bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Calcium-Calmodulin-Dependent Protein Kinase Cascade in Thyrotropin (TSH)-Releasing Hormone Induction of TSH and Prolactin Gene Expression
Authors: Murao Koji , Imachi Hitomi , Cao Wen M. , Yu Xiao , Tokumitsu Hiroshi , Inuzuka Hiroyuki , Wong Norman C. W. , Shupnik Margaret A. , Kobayashi Ryoji , Ishida Toshihiko 
Published: August 2004

AbstractTRH binds to a membrane receptor that activates several intracellular signaling pathways and increases transcription of the TSH and prolactin (PRL) genes. Although TRH induces TSH and PRL gene expression, the underlying mechanism is not clear. In this report we examined the role of the Ca2+/calmodulin-dependent protein (CaM) kinase cascade in mediating TRH-stimulated transcription of TSH and PRL. RT-PCR and Western blot analysis were used to show that CaM kinase kinase (CaM-KK) and CaM IV (CaM-KIV) were present in rat anterior pituitary and its cell line GH3. Next, the effects of constitutively active CaM-KIV (CaM-KIVc) or its dominant negative mutant (CaM-KIVdn) on TSH and PRL promoter activity were tested in GH3 cells. The results showed that either CaM-KIVc alone or an upstream kinase, CaM-KK, induced the activity of both TSH and PRL promoters. Exposure of GH3 cells to 100 μm TRH induced CaM-KIV activity within 5 min and, as expected, also increased both TSH and PRL promoter activity. In contrast, cells carrying the CaM-KIVdn isoform had suppressed TRH induction of both TSH and PRL promoter activity. These results indicate that the CaM-KK-CaM-KIV cascade probably plays an important role in TRH induction of TSH and PRL transcriptional activity in pituitary cells.
Comparison of the Pharmacological Effects of a Novel Selective Androgen Receptor Modulator, the 5α-Reductase Inhibitor Finasteride, and the Antiandrogen Hydroxyflutamide in Intact Rats: New Approach for Benign Prostate Hyperplasia
Authors: Gao Wenqing , Kearbey Jeffrey D. , Nair Vipin A. , Chung Kiwon , Parlow A. F. , Miller Duane D. , Dalton James T. 
Published: August 2004

AbstractTissue-selective androgen receptor modulators (SARMs) demonstrate tissue selectivity in both castrated and intact male rats, behaving as partial agonists in androgenic tissues (i.e. prostate and seminal vesicle), but full agonists in anabolic tissues (i.e. levator ani muscle). The partial agonist activity of SARMs (compounds S-1 and S-4) in the prostate of intact rats suggested that SARM could be used for androgen suppression in the treatment of benign prostate hyperplasia (BPH). This study was designed to explore the mechanisms of action of SARM and to characterize the tissue selectivity of S-1 in intact male rats compared with that of hydroxyflutamide (antiandrogen) and finasteride (5α-reductase inhibitor), two major drugs used for androgen suppression treatment of BPH. In intact male rats, S-1 (5, 10, and 25 mg/kg) selectively decreased the prostate weight with similar efficacy to finasteride (5 mg/kg), without affecting the levator ani muscle or increasing the plasma levels of testosterone, LH, and FSH. Hydroxyflutamide (0.5, 1, 5, 10, and 25 mg/kg), however, decreased both the prostate and levator ani muscle weights without any selectivity and increased plasma hormone levels in a dose-dependent manner. Furthermore, S-1 and S-4 showed very weak inhibitory effects toward transiently expressed type I and II human 5α-reductase (Ki, &gt;20 μm) during in vitro assays. Therefore, although S-1 and finasteride showed very similar suppressive effects in the prostate of intact male rats, they decreased prostate size via different mechanisms of action. S-1 simply worked as androgen receptor partial agonist, whereas finasteride inhibited prostatic 5α-reductase. These studies indicate that SARMs may demonstrate clinical utility as single agent or combination therapy for BPH.
Cytochrome P450-Dependent Lipid Metabolism in Preovulatory Follicles
Authors: Newman J. W. , Stok J. E. , Vidal J. D. , Corbin C. J. , Huang Q. , Hammock B. D. , Conley A. J. 
Published: August 2004

AbstractEstrogen biosynthesis and proteolysis are both important processes involved in ovarian follicular development, which may be influenced by cytochrome P450 (CYP)-dependent fatty acid metabolites. However, CYP-dependent lipid metabolism has not been characterized with respect to follicular maturation in vivo. Therefore, follicular fluid was collected in the hours before and after the LH surge in pigs, and concentrations of epoxy, hydroxy, and dihydroxy lipids were measured by liquid chromatography tandem mass spectrometry. Arachidonate oxidation and epoxyeicosatrienoic acid hydrolysis to dihydroxyeicosatrienoic acids (DHETs) were also assessed in thecal and granulosa tissue fractions, and the expression of CYP epoxygenases was evaluated by immunoblots using available antisera. To evaluate soluble epoxide hydrolase (sEH) expression, the porcine sEH was cloned from ovarian tissue, expressed and purified for antibody generation. The follicular fluid oxylipin concentrations ranged from 1–150 nm depending on the compound and estrous stage. The follicular fluid concentrations of CYP-dependent oxylipins increased at estrus, as did sEH expression; however, significant changes in epoxides were not observed, and the 11,12-DHET peak was delayed. The ratio of 14,15–DHET:11,12-DHET across all samples correlated with the log of follicular fluid estradiol concentrations (P &lt; 0.01). Epoxygenase activities were similar in theca and granulosa, varying little with follicular development, whereas the decline of a single CYP2J isoform at ovulation was observed by immunoblots. The sEH activity was higher in granulosa than in theca. Finally, the dynamic changes in follicular CYP-dependent arachidonic acid metabolites and their modulatory function in vascular models suggest roles for these metabolites in follicular maturation, which may include regulation of estradiol biosynthesis and preovulatory remodeling of the follicular wall that should be fully explored in future studies.
In the Adult Male Rhesus Monkey (Macaca mulatta), Unilateral Orchidectomy in the Face of Unchanging Gonadotropin Stimulation Results in Partial Compensation of Testosterone Secretion by the Remaining Testis
Authors: Simorangkir David R. , Ramaswamy Suresh , Marshall Gary R. , Plant Tony M. 
Published: August 2004

AbstractThis study examined, in adult monkeys, the role that gonadotropin-independent mechanisms play in compensation of testosterone (T) secretion by the testis that remains after unilateral orchidectomy (UO). We employed a model (testicular clamp), in which endogenous gonadotropin secretion was abolished with a GnRH receptor antagonist, and the gonadotropin drive to the testes was concomitantly replaced with an invariant iv pulsatile infusion of recombinant human LH and FSH (1-min pulse every 2.5 h: LH, 0.08–0.12 IU/kg·pulse; FSH, 0.12–0.32 IU/kg·pulse) that provided the Leydig cells with a physiological stimulus. Within 5 h of UO (n = 5), circulating T concentrations had declined to 43% of pre-UO levels. By d 4, however, loss of the first testis was partially compensated, as reflected by the finding that circulating T had reached a plateau of 67% of the pre-UO level, where it remained for the duration of the study (39 d). That the recovery in circulating T was the result of increased T secretion by the remaining testis was suggested by the finding that the pulsatile pattern and decay of T during the intergonadotropin pulse interval before and after UO were indistinguishable. Interestingly, inhibin B production by the remaining testis also showed a delayed, albeit, minor, compensation (13% on d 10–11; P &gt; 0.05) after loss of the first testis. These results suggest that compensation in T production by the remaining testis after UO in adult monkeys may be achieved in part by a gonadotropin-independent mechanism that probably involves direct neural inputs to the primate testis.
Identity and Regulation of Stored and Secreted Progastrin-Derived Peptides in Sheep
Authors: Paterson Adrienne C. , Lockhart Sharon M. , Baker Josephine , Neumann Greg , Baldwin Graham S. , Shulkes Arthur 
Published: August 2004

AbstractAmidated and nonamidated progastrin-derived peptides have distinct biological activities that are mediated by a range of receptor subtypes. The objective was to determine the nature of the stored and secreted progastrin-derived peptides and to investigate whether progastrin release is regulated by gastric acidity. Using an antiserum directed to the C terminus of progastrin for identification and to monitor purification, C-terminal flanking peptides (CTFP) of progastrin (prog76–83, prog77–83, and prog78–83 in approximately equivalent amounts) were isolated and identified from extracts of sheep antrum using ion exchange, HPLC, and mass spectrometry. Only trace amounts of full-length progastrin were present. Progastrin CTFP was the predominant progastrin-derived peptide in the antrum [progastrin CTFP/gastrin amide (Gamide) = 3]. Similarly, progastrin CTFP was the major circulating form in the antral (CTFP, 710 ± 62 pmol/liter; Gamide, 211 ± 35 pmol/liter) and jugular (CTFP, 308 ± 16 pmol/liter; gastrin amide, 32 ± 3 pmol/liter) veins. Alteration of gastric acidity in sheep by iv infusion of a H/K-adenosine triphosphatase inhibitor or somatostatin or by intragastric infusion of HCl demonstrated that the CTFP concentrations changed, although to a lesser extent than the changes in circulating gastrin amide. We conclude that the CTFP of progastrin is the major stored and circulating species of the gastrin gene, and that it is secreted in a regulated fashion rather than constitutively. Because full-length progastrin is bioactive, but is only a minor antral and secreted form, determination of the biological activity of the C-terminal flanking peptides will be important for a complete understanding of gastrin endocrinology.
Single-Tube Method for Nucleic Acid Extraction, Amplification, Purification, and Sequencing
Authors: Margraf Rebecca L , Page Sam , Erali Maria , Wittwer Carl T 
Published: August 2004

AbstractBackground: The hepatitis C virus (HCV) genotype determines patient prognosis and duration of treatment, but sequencing of the gene is lengthy and labor-intensive. We used a commercially available nucleic acid extraction system to develop a single-tube extraction-to-sequencing (STETS) method for HCV genotyping.Methods: HCV RNA was purified and amplified in tubes coated with a solid-phase matrix that irreversibly bound nucleic acid during the extraction step. After reverse transcription-PCR, the amplicon was adsorbed to the original extraction matrix for purification and use in the subsequent sequencing reactions.Results: The STETS method generated genotyping-quality sequence for a range of HCV titers from 500 to 6 000 000 IU/mL. If a viral sample was detected during real-time reverse transcription-PCR, it could be sequenced and genotyped. Read lengths &gt;600 bases were observed with the STETS method. Mixed infections were detected and genotyped if at least 15% of the minor species was present. Combining the STETS method with consecutive sequencing provided a means of performing both forward and reverse sequencing in a single tube.Conclusions: A single-tube nucleic acid extraction-to-sequencing method, which requires less time and labor than conventional methods, generates HCV sequence data that are equivalent to conventional methods and can be used to genotype HCV.
C-Reactive Protein and Features of the Metabolic Syndrome in a Population-Based Sample of Children and Adolescents
Authors: Lambert Marie , Delvin Edgard E , Paradis Gilles , O’Loughlin Jennifer , Hanley James A , Levy Emile 
Published: August 2004

Abstract
Background: C-Reactive protein (CRP) is a risk marker for type 2 diabetes and cardiovascular diseases. In youth, limited data are available on the distribution of high-sensitivity CRP as well as on its association with components of the metabolic syndrome.
Methods: In 1999, we conducted a school-based survey of a representative sample of youths 9, 13, and 16 years of age in the province of Quebec, Canada. Standardized clinical measurements and fasting plasma lipid, glucose, insulin, and CRP concentrations were available for 2224 individuals.
Results: The distribution of CRP was positively skewed. The median and 95th percentile values by age and sex ranged from &lt;0.2 to 0.56 mg/L and from 2.72 to 6.28 mg/L, respectively. A total of 7.7% of 9-year-olds, 5.5% of 13-year-olds, and 12.8% of 16-year-olds had CRP concentrations &gt;3.0 mg/L, the threshold defining the adult high-risk category. We observed a strong relationship between CRP concentrations and both body mass index (BMI) and fasting insulin values. The association between CRP and insulin concentration was markedly attenuated after adjustment for BMI, whereas that between CRP and BMI remained unchanged after adjustment for insulin: a 1 SD increase in BMI was associated with a 52% increase in CRP concentration. An increased CRP concentration was independently associated with a worsening of the lipid profile, whereas the association between increased CRP values and high systolic blood pressure was no longer statistically significant after adjustment for BMI.
Conclusions: The metabolic correlates of excess weight, including a state of low-grade systemic inflammation, are detectable early in life. Their health impact in adults remains to be fully examined.
Noninvasive Measurement of Glucose by Metabolic Heat Conformation Method
Authors: Cho Ok Kyung , Kim Yoon Ok , Mitsumaki Hiroshi , Kuwa Katsuhiko 
Published: August 2004

AbstractBackground: We developed a method, called the metabolic heat conformation (MHC) method, for the noninvasive measurement of blood glucose. The MHC method involves the measurement of physiologic indices related to metabolic heat generation and local oxygen supply, which correspond to the glucose concentration in the local blood supply.Methods: We used noninvasive thermal and optical sensors on the fingertip of an individual to measure thermal generation, blood flow rate, hemoglobin (Hb) concentration, and oxyhemoglobin concentration. The calibration model incorporates mathematical procedures to convert signals from the sensor pickup to final glucose concentrations. The mathematical procedures are multivariate statistical analyses, involving values from sensor signals, polynomials from various values, regression analyses of individual patients, and cluster analyses of patient groups. The glucose value is calculated for each patient measurement, applying one of the clusters by discriminant analysis.Results: Regression analysis was performed to compare the noninvasive method with the hexokinase method, using 127 data points (109 data points from diabetic patients, 18 data points from nondiabetic patients) with glucose concentrations ranging from 3.0 to 22.5 mmol/L (54–405 mg/dL). The correlation coefficient (r) was 0.91. Reproducibility was measured for healthy fasting persons; the CV was 6% at 5.56 mmol/L (100 mg/dL).Conclusions: These data provide preliminary evidence that the MHC method can be used to estimate blood glucose concentrations noninvasively.
Diagnostic Probes for Bacillus anthracis Spores Selected from a Landscape Phage Library
Authors: Brigati Jennifer , Williams David D , Sorokulova Iryna B , Nanduri Viswaprakash , Chen I-Hsuan , Turnbough Charles L , Petrenko Valery A 
Published: August 2004

AbstractBackground: Recent use of Bacillus anthracis spores as a bioweapon has highlighted the need for a continuous monitoring system. Current monitoring systems rely on antibody-derived probes, which are not hardy enough to withstand long-term use under extreme conditions. We describe new, phage-derived probes that can be used as robust substitutes for antibodies.Methods: From a landscape phage library with random octapeptides displayed on all copies of the major phage coat protein of the phage fd-tet, we selected clones that bound to spores of B. anthracis (Sterne strain). ELISA, micropanning, and coprecipitation assays were used to evaluate the specificity and selectivity with which these phage bound to B. anthracis spores.Results: Peptides on the selected clones directed binding of the phage to B. anthracis spores. Most clones exhibited little or no binding to spores of distantly related Bacillus species, but some binding was observed with spores of closely related species. Our most specific spore-binding phage displayed a peptide EPRLSPHS (several thousand peptides per phage) and bound 3.5- to 70-fold better to spores of B. anthracis Sterne than to spores of other Bacillus species.Conclusions: The selected phage probes bound preferentially to B. anthracis Sterne spores compared with other Bacillus species. These phage could possibly be further developed into highly specific and robust probes suitable for long-term use in continuous monitoring devices and biosorbents.
Functional genomics identifies novel and diverse molecular targets of nutrients in vivo
Authors: Gohil Kishorchandra 
Published: August 2004

Abstract
Genomic responses to nutrients are important determinants of physiological and pathological functions of living systems. Many of these responses are mediated by changes in mRNA concentrations that are primarily regulated by gene transcription. Transcriptional networks that regulate the expression and activities of transcription factors and structural genes in response to nutrients need to be defined. The tools of functional genomics and bioinformatics offer powerful means to address these needs. The application of global mRNA profiling tools to define genome-wide responses to nutrients and micronutrients with a primary focus on in vivo genomic responses of vital organs of laboratory mice is reviewed here. The studies show that major and minor nutrients affect the expression of mRNAs that are related to aging and inflammation, and chemically diverse micronutrients such as polyphenols and tocopherols may exert their effects through modulating the expression of functionally related genes.
Mycobacterium tuberculosis Transmission From a Pediatrician to Patients
Authors: Askew George L. , Finelli Lyn , Hutton Mary , Laraque Fabienne , Porterfield Debra , Shilkret Kenneth , Valway Sarah E. , Onorato Ida , Spitalny Kenneth 
Published: August 2004

The following report describes the contact investigation of a pediatrician with tuberculosis (TB). The pediatrician's disease was discovered in late February 1993 after tuberculin skin testing (TST) of his 15-month-old son was positive (13-mm induration). Further investigation to identify the source of the child's infection revealed a positive (15-mm induration) TST in the pediatrician. The pediatrician had been symptomatic with a cough since September 1992. The pediatrician had a chest radiograph that revealed numerous cavitary lesions and a sputum smear that was positive for acid-fast bacilli. An investigation was initiated to assess whether the transmission of Mycobacterium tuberculosis had occurred in the pediatrician's office to patients, families, or other visitors. The investigation was later extended to include the hospitals and the day care center where the pediatrician worked.
Methods. A letter was mailed to parents of children served by the practice, explaining the potential exposure to TB and requesting that all persons who visited the office after September 1, 1992 complete an interview and Mantoux TST. Mass interviewing, testing, and test interpretation within the practice took place seven times during March and April 1993.
Results. At the completion of screening, 181 (87%) of 208 children who had close contact with the index case were reliably skin-tested and returned for interpretation. Three (1.7%) of the 181 children were TST-positive (≥5 mm). Thirty-seven (13%) of the 286 adults tested and returning for interpretations were TST-positive (≥10 mm). Thirty-two (86%) of the 37 adults who tested positive were foreign-born.
Conclusion. This investigation highlighted the need for identifying childhood TB infection as a sentinel event for adult disease. It also demonstrated the difficulty associated with deciding the extent of contact investigation of a health care worker with TB. Finally, the investigation emphasized the importance of maintaining regularly scheduled and appropriate testing for TB infection in health care workers and the need for health care workers to be cognizant of their own risk and be able to identify, especially in themselves, signs and symptoms of potential TB disease.
Comparison of Infasurf (Calf Lung Surfactant Extract) to Survanta (Beractant) in the Treatment and Prevention of Respiratory Distress Syndrome
Authors: Bloom Barry T. , Kattwinkel John , Hall Robert T. , Delmore Paula M. , Egan Edmund A. , Trout J. Richard , Malloy Michael H. , Brown David R. , Holzman Ian R. , Coghill Carl H. , Carlo Waldemar A. , Pramanik Arun K. , McCaffree Mary Anne , Toubas Paul L. , Laudert Susan , Gratny Linda L. , Weatherstone Kathleen B. , Seguin John H. , Willett Lynne D. , Gutcher Gary R. , Mueller Dawn H. , Topper William. H 
Published: August 2004

Objective. To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS.Design. A prospective, randomized, double-blind, multicenter clinical trial.Setting. Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm.Patients. The treatment arm enrolled infants of ≤2000 g birth weight with established RDS, and the prevention arm enrolled infants of ≤29 weeks' gestation with birth weights &lt;1250 g.Intervention. Infants were randomly assigned to receive Infasurf (n = 303, treatment arm; n = 180, prevention arm) or Survanta (n = 305, treatment arm; n = 194, prevention arm) in accordance with the Survanta package insert instructions.Outcome Measures. We projected a 25% reduction between groups in the need for a third dose of surfactant for infants with established RDS, and a 25% reduction in the need for a second dose of surfactant for infants who received prophylactic surfactant. Secondary outcomes included the severity of RDS measured by inspired oxygen concentrations and mean airway pressure, air leaks, complications associated with surfactant administration, and survival to 36 weeks' postmenstrual age without the need for oxygen supplementation.Results. In the treatment arm, there was no difference between groups in the number of infants requiring more than two doses of surfactant. The interval between doses was significantly longer for Infasurf, suggesting an increased duration of treatment effect. The inspired oxygen concentration and mean airway pressure were lower in the Infasurf infants during the first 48 hours in the treatment arm.In the prevention arm, there were no differences with respect to the number of surfactant doses. The dosing intervals were longer for Infasurf infants after the second dose. No difference in inspired oxygen or mean airway pressure was noted during the first 72 hours.There were no significant differences in the incidence of air leaks, complications associated with dosing, complications of prematurity, mortality, or survival without chronic lung disease in the prevention or treatment arm.Conclusions. Infants treated with Infasurf have a modest benefit in the acute phase of RDS. Infasurf seems to produce a longer duration of effect than Survanta.