatively high levels they attain in GCF. J Periodontol 2004;75:1663‐1667.
Periodontal Repair in Dogs: Analysis of Histometric Assessments in the Supraalveolar Periodontal Defect Model
Authors: Koo Ki‐Tae , Polimeni Giuseppe , Albandar Jasim M. , Wikesjö Ulf M.E.
Published: February 2005

Background: Traditionally, the mean value from histometric assessments of several histologic sections from the same site has been, used for the histometric characterization of the site. The histometric analysis of the supraalveolar periodontal defect model uses observations from buccal and lingual sites in three stepserial sections representing the central aspect of the mesial and distal root for the third and fourth mandibular premolar teeth. The objectives of this study were to investigate the correlations and determine whether there are significant differences in the measurement values of various histometric parameters between the three step‐serial sections and to test the hypothesis that, in this animal model, histometric assessments using the most central section of each root are comparable to the mathematical means of corresponding assessments of the site using the three step‐serial sections.

Methods: Histometric analysis using light microscopy, an attached digital camera system, and a personal computer‐based image analysis system including a custom program for the supraalveolar periodontal defect model was performed on histologic sections acquired from one jaw quadrant in each of 12 dogs. The animals had received a protocol including placement of a coral biomaterial and guided tissue regeneration (GTR) membranes, and were evaluated following a 4‐week healing interval. Twelve parameters were assessed using three central step‐serial sections from each root. For each parameter, pair‐wise comparisons were performed using the mixed models analysis of variance, and the correlations between measurements were assessed by the intraclass correlation coefficient (ICC).

Results: For all parameters assessed, there were no significant differences (P >0.05) among the three sections. The differences between the central section and the means of the three step‐serial sections were small and not statistically significant. Parameters that could be assessed on most or all specimens, such as defect height and area, membrane height, and bone regeneration area, showed high correlations among the three step‐serial sections (intraclass coefficient [ICC] ∼ 0.91 to 0.98), and between each of the three sections and the mean for the three step‐serial sections (ICC ≥0.95). The most central section had somewhat higher correlation with the mean than measurements made on the lateral sections.

Conclusion: The results suggest that using the supraalveolar periodontal defect model representative histometric data can be obtained evaluating only the central section from each defect site. J Periodontol 2004;75:1688‐1693.
In Vitro Biocompatibility of a New Titanium‐29Niobium‐13Tantalum‐4.6Zirconium Alloy With Osteoblast‐Like MG63 Cells
Authors: Naganawa T. , Ishihara Y. , Iwata T. , Koide M. , Ohguchi M. , Ohguchi Y. , Murase Y. , Kamei H. , Sato N. , Mizuno M. , Noguchi T.
Published: February 2005

Background: Titanium‐29niobium‐13tantalum‐4.6zirconium (TiNb) has recently been developed as a new implant material. TiNb is composed of non‐toxic elements and has a lower modulus of elasticity than the other titanium alloys. However, its biocompatibility has not been adequately characterized. The aim of this study was to evaluate the biocompatibility of TiNb using an osteoblast‐titanium co‐culture system.

Methods: MG63 cells were cultured on three kinds of titanium disks: TiNb, pure titanium (pTi), and titanium‐6aluminum‐4vanadium (TiAl), prepared with two different surfaces, a polished and acid‐etched surface and a machined‐grooved surface. The surface topography and roughness were evaluated by scanning electron microscopy (SEM). After 48 hours culture, the number of proliferating cells and prostaglandin E2 (PGE2) production in the culture supernatant were determined.

Results: There was no significant difference in surface roughness among the three titanium disks with a polished and acidetched surface. After 48 hours of culture, the number of cells was significantly reduced on pTi and TiAl compared to TiNb and the control. PGE2 production was significantly higher on pTi than on TiAl, TiNb, and the control. We further examined the effect of surface roughness on PGE2 production using machine‐grooved titanium disks. While pTi and TiAl stimulated the production of PGE2 depending on surface roughness, roughened TiNb did not affect PGE2 production.

Conclusions: These results suggest that TiNb may exhibit favorable biocompatibility because it has an efficient surface topography for cell proliferation, and the level of PGE2 production does not depend on surface roughness. We conclude that TiNb may be useful as an implant material. J Periodontol 2004;75: 1701‐1707.
Cementodentinal Tear: A Case Report With 7‐Year Follow‐Up
Authors: Chou James , Rawal Yeshwant B. , O'Neil Joseph R. , Tatakis Dimitris N.
Published: February 2005

Background: Cemental tears are an uncommon form of root fracture that can lead to rapid localized attachment loss. Typically, the separation of the fragment occurs at the cementodentinal junction. In this report, we present a case of periodontal involvement associated with a cemental tear‐like fragment that proved to be a cementodentinal tear. We also review the literature on the clinical presentation of cemental tear associated periodontal lesions.

Methods: A 52‐year‐old male presented with acute pain on the maxillary right second premolar. Clinically, probing depth of 7 mm and inflammation were noted on the distal aspect of tooth #4. Radiographic examination revealed separation of cervical root structure on the distal aspect of the tooth, involving two‐thirds of the root length. The root fragment was removed, and the localized defect was treated by open flap debridement along with scaling and root planing. The patient was then placed on a regular periodontal maintenance schedule.

Results: A postoperative probing depth of 2 mm with 1 mm recession was recorded at 3 months, and maintained for 7 years. Histological examination indicated that the detached root fragment contained dentin with overlying acellular cementum and associated periodontal ligament tissue. The fragment was estimated to represent as much as 20% of the total root surface area.

Conclusion: Moderate to severe periodontal attachment loss associated with cemental or cementodentinal tears, even ones constituting a significant portion of the root surface, can be successfully treated with conventional periodontal surgical procedures and maintained long term with a proper maintenance regimen. J Periodontol 2004;75:1708‐1713.
Desquamative Gingivitis Associated With IgG/IgA Pemphigoid Presents a Challenging Diagnosis and Treatment: A Case Report
Authors: Sánchez Andrés R. , Rogers Roy S. , Kupp Leo I. , Sheridan Phillip J.
Published: February 2005

Background: Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune blistering disorders characterized by subepithelial separation and the deposition of immunoglobulins and complement along the basement membrane zone (BMZ). This disease is diagnosed with direct immunofluorescence testing showing a linear deposition of immunoglobulins and/or complement along the BMZ and indirect immunofluorescence testing showing circulating IgG (and sometimes IgA) autoantibodies along the BMZ. In this case report we describe desquamative gingivitis secondary to IgG/IgA pemphigoid and the management of this challenging variant of MMP.

Methods: Routine histology, direct immunofluorescence testing, and indirect immunofluorescence testing were utilized and correlated to the clinical findings to diagnose this unusual immunobullous disease.

Results: Direct and indirect immunofluorescence testing confirmed the clinical diagnosis of IgG/IgA pemphigoid as the cause of desquamative gingivitis and the other mucosal findings in this patient. A treatment program including dapsone and other drugs completely resolved the oral lesions after 14 months of therapy.

Conclusions: Desquamative gingivitis associated with IgG/IgA pemphigoid can be challenging to diagnose and treat. After 14 months of treatment, a combination therapy consisting of dapsone with cimetidine and vitamin E to enhance drug efficacy and frequent intramuscular administrations of triamcinolone achieved control of both the oral and genital elements of IgG/IgA pemphigoid in this patient. J Periodontol 2004;75:1714‐1719.
Duplication of chromosome 4q: Renal pathology of two siblings
Authors: Otsuka Taketo , Fujinaka Hidehiko , Imamura Masaru , Tanaka Yasuki , Hayakawa Hiroshi , Tomizawa Shuichi
Published: February 2005

We report on two sibs with partial 4q trisomy: dup (4)(q35.2‐q31.22) and their renal biopsy findings. Both of them show renal hypoplasia, although their chromosomal aberration lacks the minimal duplicated region 4q22‐q23 and/or 4q25‐q31.3, which had been shown to be associated with urogenital abnormalities and thumb malformations in previous reports. From the renal biopsy findings, the two sibs were diagnosed as oligonephronia. We summarize the 13 having published cases of duplication of chromosome 4q, and examine which segments have a close relationship to renal hypoplasia. We suggest that renal hypoplasia may be female‐prone, and may have a close relationship with duplication of 4q33‐q34. © 2005 Wiley‐Liss, Inc.
Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease
Authors: Holmans Peter , Hamshere Marian , Hollingworth Paul , Rice Frances , Tunstall Nigel , Jones Sue , Moore Pamela , DeVrieze Fabienne Wavrant , Myers Amanda , Crook Richard , Compton Danielle , Marshall Helen , Meyer David , Shears Shantia , Booth Jeremy , Ramic Dzanan , Williams Nigel , Norton Nadine , Abraham Richard , Kehoe Pat , Williams Hywel , Rudrasingham Varuni , O'Donovan Mick , Jones Lesley , Hardy John , Goate Alison , Lovestone Simon , Owen Michael , Williams Julie
Published: February 2005

We performed an affected sib‐pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late‐onset Alzheimer's disease (AD) in a sample comprising 428 sib‐pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD = 3.62), and was strongest in pairs with high mean AAO (>80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD = 2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD = 2.33) in the vicinity of APOE and 12p (max LOD = 2.22), with linkage strongest in sib‐pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD = 2.29), with the effect strongest in the NIMH sample (max LOD = 3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD = 2.44) and 15p (max LOD = 1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD = 2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE ε4 homozygotes on chromosome 1 (max LOD = 3.08) and chromosome 9 (max LOD = 3.34). The previously reported genome‐wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied. © 2005 Wiley‐Liss, Inc.
Association between the serotonin transporter gene and alcohol consumption in social drinkers
Authors: Munafò Marcus R. , Lingford‐Hughes Anne R. , Johnstone Elaine C. , Walton Robert T.
Published: February 2005

Relatively few studies have investigated the role of the 5HTT gene in intermediate phenotypes such as alcohol consumption in non‐alcohol dependent populations. A recent study reported an association with alcohol consumption in a student population. We attempted to replicate these findings and extend on this work in a representative, ethnically homogenous, non‐alcohol dependent sample of social drinkers in the United Kingdom. The short allele of the 5HTT gene was significantly associated with increased alcohol consumption (P = 0.03). There was suggestive evidence of a genotype–sex interaction (P = 0.04). Post‐hoc tests indicated higher alcohol consumption in men with one or more copies of the short allele, while in women consumption was highest among heterozygotes compared to both homozygote groups. Age at time of data collection and cigarette consumption were entered as covariates. These results replicate recent previous findings and suggest a possibility that this association may differ in men and women. © 2005 Wiley‐Liss, Inc.
Vascular endothelial growth factor gene variability is associated with increased risk for AD
Authors: Del Bo Roberto , Scarlato Marina , Ghezzi Serena , Martinelli Boneschi Filippo , Fenoglio Chiara , Galbiati Sara , Virgilio Roberta , Galimberti Daniela , Galimberti Gloria , Crimi Marco , Ferrarese Carlo , Scarpini Elio , Bresolin Nereo , Comi Giacomo P.
Published: February 2005

Converging evidence points to a pivotal role of vascular endothelial growth factor (VEGF) in neuronal protection and a lack of its activity in neurodegenerative disorders. To investigate this possible association, we screened the VEGF gene promoter for various well‐known single‐nucleotide polymorphisms in a series of 249 consecutively recruited Italian patients with sporadic Alzheimer's disease (AD). Genetic analysis indicated different distributions of two single‐nucleotide polymorphisms in the AD population compared with healthy control subjects. In particular, the frequencies of −2578A/A and −1198C/T genotypes were significantly greater in AD patients than in control subjects (23.7 vs 14.7% and 2.8 vs 0%, respectively). The −2578A/A genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype. The risk was significantly increased with respect to various VEGF genotype combinations. In contrast, no difference in serum VEGF levels was detected comparing 96 patients and 49 control subjects. These findings suggest that polymorphisms within the promoter region of the VEGF gene confer greater risk for AD, probably by reducing its neuroprotective effect, and confirm the biological role of VEGF in neurodegenerative processes. Ann Neurol 2005;57:373–380
Clinical and positron emission tomography of Parkinson's disease caused by LRRK2
Authors: Hernandez Dena G. , Paisán‐Ruíz Coro , McInerney‐Leo Aideen , Jain Shushant , Meyer‐Lindenberg Andreas , Evans E. Whitney , Berman Karen F. , Johnson Janel , Auburger Georg , Schäffer Alejandro A. , Lopez Grisel J. , Nussbaum Robert L. , Singleton Andrew B.
Published: February 2005

We have recently identified mutations in a gene leucine‐rich repeat kinase–2 (LRRK2), which cause autosomal dominant Parkinson's disease. Here, we describe two families with autosomal dominant Parkinson's disease caused by a LRRK2 G2019S mutation. We present here a clinical description of patients, including 6‐18F‐fluoro‐L‐dopa positron emission tomography and discuss the potential implications of this mutation, which alters a conserved residue in a domain required for kinase activation. Ann Neurol 2005;57:453–456
Subthalamic stimulation activates internal pallidus: Evidence from cGMP microdialysis in PD patients
Authors: Stefani Alessandro , Fedele Ernesto , Galati Salvatore , Pepicelli Olimpia , Frasca Stefania , Pierantozzi Mariangela , Peppe Antonella , Brusa Livia , Orlacchio Antonio , Hainsworth Atticus H. , Gattoni Giuseppe , Stanzione Paolo , Bernardi Giorgio , Raiteri Maurizio , Mazzone Paolo
Published: February 2005

Parkinson's disease patients benefit from deep brain stimulation (DBS) in subthalamic nucleus (STN), but the basis for this effect is still disputed. In this intraoperative microdialysis study, we found elevated cGMP extracellular concentrations in the internal segment of the globus pallidus, despite negligible changes in glutamate levels, during a clinically effective STN‐DBS. This supports the view that a clinically beneficial effect of STN‐DBS is paralleled by an augmentation (and not an inactivation) of the STN output onto the GPi. Ann Neurol 2005;57:448–452
Depressive symptoms, sex, and risk for Alzheimer's disease
Authors: Dal Forno Gloria , Palermo Mark T. , Donohue Janet E. , Karagiozis Helen , Zonderman Alan B. , Kawas Claudia H.
Published: February 2005

Depression associates with increased risk for dementia and Alzheimer's disease (AD), although it is unclear whether it represents an actual risk factor or a prodrome. To determine the relative hazard of premorbid depressive symptomatology for development of dementia and AD, we studied risk for incident dementia and AD over a 14‐year period in 1,357 community‐dwelling men and women participating in the 40‐year prospective Baltimore Longitudinal Study of Aging. Screening for depressive symptoms, comprehensive medical and neuropsychological evaluations were prospectively collected every 2 years. Time‐dependent proportional hazards of development of AD or dementia were calculated separately for men and women, with symptoms of depression detected at 2‐, 4‐, and 6‐year intervals before onset of dementia symptoms. Vascular risk factors were analyzed as covariates. Premorbid depressive symptoms significantly increased risk for dementia, particularly AD in men but not in women. Hazard ratios were approximately two times greater than for individuals without history of depressive symptoms, an effect independent of vascular disease. We conclude that the impact of depressive symptoms on risk for dementia and AD may vary with sex. Further studies assessing separately the role of depression as a risk factor in men and women are necessary. Ann Neurol 2005;57:381–387
Interaction between the strong anionic character of strong anions and the hydrophobic association property of hydrophobic blocks in macromolecular chains of a water‐soluble copolymer
Authors: Gao Baojiao , Wu Nian , Li Yanbin
Published: February 2005

The copolymerization of acrylamide, sodium 2‐acrylamido‐2‐methyl propane sulfonate, and styrene was carried out in a microemulsion medium, and ternary copolymers based on polyacrylamide, which contained both strong anionic groups (SO3Na) and hydrophobic blocks (polystyrene), were synthesized. The structures and compositions of the copolymer were characterized by various means (Fourier transform infrared, ultraviolet, and elemental analysis). The aqueous solution properties were investigated with a florescence probe technique and apparent viscosity measurements, and the interactions between the strong anionic character of the anionic groups and the hydrophobic association behavior of the hydrophobic blocks was intensively examined. After the simultaneous addition of the strong anionic groups and hydrophobic association blocks to the main chains of polyacrylamide, the synergism of the electroviscosity effect of the strong anionic groups and the hydrophobic association effect of the hydrophobic blocks obviously enhanced the apparent viscosity of aqueous copolymer solutions, and the synergism of greater salt tolerance of the strong anionic groups and the strengthened hydrophobic association of the hydrophobic blocks in brine solutions resulted in increased salt resistance for the copolymer. However, the presence of strong anionic groups (SO) in the macromolecules weakened the intermolecular hydrophobic association effect of the copolymer in aqueous solutions to a certain degree; that is, the strong anionic groups produced a certain negative influence on the hydrophobic association effect of the hydrophobic blocks. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 714–722, 2005
Synthesis and characterization of PT/PS/SiO2 nanocomposite in nonaqueous medium by chemical method
Authors: Gök Ayşegül , Koçak E.Derya , Aydoǧdu Sibel
Published: February 2005

The PT/PS/SiO2 nanocomposite of polythiophene (PT), polystyrene (PS), and SiO2 with a grain size of 100–150 nm was synthesized by chemical polymerization using FeCl3 oxidant in nanoqueous medium (CHCl3). The properties of PT/PS/SiO2 synthesized were compared to those of PT, PT/PS, and PT/SiO2 synthesized in the same conditions. The synthesized materials were subsequently characterized by FTIR spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The incorporation of PT in the composite was endorsed by FTIR studies. TGA revealed enhanced thermal stability of the PT/PS/SiO2 nanocomposite compared to that of PT. SEMs showed globular particles and the presence of clusters of composite particles. The conductivity of the PT/PS/SiO2 nanocomposite was measured as 1.30×10−7 Scm−1 and the conductivity value of PT (1.02×10−4 Scm−1) decreased with entiring PS and SiO2 to PT structure. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 746–752, 2005
Properties of chitosan/poly(vinyl alcohol) films for drug‐controlled release
Authors: Wang Qun , Du Yu‐min , Fan Li‐hong
Published: February 2005

With bovine serum albumin (BSA) as a model drug, drug‐loaded films of chitosan (CS) and poly(vinyl alcohol) (PVA) were obtained by a casting/solvent evaporation method and crosslinked by tripolyphosphate (TPP). The films were characterized by FTIR, XRD, and SEM. The influential factors of drug‐loaded films on drug‐controlled release were studied. These factors included, primarily, the component ratio of CS and PVA, the loaded amount of BSA, the pH and ionic strength of the release solution, and the crosslinking time with TPP. The results showed that within 25 h, when the weight ratios of CS to PVA in the drug‐loaded films were 90 : 10, 70 : 30, 50 : 50, and 30 : 50, the cumulative release rates of BSA were 63.3, 72.9, 81.8, and 91.8%, respectively; when the amounts of model drug were 0.1, 0.2, and 0.3 g, the release rates were 100, 81.8, and 59.6%, respectively; when the pH values of the drug release medium were 1.0, 3.8, 5.4, and 7.4, the release rates reached 100, 100, 37.9, and 7.8%, respectively; the cumulative release rates of BSA were 78.4, 82.3, 84.3, and 91.7% when the ionic strengths of the release solution were, respectively, 0.1, 0.2, 0.3, and 0.4M; when the crosslinking times of these drug films in the TPP solution were 0, 5, 15, 30, and 60 min, the release rates attained 100, 100, 81.8, 65, and 43.3%, respectively. All the results indicated that the CS/PVA film was useful in drug delivery systems. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 808–813, 2005
Novel nitrogen‐containing epoxy resin. I. Synthetic kinetics
Authors: Zhang Xing Hong , Wan Hong Mei , Min Yu Qin , Qi Guo Rong
Published: February 2005

A novel nitrogen‐containing epoxy resin was synthesized by two steps: (1) condensation reaction between xyleneformaldehyde resin and phenol, to obtain thermoplastic xylenephenolformaldehyde (XPF) resin; and (2) addition reaction between XPF resin and triglycidyl isocryanurate (TGIC). The synthetic kinetics of XPF resin were intensively investigated by gel permeation chromatography (GPC). The results showed that XPF resin, with different molecular weights and low content of free phenol, could be obtained by changing the reaction conditions. The kinetics of reaction between XPF resin and TGIC was monitored by GPC and epoxy value titration. The results showed that the percentage conversion of TGIC was >85% within 60 min at 140°C and the epoxy value, about 0.3–0.4 mol/100 g, varied with the reaction conditions. This novel epoxy resin exhibited good stability of storage and could be used as a basic resin for making prepreg and laminate. The structures of XPF and XT resins were characterized by IR and 1H‐NMR spectra. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96:723–731, 2005
Partial purification and characterization of phenobarbital‐induced house fly cytochrome P‐450
Authors: Fisher Charles W. , Mayer Richard T.
Published: February 2005

Two forms of phenobarbital‐induced cytochrome P‐450 were partially purified from the Rutgers diazinon‐resistant strain of house fly using cholate solubilization, polyethylene glycol 6000 precipitation, and chromatography on DEAE cellulose. The preparation of highest purity had an absorbance maximum of 452 nm, a specific content of 10.0 nmol/mg protein, and an apparent molecular weight of 60,000 when examined by sodium dodecyl sulfate polyacrylamide electrophoresis. The yield of the highly purified cytochrome P‐450 was 2–3%. This form contained proportionately less cytochrome P‐420 than the original cholate solubilized microsomes, and is thus apparently more stable. A second form of cytochrome P‐450 having a specific content of 0.50–0.89 nmol/mg protein was eluted from DEAE cellulose with a 0‐0.25 M salt gradient. This is consistent with a previously reported elution pattern for Emulgen 913‐solubilized house fly microsomes. Several methods of solubilizing house fly microsomes were examined. High salt, 2M KCI, in the absence of detergents effectively solubilized cytochrome P‐450 (50–70% recovery) with little or no conversion to cytochrome P‐(420).
Identification of 20‐hydroxyecdysone and ecdysone from the pupa of the gypsy moth, Lymantria dispar
Authors: Feldlaufer M. F. , Lusby W. R. , Svoboda J. A. , Thompson M. J.
Published: February 2005

Normal and reverse‐phase high‐performance liquid chromatography in conjunction with radioimmunoassay and mass spectrometry were used to identify the free and conjugated ecdysteroids (after enzymatic hydrolysis) from day‐4 pupae of the gypsy moth, Lymantria dispar L. Seven ecdysteroids were searched for, but only 20‐hydroxyecdysone (964 ng/g fresh weight) and ecdysone (367 ng/g fresh weight) were detected. Analysis of conjugated ecdysteriods after liberation by hydrolysis also indicated the presence of 20‐hydroxyecdysone (21.6 ng/g fresh weight) and ecdysone (2.4 ng/g fresh weight). Neither 26‐hydroxyecdysone nor the 3α‐epimers of 20‐hydroxyecdysone or ecdysone were detected.
Juvenile hormone and 20‐hydroxyecdysone as primary and secondary stimuli of vitellogenesis in Aedes aegypti
Authors: Borovsky Dov , Thomas Billy R. , Carlson David A. , Whisenton Lavern R. , Fuchs Morton S.
Published: February 2005

Female Aedes aegypti that were fed blood and immediately abdominally ligated did not deposit yolk. Injection of 20‐hydroxyecdysone (1.5–5.0 ng) or topical application of juvenile hormone (JH) analogue methoprene (25 pg) did not induce vitellogenesis in these abdomens. When blood‐gorged ligated abdomens were treated with both hormones, however, vitellogenesis was stimulated in 60% of treated animals. Rocket immunoelectrophoresis indicated that vitellin concentration per follicle in treated animals was similar to that in intact controls. When ligated abdomens were first treated with methoprene and immediately injected with a crude head extract of egg development neurosecretory hormone, vitellogenin synthesis was induced at a rate similar to that in blood‐fed controls. Methoprene at this concentration (25 pg), did not cause an increase in whole‐body ecdysteroid titers. Larger amounts of methoprene (1.65 ng) were needed to stimulate egg development and ecdysteroid production.

Implantation of ecdysone‐secreting ovaries into ligated abdomens did not stimulate vitellogenesis in the recipients. However, in recipients that were first treated with methoprene (25 pg), implantation of ecdysone‐secreting ovaries resulted in normal egg development.

These experiments indicate that the appearance of JH precedes 20‐hydroxyecdysone in stimulating vitellogenesis following blood feeding in Ae. aegypti.
Developmental pathology of Heliothis virescens larvae parasitized by Microplitis croceipes: Parasite‐mediated host developmental arrest
Authors: Webb Bruce A. , Dahlman D. L.
Published: February 2005

The developmental pathology of Heliothis virescens larvae parasitized by the braconid wasp Microplitis croceipes was examined. Parasitized host larvae begin the same precise sequence of developmental events in preparation for pupation as observed in unparasitized larvae. This sequence is initiated even though the host larval weight is below the normal developmental threshold for larval‐pupal transformation. After parasite emergence, the host remains in a suspended advanced developmental state but never pupates. The developmental parameters altered by parasitization are normally under the host's endocrine control.

Neck ligation of control larvae was used to identify the critical periods in parasitized and unparasitized fourth‐ and fifth‐instar larvae. Control ligated fourth‐instar larvae apparently released PTTH between 21:00 AZT of the second day of the instar and 1:00 AZT of the third day. Parasitized fourth‐instar larvae were smaller and apparently released PTTH between 18:00 and 23:00 AZT of the third day. Control ligated fifth‐instar larvae apparently released PTTH between day 1 and day 2 of the cell formation phase. Ligated fifth‐instar parasitized larvae never molted to the pupal stage. Parasite larvae were adversely affected by host neck ligation with their pupal plus cocoon weight being proportional to the age of the host at the time of ligation.