bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capsaicin‐sensitive nerve fibers: A potential extra‐ACTH mechanism participating in adrenal regeneration in rats
Authors: Ulrich‐Lai Yvonne M. , Fraticelli Ada I. , Engeland William C. 
Published: May 2003

AbstractPituitary‐derived factors, including ACTH, have been widely implicated in initiating adrenal regeneration. However, recent work has demonstrated that adrenal regeneration is also modulated by adrenal nerves that extensively reinnervate the regenerating adrenal. Moreover, transection of the splanchnic nerve removes sensory calcitonin gene‐related peptide (CGRP) and preganglionic sympathetic vesicular acetylcholine transporter (VAChT)‐positive fibers from the regenerating gland and delays regeneration. However, it is not known whether the splanchnic nerve effects on adrenal regeneration are mediated by the CGRP‐positive or VAChT‐positive innervation. The present studies use the drug capsaicin, a neurotoxin selective for a subset of primary afferent neurons, to specifically remove CGRP‐positive fibers from the adrenal gland and assess subsequent effects on the recovery of adrenal mass and function after surgical enucleation. Male, Sprague‐Dawley rats were anesthetized and treated with capsaicin (vs. vehicle) periaxonally to the thoracic splanchnic nerve (33 mM, 15 minutes) or systemically (30–100 mg/kg for 4 days, s.c.). After 7–12 days of recovery, rats received right adrenalectomy and left adrenal enucleation. At 14 and 21 days postenucleation, prestress and poststress plasma and adrenals glands were collected; adrenals were weighed and fixed for immunolabeling of CGRP‐positive nerve fibers. Periaxonal capsaicin treatment decreased adrenal CGRP content prior to surgical enucleation; however, reinnervation by CGRP‐positive fibers was not prevented and regeneration was not affected. Systemic capsaicin treatment attenuated the reinnervation by CGRP‐positive fibers and increased the rate, but not extent, of adrenal regeneration. These results support the hypothesis that adrenal innervation represents an extra‐ACTH mechanism to modulate the rate of adrenal regeneration. Microsc. Res. Tech. 61:252–258, 2003. © 2003 Wiley‐Liss, Inc.
Adrenal neuropeptides: Regulation and interaction with ACTH and other adrenal regulators
Authors: Whitworth E.J. , Kosti O. , Renshaw D. , Hinson J.P. 
Published: May 2003

AbstractIt is now well accepted that both the cortex and medulla of the mammalian adrenal gland receive a rich innervation. Many different transmitter substances have been identified in nerves supplying both cortex and medulla and, as well as catecholamines, a wide range of neuropeptides has been found in the adrenal gland. There have been several studies on the affects of age, sodium intake, stress, ACTH, and splanchnic nerve activity on the regulation of adrenal neuropeptide content. There is evidence that the abundance of each of these peptides is actively regulated. Although there have been many studies addressing the individual actions of various neurotransmitters on steroid secretion, adrenal blood flow, and adrenal growth, few have attempted to determine the nature of any interaction between neurotransmitters and the classical adrenal stimulants. There are, however, some significant interactions, particularly in the regulation of zona glomerulosa function. This review necessarily focuses on vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), as these are the most abundant transmitter peptides in the adrenal gland and the majority of studies have investigated their regulation and actions. However, substance P, calcitonin gene‐related peptide (CGRP), neurotensin, and the enkephalins are included where appropriate. Finally, it has been suggested that certain neurotransmitters, particularly VIP, may interact with classical hormone receptors in the adrenal, notably the ACTH receptor. This review attempts to evaluate our current state of knowledge in each of these areas. Microsc. Res. Tech. 61:259–267, 2003. © 2003 Wiley‐Liss, Inc.
Deconstructing the molecular mechanisms of cell cycle control in a mouse adrenocortical cell line: Roles of ACTH
Authors: Rocha Kátia M. , Forti Fábio L. , Lepique Ana P. , Armelin Hugo A. 
Published: May 2003

AbstractThis is a progress report of an attempt to deconstruct the signaling network underlying cell cycle control in the mouse Y1 adrenocortical cell line, aiming to uncover ACTH growth regulatory pathways. Y1 adrenocortical tumor cells possess amplified and overexpressed c‐Ki‐ras proto‐oncogene. Despite this oncogenic lesion, Y1 cells retain tight regulatory mechanisms of cell cycle control typified by the sequential events comprising the mitogenic response triggered by FGF2 in G0/G1‐arrested Y1 cells: 1) activation of ERK1/2 and PI3K, by 5 minutes; 2) induction of c‐Fos and c‐Myc proteins by 2 hours; 3) induction of cyclin D1 protein by 5 hours; 4) phosphorylation of Rb protein between 6 and 8 hours; 5) onset of DNA synthesis by 8–9 hours. In this cell line, ACTH‐receptor (ACTH‐R) activates contradictory pathways of growth regulation. First, ACTH coordinately induces fos and jun gene families via activation of both ERK1/2 and cAMP/PKA pathways, resembling a mitogen. Second, ACTH‐R triggers cAMP/PKA‐mediated antimitogenic mechanisms comprised of Akt/PKB dephosphorylation/deactivation, c‐Myc protein degradation, and p27Kip1 protein induction. Induction of cyclin D1 depends on activation of both ERK1/2 and PI3K, but is not affected by ACTH action. As a consequence, ACTH antagonizes FGF2 mitogenic activity but ectopic expression of the c‐Myc protein (via MycER fusion protein) is sufficient to abrogate this ACTH antagonistic effect over FGF2 mitogenic activity. Ectopic expression of both c‐Myc and cyclin D1 is not sufficient to drive G0/G1‐arrested Y1 cells into S phase, but when the sustained expression of these two proteins is complemented by ACTH treatment it promotes G1 phase progression and DNA synthesis initiation. In conclusion, ACTH‐receptor lacks signaling potential sufficient to initiate a mitogenic response in Y1 adrenocortical cells and, therefore, cannot substitute for bona fide mitogens like FGF2. Microsc. Res. Tech. 61:268–274, 2003. © 2003 Wiley‐Liss, Inc.
Mechanism of action of ACTH: Beyond cAMP
Authors: Gallo‐Payet Nicole , Payet Marcel D. 
Published: May 2003

AbstractACTH is the major regulator of adrenal cortex function, having acute and chronic effects on steroid synthesis and secretion. The precise molecular mechanisms by which ACTH stimulates steroid synthesis and secretion, as well as cell hypertrophy, survival, and migration are still poorly understood. Several studies have shown that ACTH action is mediated not only by cyclic adenosine monophosphate (cAMP), but also by calcium (Ca2+), both interacting closely through positive feedback loops to enhance steroid secretion. However, in spite of the evidence that ACTH could stimulate other signaling pathways, such as inositol phosphates and diacylglycerol or mitogenic‐activated protein kinase pathway (MAPK), none is as potent as cAMP. Recent data indicate that duration and potency of the cAMP production could be modulated by several isoforms of adenylyl cyclases and phosphodiesterases. In addition, calcium is probably not a first second messenger per se; rather, there are several arguments indicating that its increase occurs following cAMP production. Finally, in addition to steroid secretion, ACTH, through cAMP, is a survival factor, protecting cells against apoptosis. All of the effects of ACTH are dependent on cytoskeleton integrity. In summary, after 30 years of intensive research in this field, cAMP remains the first obligatory second messenger of ACTH action. However, recent work emphasizes that cell environment (matrix and cytoskeleton) probably interacts with cAMP to coordinate functions other than steroid secretion. Microsc. Res. Tech. 61:275–287, 2003. © 2003 Wiley‐Liss, Inc.
Adrenocorticotropin regulation of steroidogenic acute regulatory protein
Authors: Lehoux Jean‐Guy , Mathieu Axel , Lavigne Pierre , Fleury Alain 
Published: May 2003

AbstractWe studied the effect of the adrenocorticotropin hormone (ACTH) on the expression of the steroidogenic acute regulatory protein (StAR) in vivo in rat and hamster adrenals and also in transfection experiments using COS‐1 cells. In vivo, ACTH increased the level of StAR mRNA within 30–60 minutes and also increased the quantity of StAR, but with a 2–3‐hour delay. ACTH induced the formation of many acidic StAR species as analyzed by two‐dimensional gel electrophoresis and immunoblotting. In the transfection experiments, (Bu)2‐cAMP also induced the formation of many acidic species for the hamster StAR; in COS‐1 cells, StAR is phosphorylated mainly on serine (S) residue(s). When alanine (A) was substituted for serine, S13A, S185A, and S194A mutants had decreased StAR activity compared to wildtype, thus determining the importance of these amino acid residues in StAR action. The full‐length WT, N46‐truncated StAR lacking its mitochondrial import sequence, and N46‐S194A had similar activities, whereas N46‐S185A had completely lost its activity. Our results suggest that S194, but not S185, functions in association with the mitochondrial import sequence for the initiation of StAR activation. Further studies showed that S185 is implicated in salt bridge stability, not in StAR phosphorylation, suggesting its importance for StAR folding. Thermodynamic calculations of the hamster StAR homology model based on MLN64 show that StAR can partially unfold to bind cholesterol and serve as a rapid transfer mechanism for eventual translocation into mitochondria. This is supportive of a StAR functioning either outside the mitochondria or in the mitochondrial intermembrane space. Microsc. Res. Tech. 61:288–299, 2003. © 2003 Wiley‐Liss, Inc.
ACTH modulation of transcription factors responsible for steroid hydroxylase gene expression in the adrenal cortex
Authors: Sewer Marion B. , Waterman Michael R. 
Published: May 2003

AbstractSteroid hormone biosynthesis in the adrenal cortex and gonads involves the coordinated transcription of the genes encoding the steroid hydroxylases, 3β‐hydroxysteroid dehydrogenase (3βHSD), the steroidogenic acute regulatory protein (StAR), and adrenodoxin (Adx). Transcriptional regulation of steroidogenic genes is multifactorial, entailing developmental, tissue‐specific, constitutive, and cAMP‐dependent mechanisms. Optimal steroidogenic capacity is achieved by the actions of ACTH which exerts transcriptional pressure on all steroidogenic genes. The actions of ACTH in the adrenal cortex have been studied in great detail and is mediated by cAMP and protein kinase A (PKA) via two temporally distinct pathways. The acute response leads to mobilization of cholesterol, the initial substrate for all steroidogenic pathways, from cellular stores to the inner mitochondrial membrane where cholesterol sidechain cleavage cytochrome P450 (P45011A1) resides. The slower, chronic response of ACTH in the adrenal cortex directs transcription of the genes encoding the steroidogenic enzymes. Although steroidogenic gene transcription in response to ACTH is cAMP‐dependent, the consensus cAMP response pathway (CRE/CREB) is not involved. Instead, each steroidogenic gene utilizes unique cAMP‐responsive sequences (CRS) found in the promoters of each gene, which bind a diverse array of transcription factors. Moreover, once specific transcription factors are bound to the promoters of the steroidogenic genes, increased gene expression requires posttranslational modification (phosphorylation/dephosphorylation) of the transcription factors and binding of coactivator proteins. This review provides a general view (with emphasis on the human) of the important factors involved in regulating steroidogenic gene expression and ultimately steroid hormone biosynthesis. Microsc. Res. Tech. 61:300–307, 2003. © 2003 Wiley‐Liss, Inc.
Ectopic adrenocorticotropin (ACTH) and corticotropin‐releasing hormone (CRH) production in the adrenal gland: Basic and clinical aspects
Authors: Vrezas Ilias , Willenberg Holger S. , Mansmann Georg , Hiroi Naoki , Fritzen Reimar , Bornstein Stefan R. 
Published: May 2003

AbstractThe hypothalamic‐pituitary‐adrenal (HPA) axis is integrated in the human stress system and controls the metabolism of many cell systems in the body. Therefore, hypofunction or hyperfunction of the HPA axis potentially threatens the life of the whole organism. Noncontrolled overproduction of its key regulators, CRH and ACTH, causes dysfunction of the stress system. Ectopic secretion of these compounds may be part of extraadrenal paraneoplastic syndromes caused by various benign or malignant tumors. However, ectopic ACTH and CRH may originate from the adrenal itself. A local CRH/ACTH system exists in the normal human adrenal medulla. Overproduction of CRH and ACTH has been documented in pheochromocytomas causing Cushing's syndrome. Finally, ectopic production of ACTH causing Cushing's syndrome has also been demonstrated in adrenocortical cells. This suggests a marked plasticity within the HPA axis and the neuroendocrine cell system. Microsc. Res. Tech. 61:308–314, 2003. © 2003 Wiley‐Liss, Inc.
Immunohistochemical study of heat shock proteins 27, 60 and 70 in the normal human adrenal and in adrenal tumors with suppressed ACTH production
Authors: Pignatelli Duarte , Ferreira Jorge , Soares Paula , José Costa Maria , Conceição Magalhães Maria 
Published: May 2003

AbstractHeat shock proteins (HSPs) are known to protect cells against various aggressions and to assist in the correct folding of nascent proteins as well as in the recovery of denatured ones. HSP70 increases its levels in the cell in response to any stress and is induced by ACTH in the adrenal gland. HSP60 is located in the mitochondria and assists in the folding of mitochondrial peptides. HSP27 is the only small HSP that is stress‐induced. HSP27 and HSP70 are known to protect cells against apoptosis while, on the contrary, HSP60 is proapoptotic, increasing caspases maturation. We studied the expression of these HSPs in human adrenal tissue both in the normal glands (12 cases) and in tumoral tissue from cortisol producing adrenal adenomas (6 cases). Besides being neoplastic, these cells live in a particular ambience of lack of ACTH due to the suppression of the hypothalamic‐pituitary ACTH secretion induced by the elevated levels of cortisol. HSP27 is highly expressed in the normal adrenal and shows a marked reduction of expression in Cushing's adrenal tissue. Although with overall lower levels of expression in the normal adrenal, HSP70 exhibited a similar pattern of reduction in tumoral tissue. HSP60, on the other hand, increased significantly and consistently in adrenal Cushing tumors. Besides the possible consequences of incorrect folding of nascent peptides, the alterations observed in tumoral tissue seem to act in an apoptotic direction. The only factor that we observed that could be contributing to these changes was the lack of plasma ACTH. Microsc. Res. Tech. 61:315–323, 2003. © 2003 Wiley‐Liss, Inc.
A simplified synthesis of 2,3,5,6‐tetrafluorophenyl 2‐(2‐nitroimidazol‐1‐yl) acetate
Authors: Wilson Hanna 
Published: May 2003

Abstract2,3,5,6‐Tetrafluorophenyl 2‐(2‐nitroimidazol‐1‐yl) acetate has been synthesized via an improved route which involves the direct coupling of 2‐(2‐nitroimidazol‐1‐yl) acetic acid with 2,3,5,6‐tetrafluorophenol. Copyright © 2003 John Wiley & Sons, Ltd.
The synthesis and characterisation of multi‐labelled [D, 13C] 2‐deuterio‐2‐methyl aromatic ketones
Authors: Coumbarides Gregory S. , Eames Jason , Weerasooriya Neluka 
Published: May 2003

AbstractA series of multi‐labelled aromatic ketones were efficiently synthesized using a deprotonation–deuteriation/alkylation strategy. The yields were high and the products are synthetically useful. Copyright © 2003 John Wiley & Sons, Ltd.
Carbon‐11 labelling of an N‐sulfonylamino acid derivative: a potential tracer for MMP‐2 and MMP‐9 imaging
Authors: Kuhnast Bertrand , Bodenstein Claudia , Wester Hans Jürgen , Weber Wolfang 
Published: May 2003

AbstractMatrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer. Non invasive imaging of MMPs would allow the evaluation of MMP activity in cancer and the assessment of the response of MMP inhibitor based therapies. In this paper, we investigated the synthesis and labelling by methylation with [11C]CH3I of an N‐sulfonylamino acid derivative, the (2R)‐3‐methyl‐2‐[[4‐[(4‐methoxybenzoyl)amino]benzenesulfonyl]amino] butanoic acid, a selective and high potent MMP‐2 and MMP‐9 inhibitor, for cancer imaging with positron emission tomography. Labelling of (2R)‐3‐methyl‐2‐[[4‐[(4‐hydroxybenzoyl)amino]benzenesulfonyl] amino] butanoic acid was carried out in a radiochemical yield of 50%–60% within 40 min with a specific activity of 11–26 GBq/µmol (EOS). In vitro inhibitory activity studies, biodistribution and in vivo serum stability in normal mice are also described. Copyright © 2003 John Wiley & Sons, Ltd.
Radiosynthesis of O‐[11C]methyl‐L‐tyrosine and O‐[18F]Fluoromethyl‐L‐tyrosine as potential PET tracers for imaging amino acid transport
Authors: Iwata Ren , Furumoto Shozo , Pascali Claudio , Bogni Anna , Ishiwata Kiichi 
Published: May 2003

AbstractTwo positron‐emitting analogues of tyrosine, O‐[11C]methyl‐L‐tyrosine and O‐[18F]fluoromethyl‐L‐tyrosine were prepared as new tumor imaging agents. The alkylating agent, [11C]methyl triflate or [18F]fluoromethyl triflate, was simply bubbled through a dimethylsulfoxide solution of L‐tyrosine disodium salt at room temperature. After subsequent HPLC purification the labeled L‐tyrosine analogues were obtained in decay‐corrected radiochemical yields of over 50%, based on their corresponding labeling agent, with radiochemical purities always higher than 98%. The quite straightforward preparation, together with the high radiochemical yields achieved, make both these syntheses suitable for routine production. Copyright © 2003 John Wiley & Sons, Ltd.
Combining microwave‐enhanced deuteriation reactions with parallel synthesis procedures
Authors: Chappelle Michael R. , Harding John R. , Kent Barry B. , Jones John R. , Lu Shui‐Yu , Morgan Alan D. 
Published: May 2003

AbstractThe development of combined microwave‐enhanced/parallel synthesis procedures and their application to the deuteriation of organic compounds via examples of solid‐state hydrogenation is reported. Other labelling procedures, such as solution state catalytic dehalogenations, hydrogenations as well as hydrogen isotope exchange reactions also benefit from the combined technology. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis, radio‐LC–MS analysis and biodistribution in mice of 99mTc–NIM–BAT
Authors: Bormans G. , Cleynhens B. , de Groot T.J. , Mortelmans L. , Moretti J.‐L. , Verbruggen A. 
Published: May 2003

AbstractS,S′‐bis‐trityl‐N‐BOC‐1,2‐ethylenedicysteamine (S,S′‐bis‐trityl‐N‐BOC–BAT) was conjugated to 2‐nitroimidazole (NIM) through a propylene spacer in order to provide a precursor for a potential technetium‐99 m labelled hypoxia tracer. For labelling with technetium‐99 m, a two‐step one‐pot procedure was developed consisting of deprotection of the ligand by heating in mild acidic conditions and subsequent exchange labelling in the presence of SnCl2, tartrate and 99mTcO.The labelling reaction mixture was analyzed using electrospray radio‐LC–MS and the observed mass spectrum corresponding to the main radiometric peak was in accordance with the predicted structure of oxo–Tc(V)–NIM–BAT.99mTc–NIM–BAT was purified using RP–HPLC and its biodistribution was evaluated in normal mice at 10 min and 4 h p.i. 99mTc–NIM–BAT was cleared from plasma mainly by hepatobiliary excretion. Copyright © 2003 John Wiley & Sons, Ltd.
A multi‐center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysis
Authors: Lee Patricia Lani , Yiannoutsos Constantin T. , Ernst Thomas , Chang Linda , Marra Christina M. , Jarvik Jeffrey G. , Richards Todd L. , Kwok Edmund W. , Kolson Dennis L. , Simpson David , Tang Cheuk Y. , Schifitto Giovanni , Ketonen Leena M. , Meyerhoff Dieter J. , Lenkinski Robert E. , Gonzalez R. Gilberto , Navia Bradford A. ,   the HIV MRS Consortium
Published: May 2003

AbstractPurposeTo demonstrate the technical feasibility and reliability of a multi‐center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N‐acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC).Materials and MethodsUsing an automated protocol (GE PROBE‐P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV‐negative subjects.ResultsA random‐effects model of the phantom and volunteer data showed no significant inter‐site differences. Feasibility of a multi‐center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV‐negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC.ConclusionThis is the first study to ascertain and validate the reliability and reproducibility of a short echo time 1H‐MRS acquisition sequence from multiple brain regions in a multi‐center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting. J. Magn. Reson. Imaging 2003;17:625–633. © 2003 Wiley‐Liss, Inc.
Three‐dimensional T1ρ‐weighted MRI at 1.5 Tesla
Authors: Borthakur Arijitt , Wheaton Andrew , Charagundla Sridhar R. , Shapiro Erik M. , Regatte Ravinder R. , Akella Sarma V. S. , Kneeland J. Bruce , Reddy Ravinder 
Published: May 2003

AbstractPurposeTo design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three‐dimensional T1ρ‐weighted MRI on a 1.5‐T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects.Materials and MethodsA three‐pulse cluster was pre‐encoded to a three‐dimensional gradient‐echo imaging sequence to create a three‐dimensional, T1ρ‐weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom‐built knee‐coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T1ρ values measured by this sequence to those obtained with a previously tested two‐dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI‐based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T1ρ‐weighted images of the knee joint of a healthy individual.ResultsCalculated T1ρ of articular cartilage in the specimen was similar for both and three‐dimensional and two‐dimensional methods (84 ± 2 msec and 80 ± 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015°C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues.ConclusionWe developed and implemented a three‐dimensional T1ρ‐weighted pulse sequence on a 1.5‐T clinical scanner. J. Magn. Reson. Imaging 2003;17:730–736. © 2003 Wiley‐Liss, Inc.