bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence of cold activation of transfusion plasma during storage at +4 °C
Authors: Suontaka A. M. , Silveira A. , Söderström T. , Blombäck M. 
Published: March 2005

Background and Objectives  The storage of transfusion plasma at +4 °C sometimes leads to the activation of several proteolytic systems. In this study the frequency of cold activation was investigated, as well as whether cold activation of plasma is an individually recurrent property of the donor.Materials and Methods  Plasma units prepared from whole blood obtained from 100 male donors were stored at +2° to +5 °C, in bags for 28 days and in cryotubes for up to 42 days. Samples from plasma units, collected by apheresis from 100 male donors, were stored in cryotubes for up to 42 days. Cold activation was measured weekly as kallikrein‐like activity of plasma. Samples from repeat apheresis plasma units from 32 donors were measured 12–20 months later. The effects of storage on the contact, coagulation and fibrinolytic systems were determined.Results  The cumulative frequency of cold‐activated plasma units stored in bags was 5% on day 7 and 18% on day 28. After 42 days in cryotubes, 49% of the plasma units were cold activated. Large intraindividual differences in the onset‐day of cold activation were observed in plasma samples of some donors. During cold activation, an increase in kallikrein‐like activity was accompanied by a decrease in C1 esterase inhibitor activity and an increase in the concentrations of activated factor VII and fibrinopeptide A. The functional plasminogen level was unchanged, while a minor decrease in plasmin inhibitor activity was combined with a corresponding increase in the concentration of plasmin–plasmin inhibitor complex.Conclusions  The cumulative frequency of cold‐activated plasma units increased in a time‐dependent manner during storage at +2° to +5 °C for 42 days. The intraindividual onset‐day of cold activation varied widely between plasma samples of some donors. Cold activation was associated with a high degree of activation of the contact and coagulation systems. The fibrinolytic system was scarcely affected.
Why Have Workers Stopped Joining Unions? The Rise in Never‐Membership in Britain
Authors: Bryson Alex , Gomez Rafael 
Published: March 2005

AbstractThis paper tracks the rise in the percentage of employees who have never become union members (‘never‐member’) since the early 1980s and shows that it is the reduced likelihood of ever becoming a member, rather than the haemorrhaging of existing members, that is behind the decline in overall union membership in Britain. We estimate the determinants of ‘never‐membership’ and consider how much of the rise can be explained by structural change in the labour market and how much by change in preferences among employees.
Cardiovascular risk at age 53 years in relation to the menopause transition and use of hormone replacement therapy: a prospective British birth cohort study
Authors: Kuh D. , Langenberg C. , Hardy R. , Kok H. , Cooper R. , Butterworth S. , Wadsworth M.E.J. 
Published: March 2005

Objectives  To investigate cardiovascular risk factors and changes in risk factor levels in relation to menopausal stage, hysterectomy status and hormone replacement therapy use in a cohort of women aged 53 years with prospective data on smoking, lifetime socio‐economic circumstances, and blood pressure and obesity at age 43 years.Design  A prospective study.Setting  England, Scotland and Wales.Population  A cohort of women from the Medical Research Council Survey of Health and Development.Methods  A total of 1303 women, aged 53 years, from a UK birth cohort study with measures of cardiovascular risk factors were classified by five menopausal status groups (premenopause, perimenopause, postmenopause, hysterectomy and hormone replacement therapy user). Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol measurements were taken, and analysed within the groups taking confounding variables into account. Changes in body mass index and blood pressure measurement in the same women obtained when 43 years of age were also compared.Main outcome measures  Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol.Results  At 53 years, body mass index, waist circumference, total and low density lipoprotein cholesterol, and glycosolated haemoglobin (HbA1c) varied by menopausal status group, but blood pressure did not. Levels of total cholesterol and HbA1c increased across the natural menopause transition, before and after adjustment for body mass index, smoking and lifetime socio‐economic circumstances. After adjustment for confounders, levels of risk factors for hysterectomised women were similar to those of naturally postmenopausal women. Women on hormone replacement therapy had lower levels of total and low density lipoprotein cholesterol, HbA1c, and were less obese than postmenopausal women. The lower obesity levels were partly due to these women already being less obese at age 43 years.Conclusions  This study showed that naturally postmenopausal or hysterectomised women had higher levels of metabolic risk factors compared with premenopausal or perimenopausal women of the same age. The long term stability of these differences and their translation into variations in incidence of cardiovascular disease remain to be seen. The lower levels of metabolic risk factors for women on hormone replacement therapy may protect against future cardiovascular disease or may be overwhelmed by other adverse, and as yet unknown, effects of hormone replacement therapy.
Effects of intense training during and after pregnancy in top‐level athletes
Authors: Kardel Kristin Reimers 
Published: March 2005

This study investigates the effects of vigorous exercise during and after pregnancy in top competitive athletes. The hypothesis tested here is that training of sufficiently high volume during pregnancy can maintain initial fitness levels. A second hypothesis, that high‐volume training during pregnancy in initially fit women does not pose a health risk for the mother or the fetus, was tested and found to hold in a prior report. The overall aim of the study was to define a safe training regime for the maintenance of fitness in top‐level female athletes during pregnancy.Forty‐one healthy athletes who had performed exercise regularly prior to conception were followed from gestational week 17 until 12 weeks postpartum while they performed standardized exercise programs. The subjects participated either in a high‐volume exercise group (HEG, n=20, 8.4 h week−1) or in a medium‐volume exercise group (MEG, n=21, 6 h week−1).The results show that well‐trained women can benefit substantially from training at high volumes during an uncomplicated pregnancy. This can facilitate a rapid return to competitive athletics and physically active life after pregnancy. Guidelines for safe exercise by sufficiently fit women during pregnancy could be modeled on the high‐volume exercise regime used here by the HEG.
A prospective analysis of incidence and severity of quadriceps inhibition in a consecutive sample of 100 patients with complete acute anterior cruciate ligament rupture
Authors: Chmielewski T. L. , Stackhouse S. , Axe M. J. , Snyder‐Mackler L. 
Published: March 2005

Background: Weakness of the quadriceps femoris muscle after anterior cruciate ligament (ACL) injury and reconstruction has been attributed to incomplete voluntary activation of the muscle. The literature is conflicting on the incidence of incomplete voluntary quadriceps activation after ACL injury because of differences in testing methods and population biases. The purpose of this study was to systematically examine the incidence and severity of quadriceps voluntary activation failure in both lower extremities after acute ACL injury. We hypothesized that the incidence of quadriceps inhibition would be higher in the ACL‐injured limbs than the uninvolved limbs, that the incidence of inhibition in the ACL‐deficient limbs would be larger than in our historical sample of healthy young individuals tested in the same manner and that there would be no difference in inhibition by gender.Study Design: Prospective, descriptive.Methods: One hundred consecutive patients with acute ACL rupture (39 women and 61 men) were tested when range of motion was restored and effusion resolved, an average of 6 weeks after injury. A burst superimposition technique was used to assess quadriceps muscle activation and strength in all patients. Dependent t‐tests were used to compare side‐to‐side differences in quadriceps strength. Independent t‐tests were used to compare incidence of activation failure by gender and make comparisons to historical data on young, active individuals.Results: The average involved side quadriceps activation was 0.92, and ranged from 0.60 to 1.00. The incidence of incomplete activation in the involved side quadriceps was 33 percent and in the uninvolved side quadriceps was 31 percent after acute ACL rupture. The incidence of incomplete activation bilaterally was 21 percent. There was no difference in incidence of quadriceps inhibition by gender.Conclusion: The incidence of voluntary quadriceps inhibition on the involved side was three times that of uninjured, active young subjects, but the magnitude was not large. The incidence of quadriceps inhibition on the uninjured side was similar to the injured side.Clinical relevance: Both the incidence and magnitude of quadriceps inhibition after ACL rupture are lower than have previously been reported. The conventional wisdom, therefore, that quadriceps inhibition is a significant problem in this population is challenged by the results of this study. Differences between this study and others include sufficient practice to ensure a maximal effort contraction and rigorous inclusion criteria. The findings have implications for strength testing as well as rehabilitation. The quadriceps index, an assessment of the injured side quadriceps strength deficit, may be affected by the presence of voluntary activation failure in the uninvolved side.
A novel firmicute protein family related to the actinobacterial resuscitation-promoting factors by non-orthologous domain displacement
Authors: Ravagnani Adriana , Finan Christopher L , Young Michael 
Published: March 2005

Abstract
Background
In Micrococcus luteus growth and resuscitation from starvation-induced dormancy is controlled by the production of a secreted growth factor. This autocrine r esuscitation-p romoting f actor (Rpf) is the founder member of a family of proteins found throughout and confined to the actinobacteria (high G + C Gram-positive bacteria). The aim of this work was to search for and characterise a cognate gene family in the firmicutes (low G + C Gram-positive bacteria) and obtain information about how they may control bacterial growth and resuscitation.

Results
In silico analysis of the accessory domains of the Rpf proteins permitted their classification into several subfamilies. The RpfB subfamily is related to a group of firmicute proteins of unknown function, represented by YabE of Bacillus subtilis. The actinobacterial RpfB and firmicute YabE proteins have very similar domain structures and genomic contexts, except that in YabE, the actinobacterial Rpf domain is replaced by another domain, which we have called Sps. Although totally unrelated in both sequence and secondary structure, the Rpf and Sps domains fulfil the same function. We propose that these proteins have undergone "non-orthologous domain displacement", a phenomenon akin to "non-orthologous gene displacement" that has been described previously. Proteins containing the Sps domain are widely distributed throughout the firmicutes and they too fall into a number of distinct subfamilies. Comparative analysis of the accessory domains in the Rpf and Sps proteins, together with their weak similarity to lytic transglycosylases, provide clear evidence that they are muralytic enzymes.

Conclusions
The results indicate that the firmicute Sps proteins and the actinobacterial Rpf proteins are cognate and that they control bacterial culturability via enzymatic modification of the bacterial cell envelope.
The role of the cytoskeleton in cell body enlargement, increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons
Authors: McIlwain David L , Hoke Victoria B 
Published: March 2005

Abstract
Background
When spinal motor axons are injured, the nucleolus, nucleus and cell body of the injured cell transiently increase in size, the nucleus becomes more eccentrically placed, and the organization of polyribosomes into Nissl bodies is temporarily disrupted. The mechanisms for these classical morphological responses to axotomy have not been satisfactorily explained.

Results
In this study we address the role of the cell body cytoskeleton in these structural changes. We show that the cytoskeleton of uninjured lumbar motor neuron cell bodies maintains nucleolar, nuclear and cell body size and nuclear position. When isolated, the relatively insoluble cell body cytoskeleton contains Nissl bodies and lipofuscin granules. After axotomy, protein labeling increases markedly and the cytoskeleton enlarges, increasing nucleolar, nuclear and cell body size, as well as nuclear eccentricity. Nearly all of the protein mass that accumulates in the cell body after axotomy appears to be added to the cytoskeleton.

Conclusion
We conclude that axotomy causes the conjugate enlargement of the nucleolus, nucleus and cell body and increases nuclear eccentricity in spinal motor neurons by adding protein to the cytoskeleton. The change in nuclear position, we propose, occurs when cytoskeletal elements of the axon cannot enter the shortened axon and "dam up" between the nucleus and axon hillock. As a consequence, we suggest that Nissl body-free axonal cytoskeleton accumulates between the nucleus and axon, displaces Nissl body-containing cytoskeleton, and produces central chromatolysis in that region of the cell.
Current and future developments in managed care in the United States and implications for Europe
Authors: Lagoe Ronald , Aspling Deborah L , Westert Gert P 
Published: March 2005

Abstract
The paper reviews and evaluates current and future approaches to cost containment in the United States. Managed care was once seen as an effective approach to supporting health care quality while containing costs in the USA. In recent years payors started to look in other directions, since prospects for limiting expenses faded. Nowadays consumer driven health plans seem to be on the rise. The reasons for the decline of managed care, the growing popularity of the consumer driven health plans and the implications for Europe are discussed.
Phase III Southwest Oncology Group 9415/Intergroup 0153 Randomized Trial of Fluorouracil, Leucovorin, and Levamisole Versus Fluorouracil Continuous Infusion and Levamisole for Adjuvant Treatment of Stage III and High-Risk Stage II Colon Cancer
Authors: Poplin Elizabeth A. , Benedetti Jacqueline K. , Estes Norman C. , Haller Daniel G. , Mayer Robert J. , Goldberg Richard M. , Weiss Geoffrey R. , Rivkin Saul E. , Macdonald John S. 
Published: March 2005

Purpose Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer. Patients and Methods After surgery, patients were randomly assigned to CIFU 250 mg/m2/d for 56 days every 9 weeks for three cycles or FU 425 mg/m2 and LV 20 mg/m2 daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS). Results The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1,135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively. Conclusion CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV.
Psychological Impact of Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer
Authors: Gritz Ellen R. , Peterson Susan K. , Vernon Sally W. , Marani Salma K. , Baile Walter F. , Watts Beatty G. , Amos Christopher I. , Frazier Marsha L. , Lynch Patrick M. 
Published: March 2005

Purpose This study examines the impact of hereditary nonpolyposis colorectal cancer (HNPCC) genetic test results on psychological outcomes among cancer-affected and -unaffected participants up to 1 year after results disclosure. Patients and Methods A total of 155 persons completed study measures before HNPCC genetic testing, and at 2 weeks and 6 and 12 months after disclosure of test results. Results Mean scores on all outcome measures remained stable and within normal limits for cancer-affected participants, regardless of mutation status. Among unaffected carriers of HNPCC-predisposing mutations, mean depression, state anxiety, and cancer worries scores increased from baseline to 2 weeks postdisclosure and decreased from 2 weeks to 6 months postdisclosure. Among unaffected noncarriers, mean depression and anxiety scores did not differ, but cancer worries scores decreased during the same time period. Affected and unaffected carriers had higher mean test-specific distress scores at 2 weeks postdisclosure compared with noncarriers in their respective groups; scores decreased for affected carriers and all unaffected participants from 2 weeks to 12 months postdisclosure. Classification of participants into high- versus low-distress clusters using mean scores on baseline psychological measures predicted significantly higher or lower follow-up scores, respectively, on depression, state anxiety, quality of life, and test-specific distress measures, regardless of mutation status. Conclusion Although HNPCC genetic testing does not result in long-term adverse psychological outcomes, unaffected mutation carriers may experience increased distress during the immediate postdisclosure time period. Furthermore, those with higher levels of baseline mood disturbance, lower quality of life, and lower social support may be at risk for both short- and long-term increased distress.
Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin in Adult Patients With Solid Tumors
Authors: Grem Jean L. , Morrison Geraldine , Guo Xiao-Du , Agnew Elizabeth , Takimoto Chris H. , Thomas Rebecca , Szabo Eva , Grochow Louise , Grollman Frank , Hamilton J. Michael , Neckers Len , Wilson Richard H. 
Published: March 2005

Purpose To determine the clinical toxicities of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) given as a 1-hour infusion daily for 5 days every 3 weeks. Patients and Methods Nineteen patients received 17-AAG over six dose levels (10 to 56 mg/m2) using an accelerated titration scheme. Drug levels of 17-AAG were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored by changes in the content of target proteins by immunoblot analysis of lysates prepared from peripheral-blood mononuclear cells. Results Toxicity was acceptable at doses up to 28 mg/m2. The cohort was expanded to three patients at 40 mg/m2 because a second occurrence of grade 2 hepatic transaminitis occurred. Two of six assessable patients who received 56 mg/m2 had reversible, grade 3 hepatic transaminitis. Five additional patients were enrolled at 40 mg/m2; none had dose-limiting toxicity. The maximum plasma concentrations (Cmax) of 17-AAG at 40 and 56 mg/m2 were 1,724 and 2,046 ng/mL, respectively; the average plasma exposures (AUC) were 2,809 and 6,708 hours·ng/mL, respectively. Less than 3% of the daily dose was excreted into the urine. Clearance did not correlate with body-surface area. Possible biologic activity was suggested by apparent increased protein content of either glucose-related 78 kd protein or heat shock protein 70 with ≥ 14 mg/m2 and decreased protein content of either Lck or Raf1 with ≥ 28 mg/m2 of 17-AAG. Conclusion 17-AAG 40 mg/m2 (median dose, 70 mg) was well tolerated when given daily for 5 days every 3 weeks.
Pulses of Prolactin Promoter Activity Depend on a Noncanonical E-Box that Can Bind the Circadian Proteins CLOCK and BMAL1
Authors: Leclerc Gilles M. , Boockfor Fredric R. 
Published: March 2005

AbstractRecent findings from our laboratory and those of others demonstrated that prolactin gene expression (PRL-GE) oscillates in single living mammotropes, but little information is available on the molecular processes that contribute to this phenomenon. To elucidate the source of this activity, we generated a series of constructs containing decreasing lengths of the PRL promoter fused to a luciferase reporter gene. These constructs were injected into single cells and assayed for photonic activity. We found pulse activity with all plasmids tested, even with the smallest promoter fragment of 331 bp. Sequence analysis of this fragment identified two potential E-boxes (elements known to bind CLOCK and BMAL1 circadian proteins). Furthermore, RT-PCR of PRL cells (pituitary, MMQ, and GH3) revealed expression of clock and bmal1 as well as five other clock genes (per1, per2, cry1, cry2, and tim), suggesting that the circadian system may function in PRL cells. Next, we mutated the core sequences of both E-boxes within the 2.5-kb PRL promoter and found that only mutation of the E-box133 completely abolished PRL-GE pulses. EMSAs revealed that CLOCK and BMAL1 were able to bind to the E-box133 site in vitro. Our results demonstrate that PRL-GE pulses are dependent on a specific E-box binding site in the PRL promoter. Moreover, the indication that CLOCK/BMAL1 can bind to this site suggests that these circadian proteins, either alone or in conjunction with other factors, may regulate intermittent PRL promoter activity in mammotropes, perhaps by acting as a temporal switch for the on/off expression of PRL.