bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Use and Control of Urination Among Community-Dwelling Older Adults
Authors: Ruby Christine M. , Hanlon Joseph T. , Fillenbaum Gerda G. , Pieper Carl F. , Branch Laurence G. , Bump Richard C.
Published: September 2005

Objective: The purpose of this study is to evaluate whether the use of medications with urological activity (UA) is associated with self-reported difficulty in control of urination. Methods: This is a cross-sectional study using data from the Duke Established Populations for Epidemiologic Studies of the Elderly. Results: Difficulty holding urine was reported by 49.5% of men and 54.0% of the women. Overall, 50.9% of men and 72.7% of the women took one or more medications with UA. Multivariable logistic regression for men revealed that neither use of any medication with UA (Adjusted [Adj.] Odds Ratio [OR] 1.12, 95% confidence interval [CI] 0.84-1.50) nor the number of medications with UA used was associated with urinary difficulties (Adj. OR 1.08, 95% CI 0.97-1.21). For women, there was a significant association (p < .05) between use of any medication with UA and reported urinary difficulty (Adj. OR = 1.31, 95% CI = 1.05-1.62). Discussion: Medications with UA may be related to difficulty in controlling urine among community-dwelling elderly women.
Do Specialist Self-Referral Insurance Policies Improve Access to HIV-Experienced Physicians as a Regular Source of Care?
Authors: Heslin Kevin C. , Andersen Ronald M. , Ettner Susan L. , Kominski Gerald F. , Belin Thomas R. , Morgenstern Hal , Cunningham William E.
Published: September 2005

Health insurance policies that require prior authorization for specialty care may be detrimental to persons with HIV, according to evidence that having a regular physician with HIV expertise leads to improved patient outcomes. The objective of this study is to determine whether HIV patients who can self-refer to specialists are more likely to have physicians who mainly treat HIV. The authors analyze cross-sectional survey data from the HIV Costs and Services Utilization Study. At baseline, 67 percent of patients had insurance that permitted self-referral. In multivariate analyses, being able to self-refer was associated with an 8–12 percent increased likelihood of having a physician at a regular source of care that mainly treats patients with HIV. Patients who can self-refer are more likely to have HIV-experienced physicians than are patients who need prior authorization. Insurance policies allowing self-referral to specialists may result in HIV patients seeing physicians with clinical expertise relevant to HIV care.
Protective Effect of a Lactobacillus salivarius Strain of Human Origin
Authors: Haza A. I. , Zabala A. , Arranz N. , Morales P.
Published: September 2005

The protective effect of a Lactobacillus salivariusstrain from human faeces (HA8) was evaluated against the cytotoxicity of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodibutylamine (NDBA) and N-nitrosopiperidine (NPIP) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. L. salivariusHA8 strain showed a moderate protective effect against NPYR and weak against NDBA and NPIP. No protective effect against cytotoxicity of NDMA was observed at the bacterial population used. To test the effect of L. salivariusHA8 on cytokine production (interleukin-1 ± (IL-1 ±), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-≥)), the human macrophage cell line (THP-1) was cultured in the presence and absence of lipopolysaccharide (LPS). L. salivariusHA8 induced IL-1 ±, IL-8 and TNF-≥ releases when cells were stimulating with and without LPS.
Wet-Milling of Flours from Red, White and Low-Polyphenol Oxidase White Wheats
Authors: Sayaslan A. , Seib P. A. , Chung O. K.
Published: September 2005

Straight-grade and high-yield flours milled from red, white and low-polyphenol oxidase (PPO) activity white wheats were wet-milled to give gluten, starch, tailings and water-soluble fractions. Wet gluten fractions were either oven-dried or freeze-dried and ground to obtain dry gluten. White wheats yielded slightly more flour with higher lightness ( L*) than the red wheat. The wet-milling properties of all flours were comparable. The wet and oven-dried gluten fractions isolated from the low-PPO flours were the lightest, followed by the gluten fractions from the white and red wheat flours. The L* of the oven-dried gluten fractions from the low-PPO flours were ~ 1-3% higher than those from the white and red wheat flours. As the flour yield increased, the L* of the dry gluten fractions from all flours decreased likewise. However, the high-yield low-PPO white wheat flour gave the dry gluten with almost equal L* to the gluten isolated from the straight-grade red wheat flour, indicating the potential of the low-PPO white wheat flour in manufacturing brighter gluten.
Effects of Grape Destemming on the Polyphenolic and Volatile Content of Fino Sherry Wine during Alcoholic Fermentation
Authors: Benítez P. , Castro R. , Natera R. , García-Barroso C.
Published: September 2005

This study has been conducted to explore the influence of different degrees of destemming on the polyphenolic and volatile content of wines from the Palomino finogrape variety. Wines obtained from destemmed grape did not present reduced polyphenolic content. No relationship was observed between degrees of destemming and changes in the polyphenolic content. Destemming prior to pressing did not modify the production of volatile compounds during fermentation and wines with similar organoleptic characteristics to those without destemming were obtained.
Growth Response of Eurotium chevalieri, Aspergillus fumigatus and Penicillium brevicompactum in Argentine Milk Jam
Authors: Char C. , Guerrero S. , González L. , Alzamora S. M.
Published: September 2005

Milk jam ( dulce de leche) is a typical Argentine sweet spread prepared from milk concentrated by evaporation to about 70% w/w total solids at atmospheric pressure with added sucrose, glucose and vanillin. Growth of xerotolerant moulds represents a severe problem in this type of product with high sugar concentration. This work aimed at analysing the influence of water activity (aw range 0.74–0.85), pH (5.5 and 6.0) and the addition of 1,000 ppm potassium sorbate on Eurotium chevalieri, Aspergillus fumigatusand Penicillium brevicompactumgrowth response in milk jam stored at 25 °C or 35 °C during 90 days. Growth curves were successfully modelled by applying the modified version of Gompertz equation. There were proposed polynomials equations relating time to detection, λ, with two independent variables: potassium sorbate and water activity at pH 6.0. Some useful combinations of these factors were found to assure inhibition of mould growth during a critical storage period. Results might contribute to optimise manufacture conditions and/or milk jam composition to obtain a safer product when failure occurs during the hot filling process or when the product is stored for a long period of time.
Self-help On-line: An Outcome Evaluation of Breast Cancer Bulletin Boards
Authors: Lieberman Morton A. , Goldstein Benjamin A.
Published: September 2005

Many breast cancer patients find help from on-line self-help groups, consisting of self-directed, asynchronous, bulletin boards. These have yet to be empirically evaluated. Upon joining a group and 6 months later, new members ( N= 114) to breast cancer bulletin boards completed measures of depression (CES-D), growth (PTGI) and psychosocial wellbeing (FACT-B). Improvement was statistically significant on all three measures. This serves as a first validation of Internet bulletin boards as a source of support and help for breast cancer patients. These boards are of particular interest because they are free, accessible and support comes from peers and not from professional facilitators.
Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
Authors: Zheng Jie , Kitajima Kenji , Sakai Eiko , Kimura Tohru , Minegishi Naoko , Yamamoto Masayuki , Nakano Toru
Published: September 2005

The zinc finger transcription factor GATA-1 is essential for both primitive (embryonic) and definitive (adult) erythropoiesis. To define the roles of GATA-1 in the production and differentiation of primitive and definitive erythrocytes, we established GATA-1-null embryonic stem cell lines in which GATA-1 was able to be conditionally expressed by using the tetracycline conditional gene expression system. The cells were subjected to hematopoietic differentiation by coculturing on OP9 stroma cells. We expressed GATA-1 in the course of primitive and definitive erythropoiesis and analyzed the ability of GATA-1 to rescue the defective erythropoiesis caused by the GATA-1 null mutation. Our results show that GATA-1 functions in the proliferation and maturation of erythrocytes in a distinctive manner. The early-stage expression of GATA-1 during both primitive and definitive erythropoiesis was sufficient to promote the proliferation of red blood cells. In contrast, the late-stage expression of GATA-1 was indispensable to the terminal differentiation of primitive and definitive erythrocytes. Thus, GATA-1 affects the proliferation and differentiation of erythrocytes by different mechanisms.
Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells
Authors: Zijlstra Andries , Seandel Marco , Kupriyanova Tatyana A. , Partridge Juneth J. , Madsen Mark A. , Hahn-Dantona Elizabeth A. , Quigley James P. , Deryugina Elena I.
Published: September 2005

A quantitative in vivo angiogenesis model employing collagen onplants placed on the chick embryo chorioallantoic membrane (CAM) has been used in this study to assess the spatial and temporal associations between neutrophil-like inflammatory cells, namely chicken heterophils, and the development of new blood vessels. Previously we have demonstrated that monocytes/macrophages infiltrating the onplants were associated with extracellular matrix remodeling and angiogenesis, in particular by delivering MMP-13 collagenase. By introducing chicken gelatinase B (chMMP-9) as a specific marker for heterophils, we now show that the onset and extent of angiogenesis induced by purified growth factors or by human HT-1080 fibrosarcoma cells correlated with the initial influx of chMMP-9–positive heterophils. This early heterophil arrival was followed by the infiltration of monocytes/macrophages and appeared to sustain further blood vessel formation. The disruption of inflammatory cell influx by 2 mechanistically distinct anti-inflammatory drugs, cortisone and ibuprofen, significantly inhibited angiogenesis, indicating a functional involvement of these inflammatory cells in new blood vessel development. A direct addition of isolated heterophils or purified chMMP-9 into the HT-1080 onplants engrafted into cortisone- or ibuprofen-treated embryos reversed the antiangiogenic effects of the drugs. The exogenously added heterophils induced in vivo a further infiltration of endogenous heterophils and monocytes and dramatically rescued the impaired angiogenesis, highlighting the importance of early inflammatory leukocytes in tumor-induced angiogenesis. Moreover, purified heterophils incorporated into onplants lacking growth factors or tumor cells induced angiogenesis in nontreated embryos, further indicating a direct proangiogenic role for neutrophil-like leukocytes.
NF-κB as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145
Authors: Vodanovic-Jankovic Sanja , Hari Parameswaran , Jacobs Paulette , Komorowski Richard , Drobyski William R.
Published: September 2005

NF-κB is a transcription factor that controls the expression of a number of genes important for mediating immune and inflammatory responses. In this study, we examined whether bortezomib and PS-1145, each of which inhibits NF-κB, could protect mice from lethal graft-versus-host disease (GVHD), which is characterized by immune activation and proinflammatory cytokine production. When administered within the first 2 days after transplantation, bortezomib and PS-1145 both protected mice from fatal GVHD, did not compromise donor engraftment, and effected marked reduction in the levels of serum cytokines that are normally increased during GVHD. Extending the course of bortezomib administration or delaying the initiation of this agent for as few as 3 days after bone marrow transplantation (BMT), however, significantly exacerbated GVHD-dependent mortality because of severe pathological damage in the colon. In contrast, prolonged administration of PS-1145, which, unlike bortezomib, is a selective inhibitor of NF-κB, caused no early toxicity and resulted in more complete protection than that observed with an abbreviated PS-1145 treatment schedule. These results confirm a critical role for NF-κB in the pathophysiology of GVHD and indicate that targeted inhibition of NF-κB may have a superior therapeutic index and may constitute a viable therapeutic approach to reduce GVHD severity. (Blood. 2006;107:827-834)
Runx1 function in hematopoiesis is required in cells that express Tek
Authors: Li Zhe , Chen Michael J. , Stacy Terryl , Speck Nancy A.
Published: September 2005

Runx1 expression marks the putative hemogenic endothelium between embryonic days (E) 8.5 to 11.5 of mouse gestation and is required for the formation of intra-aortic hematopoietic clusters, leading to the hypothesis that Runx1 is required for the transition from endothelial to hematopoietic cell. To address this hypothesis, we ablated the Runx1 gene by Cre-recombinase-mediated excision, with Cre expression under the control of the Tek promoter and enhancer. Most embryos died between E12.5 and E13.5 with a phenotype almost identical to Runx1 deficiency. We conclude that Runx1 function in establishing definitive hematopoiesis is required in a Tek+ cell.
FcϵR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells
Authors: Qiao Huihong , Andrade Marcus V. , Lisboa Felipe A. , Morgan Katrina , Beaven Michael A.
Published: September 2005

Mast cells mediate both IgE-dependent allergic reactions and protective responses against acute infections, possibly through the activation of Toll-like receptors (TLRs). We find that antigen interacts synergistically with TLR2 and TLR4 ligands to markedly enhance production of cytokines in murine mast cell lines. However, the TLR ligands neither stimulated degranulation and release of arachidonic acid nor influenced such responses to antigen, probably because these ligands failed to generate a necessary calcium signal. The enhanced cytokine production could be attributed to synergistic activation of mitogen-activated protein kinases in addition to the engagement of a more effective repertoire of transcription factors for cytokine gene transcription. The synergistic interactions of TLR ligands and antigen might have relevance to the exacerbation of IgE-mediated allergic diseases by infectious agents.
T cell avidity and tumor recognition: implications and therapeutic strategies
Authors: McKee Mark D , Roszkowski Jeffrey J , Nishimura Michael I
Published: September 2005

In the last two decades, great advances have been made studying the immune response to human tumors. The identification of protein antigens from cancer cells and better techniques for eliciting antigen specific T cell responsesin vitroandin vivohave led to improved understanding of tumor recognition by T cells. Yet, much remains to be learned about the intricate details of T cell – tumor cell interactions. Though the strength of interaction between T cell and target is thought to be a key factor influencing the T cell response, investigations of T cell avidity, T cell receptor (TCR) affinity for peptide-MHC complex, and the recognition of peptide on antigen presenting targets or tumor cells reveal complex relationships. Coincident with these investigations, therapeutic strategies have been developed to enhance tumor recognition using antigens with altered peptide structures and T cells modified by the introduction of new antigen binding receptor molecules. The profound effects of these strategies on T cell – tumor interactions and the clinical implications of these effects are of interest to both scientists and clinicians. In recent years, the focus of much of our work has been the avidity and effector characteristics of tumor reactive T cells. Here we review concepts and current results in the field, and the implications of therapeutic strategies using altered antigens and altered effector T cells.
Developing children's conversational skills in mainstream schools: An evaluation of group therapy
Authors: Godfrey J. , Pring T. , Gascoigne M.
Published: September 2005

Children from two mainstream schools who had poor communication skills were selected to take part in this study. Following formal and informal assessments of their language and pragmatic skills, they were randomly assigned to treatment and no treatment groups. Treatment consisted of attending eight weekly sessions of a social skills training group. Assessments carried out four to six months after training showed that treated children had improved their pragmatic knowledge significantly more than untreated children. However, caution is required in generalizing these results to other children. The children in this study had a variety of difficulties and it appeared that those whose communication skills were primarily the result of underlying language problems made the least progress. Further research is warranted with more homogeneous groups of children to establish which children gain the most from this approach.
Recurrent Heat-Related Illnesses During Antipsychotic Treatment
Authors: Kwok Jeffrey SS , Chan Thomas YK
Published: September 2005

OBJECTIVE

To report a case of recurrent heat-related illnesses associated with the use of benzhexol, chlorpromazine, and zuclopenthixol decanoate.

CASE SUMMARY

During the summer of 2004, a 48-year-old man with a history of diabetes mellitus and schizophrenia was twice admitted to the hospital because of heat-related illnesses. On both occasions, he had been working under the sun in an open car park. His medications included benzhexol 2 mg twice daily, chlorpromazine 650 mg at bedtime, and zuclopenthixol decanoate intramuscular injection 600 mg every 4 weeks. In the first admission, the clinical diagnosis was heat stroke. He was discharged home on day 14, with precautionary advice against heat stroke. In the second admission, the clinical diagnosis was heat exhaustion. He was discharged home on day 4 and reminded of the precautions against heat stroke. An objective causality assessment revealed that the adverse event was possibly drug related in the first admission and probably drug related in the second admission.

DISCUSSION

Several drugs can impair thermoregulation during exercise or under conditions of environmental heat stress. Anticholinergic drugs or drugs with anticholinergic effects can inhibit sweating and reduce heat elimination. Neuroleptics (antipsychotics), such as phenothiazines, have combined anticholinergic and central thermoregulatory effects. The set point of the temperature regulation center can be elevated by the antidopaminergic effect of antipsychotics, such as phenothiazines and thioxanthenes.

CONCLUSIONS

Certain drugs may induce or worsen heat-related illnesses. During a heat wave, special attention should be given to those most at risk, and the importance of preventive measures should be emphasized.
Zirconium and Niobium Affect Human Osteoblasts, Fibroblasts, and Lymphocytes in a Similar Manner to More Traditional Implant Alloy Metals
Authors: Hallab NJ , Anderson S , Caicedo M , Jacobs JJ
Published: September 2005

Implant debris remains the major factor limiting the longevity of total joint replacements. Whether soluble implant debris of Zr and Nb containing implant alloys constitute a greater risk than other implant metals remains unknown. We evaluated the relative effects of soluble forms of Zr+4 and Nb+5 (0.001–10.0 mM) relative to Cr+3, Mo+5, Al+3, Co+2, Ni+2, Fe+3, Cu+2, Mn+2, Mg+2, Na+2, and V+3 chloride solutions on human peri-implant cells (i.e., osteoblast-like MG-63 cells, fibroblasts, and lymphocytes). Metals were ranked using a 50% decrease in proliferation and viability to determine toxic concentrations. Lymphocytes, fibroblasts, and osteoblasts were, generally, similarly affected by metals where the most toxic metals, Co, Ni, Nb, and V required <1.0 mM to induce toxicity. Less toxic metals Al, Cr, Fe, Mo, and Zr generally required >1.0 mM challenge to produce toxicity. Overall, Co and V were the most toxic metals tested, thus Zr and Nb containing implant alloys would not likely be more toxic than traditional implant alloys. Below concentrations of 0.1 mM, neither Zr nor Nb reduced osteoblast, lymphocyte, or fibroblast proliferation. Zr was generally an order of magnitude less toxic than Nb to lymphocytes, fibroblasts, and osteoblasts. Our results indicated that soluble Zr and Nb resulting from implant degradation likely act in a metal- and concentration-specific manner capable of producing adverse local and remote tissue responses to the same degree as metals from traditional implant alloys, e.g., Ti-6Al-4V (ASTM F 138) and Co-Cr-Mo alloys (ASTM F 75).
Some Thoughts on the Neurobiology of Stalking
Authors: Meloy JR , Fisher H
Published: September 2005

The authors examine the crime of stalking, including the cognitive traits, emotional reactions, attachment pathology, violence patterns and sex differences of samples of stalking offenders. They focus on two common types of stalkers: 1) those who sustain pursuit of a former sexual intimate who has rejected them; and 2) those who pursue a stranger or acquaintance who has failed to return the stalker's romantic overtures. The authors discuss data from neuroimaging (fMRI) studies of romantic love which suggest that these forms of stalking may be associated with heightened activity of subcortical dopaminergic pathways of the "Reward System" of the brain, perhaps in combination with low activity of central serotonin. The authors propose that this set of neural correlates may contribute to the stalker's focused attention, increased energy, following behaviors, obsessive thinking about and impulsivity directed toward the victim. To further explore the neural systems associated with stalking behavior, they also discuss several biopsychological phenomena associated with romantic rejection, including the "protest response," "frustration attraction," "abandonment rage" and "mate guarding." They illustrate the parallels between stalking and addiction. They conclude that stalking may be associated with a specific set of biological components and they offer suggestions for further research into this pathological emotional/motivational state.
Removing Interfering Contaminations from Gelatin Lifters
Authors: Shor Y , Tsach T , Wiesner S , Meir G
Published: September 2005

Gelatin lifter is widely used for recovering shoeprints from crime scenes. Dusty shoeprints removed from paper with loose fibers, cloth or plasterboard, might be concealed by the detached fibers. A novel technique to clean the gelatin lifter from the interfering contaminations, using adhesive lifters, was developed. The adhesive lifter is applied directly on the surface of the gelatin lifter, and is removed instantly. The adhesive lifter removes the upper layer of the attached material on the gelatin lifter. After removing the concealing material from the hidden imprint, the quality of the visualized imprint is improved. The cleaning process can be applied as many times as needed and the optimum number is different for each substrate. The small dust particles comprising the shoeprint remained attached to the sticky side of the gelatin lifter even though the adhesion force applied by the adhesive lifter is great. Repeating the procedure too many times could harm the quality of the print severely, yet the advantages of this method are greater than the risks of relocation of image quality reduction.
Child Murder Committed by Severely Mentally Ill Mothers: An Examination of Mothers Found Not Guilty By Reason of Insanity
Authors: Friedman SH , Hrouda DR , Holden CE , Noffsinger SG , Resnick PJ
Published: September 2005

Forensic hospital records of 39 severely mentally ill mothers adjudicated Not Guilty by Reason of Insanity for filicide (child murder by parents) were analyzed to describe characteristics preceding this tragedy and to suggest prevention strategies. Almost three-quarters of the mothers (72%) had previous mental health treatment. Over two thirds (69%) of the mothers were experiencing auditory hallucinations, most frequently command hallucinations, and half (49%) were depressed at the time of the offense. Over one third (38%) of the filicides occurred during pregnancy or the postpartum period, and many had a history of postpartum psychosis. Almost three-quarters (72%) of the mothers had experienced considerable developmental stressors, such as death of their own mother or incest. Maternal motives for filicide were predominantly "altruistic" (meaning murder out of love) or "acutely psychotic" (occurring in the throes of psychosis, without rational motive). Psychiatrists should perform careful risk assessments for filicide in mothers with mental illnesses.
Postmortem Monocular Indirect Ophthalmoscopy
Authors: Lantz PE , Adams GGW
Published: September 2005

Postmortem monocular indirect ophthalmoscopy permits examination of the posterior fundus and peripheral retina even if there is less than perfect anterior segment media such as postmortem corneal clouding. Light directed through the decedent's pupil from a bright focal light source illuminates the fundus and reflected light from the retina is then projected out of the eye. An aspheric condensing lens positioned in front of the eye focuses the retinal image at the focal plane of the lens. The real inverted, laterally reversed image comprises a wide field of view permitting evaluation of the decedent's fundus for retinal hemorrhages and other lesions.
Corrected Procedure for Crack Length Calculation by the Unloading Compliance Technique for Charpy-sized Specimens
Authors: Džugan J
Published: September 2005

The problems with crack length determination by the unloading compliance method are well known for Charpy-sized specimens. The final crack lengths calculated for bend specimens do not fulfill ASTM E 1820 accuracy requirements. Some investigations have been performed to resolve this problem by correcting the compliance value, but satisfactory results were not obtained. In the present work the measured specimen compliance was taken as a correct value and the calculation procedure was modified. On the basis of experimentally obtained compliances of bent specimens and optically measured crack lengths, a calculation procedure enabling accurate crack length calculation up to 5 mm of plastic deflection was developed. Applying the new procedure to a sample of 238 measured crack lengths, more than 80 % of the values fulfilled the ASTM E 1820 accuracy requirement, while the presently used procedure provided only about 30 % valid results. The newly proposed procedure also can be used prospectively in modified form for specimens other than Charpy-sized.
An Experimental Study of Monitoring Internal Leakage in Water Hydraulic Cylinders Using Acoustic Emission
Authors: Chen P , Chua PSK , Lim GH
Published: September 2005

This paper studies experimentally acoustic emission (AE) to monitor internal leakage in modern water hydraulic cylinders. A series of experiments has been designed and carried out. Through these experiments, the background noise induced by the operation of a water hydraulic system is carefully determined, AE signals generated by a water hydraulic cylinder operating under different piston-sealing conditions are characterized, and AE signals generated by internal leakage in a water hydraulic cylinder are also characterized. The measured AE signals are analyzed using the power spectral density (PSD) technique. The results show that AE signals are sensitive to the internal leakage in a water hydraulic cylinder and are not affected by background noise. We conclude that AE can be used to develop an effective technique to monitor internal leakage in modern water hydraulic cylinders.
Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein Cleavage and Reduces Cerebral Amyloidosis in Alzheimer Transgenic Mice
Authors: Rezai-Zadeh Kavon , Shytle Doug , Sun Nan , Mori Takashi , Hou Huayan , Jeanniton Deborah , Ehrhart Jared , Townsend Kirk , Zeng Jin , Morgan David , Hardy John , Town Terrence , Tan Jun
Published: September 2005

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of β-amyloid (Aβ) peptides as senile plaques in the brain. Recent studies suggest that green tea flavonoids may be used for the prevention and treatment of a variety of neurodegenerative diseases. Here, we report that (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, reduces Aβ generation in both murine neuron-like cells (N2a) transfected with the human “Swedish” mutant amyloid precursor protein (APP) and in primary neurons derived from Swedish mutant APP-overexpressing mice (Tg APPswline 2576). In concert with these observations, we find that EGCG markedly promotes cleavage of the α-C-terminal fragment of APP and elevates the N-terminal APP cleavage product, soluble APP-α. These cleavage events are associated with elevated α-secretase activity and enhanced hydrolysis of tumor necrosis factor α-converting enzyme, a primary candidate α-secretase. As a validation of these findingsin vivo, we treated Tg APPswtransgenic mice overproducing Aβ with EGCG and found decreased Aβ levels and plaques associated with promotion of the nonamyloidogenic α-secretase proteolytic pathway. These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis for AD.
Radiochemical neutron activation analysis of trace impurities in high purity titanium and tungsten
Authors: Zaidi Jamshed H. , Fatima I. , Arif M.
Published: September 2005

Rapid radiochemical neutron activation analysis (RNAA) procedures were developed and employed to the determination of 36 trace impurities in high purity titanium and tungsten. Anion–exchange column chromatography procedures were developed for the sequential group chemical separation of various elements, which helped in reducing the spectral interferences and improving the sensitivity of the method. The procedure is simple and requires a very short time to separate the elements in three groups for radiometric assay. To determine very low contents of uranium and thorium, 239Np and 233Pa as activation products were separated using anion–exchange and coprecipitation methods. The impurity contents were found to be low; therefore, their deleterious effects would be negligible.
Thermochromatography of 241Am and 254Es in chlorinating carrier gases
Authors: Eichler B. , Adams J. , Eichler R. , Gäggeler H. W. , Peterson J.
Published: September 2005

Gas adsorption chromatography experiments were carried out with Es and Am in a temperature gradient tube using chlorinating carrier gas. From the observed deposition temperatures the adsorption enthalpies of AmCl3 and EsCl3 on the chromatographic surface (quartz glass surface, dynamically modified by the chlorinating carrier gases) were deduced for the first time. In good agreement, both the model of mobile adsorption and the Monte Carlo model resulted in:
Development of Farnesyl Transferase Inhibitors: A Review
Authors: Appels Natalie M.G.M. , Beijnen Jos H. , Schellens Jan H.M.
Published: September 2005

Learning Objectives

After completing this course, the reader will be able to: Describe the potential mechanisms by which farnesyl transferases inhibit tumor growth.Explain possible mechanisms by which tumor cells may develop resistance to this class of agents.Discuss the scientific requirements for developing targeted cancer treatments that will actually be useful in patients.

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com

Farnesyl transferase inhibitors are a new class of biologically active anticancer drugs. The exact mechanism of action of this class of agents is, however, currently unknown. The drugs inhibit farnesylation of a wide range of target proteins, including Ras. It is thought that these agents block Ras activation through inhibition of the enzyme farnesyl transferase, ultimately resulting in cell growth arrest. In preclinical models, the farnesyl transferase inhibitors showed great potency against tumor cells; yet in clinical studies, their activity was far less than anticipated. Reasons for this disappointing clinical outcome might be found in the drug-development process. In this paper, we outline an algorithm that is potentially useful for the development of biologically active anticancer drugs. The development of farnesyl transferase inhibitors, from discovery to clinical trials, is reviewed on the basis of this algorithm. We found that two important steps of this algorithm were underestimated. First, understanding of the molecular biology of the defective pathway has mainly been focused on H-Ras activation, whereas activation of K-Ras or other farnesylated proteins is probably more important in tumorigenesis. Inhibition of farnesylation is possibly not sufficient, because geranylgeranylation might activate K-Ras and suppress the effect of farnesyl transferase inhibitors. Furthermore, a well-defined proof of concept in preclinical and clinical studies has not been achieved. Integrating the proposed algorithm in future studies of newly developed biologically active anti-cancer drugs might increase the rate of success of these compounds in patients.
Targeted Therapies for Esophageal Cancer
Authors: Tew William P. , Kelsen David P. , Ilson David H.
Published: September 2005

Learning Objectives

After completing this course, the reader will be able to: Discuss the epidemiology of esophageal cancer.Explain the current status of diagosing and treating esophageal cancer.Describe potential novel targets for new drug development in esophageal cancer.

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com

Esophageal cancer is a highly aggressive neoplasm. In 2005, 14,520 Americans will be diagnosed with esophageal cancer, and more than 90% will die of their disease. On a global basis, cancer of the esophagus is the sixth leading cause of cancer death worldwide. In fact, gastric and esophageal cancers together accounted for nearly 1.3 million new cases and 980,000 deaths worldwide in 2000—more than lung, breast, or colorectal cancer. Although esophageal squamous cell carcinoma cases have steadily declined, the incidence of gastroesophageal junction adenocarcinoma has increased 4%–10% per year among U.S. men since 1976, more rapidly than for any other cancer type, and parallels rises in population trends in obesity and reflux disease.

With advances in surgical techniques and treatment, the prognosis of esophageal cancer has slowly improved over the past three decades. However, the 5-year overall survival rate (14%) remains poor, even in comparison with the dismal survival rates (4%) from the 1970s. The underlying reasons for this disappointingly low survival rate are multifold: (a) ineffective screening tools and guidelines; (b) cancer detection at an advanced stage, with over 50% of patients with unresectable disease or distant metastasis at presentation; (c) high risk for recurrent disease after esophagectomy or definitive chemoradiotherapy; (d) unreliable noninvasive tools to measure complete response to chemoradiotherapy; and (e) limited survival achieved with palliative chemotherapy alone for patients with metastatic or unresectable disease. Clearly, additional strategies are needed to detect esophageal cancer earlier and to improve our systemic treatment options. Over the past decade, the field of drug development has been transformed with the identification of and ability to direct treatment at specific molecular targets. This review focuses on novel targeted treatments in development for esophageal squamous cell carcinoma and distal esophageal and gastroesophageal junction adenocarcinoma.
Randomized Comparison of Epoetin Alfa (40,000 U Weekly) and Darbepoetin Alfa (200 μg Every 2 Weeks) in Anemic Patients with Cancer Receiving Chemotherapy
Authors: Waltzman Roger , Croot Christopher , Justice Glen R. , Fesen Mark R. , Charu Veena , Williams Denise
Published: September 2005

This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 μ g every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for ≥12 weeks and with baseline Hb ≤11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 μg Q2W (n = 180) s.c. for up to 16 weeks. Doses were increased for nonresponders (Hb increase <1 g/dl) after 4 (EPO) or 6 (DARB) weeks, as per National Comprehensive Cancer Network guidelines, and were reduced for a rapid rise in Hb (>1.3 g/dl [EPO] or >1.0 g/dl [DARB] within any 2-week period) or for an Hb level >13 g/dl. The proportion of patients achieving a ≥1-g/dl Hb rise by week 5, the primary end point, was significantly higher with EPO (47.0%) than with DARB (32.5%), and EPO-treated patients achieved a ≥1-g/dl Hb increase significantly earlier than those receiving DARB (median, 35 days versus 46 days). The mean increase in Hb from baseline was significantly higher at weeks 5, 9, 13, and the end of the study with EPO than with DARB. The number of units transfused per patient was significantly lower for the EPO group than for the DARB group. The proportions of patients requiring transfusions, mean QOL improvements, and tolerability profiles were similar in the two groups.
Elevated Temperature Deformation Behavior of Zr‐Based Bulk Metallic Glasses
Authors: Heilmaier M. , Eckert J.
Published: September 2005

The elevated deformation behaviour of Zr‐based metallic bulk metallic glasses is reviewed in a wide temperature and strain rate range within the supercooled liquid region. Newtonian viscous flow and homogeneous deformation at constant viscosity is observed. In accord with Spaepen's free volume theory it is experimentally verified that the extraordinarily high plastic deformability in BMGs is controlled by the competing effects of free volume generation and annihilation.
Laser Surface Modification of a Crystalline Al‐Co‐Ce Alloy for Enhanced Corrosion Resistance
Authors: Hoekstra J. G. , Qadri S. B. , Scully J. R. , Fitz‐Gerald J. M.
Published: September 2005

The surfaces of Al‐Co‐Ce bulk crystalline alloys have been successfully laser processed resulting in amorphous‐like surface layer formation with enhanced corrosion characteristics. The material system, Al84Co7.5Ce8.5, is one of several next generation alloy compositions scientifically designed to form a metallic glass under the proper processing conditions. This material system exhibits both local composition changes and enhanced corrosion resistance in comparison to their native counterparts.
Temperature‐Dependent Microstructures in Fatigued Ultrafine‐Grained Copper Produced by Equal Channel Angular Pressing
Authors: Li X. W. , Wu S. D. , Wu Y. , Yasuda H. Y. , Umakoshi Y.
Published: September 2005

Ultrafine‐grained copper samples produced by equal channel angular pressing were cyclically deformed at different temperatures under a constant stress amplitude of 200 MPa, and the corresponding microstructures were investigated by transmission electron microscope. The increase in temperature during cycling facilitated the grain coarsening and led further to the general change of microstructures from dislocation walls to well‐defined cells as well as to the occurrence of a few annealing twins in final microstructures of fatigued UFG copper at the temperature above recrystallization.
Cerebellar transcranial magnetic stimulation impairs verbal working memory
Authors: Desmond John E. , Chen S. H. Annabel , Shieh Perry B.
Published: September 2005

Previous functional magnetic resonance imaging and patient studies indicate cerebellar participation in verbal working memory. In particular, event‐related functional magnetic resonance imaging showed superior cerebellar activation during the initial encoding phase of the Sternberg task. This study used functional magnetic resonance imaging–guided transcranial magnetic stimulation (TMS) to test whether disruption of the right superior cerebellum (hemispheric lobule VI/Crus I) impairs verbal working memory performance. Single‐pulse TMS was administered immediately after letter presentation during the encoding phase on half the trials. Sham TMS and a Motor Control task were included to test for general distraction and nonmemory‐related motor effects. Results showed no effects of TMS on accuracy, but reaction times (RTs) on correct trials were significantly increased on TMS relative to non‐TMS trials for the Verbal Working Memory and Motor Control tasks. Additional analyses showed that the increased RT was significantly greater for Verbal Working Memory than for the motor task, suggesting that the effect on working memory was not caused by interference with finger responses. Sham TMS did not affect RTs, indicating that the potentially distracting effects of the postencoding click did not contribute to the increase in RT. The observed effects from cerebellar disruption are consistent with proposed cerebrocerebellar involvement in verbal working memory. Ann Neurol 2005;58:553–560
No increase of calcitonin gene–related peptide in jugular blood during migraine
Authors: Tvedskov Jesper Filtenborg , Lipka Kerstin , Ashina Messoud , Iversen Helle K. , Schifter Søren , Olesen Jes
Published: September 2005

Increased calcitonin gene–related peptide (CGRP) in external jugular venous blood during migraine attack is one of the most cited findings in the headache literature. The finding has not been convincingly reproduced and is based on comparison with historic control subjects. The validity of this finding is important for the understanding of migraine. We therefore investigated the issue using an intrapatient comparison design and two different CGRP assays. We sampled blood from the external jugular and cubital vein during, as well as outside of, an attack of migraine without aura. We succeeded in 17 patients, whereas only cubital fossa blood could be sampled in an additional 4 patients. CGRP was measured with the same assay as most previous studies (assay I) and furthermore with a more sensitive and validated assay (assay II). For assay I, mean CGRP concentration in external jugular venous blood during attack was 17.18pmol/L compared with 15.88pmol/L outside of attack. Mean difference was 1.81pmol/L (95% confidence interval [CI]: −2.88, 6.41; p = 0.44). In peripheral blood during attack, CGRP was 16.86pmol/L compared with 17.57pmol/L outside of attack. Mean difference was −0.79pmol/L (95% CI: −4.64, 3.06; p = 0.69). For assay II, external jugular venous blood concentration of CGRP during attack was 32.59pmol/L compared with 30.59pmol/L outside of attack; mean difference was 2.00pmol/L (standard error, 2.39; 95% CI: −3.07, 7.07; p = 0.416). In peripheral blood during attack, CGRP was 33.37pmol/L compared with 31.84pmol/L outside of attack; mean difference was 1.53pmol/L (standard error, 1.90; 95% CI: −2.46, 5.51; p = 0.431). Thus, no difference between CGRP level in external jugular or cubital fossa blood during and outside of attack was found. No difference was found between external jugular and peripheral venous blood. Thus, previous findings of increased CGRP level in external jugular or cubital fossa venous blood could not be confirmed. Our finding strongly suggests that CGRP is not increased in jugular venous blood during migraine without aura. CGRP cannot be used as a biomarker to validate human or animal models of migraine. Ann Neurol 2005;58:561–568
Late‐onset MNGIE due to partial loss of thymidine phosphorylase activity
Authors: Martí Ramon , Verschuuren Jan J. G. M. , Buchman Alan , Hirano Ikuo , Tadesse Saba , van Kuilenburg André B. P. , van Gennip Albert H. , Poorthuis Ben J. H. M. , Hirano Michio
Published: September 2005

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the gene encoding thymidine phosphorylase (TP). All MNGIE patients have had severe loss of TP function and prominent plasma accumulations of the TP substrates thymidine (dThd) and deoxyuridine (dUrd). Here, we report for the first time to our knowledge three MNGIE patients with later onset, milder phenotype, and less severe TP dysfunction, compared with typical MNGIE patients. This report demonstrates a direct relationship between the biochemical defects and clinical phenotypes in MNGIE and supports the notion that reduction of dThd and dUrd accumulation or TP replacement could be useful therapy for MNGIE. Ann Neurol 2005;58:649–652
Symptoms in patients with lung carcinoma
Authors: Tishelman Carol , Degner Lesley F. , Rudman Ann , Bertilsson Kristina , Bond Ruth , Broberger Eva , Doukkali Eva , Levealahti Helena
Published: September 2005

BACKGROUND

The patient perspective on distress associated with lung carcinoma is important, yet understudied. Previous research on symptom experience generally had not differentiated the dimension symptom intensity/frequency from which symptoms are associated with most distress. The objective of the current study was to determine whether patterns of symptom intensity were similar to patterns of symptom distress, whether patterns were consistent at different time points, whether patterns varied by subgroups, and whether high symptom intensity was equivalent to distress.

METHODS

Four hundred adults who were newly diagnosed with inoperable lung carcinoma completed a measure of symptom intensity/frequency and a new measure of distress associated with symptoms at six time points during the first year after diagnosis. These data were supplemented by field notes by research nurses and by less structured, qualitative interviews.

RESULTS

The mean ranking of distress in the total group and in all subgroups remained constant at all time points, with breathing, pain, and fatigue associated with the most distress. In contrast, the pattern of mean rank order of symptom intensity showed little consistency; however, fatigue had the highest intensity scores at all time points.

CONCLUSIONS

The current data challenged the uncritical use of summated scores of different symptom items in the context of lung carcinoma. Breathing and pain appeared to function as icons representing threats associated with lung carcinoma, with distress described as related to the past and the present and to expectations for the future. One of the most promising implications of these data was in fostering a preventive paradigm for symptom palliation. Cancer 2005. © 2005 American Cancer Society.
Efficient placement of rigid supports using finite element models
Authors: Friswell Michael I.
Published: September 2005

The correct design of flexible and rigid supports improves the performance of structures, by reducing deflections or increasing natural frequencies. The optimization of the location of rigid supports is difficult because the support reduces the number of modelled degrees of freedom. This paper introduces efficient methods for the analysis of models where the support occurs within the element. This allows a single relatively coarse element mesh to be used, while still providing accurate predictions of the effect of the support on the structure's static and dynamic response. Copyright © 2005 John Wiley & Sons, Ltd.