bluuebunny/crossref_metadata_2025 huggingface dataset:
EN QUÊTE DE L'ÉTHIQUE MUSULMANE I LA NOTION D'ÉGALITÉ EN ISLAM
Authors: Leites Adrien
Published: April 2003

Ce travail s'attache à explorer, conformément aux exigences d'une herméneutique de la Tradition musulmane et en vue de fixer les traits d'une éthique musulmane, le champ de l'égalité et de la différenciation en islam. La notion d'égalité fait l'objet d'une première exploration, qui révèle la prédominance de l'égalité fondée sur l'ascendance adamique. Il apparaît que cette conception s'applique exclusivement à la différentiation héréditaire, et qu'elle est généralement associée à l'affirmation de l'inégalité religieuse. Une seconde exploration met en évidence le passage de la double affirmation de l'égalité héréditaire et de l'inégalité religieuse à l'affirmation d'une double inégalité – héréditaire et religieuse. Cette dernière affirmation apparaît comme constitutive d'un modèle de différenciation associant deux principes distincts, qui recouvrent eux-mêmes des contenus variables. L'association d'un principe héréditaire et d'un principe religieux au sein d'un même modèle de différenciation est rangée, à l'issue de l'exploration, parmi les traits distinctifs d'une éthique sunnite.
MIRACLES IN SĪĪ THOUGHT A CASE-STUDY OF THE MIRACLES ATTRIBUTED TO IMĀM GAFAR AL-SĀDIQ
Authors: Loebenstein Judith
Published: April 2003

According to Imāmī doctrine, the ability to perform miracles (Mugizāt) is one of the characteristics of the Imām. This goes against the position of the Sunna, which claims that only prophets are able to perform miracles. The article discusses the various definitions of miracles in Islam and surveys the miracles attributed to Imām Gafar al-Sādiq (d. 148/765). This survey demonstrates the various capabilities attributed to the Im m and illuminates a number of patterns common to the traditions relating the Im m's miraculous deeds. The most noteworthy of these patterns is the association of a miracle performed by the Imāmī with a qurānic miracle, usually performed by a prophet. The aim of this pattern is to reinforce the Imāmī position regarding the equal status of an Imāmī and prophetic miracle.
Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting
Authors: Rahimy Mohamed Cherif , Gangbo Annick , Ahouignan Gilbert , Adjou Roselyn , Deguenon Chantal , Goussanou Stephanie , Alihonou Eusebe
Published: April 2003

Clinical severity of sickle cell anemia (SS) in Africa may not be solely determined by genetic factors. This study evaluated the effects of intensive parental education and adequate clinical care on the course of SS in children in Benin. SS children referred to the National Teaching Hospital in Cotonou were included in the study. Teaching about SS was repeated frequently, emphasizing the importance of keeping clinic appointments, improving the nutrition of the affected children, and instituting antipneumococcal and antimalarial prophylaxis. Frequency and severity of SS-related events, changes in physical growth, frequency of malarial attacks, causes of transfusion, and causes of death were the principal variables assessed. 236 young children with repeated SS-related acute complications were studied from July 1, 1993, to December 31, 1999 (983 patient-years). A marked reduction in the frequency and severity of SS-related acute events was observed. Improvement in general status and physical growth was noted in 184 patients (78%); in addition, 22 of the remaining 52 patients showed similar improvement after remotivating the parents for compliance. There were 10 deaths, primarily in this cohort of 52 patients. Intensive sociomedical intervention can produce sustained clinical improvement in many severely ill SS children in sub-Saharan Africa.
Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease
Authors: Lion Thomas , Baumgartinger Rosi , Watzinger Franz , Matthes-Martin Susanne , Suda Magdalena , Preuner Sandra , Futterknecht Barbara , Lawitschka Anita , Peters Christina , Pötschger Ulrike , Gadner Helmut
Published: April 2003

Adenovirus (AdV) infection in the course of allogeneic stem cell transplantation (SCT) is associated with high transplant-related morbidity and mortality. Disseminated AdV disease is lethal in most instances. Early detection of AdV infection and identification of patients carrying a high risk of disseminated disease therefore remain a major challenge. In view of the large number of existing AdV types, we have established real-time polymerase chain reaction (PCR) assays permitting sensitive detection and quantification of all 51 currently known human AdV serotypes. In a series of 132 consecutive pediatric patients undergoing SCT, more than 5000 samples derived from peripheral blood (PB), stool, urine, and throat were screened for adenovirus infection by PCR during the posttransplantation period. Thirty-six patients (27%) tested positive by PCR, revealing AdV types of the subgenera A, B, C, D, and F. Except for enteritis in some patients with AdV positivity in stool, detection of the virus at sites other than PB was not associated with clinical signs of virus disease, and transplant-related mortality was not significantly different from AdV-negative patients. By contrast, 82% of patients who had detectable AdV in PB died from infectious complications (P < .001). Monitoring of PB specimens by real-time PCR permitted early diagnosis of invasive AdV infection in all instances. In patients who developed disseminated AdV disease, detection of the virus in PB preceded onset of clinical symptoms by a median of more than 3 weeks. The observation of AdV in peripheral blood may therefore serve as a basis for early initiation of preemptive antiviral treatment.
Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients
Authors: Markert M. Louise , Sarzotti Marcella , Ozaki Daniel A. , Sempowski Gregory D. , Rhein Maria E. , Hale Laura P. , Le Deist Francoise , Alexieff Marilyn J. , Li Jie , Hauser Elizabeth R. , Haynes Barton F. , Rice Henry E. , Skinner Michael A. , Mahaffey Samuel M. , Jaggers James , Stein Leonard D. , Mill Michael R.
Published: April 2003

Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vβ (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
Ex vivo targeting of p21Cip1/Waf1 permits relative expansion of human hematopoietic stem cells
Authors: Stier Sebastian , Cheng Tao , Forkert Randolf , Lutz Christoph , Dombkowski David M. , Zhang Jie Lin , Scadden David T.
Published: April 2003

Relative quiescence is a defining characteristic of hematopoietic stem cells. Reasoning that inhibitory tone dominates control of stem cell cycling, we previously showed that mice engineered to be deficient in the cyclin-dependent kinase inhibitor, p21Cip1/Waf1 (p21), have an increased stem cell pool under homeostatic conditions. Since p21 was necessary to maintain stem cell quiescence and its absence sufficient to permit increased murine stem cell cycling, we tested whether reduction of p21 alone in human adult–derived stem cells could affect stem cell proliferation. We demonstrate here that interrupting p21 expression ex vivo resulted in expanded stem cell number and in vivo stem cell function compared with control, manipulated cells. Further, we demonstrate full multilineage reconstitution capability in cells where p21 expression was knocked down. Therefore, lifting the brake on cell proliferation by altering cell cycle checkpoints provides an alternative paradigm for increasing hematopoietic stem cell numbers. This approach may be useful for relative ex vivo human stem cell expansion.
IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor
Authors: Lam Vivian , Kalesnikoff Janet , Lee Corinna W. K. , Hernandez-Hansen Valerie , Wilson Bridget S. , Oliver Janet M. , Krystal Gerald
Published: April 2003

We recently demonstrated that immunoglobulin E (IgE), in the absence of cross-linking agents, activates signaling pathways in healthy murine bone marrow–derived mast cells (BMMCs) and that this activation enhances BMMC survival, at least in part, via secretion of autocrine-acting cytokines. We report herein that IgE alone also triggers the adhesion of both BMMCs and connective tissue mast cells (CTMCs) to the connective tissue component, fibronectin (FN). This adhesion occurs to the same extent as that triggered by optimal levels of Steel factor (SF) or IgE + antigen (IgE + Ag) and is mediated by an increased avidity of the integrin very late antigen 5 (VLA-5). Moreover, this IgE-induced adhesion, which is prolonged compared with that elicited by SF or IgE + Ag, requires phosphatidylinositol 3-kinase (PI3K), phospholipase C γ (PLCγ), and extracellular calcium but not extracellular-regulated kinase (Erk) or p38. Interestingly, we found, using the calcium channel blocker, 2-APB (2-aminoethoxydiphenyl borate) and Lyn–/– BMMCs that both IgE- and IgE + Ag-induced adhesion to FN require extracellular calcium entry, whereas SF does not. Furthermore, our data suggest that FN acts synergistically with IgE to prolong intracellular phosphorylation events and to enhance IgE-induced inflammatory cytokine production and BMMC survival.
Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry
Authors: Percy Melanie J. , McMullin Mary Frances , Jowitt Simon N. , Potter Michael , Treacy Marilyn , Watson William H. , Lappin Terence R. J.
Published: April 2003

The Chuvash form of polycythemia is an autosomal recessive disorder common to a large number of families in central Russia. Affected individuals have been reported to be homozygous for an Arg200Trp mutation in the von Hippel–Lindau (VHL) gene. We have screened 78 patients with erythrocytosis and found 8 of Bangladeshi and Pakistani origin to be homozygous for the Arg200Trp mutation and another of English descent to be heterozygous. Of these patients, 5 have elevated serum erythropoietin (Epo) levels, while the other 4 have Epo values in the normal range. The heterozygous patient does not fulfill the Chuvash criterion for homozygosity of the Arg200Trp mutation and consequently may harbor a further, as yet uncharacterized, mutation. This mutation has a wider geographic distribution than originally presumed and haplotype analysis suggests a common origin of the Arg200Trp mutation in the 4 families, but it still remains to be established if it has arisen independently of the Chuvash population.
Molecular and functional analysis of Shiga toxin–induced response patterns in human vascular endothelial cells
Authors: Matussek Andreas , Lauber Joerg , Bergau Anna , Hansen Wiebke , Rohde Manfred , Dittmar Kurt E. J. , Gunzer Matthias , Mengel Michael , Gatzlaff Patricia , Hartmann Maike , Buer Jan , Gunzer Florian
Published: April 2003

Enterohemorrhagic Escherichia coli (EHEC) is the major cause of hemolyticuremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. EHEC produces one or more Shiga toxins (Stx1 and Stx2), and it was assumed that Stx's only relevant biologic activity was cell destruction through inhibition of protein synthesis. However, recent data indicate that in vivo the cytokine milieu may determine whether endothelial cells survive or undergo apoptosis/necrosis when exposed to Stxs. In this study, we analyzed the genome-wide expression patterns of human endothelial cells stimulated with subinhibitory concentrations of Stxs in order to characterize the genomic expression program involved in the vascular pathology of HUS. We found that Stxs elicited few, but reproducible, changes in gene expression. The majority of genes reported in this study encodes for chemokines and cytokines, which might contribute to the multifaceted inflammatory response of host endothelial cells observed in patients suffering from EHEC disease. In addition, our data provide for the first time molecular insights into the epidemiologically well-established higher pathogenicity of Stx2 over Stx1.
CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma
Authors: Robillard Nelly , Avet-Loiseau Hervé , Garand Richard , Moreau Philippe , Pineau Danielle , Rapp Marie-Josée , Harousseau Jean-Luc , Bataille Régis
Published: April 2003

CD20 has been reinvestigated in 66 patients with multiple myeloma (MM). Twelve of the patients (18%) expressed CD20, including 5 of 50 patients at diagnosis presenting 100% CD20+ cells. Seven (58%) of 12 CD20+ patients with MM had a small mature plasma cell morphology as opposed to 4 (7%) of 54 with CD20- MM (P = .0001). Of note, 10 (83%) of 12 patients with CD20+ MM had t(11;14) as opposed to 5 of 54 (9%) CD20- patients (P < .001). All the patients with 100% CD20+ cells presented with t(11;14) and 4 of 5 with a small mature plasma cell morphology. Thus, 66% of the patients with t(11;14) expressed CD20, whereas only 4% of the 51 patients lacking such translocation expressed CD20 (P < .0001). In conclusion, CD20 expression is associated with small mature plasma cell morphology and with t(11;14) in patients with MM.
Survival of acute myeloid leukemia cells requires PI3 kinase activation
Authors: Xu Qing , Simpson Serge-Emile , Scialla Timothy J. , Bagg Adam , Carroll Martin
Published: April 2003

The mechanisms that regulate the growth and survival of acute myeloid leukemia (AML) cells are largely unknown. We hypothesized that constitutive activation of phosphatidyl-inositide 3 kinase (PI3 kinase) could regulate survival in primary cells from patients with AML. Here we demonstrate that Akt, a critical substrate of PI3 kinase, is activated in AML blasts. In a short-term culture system, most AML patient samples showed a dose-dependent decrease in survival after incubation with the PI3 kinase inhibitor LY294002. This decrease in survival was partially due to the induction of apoptosis. Furthermore, we have shown that p70 S6 kinase and 4EBP-1, downstream mediators of Akt signaling, also are phosphorylated in AML blasts. Phosphorylation of these proteins is inhibited by the mTOR inhibitor RAD001. Incubation of AML blasts with RAD001 induces only a small decrease in survival of the cells; however, when combined with Ara-C, RAD001 enhances the toxicity of Ara-C. These results demonstrate that constitutive activation of the PI3 kinase pathway is necessary for the survival of AML blasts and that targeting of this pathway with pharmacologic inhibitors may be of clinical benefit in treatment of AML.
Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization
Authors: Heeschen Christopher , Aicher Alexandra , Lehmann Ralf , Fichtlscherer Stephan , Vasa Mariuca , Urbich Carmen , Mildner-Rihm Christiane , Martin Hans , Zeiher Andreas M. , Dimmeler Stefanie
Published: April 2003

Increasing evidence suggests that postnatal neovascularization involves the recruitment of circulating endothelial progenitor cells (EPCs). Hematopoietic and endothelial cell lineages share common progenitors. Cytokines formerly thought to be specific for the hematopoietic system have only recently been shown to affect several functions in endothelial cells. Accordingly, we investigated the stimulatory potential of erythropoietin (Epo) on EPC mobilization and neovascularization. The bone marrow of Epo-treated mice showed a significant increase in number and proliferation of stem and progenitor cells as well as in colony-forming units. The number of isolated EPCs and CD34+/flk-1+ precursor cells was significantly increased in spleen and peripheral blood of Epo-treated mice compared with phosphate-buffered saline–treated mice. In in vivo models of postnatal neovascularization, Epo significantly increased inflammation- and ischemia-induced neovascularization. The physiologic relevance of these findings was investigated in patients with coronary heart disease. In a multivariate regression model, serum levels of Epo and vascular endothelial growth factor were significantly associated with the number of stem and progenitor cells in the bone marrow as well as with the number and function of circulating EPCs. In conclusion, the present study suggests that Epo stimulates postnatal neovascularization at least in part by enhancing EPC mobilization from the bone marrow. Epo appears to physiologically regulate EPC mobilization in patients with ischemic heart disease. Thus, Epo serum levels may help in identifying patients with impaired EPC recruitment capacity.
Plasminogen activator inhibitor type–1 deficiency does not influence the outcome of murine pneumococcal pneumonia
Authors: Rijneveld Anita W. , Florquin Sandrine , Bresser Paul , Levi Marcel , de Waard Vivian , Lijnen Roger , Van der Zee Jaring S. , Speelman Peter , Carmeliet Peter , van der Poll Tom
Published: April 2003

Urokinase-type plasminogen activator (uPA) and its receptor uPAR are components of the fibrinolytic system and are important for an adequate immune response to respiratory tract infection, in part through their role in the migration of inflammatory cells. PA inhibitor–1 (PAI-1) is the predominant inhibitor of soluble and receptor-bound uPA. To determine the role of PAI-1 in host defense against pneumococcal pneumonia, the following studies were performed: (1) Patients with unilateral community-acquired pneumonia demonstrated elevated PAI-1 concentrations together with decreased PA activity in bronchoalveolar lavage fluid (BALF) obtained from the infected, but not from the contralateral, site. (2) Mice with Streptococcus pneumoniae pneumonia displayed elevated PAI-1 protein and mRNA levels in their lungs. (3) PAI-1 gene–deficient mice, however, had an unaltered immune response to pneumococcal pneumonia, as measured by cell recruitment into lungs, bacterial outgrowth, and survival. Furthermore, plasminogen-gene–deficient mice also had an unremarkable defense against pneumococcal pneumonia. These data indicate that pneumonia is associated with inhibition of the fibrinolytic system at the site of the infection secondary to increased production of PAI-1; an intact fibrinolytic response is not required for an adequate host response to respiratory tract infection, however, suggesting that the previously described role of uPA and uPAR are restricted to their function in cell migration.
Changes in the lymph node microenvironment induced by oncostatin M
Authors: Louis Isabelle , Dulude Gaël , Corneau Sophie , Brochu Sylvie , Boileau Catherine , Meunier Caroline , Côté Caroline , Labrecque Nathalie , Perreault Claude
Published: April 2003

Oncostatin M (OM) transforms the lymph node (LN) into a “super lymphoid organ” with 2 striking features: massive thymus-independent T-cell development and major expansion of the memory T-cell pool. We report that T-cell development in the LckOM LN is regulated by a cyclooxygenase-2 (COX-2)–dependent neoangiogenesis involving high endothelial venules (HEVs). That LN HEVs are particularlyrich in OM-receptor β-chain provides aplausible explanation for the fact that extrathymic T-cell development in LckOM mice is limited to the LN. Moreover, we found that increased production of the CCL20 chemokine by LN stromal cells was instrumental in the expansion of the memory phenotype CD4 T-cell pool in LckOM mice. The generality of the latter finding was demonstrated by the fact that CCL20/CCR6 interactions increase the basal proliferation rate of CD62Llo CD4 T cells irrespective of their thymic (in non–OM-transgenic mice) or extrathymic (in LckOM mice) origin. To our knowledge, CCL20 is the first molecule found to increase the proliferation of memory phenotype CD4 T cells. These findings identify potential targets for the creation of thymic substitutes (LN HEVs) and for expansion of the CD4 memory T-cell compartment (CCL20).
Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells
Authors: Chadwick Kristin , Wang Lisheng , Li Li , Menendez Pablo , Murdoch Barbara , Rouleau Anne , Bhatia Mickie
Published: April 2003

Human embryonic stem cells (hESCs) randomly differentiate into multiple cell types during embryoid body (EB) development. To date, characterization of specific factors capable of influencing hematopoietic cell fate from hESCs remains elusive. Here, we report that the treatment of hESCs during EB development with a combination of cytokines and bone morphogenetic protein-4 (BMP-4), a ventral mesoderm inducer, strongly promotes hematopoietic differentiation. Hematopoietic progenitors of multiple lineages were generated from EBs and were found to be restricted to the population of progeny expressing cell surface CD45. Addition of BMP-4 had no statistically significant effect on hematopoietic differentiation but enabled significant enhancement in progenitor self-renewal, independent of cytokine treatment. Hematopoietic commitment was characterized as the temporal emergence of single CD45+ cells first detectable after day 10 of culture and was accompanied by expression of hematopoietic transcription factors. Despite the removal of cytokines at day 10, hematopoietic differentiation of hESCs continued, suggesting that cytokines act on hematopoietic precursors as opposed to differentiated hematopoietic cells. Our study establishes the first evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of hESC lines and provides an unprecedented system to study early developmental events that govern the initiation of hematopoiesis in the human.
Transformation of VLF anomaly maps into apparent resistivity and phase
Authors: Becken Michael , Pedersen Laust B.
Published: April 2003

We investigate a transformation of magnetic transfer functions into the tangential‐electric mode part of the impedance tensor in the scope of the plane‐wave electromagnetic tensor–VLF method. The transformation, which is applicable to any 2D data representing the response of arbitrary 3D geoelectric structures, overcomes the difficulties of quantitative interpretation of magnetic transfer functions, which predominantly provide a measure of the lateral changes of the electrical conductivity in the earth. We require densely sampled magnetic transfer functions of one frequency as input data. These may be decomposed into their normal and anomalous parts (deviation from the response of a layered earth) for a unit external plane‐wave source field using the Hilbert transform relationship between the magnetic field components. Faraday's law then directly provides the anomalous toroidal electric field. Unfortunately, there is no chance to estimate the normal electric field from magnetic data, since the magnetic field is not sensitive to a layered earth. This constant must be provided as a boundary condition, e.g., from one ground measurement, to derive an impedance tensor and related apparent resistivities and phases.
Analysis of conductivity of random media using dc, MT, and TEM
Authors: Bigalke Jürgen
Published: April 2003

In geophysics, the geoelectric (dc), magnetotelluric (MT), and transient electromagnetic (TEM) measuring procedures are commonly used to investigate electrical properties of the ground. Finite difference codes are available for all these methods and, in this paper, the data obtained from numerical simulations are compared with regard to two‐component cubic random lattices. Provided the usage of a convenient normalization procedure, it was expected that in case of statistically homogeneous and isotropic random lattices dc, MT, and TEM would yield the same results. Surprisingly, this is not true for the MT data; the lowest MT conductivities are only one‐fifth of the corresponding TEM values.
Seismic modeling study of the Earth's deep crust
Authors: Carcione José M. , Finetti Icilio R. , Gei Davide
Published: April 2003

We use seismic modeling methods to validate the interpretation of deep‐crust seismic exploration. An approximation of the stacked section is obtained with the nonreflecting wave equation and the exploding‐reflector approach. Using this technique and ray‐tracing algorithms, we obtain a geological model by comparing the synthetic section with the real stacked section. An isotropic constitutive equation is assumed in this phase. The exact synthetic stacked section is then obtained by applying the standard processing sequence to a set of synthetic common‐shot profiles computed with the variable‐density acoustic wave equation. We introduce elliptical P‐wave anisotropy and the effects of small‐scale inhomogeneities by using a von Kármán autocovariance probability function that simulates scattering Q effects. Verification of the geological model by poststack migration constitutes an additional test. The methodology, which is suitable for areas of complex geology, is applied to a seismic line acquired in the northern Apennines as part of the Italian deep‐crust exploration project, CROP. This area is particularly difficult to interpret because of the presence of a complex tectonic setting.
Anisotropic inversion of seismic data for stressed media: Theory and a physical modeling study on Berea Sandstone
Authors: Sarkar Debashish , Bakulin Andrey , Kranz Robert L.
Published: April 2003

Nonhydrostatic stress, an often‐ignored source of seismic anisotropy, is universally present in the subsurface and may be as common as intrinsic or fracture‐induced anisotropy. Nonhydrostatic stress, applied to an initially transversely isotropic solid with vertical symmetry axis (VTI), results in an effective medium having almost orthorhombic symmetry (provided that one of the principal stresses is aligned with the symmetry axis). The symmetry planes observed in this orthorhombic medium are aligned with the orientations of the principal stresses, and anisotropic parameters (ε(1,2), δ(1,2,3), and γ(1,2)) can reveal information about the stress magnitudes. Thus, time‐lapse monitoring of changes in anisotropy potentially can provide information on temporal variations in the stress field.

We use nonlinear elasticity theory to relate the anisotropic parameters to the magnitudes of the principal stresses and verify these relationships in a physical modeling study. Under the assumption of weak background and stress‐induced anisotropy, each effective anisotropic parameter reduces to the sum of the corresponding Thomsen parameter for the unstressed VTI background and the corresponding parameter associated with the nonhydrostatic stress. The stress‐related anisotropic parameters depend only on the differences between the magnitudes of principal stresses; therefore, principal stresses can influence anisotropic parameters only if their magnitudes differ in the symmetry plane in which the anisotropic parameters are defined.

We test these predictions on a physical modeling data set acquired on a block of Berea Sandstone exhibiting intrinsic VTI anisotropy. Uniaxial stress, applied normal to the VTI symmetry axis, i.e., horizontally, produces an effective medium that is close to orthorhombic. We use two different methods to estimate the anisotropic parameters and study their variation as a function of stress. The first method utilizes conventional measurements of transmission velocities along the principal axes of the sample. The second method uses PP and PS reflection data acquired along seven different azimuths on the surface of the block.

In accordance with theoretical predictions, the anisotropic parameters in the vertical plane normal to the stress are almost insensitive to the magnitude of the stress. In contrast, anisotropic parameters in the vertical plane of the applied stress increase approximately in a linear fashion with increasing stress. Except for the parameter δ(1), comparison of the measured values of anisotropic parameters with theoretical predictions shows satisfactory agreement.

Despite some documented discrepancies, we believe that nonlinear elasticity may provide a suitable framework for estimating pore pressure and 3D stresses from seismic data.
Theory of differential offset continuation
Authors: Fomel Sergey
Published: April 2003

I introduce a partial differential equation to describe the process of prestack reflection data transformation in the offset, midpoint, and time coordinates. The equation is proved theoretically to provide correct kinematics and amplitudes on the transformed constant‐offset sections. Solving an initial‐value problem with the proposed equation leads to integral and frequency‐domain offset continuation operators, which reduce to the known forms of dip moveout operators in the case of continuation to zero offset.
Multiple removal based on detection and estimation of localized coherent signal
Authors: Lu Wenkai , Zhang Xuegong , Li Yanda
Published: April 2003

The removal of multiples without simultaneously distorting primaries is a difficult aspect of demultiple techniques. We present a new demultiple approach based on detecting and estimating localized coherent signals (multiples and primaries) on stacking velocity spectra. The trajectories of localized coherent signals are determined from the velocity and zero‐offset traveltime; amplitude variations with offset (AVO) are modeled from known AVO properties. We estimate primaries and multiples from stacking velocities by polynomial approximation of the amplitude along the hyperbolic path. This procedure lets us predict multiples on near‐offsets using the multiples on other offsets. To further preserve the amplitude of the rebuilt primaries, stronger multiples, which are detected according to a multiple‐to‐primary energy ratio, are estimated and subtracted from the seismic data before estimating the primaries. Because the estimation of primaries and multiples is done locally in the time–space domain, our method is efficient. Comparisons are made between our method and conventional Radon filters. The results of both synthetic and field seismic data show that our method is very promising in practical applications because it can suppress the multiples efficiently while preserving the primary amplitudes well.
Human Type 3 3α-Hydroxysteroid Dehydrogenase (Aldo-Keto Reductase 1C2) and Androgen Metabolism in Prostate Cells
Authors: Rižner Tea Lanišnik , Lin Hsueh K. , Peehl Donna M. , Steckelbroeck Stephan , Bauman David R. , Penning Trevor M.
Published: April 2003

Human aldo-keto reductases (AKRs) of the AKR1C subfamily function in vitro as 3-keto-, 17-keto-, and 20-ketosteroid reductases or as 3α-, 17β-, and 20α-hydroxysteroid oxidases. These AKRs can convert potent sex hormones (androgens, estrogens, and progestins) into their cognate inactive metabolites or vice versa. By controlling local ligand concentration AKRs may regulate steroid hormone action at the prereceptor level. AKR1C2 is expressed in prostate, and in vitro it will catalyze the nicotinamide adenine dinucleotide (NAD+)-dependent oxidation of 3α-androstanediol (3α-diol) to 5α-dihydrotestosterone (5α-DHT). This reaction is potently inhibited by reduced NAD phosphate (NADPH), indicating that the NAD+: NADPH ratio in cells will determine whether AKR1C2 makes 5α-DHT. In transient COS-1-AKR1C2 and in stable PC-3-AKR1C2 transfectants, 5α-DHT was reduced by AKR1C2. However, the transfected AKR1C2 oxidase activity was insufficient to surmount the endogenous 17β-hydroxysteroid dehydrogenase (17β-HSD) activity, which eliminated 3α-diol as androsterone. PC-3 cells expressed retinol dehydrogenase/3α-HSD and 11-cis-retinol dehydrogenase, but these endogenous enzymes did not oxidize 3α-diol to 5α-DHT. In stable LNCaP-AKR1C2 transfectants, AKR1C2 did not alter androgen metabolism due to a high rate of glucuronidation. In primary cultures of epithelial cells, high levels of AKR1C2 transcripts were detected in prostate cancer, but not in cells from normal prostate. Thus, in prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5α-DHT and prevents activation of the androgen receptor. AKR1C2 does not act as an oxidase due to either potent product inhibition by NADPH or because it cannot surmount the oxidative 17β-HSD present. Neither AKR1C2, retinol dehydrogenase/3α-HSD nor 11-cis-retinol dehydrogenase is a source of 5α-DHT in PC-3 cells.
Regulation of Ovarian Primordial Follicle Assembly and Development by Estrogen and Progesterone: Endocrine Model of Follicle Assembly
Authors: Kezele Phillip , Skinner Michael K.
Published: April 2003

The assembly of the developmentally arrested primordial follicle and the subsequent transition of the primordial follicle to the primary follicle are critical processes in normal ovarian physiology that remain to be elucidated. Ovarian follicles do not proliferate and the primordial follicles present in the neonate represent the total number of gametes available to a female throughout her reproductive life. The primordial follicles are oocytes surrounded by less differentiated squamous granulosa cells and are derived from oocyte nests, and primary follicles are oocytes surrounded by a single layer of cuboidal granulosa cells that have initiated follicle development. Abnormalities in primordial follicle assembly, arrest, and development (i.e. primordial to primary follicle transition) can cause pathological conditions such as premature ovarian failure. In this study newborn rat ovaries were cultured for 7 d. The rate of primordial follicle assembly in vivo was identical with the rate in vitro. Interestingly, the rate of primordial follicle transition to the primary follicle was found to be 3 times greater in culture. This abnormal rate of primary follicle development in culture suggests the primordial follicle does not arrest in development as observed in vivo. To investigate this phenomena newborn rat ovaries were cultured in the presence of progesterone, estradiol or calf serum. Estradiol, progesterone, or calf serum significantly reduced the level of initial primordial to primary follicle transition. Approximately 60% of follicles make the primordial to primary follicle transition in control ovaries and about 30% in treated ovaries. Steroids and calf serum had no effect on the primordial to primary follicle transition in ovaries collected and cultured from postnatal 4-d-old rats, suggesting the effects observed are restricted to the initial wave of primordial to primary follicle transition. Interestingly, progesterone was also found to significantly reduce the rate of primordial follicle assembly. All viable oocytes assembled into primordial follicles in control ovaries and approximately 40% remained unassembled in progesterone-treated ovaries. Progesterone was also found to reduce primordial follicle assembly in vivo with 10% of the total follicles remaining unassembled in progesterone injected neonatal animals. Analysis of cellular apoptosis demonstrated that progesterone inhibited the coordinated oocyte apoptosis required for primordial follicle assembly. The hypothesis developed is that high levels of maternal and fetal steroids prevent premature primordial follicle assembly and primordial to primary follicle transition in the embryo. After birth steroid levels fall dramatically and the primordial follicles are free to assemble and initiate development. These observations suggest a novel role for steroids and the maternal-fetal endocrine unit in the control of ovarian primordial follicle assembly and early follicular development.
Glucocorticoid Maintains Pulsatile Secretion of Luteinizing Hormone under Infectious Stress Condition
Authors: Matsuwaki Takashi , Watanabe Erina , Suzuki Masatoshi , Yamanouchi Keitaro , Nishihara Masugi
Published: April 2003

We have previously shown that TNF-α, a major proinflammatory cytokine, suppressed hypothalamic GnRH pulse generator activity and that this inhibitory effect was enhanced by α-helical CRH, a CRH receptor antagonist. The present study was conducted to elucidate the involvement of glucocorticoid (GC) in modulating LH pulses under infectious stress condition. Adrenalectomy (ADX) markedly enhanced the suppressive effect of TNF-α (1 μg), injected iv, on LH pulses in ovariectomized (OVX) rats. Pretreatment with a sc injection of corticosterone (10 mg) almost completely restored LH pulses after TNF-α injection in OVX/ADX animals. Injection of TNF-α increased the number of c-Fos-immunoreactive cells in the supraoptic nucleus (SON), the dorsomedial hypothalamic nucleus (DMH), and the parvocellular region of the paraventricular nucleus (PVN), which was more prominent in OVX/ADX than OVX animals except in the DMH. Pretreatment with corticosterone decreased the number of Fos-immunoreactive cells in the PVN and SON but not in the DMH. These results suggest that GC has a potent protective effect on LH pulsatility under conditions of infectious stress, the mechanism of which involves at least the suppression of the excitability of PVN and SON neurons. In addition, the DMH does not seem to mediate the central action of GC, though it may play an important role in inducing pathophysiological reactions to invasive stress.
Pregnancy Enhances the Angiotensin (Ang)-(1–7) Vasodilator Response in Mesenteric Arteries and Increases the Renal Concentration and Urinary Excretion of Ang-(1–7)
Authors: Neves Liomar A. A. , Williams Aleck F. , Averill David B. , Ferrario Carlos M. , Walkup Michael P. , Brosnihan K. Bridget
Published: April 2003

The vasoactive effect of angiotensin (Ang)-(1–7) in mesenteric resistance arteries together with its plasma and kidney concentration and urinary excretion was assessed in pregnant and virgin rats. Mesenteric arteries (230–290 μm) were mounted in a pressurized myograph system and Ang-(1–7) concentration-dependent response curves (10−10–10−5m) were determined in arteries preconstricted with endothelin-1 (10−7m). The Ang-(1–7) response was investigated in vessels with and without pretreatment with the Ang-(1–7) antagonist [d-[Ala7]-Ang-(1–7)] (10−7m). Ang-(1–7) caused a significantly enhanced, concentration-dependent dilation of mesenteric vessels (EC50 = 2.7 nm) from pregnant compared with virgin female rats. d-[Ala7]-Ang-(1–7) eliminated the vasodilator effect of Ang-(1–7). There was no significant change in plasma concentration of Ang-(1–7) in pregnant animals. On the other hand, 24 h urinary excretion and kidney concentration of Ang-(1–7) were significantly higher in pregnant animals. The increased mesenteric dilation to Ang-(1–7) with enhanced kidney concentration and 24 h urinary excretion rate of Ang-(1–7) suggests an important role for this peptide in cardiovascular regulation during pregnancy.
The Soy Isoflavone Genistein Decreases Adipose Deposition in Mice
Authors: Naaz Afia , Yellayi Srikanth , Zakroczymski Melissa A. , Bunick David , Doerge Daniel R. , Lubahn Dennis B. , Helferich William G. , Cooke Paul S.
Published: April 2003

Adipose tissue is responsive to estrogen and expresses both estrogen receptor α and β. To test the hypothesis that the estrogenic soy isoflavone genistein can have effects on adipose tissue, juvenile or adult C57/BL6 mice were ovariectomized and given daily injections of vehicle, 17β-estradiol (5 μg/kg·d) or genistein (8–200 mg/kg·d) sc for 21–28 d. To test effects of dietary genistein, 25- to 27-d-old mice were fed diets containing 0–1500 parts per million (ppm) genistein for 12 d. Mice were killed and fat pads weighed. Parametrial fat pads were used for morphometric and Northern analysis. Genistein injections decreased adipose weight and adipocyte circumference at higher doses; effects in adult and juvenile mice were similar. Genistein decreased lipoprotein lipase mRNA, which may be a critical aspect of its adipose effects. Juveniles fed 500-1500 ppm dietary genistein had dose-responsive decreases in fat pad weights of 37–57%, compared with controls; 300 ppm genistein did not cause decreases. Genistein doses of 300, 500, 1000, and 1500 ppm produced serum genistein concentrations of 1.02 ± 0.14 μm, 1.79 ± 0.32 μm, 2.55 ± 0.18 μm, and 3.81 ± 0.39 μm, respectively. These results indicate dietary genistein at 500-1500 ppm produces antilipogenic effects in mice at serum levels that humans are realistically exposed to.
Ovine Placental Lactogen-Induced Heterodimerization of Ovine Growth Hormone and Prolactin Receptors in Living Cells Is Demonstrated by Fluorescence Resonance Energy Transfer Microscopy and Leads to Prolonged Phosphorylation of Signal Transducer and Activator of Transcription (STAT)1 and STAT3
Authors: Biener Eva , Martin Cyril , Daniel Nathalie , Frank Stuart J. , Centonze Victoria E. , Herman Brian , Djiane Jean , Gertler Arieh
Published: April 2003

HEK-293T cells transiently transfected with ovine (o) GH receptor (GHR) and prolactin receptor (PRLR) constructs respectively tagged downstream with cyan or yellow fluorescent proteins were used to study ovine placental lactogen (oPL)-stimulated heterodimerization by fluorescence resonance energy transfer (FRET) microscopy. The oPL-stimulated transient heterodimerization of GHR and PRLR had a peak occurring 2.5–3 min after oPL application, whereas oGH or oPRL had no effect at all. The results indicate none or only little dimerization occurring before the hormonal stimulation. The effect of heterodimerization was studied by comparing activation of Janus kinase 2, signal transducer and activator of transcription (STAT)1, STAT3, STAT5, and MAPK in Chinese hamster ovary cells stably transfected with chimeric genes encoding receptors consisting of cytosolic and transmembrane parts of oGHR and oPRLR, extracellular domains of human granulocyte and macrophage colony-stimulating factor (hGM-CSF) receptor α or β, and cells transfected with the two forms (α or β) of PRLR and GHR. Functionality of those proteins was verified by hGM-CSF-induced phosphorylation of both intracellular PRLR and GHR domains and hGM-CSF-induced heterodimerization was documented by chimeric receptor coimmunoprecipitation. Homodimerization or heterodimerization of PRLRs and GHRs had no differential effect on activation of STAT5 and MAPK. However, heterodimerization resulted in a prolonged phosphorylation of STAT1 and in particular STAT3, suggesting that the heterodimerization of α-oGHR and β-oPRLR is able to transduce a signal, which is distinct from that occurring on homodimeric associations.
Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II
Authors: Ye Ping , Kenyon Christopher J. , MacKenzie Scott M. , Seckl Jonathan R. , Fraser Robert , Connell John M. C. , Davies Eleanor
Published: April 2003

We have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and angiotensin (Ang)II infusion. Male Wistar Kyoto rats (n = 6) were fed normal, high, or low sodium diets for 12 d or were administered AngII or vehicle for 7 d. CYP11B2 and CYP11B1 expression was measured in RNA from adrenal gland and discrete brain regions using real-time QRT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 × 105 ± 0.6 × 105 to 57 × 105 ± 22 × 105 copies/μg RNA (mean ± sem; P < 0.05);in the hippocampus, 14-fold from 5.4 × 102 ± 0.8 × 102 to 74 × 102 ± 31 × 102 copies/μg RNA (P < 0.05); and in the cerebellum, 5-fold from 1.9 × 103 ± 0.7 × 103 to 9.9 × 103 ± 3.0 × 103 copies/μg RNA (P < 0.01). CYP11B2 gene expression in the brainstem and hypothalamus was not affected. High-sodium diet reduced adrenal CYP11B2 expression to 0.19 × 105 ± 0.1 × 105 copies/μg RNA (P < 0.05) but did not affect central nervous system (CNS) expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10- to 1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII. To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.
PERK eIF2α Kinase Regulates Neonatal Growth by Controlling the Expression of Circulating Insulin-Like Growth Factor-I Derived from the Liver
Authors: Li Yulin , Iida Kaori , O’Neil Jeff , Zhang Peichuan , Li Sheng’ai , Frank Ami , Gabai Aryn , Zambito Frank , Liang Shun-Hsin , Rosen Clifford J. , Cavener Douglas R.
Published: April 2003

Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2α kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk−/− mutants is manifested within the first few days of neonatal development. Growth parameters of Perk−/− mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism. Tibia growth plates exhibited a reduction in proliferative and hypertrophic chondrocytes underlying the longitudinal growth retardation. Neonatal Perk−/− deficient mice show a 75% reduction in liver IGF-I mRNA and serum IGF-I within the first week, whereas the expression of IGF-I mRNA in most other tissues is normal. Injections of IGF-I partially reversed the growth retardation of the Perk−/− mice, whereas GH had no effect. Transgenic rescue of PERK activity in the insulin- secreting β-cells of the Perk−/− mice reversed the juvenile but not the neonatal growth retardation. We provide evidence that circulating IGF-I is derived from neonatal liver but is independent of GH at this stage. We propose that PERK is required to regulate the expression of IGF-I in the liver during the neonatal period, when IGF-I expression is GH-independent, and that the lack of this regulation results in severe neonatal growth retardation.