bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular Effects of Donepezil in Patients with Dementia
Authors: McLaren A.T. , Allen J. , Murray A. , Ballard C.G. , Kenny R.A. 
Published: April 2003

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer’s disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms<sup>2</sup>; p = 0.001) but also for total power (median changed from 1,563 to 844 ms<sup>2</sup>; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.
Measurement of Electrical Current Perception Threshold of Sensory Nerves for Pruritus in Atopic Dermatitis Patients and Normal Individuals with Various Degrees of Mild Damage to the Stratum corneum
Authors: Kobayashi Hiromi , Kikuchi Katsuko , Tsubono Yoshitaka , Tagami Hachiro 
Published: April 2003

<i>Background:</i> Patients with atopic dermatitis (AD) are well known to be sensitive to irritation from the environment due to the impaired function of the stratum corneum (SC). Electrical current perception threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of the sensory nerves. <i>Objective:</i> To study the CPT in a noninvasive fashion using Neurometer<sup>®</sup> CPT/C, together with measurements of various functions of the SC. <i>Methods:</i> We measured the CPT on the flexor forearm and cheek of AD patients and normal individuals. Subsequently, we evaluated the CPT and skin sensitivity to a 30% aqueous solution of lactic acid after the infliction of various mildly disruptive measures on the SC on the flexor forearm of healthy individuals by the following three methods: (1) removal of the superficial sebum with acetone/ether, (2) scarification with a needle and (3) tape stripping of the SC. Finally, we examined the effect of topical applications of emollients such as petrolatum or a moisturizing cream to the scratched skin. <i>Results: </i>AD patients showed a lower barrier function and lower CPT than normal individuals. In subsequent studies conducted in normal individuals, the CPT was found to be inversely correlated with transepidermal water loss (TEWL) levels after tape stripping. However, most of all, the partial superficial scarification with a needle decreased the CPT and increased the lactic acid stinging response. Prolonged removal of lipids from the SC with acetone/ether for 30 min that increased the TEWL levels for only 1 day decreased the high-frequency conductance value for 2 days and the CPT only on the 2nd day after treatment. Topical applications of emollients were effective to prevent the increased sensitivity caused by scratching. <i>Conclusions: </i>AD patients showed functional abnormalities of the SC and tended to have more sensitive skin on the cheek and flexor forearm than healthy controls. Even focal SC damage caused by superficial cracking may lead to further disruption of the already damaged SC in AD patients, by eliciting scratching and facilitating the permeation of various environmental allergens and also the induction of hypersensitive skin.
Cyclic ADP-Ribose Contributes to Contraction and Ca<sup>2+</sup> Release by M<sub>1</sub> Muscarinic Receptor Activation in Coronary Arterial Smooth Muscle
Authors: Ge Zhi-Dong , Zhang David X. , Chen Ya-Fei , Yi Fu-Xian , Zou Ai-Ping , Campbell William B. , Li Pin-Lan 
Published: April 2003

The present study determined the role of cyclic ADP-ribose (cADPR) in mediating vasoconstriction and Ca<sup>2+</sup> release in response to the activation of muscarinic receptors. Endothelium-denuded small bovine coronary arteries were microperfused under transmural pressure of 60 mm Hg. Both acetylcholine (ACh; 1 nmol/L to 1 µmol/L) and oxotremorine (OXO; 2.5–80 µmol/L) produced a concentration-dependent contraction. The vasoconstrictor responses to both ACh and OXO were significantly attenuated by nicotinamide (Nicot; an ADP-ribosyl cyclase inhibitor), 8-bromo-cADPR (8-Br-cADPR; a cADPR antagonist) or ryanodine (Ry; an Ry receptor antagonist). Intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) was determined by fluorescence spectrometry using fura-2 as a fluorescence indicator. OXO produced a rapid increase in [Ca<sup>2+</sup>]<sub>i</sub> in freshly isolated single coronary arterial smooth muscle cells (CASMCs) bathed with Ca<sup>2+</sup>-free Hanks’ solution. This OXO-induced rise in [Ca<sup>2+</sup>]<sub>i</sub> was significantly reduced by pirenzepine (PIR; an M<sub>1</sub> receptor-specific blocker), Nicot, 8-Br-cADPR or Ry. The effects of OXO on the activity of ADP-ribosyl cyclase (cADPR synthase) were examined in cultured CASMCs by measuring the rate of cyclic GDP- ribose (cGDPR) formation from β-nicotinamide guanine dinucleotide. It was found that OXO produced a concentration-dependent increase in the production of cGDPR. The stimulatory effect of OXO on ADP-ribosyl cyclase was inhibited by both PIR and Nicot. These results suggest that the cADPR signaling pathway participates in the contraction of small coronary arterial smooth muscle and Ca<sup>2+</sup> release induced by activation of M<sub>1</sub> muscarinic receptors.
Impact of Epidermal Growth Factor and Transforming Growth Factor Beta-1 on the Release of Fibrinolytic Factors from Cultured Endometrial and Ovarian Endometriotic Stromal Cells
Authors: Guan Yong-Mei , Carlberg Magdalena , Bruse Christine , Bergqvist Agneta 
Published: April 2003

We have investigated whether there are any differences in the release of urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) from cultured endometrial and endometriotic stromal cells, and whether the release is regulated by epidermal growth factor (EGF) or transforming growth factor β1 (TGFβ1). The cells were isolated from endometriomas and endometrium from women with and without endometriosis. After treatment with EGF or TGF and in untreated controls, incubated media collected at 0, 24, 48 and 72 h were analyzed by ELISA. Stromal cells from all three types of tissues released uPA and PAI-1, but the soluble receptor of uPA was not measurable in any group. The basal release of uPA and PAI-1 from endometriotic cells was higher than from endometrial cells. The uPA release in endometriotic cells was reduced with and without the addition of EGF (p < 0.05) or TGFβ1 (p < 0.05). EGF increased the release of PAI-1 from stromal cells from women without endometriosis (p < 0.05) but decreased the release of PAI-1 from stromal cells from endometriotic women (p < 0.05). TGFβ1 increased the release of PAI-1 from endometriotic cells (p < 0.05) but had no effect in endometrial cells.
Influence of an Interferon Inducer on Bone Marrow Transplant Reconstitution in Irradiated, Leukemic Mice: Elevated Natural Killer Cell Numbers and Improved Life Span
Authors: Currier N.L. , Miller S.C. 
Published: April 2003

Interferon-γ and interferon inducers such as polyinosinic-polycytidylic acid (poly I:C) promote natural-killer (NK)-cell-mediated killing of a wide range of tumor cells both in vitro and in vivo. The aim of the present work was to administer poly I:C to irradiated, leukemic mice, both before and after syngeneic bone marrow transplant with the intent of boosting the host’s natural immunity in the critical peritransplant period. Briefly, DBA/2 mice were injected with Friend-virus-induced erythroleukemia cells. After 5 days of tumor growth, some mice received daily injections of poly I:C for the next 4 days while control, leukemic mice received the saline vehicle only. All mice were then irradiated (450 R × 2 at 4-hour intervals) and transplanted 1 day following irradiation with bone marrow from age- and sex-matched, normal DBA/2 donor mice. After transplant, daily injections of poly I:C (or vehicle) continued for 8 more days. On day 9 after transplant, treated and control mice were killed, and the total cellularity, total numbers of lymphoid cells, the total numbers of NK cells (identified by the presence of an immuno-labelled, specific cell surface marker) were obtained from both the spleen and the bone marrow. Other identically treated mice subjected, however, to several additional rounds of poly I:C treatment were sampled 3 and 6 months after irradiation and bone marrow transplant. The results indicated that (a) poly I:C administered in the peritransplant period (before and after transplant) significantly increases the absolute numbers of NK cells in both the bone marrow and spleen of the transplanted host at all time intervals studied, (b) no erythroleukemic tumor cells were found, even as late as 6 months after transplant in the poly-I:C-treated hosts in spite of the fact that poly I:C treatment in this group had been terminated more than 2 months prior to tissue sampling, and (c) survival was significantly improved by pre- and posttransplant treatment with poly I:C.
Natural Killer Cell Frequency and Function in Pigs Selectively Bred for High or Low Antibody and Cell-Mediated Immune Response: Response to Vaccination with Modified Live Transmissible Gastroenteritis Virus
Authors: Raymond Claudine , Wilkie Bruce N. 
Published: April 2003

Porcine NK cells are small to medium lymphocytes which are lytic for tumours and virally infected cells when co-cultured for long periods (&#8776;16 h). The frequency and function of NK cells were examined in generation 8 of pigs genetically selected for high (H), low (L), and control (C) antibody (Ab) and cell-mediated immune response (CMIR). The NK phenotype was identified using a pan-species NK-specific murine monoclonal antibody (5C6) and both binding and lysis of the NK target, K562. Vaccination with modified live transmissible gastroenteritis virus (TGEV) had no effect on blood leucocyte NK cell frequency. In interactions with K562 targets, NK cells of H and C pigs responded similarly in frequency of conjugate formation and lytic activity, while L pigs had very little or no response. Therefore, in pigs selected for high Ab and CMIR, there was no correlated enhancement of NK-cell-related traits following vaccination with TGEV, while selection for low immune response was associated with reduced NK response in pigs. This may suggest that low immune response can reflect reduced contribution of NK cells in pigs.
Uropathogenic <i>Escherichia coli</i> Toxins Induce Caspase-Independent Apoptosis in Renal Proximal Tubular Cells via ERK Signaling
Authors: Chen Ming , Jahnukainen Timo , Bao Wenjie , Daré Elisabetta , Ceccatelli Sandra , Celsi Gianni 
Published: April 2003

<i>Background:</i> Pyelonephritis is a risk factor for renal tubular epithelial cell damage. Recent studies have shown that <i>Escherichia coli</i> and/or its toxins may stimulate apoptotic cell death in renal tubular cells, but the underlying molecular mechanisms remain to be elucidated. <i>Methods:</i> Confluent LLC-PK<sub>1</sub> cells were exposed to <i>E. coli</i> toxins from overnight cultures of the uropathogenic O6K13H1 (O6) and the nonpathogenic W3110. The cell death was studied with morphological and biological assay. <i>Results:</i><i>E. coli</i> soluble toxins from uropathogenic O6:K13:H1(O6) strain were found to induce apoptosis in a dose- and time-dependent manner in LLC-PK1 cells. The expression of FasR and the phosphorylation of ERK1/2 were significantly upregulated by O6 soluble toxins in a time-dependent manner. Cell death was completely inhibited by two specific ERK1/2 inhibitors, but not by a broad caspase inhibitor, zVAD-fmk, implicating a caspase-independent pathway via ERK. Moreover, we found that lysophosphatidic acid could trigger a survival signal through G-proteins and PI3K. <i>Conclusion:</i> We demonstrate that apoptosis induced by uropathogenic <i>E. coli</i> toxins is dependent on ERK1/2. Caspases, although being activated, are not necessary for cell death, and they act after the ERK signaling at which point cells become committed to cell death or can be rescued.
Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice identify cooperating events and genetic pathways to acute promyelocytic leukemia
Authors: Le Beau Michelle M. , Davis Elizabeth M. , Patel Bhumi , Phan Vernon T. , Sohal Jastinder , Kogan Scott C. 
Published: April 2003

Abstract
Acute promyelocytic leukemia (APL) is characterized by the PML-RARA fusion gene. To identify genetic changes that cooperate with PML-RARA, we performed spectral karyotyping analysis of myeloid leukemias from transgenic PML-RARA mice and from mice coexpressing PML-RARA and BCL2, IL3, activated IL3R, or activated FLT3. A cooperating mutation that enhanced survival (BCL2) was not sufficient to complete transformation and was associated with multiple numeric abnormalities, whereas cooperating mutations that deregulated growth and enhanced survival were associated with normal karyotypes (IL3) or simple karyotypic changes (IL3R, FLT3). Recurring abnormalities included trisomy 15 (49%), trisomy 8 (46%), and -X/-Y (54%). The most common secondary abnormality in human APL is +8 or partial trisomy of 8q24, syntenic to mouse 15. These murine leukemias have a defined spectrum of changes that recapitulates, in part, the cytogenetic abnormalities found in human APL. Our results demonstrate that different cooperating events may generate leukemia via different pathways.
Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children’s Cancer Group Study
Authors: Heath John A. , Steinherz Peter G. , Altman Arnold , Sather Harland , Jhanwar Suresh , Halpern Steven , Pieters Richard , Shah Narayan , Steinherz Laurel , Tannous Raymond , Terry William , Trigg Michael E. 
Published: April 2003

Purpose: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). Patients and Methods: A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Children’s Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 μg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. Results: The mean time to neutrophil recovery (≥ 0.5 × 109/L) was reduced with G-CSF (16.7 v 19.1 days, P = .0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P = .41), positive blood cultures (57 v 61, P = .66), or serious infections (75 v 79, P = .62). Hospitalization (14.0 v 13.9 days, P = .87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P = .11; NY II, 33.4 v 32.3 days, P = .40) were not significantly altered. There were no differences in 6-year EFS (P = .24) or OS (P = .54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. Conclusion: Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.
Phase II Trial of Gemcitabine in Refractory or Relapsed Small-Cell Lung Cancer: Eastern Cooperative Oncology Group Trial 1597
Authors: Masters Gregory A. , Declerck Lieven , Blanke Charles , Sandler Alan , DeVore Russell , Miller Kathy , Johnson David 
Published: April 2003

Purpose: Gemcitabine has shown a broad range of activity in solid tumors, including previously untreated small-cell lung cancer (SCLC). The objective of this phase II trial was to investigate the activity of gemcitabine in patients with relapsed SCLC. Patients and Methods: SCLC patients with measurable disease who had experienced treatment failure with one prior chemotherapy regimen were considered eligible. Patients were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and adequate organ function; signed informed consent was also required. Treatment consisted of gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Patients were stratified according to their previous response to first-line chemotherapy (primary refractory v primary sensitive disease). Results: Forty-six patients were enrolled onto this phase II trial (20 refractory and 26 sensitive patients). Forty-two of these patients were assessable for response and survival, and 44 were assessable for toxicity. Median patient age was 60 years, and median ECOG performance status was 1. Principal grade 3/4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (27%). The main grade 3/4 nonhematologic toxicities were pulmonary (9%) and neurologic toxicity (14%). Objective responses occurred in 11.9% of patients overall, including one patient with refractory SCLC (5.6%) and four patients with sensitive SCLC (16.7%). Median survival for the overall group was 7.1 months. Survival was not significantly different for patients with refractory versus sensitive disease. Conclusion: Gemcitabine has modest activity in previously treated SCLC patients. The favorable toxicity profile warrants further investigation, either in combination chemotherapy regimens or with targeted biologic compounds.
Enrollment of Older Patients in Cancer Treatment Trials in Canada: Why is Age a Barrier?
Authors: Yee Karen W.L. , Pater Joseph L. , Pho Lam , Zee Benny , Siu Lillian L. 
Published: April 2003

Purpose: To evaluate the enrollment of older patients (≥ 65 years) in Canadian cancer treatment trials and compare accrual of older patients in Canada and the United States. Patients and Methods: A retrospective analysis of the number of older patients enrolled in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) treatment trials between 1993 and 1996 was performed. These rates were compared with the corresponding rates in the general population of patients who were ≥ 65 years old and had cancer, obtained from Statistics Canada, and those published by the Southwest Oncology Group (SWOG) in the United States. Results: Between 1993 and 1996, 4,174 patients were enrolled onto 69 NCIC CTG trials of 16 tumor types. Older patients accounted for 22% of trial enrollees, compared with 58% of the Canadian population with cancer. This discrepancy existed in all cancer types except for multiple myeloma. The percentages of older patients enrolled were also analyzed by study type: 15% in adjuvant trials, 25% in metastatic trials, 29% in investigational new drug trials, 24% in phase I trials, and 21% in supportive care trials. The overall proportion of older patients enrolled onto Canadian trials (22%) was slightly lower than that in SWOG trials (25%). Conclusion: Age remains a barrier for accrual onto cancer treatment trials, even when reimbursement is not an issue. Strategies to overcome this barrier, including the implementation of trials specifically tailored to patients aged ≥ 65 years, are prudent in light of our aging population.
Separating a Superclass of Comb Inequalities in Planar Graphs
Authors: Letchford Adam N. 
Published: April 2003

Many classes of valid and facet-inducing inequalities are known for the family of polytopes associated with the Symmetric Travelling Salesman Problem (STSP), including subtour elimination, 2-matching and comb inequalities. For a given class of inequalities, an exact separation algorithm is a procedure which, given an LP relaxation vector x*, finds one or more inequalities in the class which are violated by x*, or proves that none exist. Such algorithms are at the core of the highly successful branch-and-cut algorithms for the STSP. However, whereas polynomial time exact separation algorithms are known for subtour elimination and 2-matching inequalities, the complexity of comb separation is unknown. A partial answer to the comb problem is provided in this paper. We define a generalization of comb inequalities and show that the associated separation problem can be solved efficiently when the subgraph induced by the edges with x*e > 0 is planar. The separation algorithm runs in 𝒪(n3) time, where n is the number of vertices in the graph.
Information Privacy: Corporate Management and National Regulation
Authors: Milberg Sandra J. , Smith H. Jeff , Burke Sandra J. 
Published: April 2003

The 1990s have seen a resurgence of interest in information privacy. Public opinion surveys show that many citizens are becoming greatly concerned about threats to their information privacy, with levels of such concern reaching all-time highs. Perhaps as a response to the growing concerns of citizens, the media are devoting more attention to privacy issues, and governmental regulation of the corporate privacy environment is increasing in many countries. Almost all developed countries have grappled with the trade-offs between open access to information—which enables economic efficiency—and an individual's right to privacy. Consistent with these trade-offs, many recent incidents suggest that regulatory approaches to information privacy, corporate management of personal data, and consumer reactions are becoming tightly interwoven around the world. To provide some insights into these relationships, we develop a conceptual model and test it with a cross-cultural sample from 19 different countries. In general, we find that a country's regulatory approach to the corporate management of information privacy is affected by its cultural values and by individuals' information privacy concerns. In addition, as governments become more involved in the corporate management of information privacy, internal management of such issues seems to tighten. This result supports previous observations that most firms take a primarily reactive approach to managing privacy by waiting for an external threat before crafting cohesive policies that confront their information practices. Moreover, when corporations are not perceived to adequately manage information privacy issues, and/or when privacy concerns rise, individuals are more inclined to prefer government intervention and be distrustful of firm self-regulation. As such, citizens may look to lawmakers to enact stricter regulation to reduce their privacy concerns. These findings and several international trends suggest that the self-regulatory model of privacy governance may not be sustainable over the long term. Findings from this research constitute an important contribution to the emerging theoretical base of information privacy research and should be particularly enlightening to those managing information privacy issues. Several directions for future research are also discussed.