bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of p53, inhibition of telomerase activity and induction of estrogen receptor beta are associated with the anti-growth effects of combination of ovarian hormones and retinoids in immortalized human mammary epithelial cells
Authors: Zhang Jiahui , Tu Yifan , Smith-Schneider Sallie 
Published: March 2005

AbstractBackgroundA full-term pregnancy has been associated with reduced risk for developing breast cancer. In rodent models, the protective effect of pregnancy can be mimicked with a defined regimen of estrogen and progesterone combination (E/P). However, the effects of pregnancy levels of E/P in humans and their underlying mechanisms are not fully understood. In this report, we investigated the growth inhibitory effects of pregnancy levels of E/P and both natural and synthetic retinoids in an immortalized human mammary epithelial cell line, 76N TERT cell line.ResultsWe observed that cell growth was modestly inhibited by E/P, 9-cis-retinoic acid (9-cis RA) or all-trans-retinoic acid (ATRA), and strongly inhibited by N-(4-hydroxyphenyl) retinamide (HPR). The growth inhibitory effects of retinoids were further increased in the presence of E/P, suggesting their effects are additive. In addition, our results showed that both E/P and retinoid treatments resulted in increasedRAREandp53gene activity. We further demonstrated that p53 and p21 protein expression were induced following the E/P and retinoid treatments. Furthermore, we demonstrated that while the telomerase activity was moderately inhibited by E/P, 9-cis RA and ATRA, it was almost completely abolished by HPR treatment. These inhibitions on telomerase activity by retinoids were potentiated by co-treatment with E/P, and correlated well with their observed growth inhibitory effects. Finally, this study provides the first evidence that estrogen receptor beta is up-regulated in response to E/P and retinoid treatments.ConclusionTaken together, our studies show that part of the anti-growth effects of E/P and retinoids is p53 dependent, and involve activation ofp53and subsequent induction of p21 expression. Inhibition of telomerase activity and up-regulation of estrogen receptor beta are also associated with the E/P- and retinoid-mediated growth inhibition. Our studies also demonstrate that the potency of retinoids on cell growth inhibition may be increased through combination of estrogen and progesterone treatment.
Patient-Reported Outcome and Quality of Life Instruments Database (PROQOLID): Frequently asked questions
Authors: Emery Marie-Pierre , Perrier Laure-Lou , Acquadro Catherine 
Published: March 2005

Abstract
The exponential development of Patient-Reported Outcomes (PRO) measures in clinical research has led to the creation of the Patient-Reported Outcome and Quality of Life Instruments Database (PROQOLID) to facilitate the selection process of PRO measures in clinical research. The project was initiated by Mapi Research Trust in Lyon, France. Initially called QOLID (Quality of Life Instruments Database), the project's purpose was to provide all those involved in health care evaluation with a comprehensive and unique source of information on PRO and HRQOL measures available through the Internet.
PROQOLID currently describes more than 470 PRO instruments in a structured format. It is available in two levels, non-subscribers and subscribers, at http://www.proqolid.org. The first level is free of charge and contains 14 categories of basic useful information on the instruments (e.g. author, objective, original language, list of existing translations, etc.). The second level provides significantly more information about the instruments. It includes review copies of over 350 original instruments, 120 user manuals and 350 translations. Most are available in PDF format. This level is only accessible to annual subscribers. PROQOLID is updated in close collaboration with the instruments' authors on a regular basis. Fifty or more new instruments are added to the database annually.
Today, all of the major pharmaceutical companies, prestigious institutions (such as the FDA, the NIH's National Cancer Institute, the U.S. Veterans Administration), dozens of universities, public institutions and researchers subscribe to PROQOLID on a yearly basis. More than 800 users per day routinely visit the database.
Assessing the capacity of the health services research community in Australia and New Zealand
Authors: Pirkis Jane , Goldfeld Sharon , Peacock Stuart , Dodson Sarity , Haas Marion , Cumming Jackie , Hall Jane , Boulton Amohia 
Published: March 2005

Abstract
Background
In order to profile the health services research community in Australia and New Zealand and describe its capacity, a web-based survey was administered to members of the Health Services Research Association of Australia and New Zealand (HSRAANZ) and delegates of the HSRAANZ's Third Health Services Research and Policy Conference.

Results
Responses were received from 191 individuals (68%). The responses of the 165 (86%) who conducted or managed health services research indicated that the health services research community in Australia and New Zealand is characterised by highly qualified professionals who have come to health services research via a range of academic and professional routes (including clinical backgrounds), the majority of whom are women aged between 35 and 54 who have mid- to senior- level appointments. They are primarily employed in universities and, to a lesser extent, government departments and health services. Although most are employed in full time positions, many are only able to devote part of their time to health services research, often juggling this with other professional roles. They rely heavily on external funding, as only half have core funding from their employing institution and around one third have employment contracts of one year or less. Many view issues around building the capacity of the health services research community and addressing funding deficits as crucial if health services research is to be translated into policy and practice. Despite the difficulties they face, most are positive about the support and advice available from peers in their work settings, and many are actively contributing to knowledge through academic and other written outputs.

Conclusion
If health services research is to achieve its potential in Australia and New Zealand, policy-makers and funders must take the concerns of the health services research community seriously, foster its development, and contribute to maximising its capacity through a sustainable approach to funding. There is a clear need for a strategic approach, where the health services research community collaborates with competitive granting bodies and government departments to define and fund a research agenda that balances priority-driven and investigator-driven research and which provides support for training and career development.
Recombinant Cell Ultrasensitive Bioassay for Measurement of Estrogens in Postmenopausal Women
Authors: Wang Shuping , Paris Francoise , Sultan Charles S. , Song Robert X.-D. , Demers Laurence M. , Sundaram Bhaskar , Settlage James , Ohorodnik Susan , Santen Richard J. 
Published: March 2005

A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility.
Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean ± sd, 11.9 ± 10.9 pmol/liter (SI units, 3.23 ± 2.96 pg/ml] was significantly lower than estradiol levels measured by RIA [43.7 ± 44.0 pmol/liter (11.9 ± 12.0 pg/ml)] in our volunteer subjects (P &lt; 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.
Value of Gonadotropin-Releasing Hormone Testing in the Differential Diagnosis of Androgen Deficiency in Elderly Men
Authors: Christ-Crain M. , Meier C. , Huber P. R. , Zimmerli L. , Mueller B. 
Published: March 2005

Elderly men with low testosterone (T) levels are increasingly diagnosed to have partial androgen deficiency of the aging male (PADAM). Frequently, magnetic resonance imaging is performed to exclude pituitary adenoma. The value of GnRH testing to differentiate PADAM from secondary hypogonadism is unknown.Serum levels of T as well as LH and FSH at baseline and after GnRH were evaluated in the following groups: 1) 24 elderly men with low serum T (&lt;11.7 nmol/liter), 2) 25 elderly men with normal serum T levels (&gt;11.7 nmol/liter), 3) 10 men with primary hypogonadism, 4) 24 men with secondary hypogonadism, and 5) 13 healthy young volunteers.In elderly men, T levels were lower (P &lt; 0.001) and gonadotropin levels higher (P = 0.03) compared with younger controls. LH and FSH response to GnRH was higher in elderly men with low T levels (PADAM) compared with elderly men with normal T levels (P = 0.02 and P &lt; 0.001) in the presence of similar basal gonadotropin levels. To differentiate secondary hypogonadism from PADAM with a sensitivity of 100%, a T less than 10 nmol/liter had a specificity of 50%. This specificity was improved to 75% by using a cutoff of less than or equal to 15 mU/liter increase of LH upon GnRH stimulation.Overall, decreased T levels and increased LH levels in elderly men suggest a primary Leydig cell dysfunction. In the subgroup of elderly men with low T levels, an increased LH response to GnRH with normal basal LH levels suggests additional, possibly hypothalamic changes. To exclude secondary hypogonadism in PADAM, diagnostic accuracy can be improved by using GnRH testing.
Significantly Higher Adrenocorticotropin-Stimulated Cortisol and 17-Hydroxyprogesterone Levels in 337 Consecutive, Premenopausal, Caucasian, Hirsute Patients Compared with Healthy Controls
Authors: Glintborg D. , Hermann A. P. , Brusgaard K. , Hangaard J. , Hagen C. , Andersen M. 
Published: March 2005

Objective: To investigate whether elevated ACTH-stimulated 17-hydroxyprogesterone (17OHP) levels are caused by CYP21 genetic defects or by a general adrenal hyperresponsiveness in hirsute patients.
Methods: A total of 337 hirsute patients were evaluated by Ferriman-Gallwey score, serum testosterone, ACTH-stimulated 17OHP, and cortisol during the follicular phase. A cutoff value of 16 nmol/liter for maximum ACTH-stimulated 17OHP (M17OHP) responses was defined as the upper limit of the 95% confidence interval (CI) for the 97.5 percentile in 42 female controls. All patients were offered total screening of the CYP21 gene, and 252 healthy, premenopausal women with regular menses underwent genetic screening.
Results: Patients were divided into idiopathic hirsutism (IH) (n = 180) and polycystic ovary syndrome (PCOS) (n = 157) groups. M17OHP levels were significantly higher in IH [geometric mean value (nmol/liter ± 2 sd) 12.2 (4.6–32.3)] and PCOS [11.9 (5.3–27.2)] compared with controls [8.5 (5.1–14.2)] (P &lt; 0.001). A similar percentage of IH and PCOS patients had elevated M17OHP (20.5 vs. 20.8%, not significant), and these also had significantly higher 30-min cortisol levels compared with controls (P &lt; 0.05). The prevalence of CYP21 mutations in patients was 8.6% compared with 6.3% in controls (P = 0.38). Ten of 19 carriers had M17OHP levels below the cutoff limit.
Conclusion: The significantly higher ACTH-stimulated levels of cortisol and 17OHP in hirsute patients indicated adrenal hyperresponsiveness in IH and PCOS. CYP21-carrier status could not explain the observed high prevalence of abnormal ACTH-stimulated 17OHP levels in the hirsute population.
Discovery, Clinical Development, and Therapeutic Uses of Bisphosphonates
Authors: Licata Angelo A 
Published: March 2005

OBJECTIVE: To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. DATA SOURCES: English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. STUDY SELECTION AND DATA EXTRACTION: Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. DATA SYNTHESIS: Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R1 and R2). The R1 side chain determines binding affinity to hydroxyapatite, and the R2 side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. CONCLUSIONS: The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.
Stable Isotope Ratios as a Tool in Microbial Forensics—Part 2. Isotopic Variation Among Different Growth Media as a Tool for Sourcing Origins of Bacterial Cells or Spores
Authors: Kreuzer-Martin HW , Chesson LA , Lott MJ , Dorigan JV , Ehleringer JR 
Published: March 2005

Abstract
Since the anthrax attacks of 2001 the need for methods to trace the origins of microbial agents has become urgent. The stable isotope ratios of bacteria record information from both the nutrients and the water used to make their culture media (1) and could potentially be used to provide information about their growth environment. We present a survey of carbon (C), nitrogen (N), and hydrogen (H) stable isotope ratios in 516 samples of bacteriological culture media. The observed variation was consistent with expected isotopic variation in the plant and animal products upon which the media are based. The variation is sufficient to translate into substantial isotope variation in cultures grown on different batches of media, and thus to allow investigators to determine whether seized media could have been used to produce seized bioweapons agents.
Interpretation of Postmortem Change in Cadavers in Spain
Authors: Prieto JL , Magana C , Ubelaker DH 
Published: March 2005

Abstract
Estimating time since death is especially difficult in the examination of poorly preserved cadavers and depends on the experience of the examiner and comparison with previously documented cases showing similar characteristics.
The present study reports on information obtained over the past ten years through the work of the Laboratorio de Antropología y Odontología Forense (LAF) of the Instituto Anatómico Forense de Madrid, Spain, in particular evaluating how the type of fracture influences postmortem change.
From the original 225 forensic cases examined between 1992 and 2002 in the LAF, a sample of 29 cases were selected from various regions of the Spanish mainland.
A data collection protocol was established to reflect factors which the existing specialized literature, documenting the relation existing in the sample analyzed between time since death and the extent of postmortem change, which in the environments examined are distributed into the following phases: Phase 1 (putrefaction): one week to one month on the surface and two months in water. Phase 2 (initial skeletonization): two months on the surface and five to six months in water. Phase 3 (advanced skeltonization): six months to 1.5 years on the surface and 2.5 years buried. Phase 4 (complete skeletonization): about one year on the surface and three years buried.
This paper also provide useful information on the impact of carrion insect activity, location, climate, seasonality, and predator.
Cremation Weights in East Tennessee?
Authors: Bass WM , Jantz RL 
Published: March 2005

Abstract
In spite of increasing number of cremations in the U.S., little is known about weights of cremated remains. This research was undertaken in order to add to the limited literature on cremains weights and to explore variation. Weights of cremated remains were obtained from the East Tennessee Crematorium. The sample consists of 151 males and 155 females. Age, sex, and race were obtained for each individual. Males are about 1000 g heavier than females. Both sexes lose weight with age, but females lose weight at about twice the rate of males. East Tennessee cremation weights were compared with those from Florida reported by Warren and Maples, and those from Southern California reported by Sonek. East Tennessee results were also compared with an earlier study on ash weight of anatomical human skeletons carried out by Trotter and Hixon. East Tennessee cremations weigh about 500 g more than the samples from Florida and California, and about the same as the earlier anatomical samples. We hypothesize that variation reflects variation in body weight and activity. This variation must be taken into account when cremation weights are at issue.
The Effect of Electron Beam Irradiation on Forensic Evidence. 1. Latent Print Recovery on Porous and Non-Porous Surfaces
Authors: Ramotowski RS , Regen EM 
Published: March 2005

Abstract
The recent use of the postal system as a means of delivering anthrax spores via several contaminated envelopes has led to the selective irradiation of mail. These as yet unsolved attacks and the U.S. Postal Service's decision to irradiate certain types of mail has led to some unexpected complications. The high doses of radiation required to destroy biological agents like anthrax are sufficient to induce damage to other materials present in the envelope. There have been reports of damage to many different items that have been subjected to irradiation, including paper, precious gems, plastic, computer discs, and electronics. However, few studies have examined the effect of such treatments on items of forensic interest. In this paper, the authors focused on the impact of the irradiation process on the ability to visualize latent prints. This experiment involved using several donors, substrates (both porous and non-porous), and visualization reagents. The results indicate that the irradiation process can have a detrimental effect on the success of certain visualization reagents.
The Importance of Thin Layer Chromatography and UV Microspectrophotometry in the Analysis of Reactive Dyes Released from Wool and Cotton Fibers
Authors: Wiggins KG , Holness JA , March BM 
Published: March 2005

Abstract
Samples of reactively-dyed wool and cotton were obtained from a range of dye manufacturers, dye distributors and the Forensic Science Service (FSS) Fibre Data Collection. The wool fibers were red in color and had previously been compared using comparison microscopy (CM), visible range microspectrophotometry (VS) and thin layer chromatography (TLC). The cotton fibers were blue and black in color and had not been previously compared. Red, blue and black fibers were chosen because they are often encountered in casework. The usage of reactive dyes to color fibers has increased over the last 10–15 years and these are often seen in casework. Before techniques were available that allowed reactively-dyed fibers to be compared using TLC only CM and microspectrophotometry were routinely carried out. Many laboratories, who had a microspectrophotometer, only had a visible range instrument. It was therefore important to see which techniques provide additional information, that gives greater individuality to fibers, to that obtained from CM. The color was released from the wool and cotton fibres using alkaline hydrolysis and a cellulase enzyme respectively. Many of the red wool samples were differentiated from each other using CM. More differentiation was found using VS and even more when ultraviolet range microspectrophotometry (UV) or TLC was used. Two samples could only be differentiated using TLC because CM, VS and UV failed to separate them. The black cotton samples were predominately differentiated using CM but VS allowed for further differentiation. With the samples used in this project UV and TLC failed to separate the samples further. The blue cotton samples benefited from the use of CM, VS and either UV or TLC to reduce the number of matching pairs. All techniques aided differentiation although with this set TLC and UV proved to be complementary techniques. Results demonstrate that TLC and UV both yield important information over and above that obtained from CM and VS. Although in some parts of the project TLC and UV are complementary if the concentration of the dye in the fiber is not sufficient for TLC or the scientist doesn't wish to ‘destroy’ the fiber UV would be of more use than TLC.