bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Steroidogenic Acute Regulatory Protein Is Expressed in Steroidogenic Cells of the Day-Old Brain
Authors: King Steven R. , Ginsberg Stephen D. , Ishii Tomohiro , Smith Roy G. , Parker Keith L. , Lamb Dolores J. 
Published: June 2004

AbstractAlthough recent research has focused on the fundamental role(s) of steroids synthesized de novo in the brain on development, the mechanism by which production of these neurosteroids is regulated remains unclear. Steroid production in peripheral tissues is acutely regulated by the steroidogenic acute regulatory (StAR) protein, which mediates the rate-limiting step in steroid biosynthesis: the intramitochondrial delivery of cholesterol to cytochrome P450scc for conversion to steroid. We recently demonstrated that StAR is present in discrete cell types in the adult brain, suggesting that neurosteroid production is mediated by StAR. Nevertheless, little is known regarding the presence of StAR in the developing brain. In the present study, the presence of StAR and for the first time, its homolog, the putative cholesterol transport protein metastatic lymph node 64 (MLN64), were defined in the neonatal mouse brain using immunocytochemical techniques. Both StAR and MLN64 were found to be present in the brain with staining patterns characteristic to each protein, indicating the authenticity of StAR and MLN64 immunoreactivity. Furthermore, we found MLN64 to be expressed in the adult brain as well, apparently at higher levels than StAR. Importantly, StAR protein is present in cells that also express P450scc. These data suggest that, as with the adult, neurosteroid production during development occurs through a StAR-mediated pathway.
Site of Action of Acute Alcohol Administration in Stimulating the Rat Hypothalamic-Pituitary-Adrenal Axis: Comparison between the Effect of Systemic and Intracerebroventricular Injection of this Drug on Pituitary and Hypothalamic Responses
Authors: Lee Soon , Selvage Daniel , Hansen Keith , Rivier Catherine 
Published: June 2004

Abstract
The peripheral injection of alcohol stimulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, but the ready penetration of this drug in most bodily compartments has made it difficult to identify its specific sites of action. Here we determined whether alcohol can directly influence the corticotropes. We first determined whether alcohol acted within the brain to stimulate neurons in the paraventricular nucleus (PVN) of the hypothalamus, which synthesizes corticotropin-releasing factor (CRF) and vasopressin (VP). To test this hypothesis, we injected alcohol intracerebroventricularly (icv; 5 μl of 200-proof; 86 μmol) and compared these results with those obtained after its ip administration (3.0 g/kg). Although not causing neuronal damage and not leading to detectable levels of the drug in the general circulation, icv alcohol significantly up-regulated PVN CRF heteronuclear RNA levels and increased plasma ACTH levels, a change comparable to the one observed in the ip model. To determine whether alcohol stimulated the corticotropes independently of CRF and/or VP, we injected the drug ip or icv and measured changes in anterior pituitary proopiomelanocortin (POMC) transcripts and ACTH release in the presence or absence of endogenous CRF and/or VP. Intracerebroventricular and ip alcohol significantly increased POMC primary transcript levels, measured by ribonuclease protection assay, over a time-course that corresponded to ACTH release. Both the POMC and the ACTH responses were completely abolished by removal of CRF and VP. Collectively, these results indicate that alcohol-induced activation of the corticotropes does not represent a direct influence of the drug on the pituitary but requires CRF and VP.
Effects of Medroxyprogesterone and Estradiol on the Recovery of Spermatogenesis in Irradiated Rats
Authors: Shetty Gunapala , Weng Connie C. Y. , Bolden-Tiller Olga U. , Huhtaniemi Ilpo , Handelsman David J. , Meistrich Marvin L. 
Published: June 2004

AbstractSuppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3–7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2–4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA’s function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.
Estrogen Directly Induces Expression of Retinoic Acid Biosynthetic Enzymes, Compartmentalized between the Epithelium and Underlying Stromal Cells in Rat Uterus
Authors: Li Xiao-Hong , Kakkad Bharati , Ong David E. 
Published: June 2004

AbstractEstrogen (E2) has been shown to induce the biosynthesis of retinoic acid (RA) in rat uterus. Here we examined whether E2 could directly induce the enzymes involved in this process by using the ovariectomized rat. A retinol dehydrogenase that we have previously described, eRolDH, and the retinal dehydrogenase, RalDH II, were found to have markedly increased uterine mRNA levels within 4 h of E2 administration, independent of the prior administration of puromycin. eRolDH and RalDH II and their mRNAs were also increased in uteri of rats during estrus. This indicated that RA biosynthesis in rat uterus is directly controlled by E2 and provides a direct link between the action of a steroid hormone and retinoid action. We also examined the cell-specific localization of RalDH II by immunohistochemistry. The enzyme was observed in the stromal compartment, particularly in cells close to the uterine lumenal epithelium. eRolDH was observed only in the lining epithelial cells. Taken together with the previous observations of cellular retinol-binding protein and cellular retinoic acid-binding protein, type two also being expressed in the lumenal epithelium, we propose that RA production is compartmentalized, with retinol oxidation occurring in the lumenal epithelium and subsequent oxidation of retinal to RA occurring in the underlying stromal cells.
Prospero-Related Homeobox (Prox1) Is a Corepressor of Human Liver Receptor Homolog-1 and Suppresses the Transcription of the Cholesterol 7-α-Hydroxylase Gene
Authors: Qin Jun , Gao Da-ming , Jiang Quan-Feng , Zhou Qing , Kong Yu-Ying , Wang Yuan , Xie You-Hua 
Published: June 2004

Abstract
Cholesterol 7-α-hydroxylase (CYP7A1) catalyzes a rate-limiting step in bile acid synthesis in liver, and its gene transcription is under complex regulation by multiple nuclear receptors in response to bile acids, cholesterol derivatives, and hormones. The liver receptor homolog-1 (LRH-1), a member of the fushi tarazu factor 1 subfamily of nuclear receptors, has emerged as an essential regulator for the expression of cyp7a1. In this report, we demonstrate Prox1, a prospero-related homeobox transcription factor, identified through a yeast two-hybrid screening, can directly interact with human LRH-1 (hLRH-1) and suppresses hLRH-1-mediated transcriptional activation of human cyp7a1 gene. Biochemical analysis demonstrates that Prox1 interacts with both the ligand binding domain (LBD) and the DNA binding domain (DBD) of hLRH-1. An LRKLL motif in Prox1 is important for the interaction with the LBD but not the DBD of hLRH-1. In hLRH-1 LBD, helices 2 and 10 are essential for Prox1 recruitment. The suppression by Prox1 on the transcriptional activity of hLRH-1 can be mediated through its interaction with the LBD or the DBD of hLRH-1. Gel shift assays reveal that Prox1 impairs the binding of hLRH-1 to the promoter of human cyp7a1 gene.
Detection of Genetic Variants of Transthyretin by Liquid Chromatography–Dual Electrospray Ionization Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry
Authors: Nepomuceno Angelito I , Mason Christopher J , Muddiman David C , Bergen H Robert , Zeldenrust Steven R 
Published: June 2004

AbstractBackground: One of the numerous proteins causing amyloidosis is transthyretin (TTR), a protein usually responsible for the transport of thyroxine and retinol-binding protein. Variants within TTR cause it to aggregate and form insoluble fibers that accumulate in tissue, leading to organ dysfunction.Methods: TTR was immunoprecipitated from serum by use of a polyclonal antibody and subsequently reduced with tris(2-carboxyethyl)phosphine. The purified TTR was then analyzed by fast-gradient liquid chromatography–dual-electrospray ionization Fourier-transform ion-cyclotron-resonance (FT-ICR) mass spectrometry. DNA sequencing was performed on all samples used in this study.Results: Because of the inherent limitations in achieving high mass measurement accuracy based on the most abundant isotopic mass, we applied a fitting procedure that allowed determination of monoisotopic mass. Wild-type TTR (mean molecular mass, 13 761 Da) and its associated variant forms could be distinguished because of the high molecular mass accuracy afforded by FT-ICR (≤3 ppm) except for instances involving isobaric species or when isotopic distributions overlapped significantly. The [M + 11 H+]11+ charge state for all samples was used to determine the mass accuracies for both wild-type and variant forms of the protein. We correctly assigned seven of seven TTR variants. Moreover, using a combination of proteomic and genomic technologies, we discovered and characterized a previously unreported cis double mutation with a mass only 2 Da different from wild-type TTR. Furthermore, DNA sequencing of the TTR gene for all individuals in this study completely agreed with the intact protein measurements.Conclusions: FT-ICR mass spectrometry has sufficient mass accuracy to identify genetic variants of immunoaffinity-purified TTR. We believe that 91% of known TTR variants could be detected by this technique.
Relationship between Benign Prostatic Hyperplasia and History of Coronary Artery Disease in Elderly Men
Authors: Weisman Kenneth M. , Larijani Ghassem E. , Goldstein Mark R. , Goldberg Michael E. 
Published: June 2004

Study Objective. To assess the relationship between the occurrence of benign prostatic hyperplasia (BPH), an androgen‐dependent disease, and coronary artery disease (defined as history of coronary artery bypass grafting, coronary angioplasty, myocardial infarction) in elderly men.Design. Retrospective chart review.Setting. Urology practice.Patients. Seven hundred two elderly men aged 65–80 years.Intervention. The men's charts were reviewed for data pertaining to coronary artery disease, risk factors for coronary artery disease, and serum prostate‐specific antigen (PSA) levels. Men who had medical conditions, pharmacologic interventions, or surgical procedures that could alter PSA, and those taking lipid‐lowering agents were not included.Measurements and Main Results. PSA levels correlate positively with prostatic volume of BPH. In men with levels under 1.0 μg/L (no BPH) and over 1.0 μg/L (BPH present), the frequency of coronary artery disease was 9% and 29%, respectively (p<0.03). No significant differences were noted between groups in other accepted risk factors for coronary artery disease including age, smoking, diabetes mellitus, or hypertension.Conclusion. Smooth muscle proliferation is an important and possibly androgen‐dependent step in the development of atherosclerosis and BPH. Prospective studies are required to assess the effect of antiandrogens on atherosclerosis.
Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients
Authors: Hataji Osamu , Taguchi Osamu , Gabazza Esteban Cesar , Yuda Hisamichi , D'Alessandro‐Gabazza C.N. , Fujimoto Hajime , Nishii Yoichi , Hayashi Tatsuya , Suzuki Koji , Adachi Yukihiko 
Published: June 2004

AbstractImpairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. This study assessed the circulating level of thrombin‐activatable fibrinolysis inhibitor in patients with lung cancer and its expression by several lung cancer cell lines. The plasma concentrations of thrombin‐activatable fibrinolysis inhibitor were significantly increased in lung cancer patients compared to healthy subjects. The concentration of thrombin‐activatable fibrinolysis inhibitor was particularly higher in patients with small cell carcinoma compared to those with adenocarcinoma or squamous cell carcinoma, and in cancer patients that responded to chemotherapy compared to non‐responders. In vitro studies showed more expression of thrombin‐activatable fibrinolysis inhibitor in small cell carcinoma than in adenocarcinoma cell lines and more expression in lung cancer cell lines sensitive to anti‐cancer agents than in resistant cell lines. This study suggests that thrombin‐activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients. Am. J. Hematol. 76:214–219, 2004. © 2004 Wiley‐Liss, Inc.
Hydrops fetalis associated with homozygosity for hemoglobin Taybe (α 38/39 THR deletion) in newborn triplets
Authors: Arnon Shmuel , Tamary Hannah , Dgany Orly , Litmanovitz Ita , Regev Rivka , Bauer Sofia , Dolfin Tzipora , Yacobovich Joanne , Wolach Baruch , Jaber Lutfi 
Published: June 2004

AbstractHemoglobin Taybe is an unstable α‐chain hemoglobin variant caused by a deletion of a threonine residue at codon 38 or 39 of the α‐1 globin chain. We describe preterm infant triplets born with hydrops fetalis and anemia who were found by DNA analysis to be homozygous for hemoglobin Taybe. All three infants developed intrauterine hemolytic anemia, which subsequently led to hydrops fetalis. To the best of our knowledge, this is the first description of hydrops fetalis associated with this hemoglobinopathy. We suggest that hemoglobin Taybe be considered in the differential diagnosis of hydrops fetalis and that known affected fetuses be carefully followed both antenatally and postnatally. Am. J. Hematol. 76:263–266, 2004. © 2004 Wiley‐Liss, Inc.
Imatinib mesylate‐sensitive blast crisis immediately after discontinuation of imatinib mesylate therapy in chronic myelogenous leukemia: Report of two cases
Authors: Higashi Takehiro , Tsukada Junichi , Kato Chiaki , Iwashige Atsushi , Mizobe Takamitsu , Machida Shinichiro , Morimoto Hiroaki , Ogawa Ryosuke , Toda Yoko , Tanaka Yoshiya 
Published: June 2004

AbstractAlthough imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate‐resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate‐sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re‐introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression. Am. J. Hematol. 76:275–278, 2004. © 2004 Wiley‐Liss, Inc.
Genomic instability in bone marrow failure syndromes
Authors: Kearns William G. , Sutton Joanne F. , Maciejewski Jaroslaw P. , Young Neal S. , Liu Johnson M. 
Published: June 2004

AbstractAneuploidy is frequently seen in leukemia and myelodysplasia (MDS) but was thought to be uncommon in aplastic anemia (AA). We examined marrow cells from 96 unselected patients with bone marrow failure syndromes to assess the frequency of undetected aneuploidy for chromosomes 7 and 8 by fluorescence in situ hybridization (FISH) as compared to routine cytogenetic analysis. Twenty‐eight percent (27/96) of patients had an abnormal karyotype. FISH identified an additional 27 patients with undetected monosomy 7 or trisomy 8. Those patients with undetected monosomy 7 generally had a poor clinical outcome, suffering from lack of response to medical therapy or early death. In one AA/MDS patient with normal cytogenetics, FISH identified a large population of monosomy 7 cells, which clearly heralded a clinical relapse. In another patient, FISH studies were used to delineate instability of chromosome 8, with apparent disease progression from AA to MDS. We conclude that undetected aneuploidy exists in marrow cells of a significant percentage of patients with bone marrow failure syndromes. Am. J. Hematol. 76:220–224, 2004. Published 2004 Wiley‐Liss, Inc.
A novel MSX1 mutation in hypodontia
Authors: De Muynck S. , Schollen E. , Matthijs G. , Verdonck A. , Devriendt K. , Carels C. 
Published: June 2004

AbstractMSX1 mutations have been reported in four unrelated families with autosomal dominant tooth agenesis. In one family, some individuals also had cleft lip and/or palate. We have identified a novel MSX1 mutation (559 C → T, resulting in Gln187Stop) in three individuals of one family. © 2004 Wiley‐Liss, Inc.
Impact of excluding cases with known chromosomal abnormalities on the prevalence of structural birth defects, Hawaii, 1986–1999
Authors: Forrester Mathias B. , Merz Ruth D. 
Published: June 2004

AbstractChromosomal abnormalities are more common in the presence of structural birth defects. However, much of the literature have only provided chromosomal abnormality rates for one or a few structural birth defects at a time. This study calculated the chromosomal abnormality rates for a number of structural birth defects using data from the Hawaii Birth Defects Program (HBDP) for deliveries during 1986–1999 and evaluated the impact of exclusion of cases with chromosomal abnormalities when calculating birth prevalence. The chromosomal abnormality rates were highest for endocardial cushion defect (40%) and omphalocele (27%), while no chromosomal abnormalities were reported for pyloric stenosis, persistent cloaca, and deficiency of lower limbs. The majority of chromosomal abnormality rates fell within a certain range, with 32 (63%) of the birth defect categories having chromosomal abnormality rates of 5–15%. The chromosomal abnormality rates also tended to be higher for multiple than for isolated cases. For three of the structural birth defects (ventricular septal defect, atrial septal defect, endocardial cushion defect), the birth prevalence of the defect, when cases with a chromosomal abnormality were excluded, was significantly lower than the birth prevalence that included those cases. Chromosomal abnormality rates varied by type of structural birth defect and presence of other major structural birth defects. For at least several structural birth defects, exclusion of cases with chromosomal abnormalities significantly underestimated the birth prevalence. This underestimation may be important, depending on the purpose of the analysis. © 2004 Wiley‐Liss, Inc.
Palladiumoxidasekatalyse: selektive Oxidation durch direkte disauerstoffgekoppelte Umsetzung
Authors: Stahl Shannon S. 
Published: June 2004

AbstractDie selektive aerobe Oxidation organischer Verbindungen ist eines der fundamentalsten Probleme der modernen organischen Chemie. Effektive Lösungen müssen die spezifische Reaktivität und Selektivität von molekularem Sauerstoff berücksichtigen und unterschiedliche Klassen von Oxidationsreaktionen abdecken. Die Palladiumoxidasekatalyse kombiniert die Vielseitigkeit Palladium(II)‐vermittelter Oxidationen organischer Substrate mit der Oxidation des reduzierten Palladium‐Katalysators durch Disauerstoff und ermöglicht so einen Zugang zu einer breiten Auswahl an selektiven aeroben Oxidationsreaktionen. Neuere Ergebnisse zeigen, dass Cokatalysatoren wie Kupfer(II), Polyoxometallate und Benzochinone in der Oxidation von Palladium(0) durch molekularen Sauerstoff verzichtbar sind. Eine große Bedeutung für diese Reaktionen haben oxidativ stabile Liganden, die die Katalysatorzersetzung minimieren, die direkte Reaktion von Palladium mit Disauerstoff fördern, die Reaktivität des organischen Substrats regulieren und asymmetrische Katalysen ermöglichen.
Optimization of polyhydroxybutyrate production by mixed cultures submitted to aerobic dynamic feeding conditions
Authors: Serafim Luísa S. , Lemos Paulo C. , Oliveira Rui , Reis Maria A.M. 
Published: June 2004

AbstractActivated sludge submitted to aerobic dynamic feeding conditions showed a good and stable capacity to store polyhydroxybutyrate (PHB). The system, working for 2 years, selected a microbial population with a high PHB storage capacity. The influence of carbon and nitrogen concentrations on the PHB accumulation yield was studied in a range of 15–180 Cmmol/l for acetate and 0–2.8 Nmmol/l for ammonia. Low ammonia concentrations favored PHB accumulation. The maximum PHB content, 67.5%, was obtained for 180 Cmmol/l of acetate supplied in one pulse. However, such high substrate concentration proved to be inhibitory for the storage mechanism, causing a slowdown of the specific PHB storage rate. In order to avoid substrate inhibition, 180 Cmmol/l of acetate was supplied in different ways: continuously fed and in three pulses of 60 Cmmol/l each. In both cases the specific PHB storage rate increased and the PHB content obtained were 56.2% and 78.5%, respectively. The latter value of PHB content is similar to that obtained by pure cultures and was never reported for mixed cultures. Addition of acetate by pulses controlled by the oxygen concentration was kept for 16 days, the PHB content being always above 70% of cell dry weight. © 2004 Wiley Periodicals, Inc.