bluuebunny/crossref_metadata_2025 huggingface dataset:
Iliotibial band thickness: Sonographic measurements in asymptomatic volunteers
Authors: Goh Lesley‐Ann , Chhem Rethy K. , Wang Shih‐chang , Chee Thomas
Published: May 2003

Purpose.

The aims of this study were to measure the thickness of the iliotibial band (ITB) in asymptomatic adult volunteers and to determine whether there was any correlation between these measurements and the subjects' age, weight, or height.

Methods.

Sonography was used to measure the ITB thickness in 31 asymptomatic volunteers (13 men and 18 women) ranging from 25 to 68 years old. Two radiologists obtained the sonographic measurements of each volunteer at the levels of the femoral condyle and the tibial condyle of both knees. Findings of fluid or bursae adjacent to the ITB were recorded.

Results.

The mean ITB thickness was 1.95 mm ± 0.3 mm (± standard deviation) at the level of the femoral condyle and 3.4 mm ± 0.5 mm at the level of the tibial condyle. There was a statistically significant negative correlation between ITB thickness and subject age. There was no significant correlation between ITB thickness and subject weight or height. Joint fluid was present in the lateral recess of both knees in 29 volunteers (93.5%) and 1 knee joint in 2 volunteers (6.5%). Bursae were present in 3 volunteers (9.7%).

Conclusions.

The mean sonographic values of normal ITB thickness established using sonography may be helpful in diagnosing ITB pathology. There is no significant correlation between ITB thickness and subject weight or height, but there is a negative correlation between ITB thickness and subject age. Joint fluid in the lateral recess is present in most asymptomatic individuals, but bursae are rare. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:239–244, 2003
Color doppler imaging of orbital vessels: Personal experience and literature review
Authors: Tranquart François , Bergès Olivier , Koskas Patricia , Arsene Sophie , Rossazza Christian , Pisella Pierre‐Jean , Pourcelot Léandre
Published: May 2003

Many Doppler imaging studies have been performed in recent years in a large number of ocular disorders because of improvements in the Doppler equipment used for detecting and measuring the low blood‐flow velocities that are a requisite for the quantitative evaluation of blood flow in the orbital vessels. The ophthalmic artery, central retinal artery and vein, posterior ciliary arteries, and the superior ophthalmic vein can be easily identified using color Doppler sonography. The changes in local blood flow in these vessels assessed by spectral analysis pulsed Doppler sonography have been used to characterize and to obtain new insights into different nontumoral vascular disorders including carotid artery stenosis, central retinal vein occlusion, giant cell arteritis, glaucoma, diabetes, fistulas, and tumoral processes of the eye and orbit. Our experience has confirmed the important role of Doppler sonography in the assessment of subclinical changes in the vascular bed, in the understanding of different processes, for following up after specific treatments, and for determining the long‐term prognosis of these various conditions. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:258–273, 2003
Pseudoaneurysm of the gastroduodenal artery ruptured into the superior mesenteric vein in a patient with chronic pancreatitis
Authors: Suzuki Toshio , Ishida Hideaki , Komatsuda Tomoya , Oyaké Jinko , Miyauchi Takaharu , Heianna Joichi , Miyashita Masahiro
Published: May 2003

We report the case of a patient with chronic pancreatitis that was complicated by the rare occurrence of a pseudoaneurysm of the gastroduodenal artery that ruptured into the superior mesenteric vein. The patient, a 65‐year‐old alcoholic man, suddenly experienced hematemesis. Gastroesophagoscopy revealed bleeding from esophageal varices; the hemorrhaging was controlled with sclerotherapy. Sonography identified a 2‐cm round anechoic mass at the pancreatic head, and color Doppler imaging revealed turbulent arterial flow within the mass, leading us to the diagnosis of the pseudoaneurysm. CT and angiographic findings generally corresponded with those of sonography and confirmed our diagnosis. The pseudoaneurysm was treated successfully with embolization, and the patient was discharged 10 days after therapy. Follow‐up sonography performed 2 months later confirmed the absence of blood flow within the lesion. Color Doppler sonography was very useful for diagnosing the pseudoaneurysm and planning its treatment, and we recommend its routine use in patients with chronic pancreatitis to avoid delays in diagnosing and treating such vascular complications. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:278–282, 2003
Doppler measurement of blood flow velocities in extraocular orbital vessels in patients with obstructive sleep apnea syndrome
Authors: Erdem C. Zuhal , Altin Remzi , Erdem L. Oktay , Kargi Sebnem , Kart Levent , Cinar Fikret , Ayoglu Ferruh
Published: May 2003

Purpose.

We used color Doppler sonography to determine blood flow velocities in the extraocular orbital vessels of patients with obstructive sleep apnea syndrome (OSAS) and compared the results with those of healthy control subjects without OSAS.

Methods.

Patients with OSAS were classified according to the apnea‐hypopnea index (AHI) as having mild OSAS (AHI < 20) or severe OSAS (AHI ≥ 20). The peak systolic velocity (PSV), end‐diastolic velocity (EDV), and resistance index were measured in the ophthalmic artery (OA), central retinal artery (CRA), lateral short posterior ciliary artery, and medial short posterior ciliary artery using color Doppler sonography. Only 1 eye was measured in each study participant, and right and left eyes were chosen randomly. The blood flow velocities of patients with OSAS and those of control subjects were compared with the Kruskal‐Wallis test and Wilcoxon's rank‐sum test.

Results.

The study comprised 30 patients (15 with mild and 15 with severe OSAS) and 20 healthy control subjects. Blood flow velocities were higher in most measured vessels in patients with OSAS than they were in the control subjects. Among patients with mild OSAS, the PSVs and EDVs in the posterior ciliary arteries were statistically significantly higher than those of the control group (p < 0.05), but those in the OA and CRA did not differ significantly between the mild OSAS group and the control group (p > 0.05). However, as the severity of OSAS increased, the PSVs and EDVs of the OA and CRA were also affected (p < 0.05).

Conclusions.

Color Doppler sonographic measurements of blood flow parameters in the orbital vessels may differ significantly between patients with OSAS and those without the syndrome. Therefore, OSAS should be considered in addition to other conditions when interpreting the results of color Doppler sonography of the extraocular orbital vessels if the clinical history points toward such a diagnosis. © 2003 Wiley Periodicals, Inc. 31:250–257, 2003
Value of contrast‐enhanced power Doppler sonography using a microbubble echo‐enhancing agent in evaluation of small breast lesions
Authors: Kook Shin‐Ho , Kwag Hyon‐Joo
Published: May 2003

Purpose.

The purpose of this study was to prospectively evaluate the usefulness of contrast‐enhanced power Doppler sonography (PDUS) using a microbubble echo‐enhancing agent in differentiating between malignant and benign small breast lesions.

Patients and Methods.

Between July 1, 2000, and September 30, 2001, we performed gray‐scale sonographic examination of patients in whom diagnostic sonography or screening mammography had revealed solid breast lesions measuring less than 2 cm in the largest dimension. The patients were then examined on PDUS before and after injection of a microbubble contrast agent. The sonographic findings for all 3 techniques, as well as the morphologic features of the Doppler signals for each patient before and after injection of the contrast agent on PDUS, were independently assessed. Each lesion was classified as “benign” or “malignant” on the basis of specific criteria for sonographic interpretation. A hemodynamic study was performed in which time‐transit profiles of the Doppler signals on contrast‐enhanced PDUS were generated using a computer‐assisted program, and the results for each patient were compared with the findings of a histopathologic examination of surgical specimens.

Results.

Thirty‐six patients (35 women and 1 man) with a mean age of 43.5 years (range, 18–69 years) were evaluated. The tumors ranged from 4 to 19 mm in the largest dimension. Histopathologic examination revealed that 19 tumors were benign and 17 were malignant. For morphologic diagnosis of the malignant lesions, the sensitivity of gray‐scale sonography was 100%, compared with 29% for PDUS without contrast enhancement. The specificity of gray‐scale sonography was 47%, compared with 74% for PDUS without contrast enhancement. Contrast‐enhanced PDUS had a sensitivity of 71% and a specificity of 58%. The diagnostic accuracy was 72% for gray‐scale sonography, 53% for PDUS without contrast enhancement, and 64% for contrast‐enhanced PDUS. The time‐transit profiles of the hemodynamic study did not reveal a statistically significant difference in the accuracy rates of contrast‐enhanced PDUS between benign and malignant breast lesions.

Conclusions.

Compared with PDUS without contrast enhancement, contrast‐enhanced PDUS provides better visualization of the morphology of vascular Doppler signals that is characteristic of malignancy and therefore has a higher sensitivity and diagnostic accuracy, albeit a lower specificity. In differentiating between benign and malignant small breast lesions, contrast‐enhanced PDUS can be helpful when used with gray‐scale sonography and PDUS without contrast enhancement. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:227–238, 2003
Adrenocortical zonation and ACTH
Authors: Vinson G.P.
Published: May 2003

The clear morphological distinction between the cells of the different adrenocortical zones has attracted speculation and experiment to interpret their functions and the ways in which they are regulated. Considerable data have been produced in recent years that has benefited a fuller understanding of the processes of steroidogenesis and of cell proliferation at the molecular level. This now enables the reexamination of earlier concepts. It is evident that there is considerable species variation, and this article, dealing mainly with the rat, reaches conclusions that do not necessarily apply to other mammals. In the rat adrenal, however, the evidence suggests that the greatest differences between the functions of the zones are between the glomerulosa and the fasciculata. Here the sometimes all‐or‐nothing demarcation in their complement of components associated with steroidogenesis or with cell proliferation suggests a stark division of labor. In this model the fasciculata is the main engine of steroid hormone output and the glomerulosa is the site of cell proliferation, recruitment, and differentiation. Regulating these functions are angiotensin II and other paracrine components that modulate and maintain the glomerulosa, and ACTH, that maintains the fasciculata, and recruits new fasciculata cells by transformation of proliferating glomerulosa cells. Grafted onto this mostly vegetative function of the glomerulosa is CYP11B2, limited to just a fraction of the outer glomerulosa in rats on a normal laboratory diet and generating aldosterone (and 18‐hydroxycorticosterone) from precursors whose origin is not, from the evidence summarized here, very clear, but may include the fasciculata, directly or indirectly. The biosynthesis of aldosterone in the rat certainly requires reinterpretation. Microsc. Res. Tech. 61:227–239, 2003. © 2003 Wiley‐Liss, Inc.
ACTH and adrenocortical gap junctions
Authors: Murray Sandra A. , Davis Kevin , Gay Vernon
Published: May 2003

Since the initial identification of gap junctions in the adrenal gland, it has been proposed that a system involving direct cell–cell communication might be involved in adrenal cortical functions. Gap junction channels do, in fact, provide pathways for direct intercellular exchange of small molecules (<1,000 Da), many of which have the potential to influence a wide range of cellular activities. Gap junctions are composed of proteins called connexin which, in the adrenal cortex, have proven to be remarkably consistent in both type and zonal distribution with connexin 43 (Cx43) as the predominant component in mammalian adrenal glands thus far evaluated. Only the inner two zones of the cortex (zonae fasciculata and reticularis) exhibit significant amounts of Cx43 and functional coupling. Adrenocorticotropin (ACTH) has been shown to increase Cx43 protein in vivo and in vitro, and a strong correlation has been noted between the presence of gap junctions and certain adrenal cortical functions, especially steroidogenic capacity and cell proliferation. This review summarizes evidence of the Cx43 expression in adrenal cortical cells and the likely role of Cx43 in steroidogenesis and cell proliferation. It is concluded that control of gap junction expression in the adrenal gland is hormonally dependent and is functionally linked to adrenal gland zonation. Microsc. Res. Tech. 61:240–246, 2003. © 2003 Wiley‐Liss, Inc.
Role of adrenocorticotropic hormone in the development and maintenance of the adrenal cortical vasculature
Authors: Thomas Michaël , Keramidas Michelle , Monchaux Emmanuelle , Feige Jean‐Jacques
Published: May 2003

The adrenal cortex is a highly vascularized endocrine tissue. A dense network of blood capillaries centripetally irrigates the adrenal gland, allowing every endocrine cell to be in contact with an endothelial cell. The pituitary hormone ACTH controls the coordinated development of the vasculature and the endocrine tissue mass. This suggests that paracrine secretions between steroidogenic adrenocytes and capillary endothelial cells participate in the control of adrenocortical homeostasis. Besides its effect on the vascular tone of arteries, ACTH induces the expression of the angiogenic cytokine VEGF‐A (vascular endothelial growth factor‐A) in primary cultures of adrenocortical cells. This growth factor is a specific mitogen for endothelial cells and is likely to mediate the hormonal control of adrenocortical vascularization through a paracrine mechanism. The newly discovered angiogenic factor EG‐VEGF (endocrine‐gland‐derived vascular endothelial growth factor), the expression of which is restricted to endocrine glands and which is preferentially mitogenic for endocrine tissue‐derived endothelial cells, is another candidate mediator of great potential interest. Microsc. Res. Tech. 61:247–251, 2003. © 2003 Wiley‐Liss, Inc.
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

Pituitary‐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

It 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

This 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

ACTH 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

We 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

Steroid 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

The 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

Heat 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

2,3,5,6‐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

A 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

Matrix 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

Two 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

The 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

S,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

Purpose

To 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 Methods

Using 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.

Results

A 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.

Conclusion

This 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

Purpose

To 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 Methods

A 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.

Results

Calculated 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.

Conclusion

We 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.
Laser‐induced thermotherapy (LITT) of liver metastases: MR‐guided percutaneous insertion of an MRI‐compatible irrigated microcatheter system using a closed high‐field unit
Authors: Puls Ralf , Stroszczynski Christian , Gaffke Gunnar , Hosten Norbert , Felix Roland , Speck Ulrich
Published: May 2003

Purpose

To evaluate the efficacy and safety of a new MRI‐compatible irrigated laser microcatheter system for thermal ablation of liver metastases.

Material and Methods

The new microcatheter system consists of a titanium needle with a diameter of 1.5 mm and a surrounding Teflon catheter with an outer diameter of 1.8 mm (5.5 F). In vitro laser‐induced coagulation of bovine liver tissue was performed to determine the optimal perfusion rate of cooling saline flow, maximum laser energy, and ablation time. Laser‐induced thermotherapy using the new microcatheter system, an Nd:YAG laser (Dornier), and a flexible laser light guide (Somatex GmbH, Berlin, Germany) was performed in 28 patients with liver metastases. Percutaneous insertion and positioning of multiple microcatheters in the lesion and monitoring of therapy was performed with a closed high‐field MRI scanner using T1‐weighted gradient‐echo sequences during breath‐hold.

Results

A perfusion rate of 0.75 mL/minute, a laser energy of 15 W, and an ablation time of 20 minutes were found suitable to achieve safe and sufficient ablation of metastatic tissue. The mean volume of induced coagulation in vitro was 23.9 mL. Ablation of liver metastases in patients was technically and clinically successful.

Conclusion

The new microcatheter system allows for both catheter placement and monitoring of therapy using a single imaging modality. This shortens the procedure and enables more precise puncture and therapy of liver metastases. Due to the miniaturized design of the catheter and the real‐time monitoring, the procedure is minimally invasive and very well tolerated by patients. This new technique seems to be a safe and feasible alternative in treating liver metastases. J. Magn. Reson. Imaging 2003;17:663–670. © 2003 Wiley‐Liss, Inc.
Magnetic resonance imaging and proton MR spectroscopy of the brain in a patient with carbohydrate‐deficient glycoprotein syndrome type I
Authors: Takeuchi Mayumi , Harada Masafumi , Hisaoka Sonoka , Nishitani Hiromu , Mori Kenji , Sakama Minoru
Published: May 2003

This is a report on a case of carbohydrate‐deficient glycoprotein syndrome (CDGS) with neurological deficits. Magnetic resonance (MR) images showed remarkable atrophy of the cerebellum and brainstem, and hypointensity was seen in the pallidum on diffusion‐weighted images (DWI), suggesting deposits of metal substances. In the cerebellum, proton MR spectroscopy (MRS) showed decreased concentrations of N‐acetylaspartate and a complex of glutamine and glutamate (Glx) while the concentration of myo‐inositol was increased, indicating neuronal impairment and gliosis. In the parietal lobe, there was an increased concentration of Glx, possibly reflecting dysfunction caused by liver injury. J. Magn. Reson. Imaging 2003;17:722–725. © 2003 Wiley‐Liss, Inc.
Simple anatomical measurements do not correlate significantly to individual peripheral nerve stimulation thresholds as measured in MRI gradient coils
Authors: Chronik Blaine A. , Ramachandran Meena
Published: May 2003

Purpose

To examine peripheral nerve stimulation (PNS) thresholds for normal human subjects in magnetic resonance imaging (MRI) gradient coils, and determine if observed thresholds could be predicted based on gross physiologic measurements.

Materials and Methods

PNS thresholds for 21 healthy normal subjects were measured using a whole‐body gradient coil. Subjects were exposed to a trapezoidal echo‐planar imaging (EPI) gradient waveform and the total change in gradient strength (ΔG) required to cause PNS as a function of the duration of the gradient switching time (τ) were measured. Correlation coefficients and corresponding P values were calculated for the PNS threshold measurements against simple physiologic measurements taken of the subjects, including weight, height, girth, and average body fat percentage, in order to determine if there were any easily observable dependencies.

Results

No convincing correlations between threshold parameters and gross physiologic measurements were observed.

Conclusion

These results suggest it is unlikely that a simple physiologic measurement of subject anatomy can be used to guide the operation of MRI scanners in a subject‐specific manner in order to increase gradient system performance while avoiding PNS. J. Magn. Reson. Imaging 2003;17:716–721. © 2003 Wiley‐Liss, Inc.
Kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI
Authors: Li Luping , Storey Pippa , Kim David , Li Wei , Prasad Pottumarthi
Published: May 2003

Purpose

To examine whether the noninvasive technique of blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) can detect changes in renal medullary oxygenation following administration of a nitric oxide (NO) synthase inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME). Hypertension is associated with endothelial dysfunction and is characterized by a lack of response to endothelial‐dependent vasoactive substances, including nitric oxide synthase inhibitors. We hypothesized that the magnitude of the change would be reduced in the kidneys of hypertensive subjects relative to normal controls.

Materials and Methods

To test this hypothesis, data were obtained in spontaneously hypertensive rats (SHR, n = 6). Wistar‐Kyoto rats (WKY, n = 7) were used as normotensive controls.

Results

As expected, WKY rats showed a significant response to L‐NAME (R2* increasing from 23.6±1.5 Hz to 32.5±2.2 Hz, P < 0.05), while SHR exhibited a minimal change in medullary oxygenation (R2* measuring 31.9±2.8 Hz pre‐ and 35.5±2.2 Hz post‐L‐NAME). The baseline R2* in SHR is found to be comparable to post‐L‐NAME values in WKY rats, suggesting a basal deficiency of nitric oxide in SHR.

Conclusion

Based on the differential effect of NO synthase inhibition on medullary oxygenation, BOLD MRI can distinguish hypertensive from normal kidney. Our results are consistent with previously reported observations using invasive methods. J. Magn. Reson. Imaging 2003;17:671–675. © 2003 Wiley‐Liss, Inc.
Accuracy of cartilage and subchondral bone spatial thickness distribution from MRI
Authors: McGibbon Chris A. , Bencardino Jenny , Yeh Eren D. , Palmer William E.
Published: May 2003

Purpose

To assess three‐dimensional measurement accuracy of articular cartilage (AC) and subchondral bone (SB) thickness from MRI.

Materials and Methods

A computer program was used to calculate AC and SB thickness from MRI (three‐dimensional spoiled gradient echo (SPGR), .31‐mm resolution, 1‐mm slice thickness) of six adult femoral heads. Specimens were imaged in five anatomical planes ranging between +30° to −30° from neutral and cut into 2‐mm thick sections along the five anatomical planes. Faxitron x‐ray was used to produce microradiographic (.05‐mm resolution) images of the sections.

Results

In‐plane measurement accuracy was .165 ± .108 mm for AC thickness and .387 ± .174 mm for SB thickness. Taking into account chemical‐shift misregistration in SB thickness, accuracy of measurements improved to .213 ± 128 mm. Out‐of‐plane (three‐dimensional) thickness accuracy of the model, assessed by numerical simulation, was .015 mm. However, three‐dimensional thickness errors in specimens were .319 ± .256 mm for AC and .253 ± .183 mm for SB thickness.

Conclusion

Errors in three‐dimensional AC thickness were attributed to volume‐averaging effects caused by oblique intersection of the image plane with the joint surface. Errors in three‐dimensional SB thickness were attributed to chemical‐shift artifact. We conclude that accuracy of AC thickness is within clinically acceptable standards but that more sophisticated pulse sequences are needed to improve the measurement of SB thickness. J. Magn. Reson. Imaging 2003;17:703–715. © 2003 Wiley‐Liss, Inc.
Evaluation of sodium T1 relaxation times in human heart
Authors: Pabst Thomas , Sandstede Joern , Beer Meinrad , Kenn Werner , Neubauer Stefan , Hahn Dietbert
Published: May 2003

Purpose

To evaluate the sodium longitudinal relaxation (T1) characteristics for myocardium and blood in humans.

Materials and Methods

Eleven healthy volunteers were examined by using a 23Na heart surface coil at a 1.5 T clinical scanner equipped with a broadband spectroscopy option. 23Na MR measurements were performed by using a three‐dimensional spoiled gradient echo sequence (in‐plane resolution, 3.5 mm × 7 mm; slice thickness, 24 mm; TE, 3.1 msec; bandwidth, 65 Hz/pixel; TR, 21 to 150 msec).

Results

Longitudinal T1 relaxation time components were 31.6±7.0 msec and 31.1±7.5 msec for myocardium and blood, respectively.

Conclusion

23Na T1 relaxation times of myocardium and blood can be determined in humans. The results are in agreement with values obtained from animal studies. J. Magn. Reson. Imaging 2003;17:726–729. © 2003 Wiley‐Liss, Inc.