bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Aromatase Knockout Mouse Presents with a Sexually Dimorphic Disruption to Cholesterol Homeostasis
Authors: Hewitt Kylie N. , Boon Wah Chin , Murata Yoko , Jones Margaret E. E. , Simpson Evan R. 
Published: June 2003

AbstractThe aromatase knockout (ArKO) mouse cannot synthesize endogenous estrogens due to disruption of the Cyp19 gene. We have shown previously, that ArKO mice present with age-progressive obesity and hepatic steatosis, and by 1 yr of age both male and female ArKO mice develop hypercholesterolemia. In this present study 10- to 12-wk-old ArKO mice were challenged for 90 d with high cholesterol diets. Our results show a sexually dimorphic response to estrogen deficiency in terms of cholesterol homeostasis in the liver. ArKO females presented with elevated serum cholesterol; conversely, ArKO males had elevated hepatic cholesterol levels. In response to dietary cholesterol, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase transcript levels were significantly reduced in females, whereas males showed more modest changes. Neither low density lipoprotein nor sterol regulatory element-binding protein expression levels were significantly altered by diet or genotype. The expression of Cyp7a, which encodes cholesterol 7α-hydroxylase, was significantly reduced in ArKO females compared with wild-type females and was increased by cholesterol feeding. Cyp7a expression was significantly elevated in the wild-type males on the high cholesterol diet, although no difference was seen between genotypes on the control diet. The ATP-binding cassette G5 and ATP-binding cassette G8 transporters do not appear to be regulated by estrogen. The expression of acyl-coenzyme A:cholesterol acyltransferase 2 showed a sexually dimorphic response, where estrogen appeared to have a stimulatory effect in females, but not males. This study reveals a sexually dimorphic difference in mouse hepatic cholesterol homeostasis and roles for estrogen in the regulation of cholesterol uptake, biosynthesis, and catabolism in the female, but not in the male.
Protein Kinase B Is Obligatory for Follicle-Stimulating Hormone-Induced Granulosa Cell Differentiation
Authors: Zeleznik Anthony J. , Saxena Deeksha , Little-Ihrig Lynda 
Published: June 2003

AbstractAlthough FSH receptors are linked to the cAMP second messenger system, additional intracellular signaling pathways appear to be required for the induction of aromatase and the LH receptor during granulosa cell differentiation. We employed adenovirus vectors to modulate specific intracellular signaling systems in undifferentiated granulosa cells to identify the signaling pathway(s) that may be involved in the FSH-mediated induction of aromatase and the LH receptor. Expression of either the constitutively activated human LH receptor D578H or the constitutively active human Gsα Q227L resulted in increased cAMP production without increasing aromatase activity or mRNA levels for the LH receptor. To explore the contributions of other pathways, we expressed the constitutively activated forms MAPK kinase (MEK) and protein kinase B (PKB). Neither MEK nor PKB alone increased estrogen or progesterone production by undifferentiated granulosa cells. Stimulation of granulosa cells by FSH in the presence of the constitutively active PKB, but not MEK, led to an amplification of FSH-induced aromatase and LH receptor mRNA levels, whereas a dominant negative PKB vector completely abolished the actions of FSH. The expression of the constitutively active PKB in combination with the constitutively active LH receptor D578H, the constitutively active Gsα Q227L, or 8-bromo-cAMP led to an induction of aromatase as well as LH receptor mRNA comparable to that seen in cells stimulated with FSH alone. These results demonstrate that PKB is an essential component of the FSH-mediated granulosa cell differentiation and that both PKB and Gsα signaling pathways are required.
Functional Activation of Cerebral Metabolism in Mice with Mutated Thyroid Hormone Nuclear Receptors
Authors: Esaki Takanori , Suzuki Hideyo , Cook Michelle , Shimoji Kazuaki , Cheng Sheue-Yann , Sokoloff Louis , Nunez Jacques 
Published: June 2003

AbstractNeonatal hypothyroidism impairs structural maturation in the brain and results in diminished electrical activities and energy metabolism. We recently found that glucose utilization (CMRglc) is markedly depressed throughout the brain in mice with targeted mutations in thyroid hormone receptor α1 (TRα1), but not TRβ. Previous studies had shown that CMRglc increases linearly with spike frequency in the afferent pathways to synapse-rich regions in neuropil, but not in neuronal cell bodies. To determine whether the decreased CMRglc in mutant TRα1PV/+ mice reflected lesser synaptic density or reduced functional activity in existing synapses, we stimulated vibrissae unilaterally and measured CMRglc bilaterally in four stations of the whisker-to-barrel cortex pathway. Baseline CMRglc (unstimulated side) was markedly lower in all four stations in the TRα1PV/+ mutants than in wild-type controls, even though Northern blot and immunohistochemical examinations showed normal Na+,K+-adenosine triphosphatase expression and neuronal differentiation. Despite the lower baseline CMRglc, however, vibrissal stimulation evoked percent increases in CMRglc in the TRα1PV/+ mutants that were as great as those in wild-type mice. These results indicate that in the TRα1PV/+ mutants there it is a reduction in synaptic density that is responsible for the decrease in CMRglc, but functionality of existing synapses is retained.
Prostaglandin F2α (PGF2α) and Prolactin Signaling: PGF2α-Mediated Inhibition of Prolactin Receptor Expression in the Corpus Luteum
Authors: Stocco Carlos , Djiane Jean , Gibori Geula 
Published: June 2003

Abstract
It is well established that prolactin (PRL) sustains, whereas prostaglandin F2α (PGF2α) curtails, progesterone production by the rodent corpus luteum (CL). We have previously shown that PGF2α inhibits the expression of several luteal genes stimulated by PRL, whereas it stimulates other genes inhibited by this hormone. We have also found that PGF2α stimulation of 20α-hydroxysteroid dehydrogenase (20αHSD), an enzyme that catabolizes progesterone, at the end of pregnancy is accompanied by a dramatic decrease in PRL receptor (PRL-R) expression. These findings, and the fact that the factors that inhibit PRL-R are not known, led us to examine in vivo whether the decline in PRL-R at the end of pregnancy is due to PGF2α and to also find out whether PGF2α opposes PRL action by inhibiting PRL-R expression. Using the PGF2α receptor (PGF2α-R) knockout, we examined whether the absence of the PGF2α-R prevents the decline in the expression of both the short and long forms of the PRL-R in the CL. We found that, in sharp contrast to the wild-type mice, in which both forms of the PRL-R decline to low levels between d 18–20 of pregnancy, expression of these receptors remained elevated in the PGF2α-R null mice. Furthermore, administration of PGF2α to pregnant rats inhibited PRL-R expression. Time-course analysis revealed that PGF2α treatment decreases both isoforms of PRL-R within 1 h of treatment in vivo, whereas its stimulatory effect on 20αHSD expression was further delayed. Similar results were obtained with luteinized granulosa cells in culture. To examine whether the decline in PRL-R is involved/necessary for PGF2α action, cells were transfected with a constitutively active PRL-R. The expression of this receptor did not prevent PGF2α effect on PRL-R or 20αHSD expression. Taken together, these results demonstrate that PGF2α inhibits the expression of the PRL-R and that the decline in both forms of the PRL-R that occurs at the end of pregnancy in the CL is due to PGF2α. The results further suggest that PGF2α-mediated stimulation of 20αHSD is independent from PGF2α inhibition of PRL signaling in luteal cell.
Endogenous Hypothalamic Somatostatins Differentially Regulate Growth Hormone Secretion from Goldfish Pituitary Somatotropes in Vitro
Authors: Yunker Warren K. , Smith Sean , Graves Chad , Davis Philip J. , Unniappan Surajlal , Rivier Jean E. , Peter Richard E. , Chang John P. 
Published: June 2003

AbstractUsing Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode for SS14, goldfish brain (gb)SS28, and [Pro2]SS14, respectively, were detected in goldfish hypothalamus. PSS-I and -II mRNA, but not PSS-III mRNA, were also detected in cultured pituitary cells. We subsequently examined the effects of the mature peptides, SS14, gbSS28, and [Pro2]SS14, on somatotrope signaling and GH secretion. The gbSS28 was more potent than either SS14 or [Pro2]SS14 in reducing basal GH release but was the least effective in reducing basal cellular cAMP. The ability of SS14, [Pro2]SS14, and gbSS28 to attenuate GH responses to GnRH were comparable. However, gbSS28 was less effective than SS14 and [Pro2]SS14 in diminishing dopamine- and pituitary adenylate cyclase-activating polypeptide-stimulated GH release, as well as GH release resulting from the activation of their underlying signaling cascades. In contrast, the actions of a different 28-amino-acid SS, mammalian SS28, were more similar to those of SS14 and [Pro2]SS14. We conclude that, in goldfish, SSs differentially couple to the intracellular cascades regulating GH secretion from pituitary somatotropes. This raises the possibility that such differences may allow for the selective regulation of various aspects of somatotrope function by different SS peptides.
Effect of pathogenic mis-sense mutations in lamin A on its interaction with emerin in vivo
Authors: Holt Ian , Östlund Cecilia , Stewart Colin L. , Man Nguyen thi , Worman Howard J. , Morris Glenn E. 
Published: June 2003

Mutations in lamin A/C can cause Emery-Dreifuss muscular dystrophy (EDMD)or a related cardiomyopathy (CMD1A). Using transfection of lamin-A/C-deficient fibroblasts, we have studied the effects of nine pathogenic mutations on the ability of lamin A to assemble normally and to localize emerin normally at the nuclear rim.Five mutations in the rod domain (L85R, N195K, E358K, M371K and R386K)affected the assembly of the lamina. With the exception of mutant L85R, all rod domain mutants induced the formation of large nucleoplasmic foci in about 10% of all nuclei. The presence of emerin in these foci suggests that the interaction of lamin A with emerin is not directly affected by the rod domain mutations. Three mutations in the tail region, R453W, W520S and R527P, might directly affect emerin binding by disrupting the structure of the putative emerin-binding site, because mutant lamin A localized normally to the nuclear rim but its ability to trap emerin was impaired. Nucleoplasmic foci rarely formed in these three cases (&lt;2%) but, when they did so, emerin was absent,consistent with a direct effect of the mutations on emerin binding. The lipodystrophy mutation R482Q, which causes a different phenotype and is believed to act through an emerin-independent mechanism, was indistinguishable from wild-type in its localization and its ability to trap emerin at the nuclear rim.The novel hypothesis suggested by the data is that EDMD/CMD1A mutations in the tail domain of lamin A/C work by direct impairment of emerin interaction,whereas mutations in the rod region cause defective lamina assembly that might or might not impair emerin capture at the nuclear rim. Subtle effects on the function of the lamina-emerin complex in EDMD/CMD1A patients might be responsible for the skeletal and/or cardiac muscle phenotype.
Low-temperature NMR and IR Spectra of Photomerocyanine Form of Spirophenanthrooxazine
Authors: Lee Duck-Hyung , Lee Myunghee , Chung Chinkap , Lee Weon-Hee , Lee In-Ja 
Published: June 2003

Abstract
Low-temperature 13C NMR and IR spectra of the metastable photomerocyanine (PMC) of spirophenanthrooxazine (SPO) show that PMC is in quinoidal structure. Especially, 13C NMR study directly evidences the formation of two quinoidal PMCs in CD2Cl2 upon UV irradiation. The quantum chemical study of SPO shows that among open forms TTC and CTC are more stable than TTT and CTT because of the formation of the intramolecular hydrogen bond.
Convenient One-pot Synthesis of Functional Alkenyl Pendant-containing Silylene-divinylene Polymers
Authors: Rao Tumula Venkateshwar , Yamashita Hiroshi , Uchimaru Yuko , Asai Michihiko , Takeuchi Kazuhiko 
Published: June 2003

Abstract
Successive treatment of PhSiH3 with 1,4- or 1,3-diethynylbenzene (1 equiv.) and functional alkynes (1.05 equiv.) in the presence of Pd2(dba)3-PCy3 (dba = dibenzylideneacetone, Cy = cyclohexyl) catalyst gave new functional alkenyl pendant-containing silylene-divinylene polymers.
The First Enantioselective Hetero Diels–Alder Reaction of Nitroso Compound Utilizing Tartaric Acid Ester as a Chiral Auxiliary
Authors: Ding Xia , Ukaji Yutaka , Fujinami Shuhei , Inomata Katsuhiko 
Published: June 2003

Abstract
The first regio- and enantioselective hetero Diels–Alder reaction of nitroso compound with dienol has been realized utilizing tartaric acid ester as a chiral auxiliary and the corresponding cycloadduct was obtained in complete regioselectivity with excellent enantioselectivity up to 92% ee.
Enantioselective Addition of 2-(Trimethylsilyloxy)furan to Aldehydes Using Cr(salen) as Catalyst. Effect of Water on Enantioselectivity
Authors: Matsuoka Yuko , Irie Ryo , Katsuki Tsutomu 
Published: June 2003

Abstract
Cationic (R,R)-Cr(salen) complex 2 was found to catalyze enantioselective addition of 2-(trimethylsilyloxy)furan to aldehydes to give 5-substituted butenolides, though diastereoselectivity was only modest. The presence of a small amount of water is essential for achieving high enantioselectivity.
Synthesis of Nanosized A-type Zeolites from Sodium Silicates and Sodium Aluminates in the Presence of a Crystallization Inhibitor
Authors: Hosokawa Hiroji , Oki Kazuo 
Published: June 2003

Abstract
Nanosized A-type zeolites (primary particle size: 30–40 nm), which exhibit higher cationic exchange rate than commercially available A-type zeolites (primary particle size: 2 μm), have been synthesized from sodium silicates and sodium aluminates by using a crystallization inhibitor such as a nonionic surfactant and polyethylene glycol.
Crystal Engineering of 3D Porous Coordination Polymers through Hydrogen Bonding to Coordination from 1D Helical Chains
Authors: Zhu Long-Guan , Kitagawa Susumu , Seki Kenji 
Published: June 2003

Abstract
The combination of salicylic acid and 4-aminopyridine leads to a 3D hydrogen bonding network while the replacement of 4-aminopyridine with 4,4′-bipyridine yields the same topological net with big channels via coordination.
Synthesis and Structure of a New 3D Porous Cu(II)–Benzene-1,3,5-tricarboxylate Coordination Polymer, [Cu2(OH)(BTC)(H2O)]n·2nH2O
Authors: Chen Jinxi , Yu Ting , Chen Zhenxia , Xiao Huiping , Zhou Guoqiang , Weng Linhong , Tu Bo , Zhao Dongyuan 
Published: June 2003

Abstract
The reaction of Cu(NO3)2·3H2O with benzene-1,3,5-tricarboxylic acid (H3BTC) and H2O under hydrothermal conditions affords a new three-dimensional porous coordination polymer, [Cu2(OH)(BTC)(H2O)]n·2nH2O, which contains 5 × 7 Å dimension lozenge shaped 1D open channels along the crystallographic a axis.
Association between ACE Inhibitors and Acute Pancreatitis in the Elderly
Authors: Cheng Roger MS , Mamdani Muhammad , Jackevicius Cynthia A , Tu Karen 
Published: June 2003

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor–induced acute pancreatitis has been described in various case reports and drug surveillance databases. At present, no epidemiologic studies examining the potential association between ACE inhibitors and acute pancreatitis have been identified. OBJECTIVE: To determine whether there is an association between ACE inhibitor use and pancreatic events (acute pancreatitis, pancreatic surgery). METHODS: A retrospective cohort of Ontario residents aged ≥66 years was created using population-based administrative databases from January 1, 1994, through March 31, 2000. We compared the incidence of pancreatic events among new users of ACE inhibitors (study group), warfarin (null baseline group), and dihydropyridine calcium-channel antagonists (DCCAs; disease control group) using multivariate Cox proportional hazard models. OUTCOME MEASURES: The primary outcome measure was hospitalization with acute pancreatitis; the secondary outcome measure was incidence of pancreatic surgery. RESULTS: For acute pancreatitis, the crude incidence rates per 10 000 person-years were 9.0 for the ACE inhibitor group (n = 174 824); 7.1 for the DCCA group (n = 73 719), and 7.6 for the warfarin group (n = 40 057). Relative to warfarin users, neither ACE inhibitor users (adjusted rate ratio [aRR] = 1.35; 95% CI 0.94 to 1.93) nor DCCA users (aRR = 1.09; 95% CI 0.72 to 1.62) were at significantly higher risk of hospitalization for acute pancreatitis. For pancreatic surgery in the same population, the crude incidence rates per 10 000 person-years were 10.5 for the ACE inhibitor group, 10.6 for the DCCA group, and 10.7 for the warfarin group. Relative to subjects taking warfarin, neither ACE inhibitor users (aRR = 1.09; 95% CI 0.80 to 4.49) nor DCCA users (aRR = 1.11; 95% CI 0.79 to 1.56) were at significantly higher risk for pancreatic surgery. CONCLUSIONS: The use of ACE inhibitors does not appear to be associated with significant risk of acute pancreatitis among the elderly.
Hospital Guidelines for Use of Low-Molecular-Weight Heparins
Authors: Nutescu Edith A , Lewis Richard K , Finley Jamie M , Schumock Glen T 
Published: June 2003

OBJECTIVE: To describe the development of guidelines for initial use of low-molecular-weight heparins (LMWHs) and other anticoagulants in acute-care hospitals that are part of a national group purchasing organization (GPO). DATA SOURCES: A systematic literature search (1970–December 2001) was conducted to identify evidence on the efficacy of various anticoagulants for initial therapy in deep-vein thrombosis and pulmonary embolism, and in treatment of acute coronary syndrome. A group consensus method was then used to develop guidelines. Guidelines were reviewed and revised by an internal expert panel as well as an external expert panel. Final guidelines were disseminated to GPO members and assistance was provided with implementation at the local level. RESULTS: The final set of guidelines is described. The guidelines are organized based on recommended therapeutic options for each indication. For each option, consensus opinion is provided on the level of evidence that exists in the literature, comparisons of cost and convenience, and additional dosing information. The guidelines were disseminated along with supporting material to interested GPO member hospitals, and teleconferences were held to facilitate implementation at the local level. The guidelines were initially implemented at 18 hospitals across the country. CONCLUSIONS: The process by which these guidelines were developed, plus the final set of guidelines, may be useful to hospitals and healthcare systems contemplating or engaged in a similar effort with this class of drugs.
Potential Nontraditional Applications of Statins
Authors: McKenney James M 
Published: June 2003

OBJECTIVE: To review the current evidence for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) in nontraditional lipid-related applications, including acute coronary syndromes, peripheral arterial disease, stroke, and renal disease, and to describe ongoing trials evaluating the role of statins in these conditions. DATA SOURCES: Clinical literature was identified by a MEDLINE search (1990–November 2002) using ≥1 of the following search terms: acute coronary syndrome(s), angina pectoris, atherosclerosis, atorvastatin, clinical trials, diabetes mellitus, end-stage renal disease, fluvastatin, lovastatin, myocardial infarction, peripheral arterial disease, pravastatin, simvastatin, statins, and stroke. Treatment guidelines issued by professional and governmental organizations, such as the American Diabetes Association, American Heart Association, National Cholesterol Education Program, National Kidney Foundation, and National Stroke Foundation, were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles identified from the data sources were included if they pertained to the conditions described in the objectives and provided unique information concerning use of statins. DATA SYNTHESIS: Substantial evidence exists for the use of statins in acute coronary syndromes. Meta-analyses of data from major clinical trials indicate that statins prevent first and recurrent stroke, and large-scale trials are underway to evaluate the efficacy of statins in this setting. Accumulating evidence suggests that statins may be beneficial in reducing the morbidity and mortality associated with peripheral arterial disease and end-stage renal disease, and results from ongoing trials may confirm these benefits. Statins may also have a future role in amelioration of other conditions associated with atherosclerosis, such as diabetes mellitus. CONCLUSIONS: A large body of evidence supports the evaluation of statins in clinical settings beyond primary and secondary prevention of morbidity and mortality associated with coronary atherosclerosis.
Effect of Practitioner Education on Adherence to Asthma Treatment Guidelines
Authors: Coleman Craig I , Reddy Prabashni , Laster-Bradley N Michelle , Dorval Sheila , Munagala Bharathi , White C Michael 
Published: June 2003

OBJECTIVE: To determine whether a letter-based intervention program submitted to prescribers and pharmacists would improve drug therapy in users of high-dose β2-agonists (HDBs). STUDY DESIGN: Retrospective drug utilization review. PATIENTS AND METHODS: The intervention group consisted of 135 asthmatic patients (identified through ICD-9-CM codes) in the Connecticut Medicaid Program who submitted >1 claim per month for short-acting β2-agonists (over a 6-mo period). Patient-specific intervention packets were mailed to the patients' prescribers and pharmacists, and their use of long-term control agents and healthcare utilization was evaluated over 6 months. These variables were compared with a comparison group (n = 510) of asthmatics drawn from the same Medicaid program who were not considered to be high-dose users of short-acting β2-agonists at baseline. RESULTS: Prior to the intervention, the intervention group used fewer long-term asthma control agents as compared with the comparison group (58% vs. 96%; p < 0.001); there was no significant difference after the intervention program (65% vs. 71%; p = 0.169). The acquisition of spacers was greater in the intervention group than in the control group after the intervention (7% vs. 2%; p = 0.007). At the end of the 6-month intervention period, 46% of patients in the intervention group were no longer HDB users (p < 0.001). The higher frequency of prescriber office visits in the intervention group than the comparison group before the intervention (0.46 ± 0.82 vs. 0.25 ± 0.66; p < 0.001) was not evident after the intervention program (0.24 ± 0.63 vs. 0.18 ± 0.60; p = 0.283). CONCLUSIONS: This intervention program had modest impact on improving the use of long-term control agents and reducing prescriber office visits.