bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal color Doppler sonographic evaluation of nuchal encirclement by the umbilical cord
Authors: Aksoy Umit
Published: October 2003

Purpose

The aim of this study was to assess whether Doppler flow velocimetry of the fetal middle cerebral and umbilical arteries is affected by nuchal encirclement by the umbilical cord (nuchal cord) in the prenatal period.

Patients and Methods

The position of the fetal umbilical cord was assessed on color Doppler sonography in pregnant women who were referred to our radiology department between September 14, 1998, and January 14, 2000. Pulsatility and resistance indices and the ratio of peak systolic blood flow velocity to diastolic velocity of the umbilical arteries and middle cerebral arteries of all fetuses were prospectively obtained with Doppler flow velocimetry. The fetuses were categorized into 2 groups: group 1 consisted of fetuses without sonographic evidence of nuchal cord and group 2 of fetuses with sonographic evidence of nuchal cord. The results were statistically analyzed with independent‐groups t test. A p value of less than 0.05 was considered significant.

Results

During the study period, 230 pregnant women underwent sonographic examination of the fetus, and 68 fetuses were delivered. The sonographic examinations were performed at 24–41 weeks' menstrual age. Of the 46 fetuses in group 1, 1 fetus had nuchal cord at delivery; of the 22 fetuses in group 2, 4 did not have nuchal cord at delivery. The sensitivity of color Doppler sonography in detecting nuchal cord was 95% (18 of 19 fetuses), the specificity was 92% (45 of 49), the negative predictive value was 98% (45 of 46), and the positive predictive value was 82% (18 of 22). No statistically significant differences in middle cerebral artery or umbilical artery Doppler flow velocimetry values were detected between the 2 groups.

Conclusions

Color Doppler sonography is a sensitive and specific method of diagnosing nuchal cord, but fetal middle cerebral artery and umbilical artery Doppler flow velocimetry values are not affected by the presence of nuchal cord in the prenatal period. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:473–477, 2003
Flash‐echo gray‐scale imaging in the subtraction mode for assessing perfusion of small hepatocellular carcinoma
Authors: Wang Jing‐Houng , Lu Sheng‐Nan , Changchien Chi‐Sin , Huang Wu‐Shiung , Hung Chao‐Hung , Tung Hung‐Da , Chen Tsung‐Ming , Lee Chuan‐Mo
Published: October 2003

Purpose

The aim of this study was to evaluate the effectiveness of using flash‐echo imaging (FEI) in the subtraction mode to assess the vascularity of small hepatocellular carcinomas (HCCs) that had been unsatisfactorily assessed with power Doppler sonography.

Methods

Between May 2000 and April 2001, we prospectively assessed nodular small HCCs using FEI in the subtraction mode after power Doppler sonography resulted in unsatisfactory images. After microbubble contrast was injected, we used the FEI technique to assess tumor perfusion in the arterial, portal, and delayed phases.

Results

Our study population comprised 14 patients (10 men and 4 women) whose ages ranged from 31 to 79 years (mean, 61 ± 13.7 years) and whose tumors ranged in size from 0.8 to 3 cm (mean, 1.8 ± 0.5 cm). Power Doppler sonography was unable to assess tumor vascularity in 6 cases because of interference by heart pulsation, and it failed to detect a color signal in the other 8 cases. All tumors were enhanced with FEI. In the arterial phase, 7 of the 14 tumors (50%) showed hyperperfusion relative to liver parenchyma enhancement, 5 of 14 (36%) showed isoperfusion, and 2 of 14 (14%) showed hypoperfusion. In the portal phase, 3 of the 14 tumors (21%) showed isoperfusion, and the other 11 (79%) showed hypoperfusion. In the delayed phase, all 14 tumors showed hypoperfusion.

Conclusions

Despite heart pulsation and slow vascular flow, FEI in the subtraction mode was sensitive and effective in assessing the perfusion of small HCCs. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:451–456, 2003
Sonographic measurement of calcaneal volume for determination of skeletal age in children
Authors: Sherif Hanan , Noureldin Mona , Bakr Ahmed F. , Mahfouz Ahmed‐Emad
Published: October 2003

Purpose

The purposes of this study were first to prospectively evaluate the feasibility of using sonographic measurements of volume of the ossified part of the calcaneus to determine skeletal age in healthy children and second, to provide normal ranges of this volume by sex and age up to 6 years.

Methods

Four hundred normal girls and boys ranging in age from 1 day to 6 years were examined sonographically to determine the volume of the calcaneal ossification center. The children were randomly divided into 2 groups. The first group (300 children) was used to determine normal values for the mean calcaneal volume by age and sex. The second group (100 children) was used to validate those normal values.

Results

The sonographically determined volume of the calcaneal ossification center correlated well with the chronologic age of the children. The calcaneal ossification centers of boys were larger than those of girls within the same age groups from ages 2 to 10 months, but from 11 months to 6 years old, they were larger in the girls. The differences, however, were not statistically significant. The volume of the calcaneal ossification center increased the most between the first and second years of life, reaching 183% and 140% in girls and boys, respectively. Using the normal values obtained from the first group, we correctly predicted the chronologic age in 91% of children in the validation group. Among the remaining 9%, the error in prediction of chronologic age never exceeded 1 age interval.

Conclusions

The use of sonography provides a quantitative means of measuring calcaneal volume, and its use is feasible for determining skeletal age in children. The normal values we obtained may be used as a baseline for sonographic assessment of skeletal maturation and diagnosis of growth retardation. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:457–460, 2003
Regulation of Na,K‐ATPase Function in the Lens
Authors: Delamere Nicholas A.
Published: October 2003

The two cell types in the lens, epithelium and fiber, have a very different specific activity of Na,K‐ATPase; activity is much higher in the epithelium. However, judged by Western blot, fibers and epithelium express a similar amount of both Na,K‐ATPase α and β subunit proteins. Na,K‐ATPase protein abundance does not tally with Na,K‐ATPase activity. Studies were conducted to examine whether protein synthesis plays a role in maintenance of the high Na,K‐ATPase activity in lens epithelium. An increase of cytoplasmic sodium was found to increase Na,K‐ATPase protein expression in the epithelium, but not in the fibers. The findings illustrate the ability of lens epithelium to synthesize new Na,K‐ATPase protein as a way to boost Na,K‐ATPase in response to cell damage or pathological events. Methionine incorporation studies suggested Na,K‐ATPase synthesis may also play a role in day to day preservation of high Na,K‐ATPase activity. Na,K‐ATPase protein in lens epithelial cells appeared to be continually synthesized and degraded. Experiments with cycloheximide suggest that specific activity of Na,K‐ATPase in the lens epithelium may depend on the ability of the cells to continuously synthesize fresh Na,K‐ATPase proteins. However, other factors such as phosphorylation of Na,K‐ATPase α subunit may also influence Na,K‐ATPase activity. When intact lenses were exposed to the agonist thrombin, Na,K‐ATPase activity was diminished, but the response was suppressed by inhibitors of the Src family of non‐receptor tyrosine kinases. Thrombin elicited tyrosine phosphorylation of lens epithelium membrane proteins, including a 100 kDa protein band thought to be the Na,K‐ATPase α 1 subunit. It remains to be determined whether a tyrosine phosphorylation mechanism contributes to the low activity of Na,K‐ATPase in lens fibers. J. Exp. Zool. 300A:25–29, 2003. © 2003 Wiley‐Liss, Inc.
On the mechanism of fluid transport across corneal endothelium and epithelia in general
Authors: Fischbarg Jorge
Published: October 2003

The mechanism by which fluid is transported across epithelial layers is still unclear. The prevalent idea is that fluid traverses these layers transcellularly, driven by local osmotic gradients secondary to electrolyte transport and utilizing the high osmotic permeability of aquaporins. However, recent findings that some aquaporin knockout mice epithelia transport fluid sow doubts on local osmosis. This review discusses recent evidence in corneal endothelium that points instead to electro‐osmosis as the mechanism underlying fluid transport. In this concept, a local recirculating electrical current would result in electro‐osmotic coupling at the level of the intercellular junctions, dragging fluid via the paracellular route. The text also mentions possible mechanisms for apical bicarbonate exit from endothelial cells, and discusses whether electro‐osmosis could be a general mechanism. J. Exp Zool. 300A:30–40, 2003. © 2003 Wiley‐Liss, Inc.
Mechanisms and functional aspects of intestinal calcium absorption
Authors: Bronner Felix
Published: October 2003

Calcium absorption, in terms of mechanisms and function, is well adapted to meet the calcium needs of mammals. When calcium levels in the food are low, the active, mediated transcellular calcium transport assumes primary importance. This process is vitamin D‐dependent, largely localized in the duodenum, and involves three steps: entry across the brush border, mediated by a molecular structure, CaT1, with two components; a facilitated transport that saturates at low luminal calcium concentration; and a channel component through which most calcium enters the cell at the higher luminal concentrations. Intracellular diffusion is assured by a small, cytosolic calcium binding molecule, calbindinD9k, which carries more than 90% of the calcium that traverses the duodenal cell, thus also serving as a buffer. Extrusion is by the CaATPase and is not a limiting step. Calcium entry is reduced by more than 90% in the absence of vitamin D, with biosynthesis of calbindinD9k totally vitamin D‐dependent. Active transport is upregulated on low calcium intake and downregulated at high calcium intake, when paracellular calcium transport through the tight junctions of the intestine becomes the dominant process. The amount of calcium absorbed paracellularly is a function of the calcium gradient between lumen and plasma and of the time the chyme spends at a given intestinal site. The coexistence of mediated and nonmediated transport processes assures the organism of an adequate calcium supply, yet prevents excessive calcium absorption. J. Exp. Zool. 300A:47–52, 2003. © 2003 Wiley‐Liss, Inc.
Channels, pumps, and exchangers in the gill and kidney of freshwater fishes: Their role in ionic and acid‐base regulation
Authors: PERRY S.F. , Shahsavarani A. , Georgalis T. , Bayaa M. , Furimsky M. , Thomas S.L.Y.
Published: October 2003

In freshwater fishes, the gill and kidney are intricately involved in ionic and acid‐base regulation owing to the presence of numerous ion channels, pumps, or exchangers. This review summarizes recent developments in branchial and renal ion transport physiology and presents several models that integrate epithelial ion and acid‐base movements in freshwater fishes. At the gill, three cell types are potentially involved in ionic uptake: pavement cells, mitochondria‐rich (MR) PNA+ cells, and MR PNA− cells. The transfer of acidic or basic equivalents between the fish and its environment is accomplished largely by the gill and is appropriately regulated to correct acid‐base imbalances. The kidney, while less important than the gill in overall acid or base excretion, has an essential role in regulating systemic acid‐base balance by controlling HCO3− reabsorption from the filtrate. J. Exp. Zool. 300A:53–62, 2003. © 2003 Wiley‐Liss, Inc.
CFTR: What's it like inside the pore?
Authors: Liu Xuehong , Smith Stephen S. , Dawson David C.
Published: October 2003

The Cystic Fibrosis Conductance Regulator (CFTR) functions as a cAMP‐activated, anion‐selective channel, but the structural basis for anion permeation is not well understood. Here we summarize recent studies aimed at understanding how anions move through the CFTR channel, and the nature of the environment anions experience inside the pore. From these studies it is apparent that anion permeability selectivity and anion binding selectivity of the pore are consistent with a model based on a “dielectric tunnel.” The selectivity pattern for halides and pseudohalides can be predicted if it is assumed that permeant anions partition between bulk water and a polarizable space that is characterized by an effective dielectric constant of about 19. Covalent labeling of engineered cysteines and pH titration of engineered cysteines and histidines lead to the conclusion that the CFTR anion conduction path includes a positively charged outer vestibule. A residue in transmembrane segment 6 (TM6) (R334) appears to reside in the outer vestibule of the CFTR pore where it creates a positive electrostatic potential that enhances anion conduction. J. Exp. Zool. 300A:69–75, 2003. © 2003 Wiley‐Liss, Inc.
Voltage‐Gated ion currents of schwann cells in cell culture models of human neurofibromatosis
Authors: Fieber Lynne A.
Published: October 2003

K+ (K) channels play a role in the proliferation of many cell types in normal cells and certain disease states. Several laboratories have studied K currents in cultured Schwann cells from models of the human diseases, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). These diseases are characterized by the growth of Schwann cell tumors. In all cell culture NF models the K current properties differ in tumor‐derived and normal Schwann cells. Depending on the model however, the type of K channel abnormality differs. K channels appear to play a role in the proliferation of Schwann cell cultures of these disease models, because a link has been established between K current blockade and the inhibition of Schwann cell proliferation in NF1 and NF2. Differences in the proliferation response of normal Schwann cells to K channel blockers suggest that in vitro regulation of proliferation in neoplastic and normal Schwann cells is complex. J. Exp. Zool. 300A:76–83, 2003. © 2003. Wiley‐Liss, Inc.
Confocal imaging of xenobiotic transport across the blood‐brain barrier
Authors: Miller David S.
Published: October 2003

The brain capillary endothelium is a formidable barrier to entry of foreign chemicals into the central nervous system (CNS). For the most part it poorly distinguishes between therapeutics and neurotoxins and thus the blood‐brain barrier both protects the brain from toxic chemicals and limits our ability to treat a variety of CNS disorders. Two elements underlie the barrier function of the brain capillary endothelium: 1) a physical barrier comprised of tight junctions, which form an effective seal to intercellular diffusion, and the cells themselves, which exhibit a low rate of endocytosis, and 2) a metabolic/active barrier, comprised of specific membrane transporters expressed by the endothelial cells. We have recently developed an experimental system based on confocal microscopy to study mechanisms of transport in freshly isolated brain capillaries. Here I review studies demonstrating a major role for the ATP‐driven, xenobiotic export pump, p‐glycoprotein, in barrier function and recent experiments showing that transient inhibition of pump function can have substantial benefit for chemotherapy in an animal model of brain cancer. J. Exp. Zool. 300A:84–90, 2003. © 2003 Wiley‐Liss, Inc.
Identity and function of γ‐secretase
Authors: Kimberly W. Taylor , Wolfe Michael S.
Published: October 2003

γ‐Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid‐β precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer's disease and to normal development, this protease has eluded identification until only very recently. Four membrane proteins are now known to be members of the protease complex: presenilin, nicastrin, aph‐1, and pen‐2. Recent findings suggest that these four proteins are sufficient to reconstitute the active γ‐secretase complex and that together they mediate the cell surface signaling of a variety of receptors via intramembrane proteolysis. © 2003 Wiley‐Liss, Inc.
Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets
Authors: Evin Geneviève , Zhu Aiqin , Holsinger R.M. Damian , Masters Colin L. , Li Qiao‐Xin
Published: October 2003

Proteolytic processing of the amyloid precursor protein by β ‐and γ‐secretases results in the production of Alzheimer's disease (AD) Aβ amyloid peptides. Modulation of secretase activity is being investigated as a potential therapeutic approach. Recent studies with human brain have revealed that the β‐secretase protein, BACE, is increased in cortex of AD patients. Analysis of βCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage that is the direct precursor to Aβ, shows it is also elevated in AD, underlying the importance of β‐secretase cleavage in AD pathogenesis. The C‐terminal product of γ‐secretase cleavage of APP, ϵCTF (or AICD), is enriched in human brain cortical nuclear fractions, a subcellular distribution appropriate for a putative involvement of APP cytosolic domain in signal transduction. Analysis of AD cortex samples, particularly that of a carrier of a familial APP mutation, suggests that processing of APP transmembrane domain generates an alternative CTF product. All these particularities observed in the AD brain demonstrate that APP processing is altered in AD. The transgenic mouse model Tg2576 seems to be a promising laboratory tool to test potential modulators of Aβ formation. Indeed, C‐terminal products of α‐, β‐, and γ‐secretase cleavage are readily detectable in the brain of these transgenic mice. Finally, the finding of the same secretase products in platelets and neurons make platelets a potentially useful and easily accessible clinical tool to monitor effects of novel therapies based on inhibition of β‐ or γ‐secretase. © 2003 Wiley‐Liss, Inc.
Changes in spinal GDNF, BDNF, and NT‐3 expression after transient spinal cord ischemia in the rat
Authors: Tokumine Joho , Kakinohana Osamu , Cizkova Dasa , Smith Doug W. , Marsala Martin
Published: October 2003

Previous studies have demonstrated that the expression of several growth factors including glial cell‐derived neurotrophic factor (GDNF), brain‐derived growth factor (BDNF), and neurotrophin‐3 (NT‐3) play an important role in defining neuronal survival after brain ischemia. In the present study, using a well‐defined model of transient spinal ischemia in rat, we characterized the changes in spinal GDNF, BDNF, and NT‐3 expression as defined by enzyme‐linked immunosorbent assay (ELISA) and immunofluorescence coupled with deconvolution microscopy. In control animals, baseline levels of GDNF, BDNF, and NT‐3 (74 ± 22, 3,600 ± 270, 593 ± 176 pg/g tissue, respectively) were measured. In the ischemic group, 6 min of spinal ischemia resulted in a biphasic response with increases in tissue GDNF and BDNF concentrations at the 2‐hr and 72‐hr points after ischemia. No significant differences in NT‐3 concentration were detected. Deconvolution analysis revealed that the initial increase in tissue GDNF concentration corresponded to a neuronal upregulation whereas the late peak seen at 72 hr corresponded with increased astrocyte‐derived GDNF synthesis. Increased expression of BDNF was seen in neurons, astrocytes, and oligodendrocytes. These data suggest that the early increase in neuronal GDNF/BDNF expression likely modulates neuronal resistance/recovery during the initial period of postischemic reflow. Increased astrocyte‐derived BDNF/GDNF expression corresponds with transient activation of astrocytes and may play an active role in neuronal plasticity after non‐injurious intervals of spinal ischemia. © 2003 Wiley‐Liss, Inc.
Plastic changes of calcitonin gene‐related peptide in morphine tolerance: Behavioral and immunohistochemical study in rats
Authors: Zhou Xiang , Li Jin‐Ju , Yu Long‐Chuan
Published: October 2003

The present study was undertaken to investigate the plasticity of calcitonin gene‐related peptide (CGRP) in antinociception after morphine tolerance in rats. The hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation increased significantly after intracerebroventricular injection of 2.5 nmol of CGRP in opioid‐naive rats, indicating that CGRP produces an antinociceptive effect in the brain. Furthermore, there was an antinociceptive effect after intracerebroventricular injection of 2.5 nmol of CGRP in morphine‐tolerant rats. Interestingly, the antinociceptive effect induced by intracerebroventricular injection of CGRP was lower in morphine‐tolerant rats than that in opioid‐naive rats at the same dose. At the same time, there was downregulation of CGRP‐like immunoreactivity in both lateral septal nucleus and central nucleus of amygdala tested by immunohistochemical methods, whereas no significant changes were observed in arcuate nucleus of hypothalamus and periaqueductal gray after morphine treatment in rats. The present study demonstrates plastic changes in both CGRP‐induced antinociception and CGRP‐like immunoreactivity in rat brain after morphine tolerance, suggesting that CGRP may play an important role in morphine tolerance. © 2003 Wiley‐Liss, Inc.
Phosphoinositide 3‐kinase promotes adult subventricular neuroblast migration after stroke
Authors: Katakowski Mark , Zhang Zheng Gang , Chen Jieli , Zhang Ruilan , Wang Ying , Jiang Hao , Zhang Lijie , Robin Adam , Li Yi , Chopp Michael
Published: October 2003

Rodent adult subventricular zone (SVZ)‐derived progenitor cells abandon the rostral migratory stream (RMS)/olfactory complex postmiddle cerebral artery occlusion (MCAo) and migrate into compromised tissue, possibly playing a role in brain recovery. Using SVZ tissue explants from the adult rat, we investigated the role of the phosphoinositide 3‐kinase (PI3K) signal transduction pathway in the migration of SVZ cells. Stroke significantly (P < .01) increased migratory speed (198 ± 39 μm/day) of neuroblasts out of the SVZ explants compared with the speed (99 ± 20 μm/day) in the normal SVZ (nSVZ) explants within the first 3 days of incubation. Three‐dimensional laser scanning confocal microscopy revealed formation of neuroblast encompassing chain‐like astrocyte structures extruding from both normal and stroke explants. Western blots showed that stroke SVZ (sSVZ) explants increased Akt phosphorylation. Treatment of sSVZ explants with the selective PI3K inhibitor LY294002 significantly (P < .01) attenuated neuroblast migration and Akt phosphorylation, whereas treatment with LY294002 did not affect the number of bromodeoxyuridine (BrdU)‐ and caspase‐3‐immunoreactive cells, indicating that stroke‐enhanced neuroblast migration is independent of cell proliferation and survival. PI3K catalyzes phosphatidylinositol‐3,4,5‐triphosphate (PIP3) which facilitates Akt phosphorylation. Thus, our data demonstrate that the PI3K/Akt signal transduction pathway mediates neuroblast migration after stroke. © 2003 Wiley‐Liss, Inc.
An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH‐SY5Y cells
Authors: Shamoto‐Nagai Masayo , Maruyama Wakako , Kato Yoji , Isobe Ken‐ichi , Tanaka Masashi , Naoi Makoto , Osawa Toshihiko
Published: October 2003

In Parkinson's disease, characteristic pathological features are the cell death of nigrostriatal dopamine neurons and the formation of Lewy bodies composed of oxidized proteins. Mitochondrial dysfunction and aggregation of abnormal proteins have been proposed to cause the pathological changes. However, the relation between these two factors remains to be clarified. In this study, the effects of mitochondrial dysfunction on the oxidative modification and accumulation of proteins were analyzed using an inhibitor of mitochondrial complex I, rotenone, and antibodies against acrolein‐ and dityrosine‐modified proteins. Under conditions inducing mainly apoptosis in neuroblastoma SH‐SY5Y cells, rotenone markedly increased oxidized proteins, especially those modified with acrolein, even though the increase in intracellular reactive oxygen and nitrogen species was only transient and was not so marked. In addition, the activity of the proteasome system degrading oxidized proteins was reduced profoundly after treatment with rotenone. The 20S β subunit of proteasome was modified with acrolein, to which other acrolein‐modified proteins were found to bind, as shown by coprecipitation with the antibody against 20S β subunit. These results suggest that mitochondrial dysfunction, especially decreased activity of complex I, may reduce proteasome activity through oxidative modification of proteasome itself and aggregation with other oxidized proteins. This mechanism might account for the accumulation of modified protein and, at least partially, for cell death of the dopamine neurons in Parkinson's disease. © 2003 Wiley‐Liss, Inc.
Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome
Authors: Kim S.I. , Grum‐Tokars V. , Swanson T.A. , Cotter E.J. , Cahill P.A. , Roberts J.L. , Cummins P.M. , Glucksman M.J.
Published: October 2003

Neuropeptide processing metalloenzymes, such as angiotensin converting enzyme, neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15), are central to the formation and degradation of bioactive peptides. We present EP24.15 as a paradigm for novel functions ascribed to these enzymes in the neurome. Although the neurome typically encompasses proteomes of the brain and central nervous system, exciting new roles of these neuropeptidases have been demonstrated in other organ systems. We discuss the involvement of EP24.15 with clinical sequelae involving the use of gonadotropin‐releasing hormone (GnRH; LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood pressure regulation), and in the hematologic system (immune surveillance). Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells, induce an increase in EP24.15 transcription, suggesting that neuropeptidase‐mediated hydrolysis of pressor/depressor peptides is likely regulated by changes in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface expression of major histocompatibility complex Class I proteins in vivo, suggesting that EP24.15 may play an important role in maintenance of immune privilege in sites of increased endogenous expression. In these extraneural systems, regulation of both neuropeptide and other peptide substrates by neuropeptidases indicates that the influence of these enzymes may be more global than was anticipated previously, and suggests that their attributed role as neuropeptidases underestimates their physiologic actions in the neural system. © 2003 Wiley‐Liss, Inc.
Decrease of morphine‐induced reward effects and withdrawal symptoms in mice overexpressing γ‐aminobutyric acid transporter I
Authors: Hu Jia‐Hua , Yang Na , Ma Ying‐Hua , Zhou Xiao‐Gang , Zhang Xu‐Ying , Jiang Jie , Mei Zhen‐Tong , Fei Jian , Guo Li‐He
Published: October 2003

Morphine addiction has been shown to result from neural adaptations produced by repeated drug exposure, but the mechanism is still unclear. In the present study, we found that γ‐aminobutyric acid (GABA) uptake was increased in mouse brain 120 min after, but not 20 min after, morphine (10 mg/kg, s.c.) injection. We generated GABA transporter I (GAT1)‐overexpressing mice to investigate whether the GABAergic system and GABA transporter are involved in morphine‐induced reward effects and withdrawal symptoms. Our results revealed that the rewarding effects induced by morphine were significantly decreased in GAT1‐overexpressing mice as measured by the conditioned place preference (CPP) paradigm. Moreover, both somatic and vegetative signs of naloxone‐induced morphine withdrawal symptoms were substantially reduced in GAT1‐overexpressing mice. In addition, the decreased morphine rewarding in transgenic mice could be recovered when mice were coinjected with NO‐711 (a GAT1 selective inhibitor) in the CPP paradigm. These findings suggest that the GABAergic system plays an important role in morphine addiction and point to the possibility of developing drugs that target GAT1 and extend the clinical application of opiates. © 2003 Wiley‐Liss, Inc.
Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush
Authors: Siconolfi Lisa B. , Seeds Nicholas W.
Published: October 2003

Plasminogen activators (PAs), tissue PA (tPA) and urokinase PA (uPA), have been shown to be induced in sensory neurons after sciatic nerve crush. These findings suggested that PAs facilitate peripheral nerve regeneration by digesting adhesive cell contacts and by activation of other proteases, thereby initiating a proteolytic cascade. Both tPA and uPA activate some matrix metalloproteases (MMPs), indirectly via plasminogen activation or directly, such as the uPA activation of MMP‐2. In this study, we demonstrated, by using tPA and uPA knockout mice, that a lack of a plasminogen activator affected MMP‐9 and MMP‐2 activity after crushing of the sciatic nerve. These findings show that the PAs are important for MMP‐9 and MMP‐2 activity at the crush site. © 2003 Wiley‐Liss, Inc.
Treatment of chronically injured spinal cord with neurotrophic factors stimulates βII‐tubulin and GAP‐43 expression in rubrospinal tract neurons
Authors: Storer Paul D. , Dolbeare Dirk , Houle John D.
Published: October 2003

Exogenous neurotrophic factors provided at a spinal cord injury site promote regeneration of chronically injured rubrospinal tract (RST) neurons into a peripheral nerve graft. The present study tested whether the response to neurotrophins is associated with changes in the expression of two regeneration‐associated genes, βII‐tubulin and growth‐associated protein (GAP)‐43. Adult female rats were subjected to a right full hemisection lesion via aspiration of the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel foam saturated in brain‐derived neurotrophic factor (BDNF), glial cell‐line derived neurotrophic factor (GDNF), or phosphate‐buffered saline (PBS) was applied to the lesion site for 60 min. Using in situ hybridization, RST neurons were examined for changes in mRNA levels of βII‐tubulin and GAP‐43 at 1, 3, and 7 days after treatment. Based on analysis of gene expression in single cells, there was no effect of BDNF treatment on either βII‐tubulin or GAP‐43 mRNA expression at any time point. βII‐Tubulin mRNA levels were enhanced significantly at 1 and 3 days in animals treated with GDNF relative to levels in animals treated with PBS. Treatment with GDNF did not affect GAP‐43 mRNA levels at 1 and 3 days, but at 7 days there was a significant increase in mRNA expression. Interestingly, 7 days after GDNF treatment, the mean cell size of chronically injured RST neurons was increased significantly. Although GDNF and BDNF both promote axonal regeneration by chronically injured neurons, only GDNF treatment is associated with upregulation of βII‐tubulin or GAP‐43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons. © 2003 Wiley‐Liss, Inc.
Systemic insulin‐like growth factor‐I administration prevents cognitive impairment in diabetic rats, and brain IGF regulates learning/memory in normal adult rats
Authors: Lupien Sean B. , Bluhm Erik J. , Ishii Douglas N.
Published: October 2003

Diabetic patients have impaired learning/memory, brain atrophy, and two‐fold increased risk of dementia. The cause of cognitive disturbances that progress to dementia is unknown. Because neurotrophic insulin‐like growth factor (IGF) levels are reduced in diabetic patients and rodents, and IGF can cross the blood‐central nervous system barrier (B‐CNS‐B), the hypothesis was tested that IGF administered systemically can prevent cognitive disturbances, independently of hyperglycemia and a generalized catabolic state. Latency to escape to a hidden platform in the Morris Water Maze is used widely to test spatial memory, a hippocampus‐dependent task. Adult rats were rendered diabetic with streptozotocin and implanted 4 weeks later with subcutaneous pumps that released either vehicle (D + Veh) or 20 μg/day IGF‐I (D + IGF). Latency to escape to the hidden platform was prolonged in (D + Veh) versus non‐diabetic rats (P < 0.003) 10.5 weeks after the onset of diabetes. Such prolongation was prevented in (D + IGF) versus (D + Veh) rats (P < 0.03). The data show that IGF‐I can act across the B‐CNS‐B to prevent loss of cognition‐related performance in the water maze independently of ongoing hyperglycemia and reduction in brain (P < 0.001) and whole body weight (P < 0.001) in diabetic rats. The hypothesis that brain IGF contributes to learning/memory was tested. An anti‐IGF antibody, or preimmune serum, was infused into the lateral ventricles in non‐diabetic rats. Learning in a passive avoidance task was impaired significantly in the IGF antibody versus preimmune serum‐treated groups on test Days 1, 2, and 3 (P = 0.04, 0.02 and 0.004, respectively). The data together are consistent with a model in which brain IGF is essential for learning/memory, and a loss of IGF activity due to diabetes may contribute to cognitive disturbances. © 2003 Wiley‐Liss, Inc.
Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth
Authors: Shin Lee Ji , Seok Kim Hyung , Bok Kim Young , Cheol Lee Min , Soo Park Chang
Published: October 2003

Background and Objectives

PTEN is a candidate tumor suppressor gene in a variety of malignant tumors, including renal cell carcinoma (RCC). PTEN regulates cell cycle progression and cell survival in vivo. However, the role of PTEN alterations and their association with tumor growth and behavior in patients with RCC has not been well established. The aim of our study was to evaluate PTEN expression in RCC and its correlation with clinicopathologic features, cell proliferation, and apoptosis.

Methods

Sixty‐seven RCC specimens were examined immunohistochemically with anti‐PTEN antibody. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick‐end labeling (TUNEL) and proliferative cells were visualized by staining with Ki‐67 antibody.

Results

Twenty‐one (31.3%) of the 67 RCCs showed reduced PTEN expression. The apoptotic index (AI) varied from 0.2 to 25.5%, and the Ki‐67 index (KI) ranged from 1.6 to 69.8%. Reduced PTEN expression correlated with TNM stage (P < 0.05) and nuclear grade (P < 0.05). Tumors with reduced PTEN expression had a significantly higher KI than those with normal PTEN expression (P < 0.01). By univariate analysis, nuclear grade (P = 0.0005), TNM stage (P < 0.0001), AI (P = 0.0220), KI (P = 0.0002), and reduced PTEN expression (P < 0.0001) were associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis (P = 0.0007).

Conclusions

Our results suggest that PTEN expression is frequently reduced in advanced RCC. The PTEN gene seems to be important for the growth suppression of RCC, by inhibiting cell proliferation. J. Surg. Oncol. 2003;84:166–172. © 2003 Wiley‐Liss, Inc.
Mortality for gastric cancer in elderly patients
Authors: Eguchi Teruo , Fujii Masashi , Takayama Tadatoshi
Published: October 2003

Background

The aim of this study was to clarify the surgical outcome in elderly patients with gastric cancer.

Methods

The clinicopathological features of elderly patients (80 (3.7%), over 80 years, elderly group) were reviewed retrospectively and compared with those of younger patients (2,095 (96.3%), 23–79 years, control group).

Results

The elderly group had a significantly higher prevalence of concomitant disease (P < 0.0001), while the prevalence of T1 primary tumor, N0 lymph node metastasis, and stage I was lower (P = 0.0125, P = 0.0004, P < 0.0001). The rates of resected cases and curative operation (R0) were significantly lower in the elderly group (P < 0.0001, P = 0.0021). The mortality from other diseases was 16.3% in elderly patients and 4.4% in control patients (P < 0.0001). The 5‐year survival of stage I and stage IV were not significantly different between the two groups (P = 0.1266 and P = 0.2490). The overall survival and disease‐specific survival for all patients in the elderly group were significantly lower than those in the control group (P < 0.0001, P = 0.0102). However, disease‐specific survival for resected cases was not significantly different between the two groups (P = 0.0725).

Conclusions

In elderly patients, the reason for the poor prognosis is the high rate of advanced stage and the high rate of death from other diseases. J. Surg. Oncol. 2003;84:132–136. © 2003 Wiley‐Liss, Inc.
Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection
Authors: Fujita Shin , Shimoda Tadakazu , Yoshimura Kimio , Yamamoto Seiichiro , Akasu Takayuki , Moriya Yoshihiro
Published: October 2003

Background and Objectives

Streak type, defined by the presence of white streaks at the advancing margin of tumor invasion; focal dedifferentiation, seen as undifferentiated cancer cells with an infiltrative pattern at the invasive front; and perineural invasion have been demonstrated to be prognostic factors in patients with colorectal cancer. We performed a prospective study to examine the usefulness of these features as prognostic factors.

Methods

We reviewed a total of 391 patients who underwent curative surgery for colorectal cancer between May 1997 and June 1999. Of these, 50 patients with multiple cancers were excluded, and a total of 341 patients were finally entered into the study.

Results

Of the prognostic factors investigated, depth of invasion, lymph node status, lymphatic invasion, venous invasion, growth type, streak type, focal dedifferentiation, and perineural invasion were significant prognostic factors in univariate analysis. In multivariate analysis, lymph node status, depth of invasion, and perineural invasion were significant prognostic factors. The survival of patients with perineural invasion was significantly poorer than that of patients without perineural invasion in both stage II and III cancer.

Conclusions

Perineural invasion status can be used to facilitate the selection of colorectal cancer patients for adjuvant chemotherapy and should be described in routine pathology reports. J. Surg. Oncol. 2003;84:127–131. © 2003 Wiley‐Liss, Inc.
Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer
Authors: Norrie Mark W.A. , Hawkins Nicholas J. , Todd Alison V. , Meagher Alan P. , O'Connor Terence W. , Ward Robyn L.
Published: October 2003

Backround and Objectives

Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16INK4a gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p16 expression and its relationship to hypermethylation in sporadic colorectal cancer.

Methods

Tissue from 426 colorectal cancers underwent histological analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA was analyzed for microsatellite instability (MSI) and the presence of K‐ras mutations. In addition, DNA was bisulphite‐modified and analyzed for p16INK4a promoter methylation by methylation‐specific PCR.

Results

There were 25% of tumors with p16INK4a promoter hypermethylation. These tumors were associated with older patients, right‐sidedness, MSI and were poorly differentiated, mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's‐type lymphocytic reaction (P < 0.05). However, only right‐sidedness was significant on multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and this was associated with hypermethylation (P < 0.05).

Conclusion

p16INK4a promoter methylation, although common in colorectal cancer, does not result in a clinicopathologically distinct subgroup of tumors and infrequently results in transcriptional silencing. This suggests that p16INK4a gene inactivation does not have an important role in the pathogenesis of sporadic colorectal cancer. J. Surg. Oncol. 2003;84:143–150. © 2003 Wiley‐Liss, Inc.
Application of direct nonlinear regression from single TG curve to compounds undergoing simple and complex thermal decompositions
Authors: Rodante Fabrizio , Vecchio Stefano , Slovák Václav
Published: October 2003

Nonlinear regression of the basic kinetic equation was used to determine kinetic parameters of simple and complex decomposition processes related to some pesticides and pharmaceutical substances. The method for this calculation was carried out using a single TG curve.

These values were compared with those obtained with model‐fitting and model‐free methods.

Nonlinear regression method is able to define a single mechanism for compounds undergoing one or few steps of decomposition processes. For compounds that undergo many steps of decomposition processes, only the mechanisms of some of them can be hypothesized. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 611–622, 2003
Kinetics and mechanism for the thermal chlorination of chloroform in the gas phase: Inclusion of HCl elimination from CHCl3
Authors: Zhu Li , Bozzelli Joseph W.
Published: October 2003

HCl elimination from chloroform is shown to be the lowest energy channel for initiation in the thermal conversion of chloroform to CCl4, with chlorine gas in the temperature range of 573–635 K. Literature data on this reaction is surveyed and we further estimate its kinetic parameters using ab initio and density functional calculations at the G3//B3LYP/6‐311G(d,p) level. Rate constants are estimated and reported as functions of pressure and temperature using quantum RRK theory for k(E) and master equation analysis for fall‐off. The high‐pressure limit rate constant of this channel is k(CHCl3 → 1CCl2 + HCl) = 5.84 × 1040 × T−8.7 exp(−63.9 kcal/mol/RT) s−1, which is in good agreement with literature values. The reactions of 1CCl2 with itself, with CCl3, and with CHCl3 are incorporated in a detailed mechanistic analysis for the CHCl3 + Cl2 reaction system. Inclusion of these reactions does not significantly change the mechanism predictions of Cl2 concentration profiles in previous studies (Huybrechts, Hubin, and Van Mele, Int J Chem Kinet 2000, 32, 466) over the temperature range of 573–635 K; but Cl2, CHCl3, C2Cl6 species profiles are significantly different at elevated temperatures. Inclusion of the 1CCl2 + Cl2 → CCl3 + Cl reaction (abstraction and chain branching), which is found to have dramatic effects on the ability of the model to match to the experimental data, is discussed. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 647–660, 2003
Pyrolysis of liquefied petroleum gas assisted by radicals desorbed from mesh catalyst surface
Authors: Quah Eugene B. H. , Li Chun‐Zhu
Published: October 2003

The purpose of this study is to understand the reactions on the catalyst surface and in the gas phase during the catalytic pyrolysis of light hydrocarbons. To avoid the complexity of internal pore diffusion and heat transfer limitation, nickel mesh without pore structure was used as a catalyst for the catalytic pyrolysis of a commercial liquefied petroleum gas (LPG) sample in a quartz tube reactor and in a wire‐mesh reactor over a temperature range of 600–850°C. With a Ni mesh catalyst, no catalyst deactivation associated with coke formation was observed at high gas flow rate. Our experimental results indicate that the desorption of radicals from the catalyst surface is an important process in the catalytic pyrolysis of LPG using the Ni mesh catalyst. The desorption of radicals across the gas–catalyst interface is greatly facilitated by increasing gas flow rate passing through the mesh. The desorbed radicals would initiate and/or enhance the gas‐phase radical chain reactions and lead to improved reaction rates for the pyrolysis of LPG although the product selectivities remained unchanged. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 637–646, 2003
Spectral, kinetic, and redox properties of basic fuchsin in homogeneous aqueous and sodium dodecyl sulfate micellar media
Authors: Ramanathan N. , Priyadarsini K. I. , Guha S. N. , Mohan H.
Published: October 2003

Effect of anionic surfactant on the optical absorption spectra and redox reaction of basic fuchsin, a cationic dye, has been studied. Increase in the absorbance of the dye band at 546 nm with sodium dodecyl sulfate (SDS) is assigned to the incorporation of the dye in the surfactant micelles with critical micellar concentration (CMC) of 7.3 × 10−3 mol dm−3. At low surfactant concentration (<5 × 10−3 mol dm−3) decrease in the absorbance of the dye band at 546 nm is attributed to the formation of a dye–surfactant complex (1:1). The environment, in terms of dielectric constant, experienced by basic fuchsin inside the surfactant micelles has been estimated. The association constant (KA) for the formation of dye–SDS complex and the binding constant (KB) for the micellization of dye are determined. Stopped‐flow studies, in the premicellar region, indicated simultaneous depletion of dye absorption and formation of new band at 490 nm with a distinct isosbestic point at 520 nm and the rate constant for this region increased with increasing SDS concentration. The reaction of hydrated electron with the dye and the decay of the semireduced dye are observed to be slowed down in the presence of SDS. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 629–636, 2003
The thioredoxin system—From science to clinic
Authors: Gromer Stephan , Urig Sabine , Becker Katja
Published: October 2003

The thioredoxin system—formed by thioredoxin reductase and its characteristic substrate thioredoxin—is an important constituent of the intracellular redox milieu. Interactions with many different metabolic pathways such as DNA‐synthesis, selenium metabolism, and the antioxidative network as well as significant species differences render this system an attractive target for chemotherapeutic approaches in many fields of medicine—ranging from infectious diseases to cancer therapy. In this review we will present and evaluate the preclinical and clinical results available today. Current trends in drug development are emphasized. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 40–89, 2004