bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects
Authors: Schurgers Leon J. , Shearer Martin J. , Hamulyák Karly , Stöcklin Elisabeth , Vermeer Cees 
Published: July 2004

Abstract
Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 μg-500 μg) of vitamin K1 supplements (K1) taken daily for 7 days. The threshold K1 dose causing a statistically significant lowering of the INR was 150 μg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 μg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 μg K1/day compared with 100 μg K1/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic γ-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 μg/day of vitamin K1 do not significantly interfere with oral anticoagulant therapy. (Blood. 2004;104:2682-2689)
Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta)
Authors: Gore Andrea C. , Windsor-Engnell Bret M. , Terasawa Ei 
Published: July 2004

Abstract
Reproductive function in all vertebrates is controlled by the circhoral release of the neuropeptide, GnRH, into the portal capillary system leading to the anterior pituitary. Despite its primary role in sexual maturation and the maintenance of adult reproductive function, changes in the concentrations and pattern of GnRH release have not yet been reported in any primate species during the menopausal transition and postmenopause. Such knowledge is essential for ascertaining both the mechanisms for, and consequences of, the menopausal process. Here we used a push-pull perfusion method to measure and compare the parameters of pulsatile GnRH release in adult rhesus monkeys at 8.4 ± 1.5 yr (young adult females, early follicular phase, n = 6) and 28.8 ± 0.3 yr (aged females, n = 4, of which two monkeys were in the menopausal transition, and two were postmenopausal). Our results demonstrate that: 1) GnRH release is pulsatile in both young and aged monkeys; 2) mean concentrations of GnRH increase during reproductive aging; and 3) GnRH pulse frequency does not differ between aged monkeys and young monkeys in the early follicular phase. We conclude that not only do GnRH neurons have the continued capacity to release GnRH in a pulsatile manner but also they can do so with enhanced GnRH levels in aged primates. To our knowledge, this is the first direct demonstration of elevated pulsatile GnRH concentrations in a primate species during reproductive senescence, a result that may have implications for menopausal symptoms.
Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats
Authors: Tang-Christensen Mads , Vrang Niels , Ortmann Sylvia , Bidlingmaier Martin , Horvath Tamas L. , Tschöp Matthias 
Published: July 2004

AbstractGhrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83–132)] induced orexia, we compared the short- and long-term orexigenic capacity of the three peptides. A single intracerebroventricular injection of ghrelin (0.2, 1.0, and 5.0 μg) increased food intake in a dose-dependent manner. A prolonged and uncompensated increase in feeding was seen after the highest dose of ghrelin. The prolonged effects on feeding (+72 h) closely resembled those of AGRP (83–132) but not NPY. Surprisingly, ghrelin injections reduced overall locomotor activity by 20% during the first 24-h observation period. AGRP (83–132) had similar effects on locomotor behavior, whereas NPY had no effect. In summary, ghrelin causes long-term increases of food intake and, like AGRP, plays a previously unknown role as a suppressor of spontaneous physical activity. Expanding the current model of food intake control to include mechanisms regulating physical activity may promote our understanding of two major etiological factors causing obesity.
Down-Regulated Expression of A Disintegrin and Metalloproteinase with Thrombospondin-Like Repeats-1 by Progesterone Receptor Antagonist Is Associated with Impaired Expansion of Porcine Cumulus-Oocyte Complexes
Authors: Shimada Masayuki , Nishibori Masahide , Yamashita Yasuhisa , Ito Junya , Mori Takahide , Richards JoAnne S. 
Published: July 2004

AbstractADAMTS-1, a member of the A disintegrin and metalloproteinase family of proteases, is expressed in rodent follicles via progesterone receptor (PR)-dependent pathways. However, the functional relationship between ADAMTS-1 expression and PR has not been studied extensively in other species. In the present study, we investigated the time-dependent changes in ADAMTS-1 expression in cumulus cells of porcine cumulus-oocyte complexes (COCs), and the roles of ADAMTS-1 in cumulus expansion during in vitro maturation of oocytes. ADAMTS-1 message was not detected in cumulus cells at the time of collection from the follicles. In response to gonadotropins, ADAMTS-1 mRNA was dramatically up-regulated and reached a maximum at 20 h. The level of mature ADAMTS-1 protein increased in a time-dependent manner with a maximum level at 40 h. The induction of ADAMTS-1 mRNA and protein was significantly decreased by the addition of PR antagonist RU486 to the cultures. However, RU486 did not affect the expression of ADAMTS-4 or factors that had been reported to be required for COC expansion (TSG-6, versican, HA synthase-2). COCs cultured with FSH and LH for 40 h exhibited prominent cumulus expansion. The expansion was reduced significantly by the addition of either RU486 or Galardin, a broad-spectrum matrix metalloproteinase inhibitor. These results suggest that the expression and induction of ADAMTS-1 through receptor-mediated action of progesterone in cumulus cells is one of the essential requirements for gonadotropin-regulated cumulus expansion of porcine COCs.
A Tumor Suppressor Role for Thyroid Hormone β Receptor in a Mouse Model of Thyroid Carcinogenesis
Authors: Kato Yasuhito , Ying Hao , Willingham Mark C. , Cheng Sheue-Yann 
Published: July 2004

AbstractWe have created a knockin mutant mouse by targeting a mutation (PV) into the thyroid hormone receptor β gene (TRβPV mouse). TRβPV/PV mice, but not TRβPV/+ mice, spontaneously develop follicular thyroid carcinoma. To identify other genetic changes in the TRβ gene that could also induce thyroid carcinoma, we crossed TRβPV mice with TRβ−/− mice. As TRβPV/− mice (mutation of one TRβ allele in the absence of the other wild-type allele) aged, they also spontaneously developed follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung, but not to the lymph nodes. The pathological progression of thyroid carcinoma in TRβPV/− mice was indistinguishable from that in TRβPV/PV mice. Analyses of the expression patterns of critical genes indicated activation of the signaling pathways mediated by TSH, peptide growth factors (epidermal growth factor and fibroblast growth factor), TGF-β, TNF-α, and nuclear factor-κB, and also suggested progressive repression of the pathways mediated by the peroxisome proliferator-activated receptor γ. The patterns in the alteration of these signaling pathways are similar to those observed in TRβPV/PV mice during thyroid carcinogenesis. These results indicate that in the absence of a wild-type allele, the mutation of one TRβ allele is sufficient for the mutant mice to spontaneously develop follicular thyroid carcinoma. These results provide, for the first time, in vivo evidence to suggest that the TRβ gene could function as a tumor suppressor gene. Importantly, these findings present the possibility that TRβ could serve as a novel therapeutic target in thyroid cancer.
Dibutyryl Cyclic Adenosine Monophosphate Restores the Ability of Aged Leydig Cells to Produce Testosterone at the High Levels Characteristic of Young Cells
Authors: Chen Haolin , Liu June , Luo Lindi , Zirkin Barry R. 
Published: July 2004

AbstractThe wealth of knowledge about the function and regulation of adult Leydig cells, the cells within the mammalian testis that produce testosterone, make these cells ideal for studying principles and mechanisms of aging. A hallmark of mammalian aging is decreased serum testosterone concentration. In the Brown Norway rat, this has been shown to be associated with the reduced ability of aged Leydig cells to produce testosterone in response to LH. Herein, we demonstrate that culturing the aged cells with dibutyryl cAMP, a membrane-permeable cAMP agonist that bypasses the LH receptor-adenlyly cyclase cascade, restores testosterone production to levels comparable to those of young cells and also restores steroidogenic acute regulatory protein and P450scc, the proteins involved in the rate-limiting steps of steroidogenesis. These results strongly suggest that signal transduction deficits are responsible for reduced steroidogenesis by aged Leydig cells and that bypassing signal transduction reverses the steroidogenic decline by the aged cells.
Identification of Tissue-Restricted Transcripts in Human Islets
Authors: Maffei Antonella , Liu Zhuoru , Witkowski Piotr , Moschella Federica , Pozzo Giovanna Del , Liu Eric , Herold Kevan , Winchester Robert J. , Hardy Mark A. , Harris Paul E. 
Published: July 2004

Abstract
The purpose of our study was to identify transcripts specific for tissue-restricted, membrane-associated proteins in human islets that, in turn, might serve as markers of healthy or diseased islet cell masses. Using oligonucleotide chips, we obtained gene expression profiles of human islets for comparison with the profiles of exocrine pancreas, liver, and kidney tissue. As periislet presence of type 1 interferon is associated with the development of type 1 diabetes, the expression profile of human islets treated ex vivo with interferon-α2β (IFNα2β) was also determined. A set of genes encoding transmembrane- or membrane-associated proteins with novel islet-restricted expression was resolved by determining the intersection of the islet set with the complement of datasets obtained from other tissues. Under the influence of IFNα2β, the expression levels of transcripts for several of the identified gene products were up- or down-regulated. One of the islet-restricted gene products identified in this study, vesicular monoamine transporter type 2, was shown to bind [3H]dihydrotetrabenazine, a ligand with derivatives suitable for positron emission tomography imaging. We report here the first comparison of gene expression profiles of human islets with other tissues and the identification of a target molecule with possible use in determining islet cell masses.
Plasma Membrane Estrogen Receptors Exist and Functions as Dimers
Authors: Razandi Mahnaz , Pedram Ali , Merchenthaler Istvan , Greene Geoffrey L. , Levin Ellis R. 
Published: July 2004

Abstract
A small pool of estrogen receptors (ERα and -β) localize at the plasma membrane and rapidly signal to affect cellular physiology. Although nuclear ERs function mainly as homodimers, it is unknown whether membrane-localized ER exists or functions with similar requirements. We report that the endogenous ER isoforms at the plasma membrane of breast cancer or endothelial cells exist predominantly as homodimers in the presence of 17β-estradiol (E2). Interestingly, in endothelial cells made from ERα /ERβ homozygous double-knockout mice, membrane ERα or ERβ are absent, indicating that the endogenous membrane receptors derive from the same gene(s) as the nuclear receptors. In ER-negative breast cancer cells or Chinese hamster ovary cells, we expressed and compared wild-type and dimer mutant mouse ERα. Only wild-type ERα supported the ability of E2 to rapidly activate ERK, cAMP, and phosphatidylinositol 3-kinase signaling. This resulted from E2 activating Gsα and Gqα at the membrane in cells expressing the wild-type, but not the dimer mutant, ERα. Intact, but not dimer mutant, ERα also supported E2-induced epidermal growth factor receptor transactivation and cell survival. We also confirmed the requirement of dimerization for membrane ER function using a second, less extensively mutated, human ERα. In summary, endogenous membrane ERs exist as dimers, a structural requirement that supports rapid signal transduction and affects cell physiology.
A unique visual pigment expressed in green, red and deep-red receptors in the eye of the small white butterfly,Pieris rapae crucivora
Authors: Wakakuwa Motohiro , Stavenga Doekele G. , Kurasawa Masumi , Arikawa Kentaro 
Published: July 2004

SUMMARYThe full primary structure of a long-wavelength absorbing visual pigment of the small white butterfly, Pieris rapae crucivora, was determined by molecular cloning. In situ hybridization of the opsin mRNA of the novel visual pigment (PrL) demonstrated that it is expressed in the two distal photoreceptor cells (R3 and R4) as well as in the proximal photoreceptors(R5–8) in all three types of ommatidia of the Pieris eye. The main, long-wavelength band of the spectral sensitivities of the R3 and R4 photoreceptors is well described by the absorption spectrum of a visual pigment with absorption maximum at 563 nm; i.e. PrL is a visual pigment R563. The spectral sensitivities of R5–8 photoreceptors in ommatidial type I and III peak at 620 nm and those in type II ommatidia peak at 640 nm. The large shifts of the spectral sensitivities of the R5–8 photoreceptors with respect to the absorption spectrum of their visual pigment can be explained with the spectral filtering by pale-red (PR) and deep-red (DR)screening pigments that are concentrated in clusters of granules near the rhabdom boundary. The peak absorbance of the two spectral filters appears to be approximately 1 (PR) and 2 (DR).
Habitat-dependent transmission of male advertisement calls in bladder grasshoppers (Orthoptera; Pneumoridae)
Authors: Couldridge Vanessa C. K. , van Staaden Moira J. 
Published: July 2004

SUMMARYIt has been hypothesized that the physical properties of the environment exert selection pressure on long-range acoustic communication signals to match the local habitat by promoting signal characteristics that minimize excess attenuation and distortion. We tested this in a unique family of bladder grasshoppers notable for producing a signal with a 2 km maximum transmission distance. In direct performance comparisons, male advertisement calls of seven species were broadcast through four vegetation biomes – forest, fynbos,savanna and succulent karoo. The calls of species native to forest and fynbos biomes propagated with lower levels of distortion over distance in their respective habitats relative to those of non-native species, while fynbos species also performed best in the remaining two habitats. In addition, both forest and fynbos species had low levels of signal attenuation over distance in all environments. The fynbos biome was characterized by high inconsistency in signal degradation, while the forest biome had the highest levels of environmental noise. Innate habitat characteristics, leading to comparatively limited acoustic communication distances in the forest and fynbos relative to the savanna and succulent karoo, may therefore explain the need for a higher quality of signal transmission in grasshoppers inhabiting the former two environments.
The mechanism of action of the antidiuretic peptide Tenmo ADFa in Malpighian tubules ofAedes aegypti
Authors: Massaro Richard C. , Lee Lenora W. , Patel Ankit B. , Wu Daniel S. , Yu Ming-Jiun , Scott Brett N. , Schooley David A. , Schegg Kathleen M. , Beyenbach Klaus W. 
Published: July 2004

SUMMARYThe mechanism of action of Tenebrio molitor antidiuretic factor`a' (Tenmo ADFa) was explored in isolated Malpighian tubules of Aedes aegypti. In the Ramsay assay of fluid secretion, Tenmo ADFa(10–9 mol l–1) significantly inhibited the rate of fluid secretion from 0.94 nl min–1 to 0.44 nl min–1 without significant effects on the concentrations of Na+, K+ and Cl– in secreted fluid. In isolated perfused tubules, Tenmo ADFa had no effect on the transepithelial voltage (Vt) and resistance (Rt). In principal cells of the tubule, Tenmo ADFa had no effect on the basolateral membrane voltage (Vbl) and the input resistance of principal cells (Rpc). Tenmo ADFa significantly increased the intracellular concentration of cyclic guanosine monophosphate (cGMP) from 2.9 μmol l–1 (control) to 7.4 μmol l–1. A peritubular [cGMP] of 20 μmol l–1duplicated the antidiuretic effects of Tenmo ADFa without inducing electrophysiological effects. In contrast, 500 μmol l–1cGMP significantly depolarized Vbl, hyperpolarized Vt, and reduced Rt and Rpc, without increasing antidiuretic potency beyond that of 20 μmol l–1 cGMP. A plot of peritubular cGMP concentration vs Vbl revealed a steep dose–response between 300 μmol l–1 and 700 μmol l–1with an EC50 of 468 μmol l–1. These observations suggest a receptor- and cGMP-mediated mechanism of action of Tenmo ADFa. Tenmo ADFa and physiological concentrations of cGMP (&lt;20μmol l–1) reduce the rate of isosmotic fluid secretion by quenching electroneutral transport systems. The inhibition reveals that as much as 50% of the normal secretory solute and water flux can stem from electrically silent mechanisms in this highly electrogenic epithelium.
Gender dimorphism of body mass perception and regulation in mice
Authors: Wiedmer Petra , Boschmann Michael , Klaus Susanne 
Published: July 2004

SUMMARY
According to the set-point theory of body mass, changes in body mass are perceived by the body, leading to activation of compensatory feedback mechanisms, which in turn restores the set-point body mass. However, this theory is still under debate. To test if mass per se might be sensed and regulated, we implanted loads corresponding to 10% (HI) or 2% (LO,control) of body mass into mice in addition to sham-operated mice (SO). We recorded body mass, food intake, energy expenditure and body composition over 14 weeks. Both male and female mice showed an initial stress-induced loss of body mass, which was more pronounced in males. Subsequently, male HI mice displayed a permanently decreased biological body mass(MBB, body mass exclusive of the implant mass), equivalent to approximately half of the mass of the implant, and obtained by a decrease in fat mass compared to SO males. In contrast, female HI mice rapidly recovered and maintained their initial MBB and body composition following a mass load. Initial lean body mass was maintained in all male and female groups, and energy intake was similar in all male and female groups. Body mass changes could not be explained by measurable changes in energy intake or expenditure. We conclude that changes in body mass are perceived and partially compensated in male but not in female mice, suggesting that mass-specific regulation of body mass might not play a major role in overall body mass regulation. Different compartments of the body are possibly regulated by different signals and stimuli. Our results suggest that lean body mass rather than body mass per se seems to be tightly regulated. Higher efficiency of energy utilization in females compared to males could explain the gender-specific changes in energy balance.
Lactate accumulation, glycogen depletion, and shell composition of hatchling turtles during simulated aquatic hibernation
Authors: Reese Scott A. , Ultsch Gordon R. , Jackson Donald C. 
Published: July 2004

SUMMARY
We submerged hatchling western painted turtles Chrysemys pictaSchneider, snapping turtles Chelydra serpentina L. and map turtles Graptemys geographica Le Sueur in normoxic and anoxic water at 3°C. Periodically, turtles were removed and whole-body [lactate] and[glycogen] were measured along with relative shell mass, shell water, and shell ash. We analyzed the shell for [Na+], [K+], total calcium, total magnesium, Pi and total CO2. All three species were able to tolerate long-term submergence in normoxic water without accumulating any lactate, indicating sufficient extrapulmonary O2extraction to remain aerobic even after 150 days. Survival in anoxic water was 15 days in map turtles, 30 days in snapping turtles, and 40 days in painted turtles. Survival of hatchlings was only about one third the life of their adult conspecifics in anoxic water. Much of the decrease in survival was attributable to a dramatically lower shell-bone content (44% ash in adult painted turtles vs. 3% ash in hatchlings of all three species) and a smaller buffer content of bone (1.3 mmol g–1 CO2in adult painted turtles vs. 0.13–0.23 mmol g–1 CO2 in hatchlings of the three species). The reduced survivability of turtle hatchlings in anoxic water requires that hatchlings either avoid aquatic hibernacula that may become severely hypoxic or anoxic (snapping turtles), or overwinter terrestrially (painted turtles and map turtles).
Generic Scheme for Independent Performance Assessment in the Molecular Biology Laboratory
Authors: Birch Lyndsey , English Claire A , Burns Malcolm , Keer Jacquie T 
Published: July 2004

AbstractBackground: A variety of proficiency testing schemes are available for specific molecular analyses, but there is an acute need for more widely accessible schemes to assess and demonstrate general competence in DNA analysis.Methods: Fifteen laboratories, including academic, clinical, and commercial organizations, were recruited into the prototype assessment exercise. A range of test samples were provided, and participants were required to extract DNA from simple matrices, perform PCR amplification, and score the samples as positive or negative by electrophoretic analysis of the amplification products. Results were requested as both gel images and a completed results table, and the performance of each laboratory was then scored on the submitted analytical results.Results: Overall, laboratories performed the analysis successfully, with participants scoring a high proportion of the samples correctly in the two rounds of the scheme. However, not all of the laboratories were able to achieve amplification for all samples, and the performance of some laboratories was not consistent in the two rounds. In addition, several analytical problems were encountered at all stages of the process, including DNA extraction, PCR amplification, and correct recording of results.Conclusions: The generic approach described here has enabled effective cross-sectoral benchmarking of laboratories from a variety of analytical sectors. The problems encountered by some participating laboratories highlight the need for quality control and checks at all stages of the process to ensure accuracy of results. A statistical analysis of the results (ANOVA) allowed meaningful comparison of the consistency and sensitivity achieved by laboratories, demonstrating that an effective balance was achieved between the level of data obtained from laboratories and the time expenditure required from participants.