bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sharing BRCA1/2 Test Results With First-Degree Relatives: Factors Predicting Who Women Tell
Authors: Patenaude Andrea Farkas , Dorval Michel , DiGianni Lisa S. , Schneider Katherine A. , Chittenden Anu , Garber Judy E. 
Published: January 2006

Purpose Patient communication with relatives about cancer genetic test results is the primary means for alerting those who may benefit from identification of hereditary risk. This study identifies factors predicting patterns of disclosure of BRCA1/2 test results to first-degree relatives (FDRs) among women tested in a clinical protocol. Patients and Methods A total of 273 women completed a family communication measure 4 months after BRCA1/2 result disclosure. χ2 analyses and logistic regression models identified factors predicting sharing of the test result. Results Most FDRs were informed of the participant's test result by 4 months; female relatives were more likely to be informed than males. Tested women conveyed inconclusive results (variant or negative without known familial mutation) less frequently to their sisters than conclusive (positive/true negative) results (P = .03). Twenty-three percent of participants did not inform their father. Informing brothers was more likely when BRCA1/2 was inherited through paternal lineage (P = .04), but 29% of brothers were not informed. Women older than age 40 were less likely to share their result with their parents (P = .03) than were women ≤ 40. Children's ages influenced communication to offspring; most children were told. Conclusion Demographic, health-, and test-related factors predicted genetic test result communication to FDRs. Additional research investigating the full spectrum of discussion within families and motives for incomplete sharing of genetic test results with relatives may suggest strategies for providers and targeted educational interventions for patients to enhance family communication.
Optimal Selection of Individuals for BRCA Mutation Testing: A Comparison of Available Methods
Authors: James Paul A. , Doherty Rebecca , Harris Marion , Mukesh Bickol N. , Milner Alvin , Young Mary-Anne , Scott Clare 
Published: January 2006

Purpose Several methods have been described that estimate the likelihood that a family history of cancer is a result of a mutation in the BRCA1 or BRCA2 genes. We examined the performance of six different methods with the aim of identifying an optimal strategy for selecting individuals for mutation testing in clinical practice. Patients and Methods Two hundred fifty-seven families who had completed BRCA1 and BRCA2 mutation screening were assessed by six models representing the major methodologies used to assess the likelihood of a pathogenic mutation. The performance of each method as a selection criterion was compared with the result of mutation testing to produce sensitivity, specificity, and receiver operating curve data. The impact of incorporating breast cancer pathology data in the assessment was also analyzed. Results The highest accuracy was achieved by the Bayesian probabilistic model (BRCAPRO). The formal probabilistic methods were significantly more accurate than clinical scoring methods. The methods were further improved by the incorporation of information on breast cancer pathology (tumor grade and estrogen receptor/progesterone receptor status). The resulting combined probability figure was highly accurate when selecting individuals for BRCA1 testing. Some BRCA2 mutation carriers were missed by all of the models examined. Conclusion Formal probabilistic models provide significantly greater accuracy in the selection of families for gene testing than the use of clinical criteria or scoring methods. The accuracy is further enhanced by incorporating information on the pathology of breast cancers occurring in the families.
Tamoxifen Treatment After Adjuvant Chemotherapy Has Opposite Effects on Bone Mineral Density in Premenopausal Patients Depending on Menstrual Status
Authors: Vehmanen Leena , Elomaa Inkeri , Blomqvist Carl , Saarto Tiina 
Published: January 2006

Purpose Adjuvant chemotherapy followed by tamoxifen is a standard treatment option for women with intermediate or high-risk hormone receptor–positive breast cancer. Premenopausal women treated with chemotherapy often develop early menopause and thus, enter a period of accelerated bone loss. We conducted a prospective study of the effect of sequential adjuvant therapy with chemotherapy followed by tamoxifen on bone mineral density (BMD) in premenopausal patients. Patients and Methods One hundred eleven premenopausal women with early breast cancer were treated with adjuvant chemotherapy. Patients with hormone receptor–positive tumors went on to tamoxifen 6 months after the beginning of the chemotherapy (tamoxifen group), while those with hormone receptor–negative tumors received no further therapy (control group). The effect of tamoxifen and menstrual status on BMD was studied. Results Tamoxifen treatment and menopausal status correlated significantly with the changes in lumbar spine BMD (P < .0001). A significant bone loss was noted in those tamoxifen-treated patients who continued to menstruate after chemotherapy. At 3 years of follow-up, menstruating patients on tamoxifen had lost −4.6% of their baseline BMD values, while a modest gain of +0.6% was noted in the control group. In contrast, bone loss was reduced among tamoxifen-treated women as compared with controls in patients who developed chemotherapy-induced early menopause. In amenorrheic patients, the lumbar spine BMD values decreased −6.8% in tamoxifen users and −9.5% in the controls, respectively. Conclusion We conclude that tamoxifen usage was associated with bone loss in patients who continued to menstruate after adjuvant chemotherapy. On the contrary, tamoxifen decreased bone loss in those women who developed chemotherapy-induced amenorrhea.
Neoadjuvant Capecitabine and Oxaliplatin Followed by Synchronous Chemoradiation and Total Mesorectal Excision in Magnetic Resonance Imaging–Defined Poor-Risk Rectal Cancer
Authors: Chau Ian , Brown Gina , Cunningham David , Tait Diana , Wotherspoon Andrew , Norman Andrew R. , Tebbutt Niall , Hill Mark , Ross Paul J. , Massey Alison , Oates Jacqueline 
Published: January 2006

Purpose To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed patients with magnetic resonance imaging (MRI) –defined poor-risk rectal cancer. Patients and Methods MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3 tumors at or below levators, tumors extending ≥ 5 mm into perirectal fat, T4 tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy. TME was planned 6 weeks after CRT. Postoperatively, patients received another 12 weeks of capecitabine. Results Between November 2001 and August 2004, 77 eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the radiologic response rate was 88%. In addition, 86% of patients had symptomatic responses in a median of 32 days (ie, just over one cycle of capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to 97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME, and all but one patient had R0 resection. Pathologic complete response was observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32 patients (48%), only microscopic tumor foci were found on surgical specimens. Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism, ischemic heart disease, sudden death with history of chest pain, and neutropenic colitis. Conclusion Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.
Pregnancy Among Patients With Chronic Myeloid Leukemia Treated With Imatinib
Authors: Ault Patricia , Kantarjian Hagop , O'Brien Susan , Faderl Stefan , Beran Miloslav , Rios Mary Beth , Koller Charles , Giles Francis , Keating Michael , Talpaz Moshe , Cortes Jorge 
Published: January 2006

Purpose Imatinib has potential teratogenicity in animals, but the effect of exposure to imatinib during conception and pregnancy in humans is not known. Patients and Methods The records of all patients with chronic myeloid leukemia (CML) treated with imatinib were reviewed. We report the experience on 19 pregnancies involving 18 patients (10 females and eight males) who conceived while receiving imatinib for the treatment of CML. Results All female patients discontinued therapy immediately on recognition of pregnancy. Three pregnancies (involving two female patients and one male patient) ended in spontaneous abortion, and one patient had an elective abortion. All other pregnancies were uneventful. Two of the 16 babies had minor abnormalities at or shortly after birth (hypospadias in one baby and rotation of small intestine in one baby) that were surgically repaired. All babies have continued normal growth and development. Among female patients who interrupted therapy, five of nine in complete hematologic remission (CHR) at the time of treatment interruption eventually lost CHR, and six experienced an increase in Philadelphia chromosome–positive metaphases. At a median of 18 months after resuming therapy with imatinib, eight patients had a cytogenetic response (complete in three patients). Conclusion Although there is no evidence that a brief exposure to imatinib during conception and pregnancy adversely affects the developing fetus, most patients lose their response after treatment interruption. Patients receiving imatinib should be advised to practice adequate contraception.
Impacting Quality of Life for Patients With Advanced Cancer With a Structured Multidisciplinary Intervention: A Randomized Controlled Trial
Authors: Rummans Teresa A. , Clark Matthew M. , Sloan Jeff A. , Frost Marlene H. , Bostwick John Michael , Atherton Pamela J. , Johnson Mary E. , Gamble Gail , Richardson Jarrett , Brown Paul , Martensen James , Miller Janis , Piderman Katherine , Huschka Mashele , Girardi Jean , Hanson Jean 
Published: January 2006

Purpose The primary goal of this study was to evaluate the feasibility and effectiveness of a structured, multidisciplinary intervention targeted to maintain the overall quality of life (QOL), which is more comprehensive than psychosocial distress, of patients undergoing radiation therapy for advanced-stage cancer. Patients and Methods Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0% to 50% were randomly assigned to either an eight-session structured multidisciplinary intervention arm or a standard care arm. The eight 90-minute sessions addressed the five domains of QOL including cognitive, physical, emotional, spiritual, and social functioning. The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale (Linear Analog Scale of Assessment or modified Spitzer Uniscale). QOL was assessed at baseline, week 4 (end of multidisciplinary intervention), week 8, and week 27. Results Of the 103 participants, overall QOL at week 4 was maintained by the patients in the intervention (n = 49), whereas QOL at week 4 significantly decreased for patients in the control group (n = 54). This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group (P = .009). Intervention participants maintained their QOL, and controls gradually returned to baseline by the end of the 6-month follow-up period. Conclusion Although intervention participants maintained and actually improved their QOL during radiation therapy, control participants experienced a significant decrease in their QOL. Thus, a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment.
Constrained optimization in human running
Authors: Gutmann Anne K. , Jacobi Brian , Butcher Michael T. , Bertram John E. A. 
Published: January 2006

SUMMARYWalking humans spontaneously select different speed, frequency and step length combinations, depending on which of these three parameters is specified. This behavior can be explained by constrained optimization of cost of transport (metabolic cost/distance) where cost of transport is seen as the main component of an underlying objective function that is minimized within the limitations of specified constraints. It is then of interest to ask whether or not such results are specific to walking only, or indicate a more general feature of locomotion control. The current study examines running gait selection within the framework of constrained optimization by comparing self-selected running gaits to the gaits predicted by constrained optimization of a cost surface constructed from cost data available in the literature. Normalizing speed and frequency values in the behavioral data by preferred speed and frequency reduced inter-subject variability and made group behavioral trends more visible. Although actual behavior did not coincide exactly with running cost optimization, self-selected gait and predictions from the general human cost surface did agree to within the 95% confidence interval and the region of minimal cost+0.005 ml O2 kg-1m-1. This was similar to the level of agreement between actual and predicted behavior observed in walking. Thus, there seems to be substantial evidence to suggest that (i) selection of gait parameters in running can largely be predicted using constrained optimization, and (ii) general cost surfaces can be constructed using metabolic data from one group that will largely predict the behavior of other groups.
A potassium channel (Kv4) cloned from the heart of the tunicateCiona intestinalisand its modulation by a KChIP subunit
Authors: Salvador-Recatalà Vicenta , Gallin Warren J. , Abbruzzese Jennifer , Ruben Peter C. , Spencer Andrew N. 
Published: January 2006

SUMMARYVoltage-gated ion channels of the Kv4 subfamily produce A-type currents whose properties are tuned by accessory subunits termed KChIPs, which are a family of Ca2+ sensor proteins. By modifying expression levels and the intrinsic biophysical properties of Kv4 channels, KChIPs modulate the excitability properties of neurons and myocytes. We studied how a Kv4 channel from a tunicate, the first branching clade of the chordates, is modulated by endogenous KChIP subunits. BLAST searches in the genome of Ciona intestinalis identified a single Kv4 gene and a single KChIP gene, implying that the diversification of both genes occurred during early vertebrate evolution, since the corresponding mammalian gene families are formed by several paralogues. In this study we describe the cloning and characterization of a tunicate Kv4 channel, CionaKv4, and a tunicate KChIP subunit, CionaKChIP. We demonstrate that CionaKChIP strongly modulates CionaKv4 by producing larger currents that inactivate more slowly than in the absence of the KChIP subunit. Furthermore, CionaKChIP shifted the midpoints of activation and inactivation and slowed deactivation and recovery from inactivation of CionaKv4. Modulation by CionaKChIP requires the presence of the intact N terminus of CionaKv4 because, except for a minor effect on inactivation, CionaKChIP did not modulate CionaKv4 channels that lacked amino acids 2-32. In summary, our results suggest that modulation of Kv4 channels by KChIP subunits is an ancient mechanism for modulating electrical excitability.
Effect of pH on the rate of myosin head detachment in molluscan catch muscle: are myosin heads involved in the catch state?
Authors: Höpflinger Marion Christine , Andruchova Olena , Andruchov Oleg , Grassberger Herbert , Galler Stefan 
Published: January 2006

SUMMARY
Moderate alkalisation is known to terminate the catch state of bivalve mollusc smooth muscles such as the anterior byssus retractor muscle (ABRM) of Mytilus edulis L. In the present study, we investigated the effect of moderate alkalisation (pH 7.2-7.7 vs control pH 6.7) on the myosin head detachment rate in saponin-skinned fibre bundles of ABRM in order to investigate the possible role of myosin heads in the force maintenance during catch. The detachment rate of myosin heads was deduced from two types of experiments. (1) In stretch experiments on maximally Ca2+-activated fibre bundles (pCa 4.5), the rate of force decay after stepwise stretch was assessed. (2) In ATP step experiments, the rate of force decay from high force rigor (pCa&gt;8) was evaluated. The ATP step was induced by photolysis of caged ATP. We found that moderate alkalisation induces relaxation of skinned fibres in catch, thereby reducing both force and stiffness, whereas it does not accelerate the rate of myosin head detachment. This acceleration, however,would be expected if catch would be simply due to myosin heads remaining sustainably attached to actin filaments. Thus, the myosin heads may be less involved in catch than generally assumed. Catch may possibly depend on a different kind of myofilament interconnections, which are abolished by moderate alkalisation.
Classical conditioning of activities of salivary neurones in the cockroach
Authors: Watanabe Hidehiro , Mizunami Makoto 
Published: January 2006

SUMMARY
Secretion of saliva to aid swallowing and digestion is a basic physiological function found in many vertebrates and invertebrates. For mammals, classical conditioning of salivation in dogs was reported by Pavlov a century ago. However, conditioning of salivation or of related neural activities in non-mammalian species has not been reported. In many species of insects, salivation is regulated by salivary neurones. In this study, we found that salivary neurones of the cockroach Periplaneta americanaexhibited a strong response to sucrose solution applied to the mouth and a weak response to odours applied to an antenna, and we studied the effect of conditioning on the activities of salivary neurones. After three sets of differential conditioning trials in which an odour was presented just before the presentation of sucrose solution and the other odour was presented alone,the response of salivary neurones to sucrose-associated odour significantly increased but that to the odour presented alone was unchanged. Backward pairing trials in which an odour was presented after the presentation of sucrose solution were not effective in achieving conditioning. Our study of the change in the level of saliva secretion in response to electrical stimulation of salivary neurones suggested that the magnitude of increase in odour response of salivary neurones by conditioning is sufficient to lead to an increased level of salivation. This study suggests classical conditioning of salivation in an insect.
Suppression of Na+/K+-ATPase activity during estivation in the land snailOtala lactea
Authors: Ramnanan Christopher J. , Storey Kenneth B. 
Published: January 2006

SUMMARYEntry into the hypometabolic state of estivation requires a coordinated suppression of the rate of cellular ATP turnover, including both ATP-generating and ATP-consuming reactions. As one of the largest consumers of cellular ATP, the plasma membrane Na+/K+-ATPase is a potentially key target for regulation during estivation. Na+/K+-ATPase was investigated in foot muscle and hepatopancreas of the land snail Otala lactea, comparing active and estivating states. In both tissues enzyme properties changed significantly during estivation: maximal activity was reduced by about one-third, affinity for Mg.ATP was reduced (Km was 40% higher), and activation energy (derived from Arrhenius plots) was increased by ∼45%. Foot muscle Na+/K+-ATPase from estivated snails also showed an 80%increase in Km Na+ and a 60% increase in Ka Mg2+ as compared with active snails, whereas hepatopancreas Na+/K+-ATPase showed a 70% increase in I50 K+ during estivation. Western blotting with antibodies recognizing the alpha subunit of Na+/K+-ATPase showed no change in the amount of enzyme protein during estivation. Instead, the estivation-responsive change in Na+/K+-ATPase activity was linked to posttranslational modification. In vitro incubations manipulating endogenous kinase and phosphatase activities indicated that Na+/K+-ATPase from estivating snails was a high phosphate, low activity form, whereas dephosphorylation returned the enzyme to a high activity state characteristic of active snails. Treatment with protein kinases A, C or G could all mediate changes in enzyme properties in vitro that mimicked the effect of estivation, whereas treatments with protein phosphatase 1 or 2A had the opposite effect. Reversible phosphorylation control of Na+/K+-ATPase can provide the means of coordinating ATP use by this ion pump with the rates of ATP generation by catabolic pathways in estivating snails.
Asymmetric craniofacial remodeling and lateralized behavior in larval flatfish
Authors: Schreiber Alexander M. 
Published: January 2006

SUMMARYFlatfishes, such as flounder, are the world's most asymmetric vertebrates. It is unknown if the development of lateralized swimming behavior during metamorphosis is an adaptive response to bilaterally asymmetric eye positioning, or if this results from a vestibular response to thyroid hormone. This study describes larval development in left-sided, right-sided and bilaterally symmetric variants of southern flounder (Paralichthys lethostigma). Behavior and skull asymmetries precede metamorphosis, and the development of lateralized behaviors was independent of eye position in larvae treated with thyroid hormone and in symmetrical variants. Therefore,lateralized behavior is not an adaptive response to eye translocation, but rather must result from changing vestibular responses to thyroid hormone.
Human ATP-Binding Cassette Transporter TaqMan Low-Density Array: Analysis of Macrophage Differentiation and Foam Cell Formation
Authors: Langmann Thomas , Mauerer Richard , Schmitz Gerd 
Published: January 2006

Abstract
Background: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance.
Methods: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-μL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro–differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading.
Results: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run.
Conclusions: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.